The xanthines and isoxanthines differ in that only the latter can be methylated4 directly in the eighth position. According to Biltz and Sauer, lJ3, 9-trimethylisoxanthine is readily methylated in the eighth position with methyl sulfate. This is probably effected by addition of methyl and monomethyl sulfate radicals at the 7-8 double bond, and subsequent elimination of methyl hydrogen sulfate. Apparently the 8-9 double bond in caffeine does not favor the ...
