Miscellaneous Methods for the Oxidation of Alcohols

2 Miscellaneous Methods for the Oxidation of Alcohols Dicyclohexylcarbodiimide/DMSO 

The original discovery of Pfitzner and Moffatt [1390] that alcohols are oxidized to carbonyl compounds by dimethyl sulfoxide, dicydohexylcarbodiimide (DCC), and phosphoric acid at room temperature was immediately recognized as an effective and mild procedure for sensitive substrates. 

Typical procedure. Methyl Z3-0-isopropyUdene-fi-D-ribo-pentodialdo-l,4-furanoside 1870 [1391] A solution of anhydrous crystalline orthophosphoric add (0.98 g, 10 mmol) in dimethyl sulfoxide (2.0 mL) was added to a solution of methyl-2,3-O-iso-propylidene-/ -D-ribofuranoside (4.08 g, 20 mmol), pyridine (0.8 mL, 10 mmol), and DCC (12.4 g, 60 mmol) in dimethyl sulfoxide (50 mL). The mixture was kept at around 25 °C for 3 h by occasional ice-cooling, then diluted with ethyl acetate (100 mL), and a solution of oxalic acid dihydrate (5.04 g, 40 mmol) in methanol (10 mL) was added. The mixture was subsequently poured into saturated sodium chloride solution (200 mL), filtered, and the aqueous phase was extracted with ethyl acetate (100 mL). The combined organic phases were washed successively with dilute sodium hydrogen carbonate solution (100 mL), saturated sodium chloride solution (2 X 100 mL), and iced water (100 mL). The organic phase was dried with magnesium sulfate, concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (25 mL) and filtered to remove residual N,N -dicyclohexylurea. The solution was concentrated to a syrup (4.7 g), which was purified by sublimation at 60-70 °C (0.1 Torr) to give the product 1870 as a white crystalline solid, 3.23 g 

Typical procedure. Cholan-24-al 1871 [1392] Cholan-24-ol (1.033 g, 3 mmol) was dissolved in dry benzene (10 mL) by gentle warming and dry dimethyl sulfoxide (10 mL) was added, followed successively by dry pyridine (0.24 mL, 3.0 mmol), distilled trifluoroacetic acid (0.12 mL, 1.5 mmol), and dicyclohexylcarbodiimide (1.85 g, 9 mmol). The flask was tightly stoppered and left at room temperature for 18 h. Benzene (30 mL) was then added, and the crystalline dicyclohexylurea formed was removed by flltration and washed with benzene. The combined filtrate and washings were washed with water (3 x 50 mL), dried over sodium sulfate, and concentrated under reduced pressure to give 2.12 g of a syrup, which partially crystallized. The crude product was dissolved in benzene/hexane, 1 1, and chromatographed on 125 g of silica gel with this solvent mixture to give cholan-24-al 1871 (0.87 g, 84%) mp 102-104 °C. 

An N-protected amino aldehyde can be prepared by Swem oxidation of an N-pro-tected amino alcohol in the presence of an oxidizing agent comprising DMSO and a water-soluble carbodiimide derivative as l-ethyl-3-(3-dimethylaminopropyl)carbo-diimide hydrochloride (EDC) in an organic solvent. The N-protected amino alcohol can be derived from an L-, D-, or L-/D-amino acid, but usually is the N-protected-(S)-a-amino alcohol derived from an N-protected L-amino acid. 

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