Subscribe to RSS
DOI: 10.1055/s-2002-28521
An Interesting Synthetic Application of S-Alkyl (Aryl)bis(alkylsulfanyl)thioacetates: General Procedure for the Preparation of (±)-α-Arylpropionic Acids
Publication History
Publication Date:
14 May 2002 (online)
![](https://www.thieme-connect.de/media/synthesis/200207/lookinside/thumbnails/10.1055-s-2002-28521-1.jpg)
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
- 1
Degani I.Dughera S.Fochi R.Gazzetto S. J. Org. Chem. 1997, 62: 7228 - 2
Degani I,Dughera S, andFochi R. inventors; PCT/EP 97/01258. ; Chem. Abstr. 1997, 127, 307210 - 3
Degani I.Dughera S.Fochi R.Serra E. J. Org. Chem. 1996, 61: 952 - 4
Barbero M.Cadamuro S.Degani I.Dughera S.Fochi R. J. Org. Chem. 1995, 60: 6017 - For example, for a general survey, see:
-
6a Article 3.4: Anti-inflammatory - Antirheumatic Drugs, Arylpropionic Acids:
Hinz B.Dorn CP.Shen TY.Brune K. In Ulmann’s Encyclopedia of Industrial Chemistry 6th ed. on line: Wiley-VCH; Weinheim: 2001. -
6b
Sonawane HR.Bellur NS.Ahuja JR.Kulkarni DG. Tetrahedron: Asymmetry 1992, 3: 163 -
6c
Hamor GH. In Principles of Medicinal Chemistry Chap. 23:Foye WO. Lea & Febiger; Philadelphia: 1989. -
6d
Rieu JP.Boucherle A.Cousse H.Mouzin G. Tetrahedron 1986, 42 : 4095 -
6e
Lambardino JH. In Nonsteroidal Antiinflammatory Drugs Wiley-Interscience; New York: 1985. -
6f
Shen TY. Angew. Chem., Int. Ed. Engl. 1972, 6: 460 - Some recent examples for the synthesis of α-arylpropionic acids:
-
7a
Xie B.Zhang Y. Huaxue Jinzhan 2001, 13: 43 ; Chem. Abstr. 2001, 135, 274496 -
7b
Wang B.Ma HZ.Shi QZ. Chin. Chem. Lett. 2001, 12: 571 ; Chem. Abstr. 2001, 135, 357736 -
7c
Wang B.Ma HZ. Synth. Commun. 2001, 31: 104 -
7d
Mogensen JP, andSauerberg P. inventors; Bury P. S., Jeppesen L., Pettersson I.; PCT Int. Appl. WO 2001055085. ; Chem. Abstr. 2001, 135, 152623 -
7e
Fassina V.Ramminger C.Seferin M.Monteiro AL. Tetrahedron 2000, 56: 7403 -
Tsai S, andChang C. inventors; US 6201151. ; Chem. Abstr. 2001, 134, 17283 - 9 Dictionary of Organic Compounds on CD-ROM Version 9.2: Chapman & Hall/CRC; London: 2001.
- 10
Yamauchi T.Nakao K.Fujii K. J. Chem. Soc., Perkin Trans. 1 1987, 1433 - 11
Moreau R.Durand-Henchoz S. C.R. Acad. Sci., Ser. C 1970, 271: 862 ; Chem. Abstr. 1971, 74, 22514 - 12
Fini A.Laus M.Orienti I.Zecchi V. J. Pharm. Sci. 1986, 23 ; Chem. Abstr. 1986, 104, 155839 - 13
Froling A.Arens JF. Recl. Trav. Chim. Pays-Bas 1962, 81 : 1009 - 14
Seebach D.Gei K.-H.Beck AK.Graf B.Daum H. Chem. Ber. 1972, 105: 3280 - 15
Wladislaw B.Marzorati L.Gruber J. Synth. Commun. 1990, 2937 - 16
Barbero M.Cadamuro S.Degani I.Dughera S.Fochi R. J. Chem. Soc., Perkin Trans. 1 1993, 2075
References
Portions of this paper have appeared in the form of patent: see Ref. [2]
8Clericuzio 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%.