A Convenient Synthesis of 3,5'-Bipyrazolyl Derivatives via Hydrazonyl Halides (1990)

Cycloaddirion of N-phenyl-C-cinnamonirrilimine 3 with enolarer of various acrive merhylene compoundr afforded rhc 3-styrylpyru~ole derivatives 6-10 in high yields.3-Sryrylpyruzalez 6-13 rrhcreo with diphenylnitrilimine 20 t o give t h e corresponding 3,s'-hipyruzolyl derivarives 21-28, renpecrively.T h e derivatives of o pyrazole ring linked t o an arornaric or heteroaromaric have been found antirheumatic and antipyretic properries.1'2The compoundr ruch as n n ~i ~~r i n e , ~ dipyrone: phenylburzone,' and mepyrazole6 are well known drugs.Alrhough many synrheses far various bipyrazolyl isomers are reporred in lirerarures.anlya f e w derivatives have been reparred for 3 , 5 ' -h i p y r a o o l y l ~~~~ T h e usual merhod for t h e synthesis o f ruch compounds involves rhe reacrion of hydrarines with 7 Keilcrion of (E)N-phenyl-C-cinnalnohydr~onyl bromide 1 wirh dipo1;~rophiles.1.0 n solurion of hydrazonyl bromide 1 (1.5 g , 5 m m o l ) and r h c a p p r o p r i s r e dipolzrophile ( 5 mmol) in benzene ( 4 0 ml) was added r r i e r h y l a m i n r (0.7 ml, 5 mnrol) ;ic room remperarure.T h e mixcure war reiluxed for 12 h and filrered ro ger rid o i r r i e r h y h m i n e hydrobromide.T h e salvenr was ev.ipornred a n d t h e residue l e f t was rrirurvred wirh a small zmounr of meihvnol w h e r e upon ir solidified.T h e c r u d e solid w a r collectd and r e c r y r u l l i z a r i o n i r o m iicrric a c i d gave 3-sryrylpyrszoles 11-13. 1 4 Compound 11 had rnp 1 4 4 ' ~, 1.1 g, ( 8 0 %I (Lir.mp 1 4 4 ' ~) .0 15 Compound 1 2 had m p 140°C, 1.9 g, (85 X) ( ~i r .mp 1 4 4 C).Compound 1 3 had m p 223Oc, 1.94 g ( 8 0 X); 6 (CDc13) 6 .9 4 .3 ("1, Ar-H) ppm; u ( K B ~) 3300 ( N H ) I 6 9 0 ( C = 0 ) c m -l .A n d .Cnlcd f o r C30H22N403: C, 71.1; H, 4.6; N , 11.5.Found: C, 74.6; H, 4.7; Prepnrarion of 4,5-dihydro-4'.5'-disubsrituced1,1',3,4-ti.rr~phmyI-3,5-bipyriu.olyls21-28 General method-A m i x t u r e o f N-phmylbrnrohydraronyl chloride 1 9 (1.2 g, 5 mmol) a n d t h e apprapriare pyrazole ( 5 mmol) in chloroform (50 1111) was r e i l u r e d f o r 5 mi".T o t h e resulring rolurion rrierhylv m i n e (0.7 ml. 5 m m o l l w a s ~d d d e d a n d rhe mixture was reiluxed for 15 h.T h e solvent was evapora t e d in a r o t a r y rvaporaror a n d r h e residue w a s rrirurilred wirh merhanol ( 5 rnl).T h e solid rhar t o r m e d was collecred a n d recrysrvllized from erhanol.Compound 2 1 had m p 1 8 8 ~~, 1.98 g ( 8 0 %I; 6 ( C D C I ~) 2.3 (s, 3H), 2.5 (s, 3 ~1 , 4.7 (d, J = 6 H z .l H ) , 5.6 (d, J = 6 H r , I H ) , 6.8-7.7 ( m , 2OH) ppm; u (KBr) 1 6 7 0 ( C = O ) , 1600 ( C -N ) cm-l.Anal.Calcd f o r C H N 0. C, 79.8; H, 5.7; N , 11.3.Found: C, 79.9; H, 5.6; N, 11.2.33 28 .i ' Compound 22 h a d m p 1 4 6 ' ~, 2.23 g (85 X); 6 (CDC13) 1.0 ( r , J = 7 H r , 3H), 2.5 (s, 3H), 4.0 (4, J = 7 H z , 2 H ) , 4.7 ( d , J = 6 H z , l H ) , 5.8 ( d , J = 6 H z , I H ) , 6.7-7.8 ( m , ?OH) ppm; u (KBr) 1 7 5 0 ( C = O ) , 1 1 6 0 0 ( C = N ) c m -.Anal.Cnlcd i o r CJ4H30N402: C, 77.5; H, 5.7; N, 10.6.Found: C , 77.6; H , 5.6; N , 10.7.Compound 2 3 h a d m p 1 6 8 ' ~, 2.28 g ( 8 0 XI; 6 (CDC13) 0.9 ( r , J = 7 H z , 3H), 4.0 (9, J = 7 H z , ZH), 4.8 (d, J = 6 % l H ) , 5.8 (d, J = 6 H z , I H ) , 6.9-7.6 ( m , 25H) ppm; u ( K B r ) 1745 ( C = O ) , 1600 ( C = N ) cm'l.Anal.Cdlcd f o r C39tij2N40: C , 79.7; H, 5.5; N , 9.5.Found: C , 79.3; H, 5.8; N, 9.7.Compound 2 4 hod m p 1 2 5 ' ~, 2.29 g (85 X); 6 (CDCI 1 4.8 ( d , J = ~H L , l H ) , 5.4 ( d , J = 6 H z , l H ) , 3 7.0-7.7 ( m , 25H) ppm; u (KBr) 2220 ( C -N ) , 1595 ( C = N ) Anal.Cslcd f o r CJ7Hz7N5: C, 82.0; H, 5.0; N, 12.9.Found: C. 81.6; H, 5.3; N , 12.7.Compound 2 5 had m p 1looc, 2.17 g ( 7 0 X); 6 (CDC13) 5.1 ( d , J = 6 H z , I H ) , 5.5 ( d , 1 = 6 H i , l H ) , 6.9-7.4 ( m , 30H) ppm; u (KBr) 1690 ( C = O ) , 1595 (C:N) cm-'.Anal.Calcd f o r C43H32N40: C, 83.2; H , 5.2; N , 9.0.Found: C, 83.0; H,. 5.6; N , 8.9.Compound 2 6 had mp 1 4 9 ' ~, 2.10 g (90 %); 6 ( c D C I ~) 4.8 (d, j=6Hz., ill), 5.4 ( d , J = 6 H c , IH), 6.8-8.2 ( m , 12H) ppm; u (KBr) 2250 ( C = N ) , 1595 ( C = N ) cnr-I.Anal.Cnlcd for C31H23N5: C, 80.0; H, 5.0; N , 15.0.Found: C, 79.6; H, 5.0; N, 15.4.Compound 27 h a d mp 2 2 5 ' ~, 2.43 g (90 9,); 6 (CDC13) 4.7 (d, J = 6 H z , IH), 5.5 ( d , J = 6 H z , l H ) , -1 6.8-7.8 ( m , 25H) ppm; u (KBr) 2220 ( C = N ) , 1595 ( C = N ) c m .Anal.Cnlcd for CJ7HZ7N5: C, 82.0; H, 5.0; N, 12.9.Founi: C, 81.7; H, 5.4; N, 12.6.Compound 2 8 h a d mp 1 3 7 ' ~, 2.72 g (80 %); 6 ( C D C I ~) 4.5 (d, J = 6 H z 1 I H ) , 5.4 ( d , J = 6 H z , I H ) , 6.8-7.9 ( m , 30H) pprn; u (KBr) 3300 (NH), 1690 ( C = O ) c m -l .Anal.Cnlcd for C43H32N603: C, 75.9;H , 4.7; N, 12.4.