Indoles, sodium periodate

A. Indole Sodium. In a 100-ml., three-necked flask fitted with a reflux condenser, a magnetic stirring bar, and a gas inlet tube is placed 2.34 g. (0.02 mole) of indole (Note 1) and 15 ml. of hexamethylphos-phoramide (HMPA) (Note 2) under a static atmosphere of argon. The flask is cooled to 0° by means of an ice bath, and 0.53 g. (0.022 mole) of sodium hydride is added to the stirred solution over a period of 10 minutes (Note 3). The resulting slurry is then stirred for 5 hours at room temperature (Note 4). 

The synthesis of a C-labelled version of naratriptan (3b) is highlighted in Scheme The indole ring of naratriptan hydrochloride (3) was oxidatively cleaved using sodium periodate to give ketoformanilide 45. Cyanation of 45 with potassium [ C]cyanide in aqueous ethanol gave the intermediate amidine 46, which was reduced directly with NaBH4 in acetic acid to afford C-labelled naratriptan (3b), which was isolated as the hydrochloride salt. 

Oxidative cleavage of the indole 2,3-double bond can be achieved with ozone, sodium periodate, potassium superoxide, " with oxygen in the presence of cuprous chloride and with oxygen, photochemi-cally in ethanolic solution. ... 

Sodium periodate oxidations of several cycloalk[h]indoles and their JV-methyl analogues have been reported to give ring-expanded keto-lactams,... 

To a suspension of the 3-[(dimethylamino)acetyl]-N-methyl-lH-indole-5-methanesulphonamide (46.5 mg) in 1-propanol (5 ml) was added sodium borohydride (62 mg). The reaction mixture was brought to reflux for a period of 3 h, then an additional quantity of borohydride (60 mg) was added. After refluxing for a further 1 h, the mixture was allowed to cool to room temperature and quenched with 2 N HCI (10 ml). The aqueous solution was washed with ethyl acetate (5 ml) then neutralized (NaHC03 solution) and extracted with ethyl acetate (3 x 15 ml). The combined extracts were concentrated in vacuo and the residue chromatographed to give the 3-[2-(dimethylamino)ethyl]-N-methyl lH-indole-5-methanesulphonamide as a gum (2 mg) which was shown by TLC. 

A solution of 4.19 g of phenylchloroformate (27 mmol) in 25 mL of dichloromethane was added over a period of an hour to an ice cooled, stirred suspension of 2 g (17.1 mmol) of indole, 2 g (50 mmol) of freshly powdered NaOH, and 0.16 g of tetra-butylammonium bromide (50 mmol) in 25 mL of dichloromethane. The mixture was stirred for a further 2 h. 50 mL of water were added and the mixture was extracted with 3 x 30 mL of dichloromethane. The combined extracts were dried with anhydrous sodium sulfate, filtered and evaporated to give pink crystals. These were recrystallized from diethyl ether to yield 3.05 g (75%) of colorless crystals, mp 94 - 95 X. 

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