All name reactions and there mechanism, Study notes of Organic Chemistry

Download All name reactions and there mechanism and more Study notes Organic Chemistry in PDF only on Docsity!

C

HAPTER

^6

C

HAPTER

^6

Organic Reactions andOrganic

Reactions and

Their MechanismsTheir Mechanisms

SUBSTITUTION

REACTION

In a substitution reaction, a functional group in a particular chemicalcompound is replaced by another groupcompound is replaced by another group.

Reagent

Substrate

Reactive intermediate

Type of organic substitution

intermediate

Nucleophilic

Aliphatic

Carbocation

Aliphatic nucleophilic substitutionAromatic electrophilic substitution

Electrophilic

Aromatic

Carbanion

Free radical substitution

Electrophilic

Aromatic

CarbanionFree radical

The

electrophilic

and

nucleophilic

substitution

reactions

are

of

prime importance. 

Detailed understanding of a reaction type helps to predict the 

Detailed understanding of a reaction type helps to predict the product outcome in a reaction. It also is helpful for optimizing areaction with regard to variables such as temperature and choice of

l^

t^

solvent.

B. N

UCLEOPHILIC

S

UBSTITUTION

M

ECHANISMS AT

S

ATURATED

C

ARBON

CENTRES ^

Bimolecular Nucleophilic Substitution (S

N^ 2)

Structure of the S

2 transition stateN

The kinetic evidence:

Rate =

k [RX][Nu]



Walden inversion: (+)-chlorosuccinic

acid

1

was converted to (+) 1

was converted to (+) malic acid

^2

by action

of Ag

O 2

in water with

retention

of 4

configuration,

in

the

next

step

the

OH

was

replaced by Cl to

^3

by

reaction with PCl

4

reaction with PCl

. 5

Philips (1923)

2

2

2

2

3

o^

o^

o

There is a high probability that(a),

(c),

and

(d)

proceeded

2

2

o

with retention, leaving (b) asthe inversion. o

 Unimolecular Nucleophilic Substitution (S

N1)

 Unimolecular

Nucleophilic Substitution (S

N^ 1)

Br CH

3

H C

• 2 H O

OH CH

3

H C

• Br + H O

Br CH

3

H^3

C^

• 2 H

O 2

OH CH

3

H^3

C^

• Br + H

O 3

H^3

C^

CH

3



Reaction kinetics:rate =

k [RX]

Ionization of the

Br

H^3

C H^3

C

CH

3 C

H^3

C^

• Br

CH

3

H^

H^3

C^

H

Ionization

of the

substrate is the rate-determinating step.t B Cl

t B

Cl

CH

3 C

H^3

C^

+^

O

H H^

H^3

C H^3

C^

O

H

H^3

C^

H^

H^

H^3

C

SN

1

t-BuCl



t-Bu

+^

• Cl

630 kJ/mol (in gas phase)84 kJ/mol (in water)

H^3

C H^3

C H^3

C^

O

H H

O

H H +^

OH

H^3

C H^3

C H^3

C^

• H

O 3



Salt effect and common-ion effect: An increase in ionic strength of the solution usually increases the rate of an S

N^ 1 reaction. A common ion will

depress the S

N1 rate.

p

Steric

factor

:^

The

reactions

run

under

SN

conditions

fail

or

Steric

factor

:^

The

reactions

run

under

SN

conditions

fail

or

proceed very slowly at the bridgehead position of 2,2,1systems.^ 

Stereochemistry: An excess of inversion is usually observed, as 

Stereochemistry: An excess of inversion is usually observed, as the

leaving

group

can

remain

in

proximity

to

the

carbocation

intermediate for a short time and block nucleophilic attack.

•^

The Neighboring-Group Mechanism OBSERVATION with certain substrates:i.^

The rate of reaction is greater than expected,

g^

p^

,

ii. The configuration at a chiral carbon is retained and not inverted or

racemerized.h

i hb

i

h^

i^

i^

i ll

f^

S 2

The

neighboring-group

mechanism

consists

essentially

of

two

S^ N

substitutions,

each

causing

an

inversion

so

that

the

net

result

is

retention of configuration.retention of configuration.

C Et

Et

HO

C^

Cl

OH

-^

C

Et

Et -O

C^

Cl

-Cl

-^

C Et

Et O^

C^

Me

OH

-^

C Et

Et

- O

C^

OH

Cl

Me

H^

Me

H

H

Me

Me

H

1

2

3

B

10

构

型 翻 转

Br C

C

H Me

O 构

型 翻

转

C H

C

O^

OH

-

C^

C

HO H

O

10

构

型 翻 转

- O

Me

构 型 翻

转 Me

O^

H

Me

- O

EVIDENCE:(i)

Configurational retention. Note that both products are optically ( )

g^

p^

p^

y

inactive and so cannot be told apart by differences in rotation. Themeso and

dl dibromides have different boiling points and indexes of

refraction and were identified by these properties.refraction and were identified by these properties.

H

CH

3

B

H

CH

3

B

CH

3

H

B

CH

3

H

HBr

+

OH Br H

CH

3

Br Br H

CH

3

OH Br

CH

3

H

Br Br

CH

3

H

+

+

Br

苏式

dl 对

苏式

dl

对

H^

CH

3

Br Br

CH

3

H Br Br +

Br H^

CH

3

H^

CH

3

Br H^

CH

3

H^

CH

3

+H

Br C^

C

H^

H

CH -H^2

O

H^

CH

3

CH

3

H

OH

CH

3

OH

2

CH

3

CH

3

Br

-

(2S,3S)

(2S,3S)

(2R,3S)

(2R,3R)

(2S,3S)

(2S,3S)

(2S,3S)

(iii)

Acetolysis

of

both

methoxy

pentyl

brosylate

^1

and

methoxy

(iii)

Acetolysis

of

both

-methoxy-pentyl brosylate

^1

and 5-methoxy-

2-pentyl brosylate

^2

: the same mixture of products. In this case the

intermediate

^3

is common to both substrates.CH O

3 H

OBs

H^

CH O

3

H

H

CH O

3

H^

H

H CH

3

H

BsO

CH

3

CH

3

H

1

3

2

CH O

3

H

C

CH O

3 H H

H

C

AcO

OAc

CH

3

H CH

3

AcO

60%

40%

Important

neighboring

groups

:^

COO

• , COOR, COAr, OCOR, OR, OH,

Important neighboring groups: COO , COOR, COAr, OCOR, OR, OH, O

– , NH

, NHR, NR 2

, NHCOR, SH, SR, S 2

• , I, Br, Cl.

The effectiveness: I > Br > Cl.

CH

ClCH

CH 2

2

S

CH

2

CH

2

Cl

ClCH

2CH

2

S

CH

2 CH

2

OH

- S^ N

2

ClCH

CH 2

S 2

CH

CH 2

OH 2

邻基参与

OTs H^

OAc

H^

OTs H^

OTs H

AcO

- AcOH

k 乙酸解

(^1110)

1

AcOH

-TsO

-

AcO

-^

ONB H

ONB H^

ONB H

+

k^

酸解

H^3 C^

H^3 C CH

3

k 乙酸解

1

13.

148

O C

O^

C^

NO

2

NB

：

D.

Reactivity 

For

the

S

N^2

mechanism

branching

at

either

the

or

the

^

carbon

D.

Reactivity

-^

The Effect of Substrate Structure 

For

the

S

N^2

mechanism

, branching at either the

or the

^

carbon

decreases the rate.^ Table 1.

Average relative S

N^2

Primary and secondary

Table

Average relative S

N^2

rates for some alkyl substratesR^

Relative

t

R^

Relative

t

y^

y

substrates generally react bythe SN2 mechanism andtertiary by the SN1 mechanism.

rate

rate

Methyl

30

Isobutyl

Ethyl

1

Neopentyl

10

y^

p^

y

Propyl

Ally

10

Butyl

Benzyl

120

16

Isopropyl

Elimination

is

always

a^

possible

side

reaction

of

nucleophilic

b^

f^

b^

(^

h^

h d

substitutions of tertiary substrates (wherever a hydrogen is present).

S b t

t^

f^

th

t^

RCOX

ll^

h^

ti^

th

Substrates of the type RCOX are usually much

more reactive than

the

corresponding

RCH

X. 2

The

mechanism

here

is

always

the

tetrahedral one. Explanation: i. The carbonyl carbon has a sizable partial positive charge.ii. In an SN1 reaction a

bond must break in the rate-determining

step,

which

requires

more

energy

than

the

shift

of

a^

pair

of

electrons, which is what happens in a tetrahedral mechanism.iii. A trigonal carbon offers less steric hindrance to a nucleophile thaniii. A trigonal carbon offers less steric hindrance to a nucleophile thana tetrahedral carbon. 

Unsturation at the

-carbon.

Table 2. Relative rates for the S

N^ 1 reaction between ROTs and

ethanol at 25

C

CH3CH2-

PhCH

• 2

100

(CH

)2CH- 3

Ph

CH- 2

~ 10

5 ~^

10

CH2=CHCH2-

Ph

C- 3

~ 10

10

Table

List

of

groups

in

approximately

descending

order

of

Table

. List of groups in approximately descending order of

reactivity toward SN1 and SN2 reactions. (Z = RCO, HCO, ROCO,NC, or a similar group)

S 1

i i

S 2

i i

SN1 reactivity

SN2 reactivity

Ar3CX

RCHDX

Ar

CX 3

R3CX

A^

A

Ar2CHX

RCHDCH2X

Ar2CHX

ZCH

CH2X 2

ROCH

X, RSCH 2

X, 2

R2NCH2X

C=CX

ArCH

X 2

R^3

CCH2X

R2NCH2XR3CX

ZCH2X

ZCH

X 2

C=CX

C=CCH2X

ZCH2CH2X

C=CCH

X 2

ArX

R^2

CHX

ArX

RCH

X ~ RCHDX ~ 2 RCHDCH X

Bridgehead-X

RCHDCH2X

RCH2X ~ R

CCH2X 3

[2,2,1]bridgehead-X

R^2

CHX

•^

The Effect of the Attacking

Nucleophile

SN

1 rate: are independent of the identity of the nucleophile, since

it does not appear in the rate-determining step.

The

Effect of the Attacking Nucleophile

For S

N2 reactions in solution there are four principles that govern

the effect of the nucleophile on the rate.i^

A nucleophile with a negative charge > its conjugate acid i.^

A nucleophile with a negative charge > its conjugate acid.OH

-^

> H

O, NH 2

• 2

> NH

3

ii. In comparing nucleophiles whose attacking atom is in the same

row of the periodic table, nucleophilicity is approximately in orderof basicity. NH

• 2

>RO

-^

> OH

-^

> R

NH > ArO 2

–^ > NH

> C 3

H 6

N > F 5

> H

O > ClO 2

• 4

;^

R^3

– C

> R

N 2

-^

> RO

-^

> F

2

4

;^

3

2

iii. Going down the periodic table, nucleophilicity increases, though

basicity decreases.

I

-^ > Br -^ > Cl

–^ > F

-^ (solvation, HSAB principle)

iv. The freer the nucleophile, the greater the rate.Ex.: The rate of nucleophilic attack by (EtOOC)

CBu 2

-^ Na

+^

in benzene was

increased by the addition of 1,2-dimethoxyethane.

20

y^

,^

y^

20