JPS5976057A - Preparation of alpha-amino-cycloamide - Google Patents

Abstract

PURPOSE:To prepare the titled compound with simple process, in high efficiency, by using a basic amino acid such as ornithine as a raw material, and carrying out the dehydrative cyclization of the material simply by heating in an aqueous medium. CONSTITUTION:In the conversion of the basic amino acid of formula I (n is 2 or 3) (e.g. alpha,gamma-diaminobutyric acid) directly to the corresponding alpha-amino(cyclic amide) of formula II (e.g. alpha-aminopyrrolidone), the dehydrative cyclization of the basic amino acid is carried out in water or in an aqueous medium such as a mixture of water and a hydrophilic organic solvent such as methanol, ethanol, etc. (preferably in water) at about 80-160 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention uses a basic amino acid represented by the general formula (wherein n is an integer of 2 or 3) as a raw material to directly convert the corresponding α-7 A novel method for producing minocyclic amides is concerned.

Conventionally, a method for producing a corresponding α-amino cyclic amide using a basic amino acid represented by the above general formula, that is, ornithine or α,γ-diaminobutyric acid as a starting material, has been as follows: (1) preparing an ester of a basic amino acid; A method of synthesis and dealcoholization by heating in an organic solvent or in the absence of a solvent (J, Chem, Soc, +
943, P39) and (2) a method of cyclizing a basic amino acid ester in concentrated ammonia water (Japanese Patent Publication No. 4
6-37362) is known. However, these known methods all involve esterification of a basic amino acid in the presence of an acid in alcohol, and a step of neutralizing the used acid with a base. In addition to the desired cyclized product, 1 Kojigatopipera 6
This method has drawbacks such as the production of gin as a by-product and a decrease in the cyclization yield. Furthermore, method (2) requires highly irritating concentrated ammonia water, which is not only economically disadvantageous, but also requires measures to prevent the risk of ammonia volatilization leakage and environmental pollution. be.

The object of the present invention is to directly produce e-mail from ornithine or α,γ-diaminobutyric acid without having the disadvantages of such conventional methods.
It is an object of the present invention to provide a simple method for efficiently producing and obtaining an α-amino cyclic amide corresponding to one basic amino acid as a raw material, and the present invention V is based on the general formula (where n is an integer of 2 or 3). ) to heat the basic amino acid represented by in an aqueous medium? From this, an α-amino cyclic amide represented by the general formula (where n has the same meaning as above) can be produced and obtained in high yield.

The aqueous medium used in the present invention 1 is water or a mixed solvent of water and a hydrophilic organic solvent (e.g., methanol, ethanol, propatool, inpropatol, dioxane, tetrahydrofuran, N,N-dimethylformamide, etc.) Among them, water is the most practical.

The concentration of basic amino acids is not particularly limited to 1, but in fact 1
From the viewpoint of the viscosity and fluidity of the moss solution, it is preferably 1 to 50% by weight. Of course, the cyclization reaction can proceed even at concentrations exceeding this concentration range, but if the concentration is too high, the fluidity of the solution decreases significantly, making it difficult to handle. The reaction temperature may generally be in the range of 801:' to 1' 60C. The higher the temperature, the higher the rate of the cyclization reaction, and if the temperature is lower than 80C, the time required for one cyclization process becomes longer.

Moreover, even if the temperature exceeds 1600, the cyclization reaction rate does not improve much. Although the pressure is determined by the temperature, the cyclization reaction is usually carried out under normal pressure or increased pressure.

After the reaction is completed, the α-7 minocyclic amide is isolated and purified from the reaction solution by a conventional method, such as distillation or extraction with an organic solvent.

Hereinafter, a detailed description will be given of the embodiment. However, it goes without saying that the present invention is not limited to just one embodiment.

Example 1 Ornithine 13.2 f in a pressure-resistant container 1 volume, water 40 m
1 was added, and the mixture was heated and stirred at +60p for 3 hours. After distilling off the water, the residue was distilled at 3+nmHg 132 C to obtain α-aminopiperidone as a pale yellow-green viscous liquid when heated.9.
I got 12. Yield 79.8%. Identification was performed using infrared absorption spectroscopy, nuclear magnetic resonance spectroscopy, and thin layer chromatography.

Example 2 α,γ-diaminobutyric acid 47.2 ? was placed in a pressure-resistant container, 50 ml of water was added thereto, and the mixture was heated at 15 Orr for 5 hours.

After cooling the reaction solution to room temperature, a 1.5N aqueous solution of triram hydroxide was added and mixed uniformly.
Extracted with ml. After washing the chloroform solution with 100 m/' of 0.2N aqueous sodium hydroxide solution, chloroform was distilled off to obtain α-aminopyrrolidone 36.8 f as a viscous liquid when warm. Yield: 92%.Identification was performed using infrared absorption spectroscopy and thin layer chromatography.

Example 3 Ornithine was cyclized under the following conditions to obtain α-aminopiperidone. Quantification of α-aminopiperidone was performed using high performance liquid chromatography (ODS column, detection wavelength 2 10
methanol, eluent using 0.03 M 'J acid buffer 1 methanol 1/9).

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Claims (1)

[Claims] A general method characterized by heating a basic amino acid represented by the general formula (in the formula, n represents an integer of 2 or 3) in an aqueous medium to cyclodehydrate it. A method for producing an α-amino cyclic amide represented by the formula (where n in the formula has the same meaning as above).