JPH02104577A - Production of tetrahydropyrimidine compound - Google Patents

Abstract

PURPOSE:To simply obtain the title compound useful as an intermediate for dye, agricultural chemical and medicine or a catalyst for addition reaction of isocyanate with polyol in high yield by reacting a nitrile compound with 1,3-propanediamines in the presence of a specific catalyst. CONSTITUTION:A nitrile compound expressed by formula I (R<1> is aliphatic group, aromatic group or aliphatic group having aromatic substituent group) is reacted with 1,3-propane diamines expressed by formula II (R<2>, R<3> and R<4> are H, aliphatic group or aliphatic group having aromatic substituent group) using a salt of at least one kind of metal selected from a group of zinc, copper, iron, cobalt and manganese, preferably at a ratio of nitrile to diamine of 0.9-1.1 equivalent at 60-300 deg.C, especially 80-250 deg.C to provide the compound expressed by formula III. Furthermore, sulfur, hydrogen sulfide, etc., can be further used as the above-mentioned catalyst.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a method for producing a tetrahydropyrimidine compound.

Tetrahydropyrimidine compounds are useful as dyes, agricultural chemicals, pharmaceutical intermediates, or as catalysts for the W addition reaction between isocyanates and polyols.

<Prior art and problems to be solved by the present invention> Many methods have been proposed for producing tetrahydropyrimidine. For example, the reaction between N-alkyl-propanediamine and imidic acid ester amidine (A, Pin
ner, 1Tlie C11C11e der 工m1doe-ther Llnd 1hrer Der
ivateJ R, ○p1) enheim, Berlin (I982)), N-acyl-N- produced by hydrogenating N-acyl-N-alkylaminopropionitrile
Method for converting alkylpropanediamine into PR water fM (
J, Am, CC11e, Soc, 712850 (I
949)), the reaction of N-alkylpropanediamines with oxazolines (DE 2154948) and the reaction of propanediamine-toluenesulfonates with nitrile compounds (J, Chem, Soc, 194
7,497) etc. have been proposed.

However, in many of these methods, the reaction does not occur completely and the yield of the target product is insufficient. In addition, in the method of reacting propanediamine-toluenesulfonate with a nitrile compound, in order to isolate the tetrahydropyrimidine compound from the reaction mixture, it is necessary to dissolve the reaction mixture in water and then neutralize it with sodium hydroxide. Therefore, the process for isolating the tetrahydropyrimidine compound is complicated, and there are also problems in that a large amount of sodium toluenesulfonate and the like are produced as by-products.

<Means for Solving the Problems> As a result of examining various methods for solving the problems, the present inventors unexpectedly found that at least one type of metal selected from the group of zinc, copper, iron, cobalt and manganese was used. 1.3- with a nitrile compound in the presence of a metal salt or elemental sulfur, hydrogen sulfide, or a sulfur compound that generates these during the reaction.
The present invention was completed by discovering that a tetrahydropyrimidine compound can be obtained more easily and in higher yield and purity by reacting propanediamines than with known methods.

That is, the present invention provides a method in which a salt of at least -S metal selected from the group of zinc, copper, iron, cobalt and manganese or a nitrile compound in the presence of sulfur, hydrogen sulfide or a sulfur compound which forms these during the reaction as a catalyst; This is a method for producing a tetrahydropyrimidine compound, which is characterized by reacting 8-propanediamines.

The reaction for producing a tetrahydropyrimidine compound from the nitrile compound of the present invention and 1,3-propanediamines is as follows.

(I) (iF) (4) Salts of inorganic or organic acids of zinc, copper, iron, cobalt and manganese are used as the metal salts of the present invention. Preferably, hydrochlorides and hydrobromides of these metals are used. Sulfur compounds that generate sulfur or hydrogen sulfide during the reaction include phosphorus trisulfide, sulfur chloride, metal sulfides,
Examples include aromatic thioamide compounds, hydrogen sulfide salts of amines, and polyhydrogen sulfide compound salts of amines.

As the nitrile compound of the present invention, a nitrile compound represented by the following general formula (I) is used.

R'' CN (r) (In the formula, R1 represents an aliphatic group, an aromatic group, or an aliphatic group having an aromatic substituent.) The 1,8-propanediamines of the present invention have the following general formula ( A compound represented by II) is used (wherein R
2, R3 and R4 may be the same or different and represent a hydrogen atom, an aliphatic group, an aromatic group, or an aliphatic group having an aromatic substituent. ) The aliphatic group, aromatic group or aliphatic group having an aromatic group of the present invention may have a substituent which is inert under the reaction conditions, such as an alkyl group or an alkoxy group. Examples of aliphatic groups include lower or higher alkyl groups and cycloalkyl groups that may have branches; examples of aromatic groups include phenyl groups, alkylphenyl groups, dialkylphenyl groups, alkoxyphenyl groups, naphthyl groups,
Examples of the aliphatic group having an aromatic group include a pyridyl group, and an aralkyl group.

Specific examples of the nitrile compound of general formula (I) include the following.

Acetonitrile, propionitrile, butyronitrile,
Isobutyronitrile, 2-ethylhexanenitrile, lauronitrile, stearonitrile, cyclohexanenitrile, phenylacetonitrile, 3-phenylpropionitrile, benzonitrile, methylbenzonitrile, dimethylbenzonitrile, methoxybenzonitrile, diethylbenzonitrile, α - Naphthonitrile, cyanopyridine O Specific examples of 1,8-propanediamines of general formula (Ill) include the following: 1,8-propanediamine, N-methyl-1°8-propanediamine, N-n-butyl-1,3-propanediamine, N-stearyl-1,3-propanediamine,
N-cyclohexyl-1,3-propanediamine, N-
Benzyl-1,8-propanediamine, N-phenyl-
1,3-propanediamine, 2,2-dimethyl-1,3
-Propanediamine.

The amount of the metal salt, elemental sulfur, hydrogen sulfide, or sulfur compound that generates these during the reaction used as a catalyst is usually 0.000% per mole of 1.3-propanediamine.
001 to 0.5 mol, preferably 0, and OO5 to 02 mol. Even if more than 0.5 mol of catalyst is used, the reaction time will be shortened, but the yield will tend to remain almost the same.

Furthermore, if the amount of catalyst is less than 0.001 mol, the reaction time tends to be longer.

1.3-Propanediamines and nitrile compounds can be reacted in chemical equivalent amounts or in excess of one of the two, but it is preferable to carry out the reaction at a ratio of 0.9 to 1.1 equivalents of nitrile to diamine. .

In the method of the present invention, the reaction is usually carried out in a liquid phase;
Alternatively, it can be carried out under pressure, in a batch reaction or in a continuous reaction. Further, the reaction can be carried out at a temperature of 60 to 800°C, but is preferably carried out at a temperature of 30 to 250°C. The reaction can be carried out without a solvent, but it can also be carried out using a solvent that is inert under the reaction conditions, such as aliphatic hydrocarbons, aromatic hydrocarbons, petroleum ether, benzene, toluene, xylene, etc. The product, the tetrahydropyrimidine compound, can be isolated and purified by conventional methods, such as distillation or recrystallization.

<Effects of the Invention> According to the method of the present invention, a highly purified tetrahydropyrimidine compound can be easily obtained in high yield.

Further, when a metal salt catalyst is used, the catalyst can be used repeatedly, and unnecessary reaction by-products are extremely small.

The present invention will be explained below with reference to Examples, but the present invention is not limited thereto.

Note that the conversion rate and yield are expressed by the following formula.

Reaction 1.8-Propanediamines (number of moles) <Example-
1> In an autoclave, 264 parts of N-methyl-1,8-propanediamine, 128 parts of acetonitrile, and 1 part of zinc acetate were added.
Charge 5 parts, reaction temperature 200~220°C reaction pressure 80~
The reaction was carried out for 3.5 hours at 35 Ky/ax2 with the resulting ammonia gas being discharged via the waste gas conduit. After the reaction is complete, the reaction mixture is distilled under reduced pressure, resulting in a boiling point of 12
1.4, 5.6- of 7-128°C/11'''iV')
300 parts of titrahydro-1,2-dimethylpyrimidine were obtained. The GO purity of this product was 99.6%.

Conversion rate from N-methyl-1゜3-propanediamine 8
The yield was 95%.

<Example-2> The reaction was carried out in the same manner as in Example-1, except that the distillation still residue of Example-1 was used instead of zinc acetate of Example-1. As a result, 1,4,5,6-tetrahydro-1,2-
288 parts of dimethylpyrimidine were obtained. N-methyl-
Conversion rate from 1,3-propanediamine 87%, yield 9
It was 5%.

<Example-3> A reactor equipped with a thermometer, a reflux condenser, and a dropping funnel was filled with N.
264 parts of -methyl-1,3-propanediamine and 108 parts of copper acetate were charged, and the reaction was carried out at a reaction temperature of 115 to 120°C under normal pressure while dropping acetonitrile. After completing the dropwise addition of acetonitrile, continue for 5 hours until the reaction temperature reaches 184°C.
A time reaction was performed.

When the reaction mixture is vacuum distilled after the reaction is completed, the boiling point is 127-1.
273 parts of 1,4,5,6-tetrahydro-1,2-dimethylpyridine of 28°c/115 wHy- were obtained. The conversion rate from N-methyl-1,8-propanediamine was 85% and the yield was 89%.

<Examples-4 to 7> Example-1 except that zinc acetate in Example-1 was replaced with another metal salt and the reaction was carried out for 7 hours, and the amount of metal salt used was as shown in Table-1. This was done in the same manner as in step 1. The results are shown in Table-1.

Table-1 <Examples-8 to 10> Example-8 except that copper acetate in Example-8 was replaced with the melting medium shown in Table-2 and the amount used was as shown in Table-2. I did the same thing. The results are shown in Table-2.

Table 2 <Examples 11 to 16> The same procedure as Example 1 was carried out except that the 1,3-propanediamines and nitrile compounds shown in Table 8 were used in equimolar amounts. The results are shown in Table-3.

Claims (1)

[Claims] 1) In the presence of at least one metal salt selected from the group of zinc, copper, iron, cobalt and manganese, the following general formula (
A nitrile compound represented by I) and R^1CN(I) (wherein R^1 represents an aliphatic group, an aromatic group, or an aliphatic group having an aromatic substituent), and the following general formula 1,3-propanediamine represented by (II) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) (In the formula, R^2, R^3, R^4 may be the same or different. (also represents a hydrogen atom, an aliphatic group, an aromatic group, or an aliphatic group having an aromatic substituent). ▼(III) A method for producing a tetrahydropyrimidine compound represented by the formula (wherein R^2, R^3 and R^4 are the same as above). 2) Process according to claim 1, characterized in that the metal salt is acetate of zinc, copper, iron, cobalt or manganese. 3) A method for producing a tetrahydropyrimidine compound, which comprises using elemental sulfur, hydrogen sulfide, or a sulfur compound that generates these during the reaction instead of the metal salt according to claim 1.