SU640659A3 - Method of obtaining d- or i-isomers of amino acids - Google Patents

Description

olefin bond in the presence of an optically active coordination metal complex hydrogenation catalyst. Such a reaction is illustrated by the following equation. II Where the {b-substituent is phenyl, is a symmetric atom. In the example of {b-substituent such groups as hydrogen, alkyl, substituted alkyl, aryl, arapkyl, amino, benzyl amino can be given -, dibenyl-amino, nitro, carboxyl and carboxyl ester groups and the like, fb-Substituent can be selected from a large number of groups and limited only by the oC-amino acid that is desired by the end product. Examples of Oi-amino acids, the anti-compounds of which can be prepared according to the process of the invention, are alanine, p-chlorophenylalanine, tryptophan, phenylalanine, 3- (3 4 "dioxyphenyl) -alanine, 5-hydroxytryptopha, lysine, histidine, tyrosine , lemin, ggootaminova acid and valiv. The acyl group can be substituted or unsubstituted by an ashl group, such as acetyl, benzyl, formyl, propionyl, butnry, toluyl, nitrobenzoyl, or other acyl species that are used as blocking groups in petetidiom synthesis. Phosphine or arssov ligand.my can be blunt, for example the formulas where A is phosphorus or m to k; R, R and R are each hydrogen independently; alkyl is active with at least one 5T71 atom and max amum 12 ursad of urrod mixed alkyl with substituents representing amivo, carbokyl-, ari1 nitro, and alkoxylcarboxylic, having max 4 carbon atoms, aryl, arylo-aryl-aryl-aryl, 4 x aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, aryl, carboxylic, aryl, aryl, aryl, 4-carbon with the substituent - MHji representing alkoxy or alkyl, oxyl, arnloxvl, amino and ntro groups | moreover, the number of substituents is less than 3; cycloalkyl, having at least 3 carbon atoms, substituted cycloalkyl; pyrril, thienyl} furyl; Gshridip, piperidil or 3-choleteryl. The optical activity of the metal coordination complex according to the invention is characteristic of the phosphonic or arsine ligand. Optical activity may be the result or the presence of three different groups at the phosphorus atom or the mouse atom, or the presence of an optically active group adjacent to the phosphorus atom or mouse. In the coordination metal complex of the above formula, one ligand (L) must be optically active to carry out the reaction. If the optical activity of the ligand is due to the presence of an optically active group adjacent to a phosphorus atom or mouse, there should be only one such group, and the other two can be the same or inactive. In this case, only one of the groups I, R or K must be optically active, the other two groups may be identical or inactive. A catalyst is used that performs a focal metal com. Plexes of the given formulas. shows asymmetry n, therefore, optical activity, it also denotes an asymmetric atom or a dissymmetric group. For example, R indicates that phosphorus or pulmonary are asymmetric. The absence of an asterisk indicates no optical activity. () s; CIDM X A R RR), j (); an) MX {A R, R, R) fAR5R6R7) g (iV) MX () 3} (V) MA () (). {VI) () (OfinMXjCA R5 R RMj,) No. 4s (A R5RbR7)). aX) MJ, () (X) No. X9 {AR R {M ,; ai) Mx, () l nrfc - (AI ajM), (), 9 1 (XW) MX2fA R R) (); ift "5i 6s (XV) M-XjfAR R R7) gj (XVl) M Xj (AR n6R7HAR R (where M, X, A, RR and R have the previously mentioned meanings. The method is preferably carried out in the presence of an optically active phosphine phosphate or an arsine ligand, where the ligate is in a ratio of from 1.5 to 2.5, preferably 2, equivalents of ligand per 1 mole of metal. Preferably, the optically active catalyst is in solid form for easy handling and storage. such as benzene, ethanol, cyclohexene, and in mixtures of these solvents. Almost any aromatic or deprotected alkane or cycloalkane solvent that is inactive under the conditions of the hydrogenation reaction.Nitrobenzene solvents, preferably methanol, can also be used. The catalyst is added to the solvent either by itself or as components, which then form catalyst When the catalyst is added in the form of its components, it can be added either before or together with the addition of | i -substituted oC-cylamidoacrylate acid. The components for preparing the catalyst in place are a soluble metal compound and an optically active phosphine or arsine ligand. The catalyst can be added in any catalytic affective amount and usually in the range from O.OOOl to 5% by weight of the contained metal, based on the content of an ft-substituted oC-adyl amidoacrylic acid and / or its salts. It is necessary to take measures to avoid contact of the catalyst or the reaction mass with oxidizing agents. In particular, precaution is taken to avoid contact with oxygen. It is preferred to prepare for the hydrogenation reaction and the actual reaction in other gases as compared with Hg) which are inert with respect to reagents and catalysts, such as nitrogen or uplerod dioxide. Asymmetric hydrogenation is enhanced when there is a base in the reaction mass. Although asymmetric hydrogenation can be carried out in a base-free reaction mass and can even be carried out under acidic conditions (in an acidic medium), it is enhanced by adding a small amount, not more than one equivalent, of the basic substance per mole of acrylic acid. The bases that can be used are tertiary, such as triethylamine, MaOI, and almost any other basic substance that can form salts with carboxylic acids. Reaction temperatures can range from -2o to. Higher temperatures may be used, but they may increase side reactions. The desired product was prepared using known methods. Example 1 A device equipped with a device, a measuring pressure, a means of measuring temperature and heating devices, is loaded into a hydrogenation unit. 25 parts with β-benzamido-4-oxy-3-methoxyncinnamic acid, 186 parts of methanol and 64 parts 5 % sodium hydroxide. The bath is thoroughly cleaned of any traces of air and a final pressure of 50 psi is established. inch of hydrogen and a temperature of 25 ° C. The catalyst solution is prepared by dissolving O, OO59 of rhodium 1,5-cyclohexadne-chloro -1,5-hexadiv-Ct 2 in 2 ml of benzene under a nitrogen atmosphere. Then, 0, O139 g of (n -) - methylphenyl-o-nizylphosphanic acid in 1.3 ml of benzene is added. Hydrogen is then passed through the mixture for 5 minutes. The resulting catalyst solution is then injected into the autoclave. Hydrogenation begins immediately and ends after 3-4 hours at 25 ° C and a pressure of 50 psi. The test of the resulting solution showed an optical purity of 56.4%, corresponding to 78 (22 L) D mixture of sodium salt N- benzolyl-3- (4-ox-3-methoxyphenyl) - "lanine. N-Benzoyl-substituted amino acid can be obtained in 95% yield by evaporation of methanol and sodium hydrogen salt neurolysis. The resulting L antipode Can be converted to L-DOPA (dioxyphenylalanine by simple hydrolysis to remove the blocking groups, benzoyl and methyl in position 3 of the substituent on phenyl. Example 2. In a one-liter autoclave, 25 g of I, -benzamido-4-ox -3-methoxycinnamic acid.

ZOO ml of methanol and O, 6 ml of 5% aqueous solution of NaOH.

Mixed at 25 ° C under a pressure of 4 pounds per square inch of pure hydrogen. Then approximately 1 ml (O, O1% Rtl and 0, O5% phosphine) of the catalyst solution is added through the opening without reducing the pressure. The catalyst solution is adjusted by dissolving under Ng O, 005O g () -1,5-hexedi- (C) in 0 , 33 ml of dilute methylphenium o-ynizofosfina with a specific rotation of o13 «+ 42 (methanol) in benzene, containing O, L41 g / ml and diluted to a volume of 1 ml with methanol.

The 14OO rpm stirring rate is maintained in the reaction mass and the hydrogen begins to adsorb after a 2-5 minute induction period and the hydrogenation ends after 2 hours.

The methanol is evaporated and the acid is dissolved in one mole of an aqueous solution of NaOH. The neutral catalyst is extracted with benzene and precipitated separately for regeneration. The free amino acid is then precipitated by adding to the concentrated palate with free consumption (crystallization) .; 24 g of N-benzoi-J- 3- (4-oxy-3-methoxyphenyl) -vlanin are obtained, containing 73% L-antipode and 27% 33- antipode. L-antipod can be converted into {, α-dioxyphenylalanine by hydrolysis.

Examples 3-17. Other oggg chesky active L-amino acids are semi. The process is carried out according to the method of examples 1 and 2. The olefin compound is hydrogenated, and the phosphine ligand is used in a rhodium catalyst. Optical purity is shown in the table.

1.2

C - COOH

SNS - CH - COOH

hell

down

C-COOH

CHS-CH-COOH

I n

SNS

R СНзСН Шг6

32

eight

Uo

Sn C-Soon; Y-SN-SNSOON

with about

12

SNSN SNO

with about

 / Bsn-s-soon; -sng-sn soon tt

I

sn.

p-SNZ

45

NH

SNS

 -soon n

14.5

cacjCH-iCHjsn -sn -soon

Jcr

28

CHjCH sn 2

Sn c-soon:

SNZO

sn c-soon

but I

NH

32

(Sun; - - Sun - Soon 3 -Volvsteril D

SNZO

SNSO,

SN C-COOH YO NN i 0

 y-CH-CH-COOH

F

с о СНзО, СН С-СОО НО- (СНЗО

0,1 CH-COOH CEE n ° io-4-sn c-soon no-uning

EXAMPLE 18 An autoclave is filled with 25 g (mol) of acetate 1-acetamido 4- "8CHI" 3 "4 ethoxyaccharide, choy acid,}

ZOO ml of methanol and 0.36 ml of 5O% KaCHi. The pressure in the autoclave is maintained at about 35 pounds per square inch with a mixture (50:50) of nitrogen and hydrogen.

The catalyst solution is prepared by dissolving 0, OO5O g (0.023 mol) CHj-C-O

(Rfl-.1.5-hexadiene-Ce2 ° ash and adding under 051 mol (f) metric cyclohex1-1-0 lower phosphine (optical purity of about 90%) in 2.4 ml of benzene. Hydrogen passes a wedge through this solution for 1O.

Claims (1)

The catalyst solution is then added to the autoclave. The hydrogenation is carried out at and is completed within 4 hours. Pro0-СНз б с-сo sd, - 0-СНз 50 CHjfCH-COOH, the product obtained by evaporation of the solvent, is N "tsetil-3- (4-hydroxy) acetate. 3-methoxyphenyl) -sanine, which has a specific rotation oLj- +38, (Na salt in water). Pure acetate M acetyl 3- (4-hydroxy-3-methoxyphenyl) b-alanine, as well as the sodium salt in water, has a specific rotation CLJ, + 54, O. Thus, the optical purity of the 7O product obtained as a result of hydrogenation, 7% | those. better than 85% U-antipod and 15% 1E-antipod. Using a similar procedure with respect to (-) methylcyclohexyl and anisylphosphine (optical purity about 80%), the result is a hydrogenation product containing the predominant amount of 13-antipode (optical purity of the reaction product mixture 65%). Thus, with an appropriate selection of one of the two (+) or () phosts of the phosphine, a substance can be obtained in large quantities. Example 19. The technique used is similar to that of Example 18, using () -methylcyclohexnyl-o-anylphenol as an optical and of a k-ligand and cC-benzamide 4 ° hydroxy "-3-methoxy cinnamic acid as | 5 substituted d-acylamido acrylic acid. The product obtained as a result of gyration, N-benzoyl-3- (4-hydroxy-3-methoxysyphenyl) -alanine, contains a large amount of D-antipod (optical purity of the mixture of the reaction product is about 65%). Claim 1. Investigation of d-or E-isomers of α-amino acids by hydrogenation of derivatives of amnno-acrylic acid or its salt in the presence of a catalyst, followed by isolation of the target product in a well-known way, characterized in that, in order to simplify the process and obtain the corresponding the antipode, an optically active metal coordination complex of the general formula, or m% c de M - rhodium, ruthenium, iridium or o-II5 M - palladium or platinum, is used as a catalyst of hydrophobic; X is hydrogen, fluorine, chlorine, bromine or yop; L is phosphine, or arsia, and at least one of the L -groups is optically active; And is an integer from 1 to 3. 2, the method according to claim 1, which means that the process is held in the presence of the base. Priority points: 11.05.70 p. 1. 03.OZ.71.po p. 2.