ASSIGNMENT OF ORGANIC CHEMISTRY-III

Submitted to ; Mr. Ali Irfan

Submitted by ; Saira Arshad
Roll No. 19
Program; ; M.Sc. Chemistry-III
STRECKER REACTION AND ITS APPLICATIONS
 DEFINITION STRECKER REACTION ;

The strecker amino acid synthesis ,also known simply as the

Strecker synthesis, was devised by German Chemist Adolph
strecker , and is a term used for a series of chemical reactions that
synthesize an amino acid from an aldehyde or Ketone.

The aldehyde is condensed with ammonium chloride in the

presence of potassium cyanide to form an alpha- aminonitrile,
which is subsequently hydrolyzed to give the desired amino acid
.

In the original strecker reaction acetaldehyde, ammonia , and

hydrogen cyanide combined to form after hydrolysis alanine .

 In the original strecker reaction acetaldehyde,
ammonia,and hydrogen cyanide combined to form
after hydrolysis alanine .

NH2 NH2

O
H+ O
KCN
NH4Cl R N R
R H
OH
 While usage of ammonium salts gives unsubstiutited amino acids,
primary and secondary amines also successfully give substituted
amino acids.

Likewise ,usage of Ketones, instead of aldehydes, gives alpha

,alpha disubstituted amino acids.

The traditional synthesis of Adolph strecker from 1850 gives

racemice alpha-amino nitriles ,but several procedures utilizing
asymmetric auxiliaries or asymmetric catalysts have been
developed .
 MECHANISM

In the first part of the reaction , the oxygen

of an is protonated , followed by a of
ammonia to carbonyl carbon .

After subsequent proton exchange , water is cleaved

from the intermediate. A cyanide ion then attacks the
iminium carbon yielding an aminonitrile.
 NH3
NH3
R H
O H-NH3

R O
R OH

proton transfer

NH2

NH2

CN R NH2 H2O
R
N
R OH2
 In the second part of the strecker synthesis the nitrile nitrogen of the
aminonitrile is protonated , and the nitrile carbon is attacked by the
water molecule .

A 1,2 diamino-diol is then formed after proton exchange

and a nucleophilic attack of water to the former nitrile carbon.

Ammonia is subsequently eliminated after the protonation of the

amino group , and finally the deprotonation of a hydroxyl group
produces an amino acid.
 N OH2
H2N NH
H H2N H2N
H2O
NH

R
R
R

OH
OH PROTON OH
TRANSFER H2N
H2O
H2N H2N
OH OH2 NH2
NH3 NH2
R
R R

NH3

OH O

H2N H H2N

OH OH

R R
 One example of the strecker synthesis is a multikilogram scale
synthesis of an L-valine derivative starting from Methly isopropyl
ketone.
 NaCN NH4Cl MgSO4 OH
NH3/MgOH
o
30 C/4hrs + COOH
HOOC
2, L-tartaric acid C
O N
MeOH, rt,72hrs OH

O
o
1. 100 C, 20hrs
O 2. NaOH
EtO N H
3.EtOCOCl
H
4. HCL N
O 5.DCH H
H

HSO4
CATALYTIC ASYMMETRIC
STRECKER REACTION

Catalytic asymmetric strecker reaction can be

effected using thiourea-derived catalyst . In 2012 ,a
BINOL-derived catalyst was employed to generate
chiral cyanide anion.
 NHBoc NHBoc

R -la
10 mol o/o
R SO2Ph KCN 1.05 equiv R CN
4-10 mmol No isolation

catalyst recycling 1. 6N HCl,reflux one pot

2.recrystallisation

ORGANIC PHASE
aqueous phase
NH2-HCl

R CO2H
OH
I

R -la
O

O I

OH
O

I
 Unnatural D amino acids;
NH2-HCl NH2-HCl

CO2H
CO2H

65% ,.99% ee
55% ,>99% ee

NH2-HCl NH2-HCl

MeO

CO2H CO2H

54% ,>99% ee
65%, >99% ee
*
63% ,>99%ee
NH2-HCl

CO2H

66% ,>99% ee