JPH10130221A - Production of cyanomethyl carbamate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject compound in a high yield in two-step processes having reduced troubles with elimination of by-products by using readily available raw materials in industry. SOLUTION: (A) Aminoacetonitrile, (B) phosgene or its dimer and (C) an alcohol, preferably ethanol are used as the raw materials. At the first step, the component B and the component C are allowed to react with each other to form an alkyl chloroformate and the product is allowed to react with the component A to prepare the objective compound. In another process, the reaction of the component A with the component B affords cyanomethyl isocyanate followed by reaction of the product with the component C gives the objective compound. This process provides an industrially advantageous synthesis of the objective compound which is useful as a raw material for specialty chemicals such as medicines and agrochemicals.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a cyanomethylcarbamate useful as a raw material for specialty chemicals such as medical and agricultural chemicals.

[0002]

2. Description of the Related Art With respect to the synthesis of cyanomethyl carbamate, the following synthesis methods are known. The method of Darapski et al. (A. Darapsky et al .;
J. Prakt. chem, 92, 297 (1915)
Is based on the following reaction formula.

[0003]

Embedded image

The method of Boynesk et al. (V. Voinesc)
u et al; Revue Romaneede Chimi
e, 11, 1237 (1966) is based on the following reaction formula.

[0005]

Embedded image

All of the above reactions involve long steps, low yields, unusual raw materials, problems such as removal of by-products, and the like, and are difficult as industrial production methods. The establishment of a method that can be manufactured industrially is an important issue.

[0007]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above problems, and as a result, have established an advantageous industrial production method and completed the present invention. That is, the present invention relates to the following matters.

(1) A method for producing a cyanomethylcarbamic acid ester, comprising using aminoacetonitrile and phosgene or a dimer thereof and an alcohol as reaction raw materials. (2) A method for producing a cyanomethylcarbamate, comprising reacting phosgene or a dimer thereof with an alcohol to synthesize an alkyl chloroformate, and then reacting this with aminoacetonitrile. (3) A method for producing cyanomethyl carbamate, comprising reacting aminoacetonitrile with phosgene or a dimer thereof to synthesize cyanomethyl isocyanate, and then reacting this with alcohol. (4) The alcohol is a compound represented by the general formula R-OH (wherein R represents an alkyl group having 1 to 5 carbon atoms), and the cyanomethylcarbamate is represented by the general formula NCCH ₂ NHCO ₂ R (wherein , And R are as defined above.). (5) The method for producing a cyanomethylcarbamate according to the above item 4, wherein the alcohol is ethanol.

[0009]

Embodiments of the present invention will be described below in detail. Starting from an aminoacetonitrile represented by the general formula (1), a phosgene represented by the general formula (2) or a dimer thereof and, for example, an alcohol represented by the general formula (3), for example, a target cyano represented by the general formula (4) A method for producing methyl carbamate has been found.

NC—CH ₂ —NH ₂ (1) Cl—CO—Cl (2) R—OH (3) (R is a C1 to C5 alkyl group) NCCH ₂ NHCO ₂ R (4) (R is C1 to C5) C5 alkyl group)

[0011] The above raw materials are aminoacetonitrile (1)
Can be usually synthesized from formalin, prussic acid or sodium cyanide, and ammonia, and it is advantageous to use an intermediate of glycine by a general Strecker method. Phosgene (2) is synthesized from carbon monoxide and chlorine and is widely used as an industrial raw material. In addition, phosgene dimer is used in place of phosgene because it is a liquid at room temperature, is easy to handle, decomposes by heating under an activated carbon catalyst, and exhibits the same reactivity as 1 mol of dimer as 2 mol of phosgene. There are, for example, the following two methods for producing cyanomethyl carbamic acid esters using these raw materials.

First, the first method comprises reacting phosgene (2) or a dimer thereof (hereinafter collectively referred to as phosgene) with an alcohol (3) to form an alkyl chloroformate represented by the general formula (5). This is a method of synthesizing and then reacting this with aminoacetonitrile (1) to obtain the target compound cyanomethylcarbamate (4).

RO—CO—Cl (5) (R is a C1-C5 alkyl group)

This reaction is represented by the following reaction formula.

[0015] Cl-CO-Cl + R- OH → RO-CO-Cl RO-CO-Cl + NCCH 2- NH 2 → NCCH 2 NHCO 2 R

In the reaction conditions, phosgene is absorbed in a solvent and alcohol is added dropwise. It is necessary to select a solvent in which a non-protonic solvent does not react well with phosgene. From the viewpoint of recovery, purification and reuse after the completion of the reaction, those having a low boiling point are more preferable. For example, toluene, xylene,
Ether. In some cases, the reaction can be carried out without a solvent at a low temperature at which phosgene liquefies. The alcohol is stoichiometrically equimolar to phosgene, but is preferably not more than equimolar, preferably not more than 0.5 times by mole. If the amount of alcohol is large, the following side reactions are promoted and the yield is reduced.

Cl—CO—Cl + 2R—OH →
RO-CO-OR

On the other hand, when the amount of alcohol is small, the amount of unreacted phosgene increases. Excess phosgene is collected, recycled and reused. If the reaction temperature at room temperature is too high, loss of heating heat will occur, and if it is too low, cooling energy will be lost. An important point influencing the reaction yield is the presence of water in the reaction system, which causes phosgene hydrolysis and reduces the yield. It is necessary to remove water from the above-mentioned solvent by azeotropic distillation or dehydration with an adsorbent. In addition, since HCl is by-produced in the reaction, it is necessary to collect and remove the HCl by using a detoxification facility. After the completion of the reaction, low-boiling components are distilled off and recovered as a high-bottle bottom.

In the formula, aminoacetonitrile (1) is dissolved in water, and the alkyl chloroformate (5) obtained above is added dropwise. The amount of the alkylchloroformate (5) to be added may be equimolar to that of the aminoacetonitrile (1), but it is preferable to add the alkylchloroformate (5) slightly in a slightly insufficient manner in consideration of the further progress of the reaction and the purification after the completion of the reaction. At the same time as this addition, an alkaline aqueous solution is added dropwise to form H
Neutralize Cl. Preferably, an equivalent amount of alkali generated from the time when the alkyl chloroformate (5) having a mole number of half of the aminoacetonitrile (1) is dropped, may be started to be dropped. As the alkali, caustic alkali, tertiary amine or the like is used, and usually, caustic soda is used. If the temperature is 50 ° C. or lower, preferably 0 ° C. to 10 ° C., and the temperature is high, the yield decreases. The reaction time requires 1 to 10 hours, and usually 2 to 4 hours at 5 ° C is appropriate. After the reaction,
The target component is extracted and purified from the reaction solution, but an aprotic solvent is added and extraction is performed with the solvent. The extract layer is washed with clear water to remove water-soluble by-products. At this time, the remaining aminoacetonitrile (1) is also removed by washing with water. As the extraction solvent, for example, toluene, xylene, ether or the like is used.
This solvent may be added to the reaction system before starting the reaction, or may be used as it is without distilling off the solvent immediately after synthesizing the alkyl chloroformate (5).

The solvent is distilled off from the solvent layer to obtain crude crystals of cyanomethylcarbamate (4). The obtained crude crystals are recrystallized with a lower alcohol such as methanol, an organic solvent or the like.

The second method is aminoacetonitrile (1)
And phosgene (2) to produce a cyanomethyl isocyanate represented by the chemical formula (6), which is reacted with an alcohol (3) to obtain a cyanomethyl carbamate (4) as a target compound.

NC-CH ₂ NCO (6)

This reaction is represented by the following reaction formula.

NC—CH ₂ NH ₂ + Cl—CO—Cl → NC—CH ₂ NCO NC—CH ₂ NCO + R—OH → NCCH ₂ NHCO ₂ R

The details of the conditions are as follows. The aminoacetonitrile (1) used in the formula is prepared by adding hydrochloride or sulfate crystals or aminoacetonitrile (1) to a solvent.
Neutralize with hydrogen chloride gas or concentrated sulfuric acid before use.
The solvent is preferably an aprotic solvent, for example, toluene, xylene and the like. To this, phosgene (2) is gradually supplied by gas or liquid. The supply amount of phosgene (2) is used in excess of aminoacetonitrile (1). Preferably, it is 1.5 times or more. When the amount is small, the reaction progresses slowly. When the amount is large, the reaction rate is good, and the excess phosgene after completion of the reaction can be recovered and reused.

The most important thing in this reaction is water in the reaction system, which not only hydrolyzes the raw material phosgene (2), but also hydrolyzes the generated cyanomethyl isocyanate (6), which greatly reduces the yield. Therefore, when a salt of dried aminoacetonitrile (1) is used or when aminoacetonitrile (1) containing water is used, it is charged into a solvent,
It is necessary to remove water in the system by azeotropic distillation or the like, and the water content is preferably 0.5% or less. When water in the system is removed, the neutralized aminoacetonitrile (1) cannot be dissolved in the solvent and exists as a slurry. However, since the trace amount dissolves, it does not affect the reaction.

As the reaction proceeds, the slurry disappears. The reaction temperature is 100 ° C or lower, preferably 20 to 50 ° C. If it is too high, the yield will decrease. On the way, hydrogen chloride as a reaction by-product cannot be completely dissolved in the solvent and becomes gasified. The hydrogen chloride that has come out of the system is removed by absorption and collection in an alkali absorption bottle.

The following formula adds alcohol to this.
The addition amount is at least 1 mole, and preferably 2 to 3 moles, per mole of aminoacetonitrile (1). If it is too low, the reaction progresses slowly. After completion of the reaction, a small amount of water is added, and H
Neutralize by adding the same amount of alkali as Cl. After stirring, the mixture is allowed to stand and separate into two layers. Therefore, the lower aqueous layer is discarded, and water is added again to wash the organic layer. Thereafter, the desired compound is obtained through purification according to the above-mentioned alternative method. Thus, a method for industrially producing a cyanomethylcarbamate with a high yield has been established.

[0029]

Embodiments of the present invention will be described below. The present invention is not limited to these examples.

Example 1 A reaction vessel was charged with 300 ml of toluene as a reagent, and 50 g (0.51 mol) of gasified industrial phosgene was absorbed. Then, at room temperature, 6.9 g of reagent ethanol was added.
(0.15 mol) is added dropwise over 1 hour. Thereafter, the mixture was aged for an additional 1 hour, and simple distillation under reduced pressure was performed to distill off 50 ml of the solvent to remove residual phosgene. The solvent, ethyl chloroformate and some diethyl carbonate were detected on gas chromatography. 15. Ethyl chloroformate in the liquid.
7 g, and the yield was 96% on an ethanol basis.

Example 2 A reactor was charged with 300 ml of toluene as a reagent, and 50 g (0.51 mol) of gasified industrial phosgene was absorbed. At room temperature, 4.8 g of methanol reagent was added.
(0.15 mol) is added dropwise over 1 hour. Thereafter, the mixture is aged for 1 hour, heated to 50 ° C., and subjected to simple distillation under reduced pressure to remove 50 ml of residual phosgene. The solvent, methyl chloroformate and some dimethyl carbonate were detected on gas chromatography. The amount of methyl chloroformate in the liquid was 13.6 g, and the yield was 95 based on methanol.
%Met.

Example 3 A reactor was charged with 300 ml of a reagent, diethyl ether.
58.9 g (1.0 mol) of 95% aminoacetonitrile (others are water) synthesized from formalin, hydrocyanic acid, and ammonia according to the previously known Stricker method, and 50 g of water
Put in. While keeping this at 10 ° C or less (mainly 4 to 8 ° C
The reaction solution obtained in the same manner as in Example 1 was completely evaporated with an evaporator to remove the solvent, and 118.7 g (1.05) of ethyl chloroformate (purity: 96%) was obtained.
Mol) is added dropwise over 2 hours. At this time, one hour after the dropping, 140 g (1.05 mol) of a 30% aqueous sodium hydroxide solution prepared in advance is simultaneously added dropwise over 1 hour. After completion of the dropping, aging is further performed for 2 hours. After completion of the reaction, the reaction solution was transferred to a dropping funnel and allowed to stand,
The upper diethyl ether layer is separated. Further, 100 ml of diethyl ether was added to the aqueous layer side for extraction, and the extraction was carried out once more. The diethyl ether layer was put together, and the solvent diethyl ether was distilled off under reduced pressure using a still equipped with a precision still. 118 g of crude cyanomethylcarbamic acid ethyl ester crystals in the bottom were placed in a flask equipped with a stirrer, and 57 ml of methanol as a reagent was added and dissolved by heating. The flask was put into an ice-water bath while rotating the stirrer, and cooled to 10 ° C. for crystallization. The obtained crystals were subjected to solid-liquid separation with a small table-top centrifuge, and a small amount of methanol was sprayed on the rinse with a sprayer. The obtained crystal is kept at 30 to 40 ° C.
And vacuum-dried to obtain 40 g of crystals. Next, the filtrated methanol solution obtained by solid-liquid separation was concentrated in half by an evaporator and crystallized, solid-liquid separated and dried in the same manner to obtain a second crystal. Similarly, up to the third crystal was obtained. 34g, 21 respectively
g. All are white and mixed with
g was obtained and analyzed by high performance liquid chromatography with an RI detector to be 99.7% pure. The yield was 74% based on aminoacetonitrile. The melting point was measured to be 47.2 ° C., and the structure could be assigned by NMR and MS.

Example 4 The toluene solution of methyl chloroformate obtained in Example 2 was completely evaporated by an evaporator to obtain a liquid methyl chloroformate. This was reacted with aminoacetonitrile in the same manner as in Example 3. After completion of the reaction, the reaction solution was concentrated by an evaporator and further dried by a vacuum dryer. 17 g of brownish crystals were obtained. High performance liquid chromatography purity was 98% on RI detector. The structure could be assigned by NMR and MS. 96 yield
%Met.

Example 5 A beaker was charged with 600 ml of the reagent toluene, and 97.4 g (1.0%) of the aminoacetonitrile used in Example 3 was used.
Mol). The dried molecular sieve was added to this until the water content became 0.1% or less. The water content was determined by Karl Fischer. The molecular sieve is filtered, and a toluene solution of aminoacetonitrile is charged into the reactor. While cooling in a water bath, 37 g of hydrogen chloride gas was supplied and neutralized while maintaining the temperature at 40 ° C. or lower, and a slurry was obtained. While maintaining the temperature at 30 ° C., 198 g (2.0 mol) of phosgene was added with gas so as not to exceed 40 ° C.
Feed into the solvent slowly over time. After supply ends, 5
The temperature was raised to 0 ° C. and the reaction was continued for another 2 hours. Next, simple distillation was performed under reduced pressure to remove 200 ml of the solvent to remove residual phosgene and most of hydrogen chloride. 92 g (2.0 mol) of ethanol as a reagent was added dropwise at 50-60 ° C over 1 hour to the bottom of the kettle. After completion of the dropping, the mixture was aged for 30 minutes. After completion of the reaction, the residue was dried by an evaporator to obtain crude cyanomethylcarbamic acid ethyl ester. In the same manner as in Example 3, the same recrystallization was performed using methanol and dried to obtain 101 g of white crystals. Purity was 99.6% on RI detector of high performance liquid chromatography. The yield was 79% based on aminoacetonitrile.

[0035]

According to the method of the present invention, it is possible to produce a cyanomethylcarbamic acid ester in two steps with a high yield and using a raw material which is industrially available, with little problem in removing by-products. it can.

Claims (5)

[Claims] 1. A method for producing a cyanomethyl carbamate, comprising using aminoacetonitrile and phosgene or a dimer thereof and an alcohol as reaction raw materials. 2. A method for producing a cyanomethyl carbamate, comprising reacting phosgene or a dimer thereof with an alcohol to synthesize an alkyl chloroformate, and then reacting this with aminoacetonitrile. 3. A method for producing a cyanomethyl carbamate, comprising reacting aminoacetonitrile with phosgene or a dimer thereof to synthesize cyanomethyl isocyanate, and then reacting this with an alcohol. 4. An alcohol is a compound represented by the general formula R—OH (where R represents an alkyl group having 1 to 5 carbon atoms), and a cyanomethylcarbamic acid ester is represented by the general formula NCCH ₂ NHCO ₂ R ( In the formula, R is the same as defined above), and the method for producing a cyanomethylcarbamate according to any one of claims 1 to 3. 5. The method according to claim 4, wherein the alcohol is ethanol.
A method for producing the cyanomethylcarbamate according to the above.