Synthesis of hydrogenated indazole derivatives starting with α,β-unsaturated ketones and hydrazine derivatives

Nakhai, Azadeh; Bergman, Jan

doi:10.1016/j.tet.2009.01.041

Cited by 41 publications

(24 citation statements)

References 30 publications

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“…Carbon assignments were based on DEPT and/or HMQC experiments. 19 F NMR spectra were recorded at 376 MHz at 25 C using hexafluorobenzene as external standard (d À163.5 ppm). Melting points were determined through a B€ uchi instrument.…”

Section: Methodsmentioning

confidence: 99%

Regioselective synthesis of 1,3,5- and 1,3,4,5-substituted pyrazoles via acylation of N-Boc-N-substituted hydrazones

Tinarelli¹,

Righi²,

Rosini³

et al. 2011

Tetrahedron

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Section: Methodsmentioning

confidence: 99%

Regioselective synthesis of 1,3,5- and 1,3,4,5-substituted pyrazoles via acylation of N-Boc-N-substituted hydrazones

Tinarelli¹,

Righi²,

Rosini³

et al. 2011

Tetrahedron

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“…13 After the reaction of 6 unsubstituted 2 arylidene cyclohexanones with phenylhydrazine, the corresponding individual hexahydroindazoles were not isolated. 14 We found that the results of the reaction of 6 (4 halo benzylidene) 2,2 dimethylcyclohexanones with phenyl hydrazine depend, to a great extent, on the presence of a base (for example, pyridine). The reaction of 6 (4 chloro) benzylidene 2,2 dimethylcyclohexanone (5a) with phen ylhydrazine in methanol under reflux afforded the expected 3 (4 chlorophenyl) 7,7 dimethyl 2 phenyl 3,3a,4,5,6,7 hexahydroindazole (6a) (3,3a trans isomer) in 47% yield (Scheme 2).…”

mentioning

confidence: 94%

Reaction of 6-arylidene-2,2-dimethylcyclohexanones with phenylhydrazine. Molecular and crystal structures of 3-(4-halophenyl)-1-phenyl-4,5,6,7-tetrahydro-(2H)-indazoles

et al. 2014

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The previously unknown 3 (4 chlorophenyl) 7,7 dimethyl 2 phenyl 3,3a,4,5,6,7 hexa hydroindazole 6a and (4 halophenyl) 7,7 dimethyl 1 phenyl 4,5,6,7 tetrahydroindazoles 7a,b were synthesized by the reaction of 6 arylidene 2,2 dimethylcyclohexanones with phenylhydr azine in the presence of pyridine. The molecular and crystal structures of compounds 7a,b were determined by X ray diffraction.Key words: 6 arylidene 2,2 dimethylcyclohexanones, 3 aryl 7,7 dimethyl 2 phenyl 3,3a,4,5,6,7 hexahydroindazoles, 3 aryl 7,7 dimethyl 2 phenyl 4,5,6,7 tetrahydroindazoles, X ray diffraction study, phenylhydrazine, cyclocondensation.Many drugs and biologically active compounds con tain pyrazole and pyrazoline moieties. In recent years, the biological activity of 3,3a,4,5,6,7 hexahydro 2(1H) ind azoles I and 3,3a,4,5 tetrahydro (2H) benz[g]indazoles II has received attention from researchers.Among hexahydroindazoles I, there are monoamine oxidase inhibitors having antidepressant properties 1-3 and antibacterial agents. 4-7 A series of substituted benz[g]ind azoles II are covered by patents as insecticides. 8,9 Earlier, we have found for the first time that new 2 thiocarbamoyl substituted (R 3 = CSNH 2 ) hexahydroindazoles I exhibit fungicidal activity against certain phytopathogenic fungi, and compounds containing one or two methyl groups in the 7 position (R 1 = H, R 2 = Me or R 1 = R 2 = Me) proved to be particularly active. 10,11 The conventional procedure for the synthesis of compounds I involves the nucleophilic addition of hydrazines or (thio)semicarbazides to 2 aryl idenecycloalkanones or 2,6 bis(arylidenecyclohexanones) followed by the cyclocondensation of the adduct. 12 In order to search for new fungicides, we continued our investigation of the cyclocondensation of 6 arylidene 2,2 dimethylcyclohexanones with 1,2 dinucleophiles by studying the reactions of these ketones with phenylhydr azine under different conditions.The reactions of phenylhydrazine with a series of 2,6 bis(arylidenecyclohexanones) 1 have been studied ear lier. 13 These reactions afforded hexahydroindazoles 2 as the major products along with dehydrogenated com pounds, viz., 1 phenyl substituted tetrahydroindazoles 3, as the minor products (Scheme 1). The structures of the latter were not established. 13 In this case, the 1 H NMR spectra were non informative; however, structure 3 was assigned to these compounds 13 based on indirect evidence by analyzing the results of the chemical transformations performed in the cited study. The oxidation of hexa hydroindazole 2 (Ar = Ph) with lead tetraacetate afforded isomeric 2 phenyltetrahydroindazole 4, the properties of which (m.p., the 1 H NMR spectrum) substantially differ from those of tetrahydroindazole 3 prepared by the con densation under consideration (see Scheme 1). However, the structures of phenyltetrahydroindazoles 3 have not been definitely proved in the study. 13 After the reaction of 6 unsubstituted 2 arylidene cyclohexanones with phenylhydrazine, the corresponding individual hexahydroindazoles were not...

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“…The indazole nucleus is a pharmaceutically important and emerging heterocycle with a broad spectrum of activities, including anti‐inflammatory , antitumor , anti‐HIV , antimicrobial , contraceptive , and have also been used as nNOS inhibitors . Therefore, a number of methods have been reported for the synthesis of indazole derivatives . Nevertheless, the development of new synthetic methods for the efficient preparation of heterocycles containing indazole ring fragment is therefore an interesting challenge.…”

Section: Introductionmentioning

confidence: 99%

Ionic Liquid Catalyzed One‐Pot Synthesis of 2H‐Pyridazino[1,2‐a]indazole‐1,6,9(11H)‐triones Via Three‐Component Reaction under Solvent‐Free Conditions

Ding

Guo

2016

Journal of Heterocyclic Chem

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Synthesis of hydrogenated indazole derivatives starting with α,β-unsaturated ketones and hydrazine derivatives

Cited by 41 publications

References 30 publications

Regioselective synthesis of 1,3,5- and 1,3,4,5-substituted pyrazoles via acylation of N-Boc-N-substituted hydrazones

Regioselective synthesis of 1,3,5- and 1,3,4,5-substituted pyrazoles via acylation of N-Boc-N-substituted hydrazones

Reaction of 6-arylidene-2,2-dimethylcyclohexanones with phenylhydrazine. Molecular and crystal structures of 3-(4-halophenyl)-1-phenyl-4,5,6,7-tetrahydro-(2H)-indazoles

Ionic Liquid Catalyzed One‐Pot Synthesis of 2H‐Pyridazino[1,2‐a]indazole‐1,6,9(11H)‐triones Via Three‐Component Reaction under Solvent‐Free Conditions

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