Synthesis of 2-(Arylamino)ethanethiols via Lewis Acid Catalyzed Aminolysis of 2,2-Dimethylthiirane as Precursors of the 1,4-Benzothiazine Nucleus

Abstract

Ring opening of 2,2-dimethylthiirane by deactivated aromatic amines to afford 2-(arylamino)ethanethiols as 6-substituted 1,4-benzothiazine precursors, was investigated. The reaction takes place under mild conditions using copper(II) triflate or indium(III) triflate as catalysts. The regioselectivity of the addition depends on the catalysts and the substituents of the arylamines.

Lewis acids - catalysis - 2,2-dimethylthiirane - 2-(aryl-amino)ethanethiols - aminolysis reaction - 1,4-benzothiazines

References

1a Cecchetti V. Calderone V. Tabarrini O. Sabatini S. Filipponi E. Testai L. Spogli R. Martinetti E. Fravolini A. J. Med. Chem.  2003,  46:  3670 

1b Cecchetti V. Calderone V. Tabarrini O. Sabatini S. Filipponi E. Testai L. Spogli R. Martinetti E. Fravolini A. J. Med. Chem.  2005,  48:  6766 

1c Carosati E. Lemoine H. Spogli R. Grittner D. Mannhold R. Tabarrini O. Sabatini S. Cecchetti V. Bioorg. Med. Chem.  2005,  13:  5581 

1d Calderone V. Spogli R. Martelli A. Manfroni G. Testai L. Sabatini S. Tabarrini O. Cecchetti V. J. Med. Chem.  2008,  51:  5085 

2 Snyder HR. Stewart JM. Ziegler B. J. Am. Chem. Soc.  1947,  69:  2672 

3 Reppe W, and Nicolai F. inventors; DE  631,016.  ; Chem. Abstr. 1936, 30, 6008

4a Reynolds DD. Fields DL. Heterocyclic Compounds with Three- and Four-Membered Rings, In Chemistry of Heterocyclic Compounds   Vol. 19:  Weissberger A. John Wiley & Sons Ltd; New York: 1964.  p.576 

4b Sander M. Chem. Rev.  1966,  66:  297 

4c Zoller U. Small Ring Heterocycles, Part 1: Aziridines, Azirines, Thiiranes, Thiirenes, In Chemistry of Heterocyclic Compounds   Vol. 42:  Hassner A. John Wiley & Sons Ltd; New York: 1983.  p.333 

5 Harring SR. Livinghouse T. In Comprehensive Heterocyclic Chemistry II   Vol. 1A:  Katritzky AR. Rees CW. Scriven EFV. Elsevier; Oxford: 1996.  p.241 

6 Dong Q. Fang X. Schroeder JD. Garvey DS. Synthesis  1999,  1106 

7 Luhowy R. Meneghini F. J. Org. Chem.  1973,  38:  2405 

8 Takeuchi H. Nakajiama Y. J. Chem. Soc., Perkin Trans. 2  1998,  2441 

9a Turk SD. Louthan RP. Cobb RL. Bresson CR. J. Org. Chem.  1964,  29:  974 

9b Isaac NS. Can. J. Chem.  1966,  44:  395 

9c Usui Y. Noma J. Hirano M. Komiya S. J. Chem. Soc., Dalton Trans.  1999,  4397 

10

The molecular weights for all the compounds 3 and 4 were confirmed by mass spectrometry. In particular for all the aminoethanethiols 3, the base peak corresponds to a loss of 75 amu (Me₂CSH) from the molecular peak, and it correspond to a loss of 47 amu (CH₂SH) for aminoethane-thiols 4. This behavior, first observed by Isaac^9b and then by Usui,^9c permitted an easy identification between those regioisomers by GC-MS analysis.

11 Dittmer DC. In Comprehensive Heterocyclic Chemistry   Vol. 7:  Katritzky AR. Rees CW. Pergamon; Oxford: 1984.  p.131 

12 Kobayashi S. Sugiura M. Kitagawa H. Lam WW.-L. Chem. Rev.  2002,  102:  2227 

13 Oelschlaeger H. inventors; DE  1,168,917.  ; Chem. Abstr. 1964, 61, 47643