Pyrazoles, reaction with dimethyl acetylenedicarboxylate

The diazepines 13 react with dimethyl acetylenedicarboxylate to yield mixtures of the pyrazole 19 and the benzene derivatives 18. The reaction proceeds by cycloaddition to yield 14, followed by valence isomerization to the 1,2-diazonines 15, a further valence isomerization to 16, a Second cycloaddition to give 17 and, finally, fragmentation."... 

Triazole-fused pyridopyrimidines can be prepared by reaction of aldehydes with the substituted pyridopyrimidine 309 (Equation 106). The pyrazole-fused derivative 311 can be prepared by the reaction of the sulfonimine 310 with dimethyl acetylenedicarboxylate (DMAD) (Equation 107) <1998H(47)871>. 

Triphenylthieno[3,4-c]pyrazole (414) can be presented as a hybrid of dipolar-contributing azomethine imine ylide (415) or thiocarbonyl ylide canonical forms 416. Upon reacting this ylide with electron-poor olefins, it behaved like a thiocarbonyl ylide. Thus, with maleimide, a mixture of endo (419) and exo adducts (420) were obtained (74JA4276), which resulted from addition at the thiocarbonyl moiety. The reaction of 414 with dimethyl acetylenedicarboxylate gives the desulfurized indazole 418 in addition to the adduct 417 (Scheme 41). 

Heath and Rees corrected the earlier conclusions of Potts et al. (66JOC265) and Sai et al. [81IJC(B)10] who had reacted 1,2,4-triazolo[4,3-a]pyridine with dimethyl acetylenedicarboxylate in boiling toluene and benzene. The latter believed that 3-substituted triazolopyridines 209 and 210 were the products. Heath and Rees repeated the experiments in refluxing benzene and in refluxing toluene both in the presence and absence of 5% palladium-on-charcoal, and showed that under all sets of conditions 3-cyano-4-oxo-4f/-pyrido[l,2-a]pyrimidine-2-carboxylate 212, 5-(2-pyridyl)pyrazole-3,4-dicarboxylate 213, and an adduct 211 were isolated from the complex reaction mixtures in 20%, 20%, and 1% yields, respectively (82CC1280). When the reaction was carried out in methanol, only 3-cyano-4-oxo-4//-pyrido[ 1,2-a]pyrimidine-2-carboxylate 212 was obtained... 

Aldehyde azines 87 react with two equivalents of dimethyl acetylenedicarboxylate in a 1,3-dipolar reaction to give iV-allyl pyrazoles 88 in good yields (Scheme 48) <2002CJC1293>. 1,3-Dipolar cycloaddition of polymer-supported -silylnitrosoamides 89 with dimethyl acetylenedicarboxylate gives pyrazole derivatives 90 without the necessity for a separate cleavage operation (Scheme 49) <2000TL691>. 

Pyrazolo[l,2- ]pyrazole systems 166 can be obtained by the reaction of hydrazine with acrylic esters (Scheme 99) <2001J(P2)243, CHEC-III(12.10.12.1)406>. The betaines 167 reacts with dimethyl acetylenedicarboxylate to give products 168 which easily undergo thermal fragmentation to 169 followed by another cycloaddition to form 170 (Scheme 100) <1981JA7743>. Criss-cross addition of azines, e.g. 171, also involves two successive 1,3-dipolar cycloadditions to give pyrazolo[l,2-. 

The reaction of A -substituted pyrazoles with alkynic esters in the presence of fluoroboric acid yields Michael addition salts and not Diels-Alder adducts as was previously reported in the literature <83T2193>. Addition of 3,5-dimethyl-pyrazole to DMAD (dimethyl acetylenedicarboxylate) is highly stereoselective in aprotic solvents, yielding mono- and bis-adducts <85JCS(P2)427>. 

The formation of pyridine IV-imines by an add-catalyzed rearrangement of some diazepinones and related compounds has been extensively investigated by Moore and co-workers (Eq. 9).115 The formation of pyridine N-imines from l/f-l,2-diazepines is also known (Eq. 10).68 69,116,117 Diels-Alder reactions of pyrazoles with dimethyl acetylenedicarboxylate, in the presence of BF3, have been reported to give IV-aminopyridinium salts (Eq. II).118 l,4-Dihydropyrido[l,2-a]-as-triazinium salts and their pyrimido derivatives undergo ring contraction in boiling aqueous acid, yielding 1-aminoimidazo[l,2-a]pyridinium and pyrimidinium salts, respectively (Eq. 

Other 3-sulfolene derivatives have led to the synthesis of a variety of molecules. Thiazole-fused 3-sulfolene (131) is a synthetic equivalent to o-dimethylene thiazole <92TL420l>. Similarly, (132) is the precursor to the pyrazole analogues of o-xylylene <91TL7609>. Reaction of (133) with dimethyl acetylenedicarboxylate gives not only [4 4- 2] reaction of the 1,3-butadiene but also [4 - - 2] reaction of the pyrrole to produce novel 7-azanorbornene derivatives <92CC549,92CClioo>. Compound (127) is a ready precursor of 2,3-(ethylenedisulfonyl)-l,3-butadiene which reacts with a number of electron-... 

Pyrazole and its 3,5-dimethyl and 3,4,5-trimethyl derivatives combined with two moles of dimethyl acetylenedicarboxylate giving products of similar ultraviolet absorption spectra to the parent pyrazoles. These products [e.g., (69)] do not possess the strong broad absorption at ca. 3.20 /u, characteristic of the bonded N—H group which is present in the parent pyrazoles and are formed by two successive Michael addition reactions. In the case of 3,5-dimethylpyra-zole, the initial fumarate (68) has been isolated and possessed a more conjugated type of absorption spectrum to those of the dipyrazolyl-... 

Diazo compounds have also been used as precursors in the preparation of pyrazoles and indazoles. The copper-promoted cycloaddition reaction of lithium acetylides 18 with diazocarbonyl compounds 19 provided a direct and efficient approach to the synthesis of pyrazoles 20 <07AG(I)3242>. A facile, efficient, and general method for the synthesis of 1-arylated indazoles 22 and A-unsubstituted indazoles 23 by the 1,3-dipolar cycloaddition of benzynes, generated from 21, with diazomethane derivatives has been reported <07AG(I)3323>. Reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or dimethyl acetylenedicarboxylate <07S3371>. 

Much more recently, and with the advantage of sophisticated NMR techniques that have become available since the early 1970s, it has been shown that the spiro-3i/-pyrazole structure for 29a is incorrect. It is known that the outcome of diazocyclopentadiene addition to dimethyl acetylenedicarboxylate is dependent upon the five-membered ring substituents In the case at hand, tetraphenyldiazocyclopentadiene adds to the alkyne to give 29a as a labile product that rearranges under the reaction conditions to the 3H-indazole 30a (Scheme 3) 1,3-di-r-butyldiazocyclopentadiene behaves similarly l Thus in the formation of 31a at least, the spiropyrazole 29a is not the substrate and one must question the nature of the educt (29 versus 30) employed in cycloproparene synthesis by the spiro-3i/-pyrazole route. Nonetheless, there can be little doubt that spirocycle 29d is the substrate employed by Mataka and coworkers because, upon thermolysis, the corresponding indazole 30d was isolated. What must be noted here is that the thermal reaction did not provide any of the cyclopropa[/]phenanthrene 31d, but neither did independent photolysis of the isolable indazole 30d in benzene solution a 9,10-disubstituted phenanthrene is formed from diradical interaction with the solvent (equation 7). 

Butler has described that the treatment of l-ethoxycarbonylmethyl-2,3,4,5-tetraarylpyrazolium salts with base in the presence of DM AD (dimethyl acetylenedicarboxylate) affords l-(2 -amino-vinylpyrroles) and pyrrolo[l,2-a] pyrazines <93JCS(Pl)883> a mechanism has been proposed for this unexpected behavior. Reaction of l,3,4,5-tetraaryl-2-methylpyrazolium salts (141) with ethoxide base produces the fragmentation of the pyrazole ring with formation of 1,2-bisimines (142) the mechanism is represented in Scheme 2 <94JCR(S)12>. In both cases the structures of the resulting products were supported by x-ray determinations. 

In the historical introduction to this volume (Sect. 1.1), it was mentioned that Buchner studied reactions of ethyl diazoacetate with ethenedicarboxylic acid in 1888. In the following year, he discovered pyrazole, obtained from methyl diazoacetate and dimethyl acetylenedicarboxylate followed by thermolysis. Finally, in 1893 Buchner et al. synthesized 4,5-dihydro-l//-pyrazole (2-pyrazoline) from methyl diazoacetate and methyl acrylate. Von Pechmann, the discoverer of diazomethane, performed analogous reactions of fumarates and maleates (von Pechmann, 1894, von Pechmann and Burkard, 1890). ... 

PROBLEM 23.39 Reaction of A -phenylalanine (1) with nitrous acid affords A -nitroso amino acid (2), which on treatment with acetic anhydride yields sydnone (3). Sydnones belong to a class of compounds known as mesoionic compounds. These compounds cannot be satisfactorily represented by Lewis structures not involving charge separation. The name sydnone derives from the University of Sydney where the first examples were prepared in 1935. Reaction of 3 and dimethyl acetylenedicarboxylate (DMAD) gives pyrazole (4). Propose mechanisms for the formations of 2, 3, and 4. Hint. For the formation of 4, it may be helpful to consider the other possible Lewis structures for sydnone 3. 

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