Nucleic acid related compounds.: 116.: Nonaqueous diazotization of aminopurine nucleosides.: Mechanistic considerations and efficient procedures with tert-butyl nitrite or sodium nitrite

Nonaqueous diazotization-dediazoniation of two types of aminopurine nucleoside derivatives has been investigated. Treatment of 9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-2-amino-6-chloropurine (1) with SbCl3/CH2Cl2 was examined with benzyltriethylammonium (BTEA) chloride as a soluble halide source and tert-butyl nitrite (TBN) or sodium nitrite as the diazotization reagent. Optimized yields (> 80%) of the 2,6-dichloropurine derivative were obtained with SbCl3. Combinations with SbBr3/ CH2Br2 gave the 2-bromo-6-chloropurine product (> 60%), and SbL3/CH2I2/THF gave the 2-iodo-6-chloropurine derivative (> 45%). Antimony trihalide catalysis was highly beneficial. Mixed combinations (SbX3/CH2X'(2); X/X' = Br/Cl) gave mixtures of 2-(bromo, chloro, and hydro)-6-chloropurine derivatives that were dependent on reaction conditions. Addition of iodoacetic acid (IAA) resulted in diversion of purine radical species into a 2-iodo-6-chloropurine derivative with commensurate loss of other radical-derived products. This allowed evaluation of the efficiency of SbX3-promoted cation-derived dediazoniations relative to radical-derived reactions. Efficient conversions of adenosine, 2'-deoxyadenosine, and related adenine nucleosides into 6-halopurine derivatives of current interest were developed with analogous combinations.