JP2895329B2 - Method for producing urethane compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for industrially and advantageously producing a urethane compound by reacting a compound having an amino group with dicarbonate.

[0002]

2. Description of the Related Art A method for producing a urethane compound by reacting a compound having an amino group with dicarbonate is known. For example, a heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom, for example, 2-amino-
A method of heating 4-thiazoleacetic acid and 2.25 equivalents of a dialkyl dicarbonate has been proposed (JP-A-61-24580).

[0003]

However, in the above-mentioned method, a thermal decomposition reaction of the dialkyl carbonate occurs during the reaction, so that the heterocyclic compound as a substrate is not reacted with the dialkyl carbonate.
There is a problem that a double equivalent or more excess of dialkyl dicarbonate must be used.

On the other hand, it is known to react a compound having an amino group with a dicarbonate in the presence of a base such as pyridine or triethylamine. However, these bases having an amino group and having a nitrogen atom as a hetero atom are known. When applied to the reaction between a heterocyclic compound containing an atom and a dialkyl dicarbonate, there is a problem that the reaction yield is extremely reduced.

[0005]

Means for Solving the Problems As a result of intensive studies on the development of a new technology which compensates for the above-mentioned disadvantages of the prior art, the present inventors have developed a heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom. In the reaction with dialkyl dicarbonate, the use of an aliphatic tertiary amine or an aromatic tertiary amine in which an aromatic ring is bonded to a nitrogen atom via an alkylene group as a catalyst makes it possible to synthesize a urethane compound with high yield. They have found what they can do and have completed the present invention.

That is, the present invention relates to a method of converting a heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom into an aromatic tertiary compound in which an aromatic ring is bonded to a nitrogen atom via an aliphatic tertiary amine or alkylene group. In the presence of an amine, the following formula (1)

[0007]

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(Wherein R ¹ is an alkyl group, an alkenyl group or an aralkyl group). A process for producing a urethane compound, characterized by reacting with a dicarbonate represented by the formula:

In the present invention, the heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom is not particularly limited in the number of amino groups and the bonding position thereof, and the number of nitrogen atoms contained in the heterocycle and The position is not particularly limited. Further, the heterocyclic ring may contain a hetero atom other than a nitrogen atom, for example, an oxygen atom and a sulfur atom. In the present invention, the heterocyclic compound which can be suitably used contains at least one nitrogen atom, and may further contain an oxygen atom or a sulfur atom. It is a heterocyclic compound in which an amino group is directly bonded to a heterocyclic ring such as a condensed ring in which a benzene ring is condensed to a membered ring or a condensed ring of 5 to 6-membered rings. A substituent other than an amino group may be bonded to the ring of the heterocyclic compound. The substituent other than the amino group is not particularly limited, but is preferably an alkyl group, an alkoxy group, a hydroxyl group, a nitro group, a nitroso group, a mercapto group, a halogen atom, or the like. Alkyl groups are preferably lower alkyl groups such as methyl group, ethyl group, propyl group and butyl group, and alkoxy groups are preferably lower alkoxy groups such as methoxy group, ethoxy group, propoxy group and butoxy group, and halogen atom Is preferably fluorine, chlorine or bromine.

The number of heteroatoms is 1 to 3,
As a 6-membered ring, a condensed ring of 5 to 6-membered rings, or a condensed ring in which a benzene ring is condensed, specifically, for example,
Pyridine ring, quinoline ring, isoquinoline ring, pyrazine ring, pyrimidine ring, pyrazole ring, pyrazoline ring, imidazole ring, triazine ring, purine ring, thiazole ring,
Examples include a benzothiazole ring, a thiadiazole ring, a thiazoline ring, a triazole ring, a naphthyridine ring, a picoline ring and the like.

Specific examples of the heterocyclic compound which can be suitably used in the present invention include 2-aminothiazole and 2-aminothiazole.
Amino-4-methylthiazole, 2-amino-4-methyl-5-thiazolesulfonyl chloride, 2-amino-5-bromothiazole, 2-amino-4- (4-chlorophenyl) thiazole, 2-amino-4,5 -Dimethylthiazole, 2-amino-5- (4-nitrophenylsulfonyl) thiazole, 2-amino-5-nitrothiazole, 2-amino-4-phenyl-5-tetradylthiazole, 2-amino-4-phenylthiazole , 2-
Amino-4-thiazoleacetic acid, 2-amino-α- (methoxyimino) -4-thiazoleacetic acid, ethyl 2-amino-4-thiazole acetate, ethyl 2-amino-α-
(Hydroxyimino) -4-thiazole acetate, ethyl 2-amino-α- (methoxyimino) -4-thiazole acetate, ethyl 2-amino-4-thiazole glyoxylate, S-2-benzothiazolyl-2-amino-α Thiazole derivatives such as-(methoxyimino) -4-thiazolethiol acetate; 2-aminobenzothiazole, 2-amino-6-ethoxybenzothiazole, 2-amino-6-fluorobenzothiazole,
Amino-4-methoxybenzothiazole, 2-amino-
Benzothiazole derivatives such as 4-methylbenzothiazole, 2-amino-6-nitrobenzothiazole, 2-amino-4-chlorobenzothiazole, 2-amino-5,6-dimethylbenzothiazole; 5-amino-1,3 ,
4-thiadiazole-2-sulfonamide, 2-amino-5-ethyl-1,3,4-thiadiazole, 2-amino-6- (ethylthio) -1,3,4-thiadiazole, 2-amino-5-methyl -1,3,4-thiadiazole, 5-amino-3-phenyl-1,2,4-thiadiazole, 2-amino-1,3,4-thiadiazole,
Thiadiazole derivatives such as 5-amino-1,3,4-thiadiazole and 2-amino-5-trifluoromethyl-1,3,4-thiadiazole; thiazoline derivatives;
Amino-5,6-dimethyl-1,2,4-triazole, 3-amino-5-mercapto-1,2,4-triazole, 3-amino-5-methylthio-1H-1,2,2
Triazole derivatives such as 4-triazole, 3-amino-1,2,4-triazole, 3-amino-1,2,4-triazole-5-acetic acid; triazine derivatives; 2-aminopyridine, 2-amino-3- Nitropyridine, 2-
Amino-5-nitropyridine, 2-amino-4-methyl-3-nitropyridine, 2-amino-3-hydroxypyridine, 2-amino-4,6-dimethylpyridine, 2-aminopyridine
Amino-5-chloropyridine, 2-amino-3,5-dichloropyridine, 2-amino-3-chloro-5- (trifluoromethyl) pyridine, 2-amino-5-bromopyridine, 2-amino-5 Pyridine derivatives such as bromo-3-nitropyridine, 3-acetyl-2,6-diamino-4-methylpyridine; pyrazine derivatives; 2-aminopyrimidine, 4-aminopyrazolo [3,4-d] pyrimidine, 4-amino- 6-hydroxy-2-mercapto-
5-nitrosopyrimidine, 2-amino-4-methylpyrimidine, 2-amino-4-methoxy-6-methylpyrimidine, 4-amino-6-hydroxy-2-mercaptopyrimidine, 2-amino-4-hydroxy-6- Methyl pyrimidine, 4-amino-6-hydroxypyrazolo [3,
4-d] pyrimidine, 4-amino-6-mercaptopyrazolo [3,4-d] pyrimidine, 4-amino-2-mercaptopyrimidine, 2-amino-4-chloro-6-methylpyrimidine, 2-amino- 6-chloro-2- (methylthio) pyrimidine, 2-amino-4,6-dichloropyrimidine, 6-amino-2,4-dihydroxy-5-nitrosopyrimidine, 2-amino-4,6-dihydroxypyrimidine, 2- Pyrimidine derivatives such as amino-4,6-dimethoxypyrimidine, 2-amino-4,6-dimethylpyrimidine, 2-amino-5-bromopyrimidine; 3
-Aminopyrazole, 5-amino-1-ethylpyrazole, 3-amino-5-hydroxypyrazole, 3-amino-5-methylpyrazole, ethyl 3-amino-4-pyrazolecarboxylate, 3-amino-4-pyrazolecarbo Pyrazole derivatives such as nitrile, 3-amino-4-pyrazolecarboxamide, 3-amino-4-pyrazoleacetic acid; pyrazoline derivatives; 2-aminopurine;
6-aminopurine, 2-amino-6-chloropurine, 2
-Amino-6,8-dihydroxypurine, 2-amino-
Purine derivatives such as 6-hydroxy-8-mercaptopurine and 2-aminopurinethiol; 2-aminoimidazole, 2-amino-4,5-imidazoledicarbonitrile, 2-aminobenzimidazole, 2-amino-5,
Imidazole derivatives such as 6-dimethylbenzimidazole; naphthyridine derivatives; isoquinoline derivatives; nicotine derivatives; picoline derivatives and the like.

On the other hand, the dicarbonate used in the present invention is a compound represented by the above formula (I). In the formula, the alkyl group represented by R ¹ is a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group,
A lower alkyl group such as an i-butyl group and a t-butyl group is preferable, an alkenyl group is preferably an allyl group, and an aralkyl group is preferably a benzyl group.

Specific examples of the dicarbonate represented by the general formula (I) include di-t-butyl dicarbonate,
Examples thereof include dimethyl dicarbonate, diethyl dicarbonate, di-i-propyl dicarbonate, diallyl dicarbonate, and dibenzyl dicarbonate.

The amount of dicarbonate to be used is not particularly limited, but if it is used in excess, it is not economically advantageous. It is preferably in the range of double equivalent, more preferably 1.0 to 1.3 equivalent.

In the present invention, an aliphatic tertiary compound is used as a catalyst.
It is necessary to use an aromatic tertiary amine in which an aromatic ring is bonded to a nitrogen atom via an amine or an alkylene group. As the above-mentioned aliphatic tertiary amine or aromatic tertiary amine in which an aromatic ring is bonded to a nitrogen atom via an alkylene group, known compounds are employed without any limitation. Among them, in the present invention,
The following formula (II)

[0016]

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Wherein R ² and R ³ are the same or different alkyl groups, R ⁴ is an alkylene group, X is a hydrogen atom, an alkoxy group, an alkylthio group, an aryl group, or-｛Y (CH ^{_{2) m} n -NR 5 R}} 6 { However, R ⁵ and R
⁶ is a hydrogen atom or an alkyl group, at least one of which is an alkyl group, Y is O, S or NR ⁷ (where R ⁷ is a hydrogen atom or an alkyl group), and m is an integer of 1 or more. And n is 0 or 1. ｝. ] Can be particularly preferably employed.

Specific examples of the catalyst which can be preferably used in the present invention include N, N-dimethylbenzylamine,
N, N-diethylbenzylamine, N, N, N ', N'
-Tetramethylethylenediamine, N, N, N ', N'
-Tetramethyl-1,3-propanediamine, N, N,
N ', N'-tetramethyl-1,6-hexanediamine, N, N, N', N'-tetraethylethylenediamine, N, N, N ', N'-tetraethyl-1,3-propanediamine, N, N, N ', N'-tetraethyl-
1,6-hexanediamine, N, N, N ', N'-tetramethyl-1,3-butanediamine, N, N, N',
N'-tetramethyl-1,4-butanediamine, bis-
[2- (N, N-dimethylamino) ethyl] ether,
Bis- [2- (N, N-dimethylamino) propyl] ether, bis- [2- (N, N-dimethylamino) ethyl] sulfide, bis- [2- (N, N-dimethylamino) propyl] sulfide , 2- (N, N-dimethylamino) ethyl ethyl ether, 2- (N, N-dimethylamino) ethyl ethyl sulfide, bis- [2- (N,
[N-dimethylamino) ethyl] methylamine.

When a compound in which X is an aryl group or —NR ⁵ R ⁶ among the aliphatic tertiary amines and aromatic tertiary amines represented by the general formula (II) is used, the yield of the desired product is reduced. Since it is high, it is suitable in the present invention.

The amount of the above-mentioned aliphatic tertiary amine or aromatic tertiary amine is not particularly limited. 0001-0.3 equivalents, 0.0005-
It is preferably in the range of 0.2 equivalent.

The reaction in the present invention proceeds easily with or without an organic solvent. The solvent that can be used is not particularly limited, and aromatic hydrocarbons such as benzene, toluene, and xylene; nitriles such as acetonitrile;
Ethers such as 1,4-dioxane and tetrahydrofuran; ketones such as acetone and methyl ethyl ketone;
Amides such as N-dimethylformamide and N-methylpyrrolidone; alcohols such as 2-propanol and 2-methyl-2-propanol; and carbonates such as dimethyl carbonate and diethyl carbonate can be used. These organic solvents may be used alone or in combination of two or more.

The concentration of the starting heterocyclic compound in the organic solvent depends on the type of the substrate, the type of the organic solvent, the composition of the mixed solvent,
Although it depends on the stirring effect, it is generally preferable to select from the range of 0.5 to 60% by weight.

The reaction temperature in the present reaction is not particularly limited. However, if the temperature is too low, the reaction rate is reduced, and if the temperature is too high, the product is decomposed.
Preferably, the heat treatment is performed at 0 to 50 ° C.

The reaction can be carried out under any of normal pressure, increased pressure and reduced pressure. The time required for the reaction varies depending on the reaction temperature and the type of solvent, but is usually 0.1 to 30 hours. It is enough.

Thus, a urethane compound having a urethane bond formed by the reaction between the amino group of the heterocyclic compound and the dicarbonate can be obtained.

[0026]

According to the present invention, a urethane compound can be obtained in a high yield under mild conditions without wasteful use of dicarbonate as a raw material.

[0027]

The present invention will be described below with reference to examples and comparative examples, but the present invention is not limited to these examples.

Example 1 In a 50 ml eggplant-shaped flask, ethyl 2-amino-4- was added.
2.70 g of thiazole glyoxylate (13.49 m
mol), 3.24 g of di-t-butyl dicarbonate
(14.85 mmol), N, N, N ', N'-tetramethylethylenediamine 0.016 g (0.135 mm
ol) and 9 ml of dimethyl carbonate, and the mixture was stirred at 25 ° C.

After stirring for 24 hours, as determined by high performance liquid chromatography, ethyl 2- (t-butoxycarbonylamino) -4-thiazoleglyoxylate was obtained in a yield of 94.9%.

Examples 2 to 8 The reaction was carried out in the same manner as in Example 1 by using the heterocyclic compounds shown in Table 1 and using 1.1 times mol of di-t-butyl dicarbonate with respect to the heterocyclic compound. The results obtained are shown in Table 1.

[0031]

[Table 1]

Examples 9 to 13 The same operations as in Example 1 were carried out using the catalysts shown in Table 2, and the results are shown in Table 2.

[0033]

[Table 2]

Examples 14 to 16 The dicarbonates shown in Table 3 were added to the heterocyclic compounds in the following manner.
The reaction was carried out in the same manner as in Example 1 except for using 1-fold mol. Table 3 shows the results.

[0035]

[Table 3]

Comparative Examples 1 to 3 The same operation as in Example 1 was performed without using the catalyst or using the catalyst shown in Table 4. Table 4 shows the results.

[0037]

[Table 4]

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07D 239/47 C07D 239/47 Z 249/10 249/10 277/40 277/40 285/135 473/18 473/18 473 / 32 473/32 473/34 301 473/34 301 473/40 473/40 487/04 143 487/04 143 285 / 12F

Claims (1)

(57) [Claims] 1. A heterocyclic compound having an amino group and containing a nitrogen atom as a heteroatom in the presence of an aliphatic tertiary amine or an aromatic tertiary amine having an aromatic ring bonded to a nitrogen atom via an alkylene group. In addition, the following formula (I): (Wherein R ¹ is an alkyl group, an alkenyl group or an aralkyl group). A method for producing a urethane compound, characterized by reacting with a dicarbonate represented by the formula: