Russian Journal of Applied Chemistry, 2009, Vol. 82, No. 5, pp. 866−870.
Pleiades Publishing, Ltd., 2009.
Original Russian Text
D.V. Eremin, L.A. Petrov, 2009, published in Zhurnal Prikladnoi Khimii, 2009, Vol. 82, No. 5, pp. 812−816.
ORGANIC SYNTHESIS AND INDUSTRIAL
Optimization of Conditions for Preparing Vitamin K
by Oxidation of 2-Methylnaphthalene
with Chromium Trioxide in Acid Solutions
D. V. Eremin and L. A. Petrov
Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, Yekaterinburg, Russia
Received October 8, 2008
Abstract—Optimal conditions were found for oxidation of 2-methylnaphthalene to 2-methyl-1,4-naphthoquinone
with chromium trioxide in sulfuric and acetic acids. The following factors were varied: degree of acid dilution with
water, substrate to oxidant weight ratio, and reaction temperature and time. The influence of the rate of reactant
mixing and of the reaction temperature on the reaction course was evaluated.
dione, MNQ) belongs to the fat-soluble vitamins of
group K. It is widely used in medicine and animal and
especially poultry husbandry as an agent for improving
blood coagulation . Its relatively high activity against
various tumor cells was revealed . The water-soluble
form of vitamin K
is Vicasol (sodium 2,3-dihydro-2-
The most widely used procedure for commercial
production of MNQ is oxidation of by-product coke 2-
methylnaphthalene (MN) in sulfuric or acetic acid with
chromium(VI) compounds [3–5]:
An advantage of this procedure that Cr(III) compounds
formed in the process are starting compounds for
preparing commercial products, leather and fur hardeners.
However, under the conditions ensuring high quality of
the vitamin and hardener, the reaction yield with respect
to the vitamin does not exceed 50–60% because of the
concomitant oxidation processes.
This process is not described in detail in the available
literature. The effect of temperature, degree of acid
dilution with water, substrate to oxidant weight ratio, and
other process parameters on the reaction kinetics have not
been reported. Only oxidation of 2-methylnaphthalene
with hydrogen peroxide in acetic acid was studied in detail
. By varying various process parameters, conditions
ensuring the maximal yield of vitamin K
In view of the fact that vitamin K
is demanded but
is not produced in Russia, studies aimed to improve
its production procedures suitable for commercial
implementation are quite topical.
We optimized the conditions for 2-methylnaphthalene
oxidation to MNQ with chromium trioxide in acetic
and sulfuric acids. As optimization parameters we
chose the yield of vitamin K
and the conversion
of 2-methylnaphthalene. As factors affecting the
optimization parameters we chose the degree of acid
dilution with water, the oxidant to substrate weight
ratio, and the reaction temperature.
The reaction progress was monitored by the kinetic
curves. By so doing, we automatically determined the
fourth factor, reaction time. The experimental design
showed that the full factorial experiment in which all
the possible combinations of factor values are tested is
impossible because of enormous number of experiments.
In this model, the number of experiments N = k
(k is the
Deep oxidation products