Synthesis of Labeled Caffeine - Caffeine: Chemistry, Analysis, Function and Effects - page 82

d n 0 t 2 n g | 2

Scheme 5.11 Syntheses of [CD 3 ]caffeine from xanthine derivatives. Caffeine labeling

of unsubstituted nitrogen from a xanthine derivative by the action of
CD 3 I in the presence of base allowed for the preparation of all possible
isotopomers of [CD 3 ]caffeine.

preparative TLC (Falconnet et al 1986), silica column chromatography
(Cherrah et al 1987), liquid-liquid extraction followed by recrystallization
from ethanol (Horning et al 1979) and preparative HPLC (Regal et al 2005).
[7-CD 3 ]caffeine (39) was prepared by methylation of 1,3-dimethylxanthine (9)
in an acetone-water mixture in the presence of sodium hydroxide (Cherrah et al
1987; Falconnet et al 1986; Horning et al 1979), or in DMF in the presence of
potassium carbonate (Tserng 1983), or in DMF in the presence of sodium
hydroxide (Hill et al 1988), or finally in methanol in the presence of sodium
methylate (Balssa and Bonnaire 2007). This compound was purified by
preparative TLC (Falconnet et al 1986), silica column chromatography
(Cherrah et al 1987), liquid-liquid extraction followed by recrystallization from
ethanol (Horning et al 1979), liquid-liquid extraction (Tserng 1983), precipita-
tion (Hill et al 1988), recrystallization from water (Telo and Vieira 1997) or
recrystallization from chloroform-diethylether (Balssa and Bonnaire 2007).
Syntheses of [(CD 3 ) 2 ]caffeine
[1,3-(CD 3 ) 2 ]caffeine (43), [1,7-(CD 3 ) 2 ]caffeine (44) and [3,7-(CD 3 ) 2 ]caffeine
(45) were made from respectively 7-methylxanthine (40) (Falconnet et al 1986),
3-methylxanthine (41) (Cherrah et al 1987; Falconnet et al 1986) and 1-
methylxanthine (42) (Cherrah et al 1987; Falconnet et al 1986; Regal et al
2005). These isotopomers were prepared by the action of CD 3 I in an acetone-