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Synthetic Communications: AnInternational Journal for RapidCommunication of SyntheticOrganic ChemistryPublication details, including instructions forauthors and subscription information:http://www.tandfonline.com/loi/lsyc20

Clay Catalysis: DryCondensation of 3-Methyl-1-Phenyl-5-Pyrazolone withAldehydes Under MicrowaveIrradiationDidier Villemin a & Bouchta Labiad aa I.S.M.Ra.U.RA. 480 CNRS.Université de Caen ,F14050, Caen cedex, FrancePublished online: 24 Oct 2006.

To cite this article: Didier Villemin & Bouchta Labiad (1990) Clay Catalysis:Dry Condensation of 3-Methyl-1- Phenyl-5-Pyrazolone with Aldehydes UnderMicrowave Irradiation, Synthetic Communications: An International Journal forRapid Communication of Synthetic Organic Chemistry, 20:20, 3213-3218, DOI:10.1080/00397919008051548

To link to this article: http://dx.doi.org/10.1080/00397919008051548

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SYNTHETIC COMMUNICATIONS, 2 0 ( 2 0 ) , 3213-3218 ( 1 9 9 0 )

CLAY CATALYSIS: DRY CONDENSATION OF 3-METHYL-1- PHENYL-5-PYRAZOLONE WITH ALDEHYDES UNDER

MICROWAVE IRRADIATION

Didier Villernin* and Bouchta Labiad

I.S.M.Ra ,U.R.A.480 CNRS,Universite' de Caen, F I4050 Caen cedex, France.

ABSTRACT: 3-Methyl- 1 -phenyl-5-pyrazolone (1) and arylcarboxyaldehydes ( 2 ) were condensated to 1 -phenyl-3-methyl-4-(arylmethylene)-S-pyrazoIoiie (3) in presence of acidic clay KSF without solvent under microwave irradiation.

The derivatives of the pyrazolone are important class of antipyretic and analgesic compounds ( antipyrine, amidopyrine, phenylbutazolone). l-Phenyl-3-methyl-4- (arylmethylene)-5-pyrazolones (3) are useful intermediate in synthesis of substituted pyrazolones 2.The 5-pyrazolone like the Meldrum acid 3, the tetronic acid 4, the barbituric acid 5, the acetylhydantoine 6 and the piperazinedione 7 is a quasi-planar cyclic compound containing an acidic methylene group. W e have already described the dry condensation of these cyclic compounds with aldehydes 3-7 and we have reported that microwaves allow to activate the dry c o n d e n s a t i o n s 8. According these regards we described herein the dry condensation of 3-methyl- 1 -phenyl-5-pyrazolone (1) with aromatic aldehydes ( 2 ) by adsorption on acidic Montmorillonite clay under microwave irradiation. With basic catalyst like KF on alumina a complex mixture of product was fornicd.

'l'he condensation giving 1 -phenyl-3-methyl-4-(arylmethylene)-5-py~azolone (3) is acid catalyzed like the condensation of tetronic acid with aldehydes 4.

* To whom correspondence should be addressed

32 13

Copyright 0 1990 by Marcel Dekker, inc.

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3214 VILLEMIN AND LABIAD

3-Methyl- I-phenyl -5-pyrazolone (1) was obtained quantitatively and rapidly by the Knorr condensation of ethylacetoacetate with phenylhydrazine 9-1 0 under microwave irradiation.

The condensation of (1) with (2) gave a mixture of Z an E isomers of I-phenyl-3- methyl-4-(arylmethylene)-5-pyrazolone (3) (Table I), the stereochemistry was attributed by 1H-NMR spectra on the base of the shifting of methyl group.

\ z E , "

Generally the Z isomer was preferred, for the indole compounds (3h) the E isomer was preferred, we supposed that this was to the nitrogen interaction with acidic support during the reaction.

Combination of efficiency, speed and convenience makes microwave irradiation suitable for the synthesis of pyrazolone (1) and for the dry condensation of (1) with (2) on acidic clay.

We thank Sud-Chemie for the generous gift of Montmorillonite K10 and KSF.

EXPERIMENTAL Infrared spectra were recorded on Perkin Elmer 684 IR spectrophotometer in KBr with absorptions in cm-1 . Proton NMR spectra (PMR) absorptions recorded in ppm downfield from internal Me& were recorded on Varian EM 360 instrument

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CLAY CATALYSIS 3215

Table I : Reaction of l-phenyl-3-methyl-5-pyrazolone (1) with aldehydes (2) on Montmorillonite KSF under microwave irradiation (2450 MHz )

microwave (%) aldehyde (2) Conditions Yield 2/E

3,4-methylenedioxy benzaldehyde

3,4,5-trimethoxybenzaldehyde

4-nitrobenzaldehyde

4-dimeth ylaminobenzaldeh yde

thiophene-2 carboxaldehyde

2-furaldehyde

3-(2 furyl) acrolein

indole-3-carboxalde h yde

350 W, 2 mn

210 W, 5 mn

350 W, 2 mn

350 W, 2 mn

350 W, 2 mn

140 W, 3 mn

70 W, 5 mn

350 W, 5 mn

85

77

68

71

89

86

92

75

70130

68/32

70130

70130

80/20

7 1/29

5414 1

3 3/67

(60 MHz) from a solution in d6 -DMSO of the product. UV spectra were recorded

on Beckman Acta M VI spectrometer. Microwave irradiations were carried out with a commercial microwave oven Toshiba ER 7620 at 2450 MHz.

Synthesis of 1-phenyl -3-methyl-5-pyrazolone 11) Ethyl acetoacetate (5.4 g, 5 10-2 M) and phenylhydrazine (5.4 g, 5 10-2 M) were

mixed in open Pyrex Erlenmeyer flask (50 ml) and then the mixture was irradiated in a microwave oven (280 W) for 10 mn. After cooling, ether (30 ml) was added and crystals were filtered. The product was recrystalized in a mixture water-ethanol (111). The yield was quantitative. White crystals, Mp 129" . General Drocedure: synthesis of l-phenyl-3-methyl-4-(arylmethylene)- 5- pyrazolone (3) 3-Methyl-1-phenyl -5-pyrazolone (1) (5 mmol) and aldehyde (1) (15 mmol) were ground with Montmorillonite KSF (4 g) during 3 minutes with a IKA A10

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3216 VlLLEMIN A N D L A B I A 1 1

crusher. The mixture was placeu in a open Pyrex Elemmeyer flask (25 ml) and was irradiated in a microwave oven ( see table). The products formed was extracted with ethyl acetate (100 ml) , filtered and the solvent was evaporated in vacuo and then crystalized in an appropriate solvent.

l-Phenyl-3-methyl-4-[(3,4-met hylenedioxyphenyl)methylene]-5- pyrazolone (3a) Red solid ; Mp 178" (AcOEt) ; PMR, 6: 2.30 (Z isomer) 2.55 (E isomer) (2s, 3H, CH3), 6,20 ( s , 2H, OCHlO), 7.05 (m, lH, H arom. ), 7.20 - 7.60 (m, 4H, H

arom), 7.95 (m, 2H, H arom), 8.05 (s, lH, CH=), 8.80 (s, lH, H arom) ; IR : 1680 (vC=O), 1610 (vC=C) ; UV (EtOH) hmax (log E ) : 386 (4.14), 326 (3.70), 254 (4.04), 248 (4.07). 1 -Phenyl-3-methyl-4-[(3,4,5-trimethoxyphenyl)methylene]-5- pyrazolone (3b) Orange solid ; Mp 161' (EtOH) ; PMR, 6 : 2.40 (7, isomer), 2.60 (E isomer) (2s, 3H, CH3 ), 3.95 (s, 9H, OCH3), 7.30 - 7.60 (m, 3H, H arom), 8.05 (ni, 4H, H

arom), 8.35 (s, IH, CH=) ; 1R : 1670 (vC=O), 1610 (vC=C) ; U V (EtOH) hmax (log E ) : 372 (4.28), 254 (4.30), 248 (4.31). 1-Phenyl-3-methyl-4-[(4-nitrophenyl)methylene]-5-pyra~olone (3c)

Red solid ; Mp 174' (AcOH), lit.11 Mp 175" ; PMR 6 : 2.30 (Z isomer) 2.42 (E isomer) (2s, 3H, CH3 ), 7.25(m,2H,H arom),7.45(rn,3H,H arom), 8.05 (s, IH, CH=), 8.15 (m, 2H, H arorn.), 8.65 (m, 2H, H arom.) ; IR : 1680 (vC=O), 1620 (vC=C) ; U V (EtOH) h max (log E ) : 328 (3.61), 256 (4.01). l-Phenyl-3-methyl-4-[(4-dimethylaminopheny)methylene]-5- pyraxolone (3d) Orange solid ; Mp 196', lit 12 Mp 199-200' ; PMR 6 : 2.20 (Z isomer) 2.42 (E isomer) ( 2 s 3H, CH3), 2.80 (s,3H,NCH3) and 3.02 (s,3H,NCH3),

6.75(d,2H,H arom,J=BHz), 7.20-7.60(m,3H,H arom), 7.90(m,2H,H arom), 8.10 (s, lH,CH=), 8.60 (d, 2H,H arom,J=8Hz); IR : 1675 (vC=O), 1610 (vC=C), 1375; UV (EtOH) h max (log E ) : 458 (3.93, 345 (3.72),254(4.02), 24 8 (4.04). l-Phenyl-3-methyl-4[(2-thienyl)methylene]-5-pyra~olone (3e) Red solid ; Mp 124" (EtOH) ; PMR 6 : 2.40 (Z isomer) 2.60 (E isomer) (2s, 3H, CH9, 7.20-7.70 (m, 4H, H arom.), 8.10-8.40 (m, 5H) ; IR : 1680 (vC=O), 1610 (vC-C) ; UV h max (log E ) : 362 (3.99) , 254 (3.77). 246 (3.80).

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CLAY CATALYSIS 3217

I-Phcnyl-3-methyl-4-[(2-furanyl)methylene]-5-pyra~ol~ne (3f) Red solid ; Mp 114' (EtOH) ; PMR 6 : 2.40 (Z isomer) 2.62 (E isomer) (2s, 3H, CH3), 6.90 (m, IH, H arom.) , 7,3O - 7.7.5 (m, 4H ,H arom), 8.15 (m, 3H), 8.95 (m, 1H) ; IR : 1680 (vC=O); 161.5 (VC=C); UV (EtOH) h max (log E ) : 361

(4.20), 254 (3.90), 248 (3.91). 1 - Ph en y I -3-met h y 1-4- (2- fu ra n y 1-2- pro pen y I i dene) -5 - p y ra zol one (3 g) Brown solid ; Mp 142' (EtOH) , lit. l 3 Mp 140-141 (EtOh); PMR 6 : 2.20 ( Z isomer) 2.43 (E isomer) (2s, 3H, CH3), 6.65 (m, IH), 6.95 (111, IH), 7.10-7.50 (in, 6H), 7.80 (m, 2H), 8.20 (m, 1H) ; IR: 1670(vC=O); 1620 (vC=C),IS90-1580 ; UV (EtOH) h max (log E ): 402 (4.31), 326 (3.58), 254 (4.02), 248 (4.01).

l-Phenyl-3-methyl-4-[(3-indoly)lmethylene]-S-pyra~olone (3h) Brown solid, Mp 224' ; PMR 6 : 2.20 (Z isomer) 2.45 (E isomer) (2s, 3H, CH3),

7.30-7.75 (m, 7L1, FI arom), 7.90 (m, 2H, H arom), 8.20 (m, 2H), 10.20 (s, IH,

(EtOII) : h max (log e ) : 403 (4.12), 286 (4.17), 278 (4.17), 254 (4.34), 243 Nf 1) ; IR : 3240 ( v N-H), 1660 (V G C ) , 1630 (V C=C), 1605 (V G C ) ; UV

(4.36).

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3218 VILLEMIN AND LABIAD

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