This artience has been mentioned before in:
Post 9315
(Rhodium: "LAH alternatives refs", Methods Discourse)
Post 108634 (missing)
(dormouse: "The Good Reverend's nitrostyrene reduction contest -rev drone", Novel Discourse)
Post 78688 (missing)
(PolytheneSam: "Re: References on nitrostyrene reduction", Chemistry Discourse)
Studies on the Alkaloids of Menispermaceous Plants. CCXLIV.
Synthesis of dl-CepharanthineMasao Tomita, Kazuyoshi Fujitani, Yoshiaki Aoyagi, and Yasumichi KajitaChem. Pharm. Bull. 16(2) 217-226 (1968)
(
https://www.thevespiary.org/rhodium/Rhodium/pdf/cepharantine.ns2pea.zn-hg.pdf)
5-Bromopiperonal (
VI) obtained in relatively high yield (42-64%) from 5-bromoprotocatechuic aldehyde (
V) through methylenation reaction catalysed by cupric oxide
10 was condensed with nitromethane in the presence of ammonium acetate in acetic acid to afford a nitrostyrene (
VII), which was reduced to a phenethylamine (
VIII) under Clemmensen condition. Preparation of
VIII starting with 5-bromoprotocatechuic aldehyde was already reported by Erne and Ramirez,
11 but the modification adopted by the present authors raised the yield in every step of the reaction sequence. [...] 3-methoxy-4-hydroxy-?-nitrostyrene (
X)
12 was treated with ethyl chloroformate in pyridine and the resulted O-carbethoxy derivative (
XI) was reduced under Clemmensen condition to give a phenethylamine (
XII).
Experimental3-Bromo-4,5-methylenedioxy-?-nitrostyrene (VII) The solution of 5-bromopiperonal (64 g), nitromethane (65 g), and NH
4OAc (30 g) in AcOH (400 ml) was heated to reflux for 2 hr. After cooling, the mixture was poured into water (1 liter); a precipitated crystalline solid was collected by filtration. Recrystallization of the above crystalline substance from 50% (by vol.) CHCl
3-EtOH afforded the product. Yield 55 g. Yellow needles, mp 160-162°C (lit.
11 mp 160-161°C).
3-Bromo-4,5-methylenedioxy-?-phenethylamine (VIII)The foregoing nitrostyrene (
VII, 53 g) and amalgamated zinc prepared from zinc powder (200 g) and HgCl
2 (20 g) were suspended on EtOH (2 liter). Under vigorous stirring, conc. HCl was added portionwise into the above mixture until the yellow coloring of the reaction mixture disappeared. After the decolorization was completed, the reaction mixture was further stirred for 30 min. An excess Zn-Hg was filtered off; EtOH was evaporated in vacuo, and the residue was poured into water (1 liter). The aqueous solution was made alkaline with conc. NH
4OH after washed with ether; then the basic product was extracted into CHCl
3, and the washed CHCl
3 extracts were evaporated to give the product. Light-brown viscous oily substance, yield 32 g. Hydrochloride: Recrystallized from EtOH-acetone, colorless platelets, mp 238-240°C (dec.) (lit.
11 mp 250-251°C).
3-Methoxy-4-O-carbethoxy-?-nitrostyrene (XI)To a solution of 3-methoxy-4-hydroxy-?-nitrostyrene (15 g) in pyridine (100 ml), ethyl chloroformate (15 ml) was added dropwise with stirring on an ice bath. After the addition was completed, the mixture was further stirred for 3 hr at room temperature, then poured into water (1 liter). The precipitated crystals were collected by filtration, then washed with water and MeOH. Yellow needles, mp 125-126°C. Yield 20 g.
3-Methoxy-4-O-carbethoxy-?-phenethylamine (XII) Amalgamated zinc prepared from zinc powder (50 g) and HgCl
2 (5 g) was agitated with MeOH (100 ml) on an ice bath. To the above mixture, conc. HCl and a solution of the foregoing nitrostyrene (19 g) in tetrahydrofuran (200 ml) were added alternately. The temperature of the reaction mixture was kept below 50°C during the reaction. After the addition of the nitrostyrene solution was completed and the yellow coloring of the reaction mixture disappeared, an excess Zn-Hg was filtered off, and MeOH and tetrahydrofuran were removed by distillation in vacuo; then the residue was poured into water (500 ml), washed with ether, and the basic product was extracted into CHCl
3 after basification with conc. NH
4OH. Evaporation of the solvent gave the product as a pale yellow oily material. Yield 9.5 g. Oxalate: Recrystallized from EtOH; colorless microcrystals, mp 135-191°C (decomp.).
References[10] M. Tomita, K. Fujitani, and Y. Aoyagi, Chem. Pharm. Bull. (Tokyo), Vol. 16, No. 3, 523-526 (1968)
[11] M. Erne and F. Ramirez, Helv. Chim. Acta, 33, 912 (1950).
Post 506993
(Rhodium: "Mescaline, Amphetamine etc. by LAH reduction", Novel Discourse)[12] G. Hahn and K. Stiehl, Ber., 71, 2154 (1938).