Dimethyl 3,5-pyrazole dicarboxylate

Attempted esterification of the 7-azabicyclo[2.2.1]heptadiene-2,3-dicarboxylic acids (5) and (10) with diazomethane in mild conditions led to decomposition liberating the corresponding pjnroles. Dimethyl acetylenedicarboxylate, the other decomposition product, reacted further with an excess of diazomethane to give dimethyl pyrazole-4,5-dicarboxylate and an A-methyl derivative. ... 

Pyrazole (see also Refs. 117-119) and its 3,5-dimethyl and 3,4,5-trimethyl derivatives combined with half a mole of dimethyl acetylene-dicarboxylate give products of similar ultraviolet absorption spectra to the parent pyrazoles. These products (e.g., 100) do not possess the strong broad absorption at ca. 3310 cm-1 characteristic of the bonded N—H group that is present in the parent pyrazoles and are formed by two successive Michael addition reactions. In the case of 3,5-dimethyl-pyrazole, the initial fumarate (99) has been isolated it showed an absorption spectrum of a more conjugated type than those of the dipyra-zolylsuccinates 100. The addition of MP to pyrazole is mentioned in Section IV,B,2. 

Both azomethine imines 44 and 45 react with dipolarophiles, e.g., dimethyl acetylene-dicarboxylate (DMAD). The 4,5-dihydro-lH-pyrazol-2-ium-l-ide 45 furnishes the expected bridged [3-1-2] cycloadduct, dimethyl 6,6-dimethyl-5-oxo-7-phenyl-l,7-diazabicyclo[2.2.1]-hept-2-ene-2,3-dicar-boxylate (46, 66%) (Scheme 10) (97TH). 

Addition of dimethyl acetylene dicarboxylate to the C-glycosyldiazo-methanes 279 formed the pyrazol-3-yl C-nucleoside 280. Annulation of a pyridazine ring to 280 was accomplished by cyclocondensation of their ester groups with hydrazine hydrate to produce 281 [70JCS(CC)313,70TL4611 72CCC2798] (Scheme 86). 

A common dipolarophile for the Pechmann pyrazole synthesis is dimethyl acetylene dicarboxylate (DMAD, 41), a highly electron-deficient alkyne. Spring and co-workers used the 1,3-dipolar cycloaddition between DMAD and a fluorous-tagged diazoacetate (40) as part of studies aimed at production of structurally diverse scaffolds. As expected, the reaction proceeded efficiently to produce 42 in high yield. 

Although unintended, it was found that the a-diazobenzamide 49 readily participates in the Pechmann pyrazole synthesis with dimethyl acetylene dicarboxylate (41). While studying the reactivity of carbenes generated at the benzylic position of 49, the use of Cu(acac)2 did not effectively catalyze the decomposition of the diazo functionality, thereby allowing the Pechmann pyrazole synthesis to proceed efficiently upon treatment with dimethyl acetylene dicarboxylate. 

Pyrazole-3,4-dicarboxylic acid, 1-phenyl-dimethyl ester synthesis, 5, 150 Pyrazole-3,5-dione, 1-phenyl-alkylation, 5, 230 synthesis, 5, 290... 

Diazopropyne reacts similarly with a monosubstituted acetylene to form 3(5)-alkynylpyrazoles (68LA113). Thus, the reaction of diazopropyne with acetylene-carboxylic acid methyl ether results in 5-ethynyl-l//-pyrazole-3-carboxylic acid methyl ether in 48 h in 62% yield. 5-Ethynyl-l//-pyrazole-3,4-dicarboxylic acid dimethyl ester was prepared by reaction of diazopropyne with acetylenedicar-boxylic acid methyl ether (Scheme 10). 

The reaction of aroylhydrazines with DMAD gives rise to the hydrazones of oxaloacetic ester, which undergo thermal transformation to the corresponding diaroylhydrazines. b. Hydrazones. Ethyl l,3,5-triphenylpyrazole-4-carboxylate has been reported to be formed in the reaction of benzaldehyde phenylhydrazone with ethyl phenylpropiolate. In a detailed investigation, George and co-workers have shown that aldehyde phenylhydrazones react with DMAD, yielding a mixture of pyrazoles and pyrazolines. Thus, in the reaction of benzaldehyde phenylhydrazone with DMAD, products such as dimethyl l,3-diphenylpyrazoline-4,5-dicarboxylate (129), dimethyl... 

The following procedure represents a convenient preparative method leading to the synthesis of copper(I) pyrazolates, namely, [Cu(pz)]n (Hpz = IH-pyrazole), [Cu(dmpz)]3 (Hdmpz = 3,5-dimethyl-lH-pyrazole), [Cu(dcmpz)] (Hdcmpz = dimethyl- lf/-pyrazole-3,5-dicarboxylate), [Cu(dctpz)]n (Hdctpz = di-ferf-butyl-1 f/-pyrazole-3,5-dicarboxylate), and [Cu(dppz)]4 (Hdppz = 3,5-diphenyl-lH-pyrazole). In all cases, high yields ( >90%) of the pure products are obtained. 

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... 

The same carbene can also be generated by thermolysis of 2,2-diphenyl-5-diphenyl-methylene-2,5-dihydro-l,3,4-oxadiazole. When the reaction was carried out in the presence of either dimethyl ( )-but-2-enedioate or dimethyl (Z)-but-2-enedioate one cyclopropane, dimethyl 3,3-diphenylcyclopropane-tranj-l,2-dicarboxylate (1), was formed, most likely via a 4,5-dihydro-3//-pyrazole intermediate. ... 

The most frequently encountered examples of the first type are the addition of diazoalkanes to 3//-pyrazoles (or addition of two moles of diazoalkane to an acetylene). For example, in the reaction of 2-diazopropane with dimethyl butynedioate, addition of one mole of 2-diazo-propane generated dimethyl 3,3-dimethyl-3/f-pyrazole-4,5-dicarboxylate (1), and addition of a second mole of 2-diazopropane gave dimethyl 4,4,8,8-tetramethyl-2,3,6,7-tetraazabicy-clo[3.3.0]octa-2,6-diene-l,5-dicarboxylate (2) which on photolysis (not thermolysis or sensitized photolysis ) gave a 41% yield of dimethyl 2,2,4,4-tetramethylbicyclo[1.1.0]bu-tane-l,3-dicarboxylate (3). Similar bis-additions are known for dicyano-, diacetyl-, and diben-zoylacetylene, but only the dicyano system gives the bicyclobutane on thermal deazetization. ... 

In the case of 3-aryl-substituted 3//-pyrazoles [e.g. dimethyl 3,3-diphenyl-3//-pyrazole-4,5-dicarboxylate (7)] indene formation often competes with formation of the cycloprop-... 

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