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

Abstract

Nonaqueous diazotization-dediazoniation of two types of aminopurine nucleoside derivatives has been investigated. Treatment of 9-(2,3,5-tri-O-acetyl-β-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 SbI3/CH2I2/THF gave the 2-iodo-6-chloropurine derivative (>45%). Antimony trihalide catalysis was highly beneficial. Mixed combinations (SbX3/CH2X′2; X/X′ = Bt/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.