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All posts Subject: Myristicin-derived Cathinones (Precursor prep) Please login to post

Rhodium
(Chief Bee)
12-17-03 10:25
No 477377
User Picture Myristicin-derived Cathinones (Precursor prep)
(Rated as: excellent)

Structure and Synthesis of (±)-Wuweizisu C
Gail E. Schneiders and Robert Stevenson
J. Org. Chem. 46, 2969-2971 (1981)

3-Methoxy-4,5-Methylenedioxy-Propiophenone (7) has been reported as a natural product from Oenanthe crocata L. and named crocatone^16,17 but it has apparently not been previously synthesized. It was made readily from vanillin (3) by treatment with iodine monochloride to give 5-iodovanillin (4)¹⁸ which on being heated with sodium hydroxide and cupric sulfate solution¹⁹ yielded 3,4-dihydroxy-5-methoxybenzaldehyde (5). Methylenation of 5 by a recently described procedure²⁰ (CH₂Cl₂-KF-HCONMe₂) afforded the aldehyde 6 in 65% yield, and conversion to crocatone (7) was effected by the standard procedure of oxidation of the alcohol obtained by addition of ethylmagnesium bromide (Scheme I). Crocatone (7) cleanly afforded the -bromo derivative 8 by bromination in chloroform solution.

Experimental

4-Hydroxy-5-iodo-3-methoxybenzaldehyde (5-iodovanillin, 4)
This was prepared as previously described¹⁸ in 81% yield by treatment of vanillin 3 with iodine monochloride and isolated as prisms from ethanol: mp 180-181°C (lit.¹⁸ mp 181-182°C).

3,4-Dihydroxy-5-methoxybenzaldehyde (5-Hydroxyvanillin, 5)
This was prepared as previously described¹⁹ in 68% yield by heating 5-iodovanillin 4 with sodium hydroxide and copper sulfate solution and isolated as plates from benzene: mp 133-134°C (lit.¹⁹ mp 133-134°C).

3-Methoxy-4,5-(methylenedioxy)benzaldehyde (6)
Potassium fluoride (14.0 g) and methylene chloride (75 mL) were added to a solution of 3,4-dihydroxy-5-methoxybenzaldehyde 5 (9.0 g) in dimethylformamide (300 mL), and the mixture was heated under reflux with stirring under a nitrogen atmosphere for 1.5 h. It was then diluted with water (ca. 200 mL) and extracted with ether (3x200 mL), and the extract was washed successively with 5% aqueous sodium hydroxide solution (3x150 mL), water, and brine. Evaporation of the dried (MgSO₄ extract yielded a residue, which on crystallization from methanol gave the methoxy(methy1enedioxy)benzaldehyde 6 as prisms: 6.15g; mp 131-132°C (lit.²² mp 130°C).

3-Methoxy-4,5-(methylenedioxy)propiophenone (Crocatone, 7)
A solution of 3-methoxy-4,5-(methylenedioxy)benzaldehyde (3.53 g) in ether (150 mL) was added to a solution of ethylmagnesium bromide [from magnesium (2.75 g), Vitride (Eastman, 1 mL), ethyl bromide (10 mL), and ether (100 mL)]. The mixture was stirred for 30 min and then worked up in the usual way to give the intermediate alcohol as a colorless oil: 3.17 g.

To a solution of this alcohol (3.0 g) in acetone (25 mL) at 0-5°C was added Jones reagent (1.4 M, 8 mL) dropwise over 10 min, the mixture was stirred at room temperature for 30 min, and then 2-propanol (3 mL) was added. It was worked up by aqueous dilution, concentration, and ether extraction. The washed and dried ether extract yielded crocatone (7) as needles (2.23 g) from petroleum ether: mp 88-89°C (lit.¹⁶ mp 89°C).

-Bromo-3-methoxy-4,5-(methylenedioxy)propiophenone (8)
To a solution of the ketone 7 (2.0 g) in chloroform (12 mL) was added dropwise with stirring a solution of bromine (1.4 g) in chloroform (7 mL), and the mixture was allowed to stand for 1.5 h. It was then washed with water (25 mL) and saturated sodium bicarbonate solution (2x25 mL), dried, and evaporated to give the bromo ketone 8 as long white needles (2.20 g) from ethanol: mp 114.5-115°C.

References
(16) Janot, M.-M.; Robineau, C.; Le Men, J. Bull. Soc. Chim. Biol. 37, 361 (1955)
(17) Plat, M.; Le Men, J.; Janot, M.-M. Bull. Soc. Chim. Biol. 45, 1119 (1963)
(18) Nishinaga, A.; Matsuura, T. J. Org. Chem. 29, 1812 (1964) Post 477375 (Rhodium: "Vanillin --ICl--> 5-Iodovanillin", Novel Discourse)
(19) Banerjee, S. K.; Manolopoulo, M.; Pepper, J. M. Can. J. Chem. 40, 2175 (1962) Post 403132 (Rhodium: "5-Hydroxyvanillin from 5-Iodovanillin", Novel Discourse)
(20) Clark, J. H.; Holland, H. L.; Miller, J. M. Tetrahedron Lett. 3361 (1976)
(22) Semmler, F. W. Ber. Dtsch. Chem. Ges. 24, 3818 (1891)

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	All posts		Subject: Myristicin-derived Cathinones (Precursor prep)		Please login to post


		Rhodium (Chief Bee) 12-17-03 10:25 No 477377				Myristicin-derived Cathinones (Precursor prep) (Rated as: excellent)
						Structure and Synthesis of (±)-Wuweizisu C Gail E. Schneiders and Robert Stevenson J. Org. Chem. 46, 2969-2971 (1981) 3-Methoxy-4,5-Methylenedioxy-Propiophenone (7) has been reported as a natural product from Oenanthe crocata L. and named crocatone^16,17 but it has apparently not been previously synthesized. It was made readily from vanillin (3) by treatment with iodine monochloride to give 5-iodovanillin (4)¹⁸ which on being heated with sodium hydroxide and cupric sulfate solution¹⁹ yielded 3,4-dihydroxy-5-methoxybenzaldehyde (5). Methylenation of 5 by a recently described procedure²⁰ (CH₂Cl₂-KF-HCONMe₂) afforded the aldehyde 6 in 65% yield, and conversion to crocatone (7) was effected by the standard procedure of oxidation of the alcohol obtained by addition of ethylmagnesium bromide (Scheme I). Crocatone (7) cleanly afforded the -bromo derivative 8 by bromination in chloroform solution. Experimental 4-Hydroxy-5-iodo-3-methoxybenzaldehyde (5-iodovanillin, 4) This was prepared as previously described¹⁸ in 81% yield by treatment of vanillin 3 with iodine monochloride and isolated as prisms from ethanol: mp 180-181°C (lit.¹⁸ mp 181-182°C). 3,4-Dihydroxy-5-methoxybenzaldehyde (5-Hydroxyvanillin, 5) This was prepared as previously described¹⁹ in 68% yield by heating 5-iodovanillin 4 with sodium hydroxide and copper sulfate solution and isolated as plates from benzene: mp 133-134°C (lit.¹⁹ mp 133-134°C). 3-Methoxy-4,5-(methylenedioxy)benzaldehyde (6) Potassium fluoride (14.0 g) and methylene chloride (75 mL) were added to a solution of 3,4-dihydroxy-5-methoxybenzaldehyde 5 (9.0 g) in dimethylformamide (300 mL), and the mixture was heated under reflux with stirring under a nitrogen atmosphere for 1.5 h. It was then diluted with water (ca. 200 mL) and extracted with ether (3x200 mL), and the extract was washed successively with 5% aqueous sodium hydroxide solution (3x150 mL), water, and brine. Evaporation of the dried (MgSO₄ extract yielded a residue, which on crystallization from methanol gave the methoxy(methy1enedioxy)benzaldehyde 6 as prisms: 6.15g; mp 131-132°C (lit.²² mp 130°C). 3-Methoxy-4,5-(methylenedioxy)propiophenone (Crocatone, 7) A solution of 3-methoxy-4,5-(methylenedioxy)benzaldehyde (3.53 g) in ether (150 mL) was added to a solution of ethylmagnesium bromide [from magnesium (2.75 g), Vitride (Eastman, 1 mL), ethyl bromide (10 mL), and ether (100 mL)]. The mixture was stirred for 30 min and then worked up in the usual way to give the intermediate alcohol as a colorless oil: 3.17 g. To a solution of this alcohol (3.0 g) in acetone (25 mL) at 0-5°C was added Jones reagent (1.4 M, 8 mL) dropwise over 10 min, the mixture was stirred at room temperature for 30 min, and then 2-propanol (3 mL) was added. It was worked up by aqueous dilution, concentration, and ether extraction. The washed and dried ether extract yielded crocatone (7) as needles (2.23 g) from petroleum ether: mp 88-89°C (lit.¹⁶ mp 89°C). -Bromo-3-methoxy-4,5-(methylenedioxy)propiophenone (8) To a solution of the ketone 7 (2.0 g) in chloroform (12 mL) was added dropwise with stirring a solution of bromine (1.4 g) in chloroform (7 mL), and the mixture was allowed to stand for 1.5 h. It was then washed with water (25 mL) and saturated sodium bicarbonate solution (2x25 mL), dried, and evaporated to give the bromo ketone 8 as long white needles (2.20 g) from ethanol: mp 114.5-115°C. References (16) Janot, M.-M.; Robineau, C.; Le Men, J. Bull. Soc. Chim. Biol. 37, 361 (1955) (17) Plat, M.; Le Men, J.; Janot, M.-M. Bull. Soc. Chim. Biol. 45, 1119 (1963) (18) Nishinaga, A.; Matsuura, T. J. Org. Chem. 29, 1812 (1964) Post 477375 (Rhodium: "Vanillin --ICl--> 5-Iodovanillin", Novel Discourse) (19) Banerjee, S. K.; Manolopoulo, M.; Pepper, J. M. Can. J. Chem. 40, 2175 (1962) Post 403132 (Rhodium: "5-Hydroxyvanillin from 5-Iodovanillin", Novel Discourse) (20) Clark, J. H.; Holland, H. L.; Miller, J. M. Tetrahedron Lett. 3361 (1976) (22) Semmler, F. W. Ber. Dtsch. Chem. Ges. 24, 3818 (1891) ^{The Hive - Clandestine Chemists Without Borders}

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