1

ACILIRANJE ENOLAT -

ANIONA

CLAISENOVA REAKCIJACLAISENOVA REAKCIJA

2

Claisenova kondenzacija

• β-keto esteri se pripremaju pomoću

Claisen-ove kondenzacije.

• Koriste se etil esteri sa Na-etoksidom kao

bazom

2RCH2RCH22COR'COR'

OO1. 1. NaORNaOR''

2. H2. H33OO++

++ R'OHR'OH

OO OO

RCHRCH22CCHCOR'CCHCOR'

RR

3

Primjer:

• Produkt iz etil acetata se naziva etilacetoacetat

ili acetoacetatni ester

2CH2CH33COCHCOCH22CHCH33

OO1. NaOCH1. NaOCH22CHCH33

2. H2. H33OO++

OO OO

CHCH33CCHCCH22COCHCOCH22CHCH33

(75%)(75%)

4

Korak 1Korak 1::

CHCH33CHCH22 OO––••••••••

••••

••••

COCHCOCH22CHCH33

OO

CHCH22HH

••••

––••••

••••

COCHCOCH22CHCH33

OO

CHCH22CHCH33CHCH22 OO••••

••••HH

••••

Mehanizam:

5

Mehanizam

Korak Korak 1:1:

––••••

••••

COCHCOCH22CHCH33

OO

CHCH22

••••

––••••

COCHCOCH22CHCH33

OO

CHCH22

••••

••••

• Anion koji nastaje stabilizira se delokalizacijom elektrona (rezonancijom); to je enolat estera

6

Mehanizam

KorakKorak 2:2:

––••••

••••

COCHCOCH22CHCH33

OO

CHCH22

••••

CHCH33COCHCOCH22CHCH33

OO ••••••••

CHCH33CC

––OO••••••••••

••••••

COCHCOCH22CHCH33

OO

CHCH22

••••

OCHOCH22CHCH33••••••••

7

Mehanizam

KorakKorak 3:3:

CHCH33CC

––OO••••••••••

••••••

COCHCOCH22CHCH33

OO

CHCH22

••••

OCHOCH22CHCH33••••••••

––OCHOCH22CHCH33••••••••••••

CHCH33CC

OO••••••••

••••

COCHCOCH22CHCH33

OO

CHCH22

••••

++

8

Etoksid privlači proton iz CH2

grupe dajući stabilizirani anion:

––OCHOCH22CHCH33••••••••••••

CHCH33CC

OO••••••••

••••

COCHCOCH22CHCH33

OO

CHCH22

••••

++

KorakKorak 4:4:

++ OCHOCH22CHCH33••••

••••HH

––

••••

COCHCOCH22CHCH33

OO ••••

CHCH33CC

OO••••••••

CHCH••••

9

++

KorakKorak 5:5:

––

••••

COCHCOCH22CHCH33

OO

CHCH33CC

OO••••••••

CHCH••••

++OOHH ••••

HH

HH

OO

HH

••••

HH

••••CHCH33CC

OO••••••••

••••

COCHCOCH22CHCH33

OO

CHCH

••••

HH

+

Reakciona smjesa se zakiseli i to prevodi anion u

izolirani produkt, etil acetoacetat:

OO

10

Primjer 2:

• Reakcija uključuje

formiranje veze

izmeñu α-karbonovog

atoma jedne molekule

propanoata i karbona

karbonilne grupe

druge molekule.

2CH2CH33CHCH22COCHCOCH22CHCH33

OO

1. NaOCH1. NaOCH22CHCH33

2. H2. H33OO++

(81%)(81%)

OO OO

CHCH33CHCH22CCHCOCHCCHCOCH22CHCH33

CHCH33

11

Intramolekularna Claisenova kondenzacija:

Dieckmann-ova reakcija

12

CHCH33CHCH22OCCHOCCH22CHCH22CHCH22CHCH22COCHCOCH22CHCH33

OO OO

1. NaOCH1. NaOCH22CHCH33

2. H2. H33OO++

Primjer

COCHCOCH22CHCH33

OO OO

(74(74--81%)81%)

13

CHCH33CHCH22OCCHOCCH22CHCH22CHCH22CHCH22COCHCOCH22CHCH33

OO OO

NaOCHNaOCH22CHCH33

preko

CHCH33CHCH22OCCHOCCH22CHCH22CHCH22CHCOCHCHCOCH22CHCH33

OO OO

••••

––

••••••••

••••••••

••••••••

14

CHCH33CHCH22OCCHOCCH22CHCH22CHCH22CHCOCHCHCOCH22CHCH33

OO OO

••••

––

••••••••

••••••••

CHCOCHCHCOCH22CHCH33

OO

––

••••••••

CHCH22HH22CC

HH22CC

CC

OO••••••••

••••CHCH33CHCH22OO

••••

••••

15

CHCOCHCHCOCH22CHCH33

OO

––

••••••••

CHCH22HH22CC

HH22CC

CC

OO••••••••

••••CHCH33CHCH22OO

••••

••••

CHCH33CHCH22OO••••

••••••••––

••••••••

CHCOCHCHCOCH22CHCH33

OO

CHCH22HH22CC

HH22CC

CC

OO••••••••

++

16

Mješovita Claisen-ova kondenzacija

• Kao i kod mješovite aldolne kondenzacije, mješovitu

Claisen- ovu kondenzaciju je najbolje izvoditi

kada reakciona smjesa sadrži jedno jedinjenje koje može

formirati enolat i jedno koje ne može (da se nebi stvarala

smjesa produkata).

17

• Ovi tipovi estera ne mogu graditi enolate.

HCORHCOR

OO

ROCORROCOR

OO

ROCROC

OO

CORCOR

OO

CORCOR

OO

18

Primjer

1. NaOCH1. NaOCH33

2. H2. H33OO++

(60%)(60%)

COCHCOCH33

OO

++ CHCH33CHCH22COCHCOCH33

OO

OO OO

CCHCOCHCCHCOCH33

CHCH33

19

Aciliranje ketona sa esterima

20

Primjer

1. 1. NaHNaH

2. H2. H33OO++

(60%)(60%)

++CHCH33CHCH22OCOCHOCOCH22CHCH33

OO

OO

OO

COCHCOCH22CHCH33

OO

21

Primjer

1. NaOCH1. NaOCH22CHCH33

2. H2. H33OO++

(62(62--71%)71%)

COCHCOCH22CHCH33

OO

++

OO

CHCH33CC

OO

OO

CCHCCH22CC

22

Sinteza ketona preko ββββ-keto estera

23

Sinteza ketona

•β-keto kiseline se lahko dekarboksiliraju

dajući ketone

++

OO

RCHRCH22CCHCCH22RR

OO OO

RCHRCH22CCHCOHCCHCOH

RR

COCO22

24

Sinteza ketona

•β-keto kiseline se dobivaju hidrolizom β-

keto estera.

OO OO

RCHRCH22CCHCOR'CCHCOR'

RR

OO OO

RCHRCH22CCHCOHCCHCOH

RR

HH22OO++ R'OHR'OH

25

Sinteza ketona

β-keto esteri mogu biti pripremljeni

Claisenovom kondenzacijom.

2RCH2RCH22COR'COR'

OO1. 1. NaORNaOR''

2. H2. H33OO++

++ R'OHR'OH

OO OO

RCHRCH22CCHCOR'CCHCOR'

RR

26

Primjer

1. NaOCH1. NaOCH22CHCH33

2. H2. H33OO++

(80%)(80%)

2 CH2 CH33CHCH22CHCH22CHCH22COCHCOCH22CHCH33

OO

CHCH33CHCH22CHCH22CHCH22CCHCOCHCCHCOCH22CHCH33

OO OO

CHCH22CHCH22CHCH33

27

Primjer

1. KOH, H1. KOH, H22O, 70O, 70--8080°°CC

2. H2. H33OO++

CHCH33CHCH22CHCH22CHCH22CCHCOCHCCHCOCH22CHCH33

OO OO

CHCH22CHCH22CHCH33

CHCH33CHCH22CHCH22CHCH22CCHCOHCCHCOH

OO OO

CHCH22CHCH22CHCH33

28

Primjer

7070--8080°°CC

(81%)(81%)

OO

CHCH33CHCH22CHCH22CHCH22CCHCCH22CHCH22CHCH22CHCH33

CHCH33CHCH22CHCH22CHCH22CCHCOHCCHCOH

OO OO

CHCH22CHCH22CHCH33