JPS6130576A - Preparation of 2-amino-5-cyanopyrimidine - Google Patents

Abstract

PURPOSE:To obtain the titled substance useful as an intermediate for synthesizing drugs, agricultural chemicals, etc. industrisially advantageously, by using an alkali metal salt or a 2-hydroxymethylene-3,3-dialkoxypropane nitrile and a mineral acid salt of guanidine as raw materials, reacting them. CONSTITUTION:An alkali metal salt of a 2-hydroxymethylene-3,3-dialkoxypropane nitrile shown by the formula (R<1> and R<2> are 1-5C lower alkyl such as methyl, ethyl, etc., or R<1> and R<2> may be the same alkyl or different alkyls; M is alkali metal such as sodium, etc.) is reacted with usually 0.1-10mol, preferably 0.5-5mol based on 1mol compound shown by the formula I of a mineral acid salt of guanidine in an inert solvent such as methanol, diethyl ether, etc. at 0-100 deg.C, to give the aimed compound.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel method for producing 2-amino-5-cyanopyrimidine. 2- manufactured by the present invention
Amino-5-cyanopyrimidine.

It, the amino group at the 2nd position, and the cyanogen group at the 5th position can be variously converted into other functional groups, and both are useful compounds as synthetic intermediates for medicines, agricultural chemicals, and the like. (For example, Japanese Patent Application Laid-Open No. 507-95298, etc.) [Prior Art] No literature has been found so far describing a method for producing 2-amine-5-cyanopyrimidine.

[Problem that the invention seeks to solve]

The present inventors conducted extensive research with the aim of establishing an industrially advantageous manufacturing method for 2-amino-5-cyanopyrimidine.

[Means to Solve Problem 6] As a result, an alkali metal salt of 2-hydroxymethylene-6,6-dialkoxypropanenitrile.

The present invention was completed based on the finding that the objective can be achieved very easily by reacting mineral acid salts of guanidine.

2-hydroxymethylene-3,3- which is the raw material of the present invention
The structural formula of the alkali metal salt of dialkoxypropanenitrile can be represented by the first-order general formula (l).

HOM However, in general formula (L), R1 and R2 are.

Indicates a lower alkyl group having 1 to 5 carbon atoms such as methyl, ethyl, furoyl, phthyl, and pentyl.

R1 and B2 may be the same alkyl group or different alkyl groups. Also, general formula (1)
M in the formula represents an alkali metal such as sodium, potassium or lithium.

These alkali metal salts of 2-hydroxymethylene-6,3-dialkoxypropanenitrile.

It can be synthesized by a known method. For example, 3
, 3-dialkoxypropanenitrile can be synthesized by reacting it with a formylating agent such as a formate or carbon monoxide in the presence of an alkali metal alcohol-1 at a temperature of 0 to 100°C.

Examples of the mineral acid salt of guanidine, which is another raw material of the present invention, include guanidine hydrochloride, sulfate, nitrate, phosphate, and carbonate. These guanidine mineral acid salts are industrially preferable because if they are used in too large a quantity, many side reaction products will be produced, and if they are used in too small a quantity, a large amount of the other raw material will remain unreacted. do not have.

Therefore, the amount used is 2-hydroxymethylene-6,3
-9 Usually 0.1 to 10 mol, preferably 0.5 mol per mol of alkali metal salt of dialkoxypropanenitrile
~5 moles.

The reaction of the invention is carried out in a solvent. Any solvent that is inert to one reaction is useful. Specific examples include alcohol solvents such as methanol, ethanol, gropanol, butanol, and ethylene glycol; ether solvents such as diethyl ether, dimethoxyethane, dioxane, and tetrahydrofuran; and benzene, toluene, xylene, hexane, heptane, and cyclohexane. Hydrocarbon solvents; halogenated hydrocarbon solvents such as methylene chloride, chloroform, carbon tetrachloride, and dichloroethane; ester solvents such as methyl acetate, ethyl acetate, and butyl acetate; and acetonitrile, dimethyl sulfoxide, dimethyl formamide, and water. can be exemplified. Among these, it is particularly preferable to use alcoholic solvents or mixed solvents of alcoholic solvents and other solvents.

The reaction of the present invention is completed by carrying out the reaction at a temperature of 0 to 100°C for 0.1 to 10 hours.

After the reaction is completed, 2-amino-5-cyanopyrimidine can be isolated and purified by appropriately employing operations such as filtration, concentration, extraction, recrystallization, or sublimation.

〔Example〕

Next, nine examples of the present invention will be described. Note that the yield of the target product on each side is based on the alkali metal salt of 2-hydroxymethylene-S and 3-dialkoxypropanenitrile.

Example 1 Sodium salt of 2-hydroxymethylene-6,3-dimethoxypropanenitrile (purity 91.6 wt%) 10
, Off (55,5 mmol) in methanol 100-
After dissolving in guanidine hydrochloride 5.3
Add 0 f (55.5 mmol) little by little.

After the addition was completed, stirring was performed at room temperature for 7 hours. Next.

The precipitated crystals were filtered, washed with water, and dried under vacuum at about 50°C to obtain 5.37 pale yellow crude crystals. The purity of the crude crystals was determined to be 96.5% by liquid chromatography using an internal standard method. Therefore, the yield is 7
It was 6.8%. The elemental analysis values of white crystals obtained by recrystallizing these crude crystals from water are as follows.

Actual value (4) O: 49.58 H: 3.59 N:
46.78 Calculated value: @) C: 50.00 H: 3
．． 33 N: 46.67 Others, NMR, MS, Engineering R
From this thing.

It was confirmed that it was 2-amino-5-cyanopyrimidine.

Example 2 Potassium salt of 2-hydroxymethylene-6,3-jethoxypropanenitrile (purity 95.Owt%) 1o,o
y (45.5 mmol) in ethanol 15Drag
After dissolving in guanidine nitrate 6.1
9 (50 mmol) was added little by little, the temperature was raised to 40"CK, and the mixture was stirred for 5 hours. Next, most of the ethanol in the 9 reaction solution was concentrated under reduced pressure, water was added, and insoluble crystals were filtered. After drying this crude crystal in vacuum at about 50°C,
The yield of 2-amino-5-cyanopyrimidine was 83.7 when determined by internal standard method using liquid chromatography.
%Met.

Example 6 Sodium salt of 2-hydroxymethylene-3,3-di-n-butquine propanenitrile (purity 90.5 wt%
) 5,0f (18,2 mmol) in methanol 50m/
After dissolving 2.0 guanidine sulfate in
59 (19.0 mmol) was added little by little, and after the addition was complete, the mixture was stirred at room temperature for 8 hours.

After the reaction was completed, crude crystals were obtained according to Example 2.

The yield of 2-amino-51cyanopyrimidine was 85.1%.
Met.

Claims (1)

[Claims] A method for producing 2-amino-5-cyanopyrimidine, which comprises reacting an alkali metal salt of 2-hydroxymethylene-3,3-dialkoxypropanenitrile with a mineral acid salt of guanidine.