Process for the preparation of N-acylamino acids

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

1999-05-13

2001-01-02

Richter, Johann (Department: 1621)

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

Organic compounds

Carboxylic acids and salts thereof

C562S408000, C562S450000, C562S507000, C562S575000, C562S406000, C562S526000

Utility Patent

active

06169201

ABSTRACT:

FIELD OF THE INVENTION
The invention is directed to a process for the preparation of N-acylamino acids of the general Formula I
R is hydrogen, a carboxyl group, a (C
1
-C
12
)-alkyl group, which may be saturated, straight chain, branched or cyclic, a (C
2
-C
12
)-alkenyl residue, which may be mono- or polyunsaturated, straight chain, branch chain, or cyclic and a (C
1
-C
8
)-acyloxy group, as well as a (C
5
-C
18
)-aryl residue.
R′ is hydrogen, a saturated straight chain, branch chain or cyclic (C
2
-C
14
)alkenyl residue, a (C
6
-C
18
)-alkyl-(C
5
-C
18
)-aryl residue or a poly-unsaturated (C
2
-C
10
)-alkenyl-(C
5
-C
18
) residue.
DESCRIPTION OF THE PRIOR ART
N-acyl amino acids are important starting materials in the synthesis of peptides as well as intermediates for the preparation of bioactive materials. Furthermore, they find use as detergents, drilling additives and food additives.
It is known to produce N-acyl amino acids through the acylation of corresponding amino acids with the occurrence of salt by-products. In the case of non-natural amino acids, the corresponding amino acid must frequently be produced beforehand involving several steps. A one-step process which avoids the disadvantages is the amido carbonylation of aldehydes and amides which is set forth in the following reaction scheme.
Amido carbonylation was first described by Wakamatsu, et al., (Chemical Communications 1971, page 1540 and in DE-A2-21 15 985). The carbonylation is carried out in the presence of hydrogen in the molecular ratio of CO: H
2
=3:1. As catalyst, there is utilized the cobalt carbonyl complex CO
2
(CO)
8
, which is used in a concentration of 30 mmol of Co-metal per liter of reaction mixture.
A further cobalt catalyzed procedure based on amido carbonylation is described in British patent 2,252,770. Therein the synthesis of n-acylamino acids is carried out by reaction of a carboxylic acid amid with an aldehyde and carbon monoxide in the presence of a metal catalyst and an acid as cocatalyst.
European Publication EP-B-0 338 330 describes a procedure for the preparation of N-acyl glycine derivatives through the use of a catalyst system comprising a palladium compound and an ionic halide. In DE 195 45 641 and DE 196 29 717, there is described a procedure for the preparation of N-acyl glycine derivatives from carboxylic acid amides and an aldehyde under palladium catalysis. As cocatalyst, there are utilized ionic halides and additionally acid is added. The known procedures to amido carbonylation start with carboxylic acid amides. In many cases however, such carbon acid amides are not available in sufficient amounts to be obtained economically on a production scale so that the high variable costs of the carbon acid amide stand in the way of the technical scale realization of the corresponding procedures.
SUMMARY OF THE INVENTION
The purpose of the present invention therefore, is to provide an improved procedure for the production of amino acids through amide carbonylation that permits the reaction to be carried out in a cost effective manner.
The object of the present invention is a procedure for the preparation of N-acyl amino acids of Formula I
wherein
R is hydrogen, carboxyl group, a (C
1
-C
2
)-alkyl group which may be saturated, straight chain, branched or cyclic, a (C
2
-C
12
)-alkenyl residue, which may be mono- or polyunsaturated, straight chain, branch chain, or cyclic and a (C
1
-C
8
)-acyloxy group, as well as a (C
5
-C
18
)-aryl residue,
R′ is hydrogen, a saturated straight chain, branch chain or cyclic (C
2
-C
14
)-alkenyl residue, a (C
6
-C
18
)-alkyl-(C
5
-C
18
)-aryl residue or a poly-unsaturated (C
2
-C
10
)-alkenyl-(C
5
-C
18
) residue, which is characterized thereby that a nitrile of general Formula II
R′CN  (II),
wherein R′ has the value stated above, is reacted with an aldehyde of general Formula III
R—CHO  (III),
in which R has the meaning above in the presence of an acid; carbon monoxide and a metal catalyst. In this way, it is possible, in highly cost efficient ways, to produce the desired compounds of general Formula I. Nitriles form the precursors of the appropriate carboxylic acid amides in virtually every case, whereby their lower price may be achieved.
DISCUSSION OF THE PREFERRED EMBODIMENTS
In accordance with the present invention any nitrile may be utilized. Examples of suitable nitrites include acetonitrile, benzonitrile, substituted benzonitriles, benzyl cyanide, acrylonitrile, malondinitrile, adiponitrile, butyl cyanide, allylcyanide, mandelo cyano nitrile and fatty acid nitriles.
With respect to the procedures of the present invention, any desired aldehydes can be used: formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, valeraldeyde, 2-ethyl hexanol, isobutryaldehyde, furfural, crontonaldehyde, acrolein, benzaldehyde, substituted benzaldehyde phenyl-acetaldehyde, 2,4-dihydroxyphenyl acetaldehyde, glyoxalic acid and &agr;-acetoxy propionaldehyde. One may also utilize dialdehyde compounds. Also suitable are aldehyde oligomers such as paraformaldehyde, acetals, allyl alcohols and epoxides, substances which can form an aldehyde under the given reaction conditions.
The aldehydes can be provided to the reaction in the form of their trimers or oligomers. As acids, there may, in principle, be used all compounds which are suitable for the nitrile hydrolyses in question. It is preferred to utilize acids having a pK
a
value of <4. Preferably, sulfuric acid or a hydrogen halide such as hydrogen chloride or hydrogen bromide is utilized in this reaction.
One may also use acid mixtures of such acids. As an especially preferred modification there may be utilized a mixture of a strong acid such as sulfuric acid or hydrogen bromide in the presence of formic acid. The formic acid may be utilized in a range of 1-100 equivalents relative to the nitrile.
As active metal catalyst all those catalysts known to those skilled in the art may, in principle, be utilized for the reaction in question. Preferred are metal catalysts of palladium-(O) as well as cobalt-(O) compounds. As cobalt catalysts, suitably precatalysts, there are preferably used cobalt carbonyls for example solid CO
2
(CO
8
). The cobalt carbonyl may be formed in situ from the known cobalt (II) and cobalt (III) compounds such as for example cobalt (II) acetate, cobalt (II) chloride, or cobalt (II) bromide in the presence of carbon monoxide if necessary, under the addition of H
2
. As palladium catalysts as well as precatalysts, any palladium (II) compound, palladium-O compound and palladium on carrier materials, such as palladium on activated charcoal, may be utilized. As examples of palladium (II) compounds are palladium acetate, palladium halides, palladium nitriles, palladium nitrates, palladium carbonates, palladium ketonates, palladium acetyl acetonates, as well as allyl palladium complexes. Particularly preferred members of the group are PdBr
2
, PdCl
2
, LiAc
2
PdBr
4
, Li
2
PdCl
4
, and Pd(OAc)
2
. Examples of palladium-O compounds are palladium phosphine complexes and palladium olefin complexes. Particularly preferred representatives are palladium (dba) complexes (dba=dibenzylidene acetone) and Pd(PPh
3
)
4
.
As particularly valuable members of the palladium phosphine complex group, there may be mentioned bisphosphine palladium (II) compounds. The complexes can be added as such or generated in a reaction mixture of a palladium (II) compound such as for example PdBr
2
, PdCl
2
, or palladium (II) acetate under the addition of phosphines such as triphenyl phosphine, tritolyl phosphine, bis-(diphenylphosphino)ethane, 1,4-bis-(diphenylphos-phino) butane or 1,3-bis-(diphenylphosphinol)propane.
Of the mentioned palladium phosphine complexes bis-triphenyl phosphine palladium (II) bromide-PdBr
2
(PPh
3
)
2
and the corresponding chloride are particularly preferred. These complexes can be added as such or as a reaction mixture obtained from palladium (II) bromide or chloride and triphenyl phosphine.
The process in accordance with the present inven

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