Solutions manual to accompany Clayden, Greeves, Warren, and Wothers aoe TASTUPaMElacae W)INNINSolutions manual to accompany Organic Chemistry by Clayden, Greeves, Warren, and Wothers, STUART WARREN University of Cambridge OXFORD UNIVERSITY PRESSOXFORD Geet Clarendon Set, Oxford OX2 6D? 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Diste ened cing nt sim rine sttccounon: wech Srer arzar:atares Haag (ea, Imarened, ard ic} pee tances, Draw molecule hased an gach framewors toni bath ketone and garbotnllc aolsrunctional grou, Purpose of the problem ‘Te: go me drewing Simple atiseines well and re ster yon seep Pom neles arc marras towns dealive sunita ica Suggested solution ‘me inesr atoratedlfyeicarhon witk sever esrhon atotrs hu there iy a wld chalice offer seme nexiilitias hut pac may-~wall have thocght of ether, Ther fr fi the rez. Ar ste Aa RAR sengel onus CoO Pre po fad & fe ye el ee Oe art CC Om Problem 2 ‘Scnay tn stucuoe of breselanih op 2. 33, hla a feo? ne ena pans oF mmiserag ‘evop tee ala Frage ia here er metry es aa of fa: enters a rus ot Sines, Finely, sendy che sabe areswees branche2 Organic Chemistry Solutions Manual Purpose of the problem ‘To petsuade you that functional groups are easily recognized even in complicated molecules and that, say, an ester is an ester whatever company it may keep. You were not expected to see the full implications of the carbon framework part of the question. That was to amuse and surprise you, Suggested solution ‘The ethers are all the unmarked oxygen atoms in the rings all are cyclic, seven in six-membered rings two in seven-membered rings, and one in an eight-membered ring, Tere are two carbonyl sroups, one an ester and one an aldehyde, and three alkenes. ‘The carbon chain is branched because it has seven methyl groups branching off it and the aldehyde is also a branch. Amazingly, under this disguise, you can detect a basically linear carbon chain, shown with a thick black line, although i twists and turns thoughout the entire molecule! Purpose of the problem To shock you with two dreadful siractures and to try and convince you that well drawn realistic structures are more attractive to the eye as well as easier to understandChapter 2 Suggested solutions for Chapter 2 Suggested solution The bond angles are grotesque with square planar saturated carbon, alkynes at 120°, alkenes at 180°, ‘onds coming off benzene rings at the wrong angle, and so on, The left-hand structure would be slearer if most of the hydrogens were omitted. Here are two possible hetter structures for each molecule, There are many other correct possibilities. ea ce Problem 4 Z Draw structures comesponding to these names. In each case sugges altemative names that might corwoy the strture more clearly to someone wo is istening to you speak. (a) 14-di(2.2-dimethylethybenzene (©) 3{pr0p-2enyoxyjorop-t-ene. (©) eyclohexe-1.3.5:riene Purpose of the problem ‘To help you appreciate the limitations of names, the usefulness of names for part structures, and, in the ase of (c), to amuse. Suggested solution (a) I-di-(1,1-dimethylethyDbenzene, More helpful name para 1 di-ter-butyl benzene, an equally helpful name. i--butyl benzene. It is sold as = the LL dimenicty soo b) 3+( prop-2-enyloxy)prop-I-ene. This name does not convey the simple symmetrical structure nor that it contains two allyl groups. Most chemists would call this ‘diallyl ether though it is sold as ‘ally ether’ (©) cyclohexs-1,3,5-trione. Tis is, of course, benzene, but even IUPAC has not tried to impose this ‘correct’ name for such an important compound, Pe, Problem 5: Draw one possible structure for each of these molecules, selecting any group of your choice ‘or the ‘wild card’ substituents.Organic Chemistry Solutions Manual Purpose of the problem . ‘To help you appreciate the wide range and versatility of general structures with X, RI, Ar!, ete ‘These become more important when you stata database search fora pat structure Suggested solution ‘There are, of course, many possible solutions. X could be a heteroatom or a structural fragment while Ar could be any of a very large number of substituted benzene rings or even other types of aromatic rings. Our frst two solutions in each case are ones you might have found and the rest are mote inventive. The four-membered ring could have X = NH or CO (a Ketone) while the substituents R! and R? could be the same (both methyl groups) or differen (a benzene ring and an ether) In the last two structures X itself cartes extra groups ~ the two oxygen atoms in the SOs group oran alkene while R' and R? could be ina ring orbe diferent highly functionalized groups Of course, there are also some things that R!, R®, and X cannot be. R’ and R® cannot be N or CH; while X cannot be Ph or Cl ‘The three aryl groups in the second example might all be different or some might be the same. In the last two structures we show some unusual aromatic rings including some linked together and. fone with a nitrogen atom in the ring A AL “yy Problem6 Bee Translate these vow poor ‘alagrams of molecules into more realistic stustues. Try to get ‘the angles about right and, whatever you do. don't include ary mua) Planar carbon atoms - “oF oter bond angles of 90: _ Saeco ton ene O(CH:CH;)20 _—~_(CHy0),CHCH=CHCH(OMe}2 Purpose of the problem [An exercise in interpretation and composition — this sor of ‘structure’, which i used hen sHructures must be represented by ordinary printing, gives no clue to the shape ofthe molecule and you must decide that for yours.Chapter 2 Suggested solutions for Chapter 2 Suggested solution ‘You probably needed a few tral and error drawings first, but simply drawing out the carbon chains ‘5 you the answers, The frst is straightforward though you may not previously have sen the dot ‘9a the mile ofthe formula. This does not represent any atom but simply shows thatthe atom aamediately belore the dot is not joined to that immediately after it The (OH) group is a substituent off the chain, not part ofthe chain itsel- The second has no ends (Me groups etc.) and © must be an unbroken ring. The third gives no clue as to the shape ofthe alkene and we have shosen tras. It also uses two ways to represent MeO. Either is correct but i is best to stick to one ‘representation in any given molecule. ‘CaMeCH(OM).(CH,),00CMy OfCH:CH.I:0 ——_(CHs0),CHCH=CHEHOMe, Scam aga cfferent stuctures that woule ae emia Cite. Make 3000 realistic diagrams of each one and say which functional groups) ae present Purpose of the problem ‘demtification and naming of functional groups is more important than the naming of sompounds. This was your chance to experiment with different functional groups as well as u= Purpose of the problem Just litle practice in converting verbal descriptions into {thea naming thetn is justified. We hope you agree that the diagrams are more the description in the question and more easly understood than the name, Suggested solution ‘The structures are uniquely described by the rather verbose conn [Naming the compounds requires (1) identi ‘goup, (2) numbering the skeleton, and (3) locating the functional group by name amd = The aromatic compound is 4 ketone with (wo carbon atoms ~ an ethanone ‘evem ‘eannot be 2 two-carbon Keetone!). ‘The carbonyl group is Cl. The aromatic vy its Cl at Cl and is numbered so as to give the smallest possible numbers to the I is (2.5-dichloro~ nitrophenyl)ethanone. “The aliphatic compound is a carboxylic acid which === CL The rest is straightforward. Groups are usualy named in alphabetical order. It is 2==— {6-triluorohex-4-ynoic acid. Ifyou don't agree with our names, don’t Worry. Ht gent => matter. What does mater is: did you draw clear comprehensible structure? Problem 9 Draw full structures for these compounds, displai-g v= ~c"3c=con framework clearly and ‘showing all the bonds present in the functional gowns. Name =e Functional groups. ‘AcO(CH NOs meo;0.0H,0c08% ‘cp=CH.CO.NH(CH):ON Purpose of the problem ‘This i rather like Problem 6 except that more thought is meeded forthe details of the functional {g70ups and you may have needed to check the ‘organic ements’ Ac, Es, and so on in the chapter. Suggested solution For once the solution can be simply stated as no variation & really possible The tricks for the ist ‘one ate to see that ‘AcO” represents an ester and to have only four bonds to nitrogen in NOs. The second has two ester groups on the central CH: group but nei joined to it by a CO bond and theChapter 2 Suggested solutions for Chapter 2 sxher by a CC bond. The las is straightforward except for the dots used to separate the substituents ‘explained in the answer to Problem 6). ‘AcO(CHaaNOs ‘me04e.cH, 0coet CHiz=CH.CO.NN(CH EN DAG RS doy Ay, Problem 10 Purpose of the problem TES important exercise is one you will et used to very quickly and, before long, do without ‘Hanking I you do, it wll sve you from many trivial erors. Remember that the oxidation state of ‘atbon is +4, oF C{1V), in all these compounds. The oxidation level of a functional group tll you ‘wih which oxygen-bosed functional group iti interchangeable without oxidation or reduction. Suggested solution vant the number of bonds to heterostoms. These can range from none to fou. The only tricky es ae alkenes and alkynes, which have no heteroatoms but are formed by dehydration of -deabols, aldehydes, or Ketones. There isa summary chart on p. 36 ofthe textbook, but brie: ‘eras to nerrostoms Oxdaton lve “pe struct ° ycrocarbon| a ‘eonot on In these cases we have examples ofall oxidation levels, Check the answer against yours and the ‘able. In the case of the alkene, formally a dehydration product from an alcohol, either but not both ef the C atoms is atthe alcohol oxidation level.Organic Chemistry Solutions Manual ea seo ce ils eee Be e ne iar rraneaeene ASAIN . ncrocaton etcne Seonat ten ane reise on pp. 23 (drawing ai es) 4 44 (ening soon re 1 ‘common compounds an three common solvents). Purpose of the problem These compounds are important so drawing them again is not just a useful exercise: it also helps reinforce your knowledge of these structures. Suggested solution Hire are the drawings we suggested for the amino acids on p, 23. There are other ways. sot yes Oe aie stents Qe. te te ‘The ‘ten common compounds’ and ‘three common solvents’ are specially important and we recommend that you learn these structures. We generally pour scorn on the idea of memorizing, things, so take note when we recommend itl plier ty td a) seston er sectcence mio ete acd (erp) dete ‘ahora neoursscmy ears acy Owego Coe ein ebera) ‘The three common solvents below join ether, acetone, ethyl acetate (ELOAc), toluene, and pyridine as commonly used solvents for organic reactions. One or other of these will dissolve almost any organic compound. e ple seem aimetrtomanice OME) sired (MSO)Suggested solutions for Chapter 3 Problem 4 é oe : 5 How doos the mass spectrum gives evidence ef isotopes in the compounds of bromine, hlorne, and carbon? Assuming the molecular jon of each of these compounds is of 100% sundance, what peeks (and in what intensity) would appear around that mass number? (a) C:HsBrO, (b) Ceo, (c) CoHuBrCI? Give In cages (a) and (o) a possible structure for the ompound. What compound is (b)? Purpose of the problem "9 ve you practic in spotting the important atoms that have isotopes and in interpreting multiple ‘Seiecular ions, The molecular ion isthe most important peak in the mass spectrum and is often the eiv peak to interest us. ‘Saggested solution Beomine has two isotopes, "Br and "Br, in about a I: ratio, chlorine has two, °°Cl and "Ch in about a 31 ratio and there is about 1.196 °C in normal compounds. Hence the molecular ions of ‘Se three compounds will be a fllows 2) GHsBrO, MW 124/126, There will also be weak peaks (2.2% of each main peak) at 125 and Compaunds containing Bor 127 forthe same ions with °C. seuss have thei ole ons Ca as a molecular ion at 720 witha stong peak at 721. The chance that one C atom is Cis Sosa ei. Te st ee simply 60 x 1.1% = 66% so the M + 1 peal more than half as strong as M* itelé The Shy, hance of two atoms i small <) GcH,BrCt is more complicated a the molecule ton will contain tl rata of Br and "ie, and a 3:1 ratio of $C and Cl. The molecu in consists of four peaks (ctios in brackets): CH BP"CL (G), CoHY"BC (3), CQHYBP"C (1), and Cele" Cl (1), The masses of these peaks are 190, 192, 182, and 19, The molecular ion wil therefore have thee peaks at 19, 192, and 194 in a ratio of Sl with peaks at 191, 193, and 195 at 6x 1.196 = 646% ofthe peak before it So the complete Picture is 190 (759%), 191 (59), 192 (L008), 195 (6.6%), 194 (259), and 195 (1.73). Compound (b) is of course, buckminsterfllerene and the other compounds might be isomers such as these o omar ene Sl lee le Problem 2 : : : i i The C NMR spectrum for ethyl benzoate contains these peaks: 17.3, 61.1, 100-150. oo ‘.p1m. (four peaks), and 166.8 p.p.m. Which peak belongs to which carbon atom? Purpose of the problem To familiarize you with the four main regions of the BC NMR spectrum: saturated carbons at 0-30 ppm, saturated carbons next to oxygen at 8 1-100 p.pam. alkenes and aromatic compounds1 We have ignored the effects of the c atoms on tho othe ¢ atom, but tay wil algo erase he ‘Shama! sit toa lesser extent, Organic Chemistry Solutions Manual with unsaturated carbon at 100-150 p.p.m., and unsaturated carbon next to oxygen (usually C=O} at 150-200 ppm. Suggested solution ‘There are four different types of carbon atom in the benzene ring (don't forget the ‘ipso’ carbon joined to the substituent) and it is not easy to say which is which. The rest can be deduced from the four main regions. Problem 3 The thinner used in typists comection fds a single compound, C2HsCls, having #C NVR ‘peaks at 45.1 and 95.0 p.o.m. What its stricture? A commercial paint thinner gives two spots on chromatogrephy and has 3¢ NWR pecks at 7.0, 27:5, 35.2, 46.3, 95.6, ond 206.3 p.pm. Suggest what compounds might be used to make up this thinner. Purpose of the problem To start you on the road of structure identification with one very simple problem and then some deductive reasoning. It is necessary to think about the size of chemical shifs inthis case. Suggested solution ‘There are only two possible structures for a compound C;HsCl ~ it must be trichloroethane and the chlorines can be distributed in these two ways. meh “ye ‘The frst isomer would have a peak for the methyl group in the region 0-50 ppm. and one for the CCls group at 2 much larger chemical shift because of the three chlorine atoms. The second jsomer would have a peak for CHCl in the 50-100 p.p.m. region and one for CHCl at a langer shift Dut the two shifts would not beso far apart. The observed shifts are 50 p.p.m. apart and, in fact, the ‘compound is 1,1,l-trichloroethane. The NMR specirum of the 11,2-richloro isomer has peaks at 50.5 and 70.7 p.pam. ~ much closer together. ‘The mixture probably contains the same trchloroethane as the peaks at 45.3 and 95.6 ppm, suggest (the chemical shifts of the mixture need not be quite the same as those ofthe pure compound. as each compound is effectively dissolved in the other). The remaining peaks at 7.0, 27.3, 35.2, and 20633 p.p.m. definitely belong to a carbonyl compound, probably a ketone since 206.3 p.pam. is so large. Butanone fits the bill a t has one methyl and one CH group on the carbonyl group and one ‘methyl away fom any electronegative atoms. There are other possibilities Problem 4 ‘The ‘normal’ O-H stretch (Le. without hydrogen bonding) comes at about 3600 em-. What Is the reduced mass (u) for 0-H? Wnat heppens to the reduced mass when you double the ‘atomic weight of each atom in tum, that is, what Is 4 for O-D and what isu for $-H? Infact, ‘both O-D and S-H stretches come at about 2500 om. Why? Purpose of the problem To get you thinking about the position of IR bands in terms of the two main influences ~ reduced mass and bond strength. The relationship between the frequency (v) of the vibration,Chapter 3 Suggested solutions for Chapter 3 a Se force constant f(more or less equals bond strength), and the reduced mass (j) is given by ‘aes cquation. eV Seggested solution ‘Tbe redaced mass) ofa vibrating bond i given by this equation, Se reduced mass of OH is 16/17 oF about 0.94. When you double the mass of H, the reduced ‘as of OD becomes 32/18 oF about 1.78 which is roughly double that for OH. But when you deste the mass of O, the reduced mass for SH is 32/33 or about 0.97 ~ hardly changed from O81 The change in reduced mass is enough to account forthe changed frequency of the OD bond ~ amps by about 2 — but cannot account for the change from OTT to SH as the two reduced ‘mmmees are bout the same. The only explanation of this can be thatthe SH bond is weaker than the 5 {OH bond by 2 factor of about 2. There isan important principe tobe deduced fram this problem. Very roughly, the reduced masses € a bonds involving heavier atoms (C, N, O, 5, et) are about the same and the differences in IR seething frequency are mostly due to changes in bond strength. This s most dramatic in comparing siege. double, and triple bonds. Only with bonds involving hydrogen does the reduced mass become ‘he more important factor, though i is also significant in comparing, sy, C-O with C-CL ‘wre: are their structiires? Without +#C NMR cata, it may be easier to tackle this: problem by. ‘es! Hriting down all the. possible siuctures for C3HaNO: In what tanec aye nou SAR eta help? i | One sharp band ave 3000 em ane ston bard at bout 1700 ei "= Two sharp bands above 3000 em” twa bands between 4600 and 1700 om“! “=! One strong broad bak above 3000 én~'; a hand at about 2200.m—" Purpose of the problem 2 Sow that IR alone has some usefulness in the identification of molecules but that NMR is ‘tecesy even with very simple molecules In answets to examination questions ofthis type itis «0 show how you interpret the data as well sto give a structure you get the answer right, tation is not so important, but if you get the answer wrong, you should still get some Se Sr your interpretation Seggested solution 4 Ore sharp band above 3000 cm“ must be an N-H and one strong band at about 1700 em~! is probably a C=O. That leaves CH, and so we might have one of these (there are other ls likely | ‘sractures). °C NMR would help because a(i) would have a carbonyl group and two signal for saturated € while ali) would aso have a C=O but only one signal for saturated carbon as the : sommpound is symmetricala2 Organic Chemistry Solutions Manual {h) Two sharp bandh above 3000 cm © must be an NIL, group ant wo bands between 16 ae 7mm ern! sugges C=O aad a C=C. This leaves jst three hydrogen atoms and yives us seu EE NMR would help because the -0 shift would show whether the compouend sos an amide or a aldshyde and the alkene shitis would reveal the presence of the NHe grou in i Ws, ~~ a wa ° 4c) One strong broad hand! shove MiOO emt mnast e an OL aids baad at about 2200 cm must hea tiple hond, presumably CX as there woul esherwise be NHS as well, That leaves CoH. again hut ke de nol need & rig and we hae suet two double bonds, presumably Tike thess Problem 6 Four compouncs having the molecular formuls CaMlsOr have the IR and "*C NMR spectra fiven below, How many OBEs (Double Bond Equivslents) are thore in CaHO2? What are the ‘structures of the four compounds? You mignt again find it helpful to draw aut some or all possibilities before you stan, NMR: 214, 82, 58, and 44 p.pm. 1300 (broad) cm’: "C NMR: 62 and 79 p.p-m. {e) IR: 1770 cm™': “C NMR: 178, 86, 40, and 27 p.pm. {@) IR: 1720 and 1650 (strong) cm '; “C NMR: 165, 131, 133, and 54 p.p.m, Purpose of the problem rst steps in eal identification using two diferent methods. Because the molecules ate vo small fonly four carbon atoms} drawing ut fee trial structes gives you some ideas 28 10 the 1ypES of -ompounds key to be fou Suggested solution Here are some posible structures for C.MQ.. I and a ring are likely wo feaure, The double bonds nave pot to be C20 or C=C tor both these isn ring’. Fanetional groups ae likely to ipdude alcohol, ldebyde, aid amd ketone °. ° WAA, Poo TS ‘oH Me Ile ot ketone). 82 and 58 one saturated carbon Bot next dear that two double bonds or one double bond Ga) METAS em oop: BC NMR: 214 ppm ppm, (to saturated atbons nent wo oxygen? and Al pspan twonygen bur nea some es must be a € tron: wtharawcing proxy. The secon! ase does not show Up i the IR so i must be an ether. As thete i only one double hond. there mst be a ring. This {yy He S00 rand cay mest ean OH, CNMI 92 aad “0 gay mest he a symmetrc anolecie with no alkenes and no C nana saturated carbon next to oxygen. Tica gies one struts. Nos 6 she ane des nat in the 18 because itis spmmetrica so it mast bea eipie borChapter 3 Suggested solutions for Chapter 3 {6} IR: 1770 cm! must be some sort of C=O; !°C NMR: 178 p.pm. (C=O of ac derivative), 86 p.pam. (saturated C next to 0), 40 and 27 ppm. (saturated Cs not next to 0). Again only one double bond so it must have a ring 100. Looks lke a close relative of ( 4) TR: 1720 and 1650 (strong) em must be conjugated C=C and C=O; "C NMR: 168 ppm, (C20 of acid derivative), 131 and 133 p.p.m, (alkene), and 54 p.p.m. (saturated C next to). ‘This defines all the carbon atoms and it must be a simple unsaturated ester. Notice that we cannot tell which signa corresponds to which alkene carbon but thet this does not affect our conclusion. Problem 7 Three compouncs of molecular formula CyHeO have the IR and *C NMR spectra given below. Suggest structute for each compound, explaining how you make your deductions. ‘compound AR: 1730 om; #9C NMR: 13.3, 15.7, 45.7, and 201.6 p.p.m. compound BR: 3200 (broad) cm”; °C NMR; 36.9, 61.3, 447.2, and 134.7 ppm. compound CIR: no peaks except CH and fingerprint; #0 NMR: 25.8 and 67.8 p.p.m. ‘The rest of the problem as stated in the text is given below in the ‘Suggested solution”) Purpose of the problem More practice in the same essential skill. Notice that we have two more H atoms in tis formula so = have either a ring or a double bond but not both. In adltion, a bit of chemistry is added. Suggested solution scpound A IR: 1730 cm” (C=O of some sort); C NMR: 13.3, 157, and 45.7 pppam. (three saturated carbon atoms with one next to some electron-withdrawing group but not oxygen), and 201.6 prpam. (aldehyde oF ketone). No symmetry. A ketone would hhave two Cs next to C=O so this is just butanal. Serpound BR: 3200 (broad) em™! (OH); #C NMR: 369 ppm. (saturated ©), 613 ppm. {saturated C next to 0), 117.2 and 1347 ppm alkene). There are two possibilities here eae aarzyssar ssempound CIR: no peaks except CH and fingerprint (oxygen must be ether; °C NMR: 258 ppm. (Gaturated © not next to O) and 67.9 ppm. (saturated C next to 0). Note symmetry. As there are no double bonds, there must be a ring and it can only be THR, Xow the extra bit of the orginal problem, which may resolve our doubts on the structure of Sepound B Compound A reacts with NaBH, to give compound D. Compound B reacts with hydrogen gas seer a palladium catalyst to give the same compound D. Compound C reacts with neither reagent. Seggsst structure for compound D from the data given and explain the reactions, (Note: He ‘Sikes alkenes to alkanes inthe presence of a palladium catalyst) ‘empound DIR: 3200 (broad) em! (OH); #C NMR: 15.2, 20.3, and 36.0 ppm. (three saturated Gs not next to O) and 62.9 p.pam, (saturated C next to 0). Must be n-butanol NaBH reduces the aldehyde to the alcohol and Hy/Pd would reduce the alkene in ether of our OH > NH > CH. Why? Purpose of the problem To encourage you to think about the energies of orbital as well as just about their quantum description. Suggested solution + orbitals and p omits can combine t frm o bonds. Inthe chapter (p. 108) we discussed the structure of PH, which has bond angles of about 90" and is made of bonds beoween Is) and 5p(P)onitals. There sno special problem in overlapping ether 2p or p oxi with Is orbitals though the 3p orbital are larger. a WA ‘The difference comes in the energy of the orbitals. The 2p orbitals are much closer in energy to the 1s orbital than the 3p orbitals and so the energy gain is greater on a bond formation. 2920 is wee otra’ to omar 1840 Sect 180 Bonds between H and C, N, O, and Farell stronger than bonds between H and Si , S, and CL ‘Thisisparly because 2p AOs ate used fr the fist but 3p AOS forthe second group. The ul story Includes the fat that CH, NHs, and H;0 are hybridized (so the lower energy 2s orbitals are used as wall wile PH, and H,S ae not hybridized. Sif, is, ofcourse, tetrahedral whl itis dificlt to ay ‘whether linear HP and HCl are hybridized or not ‘Within the group C, NO, and F, the energy ofthe 1s orbital stays the same but the energy ofthe 2p (or of the sp hybrid orbitals) drops as the elements get more electronegative. These orbitals gt closer in energy tothe 1s obital and the gain in bond formation is corespondingly grater.Chapter 4 Suggested solutions for Chapter 4 Problem 4 ‘Though no helium ‘molecule’ He> exists, an ion Hej does exist. Explain Purpose of the problem To encourage You to think aboot the filing of atonnx orbitals and to accept surprising conchasions. Suggested solution The orbitals of the He atom ans the fact that 0 Hes molecule exists sre diwused in the book an pp. 97-8, The prablen is that the 1s orbitals overlap te form a bonding tc) and an antibonding {e* orbital but hoth would be filled in the Hey molecule and the bond order i 70, If there sone fewer electron, only one cletrom need go into the antibonding order of oneshalf The ion Hey loos exist, orbital (a) and there isa boc Wes Ah emtsoning at He sreoning ot " On 9G +O tenses tb sews Problem 5 You may be surprised to know that the molecule CH, with divalent carbon, can exist tis, of ‘course, very unstable but Its Known and it can have two different stuuctures. One hes an H-G-H bone angle of 180 and the other an angle of 220°. Suggest structures for these species and say which orbitals will be occupeed by all bonding and ronbonding elections, Which structure is likely 0 be move stable? Purpose of the problem To demanstate that a simple MO treatment can be applied to strange and unknown molecules, Suggested solution The hasie arrangements of the orbitals w yet the H80 and 120° bond angles rust be an sp hybridized «case but ust one p wtbital and an sp* orbital in the second. oom for 1900 and am sp? carton for 120 . Thi leaves over two g orbitals im the fies “The orbitals for the @ structuse aze straightforward wg sestamsat tA) 18 There will he fru electrons in cach of these «bonds leaving exited (civalent cazbon has any’ valency eect {wo electsons to make up the six os and cannot achieve « noble pas structre) Inthe 18D case, the two remaining p orbitals are degenerate so we can pu one ebetzon in each, It lhe 120° case, the remaining spt orbital af lower ener ecto than the p orbital and will have bath 19Organic Chemistry Solutions Manual 1m You shoud nate tht onygen hae four 2 eectons ana wil have wo Ione portal an ene each nthe ‘other two fo avis repulsion, PR can, Gores Ay Sieh ta enon p ob Structures with unpaired degenerate electrons ate usually more stable than those with a full and an empty orbital. However, we have told you only part of the story and we shall return to these ‘carbenes” in Chapter 40. Problem 6 ji i “Consiruct an MO Giagfam for ne molecule LiH and suggest what typ of bond & might have. Purpose of the problem ‘To demonstrate that a simple MO treatment can be applied to ionic as well as covalent structures Suggested solution H has, ofcourse, only one electron ina 1s orbital Liha thtee~ a falls shell and one elton in the 2 orbital. Li isalso ver electroposiive so its 2 orbital is hgh in energy (much higher than that ‘of F~ see the answer to Problem 3) The results that lithium gives its 2s electron tothe Is orbital of 1H and an ionic compound results with both ions having the same electron configuration: 1s, The hhydrides of the alkali metals ae useful sources of hydride ion (H). un? 4O- 4O- “OF "Ot Problem 7 Deduice the MOS forthe angen molecule, What is the bond oe in onion and where are “the 2p electrons? Purpose of the problem To let you try out your sil in a simple diatomic molecule that has a curious structure. ‘Suggested solution Simply dock two oxygen atoms side by side and overlap the orbitals. The Is and 2s (only the shown below) interact as usual but both bonding and antibonding MOs are occupied so there is no bonding. When we overlap the parly filed p AOs we find we can make three bonds ~ one 2pcr and ‘two 2pm bonds. Now we have two electrons left over and they have to go into antibonding 2pm” (MO. The first two up are degenerate so itis better {0 put one electon in each and avoid the ‘repulsion from two electrons in the same orbital.Chapter 4 Suggested solutions for Chapter 4 Abin buenos Bie nc ke bya 0 td lw nh ese oped Sree stboig MO. The ek ht ond or snd espace Fees orks aed on oncck O nom Th eed Sues take oa ay wae ines neato, Parpose of the problem = 2ec easy to find molecules where you can construct MOs from AOs without hybridization but s=h v= = one such, You should not be ashamed if you failed to do this problem and you should be sseuily proud if you succeeded. We shall not in general construct MOs in this way a5 it is too ‘Sica bur if you simply set up an energy diagram ofthe AOs, in ascending order as usual, you can ee setstacory MOs. ‘Seggested solution ‘Etre (acctylene) has a C-C triple hond, Each carbon bonds to only two other atoms the other C ‘ax: -=: of the Hs, Using MO theory, we can see that only the carbon 2s and 2p, have the right s=meetr to bind to two atoms at ance which leaves the 2p, and 2p. to form & MOs with the 2 saris on the other carbon atom, —@ fh ot: = {0-Q-O-0 gos 2s 2s ts combination of As in ety tra he rise to bending MOsOrganic Chemistry Solutions Manual ‘The thre lowest orbitals are o MOs because they ae symmetrical about the line H-C-C-H. They are all bonding and al filled but they do not correspond to particular bonds in the molecule. The lowes is bonding right through, the second is bonding for both C-Hs but antibonding for C-C, and the third is ‘again bonding forall three bonds. The two top orbitals are x MOs because they have a node (zero clectron density) passing through the atoms. They are degenerate and correspond roughly to the two (CC mbonds. The total number of electrons (10) is right for $ bonds (2 CHs, 1 6 CC, and 2 x Cs). Purpose of the problem ‘To give you practice in selecting the right hybridization state for carbon atoms in molecules. ‘Suggested solution ‘Simply count the number of « bonds and hybridize that many AOs: if two, then the C atom is sp hybridized (linear; if three, sp* (trigonal); and, if four, sp? (tetrahedral). A simple statement of the answer should be enough. The atoms marked with an arrow are most likely to give you trouble: make sure you understand why they are as shown, oe 4 predet r ee ay te answer tothe Don’ se these sorts of rains in your answer. Purpose of the problem ‘To give you practice in selecting the right hybridization state fr carbon atoms and translating that information ino three-dimensional structures for molecules. Suggested solution ‘Carbon dione is linear as it has only two C-O o bonds and no lone pairs on C. The C atom must bbe p hybridized and the only tick sto get the two x bonds orthogonal to each other. They must be like that because the p orbitals on C involved in the two x bonds are themselves orthogonal (2p, and 2p.). Most people would draw the O atoms as sp* hybridized, rather than sp or even unhybridized, bur this is unimportant as you cant realy tll tetoobonds —— tietwoxbande sifu ge oe |e eco oe=0 = oes ecoChapter 4 Suggestec solutions for Chapter 4 The imine has a C=N double band so it must have sp! hybridized C and N. This means that the Jone pair on Nis in an sp orbital and aot in « p orbital, the molecule is planar (except for the oup which is of cours, tetrahedral) and bent atthe nitrogen ator, 4 wo “nN es so tetrahedral wih an sy! hybridized © atom, The serangement of rhe lone pairs stound the fluorine atoms imor shown! is also probably teteahedra x ‘Thifluoromethane is, of sours ‘he next molecule, CH, C2CH- is alone and it has the same shape as COs and for the same ‘eas, except that ve ean now be sure shat the end carbon atoms are 9p? ybridized as they are slanat. However, the ta planes are arthagonal so the mole as whole is mot planae Finally, (CH:),0 must be a three-membered ring and therefore the C-C-O skeleton of the snolecule must he phinat three paints are always ina planet, However, she two carbon atoms are 1p hybridized (four t bonds) and are approrimately tetrahedral with the H atoms above and below he plane. The oxygen atom might also be sp hybridized, but whe knows?Suggested solutions for Chapter 5 Problem” z een ee Eich of these molecules (s electootlé. loentiy the eletiopnilc, tom ena dana. __ Mechanism for action win a generalized nucleophile Nu”, gir ihe prot in each case. ee a ie 4 oer ese oe Purpose of the problem ‘The recognition of electrophilic sits is half the bale in starting to understand mechanisms. Here is some practice: later you will o this automatically. Suggested solution Here we have two cations, two compounds with x bonds, and two with nothing but & bonds. One ofthe cations has only three bonds to positively charged carbon soit will react by addition of the nucleophile. The other has thre-valent oxygen and so cannot add a nucleophile (four-valent ‘oxygen would have 10 valency electrons and is unknown). The nucleophile must attack the proton instead. Some nucleophiles might attack the carbon atom next to the oxygen “ “ r some — she s r Ys The ro carbonyl compounds will be atacked atthe carbon stom with clesvage of them bond. In general, x bonds are more easly broken than o bonds and negative charges end up on electronegative atoms. If you proposed that each compound reacted further, you were right, but the expected answers do not include these extra steps shovn in square brackets. A full discussion is found in Chapter 12 of the main text. et fe een Pel Ne [oe J - tam A at Re ss LU we ‘The last two molecules are forced to break o bonds. n the case of chlorine, the two ends are the same so you can attack either Cl atom. In MeSCI, the S-Cl bond is weaker than the C-S bond and (Cis the most electrophilic atom in the molecule. The $-Cl bond is broken and the negative charge ends up as chloride ion. oN mi Sel oe worse we,‘Chanter 5 Suaaested solutions for Chaprer 5 | tach of these molecules 1s migopiic, ently the muciopniic stam and craw a ones Tor reaction wih a geneaize lecvonie E, mina product lye Purpose of the problem “The recogion of micleophili sites isthe other half ofthe bt in starting to understand mechanisms. Here is some practic: later you wil do ths too automatically, Reactions occur when the two meet. Suggested solution, ‘This time there are three anions but only two of them (the alkyne and the sulfur anions) have lone pair electrons. We can start our arrows from these and they are the points where the electrophile will atach itself c i fe gt ie a potas Le oh ‘The last anion is like the BH, anion we discussed on p. 125 of the main text. The negative charge does not show a pair of elecizons on Al but just an imbalance of protons and electrons. ll the valency electrons are in the bonds and we must use these o electrons in the reaction. The arrow should stat halfway along the o bond and emerge through the Hf atom. roe ib = TT meoNome - E ‘One nucleophile has a x bond from C to N. The nitrogen atom also has a lone pair of electrons and you could stat your arrow either there or halfway down the t bond ~it doesn't matter which, ae " ner a Me me Me “The ening two nclophies have lone pair One syminetiel(NEy-Ny hyde) and will tack trough one nitrogen stom, You may have drawn the product sa cation or you may Ive removed «proton fom i Eder ane is correc F = Hani, “2 a we ri, | Finally, the phosphorus compound has four atoms with lone pits! There ate three OMe groups and the phosphorus atom il, However the lone parson the oxygen atoms are probably in 2sp* orbitals (and are certainly in some kind of orbital with the principal quantum number 2) while that fon the phosphorus atom is in a 3sp? orbital and is of higher energy. I eats, ae ad 1 Ts pois exred in Craper 7.Organic Chemistry Solutions Manual Purpose of the problem First practice in interpreting curly arrows and drawing the products. Once the arrows are drawn, there is no more scape for decision-making, You must draw the products. Suggested solution Just break the bonds that are being broken and make the bonds that are being formed. sas simple as that, though you might straighten out the products a it so that there aren't any funny angles. Ve 5 Purpose of the problem First practice in considering different posible reactions. One ofthe eatin might seem tivial but itis’ Suggested solution In each case one ofthe electrophilic sites isan acidic proton. There is also an electrophilic x bond in cach case (C=O of C=N+), We might as wel use the same abbreviation (Nu”) for the nucleophile that we used in Problem 1. For the frst case, we draw the two reactions separately Me meme me” MeChapter 5 Suggested solutions for Chapter 5 ‘The last compound also has an electrophilic P atom so there are three possibilities. Don't worry if you missed this last one but phosphorus comes below nitrogen in the periodic table and, unlike 2a ‘am have five & bonds as in PCI “wy mm pm wt Q, Problem 5 ‘Putin the arrows on these structures (which have been drawn with all the atoms in the right lacest) to give the products shown, A508 ‘oD — CKO Purpose of the problem To encourage you to draw arrows for unknown reactions and to show you how easy its Suggested solution ‘you have todo isto see which new bonds are formed and which old bonds are broken and draw “sows out ofthe one into the other. Which way should the arraws go? Take them from an eectron- ==nating atom (an anion in both these examples) towards an electron-accepting atom (O and Br ). In the fist example, a hydrogen atom has moved from the left- tothe righthand molecule 4 this is best shown by an atom-specific arrow. A ow | ee Don't worry if your arrows are not exactly the same as ours ~ as long as they stat and finish in the right place and move the right H atom, they're allright. The notes on the mechanism are for sour guidance ~ you should not usualy include them. The second reaction looks more complicated, but the problem is easier — just move electrons through the molecule, ear 7Organic Chemistry Solutions Manual Eide et ace nese tn wg ma have i ees ‘drawmin a ee a. Purpose of the problem To encourage you to draw arrows for unknown reactions without help. This time you have to decide how to draw the molecules so that reaction can occur. The compounds and the reactions are ‘much simpler than the last set. Suggested solution In the frst example, OH has replaced Br. The reagent NaOH is salt so the reactive species is the hydroxide anion, We can draw the mechanism in one step with HO as a nucleophile displacing stable Br from the organic molecule A» = ape goalie ‘The same reagents are used in the second example with the adltion of EtCH;SH’. This change is ‘obviously important because the product contains this unt rather than OH, We should first drave ‘out this compound and use NaOH as a base to remove a proton from the SH group. The second step is example (a) with a different nucleophile Bie IN A Example (6) uses HBr as the reagent. This isa strong acid with an electrophilic proton. The best nucleophile inthe organic compound isthe oxygen atom so the fist step isa proton transfer and the second step uses the bromide ion, as « nucleophile for the methyl group. Direct attack at O* ‘would give impossible four-valent oxygen. & on RCH SH = =Chapter 5 Suggested solutions for Chapter 5 Purpose of the problem "To develop your arow-drawing cil n a more dificult example. Suggested solution Best to follow the advice given in the hint, First, draw the molecules better. If NaHCO. isa salt we need draw only the anion, 2s the very table Na* won't do anything Ifthe anion is a weak base it can remove only the most acidic proton feom the organic molecule and that ‘must be the CO,H proton. ohhh Now we need to lose one Br atom ~ the one nearer to the benzene ring - and the whole CO ‘group which must falloff as CO,. We start our arrows on the negative charge, form the new x bond, and lose Bras the sable anion.Suggested solutions for Chapter 6 Problem 4 "Draw mechanisms for these reactions. — eo oe i OF Purpose of the problem Rehearsal ofa simple but important mechanism that works for all aldehydes and Ketones. Suggested solution Draw out the BH, or AIH, anion, and the compound if necessary, and transfer the hydride ion. A ‘second protonation step is also needed ~ during the work-up inthe second cas, It is not necessary to draw out the whole metal hydride anion but you must draw out one metal-hydrogen bond es you need to take electrons from that bond. ON = Og Purpose of the problem To get you thinking about equilibria and hence stability of compounds rather than reaction -mechanisms,Chapter 6 Suggested solutions for Chapter 6 34 Suggested solution Hydration isan equilibrium reaction so the mechanism isnot strictly relevant tothe question. If you have drawn the mechanism, you should be proud rather than ashamed because it isan important mechanism. To answer the question we must consider the effect ofthe theee-membered ving. All thre-membered rings are unstable because the ring angles are about 60” instead of the usual angle. Cjclopropanone is very stained because the trigonal (5p?) carbon would lke an angle of 120" and there is‘60" of stan’. Inthe hydrate the trigonal carbon setrahedrl (sp) and theres only 49! of strin'. The hydeat is more stable than the ketone The second casei totally diferent. The hydroxy-aldehyde isnot strained but the hemiacetal has 48° of strain at each corner. Even without strain, hydrates and hemiacetals ae normally less stable than aldehydes or Ketones because one C=O bond is worth more than two C-0 single bonds. In this case the hemiacetal is even less stable because of strain, Problem 3 (One way to make cyanohycrins is ilustrated here. Suggest a detaled mechanism forthe process. meson Purpose of the problem ‘To help you get used to mechanisms involving silicon and to revise an important way to promote Additions to C=O groups Suggested solution The sill eyane isan electrophile while the cyanide ion in the catalyst is a nucleophile. Cyanide adds to the carbonyl group and the oxyanion product is captured by silicon so liberating another cyanide ion for the next cycle. “Den oN en H oN Jo BO ge i Se Problem 4 There ate three possible products from the reduction of this compound with sodium. HW borohydride. What are their structures? How would you distinguish them spectroscopiclly, ‘assuming you can Isolate pure compounds? Purpose of the problem To et you think practically about reactions that may give more than one product Suggested solution The three compounds are easly drawn: one ot ther C=O of both may be reduced, yo eronyhtone aa15 0. Wians ana Fleming (1995), Spectroscopic methods in ‘ganic chemistry (Sted, MeGranis, London, Organic Chemistry Solutions Manual ‘The diol has no C=O group in the ""C NMR or infrared and has a molecular ion in the mass spectrum at two mass units higher than the other two products. Distinguishing them is more tricky. ‘The hydroxy-ketone has a conjugated carbonyl group (about 1680 cm! in the infrared) but the Ihydrony-aldehyde is not conjugated (about 1730 em™* in the infared). The chemical shift of the (C-OH carbon atoms in the 100-150 p.p.m. region will ls be different because the benzene ring is next to this atom in the hydroxy-Ketone. Calculations from tables in Williams and Fleming suggest about 80 ppm. for the hydroxy-ketone and about 60 p.p.m. for the hydroxy-aldehyde, The mass spectra will also be different ~ simple accleavage gives quite diferent fragments Problem 5 ‘The triketone shown here is called ‘ninhysrn’ and is used forthe detection of amino acids. It exists in equeous solution as @ monohydrate, Which of the three ketones Is hydrated and wy? Purpose of the problem ‘To start you thinking about why some carbonyl groups are more stable than others. Suggested solution ‘The two Ketones next to the benzene ring are conjugated with it and thereby stabilized though they ate also destabilized by the mide carbonyl group ~ two electron- withdrawing groups next to each ‘other is bad thing. The central carbonyl group has no stabilization from the benzene ring and a double dose of destabilization from its neighbours. Problem 6 ‘This hydrow-ketone shows no peaks in Is infrared spectrum between 1600 and 1809 em: * ‘butt does show a braad absorption at 3000 to 3400 om”*. Inthe “#C NMR spectrum, there ‘are no peaks above 150 p.p.m. but there is @ peak at 140 p.p-m. Suggest an explanation, Purpose of the problem Revision of Chapter 3 with & reaction from this chapter ‘Suggested solution ‘The evidence shows that there is no carbonyl group in this molecule but that there is an OH group. ‘The peak at 110 prp.m. looks at frst sight ike an alkene but that isnot possible (try to draw any alkene structures and you will see why) so it must be an unuswal saturated carbon atom (pesheps ‘one with two oxygen atoms). You might also argue that an alcohol and a ketone could react to give a hhemiacetal, and that, of course, is what its. The compound exists asthe stable cyclic hemiacetal ~ stable because ofthe ring size, MR heChapter 6 Suggested solutions for Chapter 6 Purpose of the problem ‘To give you practic in seeing the underlying structure of a hemiacetal Suggested solution Each OH group represents a carbonyl group in disguise (marked with a black blob). Just remove the ‘other oxygen atom with whatever i attached to it and you have the two components an alcohol and. an aldehyde or a ketone. The fist example shows how it is done. oaks on es eee ‘The next is similar but the alcohol is from a different molecule, So-7-70 Do not be deceived by the next: itis not symmetical. There is one hemicetal (two oxygens on te same carbon atom) but the other end of the molecule isa simple tertiary alcohol lege Similarly, the last two examples are not quite the same, The first is indeed symmetrical but the second has one oxygen atom in a different position, There is only one hemiscetal34 Organic Chemistry Solutions Manuel Reamer ao ome Bar BR & Oo ree Wan Purpose of the problem To help you detect bad mechanisms and find concealed good ones Suggested solution rere ‘The wrong mechanism, the one the question warns you to avoid, is shown in the margin just to clear the decks. If NaBH, doesn't displace like tis, then what does it do? We know it attacks carbonyl groups to give alcohols and to get trchlorocthanol we should have to reduce chloral and ‘we have chloral hydrate. Hydrates are in equiliorium with their carbonyl compounds, so this isthe “ fenas not deen allel pa pare the adducts ae simple lochs nt wre of Such ping cle onl Sow Purpose of the problem ‘More revision of equilibria to help you develop judgement about stability. Suggested solution “This time we need a mechanism so that we can work out what would be formed, Protonation of the carbonyl group and then nucleophilic addition of chloride ion gives the supposed product. Se — ‘There’s nothing wrong with the mechanism; it’s just that the reaction is an equilibrium that wil run backwards. Hemiacetals are unstable because they decompose back to carbonyl compound and alcohol. Chloride ion is very stable and this reaction will run backwards even ‘more readily.Chapter 6 Suggested solutions for Chapter 6 35 Problem 10, \What would be the products of these reactions? In eacn case give a mechanism to justify your predictions,» nach emer Nabi —-1 ee —+1 40, wet 0 Purpose of the problem “To give you practice in the at of predicting products, more dificult chan simply jusiping a known Suggested solution Each ofthese reactions is straight out of the textbook and each is simple addition tothe carbonyl soup. The ist is cyanohydrin formation and you need to draw out the aldehyde group to make a 00d job of the mechanism. AF" Jost we Ao ‘The second is a standard Grignard reaction and you just need to remember that the aqueous work-up step is not usualy written down but is still needed, e oes y aes ene ing none ‘The only tap isin the reduction of the eylic keto-ester where you need to recall that NaBHy reduces ketones but doesn't reduce esters. Correct identification of functional groups matters. Seu Pe on ath 0 aert. re Problem 44 i “The equilbxium constant Ko, for formation ofthe cyanohycrin of cyciopentanone and HCN is 667, while for butan-2ane and HON it is 28. Explain Purpose of the problem More revision of equilibria this time with some numbers,se 36 Organic Chemistry Solutions Manual ‘Suggested solution ‘We need fist to state the problem in chemistry rather than in writing Oreos ES SS The two Ketones are very similar, the ring being the main diference. The two equilibrium constants ae also very similar as Ke isa simple rato of [eyanohydrin] to [ketone] and is not on a log scale. There is a factor of about 2.5 between the two examples. There is, ofcourse, some strain in the five-membered ring (angle 108°) but only atthe carbonyl group (ideal angle 120°). Replacing ‘the trigonal centre by a tetrahedral centre so thatthe ideal angle (109°) is almost identical to the actual angle is enough to explain this small factor.Suggested solutions for Chapter 7 Problem 4. ‘Xe these molecules conjugated? Explain your ansiner in any reasonable way, My AAR. Purpose of the problem ‘evasion of the basic kinds of conjugation and how to show conjugation with curly arrows. gested solution £5 wo are straightforward with one conjugated system (an enone) in the first example and ‘ame (2 phenyl alkyne) in the second. OF course, the benzene ring is itself conjugated in the ssxoad example. You can show either or both with curly arrows: we have done so for the first exmnple only. The last three compounds obviously form a group with the same skeleton and only the alkene ‘mene around. There i, of course, ester conjugation in all three but this the only kind inthe last ‘sempound. The firs s most conjugated with the lone pair on nitrogen delocalized into the carbonyl pmep. The middle compound just has the alkene and the ester conjugated, This time we have used ‘amcty arrow representations for all three compounds and a dottedline electron distribution smmmnary forthe frst, ae meOrganic Chemistry Solutions Manual Problem 2 raw 2 full orbital diagram for all the bonding and ontibonding * orttals in the three ‘membered cylit cation shown here, The molecule is obviously very strained. Might it survive by also being aromatic? Purpose of the problem Revision of MO diagrams for conjugated systems with aromatic. Suggested solution ‘There are only two electrons inthis simple cation but we need to mix the 2 bond (mand x” orbitals) ‘withthe empty p orbital to gie the MOs, One MO will be bonding all ound the ring and this is the ‘only one that matters to the structure. The others may have given you problems. We can mix the p- ‘AO withthe #-MO as they have the same symmetry in a three-membered ring but we cannot mix P| with 27. So our three MOs are m+ p, x — py and “Se pec oT AC fm RA Hp ‘The cyclic cation is stable and can be made because of the gain in energy in populating only the lowest all-bonding orbital. As it happens ‘sand Ws are degenerate. Ifyou count the number of bonding and antibonding interactions in cach you will see that the net result is one antibonding interaction in both orbitals. I is also aromatic, having 4 + 2 n-electrons where n=0. ‘You get the same result if you mix three p-AOs, one an each carbon atom. Then its easier if we look down on the ting showing the top lobe ofthe p orbital at each atom, The lowest, all-bonding corbizal has no nodes (except the plane of the ring) and the two degenerate, antibonding, and unoccupied orbitals have one node exeh, aChapter 7 Suggested solutions for Chapter 7 Problem 3 How extensive are the conjugated systems in these molecules? OR saptecam arene o fae Purpose of the problem A chance to delve more deeply into what is meant by conjugation. Suggested solution ‘The B-lactam has ewo clearly deined conjugating systems: the amide and the more extended ‘unsaturated acid going right through tothe sulfur atom. These are shoven by culy arrows on the first diagram. These sysems are joined by a single bonds so they really are one system: all the p covbitals on the ringed atoms in the second diagram are more of less parallel and all are conjugated. B OH FE, EG rasliihedtrnoket tie) iipenbinaber wok de oplathgene (yea arrows on the first diggram, Each benzene ring has substituents with lone pairs shown on the second diagram so this molecule has no less than six lone pairs of electrons involved in extended ‘conjugation. There are three separate conjugated systems shown in boxes on the second diagram, moo ome m ‘ome ome ome Problem 4 Draw diagrams to jtustrate the conjugation present in these molecules. You should draw tee ‘ypes of diagram: (a) conjugation arrows to give at least two different ways of representing the ‘molecule joined by the corect ‘reaction’ arrow: (b) a diagram wih dotted ines and partial charges (i any to show the double bond and charge istibution (if any; and (c) 9 diagram of the atomic oritals that make up the lawestenergy bonding molecular orbital. SAECO10 Organic Chemistry Solutions Manual Purpose of the problem ‘A more exacting exploration of the precise details of conjugation. Suggested solution “Treating each molecule separately inthe styles demanded by the question. the first compound is the guanidinium ion, a very stable cation because of conjugation. The curly arzows in the frst set of diagrams show that each nitrogen hasan equal amount of postive charge and thsi reflected in the second diagram showing exactly one-third + on each N. The thd diagram, ofthe lowest-energy ‘MO, looks down on the molecule and shows the top lobe of the p orbital on each atom. cite is its “ee ® Ls ") ee ‘The second molecule is what we shall learn to call an enolate ion. The negative charge is delocalized throughout the conjugated system but is particularly on the two oxygen atoms and, to a lesser extent, ‘onthe central carbon atom. Is dificult to represent this accurately with partial changes but the charge ‘on each oxygen atom is nearly a half. The lowest-energy MO has all the p orbitals in phase ‘The third compound is naphthalene. The structure drawn isthe best; curly arrow diagrams do rot do this molecule justice and other versions are less convincing. In particular, they do not show that the middle bond common to both rings is the shortest bond. There are no charges anywhere and al the p orbitals are conjugated. This isthe basic ten-eleetron aromatic system. 08 -€9-CO OO thy Problem 5 \Which ofthese compounds are aromatic? Justiy your answer with some electron counting. You ‘ate welcome to treat each ring separately or two or more rings togetner, whichever you prefer. SOL ee) th 0 on oH siiaone: 9 wane aeoiote c0s4 of DH ome oR Vetote rg metore “"eetus used te taat aut ciliates ature Newer pmentChapter 7 Suggested solutions for Chapter 7 Purpose of the problem A simple explor Suggested solution “The frst three compounds ae straightforward providing you count lone pair electrons on atoms in the sing and donot count electrons outside the rng such a those in the carbonyl bond in the fst compound. Nor should you count the lone pair represented by the negative charge inthe third ‘compound. They are in an sp? orbital in the plane of the ring. ion ofthe idea of aromaticty: can you count to si? at 2lona pi tcrons arse oof Seine Ue ol. wen poe ‘The rest offer variations on the benzene ring and each ring must be considered separately. Methoxatin has five- and six-membered rings with nitsogen in them. Count the lone pair in @ P orbital on the nitrogen atom in the five-membered ring but not those in an sp! orbital in the six-membered ring (pyridine). Both are aromatic. Colchicine has an aromatic seven-membered ring with six electrons (don’t count the C=O group) while cllstephin has an interesting positively charged aromatic ring with three double bonds, We summarize these answers briefly by giving the ‘umber of electrons in each conjugated ring. 2lone par evens on bon on iainone: 9 teractneaiote1 19 you notice hat on one ‘dium on is necessary ae hee ls ‘ery one sive charge onthe Organic Chemistry Solutions Manual Purpose of the problem To get you thinking sbout the relationship between conjugation and light absorption. Suggested solution Each dyestuif has essentially the same conjugated system shown here isolated from extra substituents. The positive charge is shared between the two nitrogen atoms and the whole system is symmetrical. The colour is due to excitation of the lone pair electrons, which are delocalized over the whole system, into an antibonding x* orbital of the aromatic system. There will be many bonding x orbitals and the same number of antibonding x* orbitals. The lowest (the LUMO) willbe ‘unusually low in energy and the n, x* isin the visible region. me a CT Me ‘The substituent on the middle atom is iffrent inthe wo des and is als conjugating Tis extra conjugation decides the exact shade of colour wth the highly conjugating naphthalene rin in EL42 taking the absorption all the waytheough to red ight so the dye appears green tothe eye. The OH group also helps a lone par isalso conjugated into the aromatic ings. The sulfonate groups make the compound water-solubleChapter 7 Suggested solutions for Chapter 7 43 Purpose of the problem sher thoughts on the relationship between conjugation and light absorption plus revision of Chapter Suggested solution ~e of the dyestuffs in the shaving foam, Fast Green FCF, has a conjugated system very similar to 1 we have just been discussing in Problem 6, though it has extra solubilizing substituents on the Srogen atom, Fast een For eee congo sta ‘Saree cour ans “oso¢ ‘uy in er mv sly ater Quinoline yellow is quite different. It has two conjugated ring systems linked by a single bond. However, they are also linked by conjugation from the OH group in one ring tothe nitrogen atom the other. Infact, the whole molecule is conjugated. Because the conjugation is more limited, this snolecule absorbs violet light and so appears yellow. It has the usual sulfonate solubilizing groups. he ‘quinoline’ part of the name refers to the left-hand ring system. Qunotne tor Fay _/ ? a ‘0,08 ‘Soon ‘The compounds in the ‘spectrum of molecules’ are much simpler and you may well have been surprised after reading Chapter 7 that they are coloured at all ° —~ OOF ent rete uric oto You probably found ‘red’ easiest to deal with as there is an obvious extended conjugation throughout the whole molecule The conjugation in ‘blue is less obvious but clearly more effective blue compound absorbs longer wavelength light than a red compound) and relies on a redistribution of electrons that makes both rings aromatic. This compound is called azulene (an azure alkene) as a blue hydrocarbon is very remarkable.Organic Chemistry Solutions Manual The orange and yellow compounds owe their colour to functionality. ‘Orange’ is a quinone ~ 3 conjugated six-membered ring compound with four electrons — and has a low-energy unoccupied orbital (a x* orbital, the LUMO) from the two conjugated carbonyl groups, which is easily occupied by excitation of a x electron. 'Yellow’ is diazomethane, an unstable toxic and even explosive gas hich has some conjugation in its very small framework but owes its colour mainly to the N=N functionality which again has a low-energy 2” orbital. i\efs 2 8 oH, ae GEN ‘The green compound, delightfully named 9-nitrosojulolidine, has conventional conjugation of an eflicient sort between electton-donating Nand the electron-accepting nitroso group (N=0. Nitroso compounds can be brightly coloured without any conjugation asi the case with ‘purple’. It is very unusual to have blue or purple gases and this compound has a CF; group to stabilize the nitroso group which, when not conjugated, is an odd-electron compound. The colour comes from excitation of a lone pair electron into the N=O antibonding orbital Sean Go through the list of aromatic compounds at the end of the chapter and see how many. ‘electrons there are in the ings taken separately or taken together (if they are fused}. are al the numbers of the (4n ++ 2) kind? Purpose of the problem Revision of material in the chapter explored a litle more deeply to reinforce the concept of aromatic + Suggested solution The fst two compounds are straightforward providing you put lone pais in the right orbital and don’t count C=O groups. Gas Sigmar cee = Me rghctns frnoncangand tener, ios twotrom One par lb ings tage sence noi fe inne ine teen nrg Nain oatsspied ried NaN ofan :0). It the Chapter 7 Suggested solutions for Chapter 7 45 LSD and Omeprazole have in common a fused aromatic ring system with one benzene ring and sme heterocyclic ring. You can think of these as two sx-electron rings sharing two clectons oF as ome ten-cleciron system. Omeprazole has a pyridine ring as well nsgiew 9 enon a maingpeie. rine rng OMe Aa Ea. A Awe me a l mee fi) Ns cae COE Viagra has an ordinary benzene ring and an interesting double heterocyclic ring, You can simply “Sy that there are two fused rings with six electrons eack but a couple of delocalizations show clearly sebich lone pairs can be delocalized and that the resulting system has 10 electrons delocalized round ss rim, The final example, haem, was fully analysed in the chapter as an 18-electron aromaticSuggested solutions for Chapter 8 “Problem 4 It you wanted fo separate a mixture of naphthalene, pyridine, and prtoluc acid, how would you go about it? i oe o. Purpose of the problem Revision of simple acidity and basicity in a practical situation. Suggested solution 1 Thee a contves protien - Pyridine iva weak hase (pK 5.5) and can be dissolved in aqueous acd. p-Toluic acid isa weak acid Jou cannot uaaly separate (PK, about 4.5) and canbe dissolved in agucous base. Naphthalene is neither an acid nora base and eee ‘remains insoluble in water at any pH. So, dissolve the mixture in an organic solvent immiscible with water (say ether, Et:0, or CHsCh) and extract with aqueous acid (pH < 4); this will remove the pyridine as an aqueous solution of its protonated form. Then extract the remaining organic layer with aqueous base (pH > 6) which will extract the p-toluic acd as its anion. You now have three solutions. Braporate the organic solution of naphthalene and recrystllize it to get pure naphthalene. Aci the basic solution of p-toluic acd to precipitate the fce acid and recrysalize it. Finally, add base to the pyridine solution, extract the pyridine with an organic solvent, (say ether, Et,O, or CHCl), evaporate the solvent, and distil the pyridine. Itis just as good to extract with base first and acid second. © Problem 2 ae | in the separation of benzo acid from toluene we suggested using NaQH solution. How concentrated a solution woul bo necessary to ensure thatthe pH was above the OM of boenzoieecid (0K 4.2)? How would you estimate now much solution to Use? Purpose of the problem You can check your understanding ofthe relationship between pH and concentration Suggested solution Even avery weak solution of NaOH will have a pH > 4.2 By te calculation on p. 184 ofthe chapter, fora pH of 5 we should need [Hj0*] = 10° mol dma!, We know thatthe tonic product of waters {H,0"] (OH = 10-and so for pH 5 we need 10-* mol dm! of NaOH. This is very dite! The ‘rouble is that you need one hydroxide ion for every molecule of benzoic acid so if you had, say, 1.22 g PRCOLH (= 0.01 equi) you would need 1000 lies (d=) of your NaOH solution. It makes more sense to have a much more concentrated solution, say, 0.1M. This would give an unnecessarily high pH of 13 but you would need only 100 ml (cm*) to extract your benzoic acid,Chapter 8 Suggested solutions for Chapter 8 4a ° Problem 3 i \Whot species would be present you were to clsole this hyeron-ci na) water at pH (b) aqueous alkali at nH 42; or (c) @ concentrated solution of a mineral acid? Purpose of the problem Revision of simple acidity and basicity requiring pK; values ina practical situation, Suggested solution The COsH group will have a pK; of about 4-5 and the OH group a pK, of about 10. Tis gives a comfortable margin between the two ionization At pH 7 the acid willbe ionized an a pH 12 both cups wl be ionized. In concentrated mineral acid both wil have ther protons and te carboxylic ‘i will sart to be protonated. It is more readily protonated than the isolated OH group as it gives 4 delocalized cation “oh oh Tht Problem 4 ‘What would you expect to be the site of (a) protonation and (b) deprotonation if the compounds below were treated with an appropriate acid or base? In each case suggest & suitable acié or base for both purposes. ee Purpose of the problem Progressing towards more taxing judgements on more interesting molecules, Suggested solution The simple amine, piperidine, will have a normal amine pKus of about 11 so it will be easy £0 protonate with even very weak acids. Any mineral acid like HCl will do as would weaker acids ike RCOzH. Deprotonation will remove the NH proton as nitrogen is more electronegative than carbon but a very strong base such as BuLi wil be needed as the pK, willbe about 30-3. “~ ~ sean aii eae ne hae Qe = 4 ' ‘The next example is more complicated but actually contains 2 normal tertiary amine (pK about 11) and.a normal primary alcohol (pK, about 16). Protonation at nitrogen will occur with any acid = let’s choose TSOH this time ~ and deprotonation will occur at the OH group and will need a strong, base ~ let's say NaH. °°on —O ao we 239 wee Organic Chemistry Solutions Manual The final example isthe most complicated one. There sa normal OH geoup (PK; about 16) and a slightly acidic alkyne (pK, about 32) so the OH willbe deprotonatd frst The basic group isnot a normal amine but an amidine in which the two nitrogen atoms can combine (sc arzows) to capture 2 proton It wll hae a pK, of about 12 and so would even be protonated bya phenol though most chemists would use a carboxylic acd. i ee Stati Problem 5 ‘Suggest what species viould be formed ty each of these combinations of reagents. You ere ‘advised to use pK, values to help you and to beware of some cases where ‘no change’ might be the answer. ase den A. O le Purpose of the problem Learning to compare species of similar acidity or basicity. Suggested solution In each case one of the reagents might take a proton fiom the other. In example (a), would the anion of the phenol remove a proton fom the carboxylic acid? We can answer that by considering pK, values. The answer is yes. There ate five pH unis between the two acids so the equilibrium will be well to the right. The equilibrium constant is about 10°, Tos tear” Prout preavout10 Example (b) has a similar possible reaction. This time the difference is much smaller and the oer way. The carboxylic ac is slighty stronger than protonated imidazole and the equilibrium constant is about 1072, et Sen ww Lee oa seal Example (c) aso involves @ carboxylic acid but this one is rather different. The three fluorine atoms make CFsCO,H a very strong acid, comparable to mineral acids. This equilibrium is well lover to the lel Pk stout 5 pry anauroChapter 8 Suggested solutions for Chapter 8 49 Problem 6 What is the relationship between these two molecules? Discuss the structure ofthe anion ‘hat would be formed by the deprotonation of each compound. Purpose of the problem lp you recognize that conjugation may be at the back of some related stuetures. Suggested solution They are tautomers. They der only in the position of a proton. Each is an acid ~ the frst has an NH ‘poup a part of an amide and the second has an OH group. Deprotonation may at fist appear to ‘reduce two different anions but they are actually the same because of delocalization ofthe anion, 1. =—Qe ike ‘What species would be formed by treating this compound with: (a) one equivalent; b) WO yg, ‘cqulvalents of NaNH2 in quid ammonia? Purpose of the problem 4 simple problem to help you think about the possiblity of selective deprotonation Suggested solution ae more acidic group is the OH (PK; about 16) and the les acidic i the alkyne (PK, about 35). The alkoxide wil be formed first, and then a second deprotonation is posible because the (wo ‘ezative charges are far apart inthe dianion and wil not significantly destabilize each other. Was Sp tly 5p i a i Problem 8 ‘The carbon NMR spectra of these compounds could be run in D0 under the conditions. shown. Why were these conditions necessary and what spectrum would you expect to " dee ‘eepscvum nin 0CY/0;0 $C sesamin NoO0/%0 Purpose of the problem SMR revision and practice at judging the tates of compounds at different pH, Hidden symmetry ‘20m conjugationSuggested solution Both compounds are quite pola an not very soluble inthe usual organic NMR solvents in addition, they have NH or OH protons that exchange and broaden the signals Ifthe exchange is made rapid by acid or base catalysis andthe NHs and OHs exchanged for deuterium, al these problems disappear and clean sharp spect result The ist compound isa guanidine and forms a cation in ai The cation s symmetrical and avery simple spectrum results — just tre types of carbon inthe aromatic region and ne very low feld carbon (at age 6) forthe carbon in the mide of the eatin. 0s 0-0 ‘The second compound loses a proton from the OH group in bas to give a delocalized symmetrical anion. There willbe five signals in the NMR spectrum: the two methyl groups are the same and the two CCH, groups in the ring are equivalent, Thee is one unique carbon atom jained to the two methyl groups and another in the middle of the anion and, finally, the two carbonyl groups are equivalent. Problem 9 "The phenols shown here have approximate pk, values of 4, 7,9, 10, and 44. Suggest with ‘explanations which pK value belongs to which pheno}. cee Purpose of the problem [A problem requiring detailed interpretation of electronic effets. Suggested solution Hlecron-withdrawing groups (Gland even mote so NO,) make phenols more acidic but electron- donating groups (Me) make them less acd. The nito group is very effective if it can stabilize the anion by conjugation. A pk value of about 10 is normal for a phenol, o it is pheno tsef tht has that value. The compound less acidic than phenol (pK, 11) must be the timethyl compound. One chlorine atom will make phenol slightly more acidic 30 pK, 9 must be 3-chlorophenol and the compounds with one nitro group (pK. 7) oF two (PK, 4) must be the very acidic phenols. Problem 10 Discuss the stabilization of the anions formed by the deprotonation of (a) and (b) an the Cation formed bythe protonation of (c). Consider delocalization in general and the possibilty of aromaticty in particular. @ x ird a Chapter 8 Suggested solutions for Chapter 8 Purpose of the problem ‘To get you thinking about delocalized cations and anions. Soggested solution “Fee Js only one remotely acidic proton in (a), the NH proton, Removal of ths gives an anion that “sane delocalized on to all the four nitcogen atoms in the five-membered ring. The combination of © electronegative stoms, 2 delocalized anion, and an aromatic anion (see diagram in margin) srattes this a very stable anion and the original amine is areal acid witha pK, (5) about the same a5 p2 of a carboxylic acid (RCO,HD. CA 22 =O) ‘Tez most acidic proton in (b) is that of the phenol and the anion is delocalized round the ‘Seprene ring, into the fused five-membered ring, and even out onto the ketone axygen atom so its 4 Sol: anion. However, there are only cight delocalized electrons altogether so, although the esse ring remains aromatic, there is no extra stabilizaion from any aromaticity in the “Seocalized five-membered ring or in the system as a whole, It has a pK, value of about 8.5. “OO Gogh nee diamine (c) will be protonated on the trigonal (sp?) nitrogen using the delocalized lone pair “Meera shows both rings as aromatic) as there ae 12 electrons delocalized ~ six foreach ring. The ‘eer asa whole isn't aromatic because is not ane conjugated ring stem. PAR -OVQ- 2-0 ‘Parpose of the problem ‘See. ccvsion in thinking about the acidity and basicity of functional groups ~ amino acids are gretosbely important. ‘Seggred solution “Se world expect the NH; group to have a pyc of about 11 and the SH group a pK, of about 8 so “Se ook sll right. But you would also expect the CO:H group to have a pK, of about 5 and that ‘pets al crong! We need to stat at high pH and work downwards to see what exactly we have by Se Se come to pH 5, This is what happens.Organic Chemistry Solutions Manual wey ova al its “ By the time we want to protonate the COs ion, there is an NH group next door so it will be much more difficult to make the cation and the pX, value is lower because we must go to more acidic solutions to get protonation. The structure ofthe molecule at pHs 1 (cation), 5 (awitterion), 9 (monoanion, that is, dianion and monocation in the sime molectle), and 12 (dianion) is 3s shown. Coe es Purpose of the problem To get you thinking about carbon acids, how their anions are delocalized, and what makes the anions stable. Suggested solution All dhse carbon acids give anions whose negative charge is mainly on oxygen. Similar ones are described in the chapter (Table 82, p. 193) and we expect simple carbonyl compounds to have pK,s of about 15- 20 and 1,3-diearbonyl compounds to have pKys of about 5-15. The first three compounds are all ketones on the lft and have ketone, aldehyde, and ester groups on the right respectively. The charge is ‘delocalized over both cazbonyl groups. The aldehyde is most effective asi isa simple carbonyl group. ‘The Ketone has ¢-conjugation, which reduces the electiveness ofthe carbonyl delocalization, and the «ster is worst asi has competing conjugation from the ester oxygen ator, o 9 0 0° 80 o °0 8 Ad, =A A AL AR aH 4 “ 4 o rib apt os co pp tba a uO electronegative chlorine atom — it isa proton from that side ofthe ketone that is lost. Deloclizing the charge on to the carbon atoms shows this. ° a) ° Ae fe he = é Ss rtp pe ace red ve aa a RG SE and trifluoroacety. Delocalization is very effective and most ofthe negative charge will be on one of the two oxygen atoms. 8 ise. 2 oo 0 of Jobe ick sleetChapter 8 Suggested solutions for Chapter 8 53 Purpose of the problem you thinking about carbon acis, how their anions are delocalized, and what makes the szions sable 1 Note that at no pH dose Suggested solution ‘aan ci ex Be fom wo Tee thre pK, values for glutamic acd itself must be like this (the remote COsH group is normal _fetneen 22 and 42 ts fom 0 {Se che one near the amino group is unusual as we discussed in the answer to Problem 11). eau wth the zwtein ee a poo 9428 mee oar oe eth ont ons ont Ne esanic 8 Ia glutamine, the remote CO:H group is missing and the other two pK; values are hardy ‘Sunged. The dimethyl ster has only the amino group lft and its py value isles beause we ave slaved the wo CO} anions with eleeton-withdrawingester groups. The wo monoesters are most esting. The fis is essentially the same as glutamine ~ the remote ester has tle effect on the ‘ser ovo groups. The second has, a we should expect, a remote COsH group like that of glutaric 2 iselfbut an amino group lice that ofthe diester showing thatthe neaer of the two esgrgroups the diester has the bigger eect 0 Purpose of the problem ‘Ts belp you appreciate the disastrous effects that innocent-looking groups may have because of reir weak acidity. Suggested solution ‘The OH group is the Wicked Witch ofthe Westin this problem, Whoever planned these syntheses -xpected itto lie quitly and do nothing. Bu, although an OH group is only a weak acid (pK, about54 Organic Chemistry Solutions Manual 16) it will give up its proton to the very basic Grignard reagent. Inthe first case, one equivalent of Grignard reagent is destroyed but addition ofa second would save the day. wp nen ee ‘The second case is more serious as the Grignard reagent destroys itself as it s formed with the replacement of Br with H and then nothing can be done to rescue the synthesis. The only answer is to block the OH group with something non-acidic (see Chapter 24). An mgm ok ee ° Net sy SEB mesh 2°, Hao tSuggested solutions for Chapter 9 Problem 4. pose mechanisms for the frst four reactions in the chapter. je obS os Je Pode 2m Heo Purpose of the problem ‘zhearsal of the basic reactions of Chapter 8 Suggested solution A reaction simply involves the nucleophilic attack of the + Ketone followed by protonation. You may draw the intermediate as an anion or with an O-metal 1d as you please. Note the atom-specific arrows t0 show which atom is nucleophilic. Inthe second example the alyslthium might attack through its other end, 0 organometallic reagent on the aldehyde Problem 2 i \When this reaction is caried out with allyl bromide labelled as shown with #20, the label is ‘ound equally distibuted between the ends of the aly system in the product. Expain how this is possible, How would you detect the 1%C distrbution in the product? on Py Em, bs 2. Prono » Be awe FE Fe Purpose of the problem Reminder of the way ally-metals react and revision of NMR.Organic Chemistry Solutions Manual Suggested solution ‘One explanation is that allyl Grignard reagents might reat as nucleophiles at eit system, aay Sahn = = ‘The mechanism given in the chapter (p.224) suggest that allyl Grignards aways reat atthe rem: ced by a oyic mechanism, If that isthe case, the formation ofthe Grignard must occur at both ers os. met mene, ae eee eae y ‘This could occur during the formation by attack of the metal at the other end of the ally: system, of after formation by equilibration with the aly! anion ey ao ad, mat A MM Ay AS Gun = MA In either case the two ally] Grignard reagents would have equal energies and would be forme! = equal amounts. The reaction with benzaldehyde would then follow a cyclic mechanism, end of the ea tis Ts et See ‘Your explanation may not be exactly the same as either of these ~ the only important thing is thet you should have some way of getting the eacton to occur at the other end of the alli system. The '3¢ distribution in the product would be determined by NMR spectra. Each labelled atom woule appear as much stronger signal (the natural abundance of "Cis 1.19) and each signal will be in « different part of the spectrum. The chemical shits are more accurately estimated as 115-120 and 45-50 ppm. Purpose of the problem ‘The toughest test — predicting the product. The sooner you get practice the better.Chapter 9 Suggested solutions for Chapter 9 solution a ‘on harder than explanation, you should get these right frst ime as only the last, ~ «sina I the Bist example, ethyl Grignard reagent acts a a base to remove a ‘Sayne, Whether you draw the inteemediate as an alkyne anion or Grignard reagent 1 you need not necessarily include the mechanism for the protonation step. ee Seo example just make the organometallic compound and ad itt the carbonyl group _ssssess an electrophilic ketone because of the strain of a carbonyl group in a four-membered “Grignard eagent is vinyl and not ally so the ambiguities in Problem 2 donot aise. _ cf- 6 eg ao ‘cumple raises the question of halogen replacement or orholthiation and, if the former, hen bromine is one ofthe halogens, halogen replacements usualy the reaction which + did ortho-lthiation between Cl and Br, you should not be ashamed. be 4 sows [eR “oye “Y fee — o tar i 4 ty l. z ee eee aad Seabee rt ; : (Fee 2 216) : : 4 CL “sree of the problem Ms deere ©znals, you should have measured the J values. Coupling is measured in Hz and at 400 MHz ‘=h chemical shift unit of 1 p.m. is 400 He, so each subunit of 0. p.p-m. is 40 Hz. Out withthe vr the dividers and get measuring! Sm! shi, plum) Inlegation —_ Multipcty CCouping. He Comments = tH m > alkene region = aH wih fine soting 16.3. alkene region — HW doh tne spiting 10.4 akene reson 23 4 twtr ine spiting 65 heat 10 C=0 oF C=C? ae 2 tt fe soiting 6.5 ert © C=0 or C=C? in eT quit tne spiting 6.5 ext 10 0=0 or -07 an 2 oitn ine siting eat a C=0 oF C=C? an aw toad = S alge? = Fy a os Pot nest to arth ‘That gives us three protons inthe alkene region, five CH. groups, and one solitary proton, which <= © only the alkyne proton. Ifyou were surprised by its small chemical shift, check the tables and “5-21 sight. In the alkene region, the multiplet must be H? which couples to the CH at C3 and s-On Cl, H has a large iran coupling (16 Hz) to H? while H has a smaller cis coupling 98 £21, The coupling between H* and H'® is very small Tis suring rau was repo 8. Ant end A Hasenr. Sites 3076, 932. The expected eacton nse the Beckman rearangment (Chapter 37) ta what actly Insppenes was 2 Beckmann ‘ragrontaton (Chair 38) feowes by an nomoleulr Fede tytn (Chester 22), 9 Baorluenge4 Organic Chemistry Solutions Manual (Of the five CH, groups, the quintet at small chemical shift must be at C7. Those at C4, C6, and (C8 have two neighbours and are basically triplets, but that at C3 couples to three protons and must be the quartet at 6 2.32 ppm. Problem 8 A nitration product (CpH::NsO2) ofthis pyicine has been isolated which has 2 nitro (NOs) {g70up somewhere on the molecule. From the 90 MHz *H NMR spectrum, decuce whether the nitro group is (a) on the ring, (b} on the NH ritragen atom, or {c) on the aliphatic side chain land then exactly where iti. Give a full analysis ofthe spectrum, Purpose of the problem a er Ne ee Ne Pe al reasonably easily Suggested solution ‘The tre ype of compound under cansierton eh thee ate some ofthe est ands), ye eee Lear fl ‘Checking the itera wil deal with that problem. ‘The propyl side chain i ill there with a CHy Arplet a CH quintet and a CH; wilt wit a lage chemical shift The broad signal ati 59 ppam.is ‘ppial ofan NH group 50 no reaction has happened ther. The small signal les than a quarter of « proton ~at7.2 ppm, cannot be par ofthe molecule and must be CHI, The remaining signals inthe aromatic region at 63, 8.1, and 9.1 p.pm. must be tree protons on the pyridine ing, The nitro group thas replaced one ofthe orignal four and is somewhere onthe pyridine rng. These are the posits “The most significant feature of the aromatic region is a proton at very large chemical shift (9.1 ppm) with no coupling to speak of (there might be some long-range coupling). This proton has ‘no neighbours and that rules ou the S-ntro and 6 nitro compounds. Ifyou checkin tables you will se that protons an carbons next to strogen (C2 and C6) in peidine have very lage shifts as you would expect fiom thir aldehydelike nature, The nitro group also increases the shifts of protons on neighbouring carbon atoms, The compound must be S-nito andthe spectrum can be assigned like this. “The coupling inthe side chain is all about 7 Hz as expected and that between C3 and C4 in the pyridine ring is somewhat larger also as expected for an aromatic ring. The smaller chemical shift ofChapter 14 Suggested solutions for Chapter 14 15 the proton at C3 occurs because itis not affected by the nit group but it is affected by electron donation fom the amine nitrogen atom. Problem 9 ‘The netural product ullatenone was isolated in the 1950s from a New Zealand myrtle and assigned the structure 9A. Then compound 9A was synthesized and found not to be identical ‘with natural bulatenone. Predict the expected 4H NMR spectum of 9A. Given the full spectroscopic data available nowadays, but notin the 1950s, say why 9A is defnitely wrong, fend suggest a better structure for builatenone. Spectra of bullatenone: “Mass spectrum: m/z 188 (109) (high resolution confirms C,zH:02), 105 (2096), 102 (100%), and 77 (20%), Tnared: 1604 and 1705 em" THEN: ds (p.pim) 145 (6H, 9), 5.82 (1H, 6), 7.35 GH, m), and 7.68 (2H, m). Purpose of the problem Detecting wrong structures i fun and teaches us tobe alert to what the spectra are telling us rather than what we expect. Suggested solution The mass spectrum and infared are all ight for structure 9A but dhe NMR shows at once that bullatenone cannot be 9A. There is indeed s monosubstituted berzene ring (the 2H and 3H signals in the aromatic region confirm this) but the aliphatic protons consist of a 611 signal, almost certainly a CMe; group, and a 1H singlet inthe alkene region at 5.82 p.m. ‘The fagments we have are Ph, carbonyl and CMe, groups and an alkene with one H on it That, ads up to CHO and leaves only one oxygen atom to fit in. There must stil bea ring or else there will be 109 few hyrogen toms and the ring is five-membered (just cy other possiblities yoursel). There ae three bac rings we can choose and each can ave the phenyl group on ether nd ofthe double Bond making six possibile in all ey stogebiteroe ‘The last four ae all esters (ey estes or lactones) and they would ave IR casbony stretches at higher frequency in the 1745-17H0 em” range. The hydrogen on the alkene cannot be on the same carbon atom as the oxygen or it would beat avery lage shift indeed whereas iis coset the ‘norma atkene shift of 5.25 ppm, For 9C we coud estimate 5.25 + 064 ppm. for O, + 0.36 ppm. for Ph, and + 087 ppm. for C=O making 712 ppm. along way fom the observed 5 82 pp Structure 98 is correct and the spectra can be assigned. Compound 98 was synthesized and proved ientical to natural bullatenone. hh a 1 You can 2a the ful toy in W. Panter ota J: Chom, Soc. 1958, 3874: see also T. Resin ‘and P.M. Bel, Acta Chom. Scar, 43977, BuB, 127. Tevanecion Let, 1975, 489%, and RF W Jokson 0d R.A Rape, J Chom Soe omtin Tans 1.1984, 535,78 Organic Chemistry Solutions Manual coe Op 1 Top tip er exams — terete (ata evan ithe examiners ont ‘spectealy ask you to ‘Problem 10 Imei ihe 2H RAM Spectrum (se to. 277 fr he 80 NH NM of he compu n the margin.” j eS Purpose of the problem Further correlation of chemical shift and coupling with interpretation of longer-range coupling Suggested solution ‘The ethyl group is easy to find — atypical SH triplet at 1.2 ppm. and a 2H quaret at 4.3 ppm. — not just an ethyl group but an OFC group to get the age shift for the CH, group. The methyl group is also easy ~ a 3H singlet at 2.6 ppm. typical ofa methyl on an alkene. At the other end of the spectrum te broad signa at 11.0 p.psm. can be only the NH or the OFT ~one exchanges and is not seen, That leaves the three signals inthe aromatic region: 6x (p.pam.) 675 (IH, dd 19, 2H, 7.15 (1H d, 19 He), and 7.48 (1H, d 2 Ha). The larger coupling is atypical ortho and the smaller typical meta coupling so we can assign the whole spectrum, "Problem 14. * Susyest secures for he products ofthese reactions, ierreting te spectroscopic data. You ‘¢ not expected to write mechanisms forthe reactions and you should resist the temptation to "work out what ‘should happen’ rom the reactions. These are all unexpected products. 3 Mads An ein me ‘Aetp.pm.) 179,82, 38,27 ° st sip) 120104 9.387004 9) Beads ser 748,270 Sinpan)203,170,62,982228 pain) 228,941 37 221.0 82408 9.4 200H.6 JT neue se 90 seam) 20,88 22,15, ‘Mopm) 1121645. 280K s,.98.0K8) soc eM 2.10 Purpose of the problem Practice ofa favourite exam question as well as a common sination in red life — you carry outa reaction, isolate the product, and find i's something quite diferent from what you had expected. Wha isiChapter 14. Suggested solutions for Chapter 11 “Sospound A has a carbonyl group (IR) which isan acid derivative (179 ppm. in 8C NMR). The pe "= “aul in the proton NMR must be a tbutyl group and the 3H singlet at 3.67 p.p.m. must be an a a eatin esas os se eh TTL oe “Sesier (1715 + 30 = 1745 cme). ies nS ee res cakes gee af, J y eco pn hn (145 ca 17 ppm bata a rd 718" eM pe Tae ram sous horses om geet br cane a gat 2 nop) (MBG Ca aoicfae pas cere seca nes te ees ey (SMM gs) eo osha pg ty toe ora Cah i a tore inti tc Oona oom We ot or ncn OS AS “ex can only be th carbonyls so this CH, i between the two carbonyl groups and we have the ee Bad free, 2 BRO eee 32 2: ae © empound C has no formula given, just a molecular ion in the mass spectrum. You shoul “scecer why. The most obvious formula is Hey but sulfur is 32 while O is 16 0 two of those “e2e atoms could be one slfr atom. It might be CsHioOS. We must look at the rest of the scars for clarification. There is a carbonyl group (1730 cm™) which isan aldehyde or Ketone ‘BE ppm). The proton NMR shows a CMe: group (6H, 8), methy] group at 2.8 p.p.m. which ==" look like an OMe (expected shift about 3-3.5 pipsm.) but might be an SMe (the carbon ‘germ also suggests SMe rather than OMe at By 45 p.pm.)s and one hydrogen atom at 9.8 ‘525: which looks lke an aldehyde. We know we have these fragments. Me Me L 2.0 RN a) Home vu iw © % not possible to construct a molecule with two extra oxygen atoms but without an OMe S52. One possible structure is shown below but it does not fit the data very well. Other ‘Pasdilies include having a peroxide (O-O) link and are unlikely. ee ees SE ae ‘ound is possible if there isa sulfur atom ~ this is the data much better and i, in 4 the correct answer. It contains a genuine aldehyde (by expected about 10 p.pm.) not a formate feechanoste) ester (5y expected about & p.p.m.; see Problem 1), and $Me is better than OMe for “> ognal at by 28 ppm. and by 45 p.pan. inst 3, Laz.» ne dome S0Ch/EtN ete se ond riper ae a no Mas2P-cHO mes ~ovo i, SMe 1 er ee Be fh73 Organic Chemistry Solutions Manual rely Problem 12 pi Precogene Is # compound the couses insect aide to pupate arden also be found some _ plants (Ageratum sop) where it may act as an insecticide. It was isolated ih minute amounts "and has the following spectroscopic details. Propose a a Ee Spectra of precooene: ‘Mass spectrum: m/z (high resolution gives CzaHia02), M~15 (100%) and M-3O (weak) Inrareé: CH and Singers ony 7H NMR: 3, (B.0.m.) 1.34 (6H, s), 3.80 (3H, s), 3.82 (3H, s), 5.54 (1H, d, J 10 Hz), 6.37 (QH, d, 10 Ho), 642 UH, 5), nd 6.58 AH, 8). a Purpose of the problem Your first attempt at determining the structure of a natural product without any hints — not even & ‘wrong structure. Suggested solution ‘The mass spectrm gives us the formula (C)sHi¢O), which looks ike an aromatic compound as there ae 9 few hydrogens, an the base peak at M ~ 15 suggests that amethy group is lst rather easly. The infrared suggess that all three oxygen atoms are present as ethers. The NMR shows us these details 1.34 (6H, 5): two identical methyl groups, probably CMe. Rather large shift. 380 (3H, s) and 3.82 (3H, s): two different OMe groups. 554 (IH, d, 110 Hz) and 6.37 (1H, d, J10 Hr) two cis protons on an alkene, {6.42 (1H, s) and 6.58 (1H, 5}: two isolated protons on an aromatic ring, probably 14-related as ‘there is no coupling. Rather small shifts — electron-rich ring If allthis is tue, we have these fragments Ma Me rome KO a Y ome ff Y > This adds up 10 CH\4Os, so we have one more oxjgen atom to fit in somewhere, It is very ‘important that you now start to join up these fragments and see what you get. You quickly find that no chains of atoms are possible as there are not then enough substituents to go on the benzene ring (soe the structure in the margin). We must find four substituents for the ring and there are only four other pices to be joined up. The only chain-terminating units are the two OMe groups. The obvious solution is to put the cis double bond in another ring fused on to the benzene ring and hence making two ofthe required four substituents. We can then combine the other groups in various ways such as these ‘The five-membered ring is no good because the coupling constant between the alkene protons ‘would be much smaller than 10. The two six-membered rings are good because they make the benzene ring electron-rich (three OR substituents). The middle structure is not right because theChapter 14. Suggested solutions for Chapter 11 chemical shifts ofthe alkene protons would be very diferent: H* predicted to be about 45 ppm. ‘and H? about 5, 62 ppm, ra eo, " e Moor 1" $ ‘The thied structure (which is the correct one) fits all the data. The two alkene protons are at normal shifs for such protons (estimated from tables in Wiliams and Fleming: 635 p.p.m. for Hand 5.53 p.p.m. for H?), the two OMe groups on the ring are slighty different, and the loss of a ‘methyl group in the mass spectrum is easily explained by removal of an electron from oxygen followed by loss of Me* to form a stable aromatic cation. 15D. 1. Witlans and Reming, Soecvoscon methods inorganic ‘poms (3th ear, MeGrow Hl {London (1996 1 Mere doa of te aiscoven. ‘olga! acy, and stuctural cuciation of seeacore ae gen DW. S. Bowes e a Sence, Peace se OA OL 134,0H,5 Meo” e Meo” ¢ Problem 13 ‘Suggest structures for the products of these reactions, interpreting the spectroscopic data, ‘Though these products, unlike those in Problem 1, are reasonably logical, you wil not meet ‘the mechanisms for the reactions until Chapters 22, 29, and 23, respectively, and you are ‘2evised to sot the structures through the spectra. Bee Beha ke) 148, 1790 ‘do. p) 22, 478, €2, 48, 34.72.18, iam) 1.2 (6) 2.804 17H, 224,24, ITH 4.3. 08,9 1008 0 6.eMOy alo) $730 im) 291 206, 122 190,115,644, 28 yom) 232(0H ak 308 2, JHA, “420(214, 169 697M. 7 9. Tiana, 17 ma, 297 Purpose of the problem Your second attempt at determining the structures of reaction products, now of moderate : sgullibrium is [R'OH|IMeCO,R'] (woHIpMeCO.|*Organic Chemistry Solutions Manual So, if the available concentrations of [R!OH}{R4OH]} are about 25, the ratio of esters must be about 25 the other way with a 25-fold excess of MeCO;R*. The mixture contains about 96% ‘MeCO;R? and about 4% MeCOpR!. This is quite enough to make ester exchange a practical method. Problem 4 _Wte a mechanism for the reaction to give HCI on alumina. You do not seed a orl te (le ote tuna, io Ae he fee cy cnr Purpose of the problem Practice at writing mechanisms of new reactions Suggested solution “The first step must surely be attack of water on one of the very reactive acd chlorides. - ager sre wh < ‘This intermediate, which is half acid and half acid chloride, can now decompose to produce all the products in a step greatly favoured by entropy. Ha, —= Ws co + co + ai® o 7 Propose a mechanism fer tne formation ofthe clazonium sat rete to inthe cha “frst step is be formation of nivous acid HONO. He NaNO, HCL ra OF Purpose of the problem Practice at writing the complicated mechanism of an important reaction that we shall need later. Suggested solution ‘The fist step isthe formation of HONO, we are told, and itis clear that the amine must be @ nucleophile as amines can only play that role. HONO must be the electrophile so we had better ‘combine them to form an N-N bond a that is present in the produc. ooo ot orabe we ial Chapter 13 Suggested solutions for Chapter 13 ‘We need to lose two OH groups ftom this intermediate so we must protonate it on each oxygen ‘224 use the lone pair electrons ftom the nitrogen atom to expel two molecules of water Purpose of the problem lerpretaion of unlikely kinetics in «reaction seated to some in the chapter. Suggested solution "ae hydroxide on must atack the Ketone to form a tetrahedral intermediate, The best leaving ‘evap from this intermediate is the hydroxide ion that has just come in (PK 15) rather than the Syne anion (pKa about 35). I'we use the second hydroxide ion to deprotonate the intermediate ‘fave only one possible leaving group, though itis a bad one, and the decomposition of the 2 must be the rate-determining step. This mechanism is usally found for nucleophilic -etstituton at a carbonyl group with a very bad leaving group such as amide hydrolysis. Som oe EOL ee a The benzoate ion is the product under the reaction conditions but the alkyne anion collects a ‘oton from a water molecule, eenerating the second hydroxide ion, which therefore is a base cory. Purpose of the problem atice at drawing energy profile diagrams as one way to present the energetics of mechanisms: ‘Cigars Carshetny ciation bac, Suggested solution ‘The first thing isto draw the mechanism: this reaction was discussed in Chapter 6 proton transfer between oxygen atoms and is certainly fast. The frst step must be the rat determining step and the intermediate will hve a higher energy than the starting material or t= ‘product asi isan anion. Jn this answer we have used the style of energy profile diagrams used in tee chapter but there is nothing sacred about this ~ any similar diagram is fine. Purpose of the problem Practice at drawing energy profile diagrams to show the relationship between the same reacties different compounds Suggested solution “This is an equilibrium so the mechanism is irrelevant. The two five-membered ings ate both stable than the two three-membered rings but the important thing to express is thatthe =Chapter 13 Suggested solutions for Chapter 13 95 ‘membered cyclic hydrate is es stable than cyclopentanone but the three-membered cyclic hydrate ‘© more stable than cyclopropanone. ‘hate be ta tron oe 5? woud nye ce bis ee 3 Purpose of the problem Sesstice at assessing the likely effect of solvent polarity in terms of the mechanism of reactions Suggested solution, #5 essential first to draw a mechanism for each reaction and to identify the ratedetermining step cach case. The first two reactions are one-step processs so that atleast makes life easier. navel endows Dh catia ‘Now we need to draw the transition state for each reaction so that we can assess whether it is more ‘loss polar than the starting materials. The way to do this is described on p. 318 in the text. par? orbs emit oe ae. ‘othe frst reaction, uncharged starting materials form a partly charged transition sate. A polar xt will sbilize the tanston sate and speed up the reaction. In the second case, a flly ‘Sesed (ewiteroni) starting material gives a partly charged transition tate. A pola solvent will Hc both stating material and tramsiion sat but twill stabilize the starting materials ore ie ergy gap (AGF) will ncease andthe reaction wil go more slowly.Organic Chemistry Solutions Manual ‘The third reaction is different because it has more than one step. tis a carbonyl substitution the kind we met in Chapter 12. The nucleophile (ammonia) attacks the carbonyl group to for » teirahedral intermediate that decomposes with the loss ofthe better leaving group. Sora oR OMe "Nie We have marked two steps fast because they are just proton transfers between nitrogen ‘oxygen atoms. Either of the other two steps might be rate-determining. In this substitution leaving group is relatively good (compare Problem 6) and the rate-determining step is the fis ~ usual one for carbonyl substitutions. In this step, neutral starting materials become 2 cin = (awiterionic) intermediate so the transition state is becoming more charged and the reac: « accelerated by more polar solvents I Problem 10 ‘Comment on the Ukely effect of acid or base on these equilbria, Lape bees Purpose of the problem Practice at assessing the likely effect of acid and base on particular examples of equilibria Suggested solution ‘The first example is an esterification (or lactonzation as the product isa cyclic ester or lactone’ + the forwards direction and an ester hydrolysis in the backwards direction. Ester hydrolysis catalysed by acid or base but esterification by acid only In addition, even a weak base will be enough to urn the starting material into the carboxylate anion, which will nt cyliz. The equilibrium isto the right in acid solution and to the left in basic solution, ‘The second example is the familiar one of cyanobydrin formation from a ketone. The reaction is indeed reversible but in basic solution the cyanide anion is more stable than the oxyanion in the product and the carbonyl group is very table too. In acidic solution (at pHs less than about 12) the ‘oxyanion will be protonated and the reaction driven over to the Problem 14. Elemental sufur normally exists as an eight membered ring (Ss), but itcan also be found in a number of other states. How would entropy and enthalpy affect the equilibrium between sulfur in these two forms? ek so Lohag tt 9 Purpose of the problem eee eeeChapter 13 Suggested solutions for Chapter 13 97 Suggested solution The equilibrium position is determined both by enthalpy and entropy as discussed on p. 312 of the chapter Entropy favours the larger number of molecules as they have greater randomness so heat ‘i drive the equilbsium to the right. Enthalpy will favour the eight-membered ting as it has no cing sttain and so lower temperatutes favour the lefi-hand side. Problem 12 Draw transition states and intermediates for this reaction and fit each on an energy profile diagram, Be careful to distinguish between transition states and intermediates. : ° G 7 Cs °° , ° Purpose of the problem Constructing an enecgy profile diagram for a multistep proces Suggested solution :sta meshanism is essceal, This i quite long job as there are several steps so we must patiently ‘ork our way through them, And no short cuts are allowed! ; Yon Low bon L, on ore. =OS Step 3 must be fast a8 isu proton transfer between oxygen atoans, The decomposition of the hedral intermediate is likely to be fast as the leaving group ‘carboxylate ion, pK about 5) is sash a good ene. The first step, the bimolecular attack of hydroxide on the anhydride, will be the “ate-determining step. We need only drave the structures of the transition states and we can ‘onsiruct our diagram,Suggested solutions for Chapter 14 14 "the gelatin of ne openhaifor of ucose to othe tale cata i be "afgut to work out wriat nas happened. Number the carton atoms in the optichain form ee ee a es carton aon Then ara 9 mechanism fr the eacin: ne Purpose of the problem First trial of a simple method to follow complicated locking reactions plus some revision o: carbonyl addition reactions. Suggested solution Just do what the question says! The starting material is numbered from the aldehyde group. We started numbering the product with Cé as that isthe only CH, group and then followed the earbor chain back to CI which is now the hemiacetal carbon. Q tees wo RSH epee eal eo coats wo"2"on an bn ou Numbering the carbon atoms makes it clear thatthe hydroxyl group on CS has cyclized. To draw ‘the mechanism, we need to redraw the starting material so that the reaction is possible and ti casiest way todo that i to draw it ike the product. Don’t forget to change the thick and thn lines = necessary when you flip a C atom over! ‘The mechanism is just a nucleophilic addition to t= aldehyde as described in Chapter 6 and isthe first step of the reactions in this chapter.Chapter 14 Suggested solutions for Chapter 14 Purpose of the problem see if you can daw mechanisms fortwo of the main types of reactions inthe chapter. ‘Suggested solution “+ MeOH is the solvent and present in large excess, it probably adds fist. This also makes the mediate in the addition of chloride a more stable oxonium ion. This mechanism is very ike ‘+= of acetal formation and, if you added chloride is, that isa good mechanism too. BS Fj Og cond example is imine formation ~ attack by an amine nucleophile and dehydration ofthe “ate, Don't forget to protonate the OF group so that it can leave as a water molecule. lem3 Z "1507 of these molecules is an acetal, that is, a ompounc made from an aldehyde 0 ketone £3 two aleohol groups. Which compounds were used to make these acetals? SE hw Purpose of the problem tice a the recognition of acetals and working out how to make them, Suggested solution 22 we have 1 doi to identify the hidden carbonyl group by loking fr the only carbon atom having ~>C-O bonds. This stom is marked with a lack blob in the answer below. Those ae the bonds nade ng acetal formation so, if we imagine breaking therm, we can se the alcool or dl needed. Ct ore Or Odes GoaOrganic Chemistry Solutions Manual Purpose of the problem Practice at drawing mechanisms for acetal exchange rather than straightforward acetal synthesis Suggested solution In each case the acetal provided reacts with the acid catalyst to create an oxonium jon and ar alcohol. Each has a vital part to play in the rest ofthe reaction. “ome + Moot By the usual acetal mechanism the alcotiol and the ketone combine to form a hemiacetal, which i dehydrated either by acid or by the oxonium ion. If water is lost, i is captured by the oxonium ior and the end result is the same. 8 Mog oH yo pts + meow ss Ay Enough methanol is formed in these eactions to make the final acetal and the water is consumeé in this process to give acetone as the other product. So both Ketones and both acetals are i= equilibrium but the most volatile component is acetone and this is distilled off, driving equilibrium over to the right. ‘The third example is essentially the same except that the reagent is one orthoester and product is another. The volatile by-product is methanol and disilation of this pushes t= ‘equilibrium across. The mechanism is very similar to the first example with the formation = ‘methanol and an oxonium ion starting the process off. Ths time, an oxonium ion must be involr=! in the capture of each alcohol +eChapter 14 Suggested solutions for Chapter 14 ‘The second example is different because no volatile by-product is removed and the position of -guilbrium must represent a genuine difference in stabilities of the two acetals. Some water is seeded as the first acetal must be wholly or partially hydrolysed and the water appears when the ‘ond acetal is formed, The exact details of this mechanism are uncertain but the whole process is ‘scler thermodynamic control: the ketone is more stable than the aldehyde. re es Purpose of the problem ‘Scension of simple acetal chemistry into related reactions with nitrogen. Suggested solution ‘Sith reactions start inthe same way by attack of a nitrogen nucleophile on formaldehyde, Acid “rly is not necessay for this fst step. The ist reaction ends with the formation of an iiniam fon by acid-atalyed loss of water OP a Oe =O OL = Oh In the second reaction a second amino group is wating to capture this intermediate by cyclization form a stable five-membered ring. The stereochemistry does not change but the central bond of “Se molecule has to be rotated through 180° before the cyclization can occur. ae Aisesy tse a wo? “ back into this reactive electrophile 1 give the final preduct. This is loss uf carbonyl oxygen in an unusual setting as the carbonyl group is not ‘here atthe start, a me NN Problem 8 Suggest a detailed mechanism for the acetal exchange used in this chapter to make any ‘acetal of @ ketone from an orthoester. SO te ‘emety orate seh erate Purpose of the problem Seminder of chemistry from this chapter ~ making acetals fom ketones is diffcult~ and drawing “echanism related to, bu diferent from, one in Problem 4 Suggested solution he equilibrium berween a ketone and an alcohol on the one hand and the dimethyl acetal on the ther is unfavourable and must be driven over by devices such as this. The orthoformate is even ore unstable than the acetal (three C-O bonds insiead of tw atthe same carbon atom) and the ster even more stable, because of conjugation, than the Ketone. There are various mechanisms you ight have drawn, which differ only in details such as the order of the steps. Here s one such 4 CR-Cr-Or - CO" Jinn Be LO Oe Se am “The frst line shows the normal mechanism for acetal formation snd points out the by-product, -rolecule of water. This water is consumed in the hydrolysis of the orthoformate (by an acetal =drolysis mechanism) to give a stable ordinary ester. The favourable second equilibrium pulls the ist across to the right.Organic Chemistry Solutions Manual “When we introduced eyelio acetals, we showed you this reaction. : eryco.n m0 me Ga oven orean ) 6 ~ What are te ta functional gouns nt afectedby tis acon? How weuld you hserobse then? Purpose of the problem Revision ofthe different types of acetals and their relative reactivity. Suggested solution ‘This question develops immediately from the last. The noneyclc acetal hydrolyses easily because the equilibrium favours the three molecules (one aldehyde and two alcohols). The two remaining acetals are a cyclic acetal or dioxolane and a cyclic dthioacetal or dithiane. The cyclic acetal just needs more vigorous acidic conditions but the dithiane needs a Lewis acid that likes sulfur, Mercurr ~ Hl) ~ is a good example. The precise reagents and conditions are not important. “anor oe Maone), a a non eta ‘eno “aoe noo Problem 40 eis i Wet would actualy hapoen i you tied io make the unrotected Grignard reagent shown here? Purpose of the problem Revision ofthe danger of mutually destructive functional groups ‘Suggested solution “The Grignard reagent would attack the carbonyl group inthe same molecu or in another molecule with ireversible formation of a carbon-carbon bond. The intramolecular reaction forms a fou membered ring and so may not be favoured. There are other possibilities 100 such as radical reactions (Chapter 39) or polymerization (Chapter 52). = 0 omeous workupoe Chapter 14 Suggested solutions for Chapter 14 tp ease ” is Fad the acetals in celiulose (see the answer below for he structure of cellulose). -2zrpose of the problem ‘iecznder that functional groups are the same no matter how complex the strcture. Acetals can be ete! ‘Sezgested solution “£5 Took for the carbon atoms (marked with a bab) having two C-O single bonds. Problem 12 pat | stable product can be isolated from the fea between bensaideyoe ‘and ammonia _ Sevssedin this chapter, Suggest a mechanism for ts formation. ‘Parpose of the problem "2 on of aminal formation ~ the all-nitrogen version of acetal formation. Sezgested solution “S.ce formation follows its usual course but the imine is unstable and reacts with more benzaldehyde OMto*-ot- or 2£0~ The reaction with benzaldehyde starts normally enough but the oe of the first “seemediate produces a strange looking cation with two adjacent double bonds to the same ‘seezin atom, Since the benzene rings play no part in the reaction, we abbreviate them to ‘Ph’. a ae 4 © aus per wed, I ~ oxen 205Purpose of the problem Extension of acta and aminal formation into examples where the intermediate i trapped by Aitferent nucleophile. Suggested solution ‘The first reaction starts with the usual attack of an aleohol on an aldehyde but the ‘nucleophile isa carboxylic acid. Though a poor nucleophile, itis good enough to react with ‘oxonium ion, especially when the product is eylic. eee ee “The second reaction stats with nucleophilic attack by the amine on the more carbonyl group ~ the Ketone. Ine formation is followed by cyclization and thi second te i ‘normal nudeophili substitution at the carbonyl group ofan exter (Chapter 12). The imine ‘bond moves into the ring to secure conjugation with the ester, 190.5. Fumie ot, voeo's vif 1 ‘ium ion a cere pile that captures the iin ‘and 4 second imine formation completes 3969,» 753. ‘mechanism,Chapter 14 Suggested solutions for Chapter 14 207 Purpose of the problem Extension of the mechanism for acetal formation into dithiacstal(dithiane) formation. Suggested solution. ‘The mechanism is @ direct analogue of acetal formation, The debydeation step is more dificult because the C=5 bond is less stable than the C=O bond hecause overlap of 2p and 3p orbitals is not as good as overlap of orbitals (for example, two 2px) of the same size and energy. BeseSuggested solutions for Chapter 15 j 5 Problem 2. j ‘compound CalsFO has a brood peak in the inrared at about 3100-3400 em-* and the following signals i its (oroton decoupled) “C NMR spectrum. Suggest @ stuctue forthe compound and interpret the soecta i “Bo (ppm) 157,38 (doublet, coupling constant) 229 Hz), 154.24 (single), 116.32 + (Goublet, coupling constant 7-5 Hz), 446.02 (doublet. coupling constant 23.2 Ha) Purpose of the problem Just to remind you thet coupling occurs in carbon spectra too and is useful Suggested solution All the signals are in the sp* region and two (at > 150 p.pm.) are attached to electronegative clements. As the formula is Cy, 2 benzene ring is strongly suggested. The IR peak tells us we have a OH group s0 the compound is one of these. enlaces ‘The symmety of the spectrum (only four signals) suggest the third compound asthe athe two would have six different carbon atoms inthe ring. We can therefore assign the spectrum by saying that the very large coupling (229 Hz) must be a"Jcs andthe zero coupling must be the carbor attached to the OH. The other two signals are the carbons in between and we can assume that, the laegr the coupling, the nearer the carbon isto fluorine. . siesa@sisny oe NST ase sou apse oe ene “Problem 2 Suggest structures forthe products of these reactions. © Compound 28s C:Hi202 and nas R 2725 om * {ip 1.02 (6H, 5), 1.66 (2H, t, 17 HE), 2.59 (2H, t, J7 Ha, anB 3.9 2H, sh ‘Compound 28 has: m/z 149/154 (M’ ratio 3:1}; IR 2250 cm-*, {4 (0-D.m): 2.0 (2H, quintet, J7 Hz), 2.5 (2H, t, 47 Ha), 2.9 (2H, 1,17 Ha), and 4.6 (2H, s)Chapter 18 Suggested solutions for Chapter 15 109 ezpose of the problem “dession of Chapter 11 and the frst example of total structure determination “Sezgested solution “Phe arting material for 2A is CpH:Os and has apparently lost an oxygen atom. As the reagent is 02s, 390%.) “SSE, itis more likely to have gained two hydrogen atoms and lost a water molecule. The IR ‘gem shows « C=O group and suggests an exter oF a stained Ketone. The NMIR shows two t ‘son! CH, groups, one (at 251 ppm.) next ta functional group but not oxygen, so presumably +4°2%.0 . =, ve intact CMe, group, and an isolated CH. group next to oxygen at 3.9 ppm. Theres only astiann “oe Fssonable structure. “Th: mass spectrum of compound 2B shows that thas chlorine in tthe IR shows aN group, | Bp asc) “et “he proton NMR shows eight Hs. If we assume that no C atoms have been lost, the mast ‘sSssble formula is CsHCINS. The compound has lost a water molecule. The proton NMR ‘Sor three linked CH: groups, a quintet in the middle , and two triplets atthe ends. The shifts of Bind cing (25 a 23 ppin) dow hay seas we cial gmp bo wc. 22% ie 2st “Ser és no oxygen in the molecule). This must mean that we have @ units SCHsCHCH,CN. All 2.024, aint) “Set remains is an isolated CH, group with a large shift and the chlorine atom so they must be “sees to S, The large shift (4.9 ppm.) comes from 1.3 + 1 (S) + 2 (Cl) = 45 ppm. Again one “sevcrure emerges. oe Soe Ms=pose of the problem 2 you thinking the other way round — from structure to data, What aze the important pieces of omen? ‘Seggested solution "ip are many acceptable ways in which you could answer this question ranging from choosing Se ome vital statistic for cach pair to analysing all the data for each compound. We'll adopt “=85 way and point out several important distinctions. In te ist example, one main difference is “Sp sie, sen mainly in the IR. Both ae esters (ahout 1745 em") but we should add 30 em”! ‘f % five-membered ring. The functional group next to the OCH: group is different ~ an OH “05p in one case and an ester in the othe. There are other diferences.Organic Chemistry Solutions Manual In the second case there are also differences in the IR C=O stretch between the aldehyde (about 1730 em!) and the conjugated ketone (about 1680 cm!) but the main difference isin the proton NMR. The aldehyde proton and the number of protons next to oxygen make a clear distinction. There will also be differences in the 'H and °C NMR spectra of the benzene rings since one is conjugated with a C=O group and the other is not. The reaction actually gives a z oe aan ee me Problem 4 ‘The following products might possibly be formed from the reaction of MeMgBr with the gyclic anhydride shown. How would you tell the difference between these compounds using IR and "°C NMR spectra? With *H NMR available as well, how would your task be easier? GEG AY tr be Purpose of the problem Farther thinking the other way round — from structure to data. Contrasting the limitations of IR and °C NMR with the data from 'H NMR spectra. Suggested solution ‘The molecular formula ofthe compounds varies so mass spectra would also be useful, but inthe [R the compounds with an OH group vould show a strong broad U-shaped band at above 3000 cm ‘The cyclic ester would have a C=O stretch at about 1775 em”, the ketones a band at abou: 1715 em", and the CO;H group a broad band at about 1715 cm~! as well as avery broad V-shaped ‘band from 2500 to 3800 em", In the C NMR the ester and acid would have @ carbonyl group at about 170-180 ppm. but the ketones would have one at about 200 pp.m. The number and positon of the other signals would also vary Eales ae In the proton NMR, all compounds would show the two linked CH groups a a pair of tiple ‘except in the second compound where they have the same chemical shift and do not couple. AE Ihave a GH singlet, for the CMe: group in all cates except the second where itis the two identical COME groups, The last has an isolated Me group. The OH and CO,H protons might show up as broad signals at any chemical shift.Chapter 45 Suggested solutions for Chapter 15 semeeeetindimteadie <> :oupling to luorine i fine. The carbon NMR shows the carboxylate carbon at 176 p.p.m. « small coupling to F as itis far away and the CH carbon at 86.1 p.p.m. with an enormous it is joined directly to F. But where is the ketone? We should expect it at about ‘pm. but itis at 83.5 p.pam, with the expected intermediate coupling. It cannot be a carbonyl al. So what could have happened in D,O solution? The obvious answer is that a hydrate is 13 (Chapter 6). ane) pci ayhe meme oe nee pect: 182 A Gomdin| aa ee for ‘Seactuce determination of a compound with biological activity isolated from & natural source. ‘Sepgested solution ‘Te solubility and sale formation data suggest the presence of acidic and basic groups, probably 7H and NH; as ths is @ natural compound. Ifo, the #'C peak at 170.2 p.p.m. is the COsH ‘peep. The five carbons in the sp* region and protons at 8.0 and 8.4 pp.m. suggest an ‘=>catic ving. There cannot be just one nitrogen atom as M* is an even number and that looks very like a pyridine ring (typical dy about 7-8 p.p.m. but the N atom will be Scvonated at pH < 1). The two sets of aliphatic protons aze coupled and the large shift ofthe © vgnal at 4.57 p.p.m. suggests proton between CO:H and NH (pH < 1), We have these Segnents112 1a Tre dais ofthe stuctue and spect ate in , inoue eta (hem. Pham. Bil, 1975, 23, ‘2669; S, R. Scho ota, 1. One ‘Chem, 1984, 88,6850; and B. Ye sand. Burke, J. Org. Chom, 43995, 60,2640. Organic Chemistry Solutions Manual Presumably, the aliphatic part must be X or Y and that leaves just one oxygen atom fora forms ‘of CHoN2Os = 182, Only sx ofthe ten H atoms show up in the NMR because the OH, CO-E and NH protons all exchange rapidly at pH < 1 and do not show up. Thee are vatious isome= possible and the compound is actually ‘azatrosine’ though you cannot be expected to deduce ths ‘The second diagram shows the structure in soltion at pH < 1 8 3.02 (24, m) Ho. He ~ em wot oe satin |W Problem 7 Suggest structures for the products of these two reactions. ee. ‘Compound 7A, m/z: 170 (M“, 1%), 84 (77%), and 66 (400%); IR: 1773, 1754 em-*: (ppm; CDCI): 4.82 6H, sand 4.97 (4H, 5). dc (.pm.; CDCIs): 22, 23, 28, 105, and 169 {the signals at 22 and 105 p.p.m, ere weak). ‘Compound 78. m/z: 205 (M' , 40%), 164 (50%), 160 (35%), 106 (100%), and 77 (42%) IR: 41670, 1720 om; Bx (p.p.m.; CDCl: 2.55 (2H, m), 3.74 (4H, t, J6 He), 3.92 2H, m), 7.21 (2H, d, J8 Ha), 7,35 (4H, t, 18 Hz), and 7.62 (2H, d, 18 Hz); bo (9-p.m.; CDC}: 24, 47, 48, 424, 427, 130, 198, 170, and 172 pam. Purpose of the problem ‘The other important kind of structure determination: compound Suggested solution Compound 74 is much the simpler 0 we start with that. The two reagents are CsHsOs 2 HO» which adds up t0 CioHisO¢ oF 230 50 60 has been lst. That looks like C3HjO> oF le likely CsHO (because itis saturated). Ifthe fist is right, 7A is CubfoOe which atleast fis proton NMR, ‘The IR suggests two carbonyl groups, though the !™C NMR suggests one only, but the molec: ‘must have some symmetry as there are only five signals fr eight carbon atoms. The proton N\!= shows a CMe; group and four identieal protons, which ean only be two identical CH, groups. The nly unsaturation isthe two carbonyl groups so the °C signal a 105 p.p.m. is wey strange. hike the signal at 22 pipam, is probably a quaternary carbon as tis weak and it must be next to: oxygen atoms to have such a large shift. Either 22 or 105 p.m. must be C of CMe. The last degrees of unsaturation must be rings. The cyclopropane would supply one ring and the two link== and symmetrical CH groups andthe carbon at 22 p.p.m. would be the atom joining that ring to two carbonyl groups leaving 105 ppm. tobe C of CMes. So we have: Isolated from a chemi 2 196 mt A AK PGChapter 45 Suggested solutions for Chapter 15 ‘Tat actually accounts forall the atoms so 7A must be what you get when you join these two ‘Syprents together. The carbonyls are arranged rather ike those in aeelic anhydride and the two 5 sectches must be the symmetrical and antisyrmmetrical combinations 405 192 (64.8) zaraeyo, 23728 Vv ~ AB Ak 25728 sori) “Sd, ‘Compound 7B has nitrogen in it (odd MW) and clearly has the benzene ring too from the NMR se ws can put down PHN (= 91) as part ofthe structure. Italso has two carbonyl groups (in IR, the ‘9 +t 1670 cm" looks like an amide) and they are both acid derivatives ("°C NMR). There are “Se aliphatic carbons, two CHs and one CH. Adding these together gives us C), HNO: = 188 50 “tes is 17 missing which looks like OH. Since we need a secon acid derivative and the OH is the ‘only remaining heteroatom, it must be a carboxylic acid. Given thatthe CH is a triplet, it must be +2e<:t0 one of the CHas and, a they are both multiplets, they must be joined to each other. There is ‘ace more degree of unsaturation so there isa ring, So we haves ue x { ee Zh OT OM ‘sescrved value of 3.92 p.pum. fits the fist better. A similar estimate for the CH also suggests the ‘Sew structure. This is indeed the correct answer. ‘n/a: 281 (60%) 90 400%), 691629) jes (il a9 Ho, 734 GH, 9) oe ie COLIg 62: 64, 222, 429, 126, 127,4 Purpose of the problem Perther practice at structure determination, adding ideas ofthe size ofthe coupling constant, 18 See 5, Daisetsty ant RK Singh, J. Am. Chem. Soe, 1975.97, 3258. 15 From now on. axing estabishs the general method and apoe2ch, we shal simply ge the ansners wn ary special pins apoing to ‘he question under seuss.‘Suggested solution “The compound 1 ai epoxide: th Coupling cooks ‘aftind th’ vng an! mall (Hz, cone 10 Ha in the benzene ring) because of rng size and the electronegative oxen atom, Al the Hs ‘the Ph group happen to come at the same sh but those in the nitrated ing are at ower Beld and separated bythe NO; group. | aaa Organic Chemistry Solutions Manual | | areas | | ae ase \ l : é 4 fe along 4 7ai(shs~ se0aHe TS4AKe ra < ‘, é Purpose of the problem ~ Further practice at structure determination, adding a carious chemical shi Suggested solution im See A Eschenmoser 94 8049, The compound is an alkyne formed by the Eschenmoser fragmentation (Chapter 38). It is ne= Heme Ci Aes 29744 Ar 2828. be o assign all the °C NMR with certainty but the alkyne Cs come in the region 70-85 pp. safes eran pete os ae Seat Wein soare 2115 (6-C ston (od aut) eae 298,48) | Purpose of the problem Further practice at structure determination including a change in the carbon skeleton ~ a ries contraction,Chapter 15 Suggested solutions for Chapter 15 335 Suggested solution Te compound isa simple eyclopentensl, The ®C NMR assignment is not all certain 18.6, Magnusson ana 8. Trt 4.018. Chem. 1973, 38, 1380. Wo Seno. ereahy — SatHs) Problem 44. Female boll weevils (2 cotton pest) produce two Isomeric compounds that aggregate the ‘rales for food and sex. A few mg of two isomeric active compounds, gandiso! end Zochtodencl, were ‘isolated trom 4.5 milin insects. Suggest structures for these compounds from the spectroscopic data below. Signels marked * exchange with D2O. ZOchtodenol. m/z: 154 (CyoHsa0), 139, 136, 121, 107, 69 (100%, Sax {om}; 3350, 1660. 5a (p-p.m: 0.89 (6H, s), 1.351.70 (4H, broad m), 1.41 (14, s"), 1.96 (2H, s), 2.06 (2H, t, 16 He), 4.44 (2H, d, 17 Ha), and 5.48 (1H, t, J7 Ha). Grandisol. m/z: 184 (CioHix0), 199, 136, 121, 109, 68 (100%). nx (om-*; 3630, 32503550, and 1642. 34 (o.p.m)}: 1.15 (BH, 8), 1.42 (AM, ddd, J 1.2, 6.2, 9.4, 13.4 Hz), 1.95.45 (1H, m), 1,551.67 (2H, m), 2.65 (SH, s). 1.70.84 (2H, m), 1.94.99 (4H, m), 2.52" (4H, broadt, J 9.0 Hz), 3.68 (1H, ddd, J5.6, 9.4, 10.2 Hz), 3.66 (1H, ddd, J6.2, 9.4, 10.2 Hr), 4.62 (28, road §), and 4.81 (2H, broads) 4 (ppm): 19.1, 23.4, 28.3, 29.2, 96.8, 41.2, 52.4, 59.8, 109.6, and 145.1 Purpose of the problem ther practice at struct determination of natural products wit al the data properly presented. Suggested solution structures are shown below. 18 J.M-Tumingon otal, Setnce, 1960, 266, 10:0, but soe K. Mot 3 at at Li's donate, 1969, 909 low forthe spect of eenadenet snd osm pret inate a, Bu Crem. So. phe Jn, 3991. 68,1871 forte ty secre of ganden Problem 12 Suggest structures for the products of these reactions. ° BA A.meP-et_ Aven it LI ae Ae Ser Data for compound 12h: CyoHs30P, IR (em-4): 1610, 1235; dy (p.p-m.): 6.57.5 (SH, m), 6.42 (AM, t, J27 Ha), 7.47 (AH, dd, J47, 23 Hz), and 2.43 (6H, d, J 25 Hz). Data for compound 128: Cs2HseOz: IR: CH and fingerprint ony; 8y (ppm): 7.25 (BH, 8) 4.28 (1M, d, J4.8 Ha), 3.91 (1H, d, J 4.8 H), 2.96 (3H, s), 1.26 (BH, 5), and 0.76 (3H, 5)Organic Chemistry Solutions Manual 1 S00 F. Nrdol et al, Tetrahedron tet, 1968, 5751. ae Purpose of the problem ‘Structure determination of reaction products by proton NMR alone with extra twists ~ an elemen: with spin (P) and protons on the same carbon atom that are different in the NMR. Suggested solution ‘The coupling constants Jp) across the double bond in 124 are very large. Typically is Jp shout 20 Hz and rns "J is about 40 Hz, Geminal Fp) coupling constants are also large bs ‘mote vatable. In 128 thee is a stereogenic centre so that the hydrogen atoms and methyl groups = te rng ae either onthe same side as MeO or the same side as Ph, They are diastereotopic with different chemical shifts and the Hs couple 7). We cannot say which is which 0? -sy--— zara, °. eee Pty neste amor — 243.9)-~ mee as nt 05-75 64m) @ W428 046 148) aoa gf -MSotCNe 148) Mo l Pa sana ie 276,48) Problem 43 Identity the compounds pracuced in these reactions. Warning! Do not attempt to deduce the ‘structures from the starting materials but use the datal These molecules are so smal that you can identity them from *H NMR alone. Oe hog tt te = Data for compound 13A (C,He): 54 (p.p.m.): 5.35 (2H, 8) and 1.00 (4H, s) Data for compound 138 (C Ch Gly aC a a Ce a = = OO == OL eats oS The trina ps pe 1) qu ag Te | leaving groups (HO™ and MeO) are about equally good but the formation ofthe carboxylate anion tunder the reaction conditions drives the equilibrium to the right. one mas ool =O0y- = eaten ‘or these reactions, commeriing on the choice of sates and solvents. How woul you Ha cicra Couey? Purpose of the problem Dravwing mechanisms for uscful substitutions and extending the saquence by other reactionsChapter 47 Suggested solutions for Chapter 17 ‘Suggested solution “Se at standard Sy2 reactions at primary carbon atoms. Inthe first case, the OH group has to be ced into a good leaving group. We show one reaction of each kind, though actually everything ‘pens twice. The dinitrile is converted into the diester by treatment with ethanol in acid solution; se Problem 9 in Chapter 12. Problem 6 as eS ‘raw mechanisms fr tese reactions and describe the echo o tho pec Purpose of the problem esving mechanisms for two types of substtmions in the same sequence to make a useful ioreule, Suggested solution The two reactions are an Sy2 at primary carbon and a nucleophilic substitution at the carbonyl ‘ae-9 with the amino group as the nucleophile in both cases. Substitution atthe carbony! group ‘=>bably happens first. Don't worry if you didn't draw the deprotonation of the amide and the $2 22ck of nitrogen exactly as we di The stereochemistry ofthe product isthe same as that ofthe fearing material (CO;Et group up) as no change has occurred atthe chiral centre, Purpose of the problem Aevsion of Chapter 2 and practice at drawing mechanisms of nonstandard reactions.Organic Chemistry Solutions Manual Suggested solution First draw good diagrams ofthe molecules as the question a; Me sens oe ae — ye I. at oe vi babs roto bs bolt nadie ad eephg a we sl happens when we unite them. The nitrogen atom is obviously the aucleoptile and one of Se carbony groups ofthe anhydride must be the elctrophile as nitrogen is Bonded to an acetyl = in one of the products. ‘We must lose @ -butyl group from this intermediate to give one ofthe products and unit: = the acetate anion to give the other. This must be an Sy rather than an Sy2 reaction at © Purpose of the problem Revision of stereochemistry from Chapter 16 and practice at applying i to substitution Suggested solution ‘The two sides ofthe epoxide in example (a) ate the same as the molecule has a plane of =) ‘Attack at cither side by the Sy2 mechanism must occur from the bottom face ofthe that inversion occurs, The product is a single diastereoisomer but cannot, of co=ne ‘The stereochemistry ofthe starting material in (b) was discussed in the soln = (Chapter 16. The starting material has a plane of symmetry but is a single diaste-=0iseme= centres are inverted during the double displacement by sulfur. You must be Jem =Chapter 47 Suggested solutions for Chapter 17 133 ‘sereochemistry right when twisting the molecule round to draw it as a sing, The product is a single Bastereoisomer but is not chiral. Problem 9. ‘What are the mechanisms ofthese reactions, and what is the role ofthe ZnCl, in the frst step and the Nal in the second? cl alo = soy ee h(n 6 Purpose of the problem Exploration of the roles of two different kinds of catalysts in substitution reactions. Suggested solution The ZnCl, acts as a Lewis acid and can be used either to remove chloride from MeCOCI or to ‘complex wit its carbonyl oxygen atom, in either case making ita better electrophile so that it can smzuck the unreactive oxygen atom of the cylic ether. Ring cleavage by chloride follows. ° Gj a yO a. o. eee LO ay YO. 18 You can read more about is in The second reaction is an $2 displacement ofa reasoneble leaving group (chloride) by a rather 8.5. rumise et at, Vogel's ebook ‘weak nucleophile (acetate). The reaction is very slow unless catalysed by iodide ~ a better of ogni chemist (nec, amaceophile than acetate and a better leaving group than chloride. It isa nucleophilic catalyst. Lone™ans, Haxow, 1989p. 492 Brn ey yey Problem 10. t oe ‘escrb the sterecchemisty ofthe produts ofthese reactions. el wt =oOrganic Chemistry Solutions Manual Purpose of the problem Time for nucleophilic substitution and stereochemistry again with afew exta twists this tard Suggested solution ‘The ester in the fist example is removed by reduction, leaving an oxyanion that cycizes intramolecular Sy2 reaction with inversion of configuration giving a ci-fused product. Gon CBO ‘The second case involves an intramolecular Sy2 reaction by a sulfur anion on one end of he epoxide. The reaction occurs stereospecitically with inversion and so one enantiomer of ca diastereoisomer of the product is formed. Some redrawing is needed and we have kept the epaxide ofthe starting material in its original postion to avoid mistakes, Purpose of the problem ‘Trying out substitution reactions in synthesis. Suggested solution Sequence (a) starts with a displacement of the carboxylate anion followed by acid-catalr Ihydrolysis of the nitrile to give the second carboxylic aci, Full details of the second step Chapter 12 (p. 294). (vm a ws OS OC - OCF Reaction (b) starts with two consecutive Sy2 reactions of the amine on the epoxide. At that p: there are no more NH protons to be replaced. The diol intermediate cyelizes by an intramolecd ‘Sq2 reaction with one of the primary alcohols displacing the other after protonation.Chapter 17 Suggested solutions for Chapter 17 Problem 12 ate with reasons whether these reactions wil be either Syd oF Sy2. mye 2 at so oY = oF Purpose of the problem examples of choice between our two main mechanisms with (c) and (A) difering only in Scegested solution =nple (a offers a choice between an Sy2 reaction ata tertiary carbon atom or an Syl reaction next 0 Sonyl group. In fact, thes ae about the only known examples of Ss2 reations at tertiary carbon cerk because the carbonyl group aeeerates $2 reactions so much The diagram ofthe transition ‘shows how the p orbitals on the carbonyl group are parallel tothe p orbital n the Sy2 transition SS. Auide is also an excellent nucleophile being sharp and nacrow and not afected much by steric “ance. We know the reaction is Sx2 because we find inversion of configuration. ap Ht | “ES es) o is = the chemistry described in Chapter 14 and particularly with Problems 4 and 8 atthe end of that ser. The replacement of OMe by the primary OH isa nucleophilic substitution at saturated carbon «goes by the Sx] route because ofthe caion-sabilzing effect ofthe other two oxygen atoms. amples (c) and (d) add the same group (PrO) tothe same starting material (an epoxide) under © =zrent conditions. We can tel that (c) must be Sx because the nucleophile has added to the rv rather than the secondary end ofthe epoxide and that (d) must be Sx2 because of the reverse -clectvity. Acid catalysis makes Sy better by improving the leaving group and base catalysis, 5x2 better by improving the mucleophile. Notice that inversion of configuration occurs in + reactions. This is expected in Sy2 and may be the case in Sy1 because the underside of theSuggested solutions for Chapter 18 j 8 Problem 1. Ident the char of boat sbomemaerd rings nthe following sttures and say why that particular shape is adopted. Purpose of the problem Simple examples of chair and boat forms. Suggested solution ‘The first three are relatively simple ‘oa roca maa eaistra! (ho mpsesoie ene ‘The next two have several rings each, all boat i the first. We'll link that to the sixth molecule as also has a boat and neither of these cage structures has any choice. ‘The rings are all chairs in the fifth molecule adamantane — a tiny fragment of a diamon? ‘molecule. ‘The rings don't all look very chair-like in these diagrams - making a model o= adamantane isthe only way to appreciate this beautiful and symmetrical structure and to see all the BHD Problem 2 i Draw lear confrinaina! see te these molecules, tepelng each salient as axialChapter 18 Suggested solutions for Chapter 18 137 ‘Purpose of the problem ‘Seep practic at drawing chair cyelohexanes with axial and equatorial substituents. ‘Segzested solution Bee drawings may look different from ours but make sure the rings have parallel sides and don't ‘Mew upstairs. Make sure that the axil bonds ae vertical ané the equatorial bonds paalle! tothe ‘m= ring bond-but-one. The first molecule has a fee choice soit puts both substituents equatorial. “Whe as Geo molecules are dominated by the Futyl groups, which insist on being equatorial Re eR oases tot oo! Problem 3 ‘Would the substituents in these molecules be axial or equatorial or a mixture of the two? eee *-pose of the problem practice at drawing chair cylohexanes and deciding whether the substituents are axial or sorul, Remember to decide by drawing and not by some memory trick like trans means “scvorial’ or any such nonsense Seszested solution <4 se molecules have a fiee choice asthe substitutents aren't large and are about the same sie. ‘oc: that trans means diequatorial in two cases and axiallequatorial in the third. Sei ost ag so80 = oH iat extort Problem 4 “sis it alificult for cyciohexy bromide to undergo an E2 reaction? When its treated with 23e, it does undergo an £2 reaction to glve cyclohexene, What conformational changes, '~st occur during this reaction?Organic Chemistry Solutions Manual Suggested solution CCyclohexyi bromide has the chair conformation with the bromine atom equatorial. It cannot do an E2 reaction (Chapter 19) in this conformation as £2 require the reacting C-H and C-Br bonds to be anti- periplanar. This can be achieved ifthe molecule first fips to an unfavourable axial conformation. y Sa ae Problem 5 A he “TWeetment ofthis aketosiconl win base cess an elimination feecton. Wnts the Apeeheriem, end | which conformation must the molecule adont for oe eeah enue Purpose of the problem Exploration of the relationship between conformation and mechanism in ales simple example. Suggested solution Since this is a multistep mechanism, it is best to draw the mechanism first before considering conformation. In the deprotonation step, the axial proton will be lost, though this doesn't affect the conformation ofthe molecule. Inthe elimination step the OH group enust be axial 0 that the C=O ‘bond is paral! tothe p orbitals inthe system. The molecule isa ci-decaln soit as a choice of conformations. Don’t be disheartened if you got the wrong conformation first time ~ we took several tries before geting it right 0,