JPS6253501B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing alkyl nitroacetic esters. Specifically, the present invention relates to a method for producing alkyl nitroacetic esters by reacting nitroparaffins and alkyl phenyl carbonate esters in a liquid phase. Alkylnitroacetic acids are useful compounds for producing α-nitrocarboxylic acids by reaction with alkyl halides, aldehydes, and tertiary amines, and α-nitrocarboxylic acids can be produced by hydrogenation.
It is also known that amino acids such as phenylalanine, dopa, methyldopa, tryptophan, and α-methyltryptophan can be easily produced. Various methods are known for producing alkylnitroacetic acids. That is, (1) Kornblum et al.
J. Amr. Chem. Soc., 77 6654 (1955) reported the reaction of ethyl iodoacetate with silver nitrite to obtain ethyl nitroacetate. (2) Finkseiner et al.
J.Org.Chem., 28, 215 (1963) reported that a magnesium complex of nitroacetic acid was obtained by reaction of nitromethane with methylmagnesium carbonate, and then esterified with a strong acid to obtain nitroacetic acid ester. are doing. (3)Zenara Koka Journal 74, 70 (1971)
reported that a methazonate was obtained by the reaction of 2 moles of nitromethane and 8 moles of potassium hydroxide, and then esterified with a strong acid to obtain a nitroacetate. and (4) Sifniades et al. J.Org.
Chem. 40, 3562 (1975) reported that nitroacetoacetate was obtained by reacting acetoacetate with acyl nitrate, and then decomposed with alcohol to obtain nitroacetate. Methods (1) and (2) above use expensive silver salts as raw materials,
It is impractical because it uses magnesium metal,
Method (3) involves heating the alkali metal salt of nitromethane, which carries the risk of detonation, and is difficult to implement on a large scale.Method (4) uses acetoacetic acid as a relatively expensive raw material. Problems arise because esters and acyl nitrates are used. The present inventors conducted detailed studies on a new method for producing alkyl nitroacetic esters through a liquid-phase reaction between nitroparaffins and alkyl phenyl carbonates, and found that the reaction was controlled in the presence of cyanide ions. The inventors have now discovered that the reaction rate is greatly increased when the reaction is carried out in a polar aprotic solvent, and that the reaction can be completed even at room temperature, leading to the method of the present invention. That is, the method of the present invention involves reacting nitroparaffin, which is industrially easily available, with alkyl phenyl carbonate, which can be easily obtained in high yield from phosgene, phenols, and alcohols. In this method, nitroparaffins and alkylphenyl carbonate esters are reacted in a polar aprotic solvent in the presence of cyanide ions. The nitroparaffins used as raw materials in the method of the present invention have the general formula () (wherein R ₁ and R ₂ represent a hydrogen atom, an unsubstituted or substituted alkyl group, or a phenyl group). For example, nitromethane, nitroethane, 1-nitropropane, 2-nitropropane, 1-nitrobutane, 2-nitrobutane, 1
-Nitroisobutane, 1-nitrooctane, 2-
Examples include phenylnitroethane, p-chlorophenylnitromethane, and p-nitrophenylnitromethane. Furthermore, the carbonic acid alkyl phenyl esters used in the method of the present invention have the general formula () ArOCOOR ₃ () (wherein, Ar represents an unsubstituted or substituted phenyl group,
R ₃ represents an unsubstituted or substituted alkyl group). For example, ethyl phenyl carbonate ester, methyl phenyl carbonate ester,
Examples include ethyl carbonate-p-chlorophenyl ester, propyl phenyl carbonate, isopropylphenyl carbonate, methyl chloroglucyl carbonate. In the method of the present invention, the amount of the raw material compounds represented by the general formulas () and () to be used is as follows: The molar ratio ranges from 0.01 to 100, preferably from 0.1 to 10 molar ratio. Outside the above range, the amount of raw material recovered is large and is not practical. In the method of the present invention, the cyanide ion present in the reaction system may be added to the reaction system in any form, but it is usually added in the form of a salt for ease of handling.
The partner cation forming the salt may be an inorganic cation or an organic cation. Examples of inorganic cations include Group A, Group B, Group A, Group B of the periodic table,
Examples include group metal ions and ammonium ions. Examples of organic cations include primary, secondary, and tertiary amines, and quaternary ammonium ions. Furthermore, it may be added to the reaction system as a cyanide ion type anion exchange resin. There is no particular restriction on the amount of cyanide ions added. Since the reaction proceeds according to equation (1), In order to increase the reaction rate, it is preferable to use an amount equal to or more than the amount of _Ar OH produced in formula (1). The method of the invention is carried out in a polar aprotic solvent. Examples of this type of solvent include acetonitrile, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, dimethylsulfoxide, hexamethylphosphoramide, sulfolane, N-methylpyrrolidone, and the like. There are no particular restrictions on the amount of these solvents used;
An appropriate amount is used depending on the reaction raw materials, reaction conditions, and type of solvent. Usually, it is sufficient to use less than 10 times the amount of the raw material. To carry out the method of the present invention, there are no particular limitations on the order and method of charging the reaction raw materials, cyanide ions, and solvent. As long as the reaction is carried out in a liquid phase, the reaction pressure may be reduced pressure, normal pressure or increased pressure. The reaction temperature is in the range of -20 to 150°C, preferably 0
~100℃ range. The reaction time is the reaction temperature,
Although it varies widely depending on the type of solvent, etc., it is usually in the range of 10 minutes to 20 hours. The desired product has a pH of the reaction product liquid of 4 or less,
It can be obtained by conventional methods such as separation, drying, and distillation under reduced pressure. In addition, when using a cyanide ion type anion exchange resin, the target product is adsorbed on the resin, so after separating the reaction solution, the target product is eluted with an aqueous sodium carbonate solution, and the pH of the eluent is 4 or less. The desired product can be obtained by methods such as separation, drying, and distillation under reduced pressure. The present invention will be explained below with reference to Examples. Example 1 6.1 parts by weight of nitromethane, 15.2 parts of ethyl phenyl carbonate, and 6.5 parts of potassium cyanide were added to 100 parts of dimethyl sulfoxide, and the mixture was reacted at room temperature for 5 hours with stirring. 1N reaction solution
Pour into 150 parts of acetic acid aqueous solution, then add 100 parts of ethyl acetate.
of liquid was added to perform liquid-liquid separation. After washing the obtained ethyl acetate layer with water and drying with magnesium sulfate,
Distillation was carried out under reduced pressure to obtain 11.3 parts of a 68-70°C fraction (2 mmHg). The IR of this fraction was the same as that of the standard sample of nitroacetic acid ethyl ester. The yield (same as the raw material ethyl phenyl carbonate ester standard) is
It was 85%. Reference Example 1 To 60 parts of a dimethyl sulfoxide solution containing 6.1 parts of nitromethane and 15.2 parts of ethyl phenyl carbonate was added 60 parts of a dimethyl sulfoxide solution containing 13.2 parts of potassium salt of phenol, and the mixture was reacted with stirring at room temperature for 5 hours. The reaction solution was poured into 150 parts of a 1N acetic acid aqueous solution, and 100 parts of ethyl acetate was added to perform liquid-liquid separation. The obtained ethyl acetate layer was washed with water, dried over magnesium sulfate, and analyzed by high performance liquid chromatography, which revealed that it contained 13.9 parts of ethyl phenyl carbonate and 1.0 part of ethyl nitroacetate. . The yield was 7.5%. Examples 2 to 6 Experiments were conducted in the same manner as in Reference Example 1, using different nitroparaffin, alkyl phenyl carbonate, cyanide, and solvent, and the results shown in Table 1 were obtained.

[Table] Example 7 A strongly basic anion exchange resin in which 6.1 parts of nitromethane, 15.2 parts of ethyl phenyl carbonate, and 0.1 equivalent part of cyanide ions were adsorbed was mixed with acetonitrile.
100 parts of the solution was added to the solution, left at room temperature for 5 hours, the resin was filtered out, the resulting resin was packed into a column, 200 parts of an aqueous solution containing 20.0 parts of sodium carbonate was passed through the column overnight, and 400 parts of 1N acetic acid was added to the eluent. When the same operation as in Reference Example 1 was carried out, it was found that nitroacetic acid ethyl ester was produced with a yield of 90%.

Claims (1)

[Claims] 1. A method for producing alkyl nitroacetic esters, which comprises reacting nitroparaffins and alkyl phenyl carbonate esters in a polar aprotic solvent in the presence of cyanide ions.