Csir Net Gate Advanced Organic Chemistry PDF

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ADICHEMISTRY
SOLVED PROBLEMS IN ADVANCED ORGANIC SYNTHESIS
(FOR CSIR NET & GATE)
1st EDITION
(First released on: 7th, May 2012)
Last updated on: 13th February 2016

Updates & online help through forums are only available to those who purchased this book from the author at http://www.adichemistry.com/
No. of problems solved: 226

No. of pages: 203 (This number may vary depending on the way this file is compiled)
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This book is intended for the aspirants of CSIR NET, SLET, SET, GATE, IISc and other University
entrance exams. Most of the advanced level problems in organic synthesis from previous year question
papers are solved and are thoroughly explained with mechanisms.
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It is a dynamic on-line version; updated frequently.
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:
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wholly unreliable.
Problem 1.1 (IISc 2011)

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O
i) PhMgBr
?
O ii) H+
a) Ph b) Ph c) Ph d) Ph
O O O OH
Answer: c
2
Explanation
O
O
1,2 addition of Grignard reagent
i) PhMgBr
om
BrMgO Ph
.c
O
ii) H+
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+
H
:
HO Ph
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ist
:
O acid catalysed and conjugate

 bond assisted removal of
:
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-H2O OH group
Ph
:
H O H
:
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+
O
/ / w Ad
-EtOH final removal step of EtOH

-H+
V.
Ph
O
:
tp
ht
Think different:
What will happen if 1,4 addition occurs?
O OH O O
H+
i) PhMgBr
Ph Ph
+ -EtOH
ii) H O O Ph
O
1, 4 - addtion of PhMgBr
Same product! So it might be the actual mechanism? But slim chances. Why? The possible explanation
might go like this:
i) the positive charge on 4th position is diminished due to contribution of p-electrons of adjacent ethoxy
‘O’ through conjugation (+M effect).
3
ii) The enolate ion form is less stable due to -I effect of ‘O’.
iii) We also know that: 1,2 addition is kinetically more favorable than 1,4-addition in case of Grignard
reagents. It is because the R group attached to Mg in GR is a hard nucleophile and prefers carbonyl
carbon with considerable positive charge (hard electrophile).
And if this is the mechanism, the removal of ethanol may give another product, though less likely, as
shown below.
O
Ph
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Now start arguing!
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Web Resource:
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http://www.adichemistry.com/organic/organicreagents/grignard/grignard-reagent-reaction-1.html
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ist
Problem 1.2
The most appropriate set of reagents for carrying out the following conversion is:
O Cl OH
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a) i) EtMgBr; ii) HCl b) i) (C2H5)2CuLi; ii) HCl
c) i) C2H5Li; ii) HCl d) i) HCl; ii) EtMgBr
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Answer: d
/ / w Ad
Explanation:
1,4-addition of HCl furnishes 4-chlorobutanone, which reacts with Grignard reagent to get the desired
product.
V.
H+
O HCl Cl O EtMgBr H3O+
Cl OH
:
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Cl- mechanism
OH Cl OH
ht
H2C
However, the yields may not be satisfactory due to side reaction that is possible in the second step
with Grignard reagent. It may undergo Wurtz like coupling reaction with -CH2Cl group.
Cl O EtMgBr O
MgBrCl
What about other options?
Option - a :
4
major product
O EtMgBr H3O+ OH HCl Cl Cl
H+
Cl-
-H2O Cl-
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* 1,2-addition occurs with Grignard reagent, since the ethyl group attached to Mg has considerable
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positive charge and is a hard nucleophile. It prefers to attack 2nd carbon (hard electrophile).
* In the reaction of allylic alcohol with HCl, the Cl- prefers to attack the allylic carbocation from less
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hindered end. Hence the major product is 1-chloro-3-methyl-2-pentene.
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Option - b
O Et2CuLi H3O+ O HCl
Expecting aldol reaction
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1,4-addition occurs with Lithium diethyl cuprate, since ethyl group attached to copper is a soft
nucleophile and prefers carbon at 4th position (soft electrophile).
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Option-c :
The products are same as in case of option-a. Ethyl lithium also shows 1,2 addition like Grignard
reagent.
/ / w Ad
Problem 1.3 (CSIR DEC 2011)

Choose the correct option for M & N formed in reactions sequence given below.
V.
O 1) BH3.SMe2
1) PhMgBr 2) PCC
M N
2) TsOH 3) mCPBA
:
tp
Ph Ph HO Ph Ph
O
ht
a) M= N= O b) M= N=
O O
Ph Ph Ph Ph
O
c) M= N= O d) M= N=
Answer: a
Explanation:
* A tertiary alcohol is formed upon 1,2 addition of PhMgBr and is dehydrated in presence of Tosylic
acid.
5
O HO Ph Ph
+
PhMgBr H3O TsOH
-H2O
* Thus formed product is subjected to hydroboration with BH3.Me2S complex to yield 2-

phenylcyclohexanol, an anti-Markonikov’s product, which is oxidized to a ketone in presence of PCC.
The keto compound is subjected to Baeyer Villiger oxidation with mCPBA to get a lactone. The
PhCH- group is migrated onto oxygen in preference to CH2 group.
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Baeyer Villger
Ph Ph Ph oxidation Ph
BH3.SMe2 OH PCC O O
mCPBA
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O
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Anti Markonikov's Ph-CH- group has more
product migratory aptitude than
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CH2 group
ist
Problem 1.4 (CSIR JUNE 2011)
The major product formed in the following transformation is:
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O
1) MeMgCl, CuCl
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2) Cl
Ph
O
/ / w Ad
O O O
a) b) c) d)
Ph Ph Ph
V.
Ph
Answer: d
Explanation:
* The Grignard reagent reacts with CuCl to give Me2CuMgCl, an organocopper compound also
known as Gilman reagent that is added to the -unsaturated ketone in 1,4-manner.
:
Initially copper associates with the double bond to give a complex, which then undergoes oxidative
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addition followed by reductive elimination.

Thus formed enolate ion acts as a nucleophile and substitutes the Cl group of allyl chloride.
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The attack on allyl chloride is done from the opposite side of more bulky phenyl group.
2 MeMgCl + CuCl Me2CuMgCl + MgCl2
6
Me Me Me Me
O
MgCl
Cu Cu
Me2CuMgCl - +
O O O MgCl
Ph Ph Ph Ph
1,4-addition
-
-Cl
Cl +
CH2
om
+ Me
Me MgCl - +
Attack of allyl cation O MgCl
from sterically less - O
CH
hindered side. Ph
Ph
.c
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O
Me
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O
Ph Ph
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Why 1,4-addition occurs with Gilman reagent?
The methyl group on copper is a softer nucleophile and hence prefers softer electrophile. The carbon
at 4th position is less polar and hence is a softer electrophile. That is why the attack of Me group occurs
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at 4th position.
Whereas the carbonyl carbon is more polar and a hard electrophile.
/ / w Ad
Note: The atoms with more polarity i.e., high charge are harder.
V.
Why not the O- end of the enolate ion forms bond with allyl group?
The very polar O- end is a hard nucleophile whereas the CH- end is a softer nucleophile. The allyl
group with positive charge on carbon is also a softer electrophile and hence the bond is formed
preferentially between the C-end of enolate and allyl group.
Problem 1.5 (CSIR OLD MODEL PAPER)

:
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The major product formed in the reaction, given below, is

CN 1. EtMgBr
ht
2. H3O+
O CN
1) CHO 2) 3) NH2 4)
Explanation:
7
 -
C N -  H+ H HOH
Et-MgBr N N O
MgBr HOH -NH3
An imine salt complex imine
Problem 1.7 (GATE 1991)

Predict the major product in the following reaction.
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O i) CH MgBr
3
ii) H3O+
.c
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Explanation:
* The product mixture contains both axial and equatorial alcohols in equal proportions. There is no
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ist
diastereoselectivity observed during this addition reaction due to steric and stereoelectronic effects
operating equally.
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CH3
axial  
attack CH3MgBr OH 51%
O H3O+
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+
equatorial HO
/ / w Ad
attack
CH3 49%
V.
* When steric factor alone is considered, the moderately bulkier methylmagnesium bromide (GR) prefers
to attack the cyclohexane ring from the convex side i.e. equatorial.
However this steric factor is cancelled out by stereoelectronic effect which favors axial attack of GR.The
stereoelectronic effect can be explained by relatively stronger hyperconjugative interaction between -
MO of incipient CH 3-C bond and *-MO of axial C-H bond on the adjacent carbon during late transition
:
state when the GR approaches axially.

tp
ht
MgBr
H3C
-MO of incipient CH3-C bond
O Relatively stronger hyperconjugative
C interaction between -MO of incipient
CH3-C bond and *-MO axial C-H bond
*-MO of axial C-H bond during axial attack.
H
Hyperconjugative interaction between -MO of incipient CH 3-C bond and *-MO of ring C-C bond
is also possible during equatorial attack. However this is relatively less effective and hence axial attack is
more favored on stereoelectronic grounds.
8
O
-MO of incipient CH3-C bond
C Relatively weaker hyperconjugative
CH3 interaction between -MO of incipient
CH3-C bond and *-MO of ring C-C bond
MgBr
H during equatorial attack.
*-MO of ring C-C bond

However steric factor will outweigh stereoelectronic factor and improves the diastereoselectivity by
favoring more equatorial attack, if alkylmagnesium sulfonates (otherwise known as Reetz-Grignard reagents)
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are used. The larger the sulfonate group, the more it favors an equatorial approach.
Problem 1.8
Which of the following options is the most likely product formed in the following reaction?
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O
1) BrMg MgBr
O
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ist
2) H3O+
OH OH OH
HO HO HO HO
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1) 2) 3) 4) \
OH O
Answer: 4
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Explanation:
* In this reaction, a lactone is made to react with a bis-Grignard reagent to get a diol. One of the
/ / w Ad
alcoholic group is tertiary and is derived from the carbonyl group of lactone. The other hydroxyl group is
primary and takes on shape from the ring oxygen of lactone.
This coversion is akin to the reaction of esters with excess of GR.
V.
MgBr
O O O O
MgBr MgBr MgBr
BrMg
O O OMgBr
:
MgBr
tp
OMgBr
ht
BrMgO OH
+
HO HO
H3O
OMgBr OH
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Problem 1.9 (CSIR NET JUNE 2015)
The major products A and B in the following synthetic sequence are:
O 1) PhMgBr
CuI NaOEt
A B
2) H3O+ Br2
om
O O
1) A= B= CH2Br
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Ph Ph
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O O
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ist
2) A= B= CH2Br
Ph Ph
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O O
Br
3) A= B=
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Ph Ph
/ / w Ad
O O
Br
4) A= B=
Ph Ph
V.
Answer: 1
Explanation:
:
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* The reactant, 1-acetylcyclohexene undergoes 1,4-conjugate addition with GR in presence of CuI to

give a bromomagnesio complex (I) in which the phenyl group is axially oriented.
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(II) is not formed due to 1,3-Allylic strain.
* Protonation of complex (I) takes place from axial side to give a cis ketone (II).
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O
Ph Ph O
H+
Me Me
Ph
- + H
O O MgBr
PhMgBr I III
Major
CuI
om
x
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Me
Ph
em an
- +
ry
O MgBr
II
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ist
1,3 Allylic strain
Not formed
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* The cis ketone, (III) can exist in another conformer, (IV), which is epimerized in presence of NaOEt
to give more stable trans ketone (V).
Ph O O
NaOEt
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H
Me Me
Ph Ph
H
/ / w Ad
H Me O
III IV V
trans ketone
V.
* The trans ketone, V can be enolized either by removal of axial ring proton or one of the methyl proton
to give VI or VII.
However, VI is not stable due to 1,3-Allylic strain and hence VII is formed exclusively, which upon
bromination gives VIII.
:
tp
ht
11
Ph OH
Me
VI O
O Unstable
Not formed CH2Br
Me
Ph Ph
H
V
om
OH O
Br2
CH2 CH2Br
Ph Ph
H
.c
H
VII VIII
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Followup questions
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ist
* What is the major product formed if ‘A’ is brominated in presence of acid?
Hint: (III) is enolized by the removal of ring proton. Thus bromination of ring takes place.
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* What is the product formed if COMe is replaced by COPh in (V)?
Hint: No enolization
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/ / w Ad
O
KOH
V.
H what is the major product?

EtOH
O
a) b) c) d) O
:
O
CHO
tp
Answer: b
ht
12
Explanation
O
O
The -hydrogen adjacent to
H ketone is more acidic and hence
H
abstracted by base.
O H
OH- O Why not the other -hydrogens
are abstracted?
-H2O
om
-
O
INTRA MOLECULAR ALDOL
.c
REACTION
The -CHO group is more
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H electrophilic and is attacked
O by the C-end of enolate ion.
ich rdh
ist
O
.ad a va
O
H2O
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-
O H OH- O O
/ / w Ad
-OH-
HO HO
H
V.
Dehydration through
E1cB mechanism.
:
tp
Web Resource:
http://www.adichemistry.com/organic/namedreactions/aldol/aldol-addition-condensation-1.html
ht
Think different:
Why not other -hydrogens are abstracted leading to different products?
There are three different types of -hydrogens, one adjacent to -CHO group and two adjacent to
keto group. If these hydrogens are abstracted, three different types of products are possible as explained
below.
However formation of 7-membered ring is not favorable due to entropy considerations, even
though the abstraction of proton from CH3 group adjacent to keto group is kinetically favored.
Abstraction of proton adjacent to -CHO group also leads to formation of five membered ring. But
keto group is less electrophilic and the equilibrium does not move in forward direction.
13
1 O
H
2
H 3
H
OH- H
Abstraction Abstraction
of H-1 O of H-3
Abstraction
om
of H-2
-
- O O
O
.c
H
em an
H
ry
-
H O O
O
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ist
O
O HO
.ad a va
OH HO H O
ww ity
/ / w Ad
O
O
V.
H O
Major product Another 5-membered ring

7-membered ring 5-membered ring Not a major product
not entropy favored more electrophilic nature of Since the keto carbon is less
-CHO favors this product electrophilic
:
tp
ht
Problem 2.2 (IIT JEE 2012)

The number of aldol reaction(s) that occurs in the given transformation is:
OH
O HCHO HO
H3C
H Conc. NaOH OH
HO
a) 4 b) 3 c) 2 d) 1
Answer: b
Explanation:
* Since there are 3 -hydrogens in acetaldehyde it undergoes crossed aldol reactions with 3 moles of
formaldehyde i.e., three aldol reactions.
14
O
H
OH- - H O- O H2O HO
H O -H2O O
-
O O
CH2 H2C H2C CH2 CH2 CH2 CH2
H H H H -OH- (I) H
O
H OH
- H2C
OH H H H2O HO O
om
HO O -H2O HO -
O
CH2 CH CH2 CH CH2 CH
H H -OH- (II)
H
.c
OH OH OH
em an
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H2C H2C H2O HO H2C O
HO O -H2O HO -
O
CH2 C CH2 C CH2 C
ich rdh
ist
H H H -OH- CH2 H
H
OH- HO
H (III)
O
.ad a va
* Thus formed product (III) contains no -hydrogens and hence undergoes crossed Cannizzaro reaction
with formaldehyde. In this step, formaldehyde is oxidized and -CHO group of (III) is reduced to CH2OH.
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The final product formed is also known as pentaerythritol.

OH
/ / w Ad
OH
H2C H2C
HO O Conc. NaOH HO
CH2 C + HCHO CH2 C CH2 + HCOONa
CH2 OH
V.
CH2 H
HO HO
Mechanism:
:
tp
ht
15
- - -
O HO O OH- O
H H H H H OH
-
H OH O
HO H2C
Hydrate anion Dianion
R= CH2 C
- -
O O O O CH2
H H + R
H + R H HO
- -
O H O H
transfer of
hydride ion
om
What are the other products possible in this reaction?
* Aldol and crotonaldehyde are also formed due to self condensation of acetaldehyde.
.c
Why formaldehyde is preferentially oxidized in the final step?
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* The carbonyl group of formaldehyde is more electrophilic due to absence of electron withdrawing
groups and hence the initial attack of OH- occurs on formaldehyde.
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ist
Problem 2.3 (UOH MSC 2012)
The most favorable product obtained in the following reaction is:
.ad a va
O KOH
CO 2H 
O O O O
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CO 2H
A) B) C) D)
O CO 2H
/ / w Ad
O
Answer: D
Explanation:
V.
* 2,5-diketones undergo aldol condensation reactions in presence of a strong base to give cyclized
products. Among the possible cyclizations, those result in 5 membered ring are more favored over 3
membered ones.
There are two acidic hydrogens on C-1 and C-6, abstraction of which lead to 5 membered rings.
However the abstraction of more acidic hydrogen on C-6 carbon is kinetically more favored.
:
tp
- O O
HO O CO 2H CO 2H
O H
ht
CO 2H CO 2H -H2O
-
O O HO

In the given reactions, identify the correct combination of their major products P and Q.
[LDA = LiN(i-Pr)2]
O
O LDA, THF, -78 oC LDA, THF, -78 oC
P ; Q
t-Bu PhCHO PhCHO

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Last updated on: 13th February 2016

No. of problems solved: 226

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Problem 1.1 (IISc 2011)

O acid catalysed and conjugate

-EtOH final removal step of EtOH

What about other options?

O EtMgBr H3O+ OH HCl Cl Cl

Problem 1.3 (CSIR DEC 2011)

* Thus formed product is subjected to hydroboration with BH3.Me2S complex to yield 2-

addition followed by reductive elimination.

Problem 1.5 (CSIR OLD MODEL PAPER)

The major product formed in the reaction, given below, is

Problem 1.7 (GATE 1991)

state when the GR approaches axially.

*-MO of ring C-C bond

* The reactant, 1-acetylcyclohexene undergoes 1,4-conjugate addition with GR in presence of CuI to

(II) is not formed due to 1,3-Allylic strain.

Problem 2.1 (GATE 2012)

H what is the major product?

Major product Another 5-membered ring

Problem 2.2 (IIT JEE 2012)

The final product formed is also known as pentaerythritol.

Problem 2.4 (GATE 2005)

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