FI70707B - PROCEDURE FOR FRAMSTATING AV 4-SUBSTITUTES 1,2-DIPHENYL-3,5-DIOXOPYRAZOLIDINE - Google Patents

Description

rftl Μ1. ADVERTISEMENT r? n 7 nr, B 11 UTLÄG G NIN G SSKRI FT / U / U / c / 45, i granted ® '' D · * '1 «v> f .. ^ 1, V, 1 λ i Ί ^ f)" P9 1 ·· '' '· -] o uvi (.. lU -vj jl J aJOu' '^ (51) Kv.lk. * / Lnt.CI. * e 07 D 231/32, 491/048 FINLAND— “FINLAND (21) Patent application - Patentansökning 791139 (22) Application date - Ansökningsdag 06.04.79 0 = 1) (23) Starting date - Glltlghetsdag 06.04.79 (41) Published public - Blivit offentllg 09.1 0.79

National Board of Patents and Registration / 44) Date of publication and publication - 26 06 86

Patent and registration authorities V 'Ansökan utlagd ooh utl.skrlften publicerad (86) Kv. application - Int. ansökan (32) (33) (31) Privilege requested - Begärd priority 08.04.78 Federal Republic of Germany-Förbundsrepubliken Germany (DE) P 2815302.8 (71) Istituto de Angeli SpA, Milan, I ta 1 ia-I ta 1 ien (IT) ) (72) Arturo Donetti, Milan, Enzo Cereda, Tortona, Thailand (IT) (74) Lei tzinger Oy (54) Method for the preparation of 4-substituted 1,2-diphenyl-3,5-dioxopyrazolidines - Förfarande för framstälIning av 4-substituerade 1,2-difeny1-3,5 ~ d ioxopyrazolid iner

The invention relates to a new process for the preparation of 4-substituted 1,2-diphenyl-3,5-dioxopyrazolidines of the general formula I v / “-» - O — a C = CH - CH? - CH ___ (I)

R. ^ \ C0_N_Q

wherein R and R ', which may be the same or different, are a hydrogen atom, a lower alkyl group, a phenyl group or a group -COOR "(wherein R" represents hydrogen or a lower alkyl group), and A is a hydrogen atom or a hydroxyl group. The compounds of the general formula I exist in the so-called Z and isomeric E forms, both of which (and mixtures thereof) are included in the general formula given above.

It is already known from GB-PS 1 301 857 that e.g.

The compounds of general formula I 70707 are valuable antiphlogistic compounds which, due to their absence of main and side effects, are superior to butazolidine of similar structure. This publication also describes several methods for preparing this compound.

Spanish patent publication 417 378 discloses a process for the preparation of compounds of the formula I in which a triphosphonium salt and a pyrazolidine aldehyde are used as starting material. However, the aldehyde used is difficult to isolate and also leads to the formation of various oxidation products. The process thus known is difficult to carry out and leads to the formation of by-products, reducing the yield of the process.

It has now been found that compounds of general formula I can also be prepared by reacting a cyclo-hemiacetal of general formula II

^ O

HO - CH C - NM VS-A '\ f αι) wherein A * is a hydrogen atom or an etherified hydroxyl group, preferably a p-methoxyethoxymethoxy (= MEM) group, is reacted with a triarylphosphorane derivative of general formula III ^ Ar C = P-Ar (III ) R, X 1, Ar wherein R and R 1 are as defined above, and Ar is a phenyl group (optionally substituted with an inert group such as methyl, nitroxy or phenyl) followed by optionally releasing a hydroxyl group etherified with a mild Lewis acid. Suitable Lewis acids are in particular T1Cl4 and ZnBr2, but also ZnCl2, 70707 3

ZnJ2, SnCl4, MgCl2 »MgBr2 and similar metal halides.

The reaction of compounds II and III can be carried out in an aprotic solvent such as dimethylformamide or, preferably, dimethyl sulfoxide under anhydrous conditions.

The process can also be carried out, for example, by, after stirring at room temperature, heating the reaction mixture at a temperature between 30 and 100 ° C, preferably 50 to 70 ° C, allowing to cool and stirring further at room temperature.

After completion of the reaction, further work-up is carried out, for example, by pouring the reaction mixture onto ice, extracting with a suitable organic solvent such as ethyl acetate or dichloromethane and column chromatography or also re-extracting the organic solvent with basic aqueous medium. In the latter case, the product is obtained only by acidification with mineral acid (for example hydrochloric acid) and extraction as a suitable solvent. By further purification, the separation of geometric (E, Z) isomers can be performed by column chromatography.

When A 'represents an etherified hydroxyl group in the starting compounds, this still has to be liberated in order to obtain compounds of the formula I in which A = OH, since during the reaction the OH group is protected. This can be done, for example, by cleaving an etherified OH group, for example converted to N-methoxyethoxymethyl (= MEM) ether, with weak Lewis acids (for example T1Cl4 in dichloromethane) after reacting the etherified cyclohemiacetal II with a triphenylphosphorane of formula III. .

Compounds of general formula I in which R = CH3 and R '= COOH are obtained by mild alkaline saponification of the corresponding ester (R = CH3, R' = COOR ").

Compounds of general formula II can also be obtained in a simple manner by rearrangement of the corresponding 4,70707 cyclic acetal of general formula IV CH 2 - O 2 - CO N - yA 'I CH - CH 2 - CH "f (IV) CH 2 - O 2 CO 2 - wherein A' means the same as above.This conversion can be realized, for example, only by heating in aqueous ethanol.

The process according to the invention takes place easily and in high yield without substantial by-products, since it is possible to attach the double bond to the desired site and because the formation of disubstituted products in the C-4 atom of the pyrazolidine ring is avoided.

The following examples illustrate the invention:

Example 1 p-Hydroxyazobenzene-β-methoxyethoxymethyl ether (MEM)

To a stirred suspension of 66.14 g (1.516 moles) of sodium hydride (55% dispersion in mineral oil) in tetrahydrofuran (400 mL) was added dropwise a solution of p-hydroxyazobenzene (191 g, 0.963 moles) in 810 mL of tetra -hydrofuraania. The solution was stirred for 15 minutes, then cooled and then MEM chloride E.J. was added dropwise at 0 ° C. Corey, J.L. Gras and P. Ulrich, Tetrahedron Lett., 809 (1976) (1.44 g, 1.156 moles) and the mixture was then stirred at this temperature for 30 minutes. After stirring at room temperature for another hour, the excess sodium hydride was discarded by adding water and the mixture was concentrated in vacuo. The residue was taken up in ether and washed successively with water, 5% sodium hydroxide and water until it remained neutral. The ether extract was dried and evaporated under reduced pressure. This gave the title compound as a thick reddish oil (271.44 g, 98%) which was used without further purification.

Il 5 7070 7

Example 2 f v f i

p-hydroxyhydrazobenzene ether MEM

A solution of p-hydroxyazobenzene MEM ether (220 g, 0.768 mol) in 1300 ml of ethanol was hydrogenated at room temperature and atmospheric pressure with 2.2 g of Pd / C. After the calculated amount of hydrogen was consumed, the solution was filtered and evaporated to leave 220 g (99%) of a thick yellow oil, which was used in the next step due to its easy oxidation.

Example 3

Diethyl 2- (2-ethylenedioxyethyl) malonate

To a stirred suspension of 141.38 g (3.24 moles) of sodium hydride (55% dispersion in mineral oil), dimethylformamide (1300 ml) and benzene (500 ml) was added dropwise diethyl malonate (471.8 g). , 2.94 moles). After stirring at room temperature until the evolution of hydrogen ceased, then 2-ethylenedioxyethyl bromide S.M. Gurvich Zh. Obshch. Khim. , 2-7, 2888 (1957) (492 g, 2.94 moles) in 500 ml of benzene and the solution was stirred for 16 hours at 80 ° C. The mixture was then cooled, poured into excess ice water and the product isolated with ether. Evaporation of the dried extract gave 2- (2-ethylenedioxyethyl) malonate. Boiling point: 105-108 ° C (0 "5 mm).

Analysis Ο ,, Η, .Ο ,: Result% C 53.42 H 7.42

11 lo O

Lask. % 53.65 7.37

Example 4 4- (2-ethylenedioxyethyl) -1,2-diphenyl-3,5-dioxopyrazolidine

Hydrazobenzene (53.4 g, 0.317 mol) was added to a stirred solution of sodium solution (8.02 g, 0.348 mol) in 480 ml of anhydrous ethanol, followed by dropwise addition of diethyl 2- (2-ethylenedioxyethyl) malonate over 2 hours at reflux temperature. (78.05 g, 0.317 mol). The mixture was further heated at reflux for 1 hour, the solvent was evaporated to near dryness and the residue was heated for 1 hour under reduced pressure (15 mm) at 130-140 ° C. The reaction mixture was cooled, taken up in water, washed with ether and then filtered through activated carbon. The solution was acidified with cooling to give a white solid (72.95 g, 68%) which was dried in vacuo over phosphorus pentoxide and used in the next step without purification.

Melting point; 150 ° C.

Analysis for C 19 H 18 N 2 O 4: Result% C 67.71 H 5.33 N 8.23

Lask. % 67.44 5.36 8.28

Example 5 4- (2-Ethylenedioxyphenyl) -1- (p-MEM-oxyphenyl) -2-phenyl-3,5-dioxopyrazolidine-p-hydroxyhydrazobenzene MEM ether (137 g, 0.475 mol) in 140 ml of anhydrous ethanol was added with stirring. to a solution of sodium (1092 g, 0.475 mol) in ethanol (330 ml) and then diethyl 2- (2-ethylenedioxyethyl malonate (177 g, 0.475 mol) in 120 ml of ethanol was added dropwise over 2 hours at reflux temperature. the solvent was evaporated to near dryness and the residue was heated for 1 hour under reduced pressure at 130-140 [deg.] C. The reaction product was cooled, taken up in water, washed with ether and then filtered through charcoal, acidified to pH 4 with 10% hydrochloric acid and the oil separated The dried extract was evaporated to dryness to leave an oily residue which was dissolved in a saturated solution of piperazine in acetone. The piperazine salt of 4- (2-ethylenedioxyethyl) -1- (p-MEM-oxy-phenyl) -2-phenyl-3,5-dioxopyrazolidine was filtered and then dissolved in water. Acidified with glacial acetic acid and then the product was isolated with ether. Evaporation of the dried extract gave the desired pyrazolidine as a pale yellow oil (105 g, 50%) which was sufficiently pure 1,2,4,5-tetrahydro-1- (p-MEM-oxyphenyl) -2-phenyl-3H-5- for conversion to hydroxy-furo (2,3-c] -pyrazol-3-one.

7 7 0 7 0 7

Example 6 N- [1,2,4,5-Tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo [2,3-c] pyrazol-3-one] -4- (2-ethylenedioxyethyl) -1,2-diphenyl A solution of -3,5-dioxopyrazolidine (51.36 g, 0.152 mol) in 510 mL of 50% aqueous ethanol was refluxed for 3 hours. The solid crystallized from the still hot solution was collected by filtration and dried in vacuo. 36.66 g (82%) of 1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo- [2,3-c] pyrazol-3-one were obtained.

>: o

Melting point: 267 C, decomposes.

Analysis: C _H N0_: Result% C 69.18 H 4.75 N 9.63 1/14 2 3

Lask. % 69.37 4.80 9.52

Example 7 1.2.4,5-Tetrahydro-1- (p-MEM-oxyphenyl) -2-phenyl-3H-5-hydroxyfuro [2,3-c] pyrazol-3-one 4- (2-ethylenedioxyethyl) - A solution of 1- (p-MEM-oxyphenyl) -2-phenyl-3,5-dioxopyrazolidine (130 g, 0.294 mol) in 1200 ml of 75% ethanol was refluxed for 6 hours and then evaporated to dryness. The resulting residue was recrystallized from ethyl acetate to give 66 g (56%) of 1,2,4,5-tetrahydro-1- (p-MEM-oxyphenyl) -2-phenyl-3H-5-hydroxy-furo / 2,3- cis-pyrazol-3-one as colorless crystals.

Melting point: 203 ° C, decomposes.

Analysis: C 21 H 22 N 2 O 6: Yield% C62.99 H 5.49 N 6.95 Calc. % 63.31 5.57 7.03 8

Example 8 70707 4- (2-Formylmethyl) -1,2-diphenyl-3,5-dioxopyrazolidine 4- (2-ethylenedioxyethyl) -1,2-diphenyl-3,5-dioxopyrazolidine (2.54 g, 7.5 to a solution of boron tribromide (18.79 g, 75 mmol) in 50 mL of dichloromethane was added dropwise and at -70 ° C with stirring. Stirring was continued at this temperature for 24 hours. The temperature was then allowed to rise to room temperature and then the mixture was poured into excess ice water.

The organic layer was separated and washed (NaHCO 3 solution) until neutral, dried (MgSO 4) and evaporated to dryness. The viscous residue was crystallized from ethyl ether-dichloromethane (8: 2) to give 0.7 g (31.7%) of the desired pyrazolidine as a colorless solid. Melting point: 240-242 ° C.

Analysis: C17H14N2O3: Yield% C 69.54 H 4.92 N 9.44 Calcd. % 69.37 4.80 9.52

Example 9 4- (3-methyl-2-butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine

Isopropyl triphenylphosphonium iodide (35.24 g, 0.1 mol) / G. Wittig and D. Wittenberg, Ann., 606, 1 (1957) / To a solution in 180 ml of dimethyl sulfoxide was added dropwise a stirred suspension of sodium methylsulfinylmethide at 20-25 ° C (R. Greenwald, M. Chaykovsky, and EJ Corey, J Org. Chem., 28, 1128 (1963)) prepared in situ from a 55% dispersion of 4.15 g (0.095 mol) of sodium hydride in mineral oil from 120 ml of dimethyl sulfoxide. The mixture was stirred at room temperature for 30 minutes and then 1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo [2,3-c] pyrazol-3-one (14 g) was added portionwise. , 0.047 mol). The mixture was stirred for 2 hours at room temperature and then heated at 70 ° C for 1 hour.

The reaction mixture was stirred for 16 hours at room temperature, then poured into excess water and extracted with dichloromethane.

9 70707

The organic phase was separated, washed (H 2 O), dried (MgSO 4) and then evaporated to dryness. The resulting residue was dissolved in benzene and adsorbed onto a silica gel column. Elution with 10% acetone in benzene gave 8.79 g (58.4%) of the desired pyrazolidine as a colorless solid.

Melting point: 155-157 ° C.

Analysis: C 20 H 20 N 2 O 2: Yield% c 75/20 H 6.23 N 8.64

Lask. % 74.98 6.29 8.74

Example 10 4- (2-Propenyl) -1,2-diphenyl-3,5-dioxopyrazolidine This compound was prepared as in Example 9 starting from 1,2,4,5-tetrahydro-1,2-diphenyl-3H- 5-hydroxy-furo [2,3-c] pyrazol-3-one (5.88 g, 0.02 mol) and methyltriphenylphosphonium iodide / CH Collins and G.S. Hammond, J. Org. Chem., 25, 1434 (1960) / (17.78 g, 0.044 mol) and sodium methylsulfinylmethide (0.04 mol) in dimethyl sulfoxide (prepared as described above) was used. The title compound was obtained on column gel (10% acetone in benzene) after column chromatography as a colorless solid (64.5%). Melting point: 133-135 ° C (95% EtOH).

Analysis: C 18 H 16 N 2 O 2: Yield% c 74 * 12 H 5.63 N 9.37

Lask. % 73.95 5.52 9.58

Example 11 (E, Z) -4- (2-Butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine This compound was prepared according to Example 9 starting from 1,2,4,5-tetrahydro-1,2 -diphenyl-3H-5-hydroxy-furo- [2,3-c] pyrazol-3-one (5.88 g, 0.02 mol) and ethyltriphenylphosphonium bromide (16.33 g, 0.044 mol) / G . Wittig and D. Wittenberg Ann., 606, 1 (1957), using sodium methylsulfinylmethide (0.04 moles) prepared as described above in dimethyl sulfoxide. Column chromatography on silica gel (10% acetone in benzene '70707) gave the compound as a mixture of E and Z forms with more Z isomer (60%). Melting point: 167 ° C (EtOAc / H 2 O 1: 1). Literature melting point: 128 ° C for the compound obtained by the conventional malonate-hydrazobenzene route.

Analysis: C 19 H 18 N 2 O 2: Yield% C 74/32 H 5 • 87 N 9.22 Calc. % 74.49 5.92 9.15

Example 12 (E, Z) -4- (3-Phenyl-2-propenyl) -1,2-diphenyl-3,5-dioxopyrazolidine This compound was prepared as described in Example 9 starting from 1,2,4,5-tetrahydro -1,2-diphenyl-3H-5-hydroxy-furo- [2,3-c] pyrazol-3-one (5.88 g, 0.02 mol) and benzyltriphenylphosphonium chloride (17.11 g, 0 , 02 moles) / G. Wittig and M. Schöllkopf, Chem. Ber. J37, 1318 (1954) / and sodium methylsulfinylmethide (0.04 mol) in dimethyl sulfoxide prepared as described above was used. The compound was obtained in 64% yield crude.

Forms Z and E could be separated by column chromatography on silica gel (10% acetone in benzene). (Z) -isomer: Melting point: 124 ° C

(etOH 95 °).

Analysis: C24H20N2O2: Yield% C 78-29 H 5.31 N 7.48

Lask. % 78.23 5.47 7.60 (E) -isomer: Melting point: 133 ° C (EtOH 95 °) C 24 H 20 N 2 O 2: Yield% c 78/42 H 5.54 N 7/48

Lask. % 78.23 5.47 7.60

Example 13 (E, Z) -4- (3-Carbethoxy-2-butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine ___ α-carbethoxyethylidene-triphenylphosphorane / 0. Isler, Helv. Chim.

70707

Acta, 40. 1242 (1957) / (65.53 g, 0.175 moles) and 1,2,4,5-tetrahydro-1,2-diphenyl-3H-5-hydroxy-furo [2,3-c] - a mixture of pyrazol-3-one (26 g, 0.088 mol) in 400 ml of anhydrous dimethyl sulfoxide was stirred for one hour at room temperature and heated for a further 1 hour at 60 ° C. The reaction mixture was stirred for 15 hours at room temperature, then poured into excess water and extracted with ethyl acetate. The organic phase was separated and extracted several times with 5% aqueous piperazine solution. The combined aqueous extracts were acidified to pH 8 with 10% hydrochloric acid and the separated waxy solid was filtered off and discarded. The filtered solution was treated with activated carbon, then acidified to pH 5.5 and extracted with ethyl acetate. The dried extract was evaporated to give a crude isomeric mixture of (E) - and (Z) -4- (3-carbethoxy-2-butenyl) -1,2-diphenyl-3,5-dioxo-pyrazolidine as a brown thick oil which was dissolved in acetone. and purified via its 2-amino-2-diazoline salt. Treatment of this salt as described in Example 5 gave, after extraction with ethyl acetate and evaporation of the dried extract, 19.5 g of an oily mixture of the desired pyrazolidine with more of the (E) form. This mixture was dissolved in benzene and adsorbed onto a silica gel column. Elution with 10% ethyl acetate in benzene gave 1.36 g (4%) of the (Z) form as a colorless solid.

Melting point: 151 ° C.

Analysis: C 22 H 22 N 2 O 4: Yield% c 69-59 H 5.97 N 17.02

Lask. % 69.82 5.86 16.91

Further elution with the same material gave an intermediate fraction consisting of a mixture of the two isomers, followed by a fraction containing 14 g (42%) of the (E) form as a colorless solid which was recrystallized from cyclohexane.

Melting point: 93 ° C.

Analysis: C 22 H 22 N 2 O 4: Yield% c 69.87 H 5.81 N 16.80

Lask. % 69.82 5.86 16.91 70707 12

Example 14 (E, Z) -4- (3-Carbethoxy-2-butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine _________________ This compound was prepared as described in Example 13 starting from α-carbethoxyethylenetriphenylphosphorane (1.46 g, 4 mmol) and 4- (2-formylmethyl) -1,2-diphenyl-3,5-dioxopyratolidine (0.59 g, 2 mmol) in 12 mL of dimethyl sulfoxide to give 0.24 g (31 mmol) of .7%) of the title compound.

The physicochemical and analytical values and also the ratio of E / Z isomers were almost identical to those obtained in the previous example.

Example 15 (E, Z) -4- (3-Carbethoxy-2-butenyl) -1- (p-MEM-oxyphenyl) -2-phenyl-3,5-dioxopyrazolidine-α-carbethoxyethylidene triphenylphosphorane (14.49 g, 0, 04 moles) and 1,2,4,5-tetrahydro-1- (p-MEM-oxyphenyl) -2-phenyl-3H-5-hydroxy-furo [2,3-c] pyrazol-3-one (15 , 96 g, 0.04 mol) in 90 ml of anhydrous dimethyl sulfoxide was reacted as described in Example 13. The reaction mixture was then poured into excess water, extracted with ethyl acetate and extracted once more with 5% aqueous piperazine solution. The aqueous phase was acidified to pH 6, after which the product was isolated with ether. Evaporation of the dried extract gave 10.2 g of an oily mixture of the desired pyrazolidine with more of the (E) form. The mixture was dissolved in benzene and adsorbed onto a silica gel column. Elution with dichloromethane gave 0.58 g (3%) of the (Z) form as a yellow oil. Continuation of the elution gave a fraction consisting of a mixture of 2 isomers, a fraction containing 6.05 g (31%) of the (E) -isomer as a yellow oil.

Example 16 (E) -4- (3-Carbethoxy-2-butenyl) -1- (p-hydroxyphenyl) -2-phenyl-3,5-dioxopyrazolidine _____ 13 70707

To a stirred solution of titanium tetrachloride (77.26 g, 0.407 mol) in 750 mL of dichloromethane at 0 ° C was added (E) -4- (3-carbethoxy-2-butenyl) -1- (p-MEM-oxyphenyl) -2 -phenyl-3,5-dioxopyrazolidine (39.3 g, 0.081 mol), prepared as in Example 15, in 400 ml of dichloromethane dropwise. Stirring was continued for 1 hour and the mixture was then poured into excess ice water. The organic phase was separated, dried and evaporated to give an oily residue which was dissolved in dichloromethane and adsorbed onto a silica gel column. Elution with 10% methanol in dichloromethane gave 25.4 g (79%) of the title compound as a colorless solid.

Melting point: 70-74 ° C.

Analysis: C 22 H 22 N 2 O 5: Yield% c 66.84 H 5.51 N 6.92 Calc. % 66.99 5.62 7.10

Example 17 (E) -4- (3-Carboxy-2-butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine (E) -4- (3-carbethoxy-2-butenyl) -1,2-diphenyl A solution of -3,5-dioxopyrazolidine (2.25 g, 5.28 moles) prepared as in Example 13 in 10 mL of 10% sodium hydroxide was stirred for 30 minutes at room temperature and then acidified with 10% hydrochloric acid. The precipitated product was isolated with dichloromethane which, after evaporation of the dried extract, gave a gummy residue which was crystallized from ethyl ether (1.05 g, 56.75%).

Melting point: 141 ° C.

Analysis: C 20 H 18 N 2 O 4: Yield% c 68.28 H 5.19 N 7.97 Calc. % 68.56 5.18 8.00

Example 18 (Z) -4- (3-Carboxy-2-butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine This compound was prepared as described in Example 17 by hydrolysis with 10% sodium hydroxide (20 ml) in Example 13 7 O 7 (Z) -4- (3-Carbethoxy-2-butenyl) -1,2-diphenyl-3,5-dioxopyrazolidine (1 g, 2.6 mmol) prepared as described. After the usual work-up, the compound was crystallized from ethyl ether to give 0.6 g (61%) of the desired pyrazolidine as colorless crystals.

Melting point: 65 ° C.

Analysis: C 20 H 18 N 2 O 4 Yield% C 68'37 H 5.28 N 7.88 Calc. % 68.56 5.28 7.88

Example 19 (E) -4- (3-Carboxy-2-butenyl) -1- (p-hydroxyphenyl) -2-phenyl-3,5-dioxopyrazolidine __ This compound was prepared in a similar manner by hydrolysis with 10% sodium hydroxide. (200 mL) (E) -4- (3-carbethoxy-2-butenyl) -1- (p-hydroxyphenyl) -2-phenyl-3,5-dioxopyrazolidine (10 g, 25 mmol) prepared in Example 16 as described. The obtained compound was recrystallized from acetonitrile. 2.15 g (23.2%) of the title compound were obtained as colorless crystals. Melting point: 170 ° C.

Analysis: ONc: Yield% C 65.30 H 5.01 N 7.61

Zu lo Z o

Lask. % 65.56 4.95 7.66

Claims (9)

70707 A process for the preparation of 4-substituted 1,2-diphenyl-3,5-dioxo-pyrazolidines of formula (I) wherein R is CO - N - (f -A 1 H, C = CH - CH 2 - CH __ , (I) r · 'wherein R and R', which may be the same or different, are a hydrogen atom, a lower alkyl group, a phenyl group or a group -COOR "(where R" represents hydrogen or a lower alkyl group), and A is a hydrogen atom or a hydroxyl group, characterized in that the compound of general formula (II) HO - CH C - N - (f V-A '\ f I / ΓΛ UI) ch2 - c - co - n - (/ y wherein A' is a hydrogen atom or an etherified hydroxyl group , preferably a β-methoxyethoxymethoxy (= MEM) group, is reacted with a triarylphosphorane derivative of general formula (III) R Ar C = P Ar (III) R '^ ^ Ar wherein R and R1 are as defined above and Ar is (such as methyl, nitro or phenyl) the phenyl group and optionally the ether group are cleaved with dilute Lewis acids to give the compound of general formula (I). and compounds where A = OH. 16 70707 Process according to Claim 1, characterized in that the reaction of the compound of the formula (II) with the compound of the formula (III) is carried out in an aprotic solvent. Process according to Claim 2, characterized in that dimethyl sulfoxide is used as the aprotic solvent. Process according to Claim 1, characterized in that the reaction is carried out at 50 to 70 ° C. Process according to Claim 1, characterized in that the cleavage of the ether group A 'is carried out in an organic solvent. Process according to Claim 5, characterized in that anhydrous dichloromethane is used as solvent. The cyclohemiacetal used as a starting material in the process according to claim 1, characterized by the formula ____ O HO - CH C - N —V VA '\ 1-ΗΓ CH2 - C - CO - N ——y wherein A' is a hydrogen atom or an etherified hydroxyl group, preferably / 3 -methoxyethoxymethoxy (= MEM) group. 1 17 70707 A process for the further preparation of 4-substituents 1,2-diphenyl-3,5-dioxopyrazolidine, in the form of formula (I) and R 1 CO - N - y - and C = CH - CH 2 - CH 1 __. (I) R · '' "co-N —Q for R och R ', an active ingredient or an alkyl atom, an alkyl group, a phenyl group or an -COOR group" (for RH is an alkyl group or an alkyl group) , and A is a hydrogen atom or a hydroxyl group, which is a compound having the formula (II) HO - CH C - N - ([-A '\ n \ ch2-c - co - n - y is A') a hydrogen atom having a hydroxyl group, a phenyl or a 3-methoxyethoxymethoxy (= MEM) group, a ring reacting with a triarylphosphorus derivative having all of the formula (III) R ^ Ar C = P -Ar (III) R1 ^ ^ Ar for R and R ' the group consisting of the group consisting of an inert group, optionally with an inert group, methoxy or a phenyl substituent), a phenyl group and an eventual group having an additional group of the same group, for which a form has been used A = OH.