Base-Mediated Reaction of Hydrazones and Nitroolefins with a Reversed Regioselectivity:  A Novel Synthesis of 1,3,4-Trisubstituted Pyrazoles

• Abstract
• Full Text HTML
• Hi-Res PDF[107 KB]
• PDF w/ Links[145 KB]

• Supporting Info
• Figures
• Citing Articles

Your current credentials do not allow retrieval of the full text.

Purchase the full-text

• PDF/HTML,
  figures/images,
  references and tables,
  (where available)

Abstract

A regioselective synthesis of 1,3,4-tri- or 1,3,4,5-tetrasubstituted pyrazoles by the reaction of hydrazones with nitroolefins is described. Mediated with strong bases such as t-BuOK, the reaction exhibits a reversed, exclusive 1,3,4-regioselectivity. Subsequent quenching with strong acids such as TFA is essential to achieve good yields. A plausible stepwise cycloaddition reaction mechanism is proposed.

Citing Articles

View all 8 citing articles

Citation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.

This article has been cited by 7 ACS Journal articles (5 most recent appear below).

• 

  From 2000 to Mid-2010: A Fruitful Decade for the Synthesis of Pyrazoles

  Santos Fustero, María Sánchez-Roselló, Pablo Barrio, and Antonio Simón-Fuentes
  Chemical Reviews2011 111 (11), 6984-7034

  • From 2000 to Mid-2010: A Fruitful Decade for the Synthesis of Pyrazoles

    Santos Fustero, María Sánchez-Roselló, Pablo Barrio, and Antonio Simón-Fuentes
    Chemical Reviews2011 111 (11), 6984-7034
    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
• 

  Convergent Synthesis of a 5HT₇/5HT₂ Dual Antagonist

  Jimmy T. Liang, Xiaohu Deng, and Neelakandha S. Mani
  Organic Process Research & Development2011 15 (4), 876-882

  • Convergent Synthesis of a 5HT₇/5HT₂ Dual Antagonist

    Jimmy T. Liang, Xiaohu Deng, and Neelakandha S. Mani
    Organic Process Research & Development2011 15 (4), 876-882

    The development of an efficient and convergent route to 3-(4-fluorophenyl)-2-isopropyl-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine (1), a potent 5HT7/5HT2 dual antagonist, is described. Significant features of this route are: (a) a regioselective ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
• 

  Practical Synthesis of a Cathepsin S Inhibitor: Route Identification, Purification Strategies, and Serendipitous Discovery of a Crystalline Salt Form

  Xiaohu Deng, Jimmy T. Liang, Matthew Peterson, Raymond Rynberg, Eugene Cheung and Neelakandha S. Mani
  The Journal of Organic Chemistry2010 75 (6), 1940-1947

  • Practical Synthesis of a Cathepsin S Inhibitor: Route Identification, Purification Strategies, and Serendipitous Discovery of a Crystalline Salt Form

    Xiaohu Deng, Jimmy T. Liang, Matthew Peterson, Raymond Rynberg, Eugene Cheung and Neelakandha S. Mani
    The Journal of Organic Chemistry2010 75 (6), 1940-1947

    A “redox economical” strategy resulted in a concise, modular synthesis of compound 1, a potent Cathepsin S inhibitor. Starting from three building blocks, crude drug substance was prepared in a two-step sequence in high yield. Efficient purification of ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
• 

  Development of an Automated Microfluidic Reaction Platform for Multidimensional Screening: Reaction Discovery Employing Bicyclo[3.2.1]octanoid Scaffolds

  John R. Goodell, Jonathan P. McMullen, Nikolay Zaborenko, Jason R. Maloney, Chuan-Xing Ho, Klavs F. Jensen, John A. Porco, Jr. and Aaron B. Beeler
  The Journal of Organic Chemistry2009 74 (16), 6169-6180

  • Development of an Automated Microfluidic Reaction Platform for Multidimensional Screening: Reaction Discovery Employing Bicyclo[3.2.1]octanoid Scaffolds

    John R. Goodell, Jonathan P. McMullen, Nikolay Zaborenko, Jason R. Maloney, Chuan-Xing Ho, Klavs F. Jensen, John A. Porco, Jr. and Aaron B. Beeler
    The Journal of Organic Chemistry2009 74 (16), 6169-6180

    An automated, silicon-based microreactor system has been developed for rapid, low-volume, multidimensional reaction screening. Use of the microfluidic platform to identify transformations of densely functionalized bicyclo[3.2.1]octanoid scaffolds will be ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
• 

  Synthesis of Fully Substituted Pyrazoles via Regio- and Chemoselective Metalations

  Christina Despotopoulou, Lydia Klier and Paul Knochel
  Organic Letters2009 11 (15), 3326-3329

  • Synthesis of Fully Substituted Pyrazoles via Regio- and Chemoselective Metalations

    Christina Despotopoulou, Lydia Klier and Paul Knochel
    Organic Letters2009 11 (15), 3326-3329

    The full functionalization of the pyrazole ring was achieved by successive regioselective metalations using TMPMgCl·LiCl and TMP2Mg·2LiCl. Trapping with various electrophiles led to trisubstituted pyrazoles. An application to the synthesis of the ...

    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links

SciFinder Links

• Get Reference Detail
• Get Substances
• Get Reactions
• Get Cited
• Get Citing