1070-4272/03/7608-1315 $25.00 C 2003 MAIK [Nauka/Interperiodica]
Russian Journal of Applied Chemistry, Vol. 76, No. 8, 2003, pp. 1315!1318. Translated from Zhurnal Prikladnoi Khimii, Vol. 76, No. 8, 2003,
Original Russian Text Copyright + 2003 by Kaabak, Stepnova, Khudenko, Tomilov.
AND POLYMERIC MATERIALS
Low-Waste Process for Preparing Ketopantolactone, with
Electrochemical Recovery of Bromine
L. V. Kaabak, N. P. Stepnova, A. V. Khudenko, and A. P. Tomilov
State Research Institute of Organic Chemistry and Technology, Moscow, Russia
Received January 17, 2003
Abstract-The process parameters of dehydrogenation of pantolactone with bromine in chloroform and the
possibility of bromine recycling by electrolysis of hydrogen bromide formed in the synthesis of ketopanto-
lactone were studied.
Ketopantolactone (KPL) shows promise for phar-
maceutical industry. The known methods for its pre-
paration are based on oxidative dehydrogenation of
There are published data on oxidation of PL with
oxygen in the presence of a catalyst [1, 2], as well as
with calcium hypochlorite , potassium bromate
[6, 7], bromine , and organic peroxides .
These data show that PL is catalytically oxidized at
1803300oC and elevated pressure, which requires
complex equipment; the target product undergoes
partial tarring. With chlorine or calcium hypochlorite,
abundant nonutilizable wastewater is formed. The re-
action with bromine as dehydrogenating agent pro-
ceeds by the scheme:
ÍO + 2HBr.
ÍO + 2HBr.
This scheme suggests formation of an equivalent
amount of hydrogen bromide, which is suitable for
high-yield recovery of recyclable bromine. This op-
tion was recognized as the most promising and was
In , dehydrogenation of PL with bromine in re-
fluxing carbon tetrachloride was recommended; the re-
action is complete within 538 h. In , this period
was reduced to 1 h by adding a minor amount of
water to the reaction mixture.
Presently, carbon tetrachloride is considered un-
suitable as solvent for environmental reasons and its
production is to be closed . Therefore, we re-
placed carbon tetrachloride with chloroform in our ex-
periments. Next, the possibility of recovery of bro-
mine from an aqueous solution of hydrogen bromide
formed in the synthesis was analyzed.
The initial experiments on dehydrogenation of PL
in chloroform failed. The reaction was incomplete
even after refluxing the PL solution in chloroform
with bromine for 14 h, probably because of the lower
boiling point of CHCl
, compared to CCl
. The situa-
tion was substantially improved by introducing minor
amounts of water to the reaction mixture: When 10 ml
of water was added to 60 ml of chloroform, the reac-
tion was complete after heating for 3.5 h. However,
further increase in the content of water decreased
the weight of the target product. For example, upon
adding 60 ml of water, the yield of KPL after reflux-
ing for 5 h was only 48%, and at water content below
10% the reaction was decelerated and HBr evaporated.
An important role is also played by the PL con-
centration in chloroform. Table 1 shows that, at the
PL : chloroform ratio of 1 : 7.5, the KPL yield remains
fairly high, but falls dramatically with the amount of
chloroform decreasing further; the reaction does not
go to completion despite longer heating time. Thus,
we developed a procedure for preparing KPL in 923
All the above-described experiments were per-
formed in a 150-ml reactor charged with 4 g of PL.
To test the suitability of the process for large-scale
application, we carried out an experiment in a 2-l reac-
tor charged with 100 g of PL, 900 ml of chloroform,
160 ml of water, and 137 g of bromine. The very
first run showed that, on passing to a larger reactor,