Condensation of 2-naphthol and naphthalenediols with o-dichlorobenzene in the presence of aluminum halides

Chem Pharm Bull (Tokyo). 2012;60(6):722-7. doi: 10.1248/cpb.60.722.

Abstract

It is known that 1-naphthol, as a result of superelectrophilic (dicationic) activation in superacid media, is able to react with such deactivated aromatic compound as o-dichlorobenzene to give 4-(3,4-dichlorophenyl)-1-tetralone (2), which is a highly valuable intermediate in the synthesis of the antidepressant, sertraline (1) and other useful derivatives. However, the analogous reactivity of 2-naphthol and a variety of naphthalenediols towards o-dichlorobenzene has not been investigated thus far, although the corresponding tetralones, bearing dichlorophenyl moiety, could be of great pharmacochemical interest. In present work, we disclose that 1,5-, 1,6-, and 1,7- naphthalenediols (6a-c) react smoothly with o-dichlorobenzene in the presence of an excess of aluminum chloride or aluminum bromide to give the pairs of isomeric 4-(3,4-dichlorophenyl)- and 4-(2,3-dichlorophenyl)- 5-, 6-, and 7-hydroxy-1-tetralones (10a-c and 11a-c) in high overall yields. 2-Naphthol and 2,7-naphthalenediol (6d) exhibited comparatively lower reactivity, which however was sufficient to obtain the corresponding dichlorophenyl-2-tetralones in moderate yields. The mechanism of these reactions involving superelectrophilic dicationic or even tricationic intermediates, is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Chloride
  • Aluminum Compounds / chemistry*
  • Chlorides / chemistry*
  • Chlorobenzenes / chemistry*
  • Molecular Structure
  • Naphthols / chemistry*
  • Stereoisomerism
  • Tetralones / chemical synthesis*
  • Tetralones / chemistry

Substances

  • 2,3-naphthalenediol
  • Aluminum Compounds
  • Chlorides
  • Chlorobenzenes
  • Naphthols
  • Tetralones
  • Aluminum Chloride
  • 2-dichlorobenzene
  • 2-naphthol