Nitropyridines 11.* recyclization of quaternary nitropyridinium salts into substituted nitroanilines

Article abstract of DOI:10.1007/s10593-011-0783-3

Substituted nitroanilines have been obtained by the recyclization of nitropyridinium quaternary salts under the action of bases.

Full text of DOI:10.1007/s10593-011-0783-3

Chemistry of Heterocyclic Compounds, Vol. 47, No. 4, July 2011 (Russian original Vol. 47, No. 4, April, 2011)
NITROPYRIDINES
11.* RECYCLIZATION OF QUATERNARY
NITROPYRIDINIUM SALTS INTO
SUBSTITUTED NITROANILINES
A. K. Garkushenko1, N. V. Poendaev1,
M. A. Vorontsova1, and G. P. Sagitullina1**
Substituted nitroanilines have been obtained by the recyclization of nitropyridinium quaternary salts
under the action of bases.
Keywords: anhydro base, biphenyl, substituted nitroanilines, 3(5)-nitropyridines, 4-nitropyridine, pseu-
do base, pyridinium quaternary salts, recyclization.
The aim of the present work was to study the synthetic possibilities of the recyclization of nitropyridi-
nium salts. The rearrangement of nitropicoline and nitrolutidine salts into nitroanilines was carried out for the
first time in the eighties [2–4].
In the early stages of investigations on drawing up a scheme for the recyclization of nitropyridinium
salts the formation of anhydro bases A and anionic σ-complexes B as intermediates were postulated.
_
O2N
O
O2N
O2N
O2N
O2N
_
_
OH
H2O
CH2
OH
HO
H
..
+
N
Me
NH
Me
HN
CH2
N
CH2
N
– H2O
_
H
I
Me
Me
Me
Me
A
B
C
_______
Dedicated to bright memories of Professor Reva Safarovich Sagitullin.
* For Communication 10, see [1].
** To whom correspondence should be addressed; e-mail: Sagitullina@orgchem.univer.omsk.su.
1 F. M. Dostoevsky Omsk State University, Department of Organic Chemistry, 55a Mira Pr., Omsk 644077,
Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 573–585, April, 2011. Original
article submitted July 6, 2010.
0009-3122/11/4704-0470©2011 Springer Science+Business Media, Inc.
470

Later, this mechanism was rejected for the following reasons.
1. In a series of cases (recyclization of indolizines, nicotyrinium salts, opening of Zincke salts, etc.) the
formation of an anhydro base is impossible in principle [5, 6].
2. Compounds, the anhydro bases of which are readily formed, proved in general to be incapable of re-
cyclization while the formation of an anhydro base was not blocked [7].
So it is more logical to suggest that neutral analogs of anionic σ-complexes act as intermediates in the
recyclization of pseudo bases [8].
X
HO
H
X
X
X
X
O
X
X
O
X
a
b
H
N
Me
HO
N
Me
HN
Me
Me
H
N
Me
Me
Me
Me
Of the two possible variants of the opening of the ring of the pseudo base, the electrocyclic (a) and the
ionic (b), the ionic variant should be preferred since:
1. The formation of the opened forms has never been mentioned for nucleophiles incapable of ionic ring
opening (X = Cl–, Br–, I–, CN–, etc.).
2. The enthalpies of formation of the ionic forms, resulting from electrocyclic opening, are greater than
the enthalpies of formation of the enamine forms from ionic opening (ΔH = –14 kcal/mole) [9].
The recyclization of nitropyridinium salts 1a–c by the action of alcoholic methylamine at room tempera-
ture leads to substituted nitroanilines 2a–c. Hydroxyl anion attacks the spatially more accessible position 6 of
the pyridinium salts 1a–c with the formation of pseudo base 1A. Ionic opening of pseudo base 1A leads to the
opened form 1B, the cyclization of which into the substituted nitroanilines 2a–c occurs by intramolecular aldol–
crotonate condensation of the resulting formyl group with the methyl group.
O
O
O
O
O2N
O2N
H
O2N
O2N
H
R
R
R
R
MeNH2/EtOH
+
NH
Me
Me
NH
Me
– H2O
N
Me
_
ClO4
N
Me
HO
O
Me
Me
1A
1a–c
1B
2a–c
1,2 a R = Me, b R = cyclo-Pr, c R = Ph
The rearrangement product of 5-nitro-2-phenacylpyridinium salt 3 is [2-(methylamino)-5-nitrophenyl]-
phenyl methyl ketone (2c). On treating a solution of the pyridinium salt 3 with base deprotonation occurs at the
CH-acidic methylene group of the phenacyl substituent with the formation of a stable anhydro base 4. Further
conversion of anhydro base 4 into pseudo base A occurs by addition of water to it. An analogous equilibrium in
the anhydro base–pseudo base system was described by O. Mumm in the example of recyclizing a 3,5-diethoxy-
carbonylcollidinium salt [10].
The formation of the benzene ring of compound 2c occurs as a result of the interaction of the generated
formyl group and the methylene unit of the phenacyl group in the opened form 4B.
5-Nitro-2-phenacylpyridinium perchlorate 3 was synthesized by acidic hydration according to Kucherov
of the triple bond of the 1-methyl-5-nitro-2-(phenylethynyl)pyridinium quaternary salt 6 and by alkylation of
5-nitro-2-phenacylpyridine (5). A 10% solution of perchloric acid was used to replace the methylsulfate anion
471

by perchlorate. It was not possible to use the saturated aqueous solution of sodium perchlorate usually used for
this purpose since the basicity of water is sufficient to deprotonate the methylene group of pyridinium
methylsulfate and form anhydro base 4.
O2N
O2N
O
NaOH
Ph
NaOH
+
N
N
Ph
_
ClO4
Me
Me
O
3
4
O2N
H
O2N
H
2c
N
NHMe
HO
O
– H2O
Me
O
Ph
O
Ph
4B
4A
O2N
O2N
O
Hg2+, H2SO4
AcOH
1. (MeO)2SO2
2. HClO4
3
+
N
Ph
N
Ph
5
_
Me
6
ClO4
On rearranging the unsymmetrical quaternary 3-nitrolutidinium salt 7 by the action of an aqueous alco-
holic solution of sodium hydroxide the isomeric o- and p-nitrotoluidine derivatives 8 and 9 were formed in a
2.1:1 ratio, in 56% overall yield. The scheme for the recyclization of salt 7 with the intermediate formation of
pseudo bases 7A and 7B assumes attack of the hydroxyl anion at positions 2 and 6 of the nucleus. The
dominating formation of o-toluidine 8 points to the predominant attack of hydroxyl anion at the para position in
relation to the nitro group of salt 7, which is sterically more available.
NO2
NO2
Me
NO2
Base
Me
HO
+
Me
OH
+
Me
N
Me
_
N
Me
N
Me
ClO4
Me
Me
7
7B
7A
NO2
NO2
+
HN
Me
Me
Me
NH
Me
8
9
Base:
10% NaOH or MeNH2/H2O
On recyclizing 3-nitrolutidinium perchlorate 7 under the action of 41% aqueous methylamine solution
the overall yield of o- and p-nitrotoluidine derivatives 8 and 9 was 52%, and the ortho/para ratio of isomers was
2.5:1. On using 25% aqueous methylamine in the recyclization of salt 7 the overall yield of isomers was the
same (51%) but the ortho/para ratio of isomers was significantly different and amounted to 4.7:1 [4].
472

TABLE 1. Physicochemical Characteristics and Preparation Conditions
of Pyridinium Quaternary Salts
Found, %
Time,h /
mp, °С* temperature, Yield, %
°С
Calculated, %
Compound Empirical formula
С
Н
N
1a
С9H11ClN2O7
С11H13ClN2O7
С14H13ClN2O7
С14H13ClN2O7
С14H11ClN2O6
С8H11ClN2O6
С10H13ClN2O7
С12H15FN2O6S
С8H10ClN3O8
С15H15FN2O6S
С7H9ClN2O6
36.66
36.69
3.67
3.76
9.25
9.51
136–137
150–151
228–229
202–203
193–194
231–232
145–146
132–133
3/70
4/80
87
72
81
64
78
81
82
83
47
86
76
52
60
1b
41.11
41.20
4.01
4.09
8.62
8.74
1c
47.37
47.14
3.85
3.67
8.02
7.85
4/80
3
47.08
47.14
3.55
3.67
7.75
7.85
2/80
6
7
49.72
49.65
3.36
3.27
8.35
8.27
2/70
36.10
36.04
4.17
4.16
11.08
10.51
8/70
10a
39.00
38.91
4.26
4.25
8.51
9.08
48/70
120/25
120/70
120/25
5/70
10b
43.07
43.11
4.56
4.52
8.41
8.38
10c
30.74
30.83
3.25
3.23
13.33
13.48
>250
(dec.)
10d
48.73
48.65
4.06
4.08
7.42
7.56
196–197
124–125
183–184
163–164
14
33.20
33.28
3.55
3.59
11.01
11.09
16a
С8H13ClN2O4
С9H15ClN2O4
40.27
40.60
5.36
5.54
11.94
11.84
72/25
72/25
16b
43.44
43.12
5.92
6.03
11.20
11.18
_______
*Solvents for recrystallization: ethanol (compounds 1a–c, 10a,b,d, 14,
16a,b), 50% acetic acid (compound 3), water (compound 6), propanol
(compound 7), 10% perchloric acid (compound 10c).
5-Nitropyridinium salts 10a,b were recyclized analogously under the action of 41% aqueous methyl-
amine solution with the formation of the isomeric nitroanilines 11a,b and 12a,b in 85–97% overall yield.
13
According to the data of C NMR spectra the most electron-deficient is the α-carbon atom in the p-position to
the nitro group. It is also predominantly attacked by base, which provides a significantly greater yield of
O
O
O
O2N
Me
O2N
HN
O2N
Me
R
MeNH2/H2O
R
R
+
+
N
Me
_
Me
NH
Me
Me
10a,b
A
Me
12a,b
NO2
11a,b
NO2
O2N
O2N
HN
MeNH2/H2O
+
N
Me
Me
_
ClO4
Me
Me
Me
11c
10c
10–12 a R = Me, A = ClO4; b R = cyclo-Pr, A = SO3F
473

substituted o-nitroanilines 11a,b. As a result of rearrangement of the symmetrical 3,5-dinitropyridinium salt 10c
only 2,4-dinitrotoluidine 11c is formed.
Rearrangement of salt 10d leads to the formation of two isomeric nitroanilines 11d and 12d in 55%
overall yield in a 1.1:1 and biphenyl 13 in 30% yield. Closure of the benzene ring with the formation of biphenyl
13 occurs with the participation of the benzoyl group in an aldol-crotonate condensation with the methyl group.
O2N
Me
COPh
O2N
Me
COPh
O2N
HN
O2N
HN
COPh
Me
COMe
Ph
MeNH2/H2O
+
+
+
N
Me
NH
Me
_
Me
SO3F
Me
Me
11d
12d
13
10d
The quaternary 4-nitropicolinium salt 14 is not recyclized by the action of aqueous alcoholic NaOH solution
into N-methyl-3-nitroaniline, which was not detected even in trace amounts. The hydroxyl ion attacks the most elec-
tron-deficient position 4 of the pyridinium salt which leads to nucleophilic ipso substitution of the nitro group [11].
The reaction proceeds under charge control and leads to 1,2-dimethylpyridin-4(1H)-one. On interacting of
4-nitropyridinium salt 14 with alcoholic methylamine and dimethylamine the nitro group is replaced by methyl-
amine and dimethylamine respectively, which leads to the formation of substituted 4-aminopyridinium salts 16a,b.
TABLE 2. Physicochemical Characteristics and Preparation Conditions
of Nitroanilines
Found, %
Calculated, %
Com-
pound
Empirical
formula
Me-
thod*
mp, °С
Yield, %
С
−
Н
N
2а
С9H10N2O3
С11H12N2O3
−
−
149–150 [12]
160–161
А
А
72
60
2b
59.86
59.99
5.42
5.49
12.64
12.72
2c
С14H12N2O3
−
−
−
160–161 [13]
А
B
B
52 (from 1с)
40 (from 3)
60 (from 4)
8
9
С8H10N2O2
С8H10N2O2
С10H12N2O3
С12H14N2O3
С8H9N3O4
−
−
−
−
−
−
73–74 [14]
92–93 [15]
213–214
148–149
171–172
149–150
167–168
106–107
186–187
139–140
B
C
38
37
B
C
18
15
11a
57.75
57.68
5.72
5.81
13.54
13.45
C
C
C
C
C
C
C
C
58
47
30
30
39
40
25
30
11b
61.59
61.53
5.82
6.02
11.74
11.96
11c
45.67
45.50
4.28
4.30
19.75
19.90
11d
С15H14N2O3
С10H12N2O3
С12H14N2O3
С15H14N2O3
С15H14N2O3
66.87
66.66
5.32
5.22
10.50
10.36
12a
57.65
57.68
5.75
5.81
13.43
13.45
12b
61.62
61.53
5.98
6.02
11.93
11.96
12d
66.80
66.66
5.18
5.22
10.45
10.36
13
66.74
66.66
5.25
5.22
10.30
10.36
_______
*A with alcoholic methylamine, B with aqueous alcoholic alkali, C with
aqueous methylamine.
474

O
anion
exchange
resin
NO2
NO2
HO
NMeR
+
RNHMe/EtOH
Me
+
N
Me
N
Me
N
N
Me
_
_
Me
Me
Me
ClO4
Me
ClO4
15
14
16a,b
16 a R = H, b R = Me
Data of elemental analysis and spectral characteristics are given in Tables 1–7 for compounds synthe-
sized for the first time.
We have therefore established the principal difference in the behavior of quaternary 3-, 4-, and 5-nitro-
pyridinium salts under the action of bases. A nitro group in positions 3 and 5 of the nucleus of the pyridinium
salt activates addition of nucleophile at positions 2 and 6 of the nucleus, accompanied by recyclization, but the
nitro group in position 4 of the nucleus directs attack of the nucleophile to position 4, which leads to
nucleophilic ipso substitution of the nitro group.
1
TABLE 3. H NMR Spectra of Pyridinium Salts
Chemical shifts, δ, ppm (J, Hz)*
Compound
N–CH3
Other protons
(s)
1a
1b
1c
3
4.44
4.44
4.39
4.34
2.75 (3H, s, COCH3); 2.86 (3H, s, 2-CH3); 9.52 (1H, d, 4J = 2.4, H-4);
10.21 (1H, d, 4J = 2.4, H-6)
1.27–1.35 (4H, m, 2CH2); 2.57–2.88 (1H, m, CH); 2.88 (3H, s, 2-CH3);
9.43 (1H, d, 4J = 2.2, H-4); 10.22 (1H, d, 4J = 2.2, H-6)
2.73 (3H, s, 2-CH3); 7.61–7.90 (5H, m, C6H5); 9.12 (1H, d, 4J = 2.2, H-4);
9.68 (1H, d, 4J = 2.2, H-6)
5.22 (2Н, s, СН2); 7.58–7.73 (3H, m, C6H5); 8.08–8.13 (2H, m, C6 H5);
8.24 (1Н, d, 3J = 8.8, Н-3); 9.14 (1Н, dd, 3J = 8.8, 4J = 2.4, Н-4);
9.69 (1H, d, 4J = 2.4, H-6)
6
4.54
4.15
4.21
4.21
7.53–7.72 (3H, m, C6H5); 7.83–7.88 (2H, m, C6H5); 8.39 (1Н, d, 3J = 8.8,
Н-3); 9.10 (1Н, dd, 3J = 8.8, 4J = 1.8, Н-4); 9.65 (1H, d, 4J = 1.8, H-6)
7
2.88 (3Н, s, 6-CH3); 2.91 (3Н, s, 2-CH3); 8.15 (1Н, d, 3J = 8.7, H-5);
8.96 (1Н, d, 3J = 8.7, H-4)
10a
10b
2.71 (3H, s, COCH3); 2.88 (3H, s, 2-CH3); 2.93 (3H, s, 6-CH3); 9.31
(1H, s, H-4)
1.23–1.37 (4H, m, 2СН2); 2.53–2.62 (1H, m, CH); 2.89 (3H, s, 2-CH3);
2.94 (3H, s, 6-CH3); 9.23 (1H, s, H-4)
10c
10d
4.26
4.24
3.00 (6H, s, 2,6-CH3); 9.28 (1H, s, H-4)
2.73 (3H, s, 2-CH3); 2.99 (3H, s, 6-CH3); 7.61–7.68 (2H, m, C6H5);
7.80–7.87 (3H, m, C6H5); 9.20 (1H, s, H-4)
14
3.97
3.78
2.60 (3Н, s, 2-CH3); 7.12 (1Н, dd, 3J = 7.1, 4J = 2.9, H-5); 7.19 (1Н, d,
4J = 2.9, Н-3); 8.55 (1H, d, 3J = 7.1, H-6)
16a
2.51 (3Н, s, 2-CH3); 2.86 (3Н, d, J = 5.0, NHCH3); 6.76 (1Н, dd,
3J = 7.2, 4J = 2.8, H-5); 6.82 (1H, d, 4J = 2.8, H-3); 8.24 (1Н, d, 3J = 7.2,
Н-6); 8.34 (1Н, br. s, NHCH3)
16b
3.83
2.53 (3Н, s, 2-CH3); 3.16 (6Н, s, N(CH3)2); 6.90 (1Н, dd, 3J = 7.8,
4J = 2.4, Н-5); 6.96 (1Н, d, 4J = 2.4, H-3); 8.18 (1H, d, 3J = 7.8, H-6)
_______
*The 1H NMR spectra were taken in DMSO-d6 (compounds 1a–c, 7, 10a,b,d, 14 and 16a,b) and CD3CN (compounds 3, 6, and 10c).
475

476

TABLE 5. IR Spectra of Nitroanilines
ν, см–1
Compound
NO2
NH
C=O
2а
2b
2c
1582, 1321
1584, 1323
1580, 1321
1580, 1330
1528, 1357
1555, 1391
1560, 1384
3301
3241
3281
3371
3357
3366
3373
3359
1632, 1612
1630, 1618
1626, 1611
−
8
9
−
11a
11b
11c
1661, 1613
1658, 1627
−
1580, 1536,
1357, 1322
11d
12a
12b
12d
13
1562, 1351
1566, 1348
1567, 1345
1552, 1352
1569, 1351
3339
3308
3282
3318
3367
1680, 1614
1638, 1612
1627, 1606
1621, 1610
1648, 1615
1
TABLE 6. H NMR Spectra of Nitroanilines
Chemical shifts (CDCl3), δ, ppm (J, Hz)
Other protons
Com-
pound
NHCH3
(br. s)
2b
2c
9.55
9.30
1.03–1.25 (4H, m, 2CH2); 2.65–2.78 (1H, m, CH); 3.00 (3Н, d, J = 5.1,
NHCH3); 6.69 (1Н, d, 3J = 9.3, Н-3); 8.24 (1Н, dd, 3J = 9.3, 4J = 2.4, Н-4);
8.98 (1Н, d, 4J = 2.4, Н-6)
3.10 (3Н, d, J = 5.0, NHCH3); 6.80 (1Н, d, 3J = 9.6, Н-3); 7.49–7.56 (2H,
m, C6H5); 7.58–7.67 (3H, m, C6H5); 8.29 (1Н, dd, 3J = 9.6, 4J = 2.5, Н-4); 8.52
(1Н, d, 4J = 2.5, Н-6)
8
8.09
8.89
8.34
8.31
2.37 (3H, s, 5-CH3); 3.03 (3Н, d, J = 5.3, NHCH3); 6.47 (1Н, dd, 3J = 8.7,
4J = 1.5, Н-4); 6.62 (1Н, br s, Н-6); 8.07 (1Н, d, 3J = 8.7, Н-3)
9
2.61 (3H, s, 3-CH3); 2.98 (3Н, br s, NHCH3); 6.96 (1Н, m, Н-2); 7.00
(1Н, m, Н-6); 8.04 (1Н, d, 3J = 8.7, Н-5)
11a
11b
2.59 (3H, s, 2-CH3); 2.64 (3H, s, COCH3); 3.10 (3Н, d, J = 5.1, NHCH3);
6.64 (1Н, s, Н-3); 8.72 (1Н, s, Н-6)
1.01–1.06 (2H, m, CH2); 1.17–1.22 (2H, m, CH2); 2.48–2.55 (1H, m, CH);
2.57 (3H, s, 2-CH3); 3.09 (3Н, d, J = 5.2, NHCH3); 6.65 (1Н, s, Н-3); 8.83
(1Н, s, Н-6)
11c
11d
12a
12b
8.41
8.31
9.36
9.34
2.72 (3H, s, 5-CH3); 3.14 (3Н, d, J = 5.3, NHCH3); 6.70 (1Н, s, Н-6); 9.11
(1Н, s, Н-3)
2.10 (3H, s, 2-CH3); 3.08 (3Н, d, J = 5.1, NHCH3); 6.72 (1Н, s, H-3);
7.29–7.35 (2H, m, C6H5); 7.42−7.47 (3H, m, C6H5); 8.63 (1Н, s, Н-6)
2.63 (3H, s, 4-CH3); 2.68 (3H, s, COCH3); 3.00 (3Н, d, J = 5.3, NHCH3);
6.48 (1Н, s, Н-3); 8.71 (1Н, s, Н-6)
1.03–1.10 (2H, m, CH2); 1.16–1.22 (2H, m, CH2); 2.67–2.74 (4H, m,
CH, 4-CH3); 2.98 (3Н, d, J = 5.1, NHCH3); 6.48 (1Н, s, Н-3); 8.98
(1Н, s, Н-6)
12d
13
9.10
8.31
2.72 (3H, s, 4-CH3); 3.06 (3Н, d, J = 4.7, NHCH3); 6.57 (1Н, s, Н-3);
7.46–7.67 (5H, m, C6H5); 8.49 (1Н, s, Н-6)
2.53 (3H, s, COCH3); 3.10 (3Н, d, J = 5.3, NHCH3); 6.73 (1Н, s, Н-3);
7.44–7.51 (2H, m, C6H5); 7.55−7.62 (1H, m, C6H5); 7.73−7.78 (2H, m,
C6H5); 8.29 (1Н, s, Н-6)
477

478

EXPERIMENTAL
The IR spectra were obtained on a Simex FT-801 instrument (with an attachment for a single broken
1
internal reflection). The H NMR spectra of compounds 1a–c, 2b, 3, and 6 were recorded on a Bruker AC-200
(at 200 MHz) spectrometer, internal standard was TMS, of compounds 4, 7–16 on a Bruker Advance DRX-400
(at 400 MHz), internal standard was the residual protons of the deuterated solvent. The 13C NMR spectra were
recorded on a Bruker Advance DRX-400 (at 100 MHz) using the solvent as internal standard. Elemental
analysis was carried out on a Perkin-Elmer CHN Analyzer. Silica gel Merck 60A, 0.060–0.200 mm was used
for column chromatography. A check on the progress of reactions and the purity of the obtained compounds
was effected by TLC on Silufol UV-254 plates.
Preparation of Quaternary Pyridinium Salts 1a–c, 6, 7, 10a, 14 (General Method). A mixture of the
corresponding pyridine (5-nitro-2-(phenylethynyl)pyridine [1], 3-acyl-2-methyl-5-nitropyridine [16], 3-acetyl-2,6-
dimethyl-5-nitropyridine [17], 2,6-dimethyl-3-nitropyridine [18], or 2-methyl-4-nitropyridine [19]) (5 mmol), and
dimethyl sulfate (1.9 g, 15 mmol) was heated (reaction conditions are shown in Table 1). The reaction mixture was
cooled, washed with dry ether (3×10 ml), and the ether decanted. The residue was dissolved in water (5 ml) and a
saturated aqueous solution of sodium perchlorate (0.64 g, 5.3 mmol) was added. The precipitated pyridinium
perchlorate was filtered off, dried, and recrystallized.
1-Methyl-5-nitro-2-(2-oxo-2-phenylethyl)pyridinium Perchlorate (3). A mixture of salt 6 (1.69 g,
5 mmol), conc. H2SO4 (0.4 ml), and mercury(II) sulfate (1.56 g, 5.2 mmol) in 90% acetic acid solution (17.5 ml)
was heated for 2 h at 80oC. The reaction mixture was filtered and concentrated perchloric acid was added with
cooling. The precipitated crystals were filtered off and washed with 10% perchloric acid solution.
[2-Methyl-5-nitropyrid-2(1H)-ylidene]acetophenone (4). A mixture of (5-nitropyrid-2-yl)aceto-
phenone [1] (0.24 g, 1 mmol) and dimethyl sulfate (0.38 g, 3 mmol) was heated for 6 h at 100oC. The mixture
was cooled, washed with dry ether (3×10 ml), and the ether decanted. The residue was triturated with water and
the precipitated red crystals filtered off. Yield 90%; mp 208–209oC (ethanol). IR spectrum, ν, cm–1: 1699 (C=O),
1
1541, 1362 (NO2). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 3.76 (3H, s, NCH3); 6.10 (1H, s, =CH–);
3
4
7.44–7.54 (3H, m, C6H5); 7.85 (1H, dd, J = 10.3, J = 2.0, H-4); 7.93–7.98 (2H, m, C6H5); 8.77 (1H, d,
4
3J = 10.3, H-3); 9.12 (1H, d, J = 2.0, H-6). Found, %: C 65.47; H 4.63; N 11.15. C14H12N2O3. Calculated, %:
C 65.62; H 4.72; N 10.93.
Preparation of Quaternary Pyridinium Salts 10b,c,d (General Method). A solution of methyl
fluorosulfonate (1.71 g, 15 mmol) in 1,2-dichloroethane (3 ml) was added dropwise with stirring to a solution of
the corresponding pyridine (5 mmol) (3-(cyclopropylcarbonyl)-2,6-dimethyl-5-nitropyridine [17], 3-benzoyl-
2,6-dimethyl-5-nitropyridine [17], or 2,6-dimethyl-3,5-dinitropyridine [17]) in 1,2-dichloroethane (15 ml) with
cooling to 0oC. The mixture was stirred for 30 min with cooling and 5 days at room temperature, diluted with
ether, and the precipitated solid filtered off.
1,2,6-Trimethyl-3,5-dinitropyridinium Perchlorate (10c). After heating, the mixture was cooled,
washed with dry ether (3×20 ml), and the ether decanted. The residue was dissolved with heating in 10%
perchloric acid (10 ml), cooled, and the precipitated crystals filtered off.
Preparation of Nitroanilines 2a–c (General Method). A. A 30% alcoholic methylamine solution
(30 ml) was added to a solution of the corresponding salt 1a–c (3 mmol) in DMF (2.3 ml) and the mixture
stirred for 20 h. The reaction mixture was diluted with water and neutralized with 50% acetic acid solution. The
precipitated solid was filtered off and purified by column chromatography (eluent chloroform). Compounds 2a–
c were recrystallized from ethanol.
[2-(Methylamino)-5-nitrobenzo]phenone (2c). B. From quaternary salt 3. A 10% sodium hydroxide
solution (6 ml) was added to a solution of salt 3 (1.07 g, 3 mmol) in ethanol (6 ml). The mixture was stirred at
room temperature for 24 h, diluted with water, and neutralized with 50% acetic acid solution. The precipitated
solid was filtered off.
C. From anhydro base 4. A 10% sodium hydroxide solution (6 ml) was added to a solution of anhydro
base 4 (0.77 g, 3 mmol) in ethanol (6 ml). The reaction was carried out analogously to the previous reaction.
479

Methyl(5-methyl-2-nitrophenyl)amine (8) and Methyl(3-methyl-4-nitrophenyl)amine (9). B. A 10%
sodium hydroxide solution (4 ml) was added to a suspension of salt 7 (0.54 g, 2 mmol) in ethanol (8 ml). The
reaction mixture was stirred for 48 h at room temperature, diluted with water, and neutralized with 50% acetic
acid solution. The precipitated oil was extracted with benzene and dried over MgSO4. After removing the
solvent the product was isolated by column chromatography (eluent chloroform).
C. A mixture of salt 7 (0.54 g, 2 mmol) and 41% aqueous methylamine solution (40 ml) was stirred at
room temperature for 48 h. The mixture was neutralized with 50% acetic acid solution, the precipitated oil was
extracted with benzene and the extract dried over MgSO4. After removing the solvent the product was isolated
by column chromatography and recrystallized from ethanol.
Preparation of Nitroanilines 11a–d, 12a,b,d, and 13 (General Method). C. A 41% aqueous solution
of methylamine (40 ml) was added to a solution of the corresponding salt 10a–d (2 mmol) in DMF (4 ml) and
the mixture was stirred at room temperature for 2 h. After neutralization with 50% acetic acid the precipitated
solid was filtered off (in the case of compound 10c after neutralization the mixture was extracted with ethyl
acetate, the extract was dried, and after removal of the solvent was purified by column chromatography).
Separation of the isomers was carried out by column chromatography (eluent chloroform). The product was
recrystallized from ethanol.
1,2-Dimethylpyridin-4(1H)-one (15). A mixture of pyridinium salt 14 (0.25 g, 1 mmol) and anion
exchange resin (OH– form) (1.84 g) in ethanol (14 ml) was boiled for 2 h. The resin was filtered from the
reaction mixture and the filtrate evaporated. The product was purified by column chromatography (eluent
1
ethanol). Yield 48%; mp 50–55oC (toluene) (lit. mp 50–55oC [20]). H NMR spectrum (DMSO-d6), δ, ppm (J,
Hz): 2.21 (3H, s, 2-CH3); 3.52 (3H, s, NCH3); 5.96 (1H, dd, 3J = 7.5, 4J = 2.4, H-5); 6.02 (1H, d, 4J = 2.4, H-3);
7.59 (1H, d, 3J = 7.5, H-6). 13C NMR spectrum (DMSO-d6), δ, ppm: 178.12 (C-4); 149.64 (C-2): 143.15 (C-6);
117.92 (C-5); 116.38 (C-3); 40.42 (NCH3); 19.48 (2-CH3).
Preparation of 4-Alkylamino-1,2-dimethylpyridinium Perchlorates 16a,b (General Method).
A solution of salt 14 (0.25 g, 1 mmol) in a 30% alcoholic solution of methylamine or dimethylamine (30 ml)
was stirred for 3 days. After removing the solvent, the residue was recrystallized from ethanol.
The work was carried out with the financial support of the Russian Fund for Fundamental Investigations
(Grant 07-03-00783-a).
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