Synthesis of Labeled Caffeine - Caffeine: Chemistry, Analysis, Function and Effects - page 84

5.4.1 Characterization by Nuclear Magnetic Resonance
Detailed 1 H, 2 Hand 13 C NMR data for seven kinds of [CD 3 ]caffeinehavebeen
published (Falconnet et al 1986). Additional data have been reported for 1 HNMR
of [7-CD 3 ]caffeine (Balssa and Bonnaire 2007), 1 H NMR of [1,3- 15 N 2 ]caffeine
(Kenani et al 1995) and 13 Cand 15 N NMR of caffeine (Stikowski 1995).

d n 0 t 2 n g | 2

5.4.2 Characterization by Mass Spectrometry
Mass spectrometry has been widely used for the characterization of labeled
caffeine. Detailed data for [1-CD 3 ]caffeine (Houghton 1982), [3-CD 3 ]caffeine
(Houghton 1982), [7-CD 3 ]caffeine (Balssa and Bonnaire 2007; Hill et al 1988;
Houghton 1982; Tserng 1983), [1,3- 15 N 2 ]caffeine (Kenani et al 1995) and
[1,7- 13 CH 3 ]caffeine (Pierce et al 1984) have been published.

Summary Points
This chapter focuses on labeled caffeine synthesis.
Syntheses of caffeine labeled with

2 H, 3 H, 11 C, 13 C, 14 C and 15 Nhavebeen

described.
Labeled caffeine can be prepared by base or metal catalyzed hydrogen-
deuterium or hydrogen-tritium exchange.
Labeled caffeine can be prepared by partial synthesis such as methylation of
xanthine derivatives (e.g. xanthine, methylxanthine and dimethylxanthine).
Labeled caffeine can be prepared by total synthesis from common labeled
building blocks such as labeled urea, formic acid or formamide.
Labeled caffeine can be easily characterized by nuclear magnetic resonance
or mass spectrometry.

Key Facts of Labeled Caffeine
Labeled caffeine constitutes a potent and irreplaceable tool in analytical
chemistry applied to biology, pharmacology, medicine, botanics …
Labeled caffeine is the native caffeine in which one or more atoms have been
substituted by one or more isotopes.
The introduced isotope in the caffeine molecule may be stable or radioactive.
Labeled caffeine is detected in a biological matrix by mass spectrometry.
Radioactively labeled caffeine is detected by an appropriate radiation detector.
Preparation of caffeine labeled with

2 H, 3 H, 11 C, 13 C, 14 C and 15 N are

described.
Labeled caffeine can be prepared by hydrogen-deuterium or hydrogen-
tritium exchange, by partial synthesis from xanthine derivative or total

synthesis from labeled building blocks.
Labeled caffeine can be characterized by mass spectrometry and by nuclear
magnetic resonance.