An efficient method for synthesis of symmetrical diketones via reaction of .alpha.-amino-.alpha.-arylacetonitriles (masked acyl anion equivalents) with alkyl dibromides

Abstract

Reduction of 1 to 3. A solution of 14.3 mg of 1 in 1 mL of absolute ethanol was treated with 5 mg of NaBH4. The mixture was stirred at room temperature for 80 min and then quenched with several drops of 5% HC1. After addition of 3 mL of water, the product was extracted four times with 3-mL portions of diethyl ether and then dried over anhydrous K2C03. Filtration and evaporation of solvent left 12.7 mg of nearly pure 3, which after HPLC had [o]D 24.3°( c 1.07, CHC13).Reduction of 2 to 4. This was analogous to preparation of 3 from 1 above. From 25 mg 2, 22 mg of crude 4 was obtained. After purification by HPLC, its spectral properties matched those of natural 4.Acetylation of 3 to 4. To a solution of 13.0 mg of 3 in 1 mL of dry pyridine, 50 µ * of freshly distilled acetic anhydride was added, and the reaction was allowed to proceed at room temperature for 17 h. Methylene chloride (10 mL) was added, and the solution was washed with 10% HC1 (2X), saturated CuS04 (2x), and H20 (IX) to remove the pyridine. After drying with anhydrous MgS04 and removal of solvent, 12 mg of 4 remained, about 95% pure by *H NMR. This material was purified by HPLC on Partisil M9 and Lichrosorb-ODS. From natural 3, [a]D 14.2°(c 1.21, CHC13); from synthetic 3, [a]D 20.5°(c 0.57, CHC13).

Indium(I) Bromide-Mediated Reductive Coupling of α,α-Dichloroketones to 1-Aryl-butane-1,4-diones

“…1,4-Bis(4¢-chlorophenyl)-butane-1,4-dione (1c): mp 147-149 °C, lit 9. 148-149 °C.1 H NMR (CDCl 3 ): d = 7.97 (d, 4 H), 7.41 (d, 4 H), 3.42 (s, 4 H).…”

An Efficient and Facile Synthesis of Capsaicin‐Like Compounds as Agonists of the TRPV1 Receptor

“…[16] The THP group was, however, unsuitable for the synthesis of compounds 17, 18 and 19 according to Scheme 2, because it would be cleaved by acid hydrolysis (step iii, Scheme 2) of 10 to form 11. In this case a benzyl group, readily removed by catalytic hydrogenation, was used to protect the phenolic OH group.…”

“…The mixture was stirred at -80°C for 15 min then brought to room temperature and further stirred for 2 h. To this mixture cooled to -80°C was added dropwise a solution of 1 (2.0 g, 0.007 mol) in THF (5 mL). The mixture was stirred at -80°C for 5 h, quenched with wet ether, extracted with Et 2 O (2 × 50 mL), washed with brine solution (20 mL) and evaporated to give a residue which was refluxed with aqueous oxalic acid [16,22] (30 % w/v) in THF for 1.5 h. The resulting mixture was then extracted with ethyl acetate (2 × 50 mL). After evaporation of solvent, crude product was purified by short-column vacuum chromatography as described above to afford a colourless solid, 1.…”

“…To this oil (0.32 g) was added ethanol (10 mL), cyclohexene (5 mL) and Pd-C (10 %, 0.02 g). [16] The mixture was stirred under reflux for 3 h, filtered and the solvent evaporated under reduced pressure to give an oil which was purified by short-column vacuum chromatography to afford a colourless oil, 0.2 g, 80 % yield. Hydroxy-1-(4-hydroxy-3-methoxyphenyl)undecan-1-one (20): The synthesis was accomplished according to the general procedure as described for 14 via aldol condensation between 7 (1 g, 0.003 mol) and decyl aldehyde (0.5 g, 0.003 mol).…”

Generation and Reaction of Ammonium Ylides in Basic Two‐Phase Systems

“…All solvents used were commercially available; Me 2 SO 4 was purified before use. [56] Synthesis of Aminonitriles 1a-h and Aminoester 1i: Aminonitriles 1a1, [57] 1a2, [57,58] 1a3, [57,59] 1b, [60] 1d, [61] 1e, [62,63] 1f, [57,58] 1h, [64] and aminoester 1i [65] were synthesized according to literature methods. 1a3, 1b-d, 1g,h), acetone (10-25 mL) was added, and the crystals were filtered off, washed with acetone (4 × 5-10 mL) and dried under vacuum.…”