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Synlett 2002(2): 0319-0321
DOI: 10.1055/s-2002-19774
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New Molecular Iodine-Catalyzed Acetalization of Carbonyl Compounds

Manas K. Basu, Susanta Samajdar, Frederick F. Becker, Bimal K. Banik*
The University of Texas, M. D. Anderson Cancer Center, Department of Molecular Pathology, Box 89, 1515 Holcombe Blvd., Houston, Texas 77030, USA
Fax: +1(713)7925940; e-Mail: banik@mdanderson.org;
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Publication History

Received 4 October 2001
Publication Date:
02 February 2007 (online)

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Abstract

A new and facile molecular iodine-catalyzed acetalization of carbonyl compounds has been developed. Useful selectivity has also been demonstrated.

Key words

acetalization - iodine-catalyzed - carbonyl compounds

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General Procedure for Acetalization: The carbonyl compound (1 mmol) was dissolved in methanol (4 mL) or ethanol, and iodine (0.1 mmol) was added with stirring. After the starting material was consumed as indicated by TLC, methanol was evaporated. The crude product was extracted with dichloromethane, washed with saturated NaHCO3, and dried over Na2SO4 and the solvent was evaporated. Finally the pure products were obtained by purification through basic alumina using ethyl acetate-hexane (10:90) as the solvent.
Procedure for Competitive Reduction of Two Carbonyl Compounds: The two investigated compounds (1 mmol each) were dissolved in dry methanol (4.0 mL), and iodine (12.5 mg) was added. The mixture was then stirred for 1 h. NaBH4 (80.0 mg, 2 equiv) was then added in one portion with stirring. After the vigorous reaction subsided the reaction mixture was refluxed for 0.5 h. The reaction mixture was cooled, acidified (pH 3) by 1 N aqueous HCl, and extracted with dichloromethane. The ratio of the compounds was determined by a comparison study with known authentic samples by NMR.
Procedure for Competitive Reduction of Cinnamaldehyde and Methyl Cinnamate: The two compounds (1 mmol each) were dissolved in dry methanol (4.0 mL) and iodine (13 mg) was added. The mixture was then stirred for 1 h. After this, additional amounts of iodine (25 mg) were added and the mixture was stirred for 5 min. Samarium powder (2.0 mmol) was added under argon atmosphere with stirring. An exothermic reaction with evolution of gas was observed. After 20 min the solution was acidified (pH 3) by 1 N aqueous HCl; saturated NaCl was then added to the reaction mixture and extracted with dichloromethane. Drying of the organic solution over Na2SO4 and evaporation of the solvent gave a mixture that was analyzed by NMR.
3,3-Dimethoxyandrostan-17-one(15): Androstane-3,17-dione(14, 90 mg, 0.3 mmol) was dissolved in dry methanol (5 mL), and iodine (0.03 mmol) was added. The solution was stirred for 2 h. Methanol was evaporated off and the residue was dissolved in dichloromethane and washed with 5% NaHCO3. After being dried, the organic layer was evaporated, and 101 mg (97%) of a semi-solid mass was obtained. Pure product was obtained by recrystallization from methanol, mp127 °C.
17-β-Hydroxyandrostan-3-one(16): Androstane-3,17-dione (90 mg, 0.3 mmol) was dissolved in of dry methanol (5 mL), and iodine (0.03 mmol) was added. The solution was stirred for 2h. When TLC indicated complete disappearance of androstane-3,17-dione, NaBH4 (100 mg) was added and the mixture was stirred for 1 h. Water was then added, and the mixture was extracted with CH2Cl2. Drying of organic layer over Na2SO4 and removal of solvent under reduced pressure afforded 103 mg of a white solid: mp 171 °C, [α]D +12.5 in MeOH. [2b] Hydrolysis of this dimethoxy compound (MeOH, 1 N aq. HCl 30 min, room temperature). Crytallization of the crude solid led to 17-β-hydroxyandrostan-3-one (16, 76 mg, 83%).