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Volumn 34, Issue 11, 2013, Pages 3415-3419

Synthesis of 1H-Indol-3-ylpyrazole derivatives from 1,3,5-triketones and arylhydrazines: One-pot construction of pyrazole and indole rings

Author keywords

1,3,5 Triketones; Fischer indole synthesis; Indolylpyrazole

Indexed keywords

1,3,5-TRIKETONES; ARYLHYDRAZINES; FISCHER INDOLE SYNTHESIS; INDOLE RINGS; INDOLYLPYRAZOLE; ONE-POT REACTION; PHENYLHYDRAZINE; PYRAZOLES;

EID: 84889002012     PISSN: 02532964     EISSN: 12295949     Source Type: Journal    
DOI: 10.5012/bkcs.2013.34.11.3415     Document Type: Article
Times cited : (8)

References (39)
  • 1
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    • For the biological activities of some indolylpyrazole derivatives, see: (a)
    • For the biological activities of some indolylpyrazole derivatives, see: (a) Zhang, D.; Wang, G.; Zhao, G.; Xu, W.; Huo, L. Eur. J. Med. Chem. 2011, 46, 5868-5877.
    • (2011) Eur. J. Med. Chem. , vol.46 , pp. 5868-5877
    • Zhang, D.1    Wang, G.2    Zhao, G.3    Xu, W.4    Huo, L.5
  • 9
    • 79953196824 scopus 로고    scopus 로고
    • For the synthesis of indolylpyrazole derivatives by a transition metal-catalyzed coupling reactions see.
    • For the synthesis of indolylpyrazole derivatives by a transition metal-catalyzed coupling reactions, see: (a) Khan, T. A.; Kumar, S.; Venkatesh, C.; Ila, H. Tetrahedron 2011, 67, 2961-2968.
    • (2011) Tetrahedron , vol.67 , pp. 2961-2968
    • Khan, T.A.1    Kumar, S.2    Venkatesh, C.3    Ila, H.4
  • 16
    • 84859608186 scopus 로고    scopus 로고
    • For The Synthesis Of Indolylpyrazole Derivatives Via A Sequential Construction Of Pyrazole And Indole Rings See:
    • For the synthesis of indolylpyrazole derivatives via a sequential construction of pyrazole and indole rings, see: (a) Usachev, B. I.; Obydennov, D. L.; Roschenthaler, G.-V.; Sosnovskikh, V. Y. J. Fluorine Chem. 2012, 137, 22-26.
    • (2012) J. Fluorine Chem. , vol.137 , pp. 22-26
    • Usachev, B.I.1    Obydennov, D.L.2    Roschenthaler, G.-V.3    Sosnovskikh, V.Y.4
  • 21
    • 84889027225 scopus 로고    scopus 로고
    • A One-pot Synthesis Of Indolylpyrazole From 15-di(p-tolyl)pentane 1, 35-trione and phenylhydrazine hydrochloride was also reported however the paper prepared only one compound in very low yield ( 25%) in refluxing EtOH, see:
    • A one-pot synthesis of indolylpyrazole from 1,5-di(p-tolyl)pentane-1,3,5- trione and phenylhydrazine hydrochloride was also reported; however, the paper prepared only one compound in very low yield (25%) in refluxing EtOH, see:
  • 25
    • 84889076323 scopus 로고    scopus 로고
    • The Formation Of Pyrazole Ring Might Occur Preferentially Over The Indole Ring.1f3c3d Thus 3a 3a' And The Corresponding Hydrazones Of 3a And 3a' Could Be The Possible Intermediates. In this respect, the reaction of 1a with a limited amount (0.9 equiv) of phenylhydrazine hydrochloride was examined at low temperature (EtOH, 40 oC) in order to separate major intermediate(s) such as 3a or the hydrazone of 3a; however, so many spots were observed including 4a and 5a, and we failed to identify the major intermediate(s). Thus, we cannot exclude the possibility for the initial formation of an indole ring and a subsequent pyrazole formation at this stage
    • The formation of pyrazole ring might occur preferentially over the indole ring.1f,3c,3d Thus, 3a, 3a', and the corresponding hydrazones of 3a and 3a' could be the possible intermediates. In this respect, the reaction of 1a with a limited amount (0.9 equiv) of phenylhydrazine hydrochloride was examined at low temperature (EtOH, 40 oC) in order to separate major intermediate(s) such as 3a or the hydrazone of 3a; however, so many spots were observed including 4a and 5a, and we failed to identify the major intermediate(s). Thus, we cannot exclude the possibility for the initial formation of an indole ring and a subsequent pyrazole formation at this stage.
  • 30
    • 84889035571 scopus 로고    scopus 로고
    • During the evaluation process one of the reviewers suggested the synthesis of indolylpyrazoles with other 1 ,3,5-triketones. Thus, we prepared 1,5-di(2-pyridyl)-1,3,5-pentanetrione (1c) according to the reported method and examined the reaction with
    • During the evaluation process one of the reviewers suggested the synthesis of indolylpyrazoles with other 1,3,5-triketones. Thus, we prepared 1,5-di(2-pyridyl)-1,3,5-pentanetrione (1c) according to the reported method and examined the reaction with
  • 34
    • 67650665029 scopus 로고    scopus 로고
    • For the synthesis and biological activity of pyrimidylindole derivatives, see: (a)
    • For the synthesis and biological activity of pyrimidylindole derivatives, see: (a) Walker, S. R.; Carter, E. J.; Huff, B. C.; Morris, J. C. Chem. Rev. 2009, 109, 3080-3098.
    • (2009) Chem. Rev. , vol.109 , pp. 3080-3098
    • Walker, S.1    Carter, E.2    Huff, B.3    Morris, J.C.4
  • 37
    • 23944484971 scopus 로고    scopus 로고
    • The formation of appreciable amounts of acetophenone and 2-amino-4-hydroxy-6-phenylpyrimidine was observed on TLC. 13. Actually, the compound 13 existed as a keto/enol (2:3) tautomeric mixture in its 1H NMR spectrum. For the similar keto/enol equilibration of 1-substituted-2-azinyl-1- ethanones, see
    • The formation of appreciable amounts of acetophenone and 2-amino-4-hydroxy-6-phenylpyrimidine was observed on TLC. 13. Actually, the compound 13 existed as a keto/enol (2:3) tautomeric mixture in its 1H NMR spectrum. For the similar keto/enol equilibration of 1-substituted-2-azinyl-1- ethanones, see: (a) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Akhmedova, R. G. ARKIVOC 2005 (vi) 329-338.
    • (2005) ARKIVOC , vol.6 , pp. 329-338
    • Katritzky, A.1    Abdel-Fattah, A.A.A.2    Akhmedova, R.3
  • 39
    • 84889041635 scopus 로고    scopus 로고
    • The regioisomeric indolylpyrazole 5a was not formed at all in the reaction, and the result could be a strong evidence for the suggested mechanism
    • The regioisomeric indolylpyrazole 5a was not formed at all in the reaction, and the result could be a strong evidence for the suggested mechanism.


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