Title of Invention

"AN IMPROVED PROCESS FOR THE PREPARATION OF AMINES FROM AZIDES"

Abstract

An improved process for the preparation of amines of formula 1, wherein R represents unsubstituted or substituted alkyl or aryl groups, from azides compound which comprises : i} reacting an azide of general formula RN3 where R has the same meaning as given above with a biocatalyst such as bakers yeast at temperature in the range of 25- 40° C, ii} extracting the reaction mixture with aprotic solvents or water immisible solvents, iii} separating the organic and aqueous phases, iv} drying the organic phase, purifying the residue by conventional methods such as conventional chromatography to obtain the desired amine.

Full Text

This invention relates to an improved process for the preparation of amines from azides. This invention particularly relates to a novel, biocatalytic process for the preparation of various alkyl amines, aryl amines, aralkyl amines from the corresponding azides by using baker's yeast. This is for the first time a microbial reduction of the azide functionality has been observed and is also a new application of baker's yeast. The amine prepared by the process of this invention has general formula RNH2 where in R represents alkyl, aryl, aralkyl or substituted alkyl, aryl, aralkyl. The amines prepared by the present invention may be utilized as building blocks in organic synthesis , particularly as starting material for total synthesis of complex organic compounds. They may also be used in the synthesis and semi-synthesis of natural products and their analogues. Reactions catalyzed by enzymes and enzyme systems display far greater specificity than more conventional forms of organic reactions including those of efficiency, chemoselectivity, diastereo and enantio selectivity. Besides their substrate specificity, enzymes have the ability to function under the mildest conditions compatible with even the most labile organic molecules. Baker's yeast has been used for mostly the stereo- selective reduction of carbonyl groups as well as some of the carbon-carbon double bonds. Nowadays, baker's yeast is becoming one of the most common reagents to an organic chemist for variety of selective functional group transformations, e.g., the regeneration of carbonyl groups from their oximes, hydrazones, thiones etc., and for the reduction of nitro groups to amino groups. Reduction of the azide moiety to an amine constitutes a synthetically important process, and, since many azides can be prepared with regio- and stereo- control, subsequent reduction permits a controlled introduction of the amine function. The reaction is of wide applicability and has been effected with a variety of chemical reagents, including LiAIH 4 , NaBH 4, catalytic hydrogenation, Ph3P, H2 S, propane dithiol\NEt 3, Na2 S\Net3 diborane, Sn\HCl etc. [E. Seriven and K. Turnbell, Chem. Rev., 1988, 88 (2) , 298-368] .Most of these reagents need drastic conditions and special atmospheres and at times some of the reagents employed are hazardous. The main object of the present invention is to provide an improved process for the preparation of amines from azides. Another object of the present invention is the reduction of azido moiety to amine employing baker's yeast as biocatalyst. whirh provides a mild and convenient synthesis of amines from the corresponding azides as shown in scheme in the drawing accompanying this specification. Accordingly the present invention provides an improved process for the preparation of amines of formula 1, as shown in drawing accompanying this specification wherein R represents unsubstituted or substituted alkyl or aryl groups,from azide compound which comprises i) reacting an azide of general formula RN3 where R has the same meaning as given above with a biocatalyst such as bakers yeast at temperature in the range of 25- 40 ° C, ii) extracting the reaction mixture with aprotic solvents or water immisible solvents, iii) separating the organic and aqueous phases , iv) drying the organic phase, purifying the residue by conventional methods such as conventional chromatography to obtain the said amine. In an embodiment of the present invention, azid used may be unsubstituted and substituted aryl azides aliphatic azides. such as phenyl azide, 2-azido benzo azido benzoic acid methyl ester, 2-azido vanillin, 2- azido benzyl vanillin, 4-nitro phenyl azide, 1,4-diazido benzene, 3 - methyl 2-azido benzoic acid, 5-methyl 2-azido benzaldehyde, 1 azido benzaldehyde, 5-methyl 2-azido benzaldehyde, 1-azido octane, 2-azido octane, 1-azido decane, benzyl azide etc. In another embodiment of the invention the baker's yeast used may be Saccharomyces species such as Saccharomyces visiae. In still another embodiment, reaction may be conducted in presence of organic solvent, such as alcohol having C 1 to C 4 preferably ethyl/methyl alcohol. This biocatalytic process provides a facile synthesis of alkyl and aryl amines by the reduction of corresponding compounds, illustrated in the drawing accompanying this specification. This reaction takes place under very mild condition and good yields. The process of the present invention is described in the following general examples for illustration and should not be construed to limit the scope of the present invention. Example 1 The 2-azido benzoic acid (50 mg, 0.31 mmol) was dissolved in 50% aqueous ethanol (5 ml) and added to the prestirred s baker's yeast (yeast: 2 gm. , phosphate buffer (pH 7.2 ) 20 ml ). The resulting mixture was incubated at 37 ° c for 2 complete days . After disappearance of starting material (by TLC) the mixture was extracted with ethyl acetate (3x20 ml) .The organic layer was dried over anhydrous sodium sulphate and concentrated to dryness. The residue was purified by column chromatography to obtain pure 2-amino benzoic acid in 87% yield. Example 2 The octyl azide (155 mg, 1 mmol) was dissolved in 50% aqueous ethanol (5 ml) and added to the prestirred suspention of baker's yeast (yeast: 2 gm., phosphate buffer (pH 7.2), 20 ml) .The resulting mixture was incubated at 37 ° c for 2 days. After complete disappearance of starting material (by TLC) the reaction mixture was extracted with ethyl acetate (3x20 ml) .The organic layer was dried over anhydrous sodium sulphate and concentrated to dryness. The residue was purified by column chromatography to obtain pure octyl amine in 63% yield. We claim : 1. An improved process for the preparation of amines of formula 1 , as shown in the drawing accompanying this specification wherein R represents unsubstituted or substituted alkyl or aryl groups, from azides compound which comprises : i} reacting an azide of general formula RN3 where R has the same meaning as given above with a biocatalyst such as bakers yeast at temperature in the range of 25- 40 ° C, ii} extracting the reaction mixture with aprotic solvents or water immisible solvents, Hi} separating the organic and aqueous phases, iv} drying the organic phase, purifying the residue by conventional methods such as conventional chromatography to obtain the desired amine. 2 . An improved process as claimed in claim 1 wherein the azid compound used is selected from unsubstituted or substituted aryl azides aliphatic azides such as phenyl azide, 2-azido benzo azido benzoic acid methyl ester, 2-azido vanillin, 2- azido benzyl vanillin, 4-nitro phenyl azide, 1,4-diazido benzene, 3 - methyl 2 -azido benzoic acid, 5-methyl 2-azido benzaldehyde, 1- azido benzaldehyde, 5-methyl 2-azido benzaldehyde, 1 - azido octane, 2-azido octane, 1-azido decane, benzyl azide 3. An improved process as claimed in claims 1 & 2 wherein the bakers yeast used is Saccharomyces cerevisiae. 4. An improved process as claimed in claims 1 to 3 wherein the reaction is effected in the presence of organic solvent, such as alcohol having C i to C4, preferably ethyl or methyl alcohol. 5. An improved process for the preparation of amines from azides' compound substantially as herein described with reference to the examples and drawing accompanying this specification.

Documents:

108-del-1998-abstract.pdf

108-del-1998-claims.pdf

108-del-1998-complete specification (granted).pdf

108-del-1998-correspondence-others.pdf

108-del-1998-correspondence-po.pdf

108-del-1998-description (complete).pdf

108-del-1998-form-1.pdf

108-del-1998-form-2.pdf

108-del-1998-form-4.pdf

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