JPS62103054A - Alpha-azo ester and production thereof - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R<1> and R<2> are organic substituent group; R<3> is aryl or heterocyclic ring: R<4> is alkyl, aryl or aralkyl). EXAMPLE:Methyl (alpha-phenylazo)dimethylacetate. USE:A synthetic intermediate for alpha-amino acids useful as sweeteners, seasonings, food additives, medicines, agricultural chemicals, surfactants, etc., obtainable in good yield by simple operation. PREPARATION:A ketenesilyl acetal expressed by formula II (R<5>-R<7> are alkyl, aryl or aralkyl) is reacted with a diazonium salt expressed by the formula R<3>N2X (X is diazonium salt-forming anion) in a solvent, e.g. pyridine, under mild condition of -30 deg.C-room temperature to afford the aimed compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Technical Field] The present invention relates to α-azoesters useful as α-amino acid synthesis intermediates, and a method for producing the same. More specifically, the present invention relates to a method for producing α-azo esters, which is characterized by reacting ketene silylacetals easily obtained from esters with a diazonium salt.

[Prior art]

α-Amino acids and their derivatives are used by themselves or as raw materials in sweeteners, seasonings, food additives, pharmaceuticals and agrochemicals, surfactants, etc., and demand is expected to increase with the progress of biotechnology. It is an important group of compounds.

Some α-amino acids can be obtained by fermentation using microorganisms, but the types are limited and it is not possible to obtain any amino acids. The Strecker process, which uses a small amount of aldehyde as a starting material, is used on an industrial scale, but it requires extremely toxic hydrogen cyanide, and technological improvements in the Sohio process have reduced by-product hydrogen cyanide, making it more expensive. The Wakamatsu method, which involves carbonylation of an amide and an aldehyde, is also known, but it requires high temperature and high pressure conditions. Furthermore, the aldehydes required for these Strecker and Wakamatsu methods are generally not easy to obtain; on the other hand, the reductive amination method of α-keto acids is also known;
In addition to these methods, for which no advantageous industrial method for producing -keto acids has been developed, a method of aminating the α-position of a carboxylic acid ester can be considered. Conventionally, in this method, after halogenating the α-position, a nitrogen atom is introduced using ammonia, phthalimide, succinimide, sodium azide, etc., but the yield is not always good and the nucleophilic substitution reaction to form a halogenoester It has disadvantages such as requiring relatively high temperatures.

As described above, it must be said that each of the conventional techniques for producing α-amino acids or intermediate raw materials thereof has drawbacks.

〔the purpose〕

In view of these facts, the present inventors have conducted extensive research and exploration into the method of introducing an amino group or a functional group that can be converted into an amino group into the α-position of an ester. Diazonium salts easily react with silylacetals without releasing nitrogen molecules,
We discovered an interesting fact that an azo compound can be obtained, and based on this knowledge, we completed the present invention.

Therefore, an object of the present invention is to provide a method for producing α-azoesters in good yield by a novel reaction.

〔composition〕

That is, according to the present invention, the general formula % () (wherein RL and ul are organic substituents, R3 is an aryl group or a heterocyclic group, and R4 is an alkyl group, an aryl group, or an aralkyl group) In producing the α-azoesters represented,
A ketene silyl acetal represented by the general formula % formula % () (wherein R1, R2, nl, and R4 are the same as above, and RG, RG, and nl represent an alkyl group, an aryl group, or an aralkyl group); General formula % formula %
() (wherein R3 is the same as above and X represents a diazonium salt-forming anion) is provided.

The azoester compound obtained by the present invention is a new compound. Furthermore, the reaction of the present invention is novel and can be expressed by the following reaction formula.

R'R''C=C(O3iR'R'R' )(O
R') 10R"N 2X →R'R"C(N
zR3)(COOR')+R'R'R' SiX
(1) (In the formula, R1-R7 and X are the same as above)
A group, an alkenyl group, an alkynyl group or a heterocyclic group can be mentioned. In addition, in the general formula (III), the diazonium salt-forming anion
Examples include complex ions for stabilizing diazonium salts represented by +sVn (M is a metal cation, ■ is a halogen ion, or CN, Q, m, and n are natural numbers).

Specific examples of the above-mentioned substituents include methyl, ethyl, propyl, hexyl, octyl, etc. for alkyl groups, benzyl, phenethyl, etc. for aralkyl groups, and phenyl, tolyl, xylyl, naphthyl, etc. for aryl groups. Examples of alkenyl groups include vinyl, propenyl, butenyl, styryl, etc.; examples of alkynyl groups include ethynyl, phenylethynyl, etc.; and examples of heterocyclic groups include furyl, thiazolyl, chenyl, pyridyl, etc. Note that a functional group may be bonded to these substituents, and examples of these functional groups include a halogen atom, an alkoxy group, an alkoxycarbonyl group, a dialkylamino group, and a β-indolyl group.

dialkoxymethyl group, thioalkoxy group, nitro group,
Examples include cyano group. Examples of the substituent R3 include phenyl, chlorophenyl, bromophenyl, nitrophenyl, tolyl, anisyl, formylphenyl, ethoxycarbonylphenyl, dimethoxymethylphenyl, naphthyl, pyridyl, chenyl, furyl, and the like. To illustrate the above-mentioned X, Cf1. ) ISO4, NO
3, CaO2゜BF,,BPh4. PFs, CI 3
Co 2 , 1/2ZnCQ 4.1/2SnCQ6.
1/2HgCQ 4 , 1/2CdCQ , s , 1
/3Fe(CN)s, FeCQa, and the like.

Note that these examples of substituents or functional groups are merely illustrative, and the present invention is not limited thereto.

The amount of the diazonium salt used in the method of the present invention is sufficient to be equivalent to or in slight excess of the ketene silylacetal, but even if the amount is more or less than this, the reaction will not occur.

The reaction of the present invention usually proceeds under mild conditions of -30°C to room temperature, but heating can be applied if necessary to obtain a preferable reaction rate. However, too high a temperature is not preferable because it causes decomposition of the diazonium salt.

The solvent used in the reaction of the present invention has an active proton source such as water, alcohols, phenols, carboxylic acids, primary or secondary amines, and is itself reactive with the ketene silyl acetal or diazonium salt. Any conventional solvent can be used, except those that have Examples of these solvents include hexane, benzene, toluene,
Acetonitrile, pyridine, tetrahydrofuran, diethyl ether, acetone, dimethylformamide.

Examples include sulfolane, ethyl acetate, HMPA, etc.
Pyridine gives the most favorable results. Moreover, these solvents can also be used in combination.

Separation and purification of the target α-azo ester from the reaction solution obtained by the reaction of the present invention is carried out by removing the diazonium salt by washing with water, etc., removing the solvent by distillation, etc., and then performing further distillation, recrystallization, chromatography, etc. can do.

〔effect〕

The present invention is a method using a novel reaction, and a wide variety of ketene silylacetals and diazonium salts are used as raw materials, and various α-azoesters can be obtained with easy operations and good yields.

〔Example〕

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 In a flask with an internal volume of 20 m, (1-methoxy-2,
2-dimethylethynyl)oxytrimethylsilane (1,
Ommo Q) and pyridine 3II as a solvent.
Add Q. Benzenediazonium tetrafluoroborate (1,3 mmo Q ) was added to this mixture, and the mixture was stirred at 0° C. for 2 hours under a nitrogen atmosphere. The reaction solution was diluted with diethyl ether, washed successively with 1.5N hydrochloric acid, water, and saturated brine, then the organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. When the resulting oily mixture was separated and purified by silica gel thin layer chromatography, it was found that (α-phenylazo) dimethyl acetate methyl ester (0.90 m
wol) was obtained.

Examples 2 to 6 Reactions were carried out according to the method of Example 1 using various ketene silyl acetals. The results are shown in Table 1.

Claims (2)

[Claims] (1) General formula R^1R^2C(N_2R^3) (COOR^4) (wherein, R^1 and R^2 are organic substituents, R^3 is an aryl group or a heterocyclic group, R^4 represents an alkyl group, an aryl group, or an aralkyl group. (2) General formula R^1R^2C(N_2R^3) (COOR^4) (wherein, R^1 and R^2 are organic substituents, R^3 is an aryl group or a heterocyclic group, R^4 represents an alkyl group, an aryl group, or an aralkyl group).
General formula R^1R^2C=C(OSiR^5R^6R^7)(O
R^4) (In the formula, R^1, R^2, R^3, and R^4 are the same as above, and R^5, R^6, and R^7 are an alkyl group, an aryl group, or an aralkyl group. A method characterized by reacting a ketene silyl acetal represented by .