KR790001653B1 - Process for the preparation of s-triazolo(3,4-b)benzothiazoles - Google Patents

Abstract

Title compds. (I; R = H, C1-12 alkyl, cyclopropyl, CF3; R1 = H, Br, C1, F ; R2, R3 = H, C1-3 alkyl, C1-3 alkoxy, Br, C1, F, CF3), useful as fungicides and bactericides (no data), were prepd. by the reaction of II and same mole base at 60-200≰C, in amide anhydride. Thus, 4-(2,4-dichloro- phenyl)-5-methyl-1,2,4-triazole-3-thiol in DMF was refluxed for 24hr adding NaOH followed by extrating with ethylacetate using liq-liq extractor to give 7-chloro-3-methyl-S-triazolo [3,4-b benzothiazole.

Description

Method for producing S-triazolo [3,4-b] benzothiazoles

The present invention relates to a method for producing S-triazolo [3,4-b] benzothiazoles of the following formula (I), which is effective for controlling plant fungi.

In the above structural formula

R is hydrogen, C ₁ = C ₁₁ alkyl, cyclopropyl or trifuluromethyl;

R ₁ is hydrogen, bromine, chlorine or fluorine;

R ₂ and R ₃ are each hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, bromine, chlorine, fluorine or trifluoromethyl, provided that at least one of R ₂ and R ₃ is hydrogen and R ₁ Is halogen

R is not hydrogen and R ₂ is hydrogen).

Certain substituted S-triazolo [3,4-b] benzothiazoles (hereinafter referred to as triazolobenzothiazole compounds) are used for controlling phytopathogens, including fungi and bacteria. Therefore, these triazolobenzothiazoles can be used for the control of fungi such as myocarcinoma bacterium, rust rust bacillus, blast germ, white powder germ and anthrax. In particular, these compounds are suitable for controlling fungi, and in particular, rice has good results for controlling fever. Belgian Patent No. 789,918 describes a process for preparing these compounds by dehydration cyclization of 2-acylhydrazino benzothiazole with polyphosphoric acid.

The S-triazolo [3,4-b] benzothiazole compound of formula (I) according to the present invention is characterized by the following structural formula (III) with at least a molar equivalent of It is prepared by reacting with 4- (0-halophenyl) -1,2,4-triazole-3-thiol compound.

First, thiosemicarbazide is formed, and then the intramolecular double bond is cyclized to obtain benzothiazole: 1) triazolothiol by dehydration and 2) aromatic benzothiazole compound by aromatic halogen substitution. That is, 4- (0-halophenyl) -1,2,4-triazole-3-thiol is obtained by dehydration reaction, and an aromatic halogen substitution reaction is generated by thiol anion generated in the presence of a base, resulting in a triazolobenzothiazole compound. Becomes

In halogen substitution with thiol anion, when R ₁ is equal to X, both are bromine, chlorine or fluorine. _One of R ₁ and X is substituted to form 5-bromo, 5-chloro- or 5-fluorotriazolobenzothiazole. When R ₁ and X are bromine or chlorine or fluorine, respectively, a mixture of 5-chloro-, 5-bromo- and 5-fluorotriazolobenzothiazole is obtained. This mixture is separated by methods such as fractional crystallization or chromatography.

The reaction proceeds even when R ₁ or X is oxo, but the necessary 0-iodophenylisothiocyanate is not suitable because it is difficult and uneconomical to produce.

In general, it can be seen that the negatively phenyl substituent is obtained in high yield and the reaction time is short to promote the halogen substitution reaction. Electron-donating substituents such as methyl have a tendency to delay the halogen substitution reaction, resulting in a longer reaction time and a by-product.

In carrying out the process, it is necessary to isolate thiosemicarbazides or triazolothiols as intermediates.

As the solvent used in the present invention, an ordinary tertiary amide solvent which is inert to the starting materials and the product is used, and an anhydrous tertiary amide solvent can be generally used. "Almost anhydrous" means that a small amount of water can be tolerated in the solvent. In general, the amide solvent can be "dried" in situ by allowing the base to react with water using 1 to 10% excess base. Such amide solvents include N, N-dibutylacetamide, dimethyl acetamide (DMAC), dimethylformamide (DMF) and N-methyl-2-pyrrolidone. Higher amide solvents are effective because of their high boiling point. DMAC and DMF are preferred solvents for their ease of use and ease of removal.

In general, it is suitable to use a strong base in the process that is strong enough to generate triazolethiol anions. Although molar equivalents of base are sufficient, bases are dual. That is, the base is involved in 1) triazolothiol formation and 2) intramolecular halogen substitution by thiol anion. Suitable bases include alkoxides, amides, carbonates, hydrides and hydroxides of alkali metals in addition to lithium alkyls such as methyllidium and butyliridium. Among these are lithium ethoxide, potassium t-butoxide and sodium methylate. Carbonates and hydroxides of lithium, sodium, potassium, cesium and rubidium may also be used. Preferred bases that can be used in the present invention are lithium amide, sodium amide, potassium amide, sodium hydride and potassium hydride.

The manufacturing process is carried out at about 60 ° to 200 ° C. When reacted with the acylhydrazine and isothiocyanate compounds, the 1-acyl-4- (0-halophenyl) -3-thiosemicarbazide intermediate is reacted at about 60 ° to 100 ° C. for about 24 hours. Occur in situ. After the induction period, the desired molar equivalent of sodium hydride is added and the reaction is completed at about 160 ° C., the boiling point of the DMF solvent. When thiosemicarbazide or triazolothiol compounds are used, they are dissolved in DMF, equimolar sodium hydride is added and the reaction mixture is heated to reflux until the reaction is complete. In general, the process is completed at 60 ° to 100 ° C in 24 hours or less. The halogen substitution reaction by thiol anion depends on the properties of the phenyl substituent group. When R ₂ and R ₃ are electron donating groups such as C ₁ -C ₃ alkyl, the halogen substitution reaction is delayed and the reaction time is extended.

All triazolobenzothiazole compounds obtained by the present invention are useful for controlling plant pathogens, especially rice fever.

The triazolobenzothiazole compound (compound I) obtained by this invention is as follows.

S-triazolo [3,4-b] benzothiazole

3-methyl-S-triazolo [3,4-b] benzothiazole

7-chloro-3-methyl-S-triazolo [3,4-b] benzothiazole

5-chloro-3-methyl-S-triazolo [3,4-b] benzothiazole

3,7-dimethyl-S-triazolo [3,4-b] benzothiazole

3-heptyl-S-triazolo [3,4-b] benzothiazole

3-methyl-5-trifluoromethyl-S-triazolo [3,4-b] benzothiazole

3,6-dimethyl-S-triazolo [3,4-b] benzothiazole

6-methoxy-3-methyl-S-triazolo [3,4-b] benzothiazole

3-propyl-6-trifluoromethyl-S-triazolo [3,4-b] benzothiazole

3-cyclopropyl-S-triazolo [3,4-b] benzothiazole

5-chloro-3-cyclopropyl-S-triazolo [3,4-b] benzothiazole

5-trifluoromethyl-S-triazolo [3,4-b] benzothiazole

5-chloro-7-propoxy-3-trifluoromethyl-S-triazolo [3,4-b] benzothiazole

3-ethyl-6 = ethoxy-S-triazolo [3,4-b] benzothiazole

5-fluoro-6-methyl-3-butyl-S-triazolo [3,4-b] benzothiazole

5,7-dichloro-3-isopropyl-S-triazolo [3,4-b] benzothiazole

5-fluoro-3-nonyl-S-triazolo [3,4-b] benzothiazole

5-fluoro-6-methoxy-3-propyl-S-triazolo [3,4-b] benzothiazole

5-chloro-3,7-bis (trifluoromethyl) -S-triazolo [3,4-b] benzothiazole

3-cyclopropyl-5-fluoro-6-trifluoromethyl-S-triazolo-benzothiazole

The following examples specifically illustrate how to prepare the compounds of the invention.

(I) triazolobenzothiazole, preparation of the final product

Example 1

5 g (19 mmol) of 4- (2,4-dichlorophenyl) -5-methyl-1,2,4-triazole-3-thiol are dissolved in 100 ml of DMF. 1 g (20 mmol) sodium hydride is added dropwise to the stirred reaction mixture with a 50% inorganic oil dispersion. The mixture is refluxed for 24 hours and then poured into 600 ml of water. The aqueous mixture is extracted with n-hexane to remove inorganic oil and the aqueous phase is extracted with ethyl acetate overnight using a liquid-liquid extractor. Ethyl acetate is dehydrated over magnesium sulfate and evaporated in vacuo to give a residue. It is washed with toluene and the crystalline product is collected by filtration to yield 1.9 g (45%) of 7-chloro-3-methyl-S-triazolo [3,4, b] benzothiazole. Melting Point: About 186 ~ 188 ℃

1.6 g of benzothiazole having a melting point of about 185-188 ° C. was recovered from the aqueous phase.

Stone: C ₉ H ₆ ClN ₃ S Molecular Weight 224

Calc .: C 48.33; H 2.70; N 18.79

Found: C 48.32; H 2.89; N 18.96

4- (2,4-dichlorophenyl) -5-methyl-1,2,4-triazole-3-thiol instead of 4- (0-halophenyl) -5-substituted-1,2,4-triazole Reaction with the above method using -3-thiol affords the following products.

3-methyl-S-triazolo [3,4-b] benzothiazole, melting point about 153 to 154 ° C

S-triazolo [3,4-b] benzothiazole, melting point about 175 to 176 ° C

6-chloro-3-methyl-S-triazolo [3,4-b] benzothiazole, melting point about 246 to 266 ° C

5-chloro-3-methyl-S-triazolo [3,4-b] benzothiazole, melting point about 186-188 ° C.

3,7-dimethyl-S-triazolo [3,4-b] benzothiazole, melting point about 176 to 177 ° C

3,6-dimethyl-S-triazolo [3,4-b] benzothiazole with a melting point of about 203-207 ° C.

3-methyl-6-trifluoromethyl-S-triazolo [3,4-b] benzothiazole, melting point about 181 to 183 ° C

3-heptyl-S-triazolo [3,4-b] benzothiazole, melting point about 82-84 ° C.

Claims (1)

Equivalent molar amount of base is reacted with 4- (0-halophenyl) -1,2,4-triazolo-3-thiol of the following formula (III) in anhydrous amide solvent at a temperature of 60 to 200 캜. To prepare s-triazolo [3,4-b] benzothiazole compound of formula (I):

In the above structural formula R is hydrogen, C ₁ -C ₁₁ alkyl, cyclopropyl, trifluoromethyl, R ₁ is hydrogen, bromine, chlorine or fluorine, R ₂ and R ₃ are each hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, bromine, chlorine, fluoro, trifluoromethyl, provided that at least one of R ₂ and R ₃ is hydrogen and R ₁ When it is halogen, R is not hydrogen and R ₂ is hydrogen) X is bromine, chlorine, fluorine.