JPH0789924A - Production of carbamate compounds - Google Patents

Abstract

PURPOSE:To industrially and advantageously obtain the compound under almost neutral and mild conditions by reacting a hydroxamic acid compound with a specific haloiminium salt in the presence of a base and subsequently reacting the reaction product with an alcohol or thiol. CONSTITUTION:A hydroxamic acid compound of formula 2 (R<3> is organic group) is reacted with a haloiminium salt of formula 1 (R<1>, R<2> are lower alkyl; X is halogen; n is 2-3) in the presence of a base of formula 4 and subsequently with an alcohol or thiol of formula: R<4>YH (R<4> is organic group; Y is O, S) to obtain a carbamate compound of formula 5. The carbamate compound is utilized in the fields of medicines, fibers and plastic industries, etc., and furthermore useful as a solvent.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing carbamates, and more particularly to a method for producing carbamates industrially advantageously by reacting hydroxamic acids with a haloiminium salt and alcohols or thiols.

[0002]

2. Description of the Related Art Carbamates have been used in the fields of pharmaceuticals, textiles, plastics industry, etc., and it has been clarified that they are also useful as a solvent (New Experimental Chemistry Course, Vol. 14, III, p1652). It is a useful compound.

Conventionally, as a method for producing such a carbamate, a method of adding an alcohol to an isocyanate, a method of condensing a chlorocarbonic acid ester and an amine, and a method of condensing a carbamoyl chloride and an alcohol. A method of reacting sodium cyanate with alcohols in the presence of trifluoroacetic acid, a method of transesterification of a carbamic acid ester with an alcohol in the presence of aluminum isopropoxide, and the like are known.

However, in the method of adding alcohols to isocyanates, it is necessary to isolate isocyanates which are highly reactive, irritating and lacrimatory. In addition, the method by condensation between chlorocarbonic acid esters and amines or condensation between carbamoyl chlorides and alcohols has few commercial products of chlorocarbonic acid esters and carbamoyl chlorides, and its application range is limited. In the case of obtaining by, there is a drawback that phosgene or the like having strong toxicity and corrosiveness must be used. In addition, the method of reacting sodium cyanate with alcohols has a drawback that a nitrogen-substituted compound cannot be synthesized. Further, the method by the transesterification reaction of carbamic acid esters and alcohols has a problem that the reflux temperature of toluene is required.

[0005]

Therefore, it has been desired to develop a method for producing carbamates industrially advantageously without being affected by the properties of the raw materials and without the need for heating to a high temperature.

[0006]

Under such circumstances, the inventors of the present invention have conducted diligent research to obtain a novel method for producing carbamates, and as a result, in the presence of a base in isocyanates, the following general formula (1) By reacting a haloiminium salt represented by and then reacting with alcohols or thiols, it is possible to carry out the reaction under almost neutral and mild conditions, and further, it is possible to produce carbamates in a high yield. Completed the invention.

The present invention is shown by the following reaction formula.

[0008]

[Chemical 2]

[In the formula, R ¹ and R ² are the same or different and each represents a lower alkyl group, X represents a halogen atom, n represents an integer of 2 or 3, and R ³ and R ⁴ represent organic groups. And Y represents an oxygen atom or a sulfur atom,
B represents a base]

That is, according to the present invention, a carbamate characterized by reacting a hydroxamic acid (2) with a haloiminium salt (1) in the presence of a base (4) and then reacting with an alcohol or a thiol (3). The present invention provides a method for producing the class (5).

The haloiminium salt used in the present invention is represented by the general formula (1). In the formula, the lower alkyl group represented by R ¹ and R ² is a methyl group, an ethyl group, an n-propyl group, Isopropyl group, n-butyl group,
Examples thereof include linear or branched alkyl groups having 1 to 6 carbon atoms such as an isobutyl group. Further, examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among them, a chlorine atom is particularly preferable. Specific preferred examples of the haloiminium salt (1) include 2-
Chloro-1,3-dimethylimidazolinium chloride, 2-chloro-1,3-dimethyl-3,4,5,6-
Examples thereof include tetrahydropyrimidinium chloride.

This haloiminium salt (1) can be obtained by, for example, adding an oxalyl halogenide, a phosphorus trihalide, a phosphorus pentahalide or an oxyhalogen to a compound represented by the general formula (6) which is known as an easily available solvent. It can be easily obtained by reacting a halogenating agent known per se such as phosphorus bromide, phosgene, trichloromethyl chloroformate and the like. In this reaction, either compound (6) or a halogenating agent is dissolved in a suitable solvent such as carbon tetrachloride,
The other is added little by little to this, and the reaction is further carried out at room temperature to 70 ° C. for several hours to several tens of hours. The haloiminium salt (1) thus obtained can be isolated, but the reaction solution can also be used in the reaction of the present invention without isolation.

In the production method of the present invention, the raw material compound hydroxamic acid is not particularly limited, and for example, the general formula (2)
In, R ³ is an alkyl group which may have a substituent,
Examples thereof include alkenyl groups, aromatic groups, and heterocyclic groups. R ³ may have a substituent containing an ether bond or an olefin bond.

Examples of the base represented by B include 2,6-lutidine, pyridine, triethylamine and tributylamine.

To carry out the production method of the present invention, the haloiminium salt (1) is added to 1 mol of the hydroxamic acid (2).
After about 1 mol and about 2 mol of the base (4) are added and reacted at around room temperature, about 1 mol of alcohols or thiols (3) may be added and further reacted at around room temperature.

The reaction solvent need not be used,
It is also possible to use a solvent that does not participate in the reaction, such as a halogenated hydrocarbon such as dichloromethane or dichloroethane, a hydrocarbon, an ether, or an aromatic hydrocarbon. Further, even when the reaction apparatus is carried out on an industrial scale, it is possible to use an ordinary stainless steel reaction kettle instead of a special reaction kettle such as glass lining.

In the production method of the present invention, since the haloiminium salt (1) is changed to the water-soluble compound (6), separation and purification are easy. Therefore, the desired carbamates can be isolated from the reaction mixture simply by a conventional method such as distillation or recrystallization.

[0018]

According to the production method of the present invention, carbamates can be efficiently produced from hydroxamic acid and alcohols or thiols under mildly neutral conditions.

The present invention will be further described below with reference to examples, but the present invention is not limited thereto.

Example 1 Preparation of phenylcarbamic acid methyl ester: 3.0 g of benzohydroxamic acid (22 ml) in 50 ml of methylene chloride.
mmol) and 2-chloro-1,3-dimethylimidazolinium chloride 4.4 g (26 mmol) were added, and at room temperature,
Stir for 25 minutes. Next, under water cooling, 5.3 g (53 mmol) of triethylamine was slowly added dropwise thereto, and after the addition was completed, the water bath was removed and the mixture was stirred for 20 minutes. After adding 10 ml of methanol to the reaction solution and continuing stirring at room temperature for 21 hours, water was added to the reaction solution and the mixture was extracted with methylene chloride. The extract was washed 3 times with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 3.1 g of a yellowish brown viscous oil. This oil was purified by silica gel chromatography (solvent: methylene chloride) to give 2.7 g of the title compound (yield 8
2%) was obtained. mp .: 47.9 to 48.5 ° C (lit. 47 ° C), IRν _max ^KBr cm ^-1 : 3350, 3280, 1695.

Example 2 Preparation of phenylcarbamic acid cyclopentyl ester:
2.0 ml of benzohydroxamic acid in 30 ml of methylene chloride
g (15 mmol) and 2-chloro-1,3-dimethylimidazolinium chloride 3.0 g (18 mmol) were added,
The mixture was stirred at room temperature until it became a homogeneous solution. Next, under water cooling, 3.5 g (35 mmol) of triethylamine was slowly added dropwise thereto, and after the addition was completed, the mixture was stirred for 30 minutes.
After 1.4 g (18 mmol) of cyclopentanol was added to the reaction solution and stirring was continued at room temperature for 48 hours, the same operation as in Example 1 was carried out to obtain 4.2 g (yield 81%) of the title compound. mp .: 136.7 ℃, IRν _max ^KBr cm ^-1 : 3300, 1695.

Example 3 Preparation of phenethylcarbamic acid phenethyl ester: 2.0 g of benzohydroxamic acid in 30 ml of methylene chloride.
(15 mmol) and 3.0 g (18 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride were added, and the mixture was stirred at room temperature until it became a homogeneous solution. Next, under water cooling, 3.5 g (35 mmol) of triethylamine was slowly added dropwise thereto, and after the addition was completed, the mixture was stirred for 30 minutes. After 2.1 g (18 mmol) of phenethyl alcohol was added to the reaction solution and stirring was continued at room temperature for 5 hours, the same operation as in Example 1 was carried out to obtain 2.9 g of the title compound (yield: 82%). mp .: 77.3 ℃ (decomposition), IRν _max ^KBr cm ^-1 : 3360, 1700.

Example 4 Preparation of phenylcarbamic acid 2-thiophene methyl ester: 2.0 g (15 mmol) of benzohydroxamic acid and 3.0 g of 2-chloro-1,3-dimethylimidazolinium chloride in 30 ml of methylene chloride ( 18 mmol) was added, and the mixture was stirred at room temperature until it became a homogeneous solution. Then
Under water cooling, 3.5 g of triethylamine (35 mmo)
l) was slowly added dropwise, and after completion of the addition, the mixture was stirred for 30 minutes. 2.0 g of 2-thiophene methanol (18 mmo
l) was added and the mixture was stirred at room temperature for 6 hours, and then the same operation as in Example 1 was carried out to give 3.0 g of the title compound (yield 88
%)Obtained. mp .: 68.7 ℃ (decomposition), IRν _max ^KBr cm ^-1 : 3325, 1695.

Example 5 Preparation of n-nonylcarbamic acid methyl ester: 2.0 g of n-decanohydroxamic acid in 30 ml of methylene chloride.
(11 mmol) and 2.2 g (13 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride were added, and the mixture was stirred at room temperature until it became a homogeneous solution. Then, 2.7 g (27 mmol) of triethylamine was slowly added dropwise thereto under water cooling, and after completion of the addition, the mixture was further stirred for 30 minutes. After adding 2 ml of methanol and continuing stirring at room temperature overnight, the same operation as in Example 1 was performed to obtain 2.0 g of the title compound (yield 93%). mp .: 31.7 ℃, IRν _max ^KBr cm ^-1 : 3330, 1690.

Example 6 Preparation of cyclohexylcarbamic acid methyl ester: 2.0 g (14 mmol) of cyclohexanecarbohydroxamic acid and 2-chloro-1,3-in 30 ml of methylene chloride.
Dimethyl imidazolinium chloride 2.8g (17mm
ol) was added, and the mixture was stirred at room temperature until a uniform solution was obtained. Then, 3.4 g of triethylamine (3 g
4 mmol) was slowly added dropwise, and after the addition was completed, the mixture was stirred for 30 minutes. After adding 2 ml of methanol and continuing stirring at room temperature overnight, the same operation as in Example 1 was carried out to obtain 1.9 g (yield 87%) of the title compound. mp .: 74.4 ℃, IRν _max ^KBr cm ^-1 : 3350, 1695.

Example 7 Preparation of phenylthiocarbamic acid thio-m-tolyl ester: 2.0 g (15 mmol) of benzohydroxamic acid and 2-chloro-1,3-dimethylimidazolinium chloride in 30 ml of methylene chloride 3. 0 g (18 mmol) was added, and the mixture was stirred at room temperature until it became a homogeneous solution. Then
Under water cooling, 3.5 g of triethylamine (35 mmo)
l) was slowly added dropwise, and after completion of the addition, the mixture was stirred for 30 minutes. After 2.2 g (18 mmol) of m-toluenethiol was added and stirring was continued at room temperature overnight, the same operation as in Example 1 was carried out to obtain 2.9 g of the title compound (yield 83%). mp .: 109.4 ° C, IRν _max ^KBr cm ^-1 : 3240, 1655.

Claims (1)

[Claims] 1. Hydroxamic acids are represented by the general formula (1): [Wherein R ¹ and R ² are the same or different and each represents a lower alkyl group, X represents a halogen atom, and n represents an integer of 2 or 3] in the presence of a base. A method for producing carbamates, which comprises reacting and then reacting alcohols or thiols.