Pyrazoles, sydnone cycloadditions

Photolysis of the triazepine products produces 2,2-dimethylpropanenitrile and the corresponding pyrazole in quantitative yield <1997BSF927>. Reaction of sydnone 89 with fulvene 91 proceeds by [ji4s + jt6s]-cycloaddition followed by spontaneous loss of carbon dioxide and a molecule of dimethylamine or acetic acid from the pseudo-azulene , cyclopentaMpyridazine 92 (Equation 9) <1996CC1011, 1997T9921>. 

Isosydnones (146) react with alkynes to give pyrazoles (150). For example, 4,5-diphenylisosydnone (146, R = R = Ph) and ethyl phenyl propiolate gives 4-ethoxycarbonyl-l,3,5-triphenylpyrazole (150, R = R = R = Ph, R = CO Et) identical with the product from 4,5-diphenylsydnone (1, R = R = Ph). The rate of 1,3-cycloaddition for isosydnones (146) is relatively slow in comparison with sydnones (1).2o, 04 number of other cycloaddition reactions of isosydnones with alkenes, alkynes, and carbonyl compounds have been reported. ... 

Dumitrascu and co-workers (52) transformed 4-halosydnones into 5-halopyr-azoles by cycloaddition with DMAD and methyl propiolate followed by retro-Diels-Alder loss of CO2. Turnbull and co-workers (194) reported that the cycloadditions of 3-phenylsydnone with DMAD and diethyl acetylenedicarboxylate to form pyrazoles can be achieved in supercritical carbon dioxide. Nan ya et al. (195) studied this sydnone in its reaction with 2-methylbenzoquinone to afford the expected isomeric indazole-4,7-diones. Interestingly, Sasaki et al. (196) found that 3-phenylsydnone effects the conversion of l,4-dihydronaphthalene-l,4-imines to isoindoles, presumably by consecutive loss of carbon dioxide and A-phenylpyrazole from the primary cycloadduct. Ranganathan et al. (197-199) studied dipolar cycloadditions with the sydnone 298 derived from A-nitrosoproline (Scheme 10.43). Both acetylenic and olefinic dipolarophiles react with 298. In... 

Meier and Heimgartner (208) achieved an intramolecular sydnone-alkene cycloaddition to give adduct 306 in 50% yield. Other tether lengths did not so react, but photolysis of these other sydnones led to novel fused pyrazoles via decarboxylation and subsequent cycloadditions from the subsequent nitrile-imines. 

Ollis, and Ramsden520 treated 99, 100 and 101 with neat EPP and obtained the pyrazole 103 and the phenylpropiolic ester dimer 104, but no 105. A comparative study was carried out with phenylacetylene. When 100 was heated with DM AD in dioxane, 25% of the pyrazole 106 was obtained. These authors have concluded that the cycloaddition of alkynes to isosydnones is analogous to that of sydnones but the reactions are slower and the cycloadducts are obtained in lower yields. 

Nitrile imine cycloadditions provide access to pyrazolines and pyrazoles. Intramolecular cyclizations to alkynes were first reported in 1974.88 Perhaps the most useful method for generation of nitrile imines involves 1,3-elimination of hydrogen chloride from an a-chlorohydrazone. Tetrazoles and sydnones are also precursors to nitrile imines. 

Sydnones can be regarded as cyclic azomethine imines and as such they undergo thermal cycloaddition reactions with a range of dipolarophiles. Thus, reaction with phenyl isocyanate converts 401 into 1,2,4-triazole 402. On photolysis, 3,4-diarylsydnones lose carbon dioxide and give nitrile imines, which can also be intercepted by dipolarophiles. Thermal reactions with acetylenic dipolarophiles lead to the formation of pyrazoles (Scheme 88) however, these reactions are rarely completely regioselective with unsymmetrical alkynes, e.g., <2000BKC761, 2000TL1687>. 

Phenylsydnone is the prototype of that class of mesoionic compounds called sydnones. On acidic hydrolysis it produces phenylhydrazine, whereas basic hydrolysis regenerates N-nitroso-N-phenylglycine. This sydnone undergoes a variety of electrophilic substitutions,3,4 8-19 including mercuration n-13,16 and formylation,19 with an ease comparable to thiophene, and a number of 1,3-dipolar cycloadditions with numerous alkenes,18 18 alkynes,17 and quinones8 to form, with loss of carbon dioxide, a variety of pyrazole derivatives. 

Sydnones are crystalline compounds, stable in acid solution and ring-opened in alkaline solution. They react as a 1,3-dipole in cycloadditions, e.g. with acetylenedicarboxylate, to give the pyrazole derivative 2 ... 

The answer to this dilemma was provided by Huisgen et al. (1962 a, 1962 b) by the cycloaddition reaction of C-methyl-A-phenylsydnone (6.10) with styrene, which yields, via the bicyclic intermediate 6.11 and elimination of CO2, 4,5-dihydro-5-methyl-l,3-diphenyl-li/-pyrazole (6.12). As mentioned briefly in Section 6.2 (Table 6-1, footnote a), sydnones are cyclic azomethine imines. As Huisgen (1968) demonstrated later, sydnone and azomethine imine cycloadditions are kinetically very similar with respect to solvent effects and in the sequence of reactivity with a series of 11 dipolarophiles. 

Sydnones undergo smooth cycloaddition with acetylenes to give pyrazoles in high yield. The reaction involves a 1,3-dipolar cycloaddition of the sydnones. 

A-Unsubstituted pyrazoles have been obtained via resin-bound sydnones (Scheme 11.17). ° Sydnones are mesoionic compounds that react as azomethine im-ine-type 1,3-dipoles in 1,3-dipolar cycloaddition. The cycloaddition of sydnones with electron-withdrawing alkynes gave pyrazoles. 2-Methoxy-substituted resin acted as a... 

Sydnones are stable in acid and ring-opened in alkaline medium. Synthetically valuable is their reactivity as 1,3-dipoles in cycloadditions with activated alkynes for instance, acetylene dicarboxylate affords the pyrazole derivative 5 (after cycloreversion of the primary cycloadduct 4 by elimination of CO2) ... 

Thieno[3,4-c]pyrazoles.—Cycloaddition of dibenzoylacetylene to N-phenyl-sydnone (78) afforded the pyrazole (79), which, when thionated (P2Ss Pyridine), gave in high yield the stable triphenylthieno[3,4-c]pyrazole (80), the first reported member of this class." Compound (80) enters into cycloaddition reactions, notably with dibenzoylacetylene, with loss of sulphur, giving the diketone (81). Thionation of compound (81) gives, in high yield, the stable blue-black quadricovalent species (82). The mass spectra of... 

Dipolar cycloaddition with ring opening Pyrazoles and Zl -pyrazolines from sydnones... 

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