Technology for the industrial production of K3 series vitamins based on menadione


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Aleksey S. Antipov, Vasily A. Nizov, Anna Yu. Antipova
Chimica Techno Acta. 2020. Vol. 7, no. 2. P. 81–86.

ISSN 2409–5613

Aleksey S. Antipova, Vasily A. Nizovb, Anna Yu. 
Antipovaab

aLLC “Novokhrom”, 
462353, 51 Industrial St., Novotroitsk, Orenburg region, Russia

bUral Federal University named after the first President of Russia B. N. Yeltsin, 
620002, 19 Mira St., Yekaterinburg, Russia

e-mail: lexrus91@bk.ru

Technology for the industrial production 
of K3 series vitamins based on menadione

An improved technology for the industrial production of K3 series vitamins 
based on menadion is reported. The procedure involves the Cr(VI) — promoted 
oxidation of the corresponding methyl-naphtahelenes with the following purifi-
cation by precipitation/recrystallization. The best results were obtained under 
the process temperature between 20–40 °C, solution pH after dilution of MNB 
in a range of 5.5–5.7, and MNB content in initial solution of 25–30%. 

Keywords: Vitamin K3; methyl-naphalenes; Cr(VI) — compounds; menadione; industrial scale

Received: 15.04.2020. Accepted: 27.06.2020. Published: 30.06.2020.

© Aleksey S. Antipov, Vasily A. Nizov, Anna Yu. Antipova,  2020

Introduction
For the  industrial production 

of vitamins of the K family, the most acces-
sible and important precursor is 2-methyl-
naphthalene-1,4-dione, (menadione) [1]. 
In some sources, menadione is called vita-
min K3 [2], although derivatives 1,4-naph-
thoquinone are not natural chemicals and 
therefore cannot be qualified as vitamins. 
Menadione can be considered as  pro-
vitamin due to  the  possibility of  its me-
tabolism in the human body into vitamins 
K2, menaquinones, [3] containing vari-
ous alkyl fragments at the position of C3 
of the naphthalene-1,4-dione. 

According to the literature, the simplest 
and most cost-effective industrial meth-
od for producing menadione in the form 
of sodium bisulfite (MSB) or nicotinamide 
bisulfite (MNB) is the Cr(VI) compounds-
mediated oxidation reaction of  2-meth-

ylnaphthalene-containing raw materi-
als in an acidic medium with the release 
of menadione as an intermediate product 
[4], and the  subsequent crystallization 
of the MSB from water or the precipitation 
of  nicotinamide MNB from the  mother 
liquor. Since 2012, a domestic technology 
implemented according to this principle 
has been developed at  the  Novochrom 
LLC enterprise (Novotroitsk, Orenburg 
Region). The main problem of this technol-
ogy is associated with a strict restriction on 
the content of impurity components in fi-
nal consumer products, such as K3 series 
vitamins. For example, EU Regulation No. 
1831/2003 limits the  chromium content 
in sodium menadione bisulfite to 45 mg/
kg, and in  the  menadione nicotinamide 
bisulfite 142 mg/kg. Even trace amounts 



82

of 2-methylnaphthalene, 1-methylnaphtha-
lene, indole(s) are also excluded. 

In connection with the above, the ini-
tial stages of industrial production of K3 
series vitamins are burdened with a  sig-
nificant accumulation of substandard and 
intermediate products, as  well as  high 
costs for their recycling. Namely, the level 
of such important technical and economic 

indicator, as  the  volume of  substandard 
MNB with a chromium content from 300 
to 2500 mg/kg in an amount of more than 
30 tons for 2016 makes the industrial pro-
duction of  K3 series vitamins to  be not 
competitive in the global MSB market [5]. 
The aim of this work was to develop a meth-
odology for the processing of menadione 
nicotinamide bisulfite on an industrial scale.

Experimental part
Research Methodology
Industrial grade MNB with a  chro-

mium content of  2250 mg/kg was used 
for research. Sulfuric acid, sodium car-
bonate, butanol-1 of technical grade were 
purchased from commercial sources. 
Analytical researches were carried out ac-
cording to the methods certified by Novo-
chrom Ltd.

Investigations of the method of pro-
cessing MNB by carrying out the reac-
tions of direct and reverse synthesis

50 g of MNB was re-pulped in 125 ml 
of  water containing 12 ml of  butanol-1. 
Sodium carbonate was slowly, in  small 
portions, added to the resulting suspen-
sion to  achieve a  stable pH of  5.5–5.7. 
The reaction volume was maintained until 
the  MNB was completely dissolved, fol-
lowed by  filtration to  remove insoluble 
particles. After the filtration the obtained 
solution was acidified with 65% sulfuric till 
the pH of 2.0–2.2. The precipitated MNB 
was filtered, washed and air-dried.

Investigation of the influence of the pH 
on the fractionation size of the impurities

The influence of the pH of the medium 
on the fractionation size of chromium-con-
taining impurities was checked similarly 
to the first method, except that before fil-
tering the pH of the solution was reduced 
to 4.5 with the following addition of 5 g 
of diatomite to improve filtration.

Investigation of  the  cyclic method 
of MNB processing

To  study the  cyclic processing pro-
cess, 50 g of MNB was re-pulped in 125 
ml of water containing 12 ml of butanol-1. 
Sodium carbonate was slowly, in small por-
tions, added to  the  resulting suspension 
to reach a stable pH value in a range of 5.5–
5.7. The reaction volume was maintained 
until the MNB was completely dissolved. 
The pH of the solution was reduced to 4.4–
4.6 by the addition of 65% sulfuric acid. 
After that the 5 g of diatomite was added, 
and the  insoluble particles were filtered 
out. The filtered solution was acidified with 
65% sulfuric acid till the  pH of  2.0–2.2, 
and the resulted solution was stirred for 
15 minutes. After the filtration the precipi-
tate was washed and dried. The next cycle 
was carried out similarly to the first one, 
except using a filtrate after the separation 
of the MNB instead of water. At the end 
of  the  third cycle, all the  washings and 
the  filtrate were collected together and 
made alkaline with sodium bicarbonate 
to reach a pH of >10, followed by filtra-
tion and washing of the precipitated me-
nadione.

Investigation of the influence of wa-
ter amount on the  chromium content 
in the recycled MNB

The study of the effect of the amount 
of water on the fractionation of chromium 



83

was carried out according to the methodol-
ogy of the first cycle of the cyclic process, 

except that the amount of water was 50, 80, 
100 and 130 ml.

Results and discussion
The technology for producing K3 vi-

tamins consist of  three separate stages: 
synthesis of  menadione with Cr(VI) 
compounds, isohydric crystallization [6] 
of  MSB, and the  precipitation of  MNB 
by  reaction of  the  mother liquor with 
nicotinamide in  an  acidic media. Based 
on the classical positions of fractionation 
of impurity components in the isohydric 
crystallization mode [6], we refined the de-
pendence of the solubility of MSB in wa-
ter in  the  operating temperature range 
and compiled a nomogram for assessing 
the  possible effects of  purification from 
chromium during crystallization [7].

We have previously shown that the use 
of  additives of  water-soluble aluminum 
salts [8] leads to  a  decrease in  the  chro-
mium content during the synthesis of MSB, 

while using liquid extraction with bu-
tanol-1 leads to  the  production of  high-
quality MNB [9].

The  return of  substandard MNB 
to the scope of implementation is expected 
to be achieved through the sequential pro-
cesses presented in schemes 1–3.

The dissociation of MNB into the start-
ing reagents under the action of alkaline 
reagents, in particular sodium carbonate 
in  the  pH range of  5.5–5.7 (Scheme 1), 
makes it possible to efficiently obtain a so-
lution of MSB and nicotinamide, as well 
as  impurities, which are highly soluble 
in  water. A  further decrease of  the  pH 
of the medium to 4.4–4.6 leads to the pre-
cipitation of chromium-containing impu-
rities, the removal of some of which from 
the solution was made by the filtration, and 

Scheme 1. Decomposition of MNB into the starting reagents

Scheme 2. Synthesis of MNB

Scheme 3. Dissociation of MSB to menadione

2

O

O

SO3H

CH3
N

NH2

O

Na2CO3

O

O

SO3Na

CH32 2

N

NH2

O

H2O CO2

O

O

SO3Na

CH32 2

N

NH2

O

H2SO4 2

O

O

SO3H

CH3
N

NH2

O

Na2SO4

O

O

SO3Na

CH3
OH-

O-

O

S

O

O
O

O

O

CH3

SO3
2–



84

this step was followed by the direct synthe-
sis of MNB. This allows to obtain a product 
with a chromium content of less than 142 
mg/kg. Processing the mother liquor after 
the separation of MNB with alkaline rea-
gents allows additional extraction of MSB 
menadione and its return to  the  stage 
of  the  synthesis of  MNB. The  cleavage 
of  MSB to  menadione was carried out 
by the action of alkaline reagents at a pH 
of more than 11. It should be noted that 
earlier it was shown that in the pH range 
from 6 to 10 the equilibrium is shifted to-
wards the formation of MSB [10].

From the data collected it follows that 
the sequential reverse reaction of the cleav-
age of MNB into initial products at a pH 
of  5.5–5.7 with filtration of  undissolved 
particles, followed by  a  direct synthesis 
reaction, leads only to  a  slight decrease 
in the chromium content in the final prod-
uct.

In the course of studies, it was found 
that when alkaline reagents, in particular 
sodium carbonate and sodium bicarbonate, 
are added to the suspension of the initial 
MNB to adjust a pH to 5.5–5.7 all MNB 
decomposes into the  starting products. 
When the  solution is  acidified with sul-
furic acid to adjust a pH of less than 5.0 
a fine precipitate is formed. The precipi-
tation of  MNB usually begins at  the  pH 

of  the  solution of  less than 4.2. Studies, 
carried out with a high dilution of the so-
lution to prevent the deposition of MNB, 
showed that the precipitation of the impu-
rities continues until the pH of the solution 
is  reduced till 2.9–3.0, and with further 
acidification no precipitation is observed. 
Also, the color of the solution changes from 
dark brown at pH 5.6 to light yellow at pH 
2.5, after filtering the precipitate of impuri-
ties. To avoid precipitation of MNB at pH 
less than 4.2, the precipitation of impuri-
ties was carried out in a range of pH range 
of 4.4–4.6.

From the  results of  cyclic processing 
it follows that it is not possible to obtain 
MNB using the filtrate from the previous 
stage with a low chromium content while 
maintaining the regime of the first cycle. 
Apparently, an increase in the salt content 
of the solution leads to a different distri-
bution of the impurity between the aque-
ous and organic phases. This is confirmed 
by  the  fact that dilution of  the  solution 
of  the  second cycle after the  filtration 
of the insoluble residue leads to cloudiness 
of the solution and precipitation of the im-
purities. From the  results of  a  study 
of  the  effect of  the  amount of  water on 
the chromium content in the final MNB 
it follows that an increase in the amount 
of water leads to a decrease in the chro-

Fig. 1. Chromatogram of the processed MNB



85

mium content in  the  final product due 
to a more complete deposition of chromi-
um-containing impurities from the solu-
tion upon decreasing pH. Additional ex-
traction of  menadione from the  mother 
liquor is  achieved by  changing the  pH 
of the medium above 10.0 by adding so-
dium carbonate.

Chromatographic studies of the result-
ing MNB (Fig. 1) to demonstrate the ab-
sence of 2-methylnaphthalene and other 
organic impurities in  it, which confirms 
the effectiveness of the described purifica-
tion method.

Conclusions
In  conclusion, a  technical solution 

is developed for the processing of mena-
dione nicotinamide bisulfite with a high 
content of chromium and organic impu-
rities, as  well as  for one with an  expired 
shelf life to produce a high quality menadi-
one with low chromium content. The best 
results were obtained at the temperature 
of the reaction mixture of 20–40 °C, the pH 

after dilution in  a  range of  5.5–5.7, and 
the initial MNB content of 25–30%. This 
technical solution is  also applicable well 
for the accumulated previously substand-
ard commercial products, and it finalizes 
the cycle of the improvement of the exist-
ing industrial production of K3 series vi-
tamins based on menadione. 

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