DD202874A1 - PROCESS FOR THE PREPARATION OF 2-HYDRAZINO-PERIMIDINES - Google Patents

Abstract

The aim of the invention is to synthesize biologically active compounds of general formula III and their salts. According to the invention, a salt of an alkylthioperimidine or this itself is reacted with a hydrazine in solution or suspension at 0 to 150 ° C. and under protective gas to give hydrazine operimidines of the general formula IIIa. These can be converted into compounds of general formula IIIb under the condition that R is high 7 = R tall 8 = H, with aldehydes and ketones of the general formula R 9-CO-R high 10. By adding acids to the compounds of general formula III, the desired salts are prepared. The synthesized compounds are of interest for medicine, but can also be used in agriculture. They are obtained by the novel process in high purity and high yield.

Description

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Traversing e n to the He rs tellung of 2-Hydrazinoperimidinen

The invention relates to a process for the preparation of 2-hydrazinoperimidines of the general formula III and salts thereof.

Application sgebie t of invention

The invention is of importance to medicine, the pharmaceutical industry and agriculture.

C h ara kter is tik of known technical solutions

It is known that a series of 2-substituted derivatives of perimidine exert effects on living objects. On the one hand, 2-hydrazino-3a, 4,5,6-tetrahydroperimidines are described which lower blood pressure in normotensive and hypertensive animals (DE 28 16 123, C 07 D 239/70, DE 28 39 137, C 07 D 403/04 ). On the other hand, there are 2-carbamic acid esters of peri-anhydride, which have importance in the control of fungi, especially of Phytophthora infestans (DD 137 713, C 07 D 239/84).

Z iel the invention

It is an object of the invention to provide biologically active compounds of the general formula III and salts thereof for use as active ingredients in pharmaceuticals or in biocidal agents.

-1.FER1982 * 9872OO

Explanation of the We sens the invention

The invention has for its object to develop a simple, teohnisch well feasible process sur production of 2-hydrazinoperimidines and pharmaceutically acceptable or applicable for biocidal Zweoke salts in good yields.

According to the invention, a 2-alkyltliioperimidine of the general formula I or its salt is reacted with a hydrazine of the general formula II in solution or suspension, optionally in the presence of an acid-binding agent, at temperatures between 0 and 150 ^° C. under an inert gas atmosphere to give a 2-hydrazino-perimidine of the general formula Formula IUa um. In the event of

R = R = H, this compound can be converted with aldehydes or ketones of the general formula R-CO-R in polar protic solvents with or without addition of acid into 2-hydraainoperimidines of the general formula IHb. The compounds of general formula III are isolated as such or in the form of their salts. From the compounds of the general formula III, the desired salts are prepared by addition of the corresponding acids.

In the formulas, R, R, R and R are independently hydrogen, halogen or nitro, R is lower alkyl (C ₁ -C ₅ ), R ^{6 is} hydrogen, alkyl (C ₁ -C ₃ ), unsubstituted or substituted phenyl or hetaryl (eg furyl)

7 8

and R and R independently of one another represent hydrogen, alkyl (C 1 -C 4), unsubstituted or substituted phenyl or hetaryl (eg furyl) (in formulas II and III or IIIa) or together for an alkylene group = C 1 H 10 (in Formula III or IHb). In this formula, R 1 and R 4 independently of one another denote hydrogen, unsubstituted or substituted alkyl, aryl or hetaryl.

Suitable starting materials of the general formula I are both unsubstituted alkylthioperimines, for example 2-methylthioperimidine or 2-ethylthioperimidine, in the ring system as well

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ring-substituted alkylthioperimidines, e.g. 4-halogeno, 4-nitro, 6-halo, 6-nitro, 4,6-dihalo or 4,6-dinitro-2-alkylthioperimidines or salts thereof. The salts used are preferably hydrohalides, e.g. Hydroiodides, or methosulfates.

If a solid hydrazine is used for the reaction, it is sometimes desirable to allow the reaction to proceed in the presence of an acid-binding agent. If one uses liquid hydrazines, it is generally without acid-binding agent, but works with a large Hydrazinübersohuß (molar ratio 1: 2 to 1: 150).

The obtained 2-hydrazinoperimidines of the general formula IIIa can be used without purification for the preparation of the compounds of the general formula IIIb. However, only those compounds of the general formula IIIa are suitable for the reaction

7 8

suitable in which R '= R = H. Come as reactants

9 both aldehydes and ketones of the general formula R -

10 9 10

CO-R is used, where R and R have the abovementioned meaning. It works in polar protic solvents with or without addition of acid at room temperature or with heating (to at most 150 ⁰ C) and receives the corresponding compounds of the general formula IHb usually within a few minutes.

The inventive method is simple and technically feasible and provides the compounds of general formula III in high yields and in excellent purity, the compounds of general formula III are new. Among them are those that can potentially be used as Hypertonicura or have fungicidal activity, so that they are of interest for medicine and agriculture. However, the compounds of general formula III are also useful as starting materials for further syntheses.

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The invention will be explained below by some examples.

embodiments

Example 1:

2-Hydrazinoperimidin

3 g (8.77 millimoles) of 2-Methylthioperimidinhydroiodid in 30 ml of hydrazine hydrate 85 tigern 30 minutes under nitrogen at 140-150 ⁰ C bath temperature maintained below reflux. Then allowed to cool to room temperature, sucks quickly and sharply _? Wash with a little ice-cold methanol and dried at 40 ⁰ C after repeated seeding with nitrogen in vacuo. In the dry state, the substance can be kept undecomposed under nitrogen for several months

Light yellow, coarse crystals Yield: 2.0 g (72.2% of theory.). Mp: 181-186 ⁰ C dec. (Methanql)

^C 11 ^H 10 ^N 4 ¹⁹⁸ > ¹ MS (m / z) 198 (M ⁺ )

The substance can be used without further purification as starting material for the reaction with aldehydes and ketones.

Example 2:

2- (2-phenylhydrazino) -perimidin

6.84 g (20 mmol) of 2-methylthioperimiclinhydroiodide are suspended in 40 ml of methanol and slowly added to 10 ml of freshly distilled phenylhydrazine. The Reaktionsmisohung is then heated under reflux for 1.5 hours ^ allowed to cool slowly, filtered off with suction and washed with a little ice-cold methanol. The solid consists of O ₅ 97 g of 2-mercaptoperimidine * The mother liquor is concentrated, allowed to stand overnight and the precipitated crystals are boiled with methanol. Yellowish crystal flatterohen

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Yield: 1.679 g (30.6% of theory.). Mp 348 ⁰ C dec.

^C 17 ^H 14 ^N 4 ²⁷⁴ » ² MS (m / z) 274 (M ⁺ )

Example 3:

2- (4-nitrobenzylidene hydrazino) perimidine 99 mg (0.5 mmol) 2-hydrazinoperimidine and 75 mg (0.5 mmol / l) p-nitrobenzaldehyde are boiled for 5 minutes in a little methanol. A brick-red powder precipitates, which is sucked off. For purification is recrystallized from dimethylformamide.

Yield: 120 mg (80% of theory). Mp:> 360 ⁰ C dec. (DMF) C ₁₈ H ₁₃ O ₂ N ₅ 331.3 MS (m / z) 331 (M ⁺ )

For this 1 page formulas

23 70 7

R '

R ⁶ NHNR ⁷ R ¹

NR R '

HEa R ⁷ : hydrogenated alkyl, unsubst or subst. Phenyl, hetaryl, R ⁸ : hydrogen Aikylunsubst. or subst. Biphenyl, hetaryl,

R ⁷ + R ⁸ : = CR- ⁹ R ¹⁰

Claims (8)

invention claim 1. A process for the preparation of 2-Hydrazinoperimidinen of the general formula III and their salts, characterized} that a 2-AlkyltiiiQperimidln of all formula I or its salt with a hydrazine of the general formula II with or without the addition of an acid-binding agent in solution or suspension under inert gas atmosphere to a 2-Hydrazinoperimidinder ERAL new formula IIIa is reacted, the one in the case of R = R = H with 9 10 aldehydes or ketones of the general formula R-CO-R in polar-projtischen solvents with or without addition of acid in 2-Hydrazinoperimidines of the general formula IHb can convert, and the compounds of general formula III as such or after addition of acids in the form 1 2 3 of their salts, wherein in the formulas R, R, R and R independently of one another are hydrogen, halogen or nitro, R ^{5 is} lower alkyl (G ₁ -C ₅ ), R ^{6 is} hydrogen, Alkyl (C ₁ -C _n ), unsubstituted or substituted phenyl 7 8 '
nyl or hetaryl, R and R independently of one another are hydrogen, alkyl (C ₁ -C ₃ ), unsubstituted or substituted phenyl or hetaryl (in the formulas II and III or IIIa) or together for an alkylene group = cC-o-1! (in formula III or HIb) and R and R independently of one another are hydrogen, unsubstituted or substituted alkyl, aryl or hetaryl » 2. Method naoh point 1, characterized in that the reaction of the 2-alkylthioperimidine of the general formula I or its salt with the hydrazine of the general formula II is carried out at temperatures between 0 and 150 ⁰ C. 3. The method according to item 1 and 2, characterized in that the 2-alkylthioperimidines of the general formula I are used in the form of their hydrohalides or methosulfates. 237079 0 4. The method according to any one of items 1 to 3, characterized in that solid hydrazines are used and reacted in the presence of acid-binding agent. 5. The method according to any one of items 1 to 3, characterized in that liquid hydrazines are used in high molar excess (up to 150 times) and reacted without the addition of acid-binding agent. 6. The method according to any one of items 1 to 5, daduroh characterized in that 2-Hydrazinoperimidines of the general formula IHa be prepared. 7. The method according to any one of items 1 to 6, characterized in that the prepared 2-Hydrazinoperiraidine the In the case of R '= R = H, they are reacted with aldehydes or ketones in polar protic solvents with or without addition of acid to give compounds of the general formula IIIb. 8. The method according to item 1,6 or 7, characterized in that salts are prepared from the compounds of the general formula III duroh addition of acids.