Pyrazolines into pyrazoles

Photooxidation has also been used to transform pyrazolines into pyrazoles (74AJC2267) and 3-pyrazolidones into 3-hydroxypyrazoles (76CC685). 

A -Pyrazolines are converted into pyrazoles by oxidation with bromine or Pb(OAc)4 and... 

The synthesis of pyrazolines and pyrazoles of the [CCNN + C] type with the creation of two bonds, N(2)-C(3) + C(3)-C(4) (or N(l)-C(5) + C(5)-C(4)), has been studied by several groups. Beam and coworkers have published a series of papers on the synthetic utility of lithiated hydrazones. Thus, the methylhydrazone of acetophenone (598) is converted by butyllithium into the dianion (599), which in turn reacts with methyl benzoate to afford the pyrazole (600) (76SC5). In earlier publications Beam et al. have used aldehydes and acyl chlorides to obtain pyrazolines and pyrazoles by the same method. 

A2-Pyrazolines are converted into pyrazoles by oxidation with bromine or Pb(OAc)4 and they can also be dehydrogenated with sulfur. 3,5-Diphenylpyrazoline (419) on heating with platinum disproportionates to the pyrazole (420) and the pyrazolidine (421) (66AHC(6)347). 

In all these cases hydrazones are formed first and then, presumably, substituted pyrazolines which aromatize under the conditions of the reaction.349 Certainly acylhydrazines give hydrazones with such ketones,81,278,281,328 and certain substituted pyrazolines, particularly halogenopyrazolines, are easily converted into pyrazoles (see accompanying tabulation). Pyrazoles may be synthesized from a,/9-disubsti-tuted carbonyl compounds and the corresponding halides, from which the substituents may be cleaved. 

Several aromatization methods have been published for the conversion of pyrazolines 226 into pyrazoles 227 and conditions are presented in Table 6. 

Padwa <88JOC2232> has described the aromatization of 4-methylene-A -pyrazoline (158) into pyrazole (159) using a trace of acid or base and into pyrazole (160) on exposure to light. 

Gas-phase thermolysis of 4-methylene-A -pyrazolines <84CHEC-I(5)167> continues to arouse interest <90CBl 161 >. A novel chelotropic process has been described by which pyrazolines (168) (prepared by 1,3-dipolar cycloaddition of diphenylnitrilimine over (167)) are transformed into pyrazoles (169)... 

Results of a theoretical study of the mechanism of Br2 oxidation of IH-pyrazolines to pyrazoles suggest that a bromo substituted 2- or 1-pyrazoline is involved in the reaction. Br2 and SbCls oxidize bis(4-t-butylphenyl)nitroxyl (A) to the corresponding oxoammonium salts. The tribromide salt on heating is converted into a mixture of bromodiphenylamines which is also formed from A as a result of three-electron reductive bromination. ... 

The photorearrangement of pyrazoles to imidazoles is probably analogous, proceeding via iminoylazirines (82AHC(30)239) indazoles similarly rearrange to benzimidazoles (67HCA2244). 3-Pyrazolin-5-ones (56) are photochemically converted into imidazolones (57) and open-chain products (58) (70AHC(ll)l). The 1,2- and 1,4-disubstituted imidazoles are interconverted photochemically. 

A-Oxidation with peracids (Section 4.04.2.1.3) and the transformation of pyrazoles into 4,4-dihalogeno-2-pyrazolin-5-ones (Section 4.04.2.1.4(v)) have already been discussed. Transformation of non-aromatic 2-pyrazolin-5-ones into the 4-oxo derivatives will be examined in Section 4.04.2.2.l(ii). 

A -Pyrazolines such as (410) are oxidized by iodine, mercury(II) acetate and trityl chloride to pyrazolium salts (411), and compound (410) even reduces silver nitrate to Ag° (69JOU1480). Electrochemical oxidation of l,3,5-triaryl-2-pyrazolines has been studied in detail (74BSF768, 79CHE115). They Undergo oxidative dimerization and subsequent transformation into the pyrazole derivative (412). 

Nitrilimines (621) are another class of 1,3-dipoles which provide a useful entry into the pyrazole ring. They are often generated by cycloreversion (79AG(E)72l) of tetrazoles, triazolopyridines and oxadiazolones (79JOC2957) (Scheme 55). Pyrazolines of known stereochemistry, pyrazoles and indazoles (Section 4.04.3.1.1(iii)) have all been prepared from nitrilimines. 

Extension of the 1,3-DC approach to the synthesis of novel pyrazoline-fused chlorin 78 by the reaction of P-nitro-meso-tetraphenylporphyrin le with diazomethane has also been explored by Cavaleiro and co-workers (Scheme 27) <02S 1155>. The resulting chlorin 78 could be further converted into the pyrazole-fused porphyrin 79 by treatment with DBU or into the methanochlorin 80 by refluxing in toluene. 

Compounds of this type with an electron-withdrawing substituent at C-a can be easily prepared by condensation of 2-(benzotriazol-l-yl)acetophenone 869 with aldehydes. Exclusively (E) isomers of a,(l-unsaturated ketones 870 are formed. Treatment with hydrazines converts derivatives 870 into pyrazolines 871. Elimination of benzotriazole from 871 in the presence of mild bases furnishes pyrazoles 872. When in these reactions hydroxylamine is used instead of hydrazines, the corresponding isoxazoles are obtained (Scheme 141) <2001JOC6787>. 

The carbon-carbon double bond of an unsaturated AA reacts with 1,3-dipoles to give derivatives of pyrazole or isoxazole. When methanol is used as a solvent, the 1-pyrazolines primarily formed are tautomerized into 2-pyrazolines, which may eliminate benzamide or acetamide to give aromatic pyrazoles (Scheme 19) (88JHC851). Aromatization may also be affected with BF3 Et20. The cycloadditions are stereospecific (85JOC3167). In a... 

The use of 3 also allows for [3 + 2] cycloaddition with enaminoketones (38) (Scheme 8.3). When the morpholine-derived enaminoketon 6 was used, a mixture of A -pyrazoline 7 and pyrazole 8 was obtained. Complete transformation of 7 into 8 was achieved by treatment with water. In the case of the pyrrohdine-derived enaminoketone 9, pyrazole 11 and diazabicycloheptadiene 10 are formed competitively. In the formation of the latter compound, reaction of a second equivalent of 3 with the carbonyl group of 9 is involved. Reaction of uracil as... 

Many N-unsubstituted pyrazoles can be obtained from A-allyl-TV-nitrosamides (90H(30)789), e.g. (56) — (57). Reactions of l-azido-3-chloropropane with Grignard reagents afford intermediates (58) that cyclize into azimines of A -pyrazolines (59) (92TL4683). 

The 3 + 2-cycloaddition of commercially available Me3SiCHN2 with camphor sultam-derived dipolarophiles produces 3-trimethylsilyl-substitutcd-A1 -pyrazolincs which on acid treatment convert into optically active A2-pyrazolines.60 The nucleophilic addition of ethyl diazoacetate with /V-cthoxycarbonyl-/V-(2,2,2-trichlorocthylidcne)a-mine produces a new diazo intermediate (35), which by 1,3-dipolar cycloaddition followed by a sigmatropic rearrangement of the cycloadduct (36) furnishes a substituted pyrazole (37) (Scheme 13).61. 

Diazomethane adds to ethene to form A -pyrazoline (A in Figure 15.36). Its addition to acetylene first leads to the formation of the nonaromatic 3-//-pyrazole (B in Figure 15.36), which subsequently is converted into the aromatic l-//-pyrazole (C) by way of a fast 1,5-hydrogen... 

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