Acylation indazole derivatives

Weaker hydrazine derived nucleophiles may also participate in the amination reaction as has been reported by H. Katayama.105 They found that TV-acyl hydrazines 63 underwent a clean intramolecular cyclization to give the desired indol[l,2-A]indazole derivatives 64 using DPEphos as the ligand. 

Startg. m. warmed at 35° product. Y ca. 100%. - Ring closure to these N-acyl-pyrazole and -indazole derivs. as well as their ring opening with nucleophiles proceeds with great ease. F. e. s. T. Yamazaki and H. Shechter, Tetrah. Let. 1972, 4533. 

A well-known example of non-prototropic tautomerism is that of azolides (acylotropy). The acyl group migrates between the different heteroatoms and the most stable isomer (annular or functional) is obtained after equilibration. In indazoles both isomers are formed, but 2-acyl derivatives readily isomerize to the 1-substituted isomer. The first order kinetics of this isomerization have been studied by NMR spectroscopy (74TL4421). The same publication described an experiment (Scheme 8) that demonstrated the intermolecular character of the process, which has been called a dissociation-recombination process. 

Acylation of 270 with certain cyclic anhydrides 433 in acetic acid affords 4-oxobutyric acid derivatives 434. Cyclocondensation of these acids with acetic anhydride gives pyridazino[l,2- ]indazole-6,9,ll-triones 435 (Scheme 70) <2003MI1>. 

Rearrangements of 3-(o-aminophenyl)-l,2,4-oxadiazoles (44) or their A-acyl derivatives (R = acyl) to indazoles (45) require drastic conditions (Equation (10)) <82JCS(p1)759, 90ACH795>, for related reactions see also <82H(19)339,83T823>. 

Alkylation of 6-methylindazole with dihydropyran and acid produces the A-l-tetrahydropyranyl derivative as in N-l-acylation of indazoles, this 1-substituted product may be a thermodynamic product resulting from reversible alkylation. 

In Analogic zu alien anderen Acylierungen am Indazol werden durch Erhitzen im Acylierungs-mittel die stabilen 1-Acyl-Derivate gebildet, in der Kalte unter Basen-Zusatz oder aus dem Silber-Salz des lndazols hingegen die 2-Acyl-Derivate189 286,532. Die 2-Acyl-Derivate lagern sich beim Erwarmen in die 1 -Acyl-Derivate um. 

There have been relatively few previous reports of addition of acrylonitrile to heteroatomic systems. An examination of the reaction with indazoles revealed that alkylation rather than cycloaddition was the main course of reaction, but the diazole (213) did give two isomeric cyclobutane derivatives in poor yields. 2-Acyl-thio-... 

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