5-Substituted pyrazol-3 benzene

After a paper devoted to GIAO/B3LYP calculations of 13 monosubstituted benzenes and 21 1-substituted pyrazoles [148] that allowed discussion of some structural problems (such as conformation, tautomerism, and structure of salts) we have continued to use this combination of experimental (in solution and in the solid state, CPMAS NMR) and calculated values as a very useful exploratory technique. For instance, we have used II, 13C, and 15NNMR spectroscopy to study compounds 149-154. In para-disubstituted derivatives 149,151,152,153, in the solid state (no free rotation) the signals of the ortho carbons are split (one is close to N2) and, thanks to the calculated values, they can be assigned [149],... 

The H chemical shifts were assigned in C.I. Disperse Yellow 211,41 in sodium l-(2-,l-(3- and l-(4-trifluoromethylphenylazo)-2-hydroxy-5-benzene-sulfonate,42 in some o,o -dihydroxyazo dyes containing the sulfo group43 and l(4)-substituted pyrazol-5-one azoderivatives 8.44... 

Substituted 3-anilino-l,5-diphenylpyrazoles were oxidized with lead(iv) tetraacetate in benzene or methylene chloride solution <1997M261>. ESR measurements confirmed the formation of aminyl radicals from /irzra-CFIs-substituted pyrazoles. The radical intermediates from unsubstituted pyrazoles were recognized by their transformations to triarylaminium cation radicals. These were generated by consecutive oxidation of the dimeric products the structures of which were proved by NMR spectroscopy and labeling. 

The introduction of a carbonyl carbamate group at position 4 of the pyrazol-3-one ring can be done directly by fusion of appropriately 2-substituted /i-keto ester with a hydrazine (04TJC659) (Scheme 16). The jS-keto ester 67 was synthesized in two steps from ethyl 4,5-dioxo-2-phenyl-4,5-dihydrofuran-3-carboxylate 65 by decarbonylation to ethoxy-carbonylbenzoylketene intermediate 66 in refluxing benzene and then nucleophilic addition by methyl carbamate. Ethyl 2-benzoyl-3-[(methoxy-carbonyl)amino]-3-oxopropanoate 67 with diphenylhydrazine on heating in benzene gave 4-substituted pyrazol-3-one 68 in 44% yield. 

Annular tautomerism (e.g. 133 134) involves the movement of a proton between two annular nitrogen atoms. For unsubstituted imidazole (133 R = H) and pyrazole (135 R = H) the two tautomers are identical, but this does not apply to substituted derivatives. For triazoles and tetrazoles, even the unsubstituted parent compounds show two distinct tautomers. Flowever, interconversion occurs readily and such tautomers cannot be separated. Sometimes one tautomeric form predominates. Thus the mesomerism of the benzene ring is greater in (136) than in (137), and UV spectral comparisons show that benzotriazole exists predominantly as (136). 

Having its pyrazolic 4-position substituted, electrophilic attack on indazoles takes place in the 3-position and in the homocycle (the 5- and 7-positions). The condensation of a benzene ring results in a decrease of the aromaticity of the pyrazole moiety, as in naphthalene compared to benzene, and therefore basic ring cleavage is easier in indazoles than in pyrazoles (Section 4.04.2.1.7(v)). 

When the pyrazole ring bears two adjacent functional substituents, it reacts like an o-substituted benzene. For example, 4,5-diaminopyrazoles behave similarly to... 

A-Substituted polypyrazoles can also be obtained by using A-alkylhydrazines, and it should be noted that these polymers consist of a random mixture of head-to-head and head-to-tail structures. Other syntheses of polypyrazoles have been described in the literature. Thus polyphenylene pyrazoles (742) and (743) occurred when m- or p-diethynyl-benzene (DEB) reacted with 1,3-dipoles such as sydnones or bis(nitrilimines) (Scheme 64). 

The data obtained allow us to make some generalizations for the heterocy-clization of the functionally substituted acetylenic derivatives of the benzene and pyrazole series. Studies of the heterocyclization of the functionally substituted acetylenic derivatives of substituted benzenes and pyrazoles reveal noticeable differences in their reactivities. 

Because the reactive 4-position of pyrazole is substituted in indazole (benzo[b]pyrazole), substitution by electrophiles occurs by default in the 3-position initially, and then in the 5- and 7-positions of the fused benzene ring (ortho and para to the N-l). Anionic indazoles always halogenate at C-3 (84MI22). 

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. 

With a-hydroxy ketones and their related tosyloxy derivatives. The imidazo [2,T ]thiazole 364 was prepared by acetic acid-catalyzed cyclocondensation of 2-hydroxy-l,2-diphenyl-ethanone with thiophenyl-substituted 2-aminothiazole 363 (Equation 163) <2002MI110>. Under MW irradiation and in the presence of montmorillonite K-10 clay, a mixture of a-tosyloxyketones 365 and 2-imidazolidinethione led to the substituted 5,6-dihydro-imidazo[2,l- ]thiazoles 366 (Equation 164) <1998J(P1)4093>. When using a-tosyloxyacetophenone, prepared by reaction of acetophenone with [hydroxyl(tosyloxy)iodo]benzene (HTIB), 5-aminopyrazole 367 could be converted to imidazo[l,2- ]pyrazole 368 in basic medium (Equation 165) <2005JHC209>. 

The first dataset consisted of 91 rigid compounds (mono- and di-substituted benzenes, polycyclic aromatic hydrocarbons, cyclic amides, and pyrazole and imidazole derivatives) selected from the WDI on the basis of a count of the number of rotatable bonds computed using TSAR none of the 91 structures had rotatable bonds. The structures are listed in Table 1 together with their experimental log Poct values, which cover a range from -2.17 to +6.5 the values were retrieved from the SRC web site (27). 

The chlorinated intermediate 255 is eliminated and cycloadds to Cjq, yielding pyrazo-linofullerenes of the structure 257 (Scheme 4.42). The 4-nitrophenyl-group can be replaced by a 4-methoxyphenyl- or a phenyl substituent. In this reaction various aromatics and substituted aromatics are tolerated as residues R (e.g. furan, ferrocene, pyrazole or benzene and substituted benzene). The nitro group of the nitrophenyl residue can be reduced with Sn-HCl to the aniline derivative, which can be further functionalized by amide coupling with acid chlorides [311]. 

The acylation of a series of pyrazolo[3,4-c]pyridines has been studied.110 Acetic anhydride in refluxing benzene converted S-substituted derivatives to 1-acyl compounds (101 R2 = H), whereas the 7-methoxy derivative afforded the 2-substituted product 102 (R1 = H, R2 = OMe), attributed to peri interaction. In the absence of solvent, however, the latter reaction gave the 1-acyl isomer as the major product. Furthermore, benzoylation of the 5-chloro bicycle furnished a mixture of 101 and 102 (R1 = Cl, R2 = H). However, products benzoylated mainly at N-6 were obtained following introduction of a nitro group into the pyrazole ring. 

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... 

A quantitative study has been carried out by Ridd and co-workers126 on the nitration of imidazole and pyrazole in 98% sulfuric acid the partial rate factors for the 4-positions of imidazolium and pyrazolium cations are 3.0 xlO-9 and 2.1 x 10-10, respectively. Thiazole and isoxazole cations are also far less reactive than benzene. As a consequence, phenyl derivatives give products substituted in the benzene ring, on sulfonation or nitration.208-210... 

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