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Synthesis 2002(7): 0921-0927
DOI: 10.1055/s-2002-28521
PAPER
© Georg Thieme Verlag Stuttgart · New York

An Interesting Synthetic Application of S-Alkyl (Aryl)bis(alkylsulfanyl)thio­acetates: General Procedure for the Preparation of (±)-α-Arylpropionic Acids

Marco Clericuzio, Iacopo Degani*, Stefano Dughera, Rita Fochi*
Dip.to di Chimica Generale ed Organica Applicata dell’Università, C.so M. D’Azeglio 48, 10125 Torino, Italy
e-Mail: rita.fochi@unito.it;
Further Information

Publication History

Received 24 January 2002
Publication Date:
14 May 2002 (online)

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Abstract

Reported here is a new procedure for the synthesis of α-arylpropionic acids 1 in the racemic form, starting from derivatives of aromatic carboxylic acids 2 (i.e., esters), via 1-aryl-2,2,2-tris(alkylsulfanyl)ethanones 4-6, S-alkyl (aryl)bis(alkylsulfanyl)thioacetates 7-9, S-alkyl α-aryl-α-(alkylsulfanyl)thiopropionates 10-12 and S-alkyl α-arylthiopropionates 13-15. Each stage takes place easily and yields are always high.

Key words

thioacetates - desulfurizations - thiols - arylpropionic acids - drugs

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5

Portions of this paper have appeared in the form of patent: see Ref. [2]

8

Clericuzio M., Degani I., Dughera S., Fochi R., manuscript in preparation: some suitable racemic S-alkyl α-arylthiopropionates were deracemized by conversion into the corresponding trimethylsilyl or (tert-butyldimethyl)silyl enol ethers and their subsequent enantioselective protonation with (R)-1,1′-binaphthalene-2,2′-diol/SnCl4, to afford the enantiomerically enriched S-alkyl α-arylthiopropionates. These, by oxidative hydrolysis, yielded the (S)-enantiomers of Ibuprofen and Naproxen with enantiomeric excesses up to 82%.