Pharmaceutical Chemistry Journal
Vol. 36, No. 1, 2002
DRUG SYNTHESIS METHODS
AND MANUFACTURING TECHNOLOGY
CATALYTIC CONVERSION OF NICOTINE INTO NICOTINONITRILE –
A PHARMACEUTICAL INTERMEDIATE PRODUCT
A. D. Kagarlitskii,1 M. K. Iskakova,2 and A. Zh. Turmukhambetov2
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 36, No. 1, pp. 26 – 27, January, 2002.
Original article submitted August 30, 2001.
An important problem of the tobacco industry is related
to the utilization of wastes. The amount of such products is
quite large: for example, the Alma-Ata Tobacco Plant (Philip
Morris – Kazakhstan Company) alone puts into storage more
than one thousand tons of wastes a year. As is known, until
the middle 1960s tobacco wastes were reprocessed into nico-
tinic acid by extracting the alkaloid nicotine, followed by ox-
idation with nitric acid or potassium permanganate. How-
ever, this technology turned out to be economically ineffec-
tive and went out of use.
We believe that a promising course of action is to convert
nicotine, as well as the accompanying alkaloids (anabasine,
nornicotine, nicotyrine, myosmine, anatabine) extracted
from tobacco, into nicotinic acid nitrile by means of oxida-
tive ammonolysis – an effective pathway for the synthesis of
pyridinecarboxylic acid nitriles from alkylpyridines [1]. The
possibility of such transformation is confirmed by the results
of our experiments on the oxidative ammonolysis of
anabasine, a nicotine isomer [2]. Nicotinonitrile synthesized
in this way can be used for the synthesis of vitamin PP (nico-
tinic acid and nicotinamide) and a series of drugs such as
cordiamine, nicodine, coamide, feramide, etc.
The results of our experiments showed that the composi-
tions of reaction mixtures obtained in the presence of cata-
lysts K1 – K3 are qualitatively the same. The main reaction
mixture components are nicotinonitrile and deeper oxidation
products – ammonium cyanide and carbon and nitrogen ox-
ides. The overall process of nicotine transformation can be
described by the following scheme:
CN
+
H2O, NH3
N
CH3
N
N
+
NH CN + CO + CO
+
2
4
N
As the reaction temperature is increased from 380 to
460°C, the target product yield initially grows to reach a
maximum at about 420°C and then drops as a result of the in-
creasing proportion of deeper oxidation products (Table 1).
Approximately the same pattern is observed on increas-
ing the reaction duration on catalysts K1 and K2 (Table 2),
for which the optimum contact time is 0.5 sec. A somewhat
The process of oxidative ammonolysis was effected with
three oxide catalysts that proved to be most effective in the
synthesis of nicotinonitrile from 3-methylpyridine [3]. Two
of these catalysts, representing vanadium pentoxide (catalyst
K1) and a mixture of vanadium pentoxide with titanium di-
oxide (V2O5 – TiO2) in a molar ratio of 1 : 0.5 (catalyst K2),
were prepared by melting. The third catalyst was prepared by
pelletizing a mixture of the same initial components
V2O5–TiO2 taken in the ratio 1 : 16 (catalyst K3), followed
by calcining the pellets at 850 – 900°C.
TABLE 1. Dependence of Nicotinonitrile Yield on Process Tem-
perature for Catalysts K1 – K3 (Reagent Ratio: Nicotine–NH3–H2O,
1 : 16 : 100; Contact Time: t = 0.76 sec)
Yield, %
T, °C
K1
K2
K3
380
400
420
440
460
30.0
48.0
50.0
48.0
45.0
25.0
39.0
60.0
45.0
37.0
42.0
44.0
46.5
44.0
42.0
1
Kazakh State Medical University, Alma-Ata, Kazakhstan.
Institute of Phytochemistry, Ministry of Education and Science of the Re-
2
public of Kazakhstan, Karaganda, Kazakhstan.
26
0091-150X/02/3601-0026$27.00 © 2002 Plenum Publishing Corporation
Kagarlitskii
