SU1439977A1 - Method of producing 1-aryl-3-aroyl-4,5-dihydro-6.3-pyrazol dions - Google Patents

Abstract

The invention relates to / heterocyclic compounds, in particular to the preparation of 1- (4-K | -aryl) -3- (4-K4 arosch1) -4,5-DIHYDRO-4,5-pyreneoldion (PD), where a) R, H, b) Rr «OCH ,, c), which can be used in the synthesis of heterocyclic compounds and as biologically active substances. The goal is a way to get new PD. Their synthesis is carried out from aroyldiazonium followed by cyclization of the obtained product in the presence of thionyl chloride in anhydrous benzene at boiling for 1.5–2 h. Yield, Z; t.SH1., s, gross f-la; 1) 37; 154-156; C, 6H, ClNiO ,; 2) 54; 160-162; C, gH, i4Nj04; 3) 50; 188.5-189.5; H „ClN2; 0). The minimum inhibitory concentration, µg / ml, for PD is 250-500 µg / ml for Staphylococcus aureus and 500 µg /, / ml for Bactereum Coli (for a known Edacidine lactate 500 µg / ml in both cases) .. 1 tab.

Description

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This invention relates to a process for the preparation of 1-aryl-3-aroyl 4,5-dihydro-A, 5-pyrazoptions, which are not previously described, of the general formula:

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im. J., o

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where a) R, -H, b) Rj-OCH p Rj, “CHj; c) R, Cl, which can be used as biologically active compounds, as well as starting materials for the synthesis of heterocyclic compounds.

The chain of the invention is a process for the preparation of 1-aryl-3-aro-L-4,5-dihydro-4,5-pyrazolidinone not previously described, having an antimicrobial effect. 25

An example. 1-phenyl-3- (4-chlorobenzoyl) -4 5-dihydro-4,5-pyrazol-dione (1a),

To a solution of 17.0 g (0.075 mol)

p-chlorobenzoyl pyruvic acid in 500 ml of ethanol and ZOO ml of dioxane with stirring and cooling (temperature of the reaction mass O C) was added phenyl diazonium chloride solution prepared from 6.8 ml (0.075 mol of aniline, 6.38 g (0.092 mol) of nitrite sodium, 19 ml of conc. HCl and 90 ml of water. Then 11.4 g of sodium acetate is added and stirred at room temperature. After a day, the reaction mass is poured into 3 liters, the precipitated precipitate is filtered off and dried. The dry product is suspended in 100 ml absolute .. benzene, add 13.0 ml of thionyl chloride and boil in t cheni.e 2h.

Absolute hexane is added to the hot reaction mixture until the solution becomes cloudy, heated again to a boil and cooled. Fallen dark cherry

35

40

45

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the precipitate is filtered off, dried in an excimeter above n-recrystallization from absolute chloroform. The yield of 8.66 g (37%). M.p. 154-15b C.-Found,%: G 61.90; H 2.40; C1 11.75; N 8.76.

e ,, bn ,,

Calculated,%; C 61.45 | H 2.90 | C1 11.34, N 8, 96.

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The compound fa is a dark cherry crista, well soluble in common organic solvents. Compound 1a is hygroscopic.

1- (4-matoksifennp) -3 (4-methylbei-3onl) 4,5-DIHIDRO-4,5-pyrazolidione (16) ..

Synthesized similarly to 1a.

Yield 54%. M.p. 160-162 C (absolute chloroform). .

Found,% s C 67.80; H 4.03; N 8.62.

CigHj NiO.

Calculated,%: C 67.08; H 4.38; N 8.69.

1- (4-chlorophenyl) -3- (4-methylbenzoyl) - 4,5-DIHIDRO-4,5-pyrazol-dione (1c).

Synthesized analogously to 1a,

Yield 50%. Mp 188.5-189.5 ° C (absolute chloroform).

Found,%: C 62.13; H 3.30; N 8.21; Pp. 10.75.

С, 7Н „С1ЫГО ,.

Calculated,%: C, 62.49; H.3539; N 8.57; 01 10.85.

All compounds are not previously described.

The individuality of all the synthesized compounds was proved by thin-layer chromatography on Silufol plates. The structure was confirmed by IR, PIR, and mass spectrometry data.

The IR spectra were recorded in petroleum jelly on the UR-20 instrument, the PMR spectra in CDC1, on the PAN 2310 instrument (60 kHz), and the mass spectrum on the MX 1320 instrument.

In the IR spectra of compounds 1a –c, the absorption bands of lactic carbonyl are observed in the region of 1748–1765, the two carbonyl groups at 1722–1732 and 1633-1639, as well as the absorption bands of the aromatic ring, and - bonds in the region 1587–1559 cm and 1530-1540 cm.

In the PMR spectra of the 1XGx connections, multiplet signals are observed. aromatic protons centered at 7.60-7.40 MD, the singlet of three protons of the methyl group at 2.33-2.35 ppm (compounds 16, c). and the singlet of the three protons of the methoxy group. at 3.69 m, d. (compound 1c).

The mass spectrum of compound 1a contains: gips with the following values: m / g: 312.314 (M), 256.258 (M-2C01) 5,139.141 (ClCsHsCO); 119 (CeHy-N C 01); 111.113 (), 91 (CfcHjN).

Carrying out the cyclization reaction by the action of thionyl chloride in anhydrous benzene at reflux for 1.5-2.0 hours allows to obtain a pure product with maximal excess solution. The use of anhydrous solvents is due to the hygroscopicity of imported products.

Below are examples of carrying out the synthesis of Compound 1a under conditions different from those claimed.

a) From 2.27 g (0.01 mol) p-chloro benzoyl pyruvic acid, after carrying out the azo coupling reaction according to the described procedure and cyclization in boiling absolute toluene at a temperature of 110 ° C for t hours, g (21%) of the final product is obtained

5) From 2.27 g (0.01 col) of p-chlorobenzoyl-pyruvic acid, after carrying out the azo coupling reaction according to the described procedure and cyclization in boiling absolute benzene, the target mixture is obtained for 1 hour. and source products.

c) From 2.27 g (0.01 mol) of p-chlorobenzoyl pyruvic acid, after conducting the azo coupling reaction according to the described procedure and cyclization with thionyl chloride in boiling absolute benzene for 3 hours, obtain 1.09 (35%) of the desired Thus, benzene is the best solvent for this reaction, with the highest yield being achieved at its boiling point. Carrying out the reaction in a higher boiling inert solvent (for example, toluene) at the boiling point of benzene (80 ° C) does not significantly alter the flow of the product, but requires constant control of the temperature of the reaction mass, which complicates the reaction.

The optimal cyclization time is 1.5-2.0 hours. Reducing the reaction time results in a mixture of the initial and desired product. Increasing the reaction time does not increase the yield of the target product.

The compounds exhibit antimicrobial activity against Staphylococcus aureus and Bacterium cpli (see table). .

Thus, the minimum concentrations of compounds that inhibit the growth of microorganisms are comparable with the minimum inhibitory concentration of ethacridine lactate used in medicine as an antiseptic preparation. The method makes it possible to obtain, from simple acryl pyroninic acids, by simple chemical transformations, previously unknown 1-aryl-3-aroyl-4,5-digidro-4,5-pyrazo-dions, which are highly reactive and can be used to create - drugs with biological activity,

Claims (1)

Invention Formula The method of obtaining 1-aryl-3-aroyl-4,5-dihydro-4,5-pyrazol-diaons of general formula 1: where a), R ,, C1; b) ,, r CHj; c) R, C1, characterized in that aroyl pyruvic acid is reacted with aryl diazonium chloride and the resulting product is subjected to cyclization c. in the presence of thionyl chloride in anhydrous benzene at boiling for 1.5-2 hours with the desired product. Antimicrobial - active compounds 1a 500 500 sixteen 250 500 55-1c 250 500 - ethacridine lactate 500 500