Pyrazoles, reaction with dimethyl

The imonium salt (199), obtained from ynamines and phosgeneimonium chloVide, underwent ready reaction with monosubstituted hydrazines to give the 3,5-bis(dimethyl-amino)pyrazole (200) (68T4217, 69T3453). Similarly, the adduct (201), resulting from the addition of phosgene to ynamines, likewise reacted with sym-disubstituted hydrazines to give pyrazoles (202). With hydroxylamine derivatives the isoxazolinone (203) was obtained. 

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."... 

Heteroaromatic diazonium salts can also be used for Gomberg-Bachmann aryla-tions. Fukata et al. (1973) refluxed 3,5-dimethyl-4-diazopyrazole (10.27) in benzene and obtained 3,5-dimethyl-4-phenylpyrazole (10.28, 36%), biphenyl (10.29, 17%), 3,5-dimethylpyrazole (10.30, 12%), and pyrazolo[4,3-c]pyrazole (10.31, 15%). In nitrobenzene the three isomeric 3,5-dimethyl-4-(nitrophenyl)-pyrazoles were formed in the ratio o m p = 10 3 3. In the opinion of Fukata et al. this ratio and the course of the reaction indicate a homolytic process. The present author thinks that the data do not exclude a competitive heterolytic reaction with the pyrazolyl cation, because equal amounts of substitution of nitrobenzene in the 3- and 4-positions are not typical for a homolytic aromatic substitution. 

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>. 

Reaction of PTAD with a-angelica lactone gives the pyrazolotriazole 97 via an acyl ene reaction,152 and reaction with 4,4-diethyl-3,5-dimethyl-4//-pyrazole 2-oxide gives 98 after heating.153 A mesoionic bicyclic system 99 is proposed as a product from the reaction of DEAZD with triethylborane.154... 

The intermediate acylamidine 244 functions as the three-atom component in reaction with hydroxylamine to give the [l,2,4-oxadiazol-5-yl]pyrazole 245, where the intermediate acylamidine 244 was obtained in good yield from reaction of the corresponding amide 243 with dimethylacetamide-dimethyl acetal (Scheme 37) <1999JME2218>. 

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). 

Reaction of the quaternized salts of 4-ethoxycarbonyl-3,5-dimethyl-f-phenylpyttolo(furo or thieno)[2,3-c]pyrazole 34 with the iodomethane quaternary salts of pyridine, quinoline, and isoquinoline in ethanol with catalytic piperidine gave 3-[4(f)]-monomethine cyanine dyes (e.g., 35). Additionally, 3-[2(4)]-trimethine cyanine dyes and 4-[2(4)]-di-3[2(4)]-tri-mixed methine cyanine dyes (e.g., 36 and 37, respectively) were similarly prepared from the intermediates derived by reaction of 34 with triethyl orthoformate in the presence of piperidine (Scheme 8) <2002CCS106f>. 

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... 

Substituted imidazole 1-oxides 263 upon treatment with dimethyl or diethyl sulfate furnish l-alkoxy-3-subtituted imidazolium salts 283 that were converted to the tetrafluoroborate 283 (A- = BF4 ) or hexafluorophos-phates 283 (A = PF6-) by treatment with sodium tetrafluoroborate or hexa-fluorophosphate (2007ZN(A)295). The tetrafluoroborates 283 (A = BF4 ) reacted with cyanide ion to give 2-cyanoimidazoles 285 (1975JCS(P1)275). The reaction probably follows a mechanism similar to that suggested to be operative in the pyrazole series encompassing O-alkylation succeeded by nucleophilic addition and elimination of methanol (Scheme 85). 

Dichloroacetamido)-l-methyl-5-nitroimidazole undergoes a 1,3-dipolar cycloaddition reaction with diazomethane to give (dichloroacetimino)tetrahydroimidazo[4,5-c]pyrazoles in about 10% each (Scheme 5). The failure to observe cycloaddition with l,2-dimethyl-5-nitroimidazole underlines the role of the N- methylated imidazole intermediate (184), a typical non-aromatic a, j6-unsaturated nitro compound acting as a dipolarophile (80TL4757). 

Dimethylpyrazole has been prepared from acetylacetone and hydrazine hydrate in ethanol3 or hydrazine sulfate in aqueous alkali.4 6 The latter method is preferred, because the reaction with hydrazine hydrate is sometimes violent.3 4 3,5-Dimethyl-pyrazole has also been prepared by hydrolysis and decarboxylation of the 1-carbamido- or 1-carboxamidine derivatives, obtained by reaction of semicarbazide 7 or aminoguanidine 8 with acetylacetone. 

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 chemical properties of 1,4-dinitropyrazole [654] and l,4-dimethyl-3,5-dini-tropyrazole obtained by the nitration of 1,4-dimethylpyrazole [655], nitrotriazoles [656-663], and other nitroazoles [662, 664-666] have been studied. 1,4-Dinitro-pyrazole undergoes ring transformation reactions with primary amines, hydrazines, hydroxylamine, and amidines [654], Acid hydrolysis of dinitropyrazole leads to (l-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde, and the reaction with sodium nitrite in hydrochloric acid furnishes 2-hydroxymino-2-(l-methyl-3,5-dinitropyra-zol-4-yl)acetaldehyde [655],... 

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>. 

It should be noted that the reaction of K[BHJ with pyrazole cannot be stopped at the K[H3B(pz)] stage from an incomplete reaction only K[BHJ and K[H2B(pz)2] could be isolated. It has been possible, though, to synthesize the ion [H3B pz-3,5-(CHj) ] by reaction of the borane adduct of 3,5-dimethylpyrazole with sodium hydride, and from it by a carefully controlled reaction with pyrazole in N,N-dimethyl-acetamide to prepare the first example of an asymmetric poly(l-pyrazolyl)borate ligand, i.e., Na[H2B(pz) pz-3,5-(CH3)2 ]... 

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