Chemical & Pharmaceutical Bulletin 2012-01-01

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

Konstantin Yuryevich Koltunov, Aleksey Nikolaevich Chernov, Gubbi Krishnamurthy Surya Prakash, George Andrew Olah

Index: Chem. Pharm. Bull. 60(6) , 722-7, (2012)

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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.