DE2350875C3 - Process for the preparation of 2-hydrazinobenzothiazoles - Google Patents

Description

N (R ¹ ),

wherein R 'each independently represents hydrogen or methyl, with hydrazine, characterized in that the reaction is carried out at a temperature of 100 ^° C. to 150 ^° C. in an inert solvent and in the presence of 0.1 to 1.0 mol of a mineral acid , Acetic acid, benzoic acid, formic acid, malonic acid, oxalic acid, p-toluene-sulfonic acid, phenylacetic acid or citric acid per mole of hydrazine

2. The method according to claim I _1, characterized in that the reaction in C2-Q-alkylenediols, di- or tri (ethylene or propylene) glycols, Moiio (Ci-C4-alkyl) ether of ethylene or propylene glycols, mono (Ci - Q-alkyF ethers of di- or tri (ethylene or propylene glycol, triethanolamine, sulfolane or dimethyl sulfoxide are used as solvents.

3. The method according to claim 2, characterized in that that propylene glycol or ethylene glycol is used as the solvent.

description

A wide variety of processes are already known which are based on a so-called exchange lamination based, namely the exchange of one amino group for another, including under Inclusion of exchanging an amino group for a hydrazino group. Reactions of this type are described in Houben-Weyl, Methods of Organic Chemistry, Volume 10/2, 278 (Georg Thieme Verlag, Stuttgart, 1967); Ann. 686: 134 (1965); J. Amer. Chem. Soc. 74: 1648 (1952); J. Amer. Chem. Soc. 82: 3971 (1960); and |. Gen. Chem. U.S. S. R. (English) 29, 2036 (1959).

In the latter reference, the manufacture and attempted manufacture become more numerous 2-Mlydrazinobenzothiazole by converting hydrazine with 2-aminobenzothiazQl and various ring-substituted 2-aminobenzothiazoles described. However, the results obtained in this way cannot be considered satisfactory. In some reactions, no hydrazinobenzothiazole is obtained at all. The unsubstituted 2-aminobenzothiazole gives the desired product, but at the same time also a fair amount of o-aminothiophenol, which arises through ring opening and is isolated in the form of the disulfide. Only the carboxy-substituted ones Aminobenzothiazoles lead to good yields. As a result of these disadvantages of the known methods for Production of 2-aminobenzothiazoles, the invention has set itself the task of a new production process for these compounds to provide the desired 2-aminobenzothiazoles in very good form Yields and without the usual side reactions

in nen results

This object is now achieved according to the invention in the manner that emerges from the claims. The use of an acid is critical to the success of the process of the invention. examples for suitable mineral acids are hydrochloric acid, hydrobromic acid or sulfuric acid. The respective Acid can be added to the reaction mixture in any way. You can separate them add or add in the form of a salt, either of the 2-aminobenzothiazole or the Hydrazine.

There are 0.1 to in the process according to the invention 1.0 mol of acid is used per mol of hydrazine. 0.33 to 0.5 mol of acid is preferably used per mol of hydrazine.

The known methods often work with the use of excess hydrazine, some of which serves as a solvent In contrast, it has now been found that working in the presence of an inert Solvent for the particular success of the invented

jo the method according to the invention is also important. The solvent used should be miscible with hydrazine and, in combination with the reactants, at temperatures of at least about 100 ^° C., preferably at temperatures above 120 to

Jj 150 ⁰ C, boil under reflux. Preferred solvents are alkylene diols having 2 to 4 carbon atoms, such as ethylene glycol, propylene glycol, 1,4-butanediol or 2,3-butanediol, di- or tri (ethylene and propylene) glycols, such as diethylene glycol, triethylene glycol, dipropylene glycol or tripropylene glycol, mono (Ci— G »-alkyi) ethers of ethylene or propylene glycols, such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol mono-n-butyl ether or propylene glycol monomethyl ether, mono (Ci - C4-alkyl) ether

4 ") of di- or tri (ethylene and -propylene) glycols, such as diethylene glycol monomethyl ether, diethylene glycol monoethyl ether or diethylene glycol mono-n-butyl ether, triethanolamine, sulfolane or dimethyl sulfoxide. C ₂ -GrAlkylenediols are only not mentioned below

V) understood geminal diols. Water "does not divide anything The preferred solvent is, but smaller amounts are not detrimental to the reaction. That Therefore, hydrazine can be added in any of the many commercially available forms containing water.

M ben be.

It is not critical that the 2-aminobenzothiazole and the hydrazine are used in a certain ratio to each other. However, according to the prior art, quite an excess is often used

Wed of hydrazine. However, it has now been found that some 2-amine Qbenzothiazgjen at higher hydrazine concentrations is more likely to lead to the formation of by-products. The respondents will be at the Implementation only in equimolar amounts

h'i needs and use of excess Hydrazine is therefore uneconomical. Good results when carrying out the method according to the invention one obtains with amounts of hydrazine from 1 to not

about 10 moles per mole of 2-aminobenzothiazole, to Better results are obtained by using from about 3 to about 5 moles of hydrazine per mole 2-aminobenzothiazole.

The inventive process is carried out at temperatures between 100 and 150 ⁰ C, is said to operate at reaction temperatures between 120 and 150 ° C preferably

The desired product typically precipitates in the reaction mixture and can be obtained therefrom filter off. However, other customary processes can also be used for the separation. According to the invention The product obtained is generally highly pure, the purity in some cases even being up to 98% If desired, the separated product can, however, also be purified by customary methods.

The invention is explained in more detail with the aid of the examples

Example 1 24iydrazinobenzothiazole

A slurry of 30 g (0.2 mol) of 2-aminobenzothiazole in 150 ml of ethylene glycol is mixed with 23.7 g (0.4 mol) of 85 percent hydrazine hydrate and 13.7 g (0.2 mol) of hydrazine monohydrochloride. The reaction mixture is under nitrogen stirred and ^{heated to 140 °} C. for 2 hours. The product crystallizes out on cooling. Then are added 50 ml of water are added and stirred, followed by filtration, washed with water tOOml in three portions and dried in vacuum at 60 ⁰ C. In this manner, 2 ⁿ $ g is obtained (90.6% of theory) of 2-hydrazinobenzothiazole of melting point 194-198 ° C, in a purity (titration) of 97.0%. After recrystallization from ethanol to obtain 20 g of product which melts at 198-199 ° C for this purpose, a melting point of 199-200 ⁰ C is given in oer literature (J. Gen. Chem. USSR 29, 2036 (1959)). Further 4 g of product having a melting point of 1964- 198.5 ⁰ C is obtained from the second crystals.

Example 2 5,6-Dimethyl-2-hydrazinobenzothiazole

S.e-Dimethyl ^ -aminobenzothiazole (5.0 g, 0.028 mol), 85 percent hydrazine hydrate (3.49 g, 0.056 mole) and hydrazine monohydrochloride (159 g, 0.028 mole) are used implemented according to the method described in Example 1. This gives 5,6-dimethyl-2-hydrazinobenzothiazole in a yield of 82% and with a melting point of 233 to 228 "C. The purity of the product (titration) is 97.2%. After recrystallization from ethanol one arrives at a 235 to 237 ° C with decomposition melting material.

Analysis for C ₉ HhN) S:

calculated:

C 55.93; H 5.74; N 21.74; S 16.59; found:

C 55.96; H 5.78; N 21.55; S 16.72.

Example 3 4-chloro-2-hydrazinobenzothiazole

4-chloro-2-aminobenzothiazole (10.09 g, 0.054JMoI), 85 percent hydrazine hydrate (6.45 g, 0.109 mole) and hydrazine monohydrochloride (3.72 g, 0.109 mole) are used implemented according to the procedure described in Example 1. This gives 9.77 g (90% of the Theory) 4-CbJor-2-hydrazinobenzotbiazo | with a Melting point from 226 to 229 ° C. The purity of the product (titration) is 96.2%. After recrystallization 7.2 g of product are obtained from isopropanol Melts 239 to 24 Γ C.

Analysis WrC ₇ H ₆ N ₃ ClS;

calculated:

C42.ll; H 3.03; N 21.05; S 16.06; Cl 17.76;

found:

C 42.07; H 2.94; N 20.82; S 16.11; Cl 17.81.

Example 4
4-methoxy-2-hydrazinobenzothiazole

4-Methoxy-2-aminobenzothiazole (5.0 g, 0.028 mol), 85 percent hydrazine hydrate (33 g 0.057 mol) and hydrazine monohydrochloride (1.9 g, 0.028 mol) are reacted according to the procedure described in Example 1. This gives 4, 85 g of 4-methoxy-2-hydrazif.obenzothiazol of melting point 215-220 ⁰ C. the purity of the product (titration) is 97.1%. The analytical sample melts at 224 to 2263 ° C (from methanol).

Analysis for C ₈ H ₉ N ₃ OS:

calculated:

C 49.21; H 4.65; N 21.52; S 16.42;
i "found:

C 49.25; H 4.54; N 21.67; S 16.40.

Example 5
_J5 4-methyl-2-hydrazinobenzothiazole

A mixture of 1135 g (0.049 mol) of 4-methyl-2-aminoaminobenzothiazolhydrobromid and 8,60g (0, l5 mole) 85prozentiges hydrazine hydrate in 40 ml of ethylene glycol is heated under nitrogen 2 hours at 140 ⁰ C. The reaction mixture is cooled ac> f Rah temperature and add 40 ml of water. As the product cools down, it begins to precipitate. It is filtered off, washed with water and dried ^{at 60 ° C. in vacuo.} In this way, 830 g (93% of theory) of 4-methyl-2-hydrazinobenzothiazole with a melting point of 165 to 168 ° C. are obtained. The crude product is examined by thin-layer chromatography. According to this, it is free of raw material and practically pure. The analytical sample melts at 167 to 169 ° C (from

ίο ethanol).

Analysis for C ₈ H, NjS:

calculated:

C, 53.61; H 5.06; N 23.44; S 17.89;
" found:

C, 53.84; H 4.98; N 23.44; S 17.68.

Example 6
δ-methoxy 4-hydrazinobenzothiazole

6-methoxy-2-aminobenzothiazole (2.70 g, 0.015MoI), 85 percent hydrazine hydrate (1.77 g, 0.015 mol) and hydrazine monohydrochloride (1.0Jg, 0.015 mol) are used implemented according to the procedure described in Example I. This gives 2.63 g (90% of theory) ö-Metnoxy ^ -hvclrazinobenzothiazol of the melting point 172 to I75 "C. The purity of the product

(Titration) is 97.0%, the melting point of the literature is according to US-PS 20 73 600 at 168 to 169 "C.

Example 7 6-MethyHhio-2-hydrazinobenzQth! Azole

6-MethyIthio-2-aminobenzothiazoI (10.0 g, 0.05 mol), 85 percent hydrazine hydrate (6.05 g, 0.10 mol) and hydrazine monohydrochloride (3.5 g, 0.05 mol) are used implemented according to the procedure described in Example 1. This gives 9.95 g (92.5% of Theory) 6-methylthio-2-hydrazinobenzothiazoI from melting point 173 to 176 ° C. The purity of the Product (titration) is 98.0%. The analytical sample melts at 178 to 180 ° C (from ethanol).

IO

15th

Analysis of JQrC ₈ H ₉ N ₃ S ₃ :

calculated; C 45.47; H 4.29; N 19.89; S 30.30;

found: C 45.69; H 4.30; N 19.67; S 30.63.

Examples 8-14

According to the process according to the invention, numerous reactions of 4-methyl-2-aminobenzothiazole hydrobromide with hydrazine hydrate are carried out, for which various solvents are used. The solvents used in each case, the The reaction times, the reaction temperatures and the yields obtained are as follows:

solvent Example 15 Implementation time Conversion temperature Bulge Diethylene glycol 80 minutes 140C 91% Propylene glycol 2 hours 140 C 93% 2,3-butanediol 3 hours I25 "C 88% Triethanolamine 3 hours 134-140 ⁰ C 91% Sulfolane 5.5 hours 129 ° C 85% DMSO 4 hours 125 C > 95% Ethylene glycol monomethyl 5.5 hours 110 C 85% ether 89% melting at 143-151 ° C Die '

4-methyl-2-hydrazinobenzothiazole

4-methyl-2-dimethyIaminobenzothiazolhydrobromid (10.95 g, 0,04MoI) 85prozentiges hydrazine hydrate (8.01 g, 0.12 mole) and 33 ml Athylenglycol are mixed at room temperature, after which the reaction mixture under nitrogen at 140 ⁰ C The reaction mixture is kept at this temperature overnight. After a reaction time of 39 to hours, the reaction mixture is cooled, diluted with 33 ml of water and the desired 4-methyl-2-hydrazinobenzothiazole is filtered off. It is washed with water and dried in vacuo at 65 ° C. for 2 hours. This gives 5.43 g of product in a yield of 79%. The product is in the NMR. examined, resulting in an amount of about 5 to 10% starting material. The melting point is 161-166 ° C

50

Deispie! 16 4-methyl-2-hydrazinobenzothiazole

4-Methyl-2-aminobenzothiazole (8.21 g, 0.05 mol), hydrazine monohydrochloride (1.14 g, 0.017 mol), 85 percent hydrazine hydrate (1.96 g, 0.033 mol) and 41 ml of ethylene glycol are mixed and the mixture is heated under nitrogen to 140 ⁰ C. the reaction conditions are maintained for 15 hours, then allowed to cool slowly to room temperature, the reaction mixture and stored for convenience under nitrogen overnight the reaction mixture is treated for the crystallization with water (45 ml) the next morning, whereupon the reaction mixture is filtered to separate off the desired 4-methyl-2-hydrazinobenzothiazole. It is then dried overnight under vacuum at 6O ⁰ C. This gives 30 g of product in a yield from a non-aqueous medium gives a purity of 85.80 / 0.

Example 17

4-chloro-2-hydrazinobenzothiazole

4-chloro-2-aminobenzothiazole (2.0 g, 0.0108 mol) is dissolved in 10 ml of diethylene glycol monomethyl ether, whereupon 0.9 ml of concentrated hydrochloric acid is added with stirring oil bath at 110 ⁰ C heated mixture is allowed to run the reaction for 22 hours wherein the final temperature is 120 ⁰ C. The 4-chloro-2-hydrazinobenzothiazole obtained in this way is isolated by adding water and separated off by filtration, giving 1.69 g of product in a yield of 78%, which melts at 232-235.degree

Example 18 4-methyl-2-hydrazinobenzothiazole

A suspension of 4-methyl-2-aminobenzotniazole (5.0 g, 0.03 mol) in 20 ml of ethylene glycol is mixed with 5.4 g of 85 percent hydrazine hydrate (0.09 mol) and 2.75 g (0.046 mol) of acetic acid ^{The mixture is heated to 126 °} C. under nitrogen for 3 hours. On cooling and diluting with about half the volume of water, the product crystallizes out. This gives 4.73 g (87% of theory) of 4-methyl-2-hydroazinobenzothiazole. The product is identified by thin-layer chromatography. It is therefore practically pure.

Example 19 4-methyl-2-hydrazinobenzothiazole

4-methyl-2-methylaminobenzothiazole hydrobromide (443 g, 1.71 mol) is added to 1.7 l of ethylene glycol with stirring

col geber .. 85% hydrazine hydrate (400 g, 6.75 mol) is added to the batch in several partial amounts. The reaction mixture is ^{heated to 130 to 135 °} C. under nitrogen and kept at this temperature for about 4 hours, after which it is slowly cooled while stirring. The product is isolated by adding water and separating it off by filtration. It is then dried overnight in a vacuum cabinet, and 275.5 g (50% yield) of 4-methyl-2-hydrazinobenzothiazole are obtained in this way. The NMRSpektnjm agrees with a corresponding reference spectrum. It is therefore also free from the starting product or any other contamination. A purity of 97.5% is determined by titration in a non-aqueous medium.

Those produced by the process according to the invention Compounds of the general formula

-MI-NH.

NJ -

are interesting starting materials, from which one s-Triazolo (3.4-b) benzothiazole of the general Formula

K-

K ^;

C = N

can produce, wherein R- inter alia for hydrogen or lower alkyl such as methyl. The transformation the 2-hydrazinobenzothiazoien in the s-triazolo (3.4-b) benzothiazole can by various processes be performed. One of these methods is that you can 2-H \ dra7inoben / othiazol directly through Implementation with an orthoester of the general formula

R ^ -C (O-alkyl),

converts. According to a different procedure, the 2-hydrazinobenzothiazole is acsher ;. and the 2- (2- ^ yWiydrazmnfac-imhiaml obtained thereby is cydized

by refluxing with phenol. Similarly, a third method is direct conversion of 2-hydrazinobenzothiazole by reaction with an acid of the general formula

R'COOH.

These s-triazolo (3.4-b) benzothiazoles are suitable as agents for controlling phytopathogenic organisms, mainly of fungi, and in particular of organisms that cause powdery mildew in rice (Piricularia oryzae) are responsible. If these products are used for the above purpose, then they can be used on can be used in different ways. For example, you can put them on the foliage of plants, on the seed or on the surface of the soil or add to water where the to be treated Plants grow in each case, for example as a soaking solution for the roots when transplanting. the Active ingredients are usually delivered in a formulated form Application, together with the usual tools, such as. B. Surfactants. The respectively effective amount is not critical and it depends in part on the mode of application and the type of use treating organism. Good control of powdery mildew in rice is obtained with liquid preparations for treating seeds, for soaking the roots, for transplanting or for spraying the BlattwerV> with active ingredient concentrations of about 0.001 to 0.2 percent by weight. For application to the Soil surface the amount of active ingredient is, for example, about 0.5 to 2.0 kg / ha or more.

The compounds of the general types used as starting materials for the process according to the invention formula

N (R ¹ ):

are known and some of them are even commercially available. They can all be prepared by known processes. A simple process for their preparation is described in Heterocyclic Compounds, Volume 5, edited by Elderfield (John Wiley & Sons. Ine New York. 1957), page 506.

Claims (1)

Patent claims: 1, Process for the preparation of 2-hydrazinobenzothiazoles the general formula NH-NH ₁ where R is independently hydrogen, bromine, chlorine, fluorine, alkyl with 1 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms or alkylthio with 1 to 3 carbon atoms and π denotes the number 0, 1 or 2, by reacting 2- Aminobenzothiazoles of the general formula