JPS6112664A - Production of thiocarbamate derivative - Google Patents

Abstract

PURPOSE:The reaction of an alkylphenyl chloroformate with an aminopyridine derivative in the presence of a dehydrohalogenation reagent in a secondary or tertiary alcohol of 4-5C atoms is followed by addition of water to enable the production of the titled compound with industrial advantage. CONSTITUTION:The reaction between a compound of formula I (R1 is 2-5C alkyl) and another compound of formula II (R2 is H, halogen, lower alkyl, lower alkoxy) is carried out in the presence of a dehydrohalogenation reagent in an aqueous or absolute secondary or tertiary alcohol, then water is added to the reaction mixture to avoid the reduction in yield caused by formation of by- products and contamination with them. Thus, the objective compound of formula III, which is used for medical, agricultural, and horticultural purposes, are obtained with no need of special purification processes in high purity and high yield. The amount of the alcohol is about 5-20 times the weight of the compound of formula II and water is added so that its amount becomes 40-75%, preferably 50-70% based on the alcohol-water mixture.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing thiocarbamate derivatives. More specifically, a thioformate is produced by reacting an argylphenyl chlorothioformate with an aminopyridine derivative in a hydrous or anhydrous C4-, C502- or tertiary alcohol in the presence of a dehydrohalogenating agent. This invention relates to a method for producing carbamate derivatives.

Thiocarbamate derivatives are compounds useful as agricultural chemicals.

(Prior Art) Regarding the method for producing the thiocarbamate derivative of the present invention, the present inventors have proposed a method in which an alkylthionichlorothioformate and an aminopyridine derivative are reacted in the presence of a dehydrohalogenating agent.

[Problems to be solved by the present invention]

In the conventional technology, highly pure thiocarbamate derivatives require purification by column chromatography, recrystallization, etc., and industrial operations are extremely complicated.

A further object of the present invention is to obtain industrially advantageously highly purified thiocarbamate derivatives.

[Means to solve the problem]

As a result of various tests and intensive studies, the inventors of the present invention found that alkylphenyl chlorothioformates and aminopyridine derivatives can be converted into hydrous or anhydrous secondary or hexavalent compounds having 4 or 5 carbon atoms in the presence of a dehydrohalogenating agent. By performing the reaction in alcohol and then adding water, it is possible to prevent the formation of alkylphenyl-alkylthiocarbonate esters due to the reaction between alcohol and alkylphenylchlorothioformate, and not only increase the yield of the desired thiocarbamate derivative, but also prevent side reactions. The present invention has been completed based on the discovery that it is extremely effective in preventing solvent loss due to oxidation and contamination of thiocarbamate derivatives by by-products.

That is, the present invention relates to an alkylphenyl chlorothioformate represented by the general formula (I) (wherein represents an alkyl group having 2 to 5 carbon atoms) and an alkylphenyl chlorothioformate represented by the general formula (In (in which the horse is a hydrogen atom, halogen atom, lower alkyl group,
Indicates a lower alkoxy group. The general formula (
This invention provides a method for producing a thiocarbamate derivative represented by the formula (wherein R1+R2 are the same as above).

[For production]

Next, a method of implementing the present invention will be described in detail.

An aminopyridine derivative and a dehydrohalogenating agent are added to a hydrous or anhydrous alcohol having 4, 502 or 6 carbon atoms. Then, alkylphenyl chlorothioformate is added dropwise. After dropping the entire amount of alkylphenyl chlorothioformate, a predetermined amount of water is added to precipitate a thiocarbamate derivative, which is a reaction product. Also,
Do you also react with alkylphenyl chlorothioformate and aminopyridine derivatives? 7j, reacting hydrogen hydride with a dehydrohalogenating agent to precipitate a salt (hereinafter referred to as salt).

After the reaction is complete, the reaction solution is filtered to collect the thiocarbamate derivative and salt. Next, the collected thiocarbamate derivative and salt are washed with water to remove the salt and obtain a highly pure thiocarbamate derivative.

The aminopyridine derivative is used in an equimolar amount to the alkylphenyl chlorothioformate, and the dehydrohalogenation reagent is used in an equivalent or more amount.

The dehydrohalogenating agent is carbonic acid (IJ).

Alkali carbonates such as potassium carbonate, alkali hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate.

salt, and triethylamine, dimethylaniline.

Organic bases such as pyridine can be mentioned.

Water-containing or anhydrous carbon number 4 or 50 used as a solvent
Secondary or tertiary alcohols include sec-butanol, tart-butanol, 5ec-amyl alcohol, 3-pentanol and tert-pentanol.

These alcohols are used in an amount of about 5 to about 20 times the weight of the aminopyridine derivative.

The amount of water added after the reaction is related to the mixing ratio of alcohol and water used in the reaction, but if the ratio of water in the alcohol-water mixed solution after addition is less than 40%, the recovery rate of high-purity thiocarbamate derivatives will decrease. If it exceeds 75%, the purity of the thiocarbamate derivative decreases, so the amount is preferably such that the proportion of water in the alcohol-water mixed solution is 50 to 70%.

The reaction temperature is usually selected between 0''C and about 50C.

The reaction time can usually be completed within 10 hours.

〔Example〕

Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.

Example 1 2-methoxyl 6-methylaminopyridine 1 (L4 gr, sodium carbonate 8 gr
,, 17.2 g of 4-tθi-butylphenylchlorothioformate was added dropwise to 90% of tert-butanol containing 10% water over 20 minutes while stirring at room temperature. After the dropwise addition, the mixture was further stirred for 2 hours to complete the reaction.

After the reaction was completed, 190 d of water was added, the contents of the flask were taken out, and the solid was collected by filtration. The solid was then washed with 100 ml of water and O-4-ta having a melting point of 87-88°C was added.
259 gr of rt-butylphenyl N-methyl-N-(6-medoxy-2-pyridyl)thiocarbamate was obtained. (Yield: 95.5%) Analysis by high performance liquid chromatography showed that the purity was 99.6%.

Comparative Example 1 11 L of 2-methoxy-6-methylaminopyridine, 4 gr of sodium carbonate, and 8 gr of sodium carbonate were placed in a 500-meter three-bottle flask.
90 g of 10% water-containing tert-butanol was taken, and while stirring at room temperature, 17.2 g of 4-tert-butylphenylchlorothioformate was added dropwise over 20 minutes.

After the dropwise addition, the mixture was further stirred for 2 hours to complete the reaction.

After the reaction was completed, the contents were taken out from the flask without adding water, and the solids were collected by filtration. The solid was then washed with 100 ml of water and dissolved in O-4-tart having a melting point of 87-88°C.
-butylphenyl N-methyl-N-(6-medoxy-2-pyridyl)thiocarbame) 19.1 g was obtained. (Yield: 7% and 1%) High performance liquid chromatography analysis revealed a purity of 990%.

Examples 2 to 8 and Comparative Example 2 In the same reaction apparatus as in Example 1, an aminopyridine derivative, a dehydrohalogenating agent, and a hydrochloric acid containing 4 carbon atoms, 502 carbon atoms, or tertiary carbon atoms (7) 7 A/ =
Then, alkylphenyl lyrothioformate was added dropwise to react under the conditions shown in Table 1.

After the reaction was completed, a thiocarbamate derivative was obtained by the same reaction procedure as in Example 1. The results are shown in Table 1.

The yield in these cases was 958-95.5%.

Further, Table 2 (Comparative Example 2) shows the case where acetone was used as the solvent. The yield in this case was 88.

〔Effect of the invention〕

In this way, the target thiocarbamate derivative of the present production method can be obtained with high purity and high yield without special purification such as recrystallization.

It is also extremely effective in preventing solvent loss due to side reactions and contamination of thiocarbamate derivatives by by-products.

Patent Applicant: Toyo Soda Kogyo Co., Ltd. Procedural Amendment - 1: August 27, 1982 Manabu Shiga, Commissioner of the Patent Office 1. Indication of the case 1982 Patent Application No. 132045 2. Name of the invention Production of thiocarbamate derivatives Act 4 Date of amendment order Spontaneous 5 Subject of amendment ``Claims column of the specification'' ``Detailed explanation of the invention column of the specification'' 6 Contents of amendment (I) Scope of description and claims `` (2) Same book, page 6, line 4 “Alkylphenyl-alkylthiocarbonate-r-ster”
is corrected to "alkylphenyl alkylthiocarbonate".

(3) Same book, 1st line from the bottom of page 4 0H8J I am corrected.

°2 Claims Alkylphenyl chlorothioformate represented by general formula (I) (wherein R1 represents an alkyl group having 2 to 5 carbon atoms) and general formula (II) (wherein R1 is a hydrogen atom) , a halogen atom, a lower alkyl group, or a lower alkoxy group) is reacted in a hydrous or anhydrous carbon number 4, 502, or 6-ary alcohol in the presence of a dehydrohalogenating agent, and then reacted with water. A method for producing a thiocarbamate derivative represented by the general formula (■ (in the formula, "It R2" is the same as before), characterized by adding.

”

Claims (1)

[Claims] General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc. are available▼(I) Alkylphenylchlorothioformate represented by (in the formula, R_1 represents an alkyl group having 2 to 5 carbon atoms) and general formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) (In the formula, R_2 represents a hydrogen atom, a halogen atom, a lower alkyl group, or a lower alkoxy group.) Dehalogenation of the aminopyridine derivative represented by General formula (III) characterized by reacting in a hydrous or anhydrous secondary or tertiary alcohol with 4 or 5 carbon atoms in the presence of a hydrogenation reagent, and then adding water ▲There are mathematical formulas, chemical formulas, tables, etc. ▼(III) A method for producing a thiocarbamate derivative represented by (in the formula, R_1 and R_2 are the same as before).