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.

Key words

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).