Oxidative ammonolysis of 2,4,6-collidine at vanadium-titanium oxide catalyst

Article abstract of DOI:10.1023/A:1023958625482

4-Cyanopyridine was synthesized from the readily obtainable 2,4,6-collidine by oxidative ammonolysis in the presence of vanadium-titanium oxide catalyst. Conditions under which the yield of the product amounted to 73% on the amount of the trimethylpyridin

Full text of DOI:10.1023/A:1023958625482

Chemistry of Heterocyclic Compounds, Vol. 39, No. 3, 2003
OXIDATIVE AMMONOLYSIS OF 2,4,6-COLLIDINE
AT VANADIUM-TITANIUM OXIDE CATALYST
A. D. Kagarlitsky and L. A. Krichevsky
4
-Cyanopyridine was synthesized from the readily obtainable 2,4,6-collidine by oxidative ammonolysis
in the presence of vanadium-titanium oxide catalyst. Conditions under which the yield of the product
amounted to 73% on the amount of the trimethylpyridine were found.
Keywords: 2,4,6-collidine, oxidative ammonolysis, vanadium-titanium oxide catalyst.
The nitriles produced during the oxidative ammonolysis of alkylpyridines [1] have been used as
intermediates in the production of drugs – tuberculostatics [2, 3], vitamins [4], cardiotonic agents [5] – and also
in the synthesis of heat-resistant polymeric materials [6].
2
,4,6-Collidine (1) numbers among the readily obtainable compounds, but its oxidative ammonolysis
has hardly been studied at all. In the single paper devoted to this question [7] it was shown that in the presence
of vanadium oxide catalyst promoted with silver (V:Ag = 1:0.003 at.%) the main reaction products were
2
-cyano-4,6-dimethylpyridine and 2,4-dicyano-6-methylpyridine with yields of 19.4 and 11.5% respectively,
calculated on the reacted material.
We investigated the oxidative ammonolysis of compound 1 in the presence of vanadium-titanium oxide
catalyst with V
2
O
5
:TiO = 1:16 (molar ratio). The basis for the choice of such a catalyst was the fact that, as
2
previously established by one of us with colleagues, methyl groups at position 2 of the pyridine ring underwent
dealkylation in this reaction, where the reaction mixture was rich in water [8], while those at position 4 were
converted under analogous conditions into a cyano group [9]. Thus, it was proposed to attempt the
transformation of compound 1 into isonicotinonitrile 2:
Me
CN
Me
N
Me
N
1
2
This conclusion was supported by experiment. The main product from oxidative ammonolysis of the
collidine 1 under the selected conditions was cyanopyridine 2. The minor products of the reaction were
2
-amido-4-methylpyridine 3 and 2-amido-4-cyanopyridine 4 and also the pyridine 5 and picolinic acid 6
(
Table 1), formed as a result of hydrolysis of the 2-cyanopyridine.
_
_________________________________________________________________________________________
Institute of Phytochemistry, Ministry of Education and Science of the Kazakhstan Republic, Karaganda
70032; e-mail: arglabin@phyto.karaganda.su. Translated from Khimiya Geterotsiklicheskikh Soedinenii,
4
No. 3, pp. 358-360, March, 2003. Original article submitted November 22, 2001.
0
009-3122/03/3903-0315$25.00©2003 Plenum Publishing Corporation
315

TABLE 1. The Dependence of the Yield of the Products from Oxidative
Ammonolysis of Collidine 1 on the Process Parameters (Delivery Rate of
2
,4,6-Collidine 21.32 g/lcat·h, Oxygen 17 mol/mol of 2,4,6-Collidine)
Experi-
ment
NH
3
:1,
H
2
O:1,
Yield, %
T, °C
1*, %
mol/mol
mol/mol
2
3
4
5
6
1
2
3
4
5
6
7
8
9
300
320
340
360
380
300
320
340
360
380
300
320
340
360
380
400
8
8
8
8
8
8
8
8
8
8
6
6
6
6
6
6
10
10
10
10
10
20
20
20
20
20
30
30
30
30
30
30
92
82
54
28
20
48
44
36
20
14
30
20
10
6
2
8
2
4
4
1
—
4
1
2
—
—
—
—
8
4
5
—
—
—
—
—
—
—
3
26
48
51
2
18
40
52
56
48
60
70
72
76
74
8
4
2
20
24
2
10
14
24
28
5
16
20
22
21
20
—
—
8
—
2
—
—
14
1
—
—
—
—
—
28
16
5
—
—
—
—
—
—
—
—
1
1
1
1
1
1
1
0
1
2
3
4
5
6
3
1
_
*
______
Unreacted collidine 1.
Under optimum conditions (380°C, molar ratio 1:oxygen:ammonia:water = 1:17:6:30) the yield of
cyanopyridine 2 amounted to 76%. This makes it possible to use the oxidative ammonolysis of collidine 1 for
the production of this compound, which is an intermediate in the synthesis of the antituberculosis product
Izoniazid.
EXPERIMENTAL
The oxidative ammonolysis of collidine 1 was studied in the range of 300-400°C. The flow rate of the
-1
reaction mixture was 370-555 h by volume, and the molar ratio collidine 1:oxygen:ammonia:water was
3
1
:17:(2-10):(10-50). A flow-type stainless steel reactor, in which 43 cm of the catalyst was placed, was used for
the experiments. The reaction products were isolated by column chromatography (a column of silica gel
L100/160) and identified by elemental analysis and IR and NMR spectroscopy.
The amounts of the unreacted compound 1 and the reaction products were determined by GLC on a
Chrom-5 chromatograph with a flame-ionization detector. Silicone elastomer SE-30, deposited on Chromaton
NAW-HMDS at the rate of 5% was used as stationary phase (column temperature 130°C, length 2.5 m, internal
diameter 3 mm). Benzonitrile was used as internal standard for quantitative analysis.
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.
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