A New Molecular Iodine-Catalyzed Acetalization of Carbonyl Compounds

Abstract

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

acetalization - iodine-catalyzed - carbonyl compounds

References

1a Cameron FB. Hunt JS. Oughton JF. Wilkinson PA. Wilson BM. J. Chem. Soc.  1953,  3864 

1b Lorette NB. Howard WL. Brown JH. J. Org. Chem.  1959,  24:  1731 

1c Zajac WW. Byrne KJ. J. Org. Chem.  1970,  35:  3375 

1d Thuy VM. Maitte P. Bull. Soc. Chim. Fr.  1975,  2558 

1e Wenkert E. Goodwin TE. Synth. Commun.  1977,  7:  409 

1f Taylor EC. Chiang C.-S. Synthesis  1977,  467 

1g Vandewalle M. Vander Eychen J. Vullioud C. Tetrahedron  1986,  42:  4035 

1h Ishihara K. Karumi Y. Kubota M. Yamamoto H. Synlett  1996,  839 

1i Clerici A. Pastori N. Porta O. Tetrahedron  2001,  57:  217 ; and references cited therein

2a Luche J.-L. Gemal AL. J. Chem. Soc., Chem. Commun.  1978,  976 

2b Gemal AL. Luche J.-L. J. Org. Chem.  1979,  44:  4187 

3a Ott J. Ramos Tombo GM. Schmid B. Venanzi LM. Wang G. Ward TR. Tetrahedron Lett.  1989,  30:  6151 

3b Gorla F. Venanzi LM. Helv. Chim. Acta  1990,  73:  690 

4a Banik BK. Mukhopadhyay C. Venkatraman MS. Becker FF. Tetrahedron Lett.  1998,  39:  7343 

4b Banik BK. Zegrocka O. Banik I. Hackfeld L. Becker FF. Tetrahderon Lett.  1999,  40:  673 

4c Banik BK. Zegrocka O. Becker FF. J. Chem. Res.  2000,  7:  321 

4d Mukhopadhyay C. Becker FF. Banik BK. J. Chem. Res.  2001,  28 

5 Ghatak A. Becker FF. Banik BK. Tetrahedron Lett.  2000,  41:  3793 

6 Inanage J. Handa Y. Tabuchi T. Otsubo K. Hanamoto T. Tetrahedron Lett.  1991,  32:  6557 

7

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%).