JPS6035997B2 - Method for producing N-substituted phenylglycine - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing N-substituted phenylglycine.

Specifically, the present invention provides a method for producing N-substituted phenylglycine in good yield by electrolytically reducing penzylideneamines in the presence of carbon dioxide using a solid electrode as a cathode. N-substituted phenylglycine is used as a raw material for the production of pharmaceuticals and as a stabilizer for polymers, and is an industrially useful compound. The following two or three methods are known as methods for producing N-substituted phenylglycine.
'1} A method in which a benzaldehyde derivative is reacted with sodium cyanide or potassium cyanide in the presence of an amine or a mineral acid salt of an amine to form an aminonitrile derivative, which is then hydrolyzed to synthesize it.

(2) A method in which phenylacetic acid or its derivatives (camido, ester, nitrile) is once brominated to give a Q-fromphenylacetic acid derivative, and this product is treated with an amine.

however.

The former method (m) requires the use of highly toxic hydrocyanic acid derivatives as a reaction reagent, and has a major drawback that cannot be avoided from the viewpoint of reaction operation and waste disposal. Furthermore, it is also difficult that a considerable amount of tar-like polymer is produced when the intermediate product, the aminonitrile derivative, is hydrolyzed to produce the corresponding phenylglycine. In addition, the latter method (1) also has major drawbacks in that phenylacetic acid derivatives generally have extremely strong lachrymatory properties, and that bromine, which is toxic and difficult to handle, must be used as a reaction reagent. As a result of intensive research into a method for producing N-substituted phenylglycine by electrolytic carbonization, the present inventors discovered that benzylidene amines were electrolytically reduced in a polar non-aqueous solution in the presence of carbon dioxide using a solid cathode as the cathode. N- with good yield
It was discovered that substituted phenylglycine could be obtained, and the present invention was completed.

That is, the present invention is a method for producing N-substituted phenylglycine in which penzylidene amines are electrolytically reduced in a gutter nonaqueous solution in the presence of carbon dioxide using a solid electrode as a cathode.
Penzylideneamines, which are the raw materials of the present invention, are substances represented by the general formula R-CH=N-R', where R is a substituted or unsubstituted aromatic hydrocarbon residue, Generally, the case where R is a substituted or unsubstituted phenyl group is most widely used.

Furthermore, the above-mentioned substituents are not particularly limited as long as they are inert under the electrolytic conditions of the present invention, and typical examples of commonly used substituents include fluorine, chlorine, bromine, or iodine. These are atoms or groups such as halogen atom; alkyl group: ester group; ether group; carpoxyl group: phenyl group. Further, R' in the general formula is not particularly limited as long as it is inert under the electrolysis conditions of the present invention, but is generally an aromatic hydrocarbon residue exemplified as R in the general formula; a methyl group, an ethyl group, Straight chain or branched alkyl groups having 1 to 20 carbon atoms such as butyl group, amyl group, hexyl group, lauryl group; cycloalkyl groups such as cyclobentyl and cyclohexyl; the above-mentioned aromatic hydrocarbon residues, alkyl Substituted or unsubstituted phenyl, cycloalkyl group, halogen atom such as fluorine, chlorine, bromine, iodine, ester group, ether group, etc., where one or several hydrogen atoms of the group or cycloalkyl group are exemplified as substituents of R above , a carboxyl group, such as a phenethyl group, a P-chlorobenzyl group, an r-methoxy n-bentyl group, a benzylideneamino group, etc., are preferable. As the electrolytic solvent used in the present invention, a gutter nonaqueous solvent is preferably used.

In general, acetonitrile, propionitrile, N-dimethylformamide, dimethylsulfoxide, hexamethylphosphotriamide, benzonitrile and the like are preferably used alone or in combination. Acetonitrile is particularly suitable because it is easily available, inexpensive, has a low boiling point, and is easy to remove by distillation. The carbon dioxide gas used in the present invention may be produced by blowing carbon dioxide gas into the electrolytic solution.
Electrolysis may be carried out under pressure of carbon dioxide gas, or electrolysis may be carried out while appropriately adding solid carbonic acid (dry ice) little by little.

In addition, means for causing carbon dioxide gas to exist in the electrolytic system may be appropriately selected and employed as required. The present invention requires the use of a solid electrode as a cathode, and the material of the solid electrode is not particularly limited and any material may be used as long as it has sufficient conductivity under electrolytic conditions.

Examples of representative solid cathodes that are generally suitably used include brass, graphite, Inconel, copper, nichrome, zinc, lead, platinum, nickel, stainless steel, and aluminum. Generally, mercury is most widely used as a cathode for electrolysis, but the use of a mercury cathode in the present invention is not preferred because the yield of N-substituted phenylglycine obtained is insufficient compared to the case of a solid cathode. The anode is not particularly limited as long as it is resistant to corrosion under the electrolytic conditions of the present invention, and commonly known platinum, graphite, etc. are used. In carrying out the present invention, it is a very preferred embodiment to add an electrolyte that is soluble in the polar non-aqueous solution and is difficult to reduce under electrolytic conditions for the purpose of imparting conductivity to the electrolytic system.

The above-mentioned electrolyte is not particularly limited and any known one can be used, but it is generally best to choose one that can be easily separated from the product obtained by electrolytic reduction. An example of what is generally preferably used is a tetraalkyl ammonium salt represented by the general formula R''4N derived Xe.In the above general formula, R''
is an alkyl group having 1 to 6 carbon atoms, and X is CI, Br,
1, OH, OSQCH3, BF4, CI04, etc. are commonly used.

More specifically, tetraalkylammonium halides, particularly tetraethylammonium iodide, are most suitable. Further, as the electrolyte, a phosphonium salt such as tetraphenylphosphonium tetrafluoroporate or a key reducing compound under electrolytic conditions using magnesium perchlorate may be used as required. As the electrolytic means in the present invention, a constant current electrolysis method, a constant voltage electrolysis method, etc. may be selected as necessary, as long as the conditions for reducing at least the raw material penzylidene amines can be set.

Although it is generally convenient to carry out electrolytic reduction at room temperature, the temperature is not particularly limited, and there is no particular problem as long as it is between the freezing point and boiling point of the solvent. Although it is convenient to carry out the reaction at normal pressure in a carbon dioxide atmosphere, there is no problem in carrying out the reaction under pressure using carbon dioxide or an inert gas which cannot be cathodically reduced in the presence of carbon dioxide. It is desirable to pour the electrolyte solution into the solution, but when electrolysis is carried out while blowing carbon dioxide gas or other inert gas into the solution, it may be sufficient to pour the electrolyte solution into the solution. The electrolytic cell used in the present invention is not particularly limited, and any known electrolytic cell can be used.

The anode and anode chambers of the decomposition tank may be separated by a sieve-like glass partition of appropriate roughness, but if there is a risk of deterioration in product yield or current efficiency due to mass transfer, cation exchange may be used. It is preferable to partition with a membrane. The electrolytic reduction reaction mechanism in the present invention is shown by the following equation.

As mentioned above, the target product of the present invention is N-substituted phenylglycine in which carbon dioxide gas is involved in the reaction, but penzylamines are also obtained as by-products.

Penzylamines alone are known as polymer stabilizers and pharmaceutical intermediates. Therefore, in the present invention, if penzylamines are separated from the reaction product together with N-substituted phenylglycine as necessary, the method can be industrially advantageously implemented as a rice cake production method. Furthermore, as is clear from the above formula, in the present invention, it is necessary to first involve carbon dioxide gas in the reaction, and in this point, the intervention of a proton donor such as water in the electrolyte solution increases the yield of N-substituted phenylglycine. It is desirable to avoid this as much as possible in order to improve If the desired product obtained by the present invention is insoluble in the electrolyte, it can be isolated simply by filtration.

On the other hand, if the desired product is soluble in the electrolyte, it can be isolated in a free form by post-treatment, usually by adding water and a mineral acid as a proton donor. The method of isolation by the above-mentioned post-treatment is not particularly limited, and any necessary means may be employed as appropriate, but typical isolation methods are exemplified below. That is, after the electrolysis is completed, the solvent is removed by distillation, water is added to the residue, and penzylamines are extracted with a solvent that does not mix with water, such as chloroform, benzene, or ether. If this extraction solvent is distilled off, penzylamines will be obtained. If N-substituted phenylglycine becomes solid and precipitates as a result of the above operation of adding water, it can be isolated by simply heating it in a furnace, but if it does not precipitate, perform the solvent extraction. The remaining alkaline water layer is made neutral or weakly acidic (p
H2-6), and the corresponding N-directly substituted phenylglycine is monopolized. Most of the N-substituted phenylglycine thus obtained is a pure tin compound product, but if further purification is required, it may be recrystallized from a solvent such as alcohol or ethyl acetate. EXAMPLES In order to describe and explain the present invention in detail, Examples and Comparative Examples will be given below, but the present invention is not limited to these Examples.

Note that the yield of the desired product in the Examples was calculated from the weight of the desired product relative to the weight of penzylidene amine used. Example 1 Penzalaniline (1.00 hours, 5.52 hmole), tetraethylammonium iodide (1.0 hours), and anhydrous acetonitrile (100M) were placed on the cathode side of an H-type cell partitioned with an ion exchange membrane. .

Next, tetraethylammonium iodide (5.
0) and acetonitrile (Z of 70). A brass pole (4 x 8 squares, 2 walls thick) was used as the cathode, and a platinum cylinder (6 x 8 squares, 0.2 inch thick) was used as the anode, and the cathode potential was -1 relative to the saturated Kanto electrode. While maintaining the voltage at .85V, a current of 1940 coulombs was applied while constantly blowing carbon dioxide gas under the electric lamp. At this time, the initial current value is 5
The current value at the end was 0.3 hA. After the electrolysis was completed, the catholyte was transferred to an eggplant-shaped flask, acetonitrile was distilled off, and 20 parts of water was added to the residue.

First, after removing benzene solubles (mainly amine derivatives) with Penzel 100', the remaining alkaline aqueous solution was carefully acidified with hydrochloric acid, and the melting point was 190~
N,2-diphenylglycine 1.0 at 191°C (decomposed)
I got 67 evenings. The yield was 85.1%. Comparative Example 1 Electrolytic reduction was carried out at −1.90 V in substantially the same manner as in Example 1, except that purified mercury (15 [) was used as the cathode.

After electrolysis, the catholyte was treated in the same manner as penzylidene aniline from 1.00 to N. 2-diphenylglycine 0.485
I got the evening. The yield was 387%. Example 2 1.00 g of penzylidene aniline was subjected to potentiostatic electrolytic reduction in substantially the same manner as in Example 1, except that various solid metal electrodes with approximately the same area were used as the cathode instead of a brass cathode. Ta.

The main electrolysis conditions and the yield of N,2-diphenylglycine were as shown in Table 1. Example 3 The same procedure as in Example 1 was carried out except that various penzylideneamines shown in Table 2 were used instead of penzalaniline in Example 1, and the current values were changed to those shown in Table 2.

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Claims (1)

[Claims] 1. A method for producing N-substituted phenylglycine, which comprises electrolytically reducing benzylidene amines in the presence of carbon dioxide gas in a polar nonaqueous solution using a solid electrode as a cathode.