JPH06263739A - Production of urethane compound - Google Patents

Abstract

PURPOSE:To produce a urethane compound under mild conditions in a high yield without wastefully using dicarbonate. CONSTITUTION:A heterocyclic compound having an amino group and containing an N atom as a hetero atom (e.g. a thiazole derivative, a triazole derivative or a pyrimidie derivative) is made to react with a dicarbonate of formula I (R<1> is alkyl, alkenyl or aralkyl) of 0.8-1.5 times by equivalent, preferably 1.0-1.3 times by equivalent based on the heterocyclic compound, in a solvent consisting a halogenated hydrocarbon in the presence of an aliphatic t-amine or an aromatic t-amine having an aromatic ring bonded through alkylene group to its N atom, preferable at 0-50 deg.C to obtain the objective urethane compound. As the t-amine, a compound of formula II {R<2> and R<3> are alkyl; R<4> is alkylene; X is H, alkoxy, alkylthio, aryl or [Y(CH2)m]n-NR<5>R<6> (R<5> and R<6> are H, alkyl or at least either one is alkyl; Y is O, SNH or N-alkyl; (m) is >=1; (n) is 0 or 1} is preferably used.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for industrially 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-thiazole acetic acid and 2.25 times equivalent of dialkyl dicarbonate has been proposed (JP-A-61-24580).

[0003]

However, in the above-mentioned method, since the decomposition reaction of the dialkyl carbonate due to heat occurs during the reaction, the dicyclic carbonate as a substrate has a heterocyclic compound content of 2%.
There has been a problem that an excess amount of dialkyl dicarbonate of not less than double equivalent has to 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, but these bases have the above-mentioned amino group and have nitrogen as a hetero atom. When applied to the reaction of a heterocyclic compound containing atoms and a dialkyl dicarbonate, there was a problem that the reaction yield was extremely reduced.

[0005]

DISCLOSURE OF THE INVENTION As a result of intensive studies on the development of a new technique for compensating for the above-mentioned drawbacks of the prior art, the present inventors have found that a heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom In the reaction with a dialkyldicarbonate, by using an aliphatic tertiary amine or an aromatic tertiary amine having an aromatic ring bonded to a nitrogen atom via an alkylene group as a catalyst in a solvent composed of a halogenated hydrocarbon, The inventors have found that a urethane compound can be synthesized with high yield, and have completed the present invention.

That is, according to the present invention, a heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom is introduced into an aromatic tertiary amine or alkylene group via a nitrogen atom in a solvent composed of a halogenated hydrocarbon. In the presence of an aromatic tertiary amine having an aromatic ring bound to the following formula (1)

[0007]

[Chemical 2]

(Wherein R ¹ is an alkyl group, an alkenyl group or an aralkyl group) is reacted with a dicarbonate, which is a method for producing a urethane compound.

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

The above-mentioned number of heteroatoms is 1 to 3
Specific examples of the 6-membered ring, the condensed ring of 5 to 6-membered rings, or the condensed ring in which a benzene ring is condensed thereto include, 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 thereof include a benzothiazole ring, a thiadiazole ring, a thiazoline ring, a triazole ring, a naphthyridine ring and a picoline ring.

Specific examples of the heterocyclic compound that can be preferably 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-tetrazylthiazole, 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 -(Methoxyimino) -4-thiazole thioacetate and other thiazole derivatives; 2-aminobenzothiazole, 2-amino-6-ethoxybenzothiazole, 2-amino-6-fluorobenzothiazole, 2-
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; 3-
Amino-5,6-dimethyl-1,2,4-triazole, 3-amino-5-mercapto-1,2,4-triazole, 3-amino-5-methylthio-1H-1,2,
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-
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 and 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- Methylpyrimidine, 4-amino-6-hydroxypyrazolo [3,3
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-imidazole dicarbonitrile, 2-aminobenzimidazole, 2-amino-5.
Examples include imidazole derivatives such as 6-dimethylbenzimidazole; naphthyridine derivatives; isoquinoline derivatives; nicotine derivatives; picoline derivatives.

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 i-butyl group and 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, dibenzyl dicarbonate and the like.

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

The solvent used in the present invention is a solvent composed of a halogenated hydrocarbon. The kind, number or position of halogen of the halogenated hydrocarbon is not particularly limited, and a known solvent in which a halogen atom is replaced with an aliphatic hydrocarbon or an aromatic hydrocarbon can be used without any limitation. In the present invention, a halogenated hydrocarbon in which halogen is chlorine, bromine, or fluorine is particularly preferably used because a remarkable effect can be obtained.

Specific examples of the halogenated hydrocarbons that can be preferably used in the present invention include dichloromethane, chloroform, 1,2-dichloroethane, 1,1,1-trichloroethane, trichloroethylene, pentachloroethylene and n-butyl chloride. , 1,4-dichlorobutane, chlorobenzene, o, p-chlorotoluene, p-chlorobenzotrichloride, benzyl chloride, 3,
Chlorinated hydrocarbons such as 4-dichlorotoluene, o, m, p-dichlorobenzene, 1,3,5-trichlorobenzene; n-propyl bromide, i-propyl bromide, n-butyl bromide, 1-bromooctane, 1 ，
3-dibromopropane, 1,4-dibromobutane, 1,
Brominated hydrocarbons such as 5-dibromopentane, o-bromotoluene and β-bromoethylbenzene; 1-bromo-2
-Chlorinated hydrocarbons such as chloroethane and 1-bromo-3-chloropropane; Fluorinated hydrocarbons such as 1,4-bis (trifluoromethyl) benzene; tetrachlorodifluoroethane, trichlorofluoroethane, dibromotetrafluoroethane, etc. And the like.

The concentration of the heterocyclic compound having an amino group as a raw material and containing a nitrogen atom as a hetero atom in a solvent composed of a halogenated hydrocarbon varies depending on the kind of the heterocyclic compound or the solvent and the stirring effect. However, in general, 0.
It is preferable to select from the range of 5 to 60% by weight.

In the present invention, an aliphatic third group is used as a catalyst.
It is necessary to use aromatic tertiary amines in which the aromatic ring is attached to the nitrogen atom via an amine or 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 can be adopted without any limitation. Above all, in the present invention,
Formula (II) below

[0019]

[Chemical 3]

[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 is an alkyl group, Y is O, S or NR ⁷ (provided that 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. }. ] The compound represented by the following can be particularly preferably adopted.

A specific example of the catalyst that can be preferably used in the present invention is 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 and the like can be mentioned.

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

The amount of the above-mentioned aliphatic tertiary amine or aromatic tertiary amine used is not particularly limited, but in order to obtain a sufficient reaction rate, it is 0 relative to the starting heterocyclic compound. 0.0001 to 0.3 times equivalent, and further 0.00
It is preferably in the range of 05 to 0.2 times equivalent.

The reaction temperature in this reaction is not particularly limited, but if the temperature is too low, the reaction rate becomes small, and if the temperature is too high, the product decomposes.
It is preferably carried out at 0 to 50 ° C.

The reaction can be carried out under any conditions of normal pressure, increased pressure and reduced pressure, and 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.

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

[0027]

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

[0028]

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-
2.70 g (13.49 m) of thiazole glyoxylate
mol), 3.24 g of di-t-butyl dicarbonate
(14.85 mmol), N, N, N ', N'-tetramethylethylenediamine 0.014 g (0.135 mm)
ol) and 9 ml of 1,2-dichloroethane were added, and the temperature was 25 ° C.
And stirred.

After stirring for 24 hours, quantitative analysis by high performance liquid chromatography revealed that ethyl 2- (t-butoxycarbonylamino) -4-thiazoleglyoxylate was obtained in a yield of 85.6%.

Examples 2 to 7 Using the heterocyclic compounds shown in Table 1 and using 1.1 times mol of di-t-butyl dicarbonate to the heterocyclic compounds, the reaction was carried out in the same manner as in Example 1. The results obtained are shown in Table 1.

[0032]

[Table 1]

Examples 8 to 14 The same operation as in Example 1 was carried out using the solvents shown in Table 2, and the results are shown in Table 2.

[0034]

[Table 2]

Examples 15 to 19 The same operation as in Example 1 was carried out using the catalysts shown in Table 3, and the results are shown in Table 3.

[0036]

[Table 3]

Examples 20 to 22 Dicarbonates shown in Table 4 were added to the heterocyclic compound in the following amounts: 1.
The reaction was carried out in the same manner as in Example 1 using a 1-fold molar amount. The results are shown in Table 4.

[0038]

[Table 4]

Comparative Examples 1 to 3 The same operation as in Example 1 was carried out without using the catalyst or using the catalyst shown in Table 5. The results are shown in Table 5.

[0040]

[Table 5]

[Procedure amendment]

[Submission date] October 4, 1993

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be corrected] 0029

[Correction method] Change

[Correction content]

Example 1 In a 50 ml eggplant-shaped flask, ethyl 2-amino-4-
2.70 g (13.49 m) of thiazole glyoxylate
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 1,2-dichloroethane were added, and the temperature was 25 ° C.
And stirred.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI Technical display location C07D 233/90 B 235/32 Z 239/42 8615-4C 239/47 Z 8615-4C 239/52 8615-4C 249/14 277/48 277/54 277/82 285/135 417/04 257 9051-4C 471/04 114 A 7019-4C 473/18 473/32 473/34 361 487/04 143 7019-4C

Claims (1)

[Claims] 1. A heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom is prepared by converting an aromatic ring to a nitrogen atom through a aliphatic tertiary amine or an alkylene group in a solvent composed of a halogenated hydrocarbon. In the presence of a bound aromatic tertiary amine, the following formula (I): (However, R ¹ is an alkyl group, an alkenyl group or an aralkyl group.) A method for producing a urethane compound, which comprises reacting with a dicarbonate.