Weygand/Hilgetag Preparative Organic Chemistry

Isotope exchange methods 99
readily converted into their perdeuterated derivatives at room temperature.
The exchange rate is particular great for ^-positions in side chains of alkylaromatic
compounds; thus the a-hydrogen atoms df toluene are exchanged
300 times faster than the hydrogen atoms of benzene, and this fact can be
utilized for selective deuteration of such positions, achieved by shortening the
reaction period. On the other hand, increasing both the concentration of
potassium amide and the temperature (to 120°) leads to exchange also of the
^-hydrogen atoms of ethylbenzene.
ND3 and KND2 lead also to isotope exchange in olefins, though here appreciably
more slowly. A small amount of replacement of hydrogen by deuterium
has even been observed for some aliphatic hydrocarbons.
IV. Exchange reactions in acid media
Labeling in acid media is favored by substituents such as OH, OCH3, NH2,
and NR2, this being the reverse of the relations for base-catalyzed isotope
exchange. The order of relative substitution rates and the directing effects of
substituents for exchange of hydrogen follow the rules of normal electrophilic
substitution. Accordingly, aniline is deuterated even by dilute deuterium
chloride, giving 2,4,6-trideuterioaniline, which is used for preparation of
[1,3,5-D3]benzene by diazotization and reduction with sodium stannite. 45
D3O + ions are, however, normally insufficiently powerful deuteron-donors
for labeling aromatic hydrocarbons; but as early as 1936 Ingold and his
colleagues 94 found that deuterium sulfate constituted a suitable reagent for
preparation of labeled compounds. A concentration of 65 mole-% of acid
caused side reactions as well as exchange, and at a concentration of 40 mole-%
exchange is very slow, so experiments are carried out at acid concentrations of
51-52 mole-% in D2O.
Pure benzene is carefully dried over P2O5, then distilled into deuterium sulfate, and the
mixture is shaken for 3-4 days, after which the benzene is distilled off in a vacuum into a
fresh batch of D2SO4. After four repetitions of these operations the benzene is transferred
to a flask containing roasted barium oxide, after 12 hours to a flask containing P2O5, and
after a further 15min to a storage flask. The [D6]benzene obtained contains 99.8% of
deuterium.
D3PO4 is less powerful, but correspondingly more selective, azulene, for
instance, being labeled by it in the 1,3-positions. 95 One the other hand, DC1
containing A1C13 is a more powerful reagent than D2SO4; equilibrium is
established already after 3 hours at 25° if DC1 is led into a suspension of A1C13
in benzene; 40 hours suffice for obtaining 36 ml of [D6]benzene containing
99.3% of deuterium. 96
94 C. K. Ingold and co-workers, /. Chem. Soc, 1936, 915, 1637; Z. Elektrochem. Angew.
Phys. Chem., 44, 62 (1938).
95 A. Bauder and H. H. Gunthard, Helv. Chim. Acta, 41, 889 (1958).
96 M. Briillmann, H.-J. Gerber, and D. Meier, Helv. Chim. Acta, 41, 1831 (1958).