3- Pyrazolin-5-ones substitution reactions

Solid-phase synthesis of substituted pyrazolones 550 from polymer-bound /3-keto esters 549 has been described (Scheme 68) <2001EJ01631>. Trisubstituted pyrazole carboxylic acids were prepared by reaction of polymer-bound arylidene- or alkylidene-/3-oxo esters with phenylhydrazines <1999S1961>. 2-(Pyrazol-l-yl)pyrimi-dine derivatives were prepared by cyclocondensation of ethyl acetoacetate and (6-methyl-4-oxo-3,4-dihydropyrimi-din-2-yl)hydrazine with aromatic aldehydes <2004RJC423>. Reactions of acylated diethyl malonates with hydrazine monohydrochloride in ethanol afforded 3,4-disubstituted-pyrazolin-5-ones <2002T3639>. Reactions of hydrazines with A -acetoacetyl derivatives of (45 )-4-benzyloxazolidin-2-one (Evans oxazolidinone) and (2R)-bornane-10,2-sultam (Oppolzer sultam) in very acidic media gave pyrazoles retaining the 3(5)-chiral moiety <1999S157>. 

Both 2-pyrazolin-5-ones and 3-pyrazolin-5-ones undergo substitution at C-4 in an aromatic fashion. Halogenation, nitration and coupling with diazonium salts occur readily. In 2-pyrazolin-5-ones such reactions... 

A synthesis of the 17/3-[3-pyrrolin-2-on-4-yl]androstane (361) from acetyl-digitoxigenin (339) has been reported. The conversion of the iV-acetyl compound (362) into dihydrosolacongestidine (363) was improved by use of BU2AIH and thereby improved the synthesis of solacongestidine (364). Addition of diarylnitrilimines to a series of 17-substituted androst-16-enes gave the [16a,17o -f ]-2 -pyrazolines (365) or, when R = OAc, the [16,17-rf]-pyrazoles (366). The pyrazolines (367) were synthesized from 3/3-acetoxy-21-benzylidenepregn-5-en-20-one by reaction with phenyl- or p-methoxyphenyl-hydrazine. " Reaction of cholest-4-en-6-one with hydrazines and o-phenylenediamine led to the heterocyclic structures (368) and (369)... 

A mechanism has been proposed to rationalize the results shown in Figure 23. The relative proportion of the A -pyrazolines obtained by the reduction of pyrazolium salts depends on steric and electronic effects. When all the substituents are alkyl groups, the hydride ion attacks the less hindered carbon atom for example when = Bu only C-5 is attacked. The smaller deuterohydride ion is less sensitive to steric effects and consequently the reaction is less selective (73BSF288). Phenyl substituents, both on the nitrogen atom and on the carbon atoms, direct the hydride attack selectively to one carbon atom and the isolated A -pyrazoline has the C—C double bond conjugated with the phenyl (328 R or R = Ph). Open-chain compounds are always formed during the reduction of pyrazolium salts, becoming predominant in the reduction of amino substituted pyrazoliums. 

Substituted pyrazolin-5-ones have only three and -substituted pyrazolin-3-ones only two tautomers, since now the corresponding 19c and 19d structures are isomers. The calculations involved l-methylpyrazolin-5-one (PM3/6-3H-G, anions and cations), l-phenyl-3-methyl-2-pyrazolin-5-one (DFT, radical reactions) [97JPC(A)3769], and l-(2, 4 -dinitrophenyl)-3-methyl-2-pyrazolin-5-one [B3LYP/6-31G and the crystal structure (Section V,D,2)] (98NJC1421). 

The general method for the preparation of diphenylpyrazolines is shown in Scheme 11.8, in which X is a suitable leaving group, usually chloro but sometimes dialkylamino. This reaction normally proceeds readily, although pH control may be important. Preparation of the substituted ketone and hydrazine intermediates needed for the synthesis may involve lengthy and complicated sequences. Further reactions are often required to modify the substitution in ring B after formation of the pyrazoline ring. The preparation of compound 11.26 shown in Scheme 11.9 illustrates one of the simpler instances. 

Diazoacetaldehyde dimethylacetal (12) has been used as a substitute for diazoacetaldehyde in 1,3-dipolar cycloadditions with l-benzopyran-2(//)-ones (40), styrene, methyl methacrylate, 1-cyanocyclopentene, and methyl cyclohexene-1-carboxylate (41). The resulting A -pyrazolines were readily transformed in two steps into cyclopropanecarbaldehydes [e.g., 13 —> 14 (Scheme 8.4)]. In a similar manner, 3-phenylcyclopropane-l,2-dicarbaldehyde was obtained from the reaction of 12 with dimethyleneketal of cinnamic aldehyde. 

Pyrazolin-5-one, 3-methyl-1 -phenyl-in colour photography, 5, 299 Pyrazolinones 13C NMR, 5, 193 H NMR, 5, 185, 187 colour couplers in colour photography in non-silver photography, 1, 384 IR spectra, 5, 200-202 structure, 5, 170 Pyrazolinones, dichloro-reactions with alkali, 5, 78 Pyrazolin-3-ones 1-substituted tautomerism, 5, 214 Pyrazolin-5-ones reactions... 

RC=CKWG) yields 2,4-di-EWG-substituted pyrroles in the presence of copper catalyst but 2,3-di-EWG-substituted pyrroles in the presence of a phosphine catalyst.74 The 3 + 2-cycloaddition of diazoalkanes to (6 )-3-p-tolylsulfinylfuran-2(5//)-one produces diastereoisomeric pyrazolines in almost quantitative yield and with des >98%. (g) The sulfinyl group is responsible for the complete control of the n-facial selectivity in all these reactions.75 The Rh(II)-catalysed intramolecular 1,3-dipolar cycloaddition reaction of diazoamides (57) with alkenyl and heteroaromatic n -bonds yields pen-tacyclic compounds (59), via the ylide (58), in good to excellent yields and in a (g) stereocontrolled manner (Scheme 15).76... 

The reaction has proceeded satisfactorily with one or two benzoyl groups present,153,507 but a benzoyl group in position 1 has also been eliminated.153 The oxidation proceeds similarly when position 4 is substituted.608 Pyrazoline itself and monoalkyl- and monoaryl-pyrazolines give the corresponding pyrazoles only in small yield on oxidation with bromine.509,510 In the majority of cases bromination occurs together with oxidation, and often brominated products are the only ones isolated. Thus 1,3,5-triphenylpyrazoline yields a tribromide of unknown constitution.49 The hydro bromide of 4-bromopyrazole (43) was obtained almost quantitatively from 3-butoxy-J1-pyrazoline (42).611A mixture of 1,5-dimethylpyrazole and the 4-bromo compound... 

IV-Alkyl-substituted phthalimides 9 were easily transformed into mono-, di- or trisubslituted pyrazoles 10 via a one-pot addition/decyclization/cyclocondensation sequence <02JCS(P1)207>. 5-Silylpyrazoles can be prepared from condensation of silylalkynones with hydrazines <02T4975>. Reactions of acylated diethyl malonates with hydrazine monohydrochloride in ethanol afforded 3,4-disubstituted pyrazolin-5-ones <02T3639>. 

The one-pot three-component reaction of polyethylene glycol-supported acrylate 623 with aldehydes 621 and hydrazines 622 in the presence of chloramine-T followed by methanolysis afforded pyrazolines 624 in good yields and high purities (Scheme 77) <2003SL1467>. 1,3-Dipolar cycloaddition of resin-supported acrylic acid 625 with the nitrilimines generated in situ by oxidation of the aldehyde phenylhydrazones with (diacetoxy)iodobenzene under microwave irradiation gave 626, which was converted into l-phenyl-3-substituted-2-pyrazolinyl-5-carboxylates 627 (Scheme 78) <2004SC3521>. 

Addition reactions of diazoalkanes, especially diazomethane, diazopropane, diphenyl-diazomethane and ethyl diazoacetate, onto olefins, substituted with one or two electron-withdrawing groups take place very smoothly affording pyrazolines which upon heating or photolysis can give rise to the corresponding substituted cyclopropanes by elimination of nitrogen. 

A number of syntheses of 2-pyrazolin-5-ones depend on the reaction of compounds, other than /3-ketoesters, substituted in the /3-position or of a,/8-unsaturated acids, esters and amides. The most frequently used unsaturated compounds are those having a triple bond in the apposition.1023,1024,1075,1548,1680 R2 can be HO,1552 RO1023,1024,1686 or H2N (eq. 8).1023,1024 A similar reaction is the condensation of ethyl... 

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