Mild and Chemoselective Deacetylation Method Using a Catalytic Amount of Acetyl Chloride in Methanol

Abstract

Efficient deacetylation of alcohol acetates under mild acidic conditions was accomplished with a catalytic amount of acetyl chloride in methanol. Acetates of various primary, secondary, aromatic and sugar alcohols were successfully deprotected. Highly chemoselective removal of acetyl groups in presence of ­other commonly employed esters was also achieved in excellent yields. The reactivity of this transesterification-mediated deacetyl­ation was found to be directly dependent upon the electronic and steric nature of the acetates.

acetyl chloride - acetate - catalytic - chemoselective - protecting group

References

1a Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   3rd ed.:  Wiley and Sons; New York: 1999. 

1b Kocienski PJ. Protecting Groups   Georg Thieme Verlag; New York: 1994. 

2a Neilson T. Werstiuk ES. Can. J. Chem.  1971,  49:  493 

2b Kunesch N. Meit C. Poisson J. Tetrahedron Lett.  1987,  28:  3569 

2c Ellervik U. Magnusson G. Tetrahedron Lett.  1997,  38:  1627 

2d Baptistella LHB. dos Santos JF. Ballabio KC. Marsaioli AJ. Synthesis  1989,  436 

2e Yanada R. Negoro N. Bessho K. Yanada K. Synlett  1995,  1261 

2f Perez MG. Maier MS. Tetrahedron Lett.  1995,  36:  3311 

2g Xu Y.-C. Bizuneh A. Walker C. J. Org. Chem.  1996,  61:  9086 

3a Corey EJ. Clark DA. Goto G. Marfat A. Mioskowski C. Samuelsson B. Hammerstrom C. J. Am. Chem. Soc.  1980,  102:  1436 

3b Byramova NE. Ovchinnikov MV. Backinowsky L. Kochetkov NK. Carbohydr. Res.  1993,  124:  C8 

3c Pozsgay V. Coxon B. Carbohydr. Res.  1994,  257:  189 

3d Pozsgay V. J. Am. Chem. Soc.  1995,  117:  6673 

3e Blay G. Cardona ML. Garcia MB. Pedro JP. Synthesis  1989,  438 

3f González AG. Brouard I. León F. Padrón JI. Bermejo J. Tetrahedron Lett.  2001,  42:  3187 

4 Demirci F. Haines AH. Jia C. Wu D. Synthesis  1995,  189 

Spectroscopic data of products are identical to reported values:

5a Verduyn R. Douwes M. van der Klein PAM. Mösunger EM. van der Marel GA. van Boom JH. Tetrahedron  1993,  49:  7301 

5b Cicero D. Varela O. De Lederkremer RM. Tetrahedron  1990,  46:  1131 

5c Nashed EM. Glaudemans CPJ. J. Org. Chem.  1987,  52:  5255 

6

Representative Procedure.
To a magnetically stirred solution of acetic acid 3-phenyl-propyl ester (1.43 g, 8.00 mmol) in MeOH (8 mL), was added acetyl chloride (0.084 mL, 1.2 mmol) at r.t. The mixture was stirred for 3 h at r.t. and the reaction was quenched upon addition of sat. aq NaHCO₃ solution (20 mL). The mixture was extracted with CH₂Cl₂ (2 × 20 mL). The combined organic extract was dried over anhyd MgSO₄, filtered and concentrated. The resulting residue was purified through a pad (ca. 5 cm) of silica gel column to provide the desired alcohol (1.05 g, 96% yield).