JPS5828251B2 - Encabenzil no seizouhouhou - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing benzyl chloride, which is useful as an intermediate in the production of agricultural chemicals, pharmaceuticals, etc., and more specifically, to a method for producing benzyl chloride in a high yield by reacting tertiary benzylamine with chloroformate. This invention relates to a method for separate manufacturing.

Regarding the reaction between tertiary benzylamine and chloroformate, see Archive der Pharmazie.
undBerichte der Deutschen
Pharmazeutischen Gesellsch
aft Vol. 289, p. 479 (1956), same magazine No. 2
Volume 95, page 690 (1962) and the same volume, volume 87 of the same magazine.
1 (1962).

However, the purpose of the reaction reported here is to react tertiary benzylamine (a) and chloroformic acid ethyl ester (b) to produce carbamic acid ethyl ester (C), as shown in the reaction formula below. It is not intended for the production of benzyl chloride (d).

Therefore, it has been suggested that benzyl chloride (d) is also produced simultaneously with carbamic acid ethyl ester (c), but there has been no report on the isolation and production of the produced benzyl chloride (d).

Furthermore, according to the research conducted by the present inventors, it is possible to isolate only benzyl chloride in good yield from a mixture product of carbamate ester and benzyl chloride obtained by the reaction of tertiary benzylamine and chloroformate. It's not easy.

Furthermore, in the reaction between tertiary benzylamine and chloroformate, the reactivity varies significantly depending on the type and position of the group (group represented by X) substituting on the benzene nucleus of tertiary benzylamine. If a strong electron-donating group such as a hydroxyl group or a methoxy group is substituted at the ortho or para position, the reaction will proceed easily, but even if the group is a strong electron-donating group, the position to be substituted is is at the meta position, or is substituted with a weak electron-donating group such as an alkyl group or halogen atom, or is substituted with an electron-withdrawing group such as a nitro group, cyano group, or sulfonic acid group. or if it is unsubstituted, the reaction will not proceed quickly.

The present inventors have made various efforts to overcome the above-mentioned drawbacks and to develop a method for producing high-purity benzyl chloride in good yield when producing benzyl chloride by reacting tertiary benzylamine and chloroformate. As a result of research, it was found that if the reaction product obtained by reacting tertiary benzylamine and chloroformate is further hydrolyzed, only the carbamate ester produced together with benzyl chloride is decomposed.
It was discovered that the desired benzyl chloride can be easily isolated and produced in good yield, and furthermore, by reacting tertiary benzylamine and chloroformate in the presence of an acid catalyst, the benzene nucleus of tertiary benzylamine can be produced. The present invention was accomplished by discovering that the reaction proceeds easily and the desired benzyl chloride can be produced in good yield even when the group is substituted with a weak electron-donating group or an electron-withdrawing group. I ended up doing it.

That is, the present invention relates to the general formula (in which R7 and R2 are the same or different alkyl groups, and R1 and R2 can also be bonded to each other to form a heterocycle with a nitrogen atom,
Further, X and Y may be the same or different, and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a nitro group, or a cyano group.

) and the general formula (R3 in the formula represents an alkyl group).

) is reacted with a chloroformic acid ester represented by the general formula (where X and Y have the same meanings as above).

) In the method for producing benzyl chloride represented by ■ tertiary benzylamine (I) and chloroformate (
It is possible to hydrolyze the reaction product obtained by reacting with tertiary benzylamine (I) and chloroformate (II), or to isolate benzyl chloride (III) in the presence of an acid catalyst. ) is a method for producing benzyl chloride, which is characterized in that benzyl chloride (III) is isolated after hydrolyzing the reaction product obtained.

Each method of the present invention 1 and 2 will be explained according to the following reaction formula.

Invention 1 (R1, R2, R3, X and Y in each formula have the same meanings as above.

) The method of invention 1 involves reacting tertiary benzylamine (I) and chloroformate (II) in an inert organic solvent, and reacting hensyl chloride (Ill) with carbamate (IV).
to obtain a reaction product (A) containing
After decomposing the carbamate ester (IV) in the reaction product into secondary amine (V), alcohol (VI) and carbon dioxide gas (■) by hydrolysis treatment, the desired benzyl chloride (IIl) is obtained. Isolate and manufacture.

In addition, the method of invention 2 involves combining tertiary benzylamine (I) and chloroformate (I) in an inert organic solvent in the presence of an acid catalyst.
t) to obtain a reaction product (A′) containing benzyl chloride (III) and carbamate ester (IV),
Furthermore, the reaction product (A'
) to decompose the carbamate ester (IV) in the reaction product into secondary amine (V), alcohol (M) and carbon dioxide gas (■), and then the desired benzyl chloride (m) Isolate and manufacture.

The tertiary benzylamine used as one of the raw materials in each method of the present invention is represented by the above general formula (I), and R1 and R2 may be the same or different, preferably Straight-chain or branched alkyl groups having 1 to 4 carbon atoms, such as methyl, ethyl, n
-propyl 1so-propyl, or n-1ISO-8
eC- or t-butyl.

Furthermore, R1 and R2 are bonded to each other to form a heterocycle with a nitrogen atom, preferably having 2 to 2 carbon atoms.
It is a heterocycle formed by the alkylene groups of 6 with or without sandwiching an oxygen atom, such as morpholino.

On the other hand, X and Y may be the same or different, and are respectively hydrogen atoms, chlorogen atoms such as chlorine, bromine, iodine, and fluorine, and methyl, ethyl, n-propyl, and 1so-7'lopyl. - Alkyl groups such as n-butyl, 1so-butyl, 5ec-butyl, t-butyl, alkoxy groups such as methoxy, ethoxy, n-propyloxy, 1so-propyloxy, n-butyloxy, 1so-butyloxy, methylthio, ethylthio, n- Propylthio・
1so-propylthio・n-butylthio・is.

An alkylthio group such as butylthio, a nitro group, or a cyano group.

The chloroformate (II) is preferably a linear or branched alkyl ester having 1 to 4 carbon atoms, such as chloroformate methyl ester, chloroformate ethyl ester, chloroformate-n-furo Biyl ester, chloroformic acid-1so-furobyl ester, chloroformic acid-n-butyl ester, chloroformic acid-1so-7
``It's a chill ester.

In each method of the present invention, the molar ratio of tertiary benzylamine (I) and chloroformate (Kawa) used is preferably approximately 1:1 from a stoichiometric perspective. Even if used in excess, there is no problem with the reaction.

In each method of the present invention, when reacting tertiary benzylamine (I) and chloroformate (II),
The inert organic solvent used is preferably...a rogen-substituted aliphatic hydrocarbon, an aromatic hydrocarbon,...a rogen-substituted aromatic hydrocarbon, such as carbon tetrachloride, chloroform, dichloromethane, dichloroethane, trichloroethylene,
Perchloroethylene benzene, toluene, xylene, chlorbento naphtha, chlorbenzene, chlorotoluenteal.

Further, the reaction between tertiary benzylamine (I) and chloroformate (Kawa) may be carried out under pressure, but the reaction proceeds satisfactorily even under normal pressure.

The reaction temperature ranges from 30°C to 150°C, preferably from 0°C to 120°C.

The acid catalyst used in the method of the present invention 2 is concentrated hydrochloric acid (
Mineral acids such as 35% or more), concentrated sulfuric acid (90% or more), nitric anhydride, concentrated nitric acid (98%), phosphoric acid, and fatty acids such as formic acid, acetic acid, flopionic acid, and butyric acid are suitable, and this acid catalyst The amount used is 0.000 per mole of tertiary benzylamine.
1-0.5 mol, preferably 0.001-0.2 mol is suitable.

In the methods of the present invention 1 and 2, tertiary pendylamine (
Reaction products (A) and (A') obtained by reacting I) and chloroformate (II) in an inert organic solvent
The hydrolysis of the resulting reaction product (A) or (A'
) is added with an aqueous mineral acid solution such as hydrochloric acid, sulfuric acid, or nitric acid, or an aqueous solution of a fatty acid such as formic acid, acetic acid, propionic acid, butyric acid, etc., at a temperature range of 0°C to 100°C, preferably 20°C to 80°C.

Furthermore, in the method of the second invention, hydrolysis may be carried out by simply adding water.

Carbon dioxide gas is generated with the start of the hydrolysis reaction.

After the hydrolysis reaction is completed, the reaction system is mixed with the organic solvent layer containing benzyl chloride and the mineral acid or fatty acid used for hydrolysis of the secondary amine (V) produced by hydrolysis of the carbamate (IV). The aqueous solution layer containing the salt and alcohol (VI) is divided into two layers, and by separating both layers, the benzyl chloride can be separated along with the organic solvent, and the desired benzyl chloride can be further separated by conventional operations such as distillation. can be easily isolated with good yield.

On the other hand, by neutralizing the remaining aqueous solution layer and performing operations such as extraction and distillation, the secondary amine (V) produced by hydrolysis can be isolated, and the final aqueous solution layer contains the alcohol (V) produced by hydrolysis. Only Vl) will remain.

In this way, benzyl chloride can be isolated and produced in good yield through the reaction of tertiary benzylamine and chloroformate.

Next, to explain the features and advantages of the present invention, firstly, the reaction product obtained by reacting tertiary benzylamine and chloroformate is further hydrolyzed to produce a product※※ The entire amount of benzyl chloride can be completely and easily isolated and purified.

That is, as shown in the reference example below, the entire amount of benzyl chloride produced is completely isolated from the mixed product of benzyl chloride and carbamate obtained by reacting tertiary benzylamine and chloroformate. is not easy.

On the other hand, according to the method of the present invention, the target benzyl chloride can be easily isolated and purified as described above.

Second, by reacting tertiary benzylamine and chloroformate in the presence of an acid catalyst, the
Even when the benzene nucleus of the benzylamine is substituted with a weak electron-donating group or an electron-withdrawing group, the reaction proceeds easily and the desired benzyl chloride can be obtained efficiently and in high yield. That's true.

Thirdly, by carrying out the present invention, benzyl chloride can be isolated and produced in good yield, while useful secondary amines can also be isolated and produced at the same time.

This advantage can be effectively utilized in a chemical reaction process using a benzyl halide and a secondary amine as raw materials.

For example, in the reaction process for producing thiol carbamates useful as herbicides or insecticides by reacting secondary amines, carbonyl sulfides, and benzyl halides, the benzyl halide is reacted with a compound having active hydrogen as shown in the reaction formula below. Because of the easy reaction, it is difficult to avoid the by-product of tertiary benzylamine due to the side reaction between the secondary amine and the benzyl halide.

(Hal in the formula represents a halogen atom.

) Therefore, the wastewater from this reaction process will be contaminated with by-product tertiary benzylamine, but this wastewater will be purified using the activated sludge method, which has been adopted as a wastewater treatment method in chemical factories in recent years. It is difficult to separate the by-produced tertiary benzylamine and dispose of it by combustion, which may induce secondary pollution due to the generation of nitrogen oxides.

For this reason, it is difficult to safely dispose of the by-produced tertiary benzylamine.

However, if the method of the present invention is adopted here, the by-product 3
Useful benzyl chloride and secondary amines can be isolated and produced from primary benzylamine, and they can also be reused.

Furthermore, since the substances produced as a result of carrying out the method of the present invention are alcohols, they can be sufficiently purified by the activated sludge method and can be safely disposed of without causing environmental pollution.

Next, the present invention will be explained in more detail with reference to Reference Examples and Examples.

Reference example l 98.9% of N-N-diethyl-P-chlorobenzylamine in 100ml of benzene? (0.5 mol) was dissolved and heated at 25°C with stirring to 55.0 ml of chloroformic acid ethyl ester.
? (0.5 mol) was heated under heat for 20 minutes, the temperature of the reaction solution was raised, and the reaction was carried out in a temperature range of 50°C to 52°C for 6 hours.

After the reaction was completed, benzene was distilled off under reduced pressure, and then distilled under reduced pressure to obtain a distillate (I) with a boiling point of 70°C to 95°C/20 mmHg.
74.2'f? boiling point 95℃~105℃/2
63.5 S' of distillate (river) of 0 mmHg was obtained.

As a result of gas chromatography analysis of each distillate obtained, it was found that the distillate (■) contained almost no N.
-N-dimethylcarbamic acid ethyl ester, but about 14% of P-chlorobenzyl chloride remained without being separated by distillation.

Further, the distillate (It) was mostly P-chlorobenzyl chloride, but about 3% of N-N-dimethylcarbamic acid ethyl ester remained without being separated by distillation.

The distillate (IF) is distilled under reduced pressure again to have a boiling point of 103 to 1.08.
57.9P of P-chlorobenzyl chloride was obtained at ℃/20 mm Hg, and the yield was 71.9%.

Example 1 NN-diethyl-P-chlorobenzylamine 98,1' (0.5 mol) was dissolved in 100 ml of benzene, and chloroformic acid ethyl ester was dissolved at 25° C. while stirring. (
After adding 0.5 mol) dropwise over 20 minutes, the reaction mixture was heated and reacted for 6 hours in a temperature range of 50°C to 52°C.

After the reaction was completed, 12Of of a 30% sulfuric acid aqueous solution was added to the obtained reaction solution, and the temperature of the reaction solution was raised to 50°C to 52°C while stirring.
Hydrolysis was carried out in a temperature range of 10°C until the generation of carbon dioxide gas ceased.

After the hydrolysis reaction, the reaction solution was allowed to cool and then separated into an organic solvent layer and an aqueous layer.

The separated organic solvent layer was washed twice with 50 ml of water, then dried over anhydrous Na2SO4, and the benzene was distilled off under reduced pressure.
20 in Hg, P-chlorobenzyl chloride 7], 5P was obtained.

The yield was 88.8% based on the N-N-diethyl-P-chlorobenzylamine used.

On the other hand, after the hydrolysis reaction, 352 sodium hydroxide was added to the separated aqueous layer to neutralize it, and the mixture was extracted three times with 30 ml of ether.

The ether extracted solution was washed twice with 50 ml of water, then dried over anhydrous Na2SO4, and then the ether was distilled off under reduced pressure, and further distilled under reduced pressure to give a boiling point of 52°C to 55°C/760°C.
27.59 mmHg of diethylamine was obtained.

The yield was 75.2% based on the N·N-diethyl-P-chlorobenzylamine used.

Example 2 98.9 N-N-diethyl-P chlorobenzylamine per 1 OOTIL of benzene? (0.5 mol) was added, and 55.0 P (0.5 mol) of chloroformic acid ethyl ester was added dropwise at 25°C with stirring for 20 minutes, and further at 25°C. The reaction was carried out at a temperature of 2 hours.

After the reaction was completed, post-treatment was performed to obtain 73.5 f of P-chlorobenzyl chloride (yield: 91.3%).

Example 3 In the same manner as in Examples 1 and 2, 05 mol of various tertiary benzyl amines and 05 mol of various chloroformates were mixed in 1.007711 l of various organic solvents with or without addition of an acid catalyst. The resulting reaction solution was subjected to hydrolysis treatment to obtain various target benzyl chlorides.

The results are shown in the table below. As is clear from each example and reference example, if the reaction product obtained by reacting tertiary benzylamine and chloroformate is hydrolyzed, the generated benzyl chloride can be completely isolated and purified. Again, in the presence of an acid catalyst, the reaction between tertiary benzylamine and chloroformate can be completed at low temperature and in a short time.

Claims (1)

[Claims] 1 General formula (in the formula, Ro and R2 are the same or different alkyl groups. R4 and R2 can also be bonded to each other to form a heterocycle with a nitrogen atom) In addition, X and Y may be the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a nitro group or a cyano group. and the general formula (R in the formula
3 represents an alkyl group. ) in a method for producing benzyl chloride represented by the general formula (in the formula, X and Y have the same meanings as above) by reacting with a chloroformate ester represented by:
A method for producing benzyl chloride, which comprises hydrolyzing a reaction product obtained by reacting tertiary benzylamine and chloroformate, and then isolating the target compound. 2 General formula (in the formula, R1 and R2 are the same or different alkyl groups. R7 and R2 can also be bonded to each other to form a heterocycle with a nitrogen atom. may be the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, a nitro group or a cyano group. In a method for producing benzyl chloride represented by the general formula (X and Y in the formula have the same meanings as above) by reacting with a chloroformate represented by R3 represents an alkyl group. ,
A method for producing benzyl chloride, which comprises hydrolyzing a reaction product obtained by reacting a tertiary benzylamine and a chloroformate in the presence of an acid catalyst, and then isolating the target compound.