Title of Invention	A PROCESS FOR THE PREPARATION OF ALKYL CYANOACETATES
Abstract	The invention relates to a process for preparing an alkyl cyanoacetate. Alkyl chloroacetate is reacted with a metal cyanide in the presence of a phase transfer catalyst. A biphasic solvent system consisting of water and a water immiscible organic solvent is used as the reaction medium. Alkyl cyanoacetate produced is recovered from the organic phase. This process is cost effective and produces alkyl cyanoacetate in high purity and very good yield.

Title of Invention

A PROCESS FOR THE PREPARATION OF ALKYL CYANOACETATES

Abstract

The invention relates to a process for preparing an alkyl cyanoacetate. Alkyl chloroacetate is reacted with a metal cyanide in the presence of a phase transfer catalyst. A biphasic solvent system consisting of water and a water immiscible organic solvent is used as the reaction medium. Alkyl cyanoacetate produced is recovered from the organic phase. This process is cost effective and produces alkyl cyanoacetate in high purity and very good yield.

Full Text	This invention relates to a process for the preparation of alkyl cyaooacetates, particularly in high purity and in good yield. Alkyl cyanoacetates are intermediates or precursors in the production of alpha cyanoacrylates monomers which polymerise rapidly and exhibit good adhesive properties. A few alkly cyanates, particularly methyl and ethyl cyanoacetates are used extensively in the synthesis of heterocyclic compounds, such as substituted pyridines and purine compounds. Conventional process for the manufacture of alkyl cyanoacetates consists of reacting cyanoacetic acid with an alcohol in the presence of p-toulenesulphonic acid and benzene. Azeotropic removal of water horn the reaction mixture resulted in the production of the desired alkyl cyanoacetate in about 95% yield. The reaction product in benzene was washed with water to remove unreacted cyanoacetic acid and the product was distilled under reduced pressure. The above process uses carcinogenic reactants which are expensive, hazardous to health and poses handling problems. In yet another known process, ethyl cyanoacetate is prepared by substituting the chlorine in chloroacetic acid with cyano group in the presence of acetonitrile or dimethyl sulphoxide as solvents followed by esterification. The chemicals used in this process also exhibit hazardous properties and are not cost effective. The object of this invention is to prepare alkyl cyanoacetates in a cost effective manner using chemicals which do not pose any health hazanls. Yet another object is to produce aikyl cyanoacetates having high purity and high yield compared to the existing processes. Alkyl cyanoacetates can be prepared by substituting the chlofo group in alky! chloroacetate by a cyano group. The chemical reaction for the preparation ofalkly cyanoacetate is represented by the following equation: CICH 2COOR + MCN -> NCCH2COOR + MCI wherein R stands for an alkyl group having Ci to C12 carbon atoms and M is an alkali metal prefer^ly sodium or potassium. The improvement over the existing process is in carrying out the reaction in the presence of a phase transfer catalyst in a biphasic reaction medium. The reaction medium consists of water and a water immiscible organic solvent. Different water immiscible solvents such as dichloromethane, dichloroediane, tetrachloroethane, chloroform, carbon tetrachloride and diethylether may be used. Reaction carried out in dichloromethane solvent medium is found to yield the best result. Any conventional phase transfer catalyst such as benzy triethylammonium bromide, benzyl triediylammonium chloride, tetra-n-butyl ammonium chloride, bromide and iodide, "18crown-6", tetraetfaytene glycol, polyethylene glycol 200 and 400, and "tween 20* are used in a molar concentration ranging from 1 to 10%. Out of these catalysts, benzyl tiietfayl ammonium chloride and bromide in 1% molar concentration is found appropriate in providing maximum yield and therefore preferred. Accordingly, this invention relates to a process for the preparation of an alkyl cyanoacetate which comprises reacting an alkyl chloroacetate with a metal cyanide in a biphasic reaction medium consisting of water and a water immiscible organic solvent in the presence of a phase transfer catalyst and recovering the resulting alkyl cyanoacetate from the organic phase in a known manner. The reaction may be carried out at a temperature ranging from -10C to 80C depending upon the solvent used. The reaction mixture may be washed with water to remove the metal halide produced during the reaction. The organic phase may be distilled to recover alkyl cyanoacetate. Alkyl groups may be methyl, ethyl, n-propyl, butyl, isobutyl, pentyl, hexyh heptyl, octyl, nonyl, dccyl, undecyl and dodecyl. The following non-limiting example describes the preparation of ethyl cyanoacetate. To a vigorously stirred solution of (1000 g, 8.16 mole) of 99% commercial grade ethyl chloroacetate and benzyl tri-ethylammonium chloride (22g. 0.0181 mole) in dichloromedane (1.75I) taken in a five litre three necked flask fitted with a mechanical stirrer, condenser and an addition flask, sodium cyanide (480 g 9.8 mole) in distilled water (870 ml) was added drop by drop for a period of one hour. The mixture was stirred for about 3 hours after the completion of the addition of sodium cyanide for completing the reaction. 870 ml of distilled water was then added to the reaction mixture to dissolve the deposited sodium chloride. The aqeuous phase was separated and the organic phase was separately washed with distilled water before subjecting the same to distillation to remove the solvent dichloromethane and unreacted ethyl chloroacetate. Distillation was then continued and the fraction boiling at about 210\C was collected to yield 96% of ethyl cyanoacetate. Unreacted sodium cyanide foimd in the aqueous extract was detroyed by the addition of potassium permangante. Obvious equivalents known to persons skilled in the art are within the scope of this invention. WE CLAIM: 1. A process for the preparation of an alkyl cyanoacetate comprising reacting an alkyl chloroacetate with a metal cyanide in a biphasic reaction medium consisting of water and a water immiscible organic solvent in the presence of a phase transfer catalyst, and recovering the resulting alkylcyano acetate from the organic phase in a known manner. 2. The process as claimed in claim 1, wherein said reaction is carried out at a temperature ranging from -10C to 80C. 3. The process as claimed in claim 1, wherein ethyl chloroacetate is reacted with sodium cyanide to produce ethyl cyanoacetate. 4. The process as claimed in claims 1- 3, herein said phase transfer catalyst is selected from quatemery ammonium halides like ben2yl triethyl ammonium chloride or bromide, tetra-n-butly ammonium chloride or bromide, tetra ethylene glycol or polyethylene glycol, 18-cr-6 or other crown ethers and is added in a molar concentration ranging from 1 to 10%. 5. The process as claimed in claim 4, wherein said phase transfer catalyst is either benzyl triethyl ammonium chloride or bromide and is added in 1% molar ratio. 6. The process as claimed in claims 1 to 5, wherein said water immiscible organic solvent is selected from dichloromethane, dichloroethane, tetrachloroethane, chloroform, carbon tetra chloride and diethyl ether. 7. The process as claimed in claim 3, wherein ethyl cfaloroacetate is reacted with sodium cyanide in a biphase reaction medium consisting of water and dichloroethane in the presence of benzyl triethy] ammonium chloride. 8. The process as claimed in claims 1 to 7, wherein said reaction is carried out under stirring and on completion of said reaction, the reaction mixture is repeatedly washed with water, the organic phase is separated from the aqueous phase and the alkyl cyanoacetate produced is recovered from said organic phase by distillation. 9. A process for the preparation of an alkkl cyanoacetate substantially as herein described and exemplied.

Full Text

This invention relates to a process for the preparation of alkyl cyaooacetates, particularly in high purity and in good yield.
Alkyl cyanoacetates are intermediates or precursors in the production of alpha cyanoacrylates monomers which polymerise rapidly and exhibit good adhesive properties. A few alkly cyanates, particularly methyl and ethyl cyanoacetates are used extensively in the synthesis of heterocyclic compounds, such as substituted pyridines and purine compounds.
Conventional process for the manufacture of alkyl cyanoacetates consists of reacting cyanoacetic acid with an alcohol in the presence of p-toulenesulphonic acid and benzene. Azeotropic removal of water horn the reaction mixture resulted in the production of the desired alkyl cyanoacetate in about 95% yield. The reaction product in benzene was washed with water to remove unreacted cyanoacetic acid and the product was distilled under reduced pressure. The above process uses carcinogenic reactants which are expensive, hazardous to health and poses handling problems.
In yet another known process, ethyl cyanoacetate is prepared by substituting the chlorine in chloroacetic acid with cyano group in the presence of acetonitrile or dimethyl sulphoxide as solvents followed by esterification. The chemicals used in this process also exhibit hazardous properties and are not cost effective.

The object of this invention is to prepare alkyl cyanoacetates in a cost effective manner using chemicals which do not pose any health hazanls. Yet another object is to produce aikyl cyanoacetates having high purity and high yield compared to the existing processes.
Alkyl cyanoacetates can be prepared by substituting the chlofo group in alky! chloroacetate by a cyano group. The chemical reaction for the preparation ofalkly cyanoacetate is represented by the following equation:
CICH 2COOR + MCN -> NCCH2COOR + MCI
wherein R stands for an alkyl group having Ci to C12 carbon atoms and M is an alkali metal prefer^ly sodium or potassium.
The improvement over the existing process is in carrying out the reaction in the presence of a phase transfer catalyst in a biphasic reaction medium. The reaction medium consists of water and a water immiscible organic solvent. Different water immiscible solvents such as dichloromethane, dichloroediane, tetrachloroethane, chloroform, carbon tetrachloride and diethylether may be used. Reaction carried out in dichloromethane solvent medium is found to yield the best result. Any conventional phase transfer catalyst such as benzy triethylammonium bromide, benzyl triediylammonium chloride, tetra-n-butyl ammonium

chloride, bromide and iodide, "18crown-6", tetraetfaytene glycol, polyethylene glycol 200 and 400, and "tween 20* are used in a molar concentration ranging from 1 to 10%. Out of these catalysts, benzyl tiietfayl ammonium chloride and bromide in 1% molar concentration is found appropriate in providing maximum yield and therefore preferred.
Accordingly, this invention relates to a process for the preparation of an alkyl cyanoacetate which comprises reacting an alkyl chloroacetate with a metal cyanide in a biphasic reaction medium consisting of water and a water immiscible organic solvent in the presence of a phase transfer catalyst and recovering the resulting alkyl cyanoacetate from the organic phase in a known manner.
The reaction may be carried out at a temperature ranging from -10C to 80C depending upon the solvent used. The reaction mixture may be washed with water to remove the metal halide produced during the reaction. The organic phase may be distilled to recover alkyl cyanoacetate. Alkyl groups may be methyl, ethyl, n-propyl, butyl, isobutyl, pentyl, hexyh heptyl, octyl, nonyl, dccyl, undecyl and dodecyl.
The following non-limiting example describes the preparation of ethyl cyanoacetate.

To a vigorously stirred solution of (1000 g, 8.16 mole) of 99% commercial grade ethyl chloroacetate and benzyl tri-ethylammonium chloride (22g. 0.0181 mole) in dichloromedane (1.75I) taken in a five litre three necked flask fitted with a mechanical stirrer, condenser and an addition flask, sodium cyanide (480 g 9.8 mole) in distilled water (870 ml) was added drop by drop for a period of one hour. The mixture was stirred for about 3 hours after the completion of the addition of sodium cyanide for completing the reaction. 870 ml of distilled water was then added to the reaction mixture to dissolve the deposited sodium chloride. The aqeuous phase was separated and the organic phase was separately washed with distilled water before subjecting the same to distillation to remove the solvent dichloromethane and unreacted ethyl chloroacetate. Distillation was then continued and the fraction boiling at about 210\C was collected to yield 96% of ethyl cyanoacetate. Unreacted sodium cyanide foimd in the aqueous extract was detroyed by the addition of potassium permangante.
Obvious equivalents known to persons skilled in the art are within the scope of this invention.

WE CLAIM:
1. A process for the preparation of an alkyl cyanoacetate comprising reacting an alkyl chloroacetate with a metal cyanide in a biphasic reaction medium consisting of water and a water immiscible organic solvent in the presence of a phase transfer catalyst, and recovering the resulting alkylcyano acetate from the organic phase in a known manner.
2. The process as claimed in claim 1, wherein said reaction is carried out at a temperature ranging from -10C to 80C.
3. The process as claimed in claim 1, wherein ethyl chloroacetate is reacted with sodium cyanide to produce ethyl cyanoacetate.
4. The process as claimed in claims 1- 3, herein said phase transfer catalyst is selected from quatemery ammonium halides like ben2yl triethyl ammonium chloride or bromide, tetra-n-butly ammonium chloride or bromide, tetra ethylene glycol or polyethylene glycol, 18-cr-6 or other crown ethers and is added in a molar concentration ranging from 1 to 10%.
5. The process as claimed in claim 4, wherein said phase transfer catalyst is either benzyl triethyl ammonium chloride or bromide and is added in 1% molar ratio.

6. The process as claimed in claims 1 to 5, wherein said water
immiscible organic solvent is selected from dichloromethane,
dichloroethane, tetrachloroethane, chloroform, carbon tetra chloride
and diethyl ether.
7. The process as claimed in claim 3, wherein ethyl cfaloroacetate is reacted with sodium cyanide in a biphase reaction medium consisting of water and dichloroethane in the presence of benzyl triethy] ammonium chloride.
8. The process as claimed in claims 1 to 7, wherein said reaction is carried out under stirring and on completion of said reaction, the reaction mixture is repeatedly washed with water, the organic phase is separated from the aqueous phase and the alkyl cyanoacetate produced is recovered from said organic phase by distillation.
9. A process for the preparation of an alkkl cyanoacetate substantially as
herein described and exemplied.

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Patent Number

217086

Indian Patent Application Number

816/MAS/2001

PG Journal Number

21/2008

Publication Date

23-May-2008

Grant Date

24-Mar-2008

Date of Filing

04-Oct-2001

Name of Patentee

HULLURU SURYA PRAKASH RAO AND SIVAPACKIAM JOTHILINGAM

Applicant Address

DEPARTMENT OF CHEMISTRY, PONDICHERRY UNIVERSITY, PONDICHERRY -

Inventors:

#	Inventor's Name	Inventor's Address
1	SIVAPACKIAM JOTHILINGAM	DEPARTMENT OF CHEMISTRY, PONDICHERRY UNIVERSITY, PONDICHERRY - 605 014,
2	HALLURU SURYA PRAKASH RAO	DEPARTMENT OF CHEMISTRY, PONDICHERRY UNIVERSITY, PONDICHERRY - 605 014,

PCT International Classification Number

C07C 255/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA