DD251979A1 - PROCESS FOR THE PREPARATION OF S-TRIAZINYL SUBSTITUTED 2-IMINO-1,3,4-OXADIAZOLINES - Google Patents

Abstract

The invention relates to a process for the preparation of s-triazinylsubstituierten 2-imino-1,3,4-oxadiazolinen of general formula I, wherein R1, R2 is alkyl or aryl and R3, R4 alkoxy, aryloxy, alkylthio, arylthio, Alkylamino, arylamino, dialkylamino, diarylamino, alkyl-arylamino, hydrazino, substituted hydrazino groups or chlorine. The aim of the invention is the preparation of the compounds I with the simplest possible process conditions and favorable yields. According to the invention cyanuric chloride is reacted in an inert solvent at temperatures below room temperature with the 3,5-disubstituted 2-imino-1,3,4-oxadiazoline III or its salts and the resulting compound I (R3, R4 chlorine) optionally followed is further reacted with nucleophilic agents, wherein R1 and R2, the above Have meaning. Areas of application of the invention are the chemical industry, agriculture and health care. Formula I and III

Description

The invention relates to a preparation process for s-triazinyl-substituted 2-imino-1,3,4-oxadiazoline derivatives of general formula I,

• i Il I Il ι ο ι

RC C = NC .CR ^J

where R ¹ and R ² = alkyl or aryl and R ³ or R ⁴ = alkoxy, aryloxy, alkylamino, arylamino, dialkylamino, diarylamino, alkyl

arylamino, hydrazino, substituted hydrazino, hydroxy or chlorine.

Areas of application of the invention are the chemical industry, agriculture and health care.

Characteristic of the known technical solutions

Compounds of the formula I are hitherto unknown. Dovlatyan and Gevorkyan (Arm. Chim. Zh. USSR 30 [10] 851 [1977]) have made similar compounds, but in which the triazine ring is linked to the ring nitrogen of des2-imino-1,3,4-oxadiazoline. These compounds are suitable as growth regulators.

Object of the invention

The aim of the invention is to develop a process for the preparation of as uniform as possible compounds I with the simplest possible process conditions and favorable yields.

Explanation of the essence of the invention

The compounds I (R ³ = R ⁴ = Cl) are prepared according to the invention by substitution of a chlorine atom on the cyanuric chloride (II) by 3,5-disubstituted 2-imino-1,3,4-oxadiazolines (III).

- NR ² [ N ^X It Cl t ^f N I C = N-H + Il CI-C _n jC-Cl III II Meaning) ₄ R ¹ -C , , ° R ¹ and R ² have the above-mentioned

- ^HC1 (R ^3, R ^ = Cl)

For this purpose, cyanuric chloride (II) is dissolved or suspended and treated with the compound HI at reaction temperatures below 10 ⁰ C.

It is intensely stirred. The liberated hydrogen chloride is trapped with a suitable base. The reaction is carried out under constant control of the pH, which is kept at 7. After the addition of the equivalent amount of base, the pH changes only very slowly. Without raising the temperature, stirring is continued for 30 minutes. It forms a usually well crystallizing precipitate, which is filtered off with suction, washed with water, then with methanol and then with ether.

The thus rapidly drying reaction product is relatively stable. It can be recrystallized from nitromethane or other solvents which are as anhydrous as possible. Any existing hydrolysis products are hardly in nitromethane

soluble.

It is in the inventive preparation of the compounds I of advantage that the salts of imino-oxadiazoline III can be used. These form during their synthesis by known methods. They can be used directly without purification in an equivalent amount. It is then to double the amount of acid acceptor.

Under these conditions, it is possible, even previously not isolable 3,5-dialkyl-2-imino-1,3,4-oxadiazoline with the

Implement cyanuric chloride.

A small cyanuric chloride excess leads to an increase in yield of up to about 5%. It is, however, a careful one

Purification of the crude product required.

Compounds with R ³ = OH and R ⁴ = Cl are prepared according to the invention by the above-mentioned method by stirring after addition of the equivalent amount of the acid acceptor for 4 hours at room temperature.

Compounds with R ³ = Cl and R ⁴ = amine are prepared according to the invention in a process variant of I by adding this in a solvent, especially propanone, with the appropriate amine and then with the equivalent amount of an acid acceptor. As the amount of the acid acceptor increases, the salts of the amines can also be used.

Compliance with the otpimalen reaction temperature is essential for the purity of the reaction product.

According to the invention, compounds having R ³ and R "= amine are obtained analogously to the abovementioned process variant, for which the amount of amine is doubled and the reaction is carried out at the boiling point of the propanone.Weakly nucleophilic amines, such as nitroanilines, are reacted in boiling dioxane.

Compounds with R ³ and R ⁴ = hydrazine are obtained according to the invention by reacting I (R ³ = R ⁴ = Cl) with the equivalent amount of hydrazine hydrate in propanone at 50 ° C. Dihydrochlorides first form, from which the target compound can be released with a suitable base, for example potassium hydrogen carbonate. Compounds with R ³ = Cl and R ⁴ = (alkyl, aryl) oxy or thio group are obtained according to the invention by reacting I (R ³ , R ⁴ = Cl) with the corresponding phenolates, alcoholates or thioates in boiling propanone or dioxane , The compounds of formula I show biological activity. Representatives of this class of substances are suitable as growth regulators, pesticides or as pharmaceuticals.

The invention will be explained in more detail by exemplary embodiments.

Embodiment 1; I; R ¹ = R ² = phenyl; R ³ = R ⁴ = chlorine

0.1 mol of cyanuric chloride is dissolved in 500 ml of propanone. The solution is cooled to 0 ° C. With vigorous stirring, 0.1 mol of 2-imino-3,5-diphenyl-1,3,4-oxadiazoliη is added gradually. The temperature must not rise above 1O ⁰ C there. Thereafter, an approximately 20% solution of 0.1 mol of sodium hydroxide in water is added dropwise so that the pH is maintained between 5 and 8 and the temperature below 10 ⁰ C. The mixture is then stirred for a further 30 min. The precipitated substance is sucked off. It is washed with water until neutral reaction of the filtrate. The residue is stirred with methanol to a pulp. It is sucked off again. This procedure is repeated. The reaction product is concentrated in vacuo over conc. Dried sulfuric acid and then shows a melting point of 212-213 ° C. The yield is 59%.

Embodiment 2; I; R ¹ = R ² = methyl; R ³ = R ⁴ = chlorine

0.1 mol of 2-amino-5-methyl-1,3,4-oxadiazole are mixed with 0.2 mol of freshly purified dimethyl sulfate. The mixture is stirred until homogenization and allowed to stand for 2 days in a sealed vessel. Thereafter, three times with 50 ml of anhydrous ether excess dimethyl sulfate is washed out. After thorough stirring, the ether solution is separated from the sediment by decantation. The residue is stirred with 300 ml of propanone and the mixture is cooled to ⁰ ° C. It is then added to the solution of 0.1 mol of cyanuric chloride in 300 ml of propanone, being stirred vigorously. When adding the reaction temperature must be kept below 5 ⁰ C. Then, 0.2 mol of potassium carbonate dissolved in 100 ml of water are added dropwise with stirring over one hour. After a further 30 min is filtered off with suction. The residue is washed several times with a little cold water. The reaction product is dried rapidly in vacuo and recrystallized from anhydrous methanol

Melting point: 160-162 ⁰ C, yield: 40%

Embodiment 3; I; R ¹ , R ² = alkyl or aryl; R ³ = R ⁴ = Cl

0.1 mol of the freshly prepared Oxadiazoliniumsalzes are stirred rapidly with the saturated solution of 0.2 mol of potassium carbonate at 0-5 ⁰ C and the mixture was added to the solution held at ^{0 0} C of 0.1 mol of cyanuric chloride in 500 ml of propanone. While stirring for 30 min, the temperature must remain below 10 ⁰ C. The reaction product is filtered off, washed with water and recrystallized from alcohol. The reaction products, which are readily soluble in alcohol, are dissolved in the just-required amount of boiling ethanol in a nut-moist solution. Low levels of by-products are removed by decanting or aspiration. After that it is cooled in ice. The sharply extracted precipitate is dried rapidly in vacuo. Melting points and yields are shown in Tables 1 to 3.

Embodiment 4; I; R ³ = hydroxy; R ⁴ = chlorine

The reaction mixture according to Example 3 is heated after the reaction of the components to 2O ⁰ C and stirred for a further 4 hours at this temperature. It is then filtered off with suction and washed with water. The reaction product is recrystallized from ethanol (Table 6).

Embodiment 5; I; R ³ = chlorine; R "= alkylamine

0.02 mol of the dichloro-oxadiazolinylideneamino-s-triazine prepared according to Example 1, 2 or 3 are suspended in 200 ml of propanone. Thereafter, at room temperature, 0.02 mol of the corresponding alkylamine are dissolved in 100 ml of propanone and added dropwise within 10 min. With constant stirring in the suspension of triazine derivative (I). It is stirred for another hour. In this case, the reaction mixture is usually homogeneous. If appropriate, the mixture is heated to the boiling point of the propane or the undissolved substance is separated off. With a solution of 0.02 mol of potassium bicarbonate in 100 ml of water, the reaction mixture is neutralized. After standing for several hours, the disubstituted chlorotriazine is separated. Cleaning is usually not required. Optionally recrystallized from propanol (Table 4, Nos. 1 to 15). If the reaction with the reaction mixture 1, 2 or 3 is carried out instead of the isolated I, the yield is lower.

Embodiment 6; I; R ³ = R ⁴ = alkylamine

The preparation of this compound is carried out analogously to Example 5 with the difference that twice the amount of the corresponding aliphatic amine used and the reaction is carried out under reflux at the boiling point of propanone. For neutralization also double the amount of the acid acceptor is used (Table 5, No. 1 to 3).

Embodiment 7; I; R ³ = chlorine; R ⁴ = arylamine

The preparation of this compound is carried out analogously to Example 5. After the addition of the corresponding arylamine but 0.02 mol of sodium hydroxide are added dropwise with stirring in concentrated, aqueous solution. The reaction temperature is raised to 50 ° C. After about one hour, a pH of 7 sets. Now is filtered off and the residue washed with water and then with a little methanol. Recrystallization is from dioxane-water mixtures (Table 4, Nos. 16 to 19).

Embodiment 8; I; R ³ = chloro R ⁴ = phenylamine

Dichloro-oxadiazolinylidene-triazine is mixed with 4 to 10 times the amount of aniline; Quickly ignite a significant warming. After cooling, the excess aniline is removed with ether or another suitable solvent, and the residue is washed with water and then methanol (Table 4, entries 16 to 19).

Embodiment 9; I; R ³ = R ⁴ = arylamine

The preparation of this compound is carried out analogous to the embodiment 8 with the difference that after the decay of the exothermic reaction is still heated for 24 hours in an oil bath at 100 ⁰ C, or the mixture remains at room temperature for 7 days. The procedure is as in the embodiment 8 (Table 5, No. 4).

Embodiment 10; I; R ³ = R ⁴ = hydrazine

0.02 mol of the dichloro-oxadiazolinyliden-trialzins are added in 150 ml of propanone barder or a similar approach according to Embodiment 1, 2 or 3 further processed. To this mixture 0.04mol 86% hydrazine hydrate are stirred. Thereafter, the reaction temperature is raised to 5O ⁰ C and held for about 60min. After cooling, it is neutralized with 10% potassium carbonate solution. The precipitate after a few hours precipitate is separated, washed with water and then with methanol and dried in vacuo. After distilling off the propanone, about 5 to 10% of reaction product can still be obtained from the first filtrate (Table 5, No. 5).

Embodiment 11; I; R ³ = chlorine; R ⁴ = phenoxy

0,02MoI sodium hydroxide are stirred with 0.02 mole of phenol and about 1 mlWasserbiszur homogenization at 60 ⁰ C to 80 ° C. After cooling, the resulting sodium phenolate is dissolved in warm methanol and stirred with the mixture of 0.02 mol dichloro-oxadiazolinylidenamino-triazine and 150 ml of propanone at 50 ⁰ C for 30 to 60 min. Thereafter, the bulk of the solvent is also distilled off at 50 ^° C. under a slight vacuum. The residue is mixed with about 100 ml of water. The precipitated reaction product is filtered off with suction and recrystallized from methanol (Table 5, No. 6).

Table 1 R ² = methyl; R ³ , R ⁴ = chlorine

No. _ R ¹ Fp ( ⁰ C) Yield (%)

1 methyl 160-162 40

2 ethyl 168-169 46

3 i-Propyl 100-109 42

4 n-propyl 105-107 42

5 i-butyl 99-102 40

6. n-butyl 97-99 38

7 hexyl 68-72 21

8 pentadecyl 45-48 27

9 heptadecyl 43 ^ 47 15

10 cyclohexyl 75-78 22

11. Benzyl 167-169 57

12 phenyl 231-233 84

13 4-Methoxyphenyl 280-282 72

14 4-Tolyl 259-263 72

15 2-hydroxyphenyl 233-236 58

16 2-Chlorophenyl 212-213 64

17 3-Chlorophenyl 261-263 79

18 4-chlorophenyl 252-254 80

19 4-bromophenyl 288-290 78

20 2-cyanophenyl 246-249 62

21 3-cyanophenyl 255-259 70

22 4-cyanophenyl 260-263 66

23 2-nitrophenyl · decomp. 69

24 3-Nitrophenyl Zers. 82

25 4-Nitrophenyl Zers. 90

Table 2 R ² = ethyl; R ³ , R ⁴ = chlorine

No.

R ¹

Fp ("C)

Yield (%)

phenyl

4-methoxy phenyl

4-tolyl

2-chlorophenyl

3-chlorophenyl

4-chlorophenyl

2-nitrophenyl

3-nitrophenyl

4-nitrophenyl

183-184

208-211

195-197

164-167

181-183

199-202

Ze rs,

81 70 66 65 75 78 59 71 74

Table 3 R ² = phenyl; R ³ , R ⁴ = Cl

No. R ¹ chlorine R ⁴ FPCC) FPCC) yield Yield (%) 1 methyl 158-159 85 2 ethyl 132-135 79 3 i-propyl 122-124 71 4 n-propyl 119-120 76 5 phenyl 212-213 59 6 4-methoxy phenyl 236-238 57 7 4-tolyl , 222-224 52 8th 2-chlorophenyl 224-225 55 9 3-chlorophenyl 229-231 61 10 4-chlorophenyl 242-244 61 11 4-carbomethoxyphenyl 260-262 49 Table 4 R ² = methyl, R ³ = No. R ¹

1 ethyl ethylamino 104-107 92 CM ethyl diethylamino 102-103 94 3 phenyl methylamino 215-216 90 4 phenyl ethylamino 146-148 94 5 'Phenyl i-propylamino 168-171 93 6 phenyl n-propylamino 174-175 90 7 phenyl i-butylamino 161-165 88 8th phenyl benzylamino 195-198 88 9 phenyl 2-hydroxyethylamino 158-162 84 10 phenyl dimethylamino 218-220 95 11 phenyl diethylamino 154-155 96 12 phenyl Di-i-butalamino 136-138 98 13 phenyl piperidino 181-184 89 14 4-tolyl diethylamino 162-163 88 15 4-nitrophenyl diethylamino 160-161 90 16 phenyl phenylamino 295-297 65 17 4-Toiyl · phenylamino 277-282 67 18 4-Ch.lorphenyl phenylamino 276-281 68 19 4-nitrophenyl phenylamino Dec. 62

Table 5 R ¹ = phenyl, R ² = methyl

FPCC)

Yield (%)

1 dimethylamino dimethylamino CM dimethylamino diethylamino 3 dimethylamino Diethylamine! 4 phenylamino Phenylamini 5 hydrazino hydrazino 6 chlorine phenoxy

212-214 84 191-193 84 188-190 81 270-275 22 147-151 65 169-173 16

Table 6 R ³ = chlorine, R ⁴ = hydroxy

R ¹ Fp ( ⁰ C)

Yield (%)

1 ethyl methyl 2 phenyl methyl 3 3-nitrophenyl methyl 4 4-chlorophenyl methyl CJL 4-tolyl methyl 6 4-methoxyphenyl methyl 7 phenyl phenyl 8th 4-chlorophenyl phenyl 9 4-methoxyphenyl phenyl

152-156 85 222-224 88 Dec. 69 238-241 72 226-236 91 228-233 95 220-224 80 228-235 77 225-230 90

Claims (5)

1. Process for the preparation of s-triazinyl-substituted 2-imino-1,3,4-oxadiazolines of the general formula I ₍ 2 / ^ N-R NN RC C = N-C CR ^J wherein R ¹ and R ² = alkyl or aryl and R ³ or R ⁴ = alkoxy, aryloxy, alkylamino, arylamino, dialkylamino, diarylamino, Aikyl-arylamino, hydrazino, substituted hydrazino, hydroxy groups or chlorine, characterized in that cyanuric chloride (II) in an inert solvent below room temperature with the 2-lmino-oxadiazolin (III) or its salts N NR ² ·. ' ! 1 I "-," R-C C = NH implemented, wherein R ¹ and R ^{2 have} the abovementioned meaning, the liberated hydrogen chloride is bound with an acid acceptor and the formed compound I (R ³ = R ⁴ = Cl) is optionally further reacted with nucleophilic agents. 2. The method according to item 1, characterized in that for the preparation of I (R ³ = OH, R ⁴ = Cl), the further reaction without isolation of I (R ³ = R ⁴ = Cl) by stirring at room temperatures. 3. The method according to item 1, characterized in that for the preparation of I (R ³ = Cl, R ⁴ = amine), the further reaction in short-chain ketones, preferably in propanone, at room temperature with the equimolar amount of the corresponding amine. 4. The method according to item 1, characterized in that for the preparation of I (R ³ = R ⁴ = amine or hydrazine), the further reaction in short-chain ketones or dioxane, preferably in propanone, at 5O ⁰ C to the boiling point with twice molar amount of the corresponding amine or hydrazine takes place. 5. The method according to item 1, characterized in that for the preparation of I (R ³ = chlorine, R ⁴ = alkyloxy, alkylthio, aryloxy or arylthio), the further reaction takes place in short-chain ketones or dioxane with the corresponding alkoxides, phenolates or thiolates.