Process for the production of N-acylamino acids

Details Process for the production of N-acylamino acids Process for the production of N-acylamino acids

2000-06-26

2001-09-25

Carr, Deborah D. (Department: 7621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Fatty compounds having an acid moiety which contains the...

C554S068000

Reexamination Certificate

active

06294681

ABSTRACT:

DESCRIPTION OF THE INVENTION
The invention relates to a process for the production of N-acylamino acids with the general formula I
where
R denotes hydrogen, a carboxyl group, a unsaturated or saturated, straight-chain, branched or cyclic (C
1
-C
12
) alkyl group, a mono- or polyunsaturated, straight-chain, branched or cyclic(C
2
-C
12
) alkenyl radical, and a (C
1
-C
8
) acyloxy group, a (C
4
-C
8
) aryl radical, and (C
1
-C
12
) alkyl (C
4
-C
18
) aryl radical,
R′ and R″ independently and separately denote hydrogen, a saturated, straight-chain, branched or cyclic (C
1
-C
26
) alkyl, a mono- or polyunsaturated, straight-chain, branched or cyclic (C
2
-C
24
) alkenyl radical, a (C
1
-C
12
) alkyl (C
4
-C
18
) aryl radical or an optionally polyunsaturated (C
2
-C
10
) alkenyl (C
4
-C
18
) aryl radical.
BACKGROUND OF THE INVENTION
N-acylamino acids are important starting products in peptide synthesis and intermediates for the production of biologically active agents. Moreover, N-acylamino acids are useful in detergents, drilling agent additives and food additives.
The manufacture of N-acylamino acids by acylation of corresponding amino acids with accumulation of salt by-products is known in the art. Regarding non-natural amino acids, the corresponding amino acid must frequently be manufactured in a number of stages. A single-stage process that avoids these disadvantages is the amidocarbonylation of aldehydes and amides, which is illustrated in the following diagram.
Amidocarbonylation was first described by Wakamatsu et al., (Chemical Communications 1971, page 1540 and in DE-A2-21 15 985). The carbonylation is performed in the presence of hydrogen gas with a 3:1 molar ratio of CO:H
2
. The cobalt carbonyl complex Co
2
(CO)
8
is used as catalyst in a concentration of 30 mmol Co metal per litre of reaction mixture.
A further cobalt-catalysed process based on amidocarbonylation is described in GB 2 252 770. In this reaction the synthesis of N-acylamino acids is performed by reacting carboxylic acid amide with an aldehyde and CO in the presence of a metal catalyst and an acid co-catalyst.
EP-B-0 338 330 describes a process for the production of N-acylglycine derivatives with a catalyst system consisting of a palladium compound and an ionic halide. DE 195 45 641 and DE 196 29 717 describe a process for the preparation of N-acylglycine derivatives from a carboxylic acid amide and an aldehyde with palladium catalysis. In these reactions, ionic halides and additional acid may be used as co-catalysts.
DE 199 20 107.2 describes amidocarbonylation starting from nitrites in the presence of palladium or cobalt catalysts.
It is known from the literature that carboxylic acid amides react with aldehydes and carbon monoxide to N-acylamino acids. Until now only palladium and cobalt complexes have been used as catalysts for this reaction. Against this background it is surprising for the person skilled in the art that rhodium, iridium and ruthenium complexes also catalyze the reaction of amides with aldehydes and carbon monoxide. The reactions proceed with very high selectivities and good catalyst productivities. Unreacted educt can be readily recovered by recovery processes familiar to the person skilled in the art (distillation, crystallization) and can be reused, such that good yields can also be obtained in continuous processes.
SUMMARY OF THE INVENTION
An object of the present application is to provide further substances for amidocarbonylation that can catalyze said reaction.
Another object of the present invention is a process for producing N-acylamino acids of the formula I by reacting an amide of the formula II, an aldehyde of formula III in the presence of an acid, carbon monoxide, and a metal catalyst.
Another object of the present invention is the process for producing N-acylamino acids of the formula I in a dipolar aprotic solvents or solvent mixtures.
Another object of the present invention is producing enantiomer enriched N-acylamino acids by chiral modification and using the enantiomer enriched N-acylamino acids in the process for producing N-acylamino acids of the formula I.
DETAILED DESCRIPTION OF THE INVENTION
The invention provides a process for the production of N-acylamino acids of the formula I
wherein
R is selected from hydrogen, a carboxyl group, a saturated or unsaturated, straight-chain, branched or cyclic (C
1
-C
12
) alkyl group, a mono- or polyunsaturated, straight-chain, branched or cyclic(C
2
-C
12
) alkenyl radical, a (C
1
-C
8
) acyloxy group, a (C
4
-C
18
) aryl radical, and a (C
1
-C
12
) alkyl (C
4
-C
18
) aryl radical,
R′ and R″ independently and separately are selected from hydrogen, a saturated, straight-chain, branched or cyclic (C
1
-C
26
) alkyl, a mono- or polyunsaturated, straight-chain, branched or cyclic (C
2
-C
24
) alkenyl radical, a (C
1
-C
12
) alkyl (C
4
-C
18
) aryl radical or an optionally polyunsaturated (C
2
-C
10
) alkenyl (C
4
-C
18
) aryl radical,
reacting an amide with the formula II
R′—CO—NH—R″  (II),
in which R′ and R″ have the meaning given above, and an aldehyde with the formula III
R—CHO  (III),
in which R has the meaning given above,
in the presence of carbon monoxide and a metal catalyst selected from rhodium, iridium or ruthenium catalysts. This process advantageously yields the desired compounds of formula I.
According to the invention, any amides as educts can be used as starting materials. Examples of suitable amides are acetamide, benzamide, propionamide, N-methylacetamide, fatty acid amides, acrylamide, cinnamic acid amide, phenylacetic acid amide, acetanilide and urea. In the process according to the invention the amide component can also be optionally manufactured in situ from corresponding nitrites, for example by acid-catalyzed hydrolysis. Examples of suitable nitrites are acetonitrile, benzonitrile, substituted benzonitriles, benzyl cyanide, acrylonitrile, malonic dinitrile, adiponitrile, butyl cyanide, allyl cyanide, mandelic acid nitrile and fatty acid nitrites.
For the process according to the invention, any aldehydes may be used, e.g., formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, valeraldehyde, 2-ethylhexanal, isobutyraldehyde, furfural, crotonaldehyde, acrolein, benzaldehyde, substituted benzaldehydes, phenylacetaldehyde, 2,4-dihydroxyphenylacetaldehyde, glyoxylic acid and &agr;-acetoxypropionaldehyde. Dialdehyde compounds may also be used. Substances that can form an aldehyde under the stated reaction conditions, e.g., aldehyde oligomers are also suitable. Examples of such aldehyde oligomers paraformaldehyde, acetals, allyl alcohols and epoxies.
The aldehyde is conveniently used in a quantity of 0.5 to 5 equivalents, preferably 0.8 to 2 equivalents, relative to the amide. Included in this range is 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5 equivalents, and all values and subranges there between.
The aldehydes may be used in the reaction in the form of their trimers or oligomers.
Active metal catalysts for the reaction may be any catalyst known in the art and which are based on rhodium, ruthenium or iridium.
Metal carbonyls or metal halides or metal carboxylates are preferably used as the rhodium, ruthenium or iridium catalysts or pre-catalysts. Typical catalysts or precatalysts are rhodium (III) acetate, rhodium (III) chloride, acetylacetonato-bis(ethylene) rhodium(I), bis(1,5-cyclooctadiene) rhodium (I) trifluoromethane sulfonate, chloro-bis(ethylene) rhodium (I) dimer, chloro(1,5-cyclooctadiene) rhodium (I) dimer, chlorodicarbonyl rhodium (I) dimer, chloro-tris(triphenylphosphane) rhodium (I), hexarhodium hexadecacarbonyl, dicarbonyl acetylacetonatrhodium (I), rhodium (III) acetylacetonate, rhodium (II) acetate dimer, tetrarhodium dodecacarbonyl, acetatodicarbonyl ruthenium, bis(cyclopentadienyl) ruthenium, dichloro-bis[(p-cymene)chlororuthenium (II)], dichloro(1,5-cyclooctadienyl) ruthenium (II), dichlorodicarbonyl-bis(triphenylphosphane) ruthenium (II), dichloro-tris(triphenylphosphane) ruthenium (II), ruthenium (II

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