3-Cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines in the synthesis of substituted 3-(aminomethyl)pyridines

Article abstract of DOI:10.1023/A:1024472914598

The reactions of substituted 3-cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines with lithium aluminum hydride in anhydrous diethyl ether afforded the corresponding 3-aminomethyl derivatives, which were used in the synthesis of the corresponding amides.

Full text of DOI:10.1023/A:1024472914598

978
Russian Chemical Bulletin, International Edition, Vol. 52, No. 4, pp. 978—983, April, 2003
3ꢀCyanopyridineꢀ2(1H )ꢀthiones and 3ꢀcyanoꢀ2ꢀ(methylthio)pyridines
in the synthesis of substituted 3ꢀ(aminomethyl)pyridines
ꢀ
A. A. Zubarev, V. K. Zavyalova, and V. P. Litvinov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: vallen@mail.ru
The reactions of substituted 3ꢀcyanopyridineꢀ2(1H )ꢀthiones and 3ꢀcyanoꢀ2ꢀ(methylꢀ
thio)pyridines with lithium aluminum hydride in anhydrous diethyl ether afforded the correꢀ
sponding 3ꢀaminomethyl derivatives, which were used in the synthesis of the corresponding
amides.
Key words: 3ꢀcyanopyridineꢀ2(1H )ꢀthiones, 3ꢀcyanoꢀ2ꢀ(methylthio)pyridines, 3ꢀ(aminoꢀ
methyl)ꢀ2ꢀ(methylthio)pyridines, 6ꢀmethylꢀ and 4,6ꢀdimethylꢀ3ꢀ(aminomethyl)pyridineꢀ
2(1H )ꢀthiones, lithium aluminum hydride, reduction.
Since aminoalkyl groups are involved in many natural
pended substantially on the reaction conditions. When
thiones 1a,b were added to even a substantial excess of
LiAlH4, the reaction was terminated at the step of formaꢀ
biologically active compounds and pharmaceuticals, the
synthesis of new, including heterocyclic, compounds conꢀ
taining these pharmacophoric groups holds promise. From
this viewpoint, compounds of the 3ꢀcyanopyridineꢀ
2(1H )ꢀthione series are of interest. These compounds
attract widespread attention due to their unusual properꢀ
ties and broad possibilities in the synthesis of new biologiꢀ
cally active compounds. Aminoalkylꢀcontaining comꢀ
pounds of this series are unknown, although in the last
15 years considerable study was given to the chemistry of
3ꢀcyanopyridineꢀ2(1H )ꢀthione and its derivatives, includꢀ
ing transformations of the nitrile group.1,2 Thus, hydrolyꢀ
sis of the nitrile group,3,4 reactions with organometallic
compounds,1,4,5 and intraꢀ and intermolecular heteroꢀ
cyclization involving this group1,2,6—12 were examined.
However, reduction of the nitrile group in 3ꢀcyanoꢀ
pyridineꢀ2(1H )ꢀthiones has not been described, although
the nitrile group in their analogs, viz., in 3ꢀcyanoꢀ2(1H )ꢀ
pyridones, was reduced to the aldehyde group with
diisobutylaluminum hydride (DIBAH).13
Scheme 1
The aim of the present study was to examine the possiꢀ
bility of reducing the nitrile group to the aminomethyl
group in substituted 3ꢀcyanopyridineꢀ2(1H )ꢀthiones and
their Sꢀmethylꢀsubstituted derivatives. Products of these
reactions may be of interest not only as biologically active
compounds but also as synthons. We chose lithium aluꢀ
minum hydride, which is widely used in the synthetic
practice, as the reducing agent.
1—3: R1 = Me, R2 = H (a); R1 = H, R2 = Me (b)
Results and Discussion
4:
R
1 = Me, R2 = H
5, 6: R1 = R2 = Me (a); R1 = R2 = Ph (b); R1 = Me, R2 = H (c);
We found that reduction of 3ꢀcyanopyridineꢀ2(1H ) ꢀ
thione derivatives (1a,b) with LiAlH4 in diethyl ether deꢀ
R
R
1 = Me2C=CH, R2 = H (d); R1 = Me2CHCH2, R2 = H (e);
1 = Me2CH, R2 = H (f); R1 = C5H11, R2 = H (g)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 926—931, April, 2003.
1066ꢀ5285/03/5204ꢀ978 $25.00 © 2003 Plenum Publishing Corporation

Substituted 3ꢀ(aminomethyl)pyridines
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
979
Scheme 2
tion of lithium 3ꢀcyanopyridineꢀ2ꢀthiolates (2a,b), which
were reduced to the corresponding amines 3a,b in the
repeated reactions. We succeeded in reducing thiones 1a,b
by adding LiAlH4 to their suspensions in diethyl ether
(Scheme 1). The highest yields (70—80%) of the amines
(as lithium thiolates 3a,b) were attained using 2 moles of
LiAlH4 per mole of the starting nitrile.
Amines 3 can be isolated and characterized as hydroꢀ
chlorides. Thus, acidification of 3a with hydrochloric acid
and subsequent purification by recrystallization afforded
3ꢀ(aminomethyl)ꢀ6ꢀmethylpyridineꢀ2(1H )thione hydroꢀ
chloride (4). Its structure was established by IR and
1H NMR spectroscopy. The IR spectrum has absorption
bands in the region of 3500 cm–1 (NH3+). The 1H NMR
spectrum shows a singlet of the CH2 group at δ 4.00 and a
singlet of the NH fragment of the pyridine ring at δ 13.75,
which is indicative of the thione structure of the comꢀ
pound synthesized.
Since 3ꢀcyanopyridineꢀ2(1H )thiones are poorly
soluble in diethyl ether, they were used in the reactions
as readily soluble Sꢀmethyl derivatives 5a—g. The latꢀ
ter were reduced with LiAlH4 to the corresponding
3ꢀ(aminomethyl) derivatives 6a—g in 60—80% yields (see
Scheme 1).
Compounds 3a,b and 6a—g were prepared as paleꢀ
yellow crystalline compounds or liquids. Their structures
were confirmed by IR and 1H NMR spectroscopy and
mass spectrometry. The IR spectra are characterized by
the presence of a vibrational band of the amino group
at 3300—3400 cm–1 and the absence of the band of
the nitrile group at 2200 cm–1. The 1H NMR spectra
have a characteristic singlet of the methylene group at
δ 3.60—3.80. We failed to isolate compounds 6e—g in the
individual form. Hence, these compounds were characꢀ
terized as the corresponding amides 7 and used in subseꢀ
quent reactions without purification.
Lithium 3ꢀ(aminomethyl)pyridineꢀ2ꢀthiolates (3a,b)
and 3ꢀ(aminomethyl)ꢀ2ꢀ(methylthio)pyridines (6a—g)
thus synthesized were acylated with acid chlorides 8a—h
in acetonitrile in the presence of Et3N to form amides
7a—h and 9a—d and sulfamide 10 (Scheme 2).
7: R1 = R2 = Me, R3 = 3,4,5ꢀ(MeO)3C6H2 (a);
R
R
R
R
R
R
1 = R2 = Me, R3 = 2ꢀMeꢀ3ꢀNO2C6H3 (b);
1 = R2 = Ph, R3 = 3,4,5ꢀ(MeO)3C6H2 (c);
1 = Me2C=CH, R2 = H, R3 = 4ꢀClC6H4 (d); R1 = Me2CHCH2,
2 = H, R3 = 3,4,5ꢀ(MeO)3C6H2 (e); R1 = Me, R2 = H,
3 = 4ꢀButC6H4 (f); R1 = Me2CH, R2 = H,
3 = PhCH(Me)CH2 (g); R1 = C5H11, R2 = H, R3 = 4ꢀClC6H4 (h);
8: R3 = PhOCH(Me) (a); Me (b); 3,4,5ꢀ(MeO)3C6H2 (c);
2ꢀMeꢀ3ꢀNO2C6H3 (d); 4ꢀButC6H4 (e);
PhCH(Me)CH2 (f); 4ꢀClC6H4 (g, h);
9: R1 = Me, R2 = H, R3 = 4ꢀClC6H4 (a);
R
R
1 = Me, R2 = H, R3 = PhOCH(Me) (b); R1 = R2 = Me,
3 = 4ꢀClC6H4 (c); R1 = R2 = R3 = Me (d);
10: R1 = R2 = Ph, R3 = 4ꢀClC6H4
acteristics of compounds 3a,b, 4, 6a—g, 7a—h, 9a—d,
and 10 are given in Tables 1 and 2.
Amides 7a—h and 9a—d were prepared as white or
paleꢀyellow powders. The IR spectra of these amides have
characteristic absorption bands at 3250—3350 cm–1 (NH
of the amide group) and 1620—1650 cm–1 (C=O). The
1H NMR spectra of amides 7a—h and 9a—d show a douꢀ
blet (in some cases, a singlet is observed due, apparently,
to the fact that the signal remains unresolved) of the CH2
group at δ 4.40—4.70 and a triplet of NH of the amide
group at δ 8.00—9.50. In some cases (compounds 7g
and 9b), the signal of the CH2 group is observed as a
To summarize, the reactions of substituted 3ꢀcyanoꢀ
pyridineꢀ2(1H )ꢀthiones and 2ꢀ(methylthio)ꢀ3ꢀcyanoꢀ
pyridines with lithium aluminum hydride in anhydrous
diethyl ether afforded 3ꢀaminomethyl derivatives, which
were used for the synthesis of the corresponding amides.
Experimental
The IR spectra were recorded on a Specord Mꢀ80 spectroꢀ
photometer in KBr pellets. The 1H NMR spectra were measured
on a Bruker WMꢀ250 spectrometer (250 MHz) in DMSOꢀd6
and on a Bruker DRXꢀ500 spectrometer (500 MHz) in
1
quartet of doublets. In addition, the H NMR spectra of
amides 9a—d have a broadened singlet of the NH group
of the pyridine ring at δ 13.00—14.00, which indicates
that these compounds have thione structures. The charꢀ
CCl4—DMSOꢀd6. The signal of the solvent (δ = 2.50) was
H

980
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Zubarev et al.
Table 1. Yields, melting points, and elemental analysis data for the compounds synthesized
Comꢀ
pound
Yield
(%)
M.p./°C
(solvent)
Found
Calculated
Molecular
formula
(%)
C
H
Cl
N
S
4
83
59
45
62
52
72
71
46
76
82
65
69
19
64
55
77
25
77
292—296
(MeOH)
43.87
44.09
5.89
5.81
18.68
18.59
14.57
14.69
16.99
16.81
C7H11ClN2S
C9H14N2S
6a
6b
6c
6d
7a
7b
7c
7d
7e
7f
70—72
59.19
59.30
7.81
7.74
—
—
—
—
—
—
—
15.24
15.37
17.76
17.59
(C6H14
)
97—107
74.26
74.47
5.84
5.92
9.02
9.14
10.88
10.46
C19H18N2S
(C6H14
)
)
71.5
(C6H14
57.32
57.11
7.11
7.19
16.82
16.65
18.75
19.06
C8H12N2S
70—75
63.28
63.42
7.79
7.74
13.33
13.45
15.60
15.39
C11H16N2S
(C6H14
)
185—190
(EtOH/H2O)
60.73
60.62
6.40
6.43
7.36
7.44
8.66
8.52
C19H24N2O4S
C17H19N3O3S
C29H28N2O4S
C18H19ClN2OS
C21H28N2O4S
C19H24N2OS
C20H26N2OS
C19H23ClN2OS
C14H13ClN2OS
C16H18N2O2S
C15H15ClN2OS
C10H14N2OS
C25H21ClN2O2S2
189—190
(EtOH/H2O)
58.89
59.11
5.61
5.54
12.05
12.16
9.42
9.28
213—219
(EtOH/H2O)
69.49
69.58
5.70
5.64
5.51
5.60
6.53
6.40
145—148
(EtOH/H2O)
62.23
62.33
5.57
5.52
10.12
10.22
8.01
8.08
9.35
9.24
122—125
(EtOH/H2O)
62.17
62.35
7.07
6.98
—
—
—
6.71
6.92
8.18
7.93
162—165
(MeCN)
69.35
69.48
7.47
7.36
8.39
8.53
9.92
9.76
7g
7h
9a
9b
9c
9d
10
88.5—90.5
(MeOH)
70.00
70.14
7.72
7.65
8.06
8.18
9.49
9.36
105—107
(MeOH)
62.74
62.88
6.48
6.39
9.68
9.77
7.62
7.72
8.96
8.83
254—256
(AcOEt)
57.31
57.43
4.52
4.48
11.93
12.11
9.45
9.57
11.16
10.95
166—168
(AcOEt)
63.34
63.55
6.06
6.00
—
9.12
9.26
10.79
10.60
232.5—234
(MeOH)
58.59
58.72
4.98
4.93
11.41
11.56
9.02
9.13
10.58
10.45
191—196
(AcOEt)
56.93
57.11
6.77
6.71
—
13.22
13.32
15.41
15.25
175.5—177
(MeCN)
62.53
62.42
4.35
4.40
7.23
7.37
5.89
5.82
13.42
13.33
used as the internal standard. The mass spectra were obtained on
a Finnigan MAT INCOSꢀ50 instrument (70 eV). Elemental
analysis was carried out on a Perkin—Elmer 2400 instrument.
The melting points were determined on a Kofler stage.
Lithium 3ꢀcyanopyridineꢀ2ꢀthiolates (2a,b). A suspension of
pyridinethione 1a,b (10 mmol) in anhydrous Et2O (20 mL) was
added portionwise with stirring to a solution of LiAlH4 (20 mmol)
in anhydrous Et2O (60 mL) for 10 min, weak refluxing being
maintained. The resulting suspension was refluxed with stirring
for 2 h and then water (100 mL) was added dropwise. The
aqueous phase was separated and filtered. The filtrate was conꢀ
centrated. Lithium salts 2a,b were prepared in 80—90% yields.
Lithium 3ꢀaminomethylpyridineꢀ2ꢀthiolates (3a,b). A. A soꢀ
lution of LiAlH4 (10 mmol) in anhydrous Et2O (20 mL) was
added portionwise with stirring to a suspension of lithium thiolate
2a,b (5 mmol) in anhydrous Et2O (30 mL) for 10 min. Then the
reaction mixture was worked up as described above. Lithium
salts 3a,b were prepared in 70—80% yields.
B. Salts 3a,b were synthesized analogously from pyridineꢀ
thiones 1a,b in 70—80% yields.
3ꢀAminomethylꢀ6ꢀmethylpyridineꢀ2(1H)ꢀthione hydrochloride
(4). Concentrated HCl (1 mL) was added to a solution of amine
3a (2 mmol) in water (20 mL), water was distilled off, and the
residue was recrystallized from MeOH.

Substituted 3ꢀ(aminomethyl)pyridines
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
981
Table 2. Spectroscopic characteristics of the compounds synthesized
Comꢀ
pound
IR,
ν/cm–1
MS,
m/z (I (%))
1H NMR,
δ (J/Hz)
3a*
3417 (NH2)
—
2.44 (s, 3 H, Me); 3.85 (m, 2 H, CH2); 6.89 (d, 1 H, H(5), J = 7.4);
7.54 (d, 1 H, H(4), J = 7.4)
3b
4
3384 (NH2)
—
—
—
3456 (NH2),
3480 (NH2),
3504 (NH)
2.40 (s, 3 H, Me); 4.00 (m, 2 H, CH2); 6.70 (d, 1 H, H(5), J = 7.4);
7.70 (d, 1 H, H(4), J = 7.4); 8.60 (s, 3 H, NH3+); 13.75 (s, 1 H, NH)
6a
3408 (NH2)
182 (18.1) [М]+, 167 (100),
150 (22.3), 140 (5.3), 133
(26.6), 120 (12.8), 113 (4.8),
107 (24.5), 91 (10.6), 83 (5.3),
77 (18.1), 65 (13.3), 53 (9.6),
36 (30.9)
1.63 (br.s, 2 H, NH2); 2.30 (s, 3 H, Me(4)); 2.37 (s, 3 H, Me(6));
2.47 (s, 3 H, SMe); 3.72 (s, 2 H, CH2); 6.75 (s, 1 H, H(5))
6b
6c
3448 (NH2)
3328 (NH2)
306 (19.7) [М]+, 291 (100),
274 (7.8), 257 (38.3), 240
(3.9), 215 (4.3), 189 (2.1)
168 (16.42) [М]+, 153 (100),
135 (6.01), 126 (6.31), 119
(22.72), 105 (8.31), 93 (18.22),
77 (6.61), 65 (10.31),
1.52 (br.s, 2 H, NH2); 2.71 (s, 3 H, SMe); 3.71 (s, 2 H, CH2);
7.40—7.60 (m, 9 H, H(3), H(4), H(5), 4ꢀPh, 6ꢀPh);
8.10 (d, 2 H, H(2), H(6), 6ꢀPh, J = 7.9)
2.43 (s, 3 H, Me); 2.50 (s, 3 H, SMe); 3.62 (s, 2 H, CH2);
6.92 (d, 1 H, H(5), J = 7.4); 7.56 (d, 1 H, H(4), J = 7.4)
44 (9.11), 39 (7.01)
6d
3344 (NH2),
1648 (C=C)
—
1.91, 2.17 (both s, 3 H each, Me); 2.50 (s, 3 H, SMe); 3.64 (s, 2 H,
CH2); 6.24 (s, 1 H, C=CH); 6.94 (d, 1 H, H(5), J = 7.4);
7.64 (d, 1 H, H(4), J = 7.4)
6f
3368 (NH2)
3304 (NH2)
—
—
—
—
—
6g
7a**
3272 (NH),
1624 (C=O)
2.30 (s, 3 H, Me(4)); 2.41 (s, 3 H, Me(6)); 2.50 (s, 3 H, SMe);
3.71 (s, 3 H, OMe(4)); 3.81 (s, 6 H, OMe(3), OMe(5)); 4.50 (d, 2 H,
CH2, J = 5.4); 6.81 (s, 1 H, H(5)); 7.17 (s, 2 H, H(2), H(6), Ph);
8.21 (br.s, 1 H, NH)
7b**
7c**
3272 (NH),
1632 (C=O)
345 (41.5) [М]+, 330 (39),
312 (8.5), 298 (7.3), 181 (100),
164 (95.1), 147 (9.8), 136 (9.8),
118 (29.3), 106 (9.8), 90 (36.6),
77 (17.1), 65 (12.2), 53 (7.3),
40 (14.6), 34 (0.7)
500 (17.1) [М]+, 485 (2.4), 467
(1.2), 453 (18.3), 305 (75.6),
289 (43.9), 274 (6.1), 243 (4.9),
215 (6.1), 195 (100), 168 (6.1),
152 (12.2), 137 (9.8), 109 (9.3),
92 (4.9), 77 (19.5),
2.33 (s, 3 H, Me(4)); 2.39 (s, 3 H, Me(6)); 2.40 (s, 3 H, Me(Ph(2));
2.50 (s, 3 H, SMe); 4.48 (d, 2 H, CH2, J = 5.4); 6.85 (s, 1 H, H(5));
7.45 (t, 1 H, H(5), Ph, J = 8.2); 7.57 (d, 1 H, H(6), Ph, J = 7.7);
7.90 (d, 1 H, H(4), Ph, J = 8.2); 8.45 (t, 1 H, NH, J = 5.4)
3280 (NH),
1628 (C=O)
2.68 (s, 3 H, SMe); 3.72 (s, 3 H, OMe(4)); 3.83 (s, 6 H, OMe(3),
OMe(5)); 4.37 (s, 2 H, CH2); 7.16 (s, 2 H, H(2), H(6), COPh);
7.41—7.56 (m, 9 H, Ph, H(5)); 8.15 (d, 2 H, H(2), H(6),
Ph, J = 7.9); 8.31 (br.s, 1 H, NH)
57 (7.3), 40 (12.7)
7d**
3288 (NH),
1640 (C=O)
346 (34.23) [М]+, 333 (5.21),
331 (14.41), 313 (7.31), 207
(66.17), 191 (13.31), 190
(17.72), 176 (30.03), 158
(30.93), 144 (10.01), 141
1.91 (s, 3 H, Me(1)); 2.18 (s, 3 H, Me(2)); 2.55 (s, 3 H, SMe); 4.38
(d, 2 H, CH2, J = 5.4); 6.25 (s, 1 H, C=CH); 6.95 (d, 1 H,
H(5), J = 7.4); 7.44 (d, 1 H, H(4), J = 7.4); 7.56 (d, 2 H, H(3),
H(5), Ph, J = 7.9); 7.92 (d, 2 H, H(2), H(6), Ph, J = 7.9); 9.04
(t, 1 H, NH, J = 5.4)
(30.93), 140 (9.91), 139 (100),
131 (10.81), 130 (9.91), 117
(11.91), 113 (17.32), 111 (55.66),
91 (9.81), 77 (15.22), 75 (21.22),
51 (9.61), 41 (10.31), 39 (12.41)
(to be continued)

982
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Zubarev et al.
Table 2 (continued)
Comꢀ
pound
IR,
ν/cm–1
MS,
m/z (I (%))
1H NMR,
δ (J/Hz)
7e**
3288 (NH),
1624 (C=O)
404 (14.71) [М]+, 389 (9.71),
357 (13.81), 210 (12.41), 209
(100), 196 (12.01), 195 (96.90),
193 (10.91), 152 (13.51), 151
(8.91), 150 (9.71), 122 (11.81),
81 (10.51), 77 (18.92),
0.90 (d, 6 H, 2 Me, J = 6.5); 2.10 (m, 1 H, CH); 2.54 (s, 3 H, SMe);
2.58 (d, 2 H, CHCH2, J = 4.8); 3.71 (s, 3 H, OMe(4)); 3.83 (s, 6 H,
OMe(3), OMe(5)); 4.39 (d, 2 H, CH2NH, J = 5.4);
6.93 (d, 1 H, H(5), J = 7.4); 7.26 (s, 2 H, H(2), H(6), Ph); 7.42
(d, 1 H, H(4), J = 7.4); 8.84 (br.t, 1 H, NH, J = 5.4)
43 (15.72), 41 (11.41)
7f
3296 (NH),
1632 (C=O)
—
1.38 (s, 9 H, But); 2.49 (s, 3 H, Me); 2.60 (s, 3 H, SMe); 4.38 (s, 2 H,
CH2); 6.88 (d, 1 H, H(5), J = 7.4); 7.35 (d, 1 H, H(4), J = 7.4); 7.45
(d, 2 H, H(3), H(5), COAr, J = 7.9); 7.85 (d, 2 H, H(2), H(6),
COAr, J = 7.9); 8.70 (br.t, 1 H, NH, J = 5.4)
7g
3280 (NH),
1640 (C=O)
342 (53.66) [М]+, 327 (16.59),
309 (13.41), 295 (21.95), 237
(4.15), 195 (100), 189 (10.49),
181 (87.8), 164 (12.2), 150
(11.71), 134 (10.98), 119
(11.95), 105 (93.41), 91
1.25 (m, 9 H, Me2CH, PhCHMe); 2.42 (m, 2 H, COCH2); 2.55 (s,
3 H, SMe); 2.98 (m, 1 H, Me2CH); 3.22 (m, 1 H, CH2CH(Me)Ph);
4.10 (q.d, 2 H, CH2NH, J1 = 15.1, J2 = 5.4); 6.71 (d, 1 H, H(5),
J = 7.4); 6.94 (d, 1 H, H(4), J = 7.4); 7.22 (m, 5 H, Ph);
7.96 (t, 1 H, NH, J = 5.4)
(36.59), 77 (32.93), 65 (9.76),
51 (10.47), 41 (19.51)
7h
3344 (NH),
1640 (C=O)
—
1.02 (t, 3 H, Me, J = 6.6); 1.49 (m, 4 H, CH2(3), CH2(4)); 1.67
(m, 2 H, CH2(2)); 2.53 (s, 3 H, SMe); 2.81 (t, 2 H, CH2(1), J = 6.9);
4.29 (s, 2 H, CH2NH); 6.93 (d, 1 H, H(5), J = 7.4); 7.42 (d, 1 H,
H(4), J = 7.4); 7.56 (d, 2 H, H(3), H(5), Ph, J = 7.9); 7.93 (d, 2 H,
H(2), H(6), Ph, J = 7.9); 9.07 (t, 1 H, NH, J = 5.4)
9a**
3288 (NH),
1632 (C=O)
292 (5.6) [М]+, 153 (100),
139 (13.8), 126 (3.7), 111 (16),
92 (9.6), 65 (6.4), 41 (5.3)
2.35 (s, 3 H, Me); 4.41 (s, 2 H, CH2); 6.60 (d, 1 H, H(5), J = 7.4);
7.25 (d, 1 H, H(4), J = 7.4); 7.57 (d, 2 H, H(3), H(5), Ph, J = 7.9);
7.93 (d, 2 H, H(2), H(6), Ph, J = 7.9);
8.91 (d, 1 H, NH(amide), J = 5.4); 13.4 (s, 1 H, NH(pyridine))
9b
3248 (NH),
1652 (C=O)
302 (20.02) [М]+, 209 (12.81),
154 (11.51), 153 (100),
152 (15.32), 139 (12.41), 138
(36.54), 121 (22.02), 93 (15.92),
92 (20.32), 77 (44.94), 65
1.50 (d, 3 H, CHMe, J = 6.8); 2.33 (s, 3 H, Me); 4.20 (quad.d, 2 H,
CH2NH, J1 = 18, J2 = 5.8); 4.79 (q, 1 H, MeCH, J = 6.8); 6.42 (d,
1 H, H(5), J = 7.4); 6.96 (m, 5 H, Ph); 7.30 (d, 1 H, H(4), J = 7.4);
8.35 (d, 1 H, NH(amide), J = 5.8); 13.39 (s, 1 H, NH(pyridine))
(12.41), 51 (12.11), 39 (12.01)
9c
3312 (NH),
1628 (C=O)
306 (27.66) [М]+, 273 (2.13),
167 (100), 150 (13.83),
139 (12.76), 111 (8.51)
2.27, 2.29 (both s, 3 H each, Me); 4.68 (d, 2 H, CH2NH, J = 5.8);
6.52 (s, 1 H, H(5)); 7.51 (d, 2 H, H(3), H(5), Ph, J = 7.9); 7.80 (d,
2 H, H(2), H(6), Ph, J = 7.9); 8.50 (t, 1 H, NH(amide), J = 5.8);
13.35 (s, 1 H, NH(pyridine))
9d
10
3344 (NH),
1624 (C=O)
—
1.80 (s, 3 H, CH3CO); 2.21, 2.30 (both s, 3 H each, Me);
4.45 (d, 2 H, CH2NH, J = 5.8); 6.50 (s, 1 H, H(5)); 7.70 (t, 1 H,
NH(amide), J = 5.8); 13.40 (s, 1 H, NH(pyridine))
3248 (NH),
1324 (S=O),
1168 (S=O)
480 (26.8) [М]+, 305 (100),
289 (23.2), 257 (4.9), 227 (5.1),
202 (8.5), 189 (2.4), 175 (4.4),
152 (5.4), 128 (6.8), 111 (30),
91 (4.4), 75 (15.1), 69 (2.4),
57 (2.2), 43 (3.9)
2.70 (s, 3 H, SMe); 3.90 (s, 2 H, CH2); 7.25—7.50 (m, 11 H, H(5),
4ꢀPh, 6ꢀPh, H(3), H(4), H(5), SO2Ar, H(3), (5)); 7.63 (d, 2 H,
H(2), H(6), SO2Ar, J = 8.4); 7.70 (t, 1 H, NH, J = 5.4);
8.10 (d, 2 H, H (2), H(6), 6ꢀPh, J = 7.9)
1
* The H NMR spectrum was recorded in D2O.
1
** The H NMR spectrum was recorded at 500 MHz.

Substituted 3ꢀ(aminomethyl)pyridines
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
983
3ꢀAminomethylꢀ2ꢀ(methylthio)pyridines (6a—g). A solution
of 3ꢀcyanoꢀ2ꢀmethylthiopyridine 5a—g (5 mmol) in anhydrous
Et2O (25 mL) was added dropwise with stirring to a suspension
of LiAlH4 (10 mmol) in anhydrous Et2O (50 mL) for 15 min.
The resulting suspension was refluxed with stirring for 1 h and
cooled. Then water (100 mL) was added dropwise. The organic
phase was separated and the aqueous phase was extracted with
Et2O. The combined organic phases were dried over MgSO4 and
concentrated. The residue was recrystallized from hexane.
3ꢀAcylaminomethylꢀ2ꢀ(methylthio)pyridines (7a—h). Triꢀ
ethylamine (1.5 mmol) and carboxylic acid chloride 8c—g
(1.35 mmol) were added to a suspension of amine 6a—g
(1.5 mmol) in MeCN (5 mL). The reaction mixture was heated
to boiling, cooled, kept at 20 °C for 24 h, diluted with water
(30 mL), and acidified with a 3% aqueous HCl solution. The
precipitate that formed was filtered off, washed with water and a
10% NaHCO3 solution, and recrystallized from 50% aqueous
EtOH.
khimiya [Advances in Science and Technology: Organic Chemꢀ
istry], VINITI, Moscow, 1989, 17, p. 72 (in Russian).
2. V. P. Litvinov, L. A. Rodinovskaya, Yu. A. Sharanin, A. M.
Shestopalov, and A. Senning, Sulfur Reports, 1992, 13, 1.
3. V. D. Zhiryakov and P. M. Abramenko, Khim. Geterotsikl.
Soedin., 1965, 334 [Chem. Heterocycl. Compd., 1965 (Engl.
Transl.)].
4. H. Jahine, H. A. Zaher, M. Seada, and M. F. Ishak, Ind.
J. Chem., 1979, 17B, 134.
5. N. G. Frolova, V. K. Zav´yalova, and V. P. Litvinov, Khim.
Geterotsikl. Soedin., 1996, 231 [Chem. Heterocycl. Compd.,
1996 (Engl. Transl.)].
6. A. A. Krauze, Z. A. Bomika, Yu. E. Pelcher, I. B. Mazheika,
and G. Ya. Dubur, Khim. Geterotsikl. Soedin., 1982, 508
[Chem. Heterocycl. Compd., 1982 (Engl. Transl.)].
7. US Pat. 3965107; Chem. Abstrs., 1976, 85, 160072h.
8. F. S. Babichev, Yu. A. Sharanin, V. P. Litvinov, V. K.
Promonenkov, and Yu. M. Volovenko, Vnutrimolekulyarnoe
vzaimodeistvie nitril´noi i C—Hꢀ, O—Hꢀ i S—Hꢀgrupp [Intraꢀ
molecular Interactions of the Nitrile Group with the C—H,
O—H, and S—H Groups], Naukova Dumka, Kiev, 1985,
200 pp. (in Russian).
3ꢀ(Acylaminomethyl)pyridineꢀ2(1H)ꢀthiones (9a—d) were
synthesized as described above from amines 3a,b.
3ꢀ[(4ꢀChlorophenyl)sulfonylaminomethyl]ꢀ2ꢀmethylthioꢀ4,6ꢀ
diphenylpyridine (10). Triethylamine (1.5 mmol) and amide 7f
(1.35 mmol) were added to a suspension of amine 6b (1.5 mmol)
in MeCN (5 mL). The reaction mixture was heated to boiling,
cooled, kept at 20 °C for 24 h, diluted with water (30 mL), and
acidified with a 3% aqueous HCl solution. The precipitate that
formed was filtered off, washed with water and a 10% NaHCO3
solution, and recrystallized from MeCN.
9. K. Gewald, H. Shafer, and U. Schlegel, J. Prakt. Chem.,
1975, 317, 959.
10. U. Schmidt and G. Giesselmann, Chem. Ber., 1960, 93, 1950.
11. E. C. Taylor, G. S. Wong, S. R. Fletcher, P. J. Harrington,
G. P. Beardsley, and C. J. Shin, Pteridines and Folic Acid
Deriv., Proc. 8th Int. Symp. (Montreal, January 15—20, 1986),
Berlin—New York, 1986, 61.
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ
32063).
12. A. M. Shestopalov, L. A. Rodinovskaya, Yu. A. Sharanin,
and V. P. Litvinov, Zh. Obshch. Khim., 1988, 53, 840 [J. Gen.
Chem. USSR, 1988, 53 (Engl. Transl.)].
13. H. D. H. Showalter and T. H. Haskell, J. Heterocycl. Chem.,
1981, 18, 367.
References
1. V. P. Litvinov, V. K. Promonenkov, Yu. A. Sharanin, and
Received July 16, 2002;
A. M. Shestopalov, in Itogi nauki i tekhniki, Organicheskaya
in revised form November 11, 2002