A convenient synthesis of deuterium labelled diphenylhydantoin

Abstract

A simple, inexpensive method for the synthesis of deuterated diphenylhydantoin is described. moiety of the diphenylhydantoin molecule. Ten deuterium atoms a r e introduced to the 5,5-diphenyl KEY WORDS Deuterated diphenylhydantoin; Mass fragrnentographic analysis Vol. X , 469 (1974). Division of Medicinal C h e m i s t r y and Pharmacognosy:: and Division of P h a r m a c e u t i c s and P h a r m a c e u t i c a l Analysis>::< Lexington, Kentucky 40506 University of Kentucky, College of P h a r m a c y t T o whom correspondence should be a d d r e s s e d .

Synthesis of deuterium‐labelled drugs by hydrogen–deuterium (H–D) exchange using heterogeneous catalysis

“…The exchange of the valpromide hydrogens with deuterium could therefore be expected to increase the half‐life and lower the clearance value due to the isotope effect. Fully deuterated phenytoin, [ 2 H 10 ]phenytoin, was synthesized by the modified Bucherer–Bergs reaction of [ 2 H 10 ]benzophenone,33 which was prepared from [ 2 H 6 ]benzene and [ 2 H 5 ]benzoyl chloride,34 while no synthesis of the deuterated valpromide has been reported in the literature.…”

Synthesis, NMR analysis and applications of isotope-labelled hydantoins

“…[ 13 C6]Benzene (43a) has been subject to Friedel-Crafts reaction and then followed by Bucherer-Bergs reaction to produce 5-( 13 C6-phenyl)-5-phenylhydantoin (3e) (Figure 8, Scheme 13) [91]. Using a similar approach but starting with d6-benzene (43b), a deuterated form of phenytoin has been synthesised with all aromatic hydrogen atoms replaced by deuterium (3f) (Figure 8, Scheme 14) [92]. The same compound has also been produced more directly by reacting parabanic acid (24) with d6-benzene (43b) and triflic acid (Figure 8, Scheme 14) [93].…”

“…3-Methyl-2-thiohydantoin (93) has been synthesised with a 14 C label at C-4 in two steps from [1-14 C]glycine (6d) (Figure 14, Scheme 25) [116]. Reaction of the glycine with methyl isothiocyanate under basic conditions produced 14 C-labelled 5-methylthiohydantoic acid (92), which cyclises at acidic pH to [4-14 C]-3-methyl-2-thiohydantoin (93).…”