Pyrazoles rearrangement

Pyrazoles rearrange under photochemical conditions to imidazoles with yields as high as 30%. Frequently, however, mixtures of isomers are formed, decreasing the synthetic utility of the approach. Thus, photolysis of 1,5-dimethylpyrazole gives a mixture of 1,2-, 1,4- and 1,5-dimethylimidazoles [7] 3-cyanopyrazole gives 2- (25%) and 4-cyanoimidazoles (11%) [8] ... 

On exposure to light, pyrazoles rearrange to imidazoles and undergo ring-opening to form 3-aminopro-penenitriles, e.g. 1-methylpyrazole 1 ... 

The pyrazole ring is resistant to oxidation and reduction. Only ozonolysis, electrolytic oxidations, or strong base can cause ring fission. On photolysis, pyrazoles undergo an unusual rearrangement to yield imidazoles via cleavage of the N —N2 bond, followed by cyclization of the radical iatermediate to azirine (27). 

From Other Heteroeyeles by Rearrangement. Although there are numerous examples of pyrazole syntheses from other monocychc heterocycles by chemical, thermal, or photochemical means, such examples ate only of limited practical value on account of high cost. Reaction of diaziridinone (68) with the sodium salt of malondinitrile yields the di-/-butylaminopyrazolinone (69) (eq. 17) (45). 

Pyridazinones may undergo ring contraction to pyrroles, pyrazoles and indoles, the process being induced either by an acid or base. The structure of the final product is strongly dependent on the reaction conditions. For example, 4,5-dichloro-l-phenylpyridazin-6(lFT)-one rearranges thermally to 4-chloro-l-phenylpyrazole-5-carboxylic acid (12S), while in aqueous base the corresponding 4-hydroxy acid (126) is formed (Scheme 40). 

Hydroxy-6-methyl-2-phenylpyridazin-3(2Fr)-one and 4-hydroxy-5-nitropyridazin-3(2FT)-one rearrange in acidic medium to 3-methyl-l-phenylpyrazole-5-carboxylic acid and 4-nitropyrazole-5-carboxylic acid. 4-Hydroxypyridazin-3(2FT)-ones with a hydroxy group or other group at positions 5 or 6, which is easily replaced in alkaline medium, are transformed into 5-(or 3-)pyrazolones with hot alkali. An interesting example is ring contraction of 5-chloro-4-(methylthio)-l-phenylpyridazin-6(lFT)-one which gives, besides pyrazole derivative (127), 4-hydroxy-5-methylthio-l-phenylpyridazin-6(lFf)-one (128 Scheme 41). 

There are some recent examples of this type of synthesis of pyridazines, but this approach is more valuable for cinnolines. Alkyl and aryl ketazines can be transformed with lithium diisopropylamide into their dianions, which rearrange to tetrahydropyridazines, pyrroles or pyrazoles, depending on the nature of the ketazlne. It is postulated that the reaction course is mainly dependent on the electron density on the carbon termini bearing anionic charges (Scheme 65) (78JOC3370). 

Pyridazines are formed from pyrones or their thioxo analogs or from appropriate pyridones. Pyrones or pyridones react with diazonium salts to give the corresponding hydrazones (187) and (188) which are rearranged under the influence of acid or base into pyridazinones as shown in Scheme 107. On the other hand, kojic acid is transformed with hydrazine into a 1,4-dihydropyridazine and a pyrazole derivative. 4H-Pyran-4-thiones... 

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. 

Migrations of C- linked substituents around the ring, on to carbon or nitrogen atoms, are common amongst these compounds. This is the van Alphen-Huttel rearrangement and by it 3H-pyrazoles are converted into 1//-pyrazoles, and 2H-imidazoles are thermally iso-merized into IH-imidazoles. 

A book (B-71MS) and a review by Nishiwaki (74H(2)473) contain much information about the behaviour of pyrazoles under electron impact. The Nishiwaki review covers mainly the hydrogen scramblings and the skeletal rearrangements which occur. One of the first conclusions reached was that pyrazoles, due to their aromatic character, are extremely stable under electron impact (67ZOR1540). In the dissociative ionization of pyrazole itself, the molecular ion contributes about 45% to the total ion current thus, the molecular ion is the most intense ion in the spectrum. 

Table 27 Kinetic Data for Autotrope Rearrangements in Pyrazoles...

The azido/tetrazole rearrangement of pyrazole and indazole derivatives will be discussed in the corresponding section (4.04.2.3.4(v)). 

A new type of rearrangement has been reported for certain l-(o-nitrophenyl)pyrazoles (169), giving cis- and trans-benzotriazole 1-oxides (170 Scheme 12) (73TL891). The reaction was rationalized in terms of an intermediate azo compound (171 formed in turn either from the diradical species (172) or from the intramolecular 1,4-adduct (173). Subsequently... 

A-Halogenated pyrazoles are unstable compounds (Cl>Br>I) that are seldom isolated. 1-Bromopyrazoles resemble NBS and may be important in the process of C-bromination, not because of an A to C rearrangement but by acting as a source of the powerfully electrophilic brominium ion (Section 4.04.2.1.4(v)). 4-Substituted pyrazoles can form... 

The chemical behaviour of the mesoionic pyrazole (459) has been studied by Boyd et al (74JCS(P1)1028). Protonation and alkylation take place on the exocyclic nitrogen atom and a thermal rearrangement of a methyl group is observed when (459) is boiled in benzonitrile for several hours giving (460). 

In addition to (461), Dorn has described the imine (463) isolated from 5-amino-l-methylpyrazole and arenesulfonyl chloride (80CHE1). Upon heating, or in the presence of triethylamine, it undergoes rearrangement to the more stable 5-bis(arylsul-fonamido)pyrazoles (464). 5-Iminopyrazolines (461) react with acyl chlorides at the exocyclic nitrogen atom to afford amidopyrazolium salts (B-76MI40402). 

Methylvinyldiazirine (199) rearranges at room temperature in the course of some days. Formation of the linear isomer is followed by electrocyclic ring closure to give 3-methyl-pyrazole. The linear diazo compound could be trapped by its reaction with acids to form esters, while the starting diazirine (199) is inert towards acids (B-71MI50801). 

Boulton-Katritzky rearrangement, 5, 258 Pyrazol-5-one, 4-arylazo-reactions, 5, 262 Pyrazol-5-one, 4-arylidene-configuration, 5, 208... 

Pyrazolo[3,4-c]pyrazole, tetrahydro-rearrangement, 5, 250 Pyrazolo[4,3-c]pyrazole, tetraaryl-electrophilic substitution, 6, 1035 oxidation, 6, 1034-1035 reduction, 6, 1035 vacuum pyrolysis, 6, 1035 Pyrazolo[ 1,2-n]pyrazole-1,5-diones synthesis, 6, 991 Pyrazolo[ 1,2-n]pyrazoles reactions, 6, 1038 ring opening, 6, 983... 

H,3H- Pyrrolo[l, 2-c]oxazole-l, 3-dione, 5,6,7,8-tetrahydro-IR spectra, 6, 978 [2.2](2,5)Pyrrolophane, N-aryl-rearrangements, 4, 209 Pyrrolophanes natural products, 7, 764 synthesis, 7, 771 Pyrrolophanes, N-aryl-synthesis, 7, 774 (2,4)Pyrrolophanes synthesis, 7, 771 Pyrrolo[3,4-c]pyran-4-ones synthesis, 4, 288 Pyrrolopyrans synthesis, 4, 525, 526 Pyrrolopyrazines synthesis, 4, 526 Pyrrolo[l, 2-a]pyrazines synthesis, 4, 516 Pyrrolo[2,3-6]pyrazines Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolo[3,4-c]pyrazole, 1,3a,6,6a-tetrahydro-structure, 6, 976 synthesis, 6, 1019 Pyrrolopyrazoles synthesis, 5, 164 Pyrrolo[l,2-6]pyrazoles synthesis, 6, 1002, 1006 Pyrrolo[3,4-c]pyrazoles reactions, 6, 1034 synthesis, 6, 989, 1043 Pyrrolo[3,4-c]pyrazolones synthesis, 6, 989 Pyrfolopyridazines synthesis, 4, 517 Pyrrolo[l, 2-6]pyridazines synthesis, 4, 297 6/7-Pyrrolo[2,3-d]pyridazines synthesis, 4, 291 2/f-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291 6/7-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291... 

An unusual 1,4-migration of a trifluoromethyl group was observed when azomethine imines were synthesized from hexafluoroacetone azine and alkoxy-acetylenes The rearrangement, which occurs at temperatures as low as 0 "C, results in the formation of A-(perfluoro-ferf-butyl)pyrazoles [207] (equation 46)... 

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