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1

Chapter 7
Definitions
Olefin
Alkene
Alkyne
Unsaturated fatty acids
vic-dibromides
gem-dibromides

Biochemistry
Increasing the unsaturation of a fatty acid decreases mp(makes it turn from solid to liquid)
Increasing the unsaturation decreases the order which decreases mp
Cis double bonds have less order than trans double bonds
Cis double bonds decrease mp
The fluidity of cellular membranes is determined by unsaturation
Reindeers/artic fish have adapted to have a higher degree of unsaturation; this leads to more fluidity
in membrane to counterbalance extreme temperatures
Fatty acids are a long chain of carbons with a carboxylic acid on the end.
Humans and other higher animals have fatty acids that contain 16 or 18 carbons(always even). If
the chain of carbons contains no double bonds, they are saturated. One double bond means
monounsaturated. More than one is polyunsaturated. 3 fatty acids will combine with glycerol to
make a fat/oil molecule. Saturated fats contain fatty acids with no double bonds. Monounsaturated
fats contain fatty acids with one double bond.

Alkenes/alkynes
Ethylene/Acetylene/Olefin/Olefiant gas
Physical properties are similar to alkanes
Soluble in nonpolar liquids; slightly soluble in water
Density lower than water

E/Z nomenclature
Cahn/Ingold/Prelog systemR/S and E/Z. You check each half of the double bond. Identify the
largest(by atomic #) group on each half of double bond. If both of the largest groups are on the
same side it is Z. If the largest groups are on opposites sides then it is E. In first ex, Cl is bigger
than chain of 4 carbons and on the other half chain of three carbons is bigger than H. Since Cl and
three carbon chain are on same side it is Z.
E = entgegen(opposite sides)
Z = zusamment(same side)

Cl

Z
Cl
Cl

Br

CH3

OH

Stability of alkenes
H of alkene = -120 kj/mole on average
H of cis butene = -120 kj/mole
H of trans butene = -115 kj/mole
Cis are less stable than trans
This is due to steric interactions in cis vs trans
H

H
C
H

C
H
H

)(H

H
H

steric hindrance

C
H

free of steric
hindrance

More substituted double bonds are more stable than less substituted
tetrasubstituted--most stable

trisubstituted--2nd most stable

disubstituted(same carbon)--3rd most stable

disubstituted(trans)--4th most stable

disubstituted(cis)--5th most stable

monosubstituted--6th most stable

unsubstituted--least stable

Cyclic structures
In cyclopropene, cyclobutene and cyclopentene only cis double bonds are possible
In cyclohexene although the trans is hypothetically possible it is so unfavored that cyclohexenes
almost always adopt the cis configuration.
In cycloheptene the trans form has been observed spectroscopically for a very brief time. However
cycloheptene is almost exclusively cis.
In cyclooctene, cis predominates but the trans is isolatable as a pair of enantiomers.

all 3,4,5,6,7 carbon rings


form predominantly the cis
form. Although for 6 and 7
it is possible to observe trans
form fleetingly.

cis predominates
in cyclooctene but the
trans forms is also
seen.

Chemical Reactions
Synthesis of alkenes via elimination reaction
Dehydrohalogenation
H

NaOMe
Br

Dehydrohalogenation of alkyl halides is best carried out by E2 mechanism. In E1


there are too many side reactions possible. One is rearrangement due to migration
of carbocation.
To force reaction to go E2 you need to start with secondary or tertiary alkyl halide. If
you start with primary alkyl halide, use a bulky base(potassium tert-butoxide). High
temperature favors the elimination over the substitution.
Also to increase the chances of E2 mechanism use a high concentration of strong
base(alkoxide base). Also the use of a base pair is often used(ethoxide in ethanol,
methoxide in methanol, tert-butoxide in tert-butanol).
Zaitsevs Rule
When a mixture of double bonds is possible from an elimination reaction, the more
substituted double bond will form. Energetically, this is explained by a lower energy
transition state for the more substituted double bond than for a less substituted double
bond.
Exception to the ruleUsing potassium tert-butoxide often leads to the less
substituted double bond due to the size of the base and steric hindrances. This is
known as the Hoffmann Rule.

Stereochemistry of double bond


In the transition state of the elimination reaction the leaving group, the carbons of the double
bond and the hydrogen being removed are all in the same plane. This is the anti periplanar
conformation talked about in last chapter.
If anti periplanar is not possible syn periplanar eliminations will occur.
Br

NaOMe/MeOH
Ethyl

H3C

Ethyl
CH3

wedged groups
stay on same side.

rotate to get
anticoplanar,
antiperiplanar
H3C
H3C

Br
CH2

Br

H3 C
H3 C

CH2
H
CH2
H

OMe

CH3

In cyclic structures, axial Hydrogens are needed in elimination reactions. This often leads to
Hoffman products forming instead of Zaitsev products.
In cyclics, eliminations must be done with H and leaving group axial If the most stable form
of a molecule has the leaving group equatorial, it must ring flip to the axial form to undergo
elimination reactions. This leads to larger reaction rates.
If there is only one axial Hydrogen available for elimination the elimination will form that
product regardless if it is the Zaitsev or the Hofmann products. If there are two axial
hydrogens then the Zaitsev Rule will determine which product forms.
See example page 296-297.
In summary, the leaving group must be axial even if that is the unfavored ring flip. If
the axial position is in the unfavored ring flip the reaction will go much slower. With leaving
group in axial position, if there are axial hydrogens on either side, the reaction will follow
Zaitsevs rule. If there is only one axial hydrogen, the reaction will proceed with that
hydrogen even if it leads to a Hofmann product.

Ethyl

CH3

H 3C

Br

H 3C

H 3C

Propyl

Br
Ethyl

NaOMe/MeOH

Propyl

Br

Potassium tert-butoxide
H

N aO M e/M e O H
H 3C O

H 3C O

CH 3
O Tf

C H3

N O T T H IS

O Tf

H 3C O

H 3C O
H
H
CH3

O nly ax ial hyd ro ge n o n the m ol ec ule

Dehydration of alcohol
OH

Cl

H C l /

Experimental conditions
High temperature and Bronsted acids(phosphoric and sulfuric acid) favor dehydration of
alcohols.
Primary alcohols proceed through an E2 mechanism.
With primary alcohols(very difficult) concentrated sulfuric acid and high
temperatures(180 degrees) is needed.
Secondary and tertiary alcohols proceed through an E1 mechanism.
With secondary alcohols mild conditions such as 85% phosphoric acid with moderate
heat(85 degrees) is needed.
With tertiary alcohols very mild conditions will easily dehydrate the alcohol.
20% sulfuric acid and 85 degrees is a common set of conditions.
Ease of dehydrationtertiary > secondary > primary

CH 3

H2SO4/
180o -??
OH

85% H3PO4/
80-180o
OH

20% H2SO4
20-80o
OH

Mechanism for primary alcohol dehydration

H
OH

S O 4/

1 8 0 o-??
O
O

O H

O
H
O
O
O

OH

Mechanism for secondary and tertiary alcohol dehydration.


2 0% H 2 SO 4
2 0-8 0

OH
O
H

OH

O
HO
O

H
O

H
H

10

Rearrangement of carbocations
Dehydration reactions of secondary and tertiary alcohols proceed through an E1
mechanism. Since E1 goes through a carbocation rearrangements are possible.
Tertiary carbocations are more stable than secondary and secondary are more stable
than primary. Therefore if a secondary carbocation forms during dehydration and a
rearrangement can lead to a tertiary carbocation then that rearrangement will occur.
Pages 303-306.
Rearrangement of carbocations can proceed through methyl migration(1,2 shift) or
hydride migration(1,2 shift).
Rings can expand due to carbocation formations(305).
Secondary to tertiary
H 2 SO 4 /heat
OH

Explain these three products.


Which is the major product?

H2SO 4/heat

OH

Explain these three products.

Which is the major product?

B
straightforward elimination leads to #3

OR
Methyl
shift leads to
#1

OR
Methyl shift
followed by
hydride shift
leads to #2
H

11

From primary:
If there is a primary alcohol, it will proceed through the E2 mechanism. There is a
possibility for the double bond to reprotonate and form a carbocation. At this point the
original double bond may reform. A new double bond using a different -hydrogen
may form. A migration of methyl or hydrogen to form a new carbocation(then double
bonds could form). Finally a substitution may occur.
OH

HCl

Explain these products.

Which is the major?


Which is the first formed?

1 forms from straight E2 elimination.


A small fraction of 1 may reprotonate
and then encounter shifts...

4
Cl

Now leads
to elimination
#3.

H +(from HCl or water)


Now elimination leads to #2
H

Substituion
leads to #4
Cl-

B-

12

Debromination of vic-dibromides(not in text)


Br

Br

Zn, Acetic Acid(or ethanol)

Br

Br
Br

Br

NaI/acetone

Br

Br

Synthesis of alkynes via elimination reaction(double E2 elimination)


See page 307 for mechanism.
Br

Br

NaNH2 /NH3

The first product forms not the second. Why??

Vic-dibromides can eliminate twice to form an alkyne. Either the vic-dibromide will already
be present or it can be generated from any alkene.
Br

1 eq. Br 2

Br

2 NaNH2

13

Strong bases are needed to do the double eliminations(sodium amide is a good base).
How would you turn pentan-1-ol into 1-pentyne?
H2SO4(conc.)

1 eq. Br2

OH
Br

2 NaNH 2
Br

Because of the acidity of terminal alkynes, three equilvalents of sodium amide is used to
deprotonate the alkyne as it forms and drive the reaction to completion.
The solvent is usually liquid ammonia or mineral oil.
Ketones can be converted to gem-dichlorides which can be eliminated to alkynes.
O

Cl

Cl

PCl 5 /Oo

1) 3 eq. NaNH2/NH 3
2) H+
Why is the H+ added as a second step?
What does the product look like before the
H + is added?

pKa revisited
Terminal alkynes are extremely acidic when compared to alkenes and alkanes.
Looking at basicities on top of p. 309, will hydroxide deprotonate a terminal alkyne??
What base will deprotonate a terminal alkyne?

14

SOLUTION VS. GAS PHASE


In solution alkynides are more basic than hydroxides. But in gases, hydroxides are more
basic than alkynides. This is due to solvation effects. Solvent solvate smaller ions better
thus making smaller anions less basic. In gas, larger ions are more polarized than smaller.
The polarization of larger ions make them more stable. Bottom line. Smaller ions are more
stabilized in solvents. Larger ions are more stabilized in the gas phase.

Substitution of terminal alkynes


If you recall, vinylic and phenylic halides do not undergo substitution due to the presence of
the double bond. We can take advantage of the acidity of the terminal alkyne to in essence
carry out a substitution reaction. Once the alkyne is deprotonated, it acts as a nucleophile in
a SN2 type reaction.

NaNH 2 /NH3

Propylbromide

The reaction takes place with primary halides only. In secondary and tertiary halides, the
terminal alkyne acts as a base to form an E2 elimination product.
H

NaNH2 /NH3

2-propylbromide
H

+
Hydrogenation of Alkenes/Alkynes
The hydrogenation of alkenes/alkynes are examples of addition reactions. The double bond
is replaced by the two hydrogens as they add to the double bond.
Biochemically, liquid vegetable oils which contain multiple double bonds usually are partially
hydrogenated to semi-solid fats/margarines
Fats/oils are glycerol molecules with three fatty acids on them. The fatty acids can be
saturated, unsaturated or polyunsaturated. The more the unsaturation the more the subtance
will act as an oil(liquid) instead of a fat(solid). Hydrogenating fats often leads to
isomerization of some double bonds from the naturally occurring and safer cis form to the
nonnatural more dangerous trans form.

15

Hydrogenation is accompanied by a catalyst to make it occur at a favorable rate. Although


this is an exothermic reaction it has a very high activation energy and requires a catalyst to
make it go under normal conditions. Page 312.
Hydrogen gas absorbed onto rhodium, ruthenium, platinum, palladium or nickel is a very
common reagent set. Wilkinsons catalyst(Rh[(C6H5)3P]Cl) is increasingly being used.
With the presence of the catalyst the reaction can take place at room temperature and room
pressure. Harder to hydrogenate double bonds often take place at very high pressure in
special chambers called hydrogenation chambers. The stereochemistry of these reaction is
a syn addition of hydrogen.
Syn addition means both groups come from the same side; anti addition means the groups
come from opposite sides. See 313-314.

H2/Pd

With alkynes, platinum is usually used as the catalyst. The reaction usually proceeds from
alkyne to alkane(not stopping at the alkene level). This reaction also leads to
syn addition.

H2/Pt

If you want to stop at the alkene level, the use of a poisoned catalyst such as P-2 or
Lindlars Catalyst will yield to a Z-alkene.
H2/P-2

P-2 = Ni 2B; Ni 2B is generated from Nickel acetate reduction by NaBH4 see p. 315
Lindlar's catalyst

Lindlar's Catalyst = H2, Pd, CaCO3 in quinoline, see p. 316.

16

If you want to stop at the alkene level, the use of dissolving metal reactions will yield an E-alkene.
1) Li or Na/ethylamine
-78o
2) NH4Cl

Mechanism for E-alkene.


H

1) Li, C 2H5NH2
2) NH 4Cl
H

Li

C 2H5N

C 2H5N

H
H

Li

Index of hydrogen deficiency(IHD)


Alkanes = CnH2n + 2

Alkenes = CnH2n

Alkynes = CnH2n 2

Oxygen = 0 H

Nitrogen = -1 H

Halogens = +1 H

Each unit of unsaturation equals a double bond or a ring.


i.e. 1 unit of unsaturation could equal a double bond or a ring.
2 units of unsaturation could equal 2 double bonds, 2 rings, 1 ring 1 double
bond or a triple bond

STUDY PAGES 320-322

17

Chapter 7--Chemical Reactions with Mechanisms


Synthesis of alkenes via elimination reaction

Dehydrohalogenation
H

NaOMe
Br

Mechanism for Dehydrohalogenation


OMe
H

NaOMe
Br

Dehydration of alcohol
H 2SO 4/
o

180 -??
OH

85% H 3PO 4/
80-180

OH

20% H2SO 4
20-80

OH

Mechanism for primary alcohol dehydration


H 2S O

1 8 0 -? ?

O H

O
O

O H

O
H
O
O
O
H

S
O

O H

18

Mechanism for secondary and tertiary alcohol dehydration.


2 0% H 2 SO 4
2 0-8 0

OH
O
H

OH

O
HO
O

H
O

H
H

Synthesis of alkynes via elimination reaction(double E2 elimination)


Br

Br

NaNH2
Br

NaNH2

NaNH2

Br

Br

Br

Mechanism
NH 2 H

Br

N aN H 2

Br

Br

NH 2

19

Substitution of terminal alkynes


1) NaNH2
2) Pentyl Bromide

Mechanism
-

NH2

Cl

Hydrogenation of alkyne to E-alkene


1) Li or Na/ethylamine
-78o
2) NH4 Cl

Mechanism for E-alkene.


H

1) Li, C 2H5NH2
2) NH 4Cl
H

Li

C 2H5N

C 2H5N

H
H

Li

20

Chapter 7--Chemical Reactions without Mechanisms


Formation of gem-dihalide
O

PCl5/0o

Hydrogenation reactions.
H2/Pd

H2/Pt

H2/P-2

P-2 = Ni 2B; Ni 2B is generated from Nickel acetate reduction by NaBH4 see p. 315
Lindlar's catalyst

Lindlar's Catalyst = H2, Pd, CaCO3 in quinoline, see p. 316.

Debromination of vic-dibromides(not in text)


Br

Br

Zn, Acetic Acid(or ethanol)

Br

Br
Br

Br

Br

NaI/acetone

Br

21

Homework Chapter 7

Name:
Br

Br

OH

1) NaNH2
2) octyl chloride

22

H2/Pt

H2/P-2

Lindlar's Catalyst

1) Li, ethylamine
2) NH4Cl
H2/Pd

H2/Ni

H2/Pt
H2/Wilkinson's catalyst

H2/P-2

Lindlar's Catalyst

1) Li, ethylamine
2) NH4Cl

23

Give the mechanism for the following:


H

NaOMe
Br

H2SO4/!
180o-??
OH

OH

20% H2SO4
20-80o

24

Show the reagents for the following transformations

25

Homework Chapter 7 Key

Name:

Br

Zn, AcOH
or
NaI/acetone

Br

3 eq. NaNH2

1) 85% H3PO4, heat


2) Br2
3) 3 eq. NaNH2
OH

1) PCl5/0o
2) 3 eq. NaNH2
O

1) NaNH2
2) Pentyl chloride

1) NaNH2
2) octyl chloride

26

H2/Pt

H2/P-2

Lindlar's Catalyst

1) Li, ethylamine
2) NH4Cl
H2/Pd
H2/Ni

H2/Pt
H2/Wilkinson's catalyst

H2/P-2
No Reaction
Lindlar's Catalyst
No Reaction
1) Li, ethylamine
No Reaction
2) NH4Cl

27

Give the mechanism for the following:


H

NaOMe
Br

OMe

NaOMe
Br

H2SO4/!
180o-??
OH

180o-??
OH

H2SO4

B
H

OH2

OH

20% H2SO4
20-80o

OH

20% H2SO4
20-80o

OH2

28

Show the reagents for the following transformations

1) NaNH2
2) Pentyl chloride
3) H2/Pt

1) NaNH2
2) Ethyl chloride
3) Li, ethyl amine
4) NH4Cl

1) NaNH2
2) Butyl chloride
3) H2/P-2
H

29

Homework #3 (Chapter 6 and 7)


Name:
Part I: Fill in the products, show stereochemistry (if racemic mixture,
you need to show only one isomer).

NaCl, Acetone

NaSH, H2O

OTf

NaOMe/MeOH

OK

30

1) NaH, TfCl
2) 1 eq. of NaOMe/MeOH

Br

OH

2 eq. NaCN/Acetone

H2/Pd

H2/P-2

1) NaNH2
2) Butyl chloride
3) H2/Pt

31

Part II: Fill in the reagent(s) for the following reactions.

OH

Cl

OH

OH

Br

Br
Br

Br

Br

CN

32

Part III: Mechanisms.


A. For the following 2 reactions, draw the product, mechanism and energy diagram
(include EA, H and all important intermediates or transition states).
NaSH/H2O
Br

NaOMe/MeOH

TfO

33

Homework #3 (Chapter 6 and 7)

KEY

Part I: Fill in the products, show stereochemistry (if racemic mixture,


you need to show only one isomer).

NaCl, Acetone
Cl

NaSH, H2O

SH

OTf

NaOMe/MeOH

OK

34

Br

1) NaH, TfCl
2) 1 eq. of NaOMe/MeOH

Br

CN

OH

2 eq. NaCN/Acetone

OH

H2/Pd

H2/P-2

1) NaNH2
2) Butyl chloride
3) H2/Pt
3

35

Part II: Fill in the reagent(s) for the following reactions.

OH

1) NaH, TfCl
2) NaCl, Acetone

OH

Cl

1) NaH, TfCl
2) KOtBu

OH

1) NaH, TfCl
2) KOtBu 3) Br2
4) NaNH2 5) H2/P-2

Br

Zn, AcOH
or
NaI/Acetone

Br
Br

Br

3 eq. NaNH2

1) PCl5/OoC
2) 3 eq. NaNH2
3) Propyl Cl 4) H2/Pt

Br

1) NaCl, Acetone
2) NaCN, Acetone

CN

36

Part III: Mechanisms.


A. For the following 2 reactions, draw the product, mechanism and energy diagram
(include EA, H and all important intermediates or transition states).

NaSH/H2O
Br

SH

SH-

EA

EA

!H

OMe
NaOMe/MeOH

TfO
OMe
H

EA
!H

TfO

37

Homework #3

Name:

A. Show the product of the following reactions:

NaCN/DMSO

NaOMe/MeOH
OTf

Potassium tert-butoxide

NaBr/Acetone

NaSCH3/H2O
OTs

OMe

1 eq. NaOMe/MeOH

2 eq. NaOMe/MeOH

38

NaOMe/MeOH

OK

OH

1) NaH/TsCl
2) 2 eq. NaCN/DMF

NaSH/H2O

MeO

OH

NaSH/acetone

OTf

NaOH/H2O

39

NaOMe/MeOH
H

Cl

MeO

NaSCH3/DMSO

H2/Pd

1) Br2
2) NaNH2
3) Pentyl chloride
4) H2/P-2

40

B. Fill in the reagents for the following reactions.


OTs

Br

CN

Br

SH

Br

Br

Br

41

C. For the following 2 reactions, draw the product, mechanism and energy diagram
(include EA, H and all important intermediates or transition states).
OTf

NaSH/H2O

OTf

NaOMe/MeOH

42

Homework #3KEY
A. Show the product of the following reactions:

NaCN/DMSO
CN
NaOMe/MeOH
OTf
OMe
Potassium tert-butoxide

Br

OMe

NaBr/Acetone
SCH3

OMe

NaSCH3/H2O
OTs

OMe
OMe

1 eq. NaOMe/MeOH
OMe

2 eq. NaOMe/MeOH

43

NaOMe/MeOH

OH

OH

OK

OH

CN
H

1) NaH/TsCl
2) 2 eq. NaCN/DMF

H
H

CN

MeO

OH

NaSH/H2O

MeO

SH

OH

NaSH/acetone

NO REACTION
MeO

OTf

NaOH/H2O

OH

44

Cl

NaOMe/MeOH

MeO

Ethyl

H3CS

OMe

Cl

Cl

MeO

Ethyl

t-Bu

OMe

NaSCH3/DMSO

t-Bu

H2/Pd

1) Br2
2) NaNH2
3) Pentyl chloride
4) H2/P-2

MeO

45

B. Fill in the reagents for the following reactions.


OTs

NaOMe/MeOH

Br

NaCN/Acetone

CN

Br

Zn/AcOH
Br

1) KOtBu
2) Br2- 3) NaNH2
4) Ethyl Cl 5) H2/Pt

Br

Br

NaSH/H2O
1) Na, ethylamine
-78OC
2) NH4Cl

1) PCl5, OoC
2) 3 eq. NaNH2
3)
Br

4) H2/Pd

SH

46

C. For the following 2 reactions, draw the product, mechanism and energy diagram
(include EA, H and all important intermediates or transition states).
OTf

SH

NaSH/H2O

3
SH-

EA

1
!H

OTf

NaOMe/MeOH

OMe

OTf

EA

MeO

EA

!H