CS235251B1 - Method of 3-amino-delta 2-pyrazoline derivatives production - Google Patents

Abstract

The various tautomeric forms of (I):- (where R is alkyl, cycloalkyl, aralkyl or aryl, all opt. substd. but excluding unsubstd. phenyl; R1 and R2 are H or opt. substs. alkyl or aryl and R4 is H or the acid radical of an organic carboxyacid, are preped. by methods usual for such structures. Partic., R is 1-4C alkyl, 5-6C cycloalkyl, diphenylalyl, nitrophenyl-, methylphenyl- benzyl- or dimethoxyphenethyl, R1 and R2 are H and R4 acetyl. propionyl, hydroxybenzolyl or beta-piperidino-propionyl.

Description

The invention relates to a process for the preparation of derivatives

3-emino A-pyrazoline. Most of the compounds produced by the process of the invention are novel. '

235 251 It is known that β-amino-N-pyrazoline derivatives are preferably used in the photographic and pharmaceutical industries. These compounds have so far been obtained by a single method with several variations by subjecting β-cyanethyl hydrazines to intramolecular ring closure.

This known method is described in a number of publications and patent publications, for example, U.S. Pat. No. 2,726,248, British Patent Publications 776,322 and 679,678, journal. obščej. chim. 26, p. 3132 (1956), 22 »p. 498 (1959), Ann. Chim. (Rome) £ 6, p. 332 (1966), C.A. 65, p. 2244b, Chem. Ber. 98, p. 3377 (1963)> Chem. Soc. / London / 1954, 408, 1955, 3470 ·

A common feature of the above methods is that the Nj -pyralized ring bond is formed prior to the last step of the synthesis. However, this method is not entirely clear. In reactions where arylhydrazines and acrylonitriles or derivatives thereof are used, both nitrogen atoms of the hydrazine group are reactive and therefore two simultaneous reactions may occur. Thus, they may be required by

1-aryl-3-amino-Δ-pyrazoline compounds contaminated with 1-aryl-5-aminopyrazolines. The ratio of the amount of the two isomers may be influenced by the pH value (Helv.Chim. Acta £ 1, p. 306 (1958); Ber. 2§> p. 3357 (1965). hydrazine group by nitrosation and reduction of the aryl- (2-cyanethyl) amine obtained by reaction of the aromatic amine with acrylonitrile (British Patent Specifications 757,840 and 776,322).

235 251

The object of the invention is therefore a process for the preparation of J-amino-Δ-pyrazoline derivatives. of formula I ch ₂

(AND).

wherein r - represents an alkyl radical of 1 to 7 carbon atoms, optionally substituted by at least one halogen atom, one or two phenyl groups optionally substituted with an alkyl radical of 1 to 2 carbon atoms, or a naphthyl group, a cycloalkyl radical of 5 to 6 carbon atoms in a ring or phenyl or naphthyl radical, optionally subjected to C 1 -C 2 alkyl, C 1 -C 2 alkoxy, nitro or halogen, and

R ² * - ^s represents hydrogen. an acetyl, piperidinopropionyl, propionyl, beazoyl or salicyl residue, and a salt thereof, which process is characterized in that the compound of formula (II) is:

23S 291 δ ⁵

CH ₂ -. CH ₂

R ⁵ (II), wherein said meaning is a C ¹ -C 7 alkyl group,

R - 'is as ^R - means ^and optionally substituovaných'nejméně jednfo substientem such as halogen, výhodou'chloru bromine, alkylthio, amino, nitro, H ^y by hydroxyl and phenyl, or phenyl optionally stbstitoobenlct least jedním'substituentem, such as halogen, preferably chlorine or bromine, nitro, nitro, C 1 -C 2 alkyl or C 1 -C 2 -alkoxy; _ ^Á .atom sign ^says as not to of ^b and c ^y of ^the nominal oup having ¹ to 7 carbon atoms, and C, or a. salt. reacted at 5 ° ^and 110 'zádadou, mapMklad hydroxide of an alkaline' metals, and the thus obtained S ^, Compounds ohecn ^ of formula I wherein R is hydrogen, is optionally subjected to N-acylation, ^or e sjLoučenjna generally ^eh of formula 'I, where R₁ is as described above, an acyl residue popřípadě.desacyluje'za vzhiku ^sL ^ C ^ .n teaching ^{and y} ^ o general formula I wherein ^R₁ represents. . hydrogen, or the product so obtained is optionally converted into its salt, or the compound of formula Ί is liberated from its salt.

235 251

The compounds of formula I may exist in three tautomeric forms. The invention relates to all such tautomeric forms and their preparation.

An example of an alkyl radical R is methyl, ethyl, propyl, isopropyl, isobutyl, etc. The alkyl radical may be substituted by at least one halogen atom, such as chlorine or bromine, by one or two phenyl groups optionally substituted by an alkyl group C 1 -C 2 or naphthyl. Especially preferred substituted alkyl groups in the meaning of R are diphenylalkyl groups. The phenyl or naphthyl radical R may be substituted by a C1 -C2 alkyl group such as a methyl or ethyl group, a C1 -C2 alkoxy group such as a methoxy or ethoxy group, a nitro group or a halogen atom. The term cycloalkyl radical R represents radicals having 3 to 6 carbon atoms, such as, for example, a cyclopentyl or cyclohexyl radical.

An example of a phenyl group substituted with an alkyl group in the meaning of R is a benzyl or β-phenylethyl radical.

Particularly preferred compounds of formula I are those wherein R is C 1 -C 4 alkyl, C 5 or C 6 cycloalkyl, diphenylalkyl, nitrophenyl, methylphenyl, benzyl, dimethoxyphenethyl or phenyl, and R 6 is acetyl. , propionyl, benzoyl or β-piperidinopropionyl radical.

235 251

Salts of the compounds of formula I may be addition salts with inorganic acids, for example hydrochloric, hydrobromic, sulfuric, nitric, etc., or in organic acids, for example acetic, lactic, tartaric, maleic, furamic, nicotinic, etc.

Particularly preferred compounds of formula (I) are p

l- (p-nitrophenyl) -3-amino-pyrazolin βτ, l- (p-tolyl) -3-amino and ² -pyrazoline, l- (3,3-difluorobenzyl ^{t-phenylpropyl)} -> - amino and -pyrazoline, 1-benzyl-5-amino-N-pyrazoline

O-cyclohexyl-5-amino-N-pyrazoline,

The LN-butyl 5-amino--pyrazoline, aeetylový derivative of l- (3 »3-diphenylpropyl) -3-amino-4 ^beta -pyrazoline,

A -piperidinopropionylový derivative of l- (3 ^x diphenylpropyl) j A ^1-amino-Д руrazolinu derivative, l- (3,3-diphenyl) ^{propyl-3-amino-2} -pyrazoline, derived from an acid salioyitové, 1-benzyl-5-amino-- ² -pyrazoline aethyl derivative, 1-cylohexyl-3-amino-4-2-pyrazoline aeetyl derivative, 1'-butyl---amino- ^{2 2} -pyrazoline aethyl derivative, and salts thereof ·

In the process of the invention, the compound of formula (II) or a salt thereof is reacted with a base. Preferably, this reaction is carried out in the presence of water. According to a preferred embodiment, an aqueous or aqueous-alcoholic solution of alkaline sodium hydroxide or potassium hydroxide is used in this reaction.

Typically, the reaction is carried out in an aqueous medium or in a mixture of water and an organic solvent in a heterogeneous or homogeneous system.

235 251

The reaction may be carried out at elevated temperature, preferably at a temperature in the range of 50 to 110 ° C.

This yielded · obtained compounds of formula I wherein ^R represents ^a hydrogen, can be converted in cross-lušné · acyl derivatives. The N-acylation can be carried out by known acylation processes, preferably using acid halides, in particular chlorides or acid anhydrides.

^No enyne compound of the formula ^{I b} ecného ^kd · ^{e: R} represents ^and acyl group, can be transformed into the corresponding compound of formula I wherein ^R is hydrogen. ^R ESPONDING can prov · ^DET for slaughter desacylaČního per se known procedure. Preferably, the acyl derivative of the formula I is reacted with a base.

Alkali metal hydroxides such as sodium hydroxide may be suitably used for this purpose. The reaction may preferably be carried out in the presence of an organic solvent.

Suitable organic solvents are aliphatic alcohols such as ethanol.

The starting oxadiazole compound of formula (II) wherein R is a phenyl or naphthyl radical may be prepared such that the amidoxine of formula (III)

(III) where.

^R has the above ^{e d} Uve Eny defined and R represents ^and hydrogen is subjected oxadiazole ring closure. Reaction conditions are described in British Patent Specification 1,063,323.

235 251

The amodoxime starting compound of formula III can be obtained in good yield by the nitrile of formula VI

R-NH-CH2-CH2-CN (VI), wherein R is as defined above, is reacted with hydroxylamine. The nitriles of formula (VI) can then be obtained by known methods, for example by reacting the corresponding amine with acrylonitrile or -halogenittil with an amine.

The thus obtained compound of formula I wherein R * is yodik may odrobit ^N -acylaci ^p. The reaction is carried out according to known methods, preferably using acid halides. Thus obtained compounds of formula I wherein R ² * represents an acyl unnecessary · ^K or ^g anic ^k? K: arboxylov ^é acid.

The compounds of the formula I thus obtained can be converted into their salts with inorganic or organic acids. Salt formation can be achieved by methods known per se, preferably by reacting a compound of formula I in an organic reagent with an equivalent amount of the appropriate acid.

The process according to the invention makes it possible to obtain valuable [beta] -amino- [alpha] -pyrazoline derivatives and can be readily sold commercially. scale. The process according to the invention is fundamentally different from the known processes, since the bond of the N @ 4 -pyrazoline ring is formed during the last cyclization step.

235 251

The invention also relates to pharmaceutical compositions comprising as active ingredient at least one compound of the formula I or a salt thereof together with suitable inert or liquid carriers and / or excipients. As carriers, for example, talc, starch, potassium carbonate, magnesium carbonate, magnesium sulfate, polyethylene glycols, water, etc. The compositions may take the form of a solid, for example, tablets, pills, coated pills, capsules, or a liquid, for example, suspension, emulsion or injection. preparations.

The compositions are prepared by conventional pharmaceutical industry procedures.

The pharmaceutical compositions containing the active compounds obtained by the process according to the invention are characterized, among other effects, by central nervous system and antispasmodic effects, as shown in the table below.

Table

Compound potentiation of anesthesia achieved thiobarbiturates iv dose (mice, po) ⁺ inhibition of writhing inhibition increases pravyvolaných electrical nicotinic threshold values Tricky shock-toxicity, convulsions vyvolamyších ел ED ED _R n NYCHA 200 mg / ^kg? strichninu

100 mg / kg, very strong significant, more than three times the control extension 24.6 mg / kg 31.4 mg / kg + 41% 200 mg / kg ineffective > 100 mg / kg > 100 mg / kg - 26%

23S 2S1

C 200 m < kg > 100 mggkg > 100 mg / kg

D, toxic substance that could not be tested, animals die or suffer from tremors or chronic convulsions, doses lower than 20 mg / kg

A hydrochloride = l- (3,3d (iieenyPpropyl) -5 mino- _i 4-pyrazoline (from Example 2) p

B with 1-Cyclohexyl-4-amino-A-pyrazoline hydrochloride p

C and 1-benzyl-4-emino-A-pyrazoline hydrochloride p

D = 1- (p-tolyl) -amino-N-pyrazoline hydrochloride

+) groups of 10 masses

Some of the compounds of Formula I are suitable for use as photographic developers in the art. photographer.

The invention is closer. illustrated by the following examples, which do not limit its scope in any way.

Example 1

Mixture 2.0. g (0.01 mmol) of 3) (2-phenylamino) -5-methyl-4 ', 4', 4-oxa-azole, 20 ml of 1 N aqueous sodium hydroxide solution and 20 mL of 96 Heat athamol in a water bath for 5 hours. Then, the alcohol is distilled off under reduced printing and the aqueous residue is cooled. Thus 1.21 g desacetyl weakly rust colored fθr ^l-yl) -2- ^A2 --- miУУo once ^{pn (i} nj зl yield. 75% · KytáLický melts ^P 5 s ¹⁶ s ¹⁶⁸ ° C. ^P on, cover ^ s ^ it from ettanolu. beat of ^ the melting is raised to ¹⁶ 9 ° 0. T ^ who obtained product is in all respects identical ge. compound prepared by known methods, · described in the journal J. Chem. Soc · (London) 1954.

408, as proved by tests ·

Example 2

235 251

I. g 3- [2- (3,3-Diphenylpropyl acetylamino) -ethyl] -5-methyl-1,2'-oxadiazole. The reaction mixture was heated at reflux for 8 hours with 10 ml of 2 N sodium hydroxide solution and 10 ml of 96% ethanol. The alcohol is then distilled off, the separated oil is extracted from the liquid phase with chloroform, dried and evaporated. The remaining oil was treated with a mixture of benzene and petoolethe.

p

The melting point of 1- (3,3-edypropyl) -3-thio-N-pyazazoline is ¹⁵⁰ ° C. For ^d uct is identical to the compound of manufacture ^{p p p} Raven ccording Example TJ.

The starting material can be obtained as follows:

g (0.189 mol) j- (3,3-ei0eoylpoopyl) -amino Pon0irilu ^P after ^P is dissolved in 100 mi of acetic anhydride.

The reaction mixture was heated on a water bath for 1 hour, cooled and poured onto 500 g of ice. Oily. The product by scratching the walls of the container pulls the tip. Shortened to indulge, turn water and dry. To give 53.30 g of 3- (3,3-difeoylpoopylacetyl) -j Looppop ^{m p} io ttils ^of the TAP ^ S 'point ^{of 108 F} and 109 DEG C., yield 91.7%. After přelorystalování from 96% ethanol, mp ^e raised to 1 ⁰⁹ to 110 ° C.

53.30 g (0.173 mol) of the thus obtained salt is reacted with hydroxylamine to give 60 g of an oily product which is purified over a hydro-bromide.

41.30 g amino Dorin 3- (3,3-difeoyl.poopylaceiyl) -mioo ropionov ^{p e} o ^t a ^{l t} ep point 125 and S ¹ 3 ⁰ ° C. After zetorystalování ^{characterized} enzenu of the melting pulse-OTE increased to 130 and ^z. 132 ° c.

The yield was 70.5%.

235 251

6.76 g (0.002 mol) of the amidoxime thus obtained are reacted with ethyl acetate as described in Example 6 to give 5.90 g of 5- [2- (3,3-diphenylpropylacetylamino) ethyl] -5-methanol -1,2,4-oxadiazole. o. m.p. 70-75 ° C in 80% yield. ^C o Recrystallization of ^YKL ZC ^h Exan The melting point increased to ⁸⁵ ° C.

g of 3- (3- (3-diphenylpropyl) aminopropionic acid amidoxime) is dissolved in 20 ml of acetic anhydride. The reaction mixture was allowed to stand for 1 hour and was then poured onto 100 g of ice. The precipitated crystals were aspirated and washed with water. There were obtained 12.15 g tm acid amidoxime 0-) acetyl) -3- (3-j dLifenylpropyl ·) and ^c ljmino et ^y)) - ^P ro ^P ion ^é 'of melting point ¹² 9th to ^1.2 ° C. Upon installation in ethyl acetate, the melting point is increased to 145 ° C.

To 12 g of the above acyl compound is added 50 ml of pyridine and the mixture is refluxed for 4 hours. Evaporation yields 11.30 g of crystalline 5- [2- (3 * 3-diienylpropylaaceylalmne) -eehl] -5- meehyl-l, 2,4-oxadiazole, mp 65 uo and ^z. 70 ^G C.. ^p o ^{p e} r? ^s ystalov from cyklotiexanu Tani temperature increased to 5 ° C ^8.

Following the procedure of Example 1, the following compounds were obtained. The starting materials, end products and melting points of the obtained compounds are given in the following table:

235 251 Art. Starting compound (II) Resulting product Melting point ° C ad. (Formula I)

3- (2-p-Methylanilinoethyl) -5-methyl-1,2

4-Oxadiazole 1- (p-tolvl) -3-130-132 amino-Δ-pyra- (from water) zoline

3- (2-Anilinoethyl) 5-phenyl-1,2-oxadiazole 1-phenyl-3-amino · д-pyrazoline

165-168 (from 96% ethanol)

3- (2-p-methylamilinoethyl) -5-phenyl-1,2,4-oxadiazole 1- (p-methylphenyl) -130-132-3-amino-Δ-pyra- (zolin water)

Example 6

7.16 g (0.04 mol) of phenylaminopropionic acid amidoxime and 10.6 g (0.12 mol) of ethyl acetate are dissolved in 14 ml of anhydrous ethanol, and the solution thus added is added to a sodium ethylate solution prepared from 0.92. g of sodium metal and 60 ml of anhydrous ethanol.

The reaction mixture was heated to boiling for 8 hours, whereupon crystals precipitated and the solution turned brown. The alcohol was distilled off under reduced pressure and 100 ml of water were added to the residue.

The oily product is separated from the water and crystallized by scraping on the wall of the container. The crystals are sucked off, washed thoroughly with water and dried. Thus 7.5 g of a pink product are obtained, m.p. 50-54 ° C. Extraction with petroleum ether gave 6.2 g of faintly colored 3- (2-phenylaminoethyl) -5-methyl-1,2,4-oxadiazole, m.p. 55-57 ° C, yield 76.5%. ·

Analysis: calculated for

235 251 calcd. C 65 04 04 found C 65.26

H 6.45 N 20, 68%

H 6.48 N 20.67%

Examples 7 to 10

The following compounds were prepared as described in Example 6. The starting materials, products and melting points of these compounds are shown in the following table.

Cis. ex amidoxime • ester product of formula II melting point ° C 7 J-pnitroanilinopropionic acid amidoxime ethyl 3- (2-p-nitroacetate anilinoethyl) - 5-methyl-1,2,4-exadiazole 138 - 140 (from anhydrous ethanol) 8 3- (ptoluidino) propionic acid amidoxime ethyl 3- (2, p-methylacetate anilinoethyl) - 5-methyl-1,2,4-oxadiazole 62 (from petroleum ether) 9 3anilinopropionic acid amidoxime 3- (2-Anilinoethyl) ethyl-5-phenyl-1,2,4-oxat diazole benzoate 83 - 85 (from a mixture of ethyl acetate and petroleum ether) 10 3- (p-methylanilino) propionic acid amidoxime benzoate 3- (2-p-methylanilioethyl) -5-phenylnate 1,2,4-oxadiazole 72 (from hexohexane)

Example 11

235 251

A mixture of 1.99 g (0.0062 mol) of 1- (3,3-diphenyl-propyl) -3-amino-6-pyrazoline acetyl derivative, 20 ml of 1 N aqueous sodium hydroxide solution and 20 ml of 96% ethanol is heated. to boil for 3 hours. The clear yellow solution was cooled, then the precipitated needle crystals were aspirated, washed with water until neutral and dried under an infrared lamp. Thus, 1.61 g of 1- (3,3-diphenylpropyl) -3-amino-d-pyrazoline of melting point 159 DEG-161 DEG C. are obtained in a yield of 92%. After recrystallization, the melting point was increased to 163-165 ° C.

For ^C 18 ^H 21 ^H ₃ calculated C C, γΐ H 7.50 N 15> 13% found С 77.17 H 7.42 N 15.34%

The resulting base is converted to the dihydrochloride with ethanol containing hydrochloric acid. The melting point is 160 DEG C. which is not changed by recrystallization from ethanol containing hydrochloric acid.

For ^C 18 ^H 23 ^N 3 ^Cl 2 ^: calculated Cl 20.10 C 61.40 H 6.58 N 11.92 Я found Cl 20.33 C 61.54 H 6.50 N 11.86%

Examples 12 to 16

Following the procedure described in Example 11, the following compounds were obtained:

235 251

no. ex. an acyl derivative of the formula I amino derivative of the formula I Jeplota tani c 12 -piperidinopropionyl derivative of 1- (3,3-diphanylpropyl) -3-amino-pyrazoline 1- (5 ', 5-diphenyl-propyl) -3-amino-N-pyrazoline 163-165 (from 96% ethanol) 15 Dec the ethyl ester of 1-benzyl-3-amino-4-pyrazoline 1-enyl-3-amino- д -pyrazoline 73 - 80 (from cyclohexane); hydrochloride 238 (from anhydrous ethanol) 14 an ethyl ester of 1-cyclohexyl-3-amino-1 H -pyrazoline 1-Phyclohexyl-3-amino-d-pyrazoline 86-88 (from cyclohexane)? hydrochloride 233 (from anhydrous ethanol) 15 Dec the ethyl ester of 1-n-butyl-3-amino-d-pyrazoline 1-Butyl-3-amino- Д -pyrazoline 65-70 (petroleum ether); (from anhydrous ethanol)

Example 16

To 211.3 g (1.0 mol) of 3,3-diphenylpropylamine, with stirring and cooling with water, 55.1 g (1.0 mol) of acrylonitrile are added over about 1 hour and the solution is heated in a water bath for about 8 hours. The resulting viscous solution (264 g) was cooled. By scraping the walls of the container it is obtained in good yield

- (5,5-Diphenylpropylamino) -propionitrile, m.p. 54 DEG C. and boiling point 195 DEG-197 DEG C. 13.5 Pa. The crude nitrile can be used for further processing without purification.

Analysis: for

235 251

calculated C 82.10 H, 7.67 N 10,64% found 0 81.96 H, 7.44 N 10.56% Example 17 and 18 Using the procedure described in of Example 6 se z amidoxime acid

3- (p-chloroanilino (-propionic and ethyl acetate) yields 5- [2- (p-chloroanilino) -ethyl] - ^[ > -methyl-1,2,4-oxadiazole, and from [beta] -4-p-chloroanilioo-4-poopoonic acid amidoxime methyl ethyl benzoate yields 3 (2- (p-chloroanilinyl) -5-isyl) -1,2,4-oxadiazole.

Example 19

To a solution of 0.46 g of sodium in 15 ml of anhydrous ethanol is added a solution of 4.6 g (0.02 mol) of 3- (ft-naphthylamino) propionic acid amidoxime and 5.03 g (0.06 mol) of ethyl acetate in 40 ml. of anhydrous ethanol. The mixture was heated to boiling for 8 hours, after which the solvent was distilled off under reduced pressure. 50 ml of water are added to the residue and the crystals are filtered off, washed with water and dried.

3.25 g (0.0128 mol) of colored crystals, m.p. 108-112, are obtained. Deň: 32 ° C. The yield is ⁶⁴ %. Crystallization from 96% ethanol has the product, i.e. 3- [2- (β-naitylcuaino) ethyl] -5-methyl-1,2,2-oxadiazole, m.p. 110-112. Deň: 32 ° C.

Example 20

2.54 g (0.01 mol) of 3- [2- (β-iityityl) thio] -5-methyl-1,2,4-oxadiazole were heated to boiling for 6 hours with 20 ml of a 20% strength aqueous hydroxide solution. sodium. The solidified product is triturated, suctioned off, washed with water until a neutral reaction and dried. This gives 1.8 g (0.0085 mol) of colored crystals

1- (A (.alpha.) - (- (- mii-- .beta.-pyrazole). Yield 85 V18).

235 251

Melting point: 185-190 ° C.

After recrystallization from 96% ethanol, the product melts at 173 ° C.

Example 21

Following the procedure described in Example 1, 5- (p-chloro- (anilino) methyl) -5,5-methyl-1,2,4-oxadiazole gave 1- (p-chlorophenyl) -5-amino-N-pyrazoline, m.p. Mp 144-146 ° C.

Yield 73% ·

Examples 22 to 24

Acetylderivatives of the following 3-aminopyrazolines are prepared in a similar manner:

Ex. number Compound Melting point ⁶ C Yield% 22nd p 1-Benzyl-5-amino-2-pyrazoline 145 76 23 2 1-Cyclohexyl-3-amino-D pyrazoline I30-I32 81 24 p 1-n-butyl-3-amino-4-pyrazoline 65-65 78

R is as defined above,

R 1 represents an alkyl group having 1 to 7 carbon atoms optionally substituted by at least one substituent such as a halogen atom, preferably chlorine or bromine, an amino, nitro, hydroxy and phenyl group, or a phenyl group optionally substituted by at least one substituent such as a halogen atom, preferably chlorine or bromine, an amino, nitro, C 1 -C 2 alkyl or C 1 -C 2 alkoxy group, ar is hydrogen or C 1 -C 7 acyl, or a salt thereof is reacted at a temperature of 5 ° to 110 ° C with a base, for example an alkali metal hydroxide, and the resulting compound of formula I wherein R 1 is hydrogen is optionally subjected to N-acylation, or a compound of formula I wherein R ^{2 is -} above optionally acetylating said acyl residue to form a compound of formula (I) wherein R ² is hydrogen, or the product thus obtained is if it is converted into its salt or the compound of formula I is released from its salt.

2. The method of item I for producing 3-amino2 derivatives

- a pyrazoline of the formula I, in which R represents an alkyl radical having 1 to 7 carbon atoms, optionally substituted by at least one halogen, one or two phenyl groups optionally substituted with an alkyl group having 1 to 2 carbon atoms or naphthyl, or phenyl or a naphthyl radical optionally substituted by a C 1 -C 2 alkyl, C 1 -C 2 alkoxy, nitro or halogen atom, and R 2²* is hydrogen as well as the salts thereof ', characterized in that the compound of formula (II) wherein R and R R are each

- 251 235 251 as defined in 1 and R ^ is hydrogen, reacted at 50 to 110 ° C with a base, whereupon the compound of formula I thus formed is optionally converted into its salt, or the compound of formula I is released from its salts ·

5. A process according to claim 1, wherein the reaction is carried out in the presence of water.

4. A process according to claim 3, wherein the compound of formula (II) wherein R, R5, and as defined in item 1 or 2 is reacted at a temperature of 50 to 110 ° C with an aqueous or aqueous-alcoholic alkali metal hydroxide solution.

Claims (1)

A process for the preparation of 3-amino-pyrazoline derivatives of the general formula I (1) in which R @ 1 represents an alkyl radical having 1 to 7 carbon atoms, optionally substituted by at least one halogen atom, one or two phenyl groups optionally substituted with an alkyl group having 1 to 2 carbon atoms or a naphthyl group, a cycloalkyl radical having 3 or 6 carbon atoms or a phenyl or naphthyl radical optionally substituted by a C 1 -C 2 alkyl, C 1 -C 2 alkoxy, nitro or halogen atom, and R ² * · - represents hydrogen, acetyl, piperidinopropionylový, propionyl, benzoyl and salicyl radical, and their salts, characterized in that a compound of formula II wherein