S_NAr Iodination of 6-Chloropurine Nucleosides:  Aromatic Finkelstein Reactions at Temperatures Below −40 °C¹

Abstract

Mesitoyl or toluoyl esters of inosine and 2'-deoxyinosine were deoxychlorinated at C6 to give the crystalline 6-chloropurine nucleoside derivatives, which underwent quantitative conversion to the 6-iodo analogues with NaI/TFA/butanone at -50 to -40 degrees C. The 6-iodo compounds were efficient substrates for SNAr, Sonogashira, and Suzuki-Miyaura reactions, in contrast with the 6-chloro analogues, and gave good to high yields of C-N and C-C coupled products.

Thermal N-9 → N-7 Isomerization of (6-Substituted)-9-(2,3-Dihydro-5H-1,4-Benzodioxepin-3-yl)-9H-Purines in Solution: Mechanistic Aspects

“…162.07 ppm (12), 163.78 ppm (14), 162.84 ppm (15), 160.85 ppm (16), 161.00 ppm (17), and 161.40 ppm (19). These values agree with previous findings on acyclic adenine derivatives [24].…”

Very Efficient Nucleophilic Aromatic Fluorination Reaction in Molten Salts: A Mechanistic Study

“…Various schemes were employed to separate the nucleophile from the metal cation, but even strong bases such as the crown ether are not very good for that purpose. Ionic liquids and molten salts [16][17][18][19][20][21][22][23][24] have recently been found to be quite useful for some organic reactions. For example, D'Anna and co-workers found that in S N Ar reactions amines react faster in ionic liquids than in molecular solvents by almost 1 or 3 orders of magnitude.…”

O6‐(Benzotriazol‐1‐yl)inosine Derivatives for C6 Modification of Purine Nucleosides

“…Electrophilic nucleosides are convenient reagents for access to modified nucleosides via displacement reactions of suitable leaving groups by nucleophiles. In this context, C6 chloro (Robins and Basom, 1973;Robins and Uznański, 1981a;Véliz and Beal, 2000;Francom et al, 2002;Francom and Robbins, 2003), bromo (Nair and Richardson, 1980;Lakshman et al, 1999;Véliz and Beal, 2001;Lagisetty et al, 2006), iodo (Cosstick and Douglas, 1991;van der Wenden et al, 1995;Liu et al, 2004), fluoro (Robins and Basom, 1973;Robins and Uznański, 1981b), phenoxy (Gao et al, 1992;Lakshman and Zajc, 1996;Allerson et al, 1997), aryl sulfonyl (Hayakawa et al, 1993;Allerson et al, 1997), alkyl sulfonyl (Nagatsugi et al, 1997), pyridyl (Adamiak et al, 1985;Fathi et al, 1990), sulfone (Lin and Robins, 2000), and imidazolyl (Lin and Robins, 2000;Janeba et al, 2004) derivatives have all found applications as reactive nucleoside derivatives.…”