JP3164666B2 - Process for producing N-substituted carbamate aryl esters - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel process for producing N-substituted carbamic acid aryl esters.

[0002] N-substituted carbamate aryl esters are
It is a basic organic compound and useful as a raw material for medicines, agricultural chemicals and the like.

[0003]

2. Description of the Related Art As a method for producing N-methylcarbamic acid phenyl ester from N-methylcarbamic acid alkyl ester, N-methylcarbamic acid phenyl ester is produced in the presence of a catalyst such as an alcoholate such as titanium, aluminum or tin. A method has been proposed for reacting an acid alkyl ester with phenol to synthesize the corresponding phenyl N-methylcarbamate (German Patent No. 4022605).

However, in this method, titanium is used as a catalyst,
An expensive catalyst such as an alcoholate such as aluminum or tin is used, and a high-boiling solvent such as 1,1-dichlorobenzene is used as a solvent.
° C and requires considerable high pressure steam when heated.

As a method for producing an N-methylcarbamic acid aryl ester from an N-methylcarbamic acid alkyl ester, an N-methylcarbamic acid alkyl ester is reacted with an aryl alcohol in the presence of phosphorus oxychloride to form a corresponding N-methylcarbamic acid. A method for synthesizing acid aryl esters has been proposed (Tetora
hedron, 1991, 47 , 1249-1256).

However, in this method, phosphorus oxychloride is used as an additive in an equivalent amount to N-methylcarbamic acid alkyl ester, and after the reaction, the phosphorus oxychloride as an additive is converted into a phosphoric acid ester. A phosphate ester treatment is also required.

[0007] From these facts, it has not always been industrially satisfactory.

[0008]

The present inventors have conducted intensive studies to establish a simple and inexpensive method for producing a carbamate which can improve various drawbacks in the above-mentioned known methods. The present inventors have found a method for producing an N-substituted carbamic acid aryl ester from an acid ester and an aryl alcohol by using a small amount of an inexpensive Bronsted acid catalyst, and have completed the present invention.

That is, the present invention relates to a process for producing an N-substituted carbamic acid aryl ester, which comprises reacting an N-substituted carbamic acid ester with an aryl alcohol in the presence of a Bronsted acid catalyst.

Hereinafter, the method of the present invention will be described in detail.
The N-substituted carbamic acid ester as a raw material in the method of the present invention can be easily produced by various known methods, but one having the same N-substituent as the N-substituted carbamic acid aryl ester of the target product is used. Can be Examples of types of N substituents that can be used include, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-
Butyl, t-butyl, pentyl, hexyl, heptyl,
A linear or branched saturated hydrocarbon group having 1 to 8 carbon atoms such as octyl, and 5 carbon atoms such as cyclohexyl and cyclododecyl;
And alicyclic hydrocarbon groups having 6 to 12 carbon atoms, and aromatic hydrocarbon groups having 6 to 12 carbon atoms such as phenyl, benzyl, and naphthyl.

Examples of usable ester groups include, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, pentyl, hexyl, heptyl, octyl and the like. A linear or branched saturated hydrocarbon group having 1 to 8 carbon atoms, an alicyclic hydrocarbon group having 5 to 10 carbon atoms such as cyclohexyl and cyclododecyl, and an aromatic group having 6 to 12 carbon atoms such as phenyl, benzyl and naphthyl Group hydrocarbon groups and the like.

The other raw material, aryl alcohol, is 1
An aromatic compound having one or more hydroxyl groups,
These aryl groups may have a substituent such as an alkyl group, a halogen group and an alkoxy group. The aryl alcohols used include phenol, naphthol,
Benzofuranol and the like are exemplified.

As indicated above, the process of the present invention is characterized by using a Bronsted acid (protic acid) catalyst as the catalyst. Examples of the Brönsted acid catalyst to be used include p-toluenesulfonic acid, trifluoromethanesulfonic acid, sulfuric acid, phosphoric acid, hydrochloric acid and the like.

[0014] The reaction temperature is 0 to 300 ° C, preferably 50 to 200 ° C.

The reaction pressure can be any of normal pressure, reduced pressure, and increased pressure, and is not particularly limited. Practically, it can be carried out preferably at a pressure of normal pressure to 10 kg / cm ² G.

The reaction can be promoted by removing the alcohol by-produced by the reaction by distillation or by removing it by adsorption with molecular sieves or the like.

A solvent is not necessarily required for the reaction between the N-substituted carbamic acid ester and the aryl alcohol, but any solvent may be added to improve the operability. In this case, the kind of the applicable solvent is not particularly limited as long as it is inert to the raw material N-substituted carbamic acid ester and aryl alcohol, Bronsted acid catalyst, and the product N-substituted carbamic acid aryl ester. , For example, aromatic hydrocarbons such as benzene, toluene and xylene;
-Hexane, n-heptane, aliphatic or alicyclic hydrocarbons such as cyclohexane, diisopropyl ether, tetrahydrofuran, ethers such as ethylene glycol dimethyl ether, acetonitrile, propionitrile,
Nitriles such as benzonitrile can be preferably mentioned, but dimethylformamide, dimethylsulfoxide and the like can also be used. However, the use of the above-mentioned hydrocarbon solvents is particularly preferable in consideration of the economic efficiency and the solubility of the N-substituted carbamic acid aryl ester as the target product in these solvents.

The amount of the inert solvent used is not particularly limited as long as the amount of the N-substituted carbamic acid aryl ester of the target product is dissolved or more. In order to reduce energy consumption as much as possible and enable commercial production, the amount of these solvents used must be kept to a minimum, and the amount of these solvents should be reduced to 1 part by weight of N-substituted carbamic acid ester. On the other hand, it is usually 1 to 50 parts by weight, preferably 1 to 10 parts by weight.

Incidentally, in the present invention, the charging ratio of each raw material used in the above-mentioned reaction is as follows. Of course, these values are not particularly limited, but must be practically conceivable.

The amount of the Brönsted acid catalyst is not particularly limited as long as it is normally larger than the catalyst amount. However, from the viewpoint of enabling commercial production, the amount of the Brönsted acid catalyst used is kept to a minimum. And the catalyst per mole of N-substituted carbamate is usually
It is good to use it in a ratio of about 0.001 to 1 mol, preferably about 0.01 to 0.5 mol.

The amounts of N-substituted carbamic acid ester and aryl alcohol used may be equimolar or either material may be in excess. However, the rate of the reaction decreases as the excess amount decreases, so that the amount of one of the raw materials is preferably equal to or more than the molar amount of the other. Also in this case, it is not necessary to set an upper limit because both materials can be used in a large excess, but it is necessary to consider from the viewpoint of enabling commercial production. The other is 1 to 20 moles, preferably 1.2 to 10 moles, and more preferably 2 to 5 moles.

No special equipment is required for the reaction between the N-substituted carbamic acid ester and the aryl alcohol in the method of the present invention, and a usual stirring tank may be used as the reaction equipment. The material of the reaction apparatus may be a general one such as stainless steel.

The reaction between the N-substituted carbamic acid ester and the aryl alcohol is carried out in the above-mentioned stirring tank.
It is desirable that the substituted carbamic acid ester, the aryl alcohol, and the Brönsted acid catalyst, and if necessary, an inert solvent are further supplied in predetermined amounts, and the reaction is carried out with stirring.

When the reaction between the N-substituted carbamic acid ester and the aryl alcohol is carried out in the presence of an inert solvent as described above, after completion of the reaction, excess raw materials and solvent are removed from the reaction solution, for example, After recovery by distillation or the like, the desired N-substituted carbamic acid aryl ester can be easily isolated and purified by appropriately employing a conventional method such as distillation or crystallization.

[0025]

EXAMPLES The method of the present invention will now be described specifically with reference to examples, but the present invention is not limited to these examples.

Example 1 Internal volume equipped with a stirrer, a reflux condenser, a thermometer, and a Soxhlet extractor filled with molecular sieves 4A
In a 200 ml three-necked flask, methyl-N-methylcarbamate 4.72 g (53.0 mmol), phenol 10.02 g (106.5 mmol), p-toluenesulfonic acid 1.0 g (5.3 mmol)
And 80 g of toluene. The reaction temperature was controlled at 110 ° C., and the mixture was stirred for 8 hours. The reaction solution thus obtained was quantitatively analyzed by gas chromatography, and phenyl-N
It was confirmed that -methyl carbamate was produced in a yield of 34% based on methyl-N-methyl carbamate.

Comparative Example 1 Internal volume equipped with a stirrer, reflux condenser and thermometer 2
In a 00 ml three-necked flask were charged 1.0 mol of methyl-N-methyl carbamate, 0.3 mol of phenol, 1 mmol of tetraethyl titanate and 100 ml of 1,1-dichlorobenzene. The reaction temperature was controlled at 180 ° C., and the mixture was stirred for 8 hours while distilling off by-produced methanol. The reaction liquid thus obtained was quantitatively analyzed by gas chromatography, and it was confirmed that phenyl-N-methylcarbamate was produced at a yield of 85% based on phenol.

Example 2 Internal volume equipped with a stirrer, a reflux condenser, a thermometer, and a Soxhlet extractor filled with molecular sieves 4A
In a 200 ml three-necked flask, 2.49 g (28.9 mmol) of methyl-N-methyl carbamate and 8.06 g (55.9 g) of 1-naphthol were added.
Mmol), 1.0 g (5.3 mmol) of p-toluenesulfonic acid and 80 g of toluene. The reaction temperature was controlled at 110 ° C., and the mixture was stirred for 8 hours. The reaction liquid thus obtained was quantitatively analyzed by gas chromatography, and it was confirmed that 1-naphthyl-N-methyl carbamate was produced in a yield of 28% based on methyl-N-methyl carbamate.

Example 3 Internal volume equipped with a stirrer, a reflux condenser, a thermometer, and a Soxhlet extractor filled with molecular sieves 4A
In a 200 ml three-necked flask, 2.49 g (28.9 mmol) of methyl-N-methyl carbamate and 8.06 g (55.9 g) of 1-naphthol were added.
Mmol), sulfuric acid 1.0 g (10.2 mmol) and toluene 80
g. The reaction temperature was controlled at 110 ° C., and the mixture was stirred for 8 hours. The reaction solution thus obtained was quantitatively analyzed by gas chromatography, and it was confirmed that 1-naphthyl-N-methyl carbamate was produced in a yield of 31% based on methyl-N-methyl carbamate.

Example 4 Internal volume equipped with a stirrer, a reflux condenser, a thermometer, and a Soxhlet extractor filled with molecular sieves 4A
In a 200 ml three-necked flask, 2.67 g (30.0 mmol) of methyl-N-methyl carbamate, 9.85 g (60.0 mmol) of 2,3-dihydro-2,2-dimethyl-7-benzofuranol,
1.0 g (6.6 mmol) of trifluoromethanesulfonic acid and 80 g of toluene were charged. The reaction temperature was controlled at 110 ° C,
Stir for 8 hours. The reaction solution obtained in this way was quantitatively analyzed by gas chromatography and found to be 2,3-dihydro-
It was confirmed that 2,2-dimethyl-7-benzofuranyl-N-methyl carbamate was produced at a yield of 24% based on methyl-N-methyl carbamate.

Example 5 Internal volume equipped with a stirrer, a reflux condenser, a thermometer, and a Soxhlet extractor filled with molecular sieves 4A
In a 200 ml three-necked flask, 2.54 g (16.8 mmol) of phenyl-N-methyl carbamate, 4.77 g of 1-naphthol (3
3.1 mmol), 1.0 g (5.3 mmol) of p-toluenesulfonic acid and 80 g of benzene. The reaction temperature was controlled at 80 ° C., and the mixture was stirred for 8 hours. The reaction liquid thus obtained was quantitatively analyzed by gas chromatography, and it was confirmed that 1-naphthyl-N-methyl carbamate was produced at a yield of 25% based on phenyl-N-methyl carbamate.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI B01J 27/16 B01J 27/16 X 31/02 103 31/02 103X C07B 61/00 300 C07B 61/00 300 (58) Field (Int.Cl. ⁷ , DB name) C07C 269/06 C07C 271/40-271/58 C07D 307/86 CASREACT (STN)

Claims (1)

(57) [Claims] 1. A method for producing an N-substituted carbamic acid aryl ester, comprising reacting an N-substituted carbamic acid ester with an aryl alcohol in the presence of a Bronsted acid catalyst.