Recyclization of 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2- dihydro-pyridin-2-ones into 1,6-annelated derivatives of 3-alkylcarbamoyl-5- benzoylpyridin-2-one

Article abstract of DOI:10.1007/s10593-009-0284-9

For the first time the possibility has been shown of recyclizing 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyridin-2-ones into 1,6-annelated bicyclic derivatives of 3-alkylcarbamoyl-5-benzoylpyridin-2-one, which takes place on reacting th

Full text of DOI:10.1007/s10593-009-0284-9

Chemistry of Heterocyclic Compounds, Vol. 45, No. 4, 2009
RECYCLIZATION OF 1-ALKYL-5-BENZOYL-
3-ETHOXYCARBONYL-6-METHYLTHIO-1,2-DIHYDRO-
PYRIDIN-2-ONES INTO 1,6-ANNELATED DERIVATIVES
OF 3-ALKYLCARBAMOYL-5-BENZOYLPYRIDIN-2-ONE
V. N. Britsun1*, A. N. Esipenko1, A. V. Gootov1, A. N. Chernega1, and M. O. Lozinskii1
For the first time the possibility has been shown of recyclizing 1-alkyl-5-benzoyl-3-ethoxycarbonyl-
6-methylthio-1,2-dihydropyridin-2-ones into 1,6-annelated bicyclic derivatives of 3-alkylcarbamoyl-
5-benzoylpyridin-2-one, which takes place on reacting the former with 1,4- and 1,5-nitrogen-containing
dinucleophiles. The structure of the recyclization products was demonstrated by spectral methods and
X-ray structural analysis.
Keywords: alkylamines, 1-(alkylamino)phenylmethylidene-3-methylcarbamoyl-4-oxo-1,4-dihydro-
benzo[4,5]imidazo[1,2-a]pyridines, 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyri-
din-2-ones, 3-alkylcarbamoyl-1-benzoyl-4-oxo-4H-benzo[4,5][1,3]thiazolo[3,2-a]pyridines, 3-alkyl-
carbamoyl-1-benzoyl-4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyridines,
6-alkylcarbamoyl-
8-benzoyl-5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridines, 7-alkylcarbamoyl-9-benzoyl-6-oxo-1,2,3,5-
tetrahydro-2H-pyrido[1,2-a]pyrimidines, 1-amino-2-mercaptoethane, 1,3-diaminopropane, o-amino-
thiophenol, diaminoethane, o-phenylenediamine, recyclization X-ray structural analysis.
We showed recently that 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyridin-2-ones
1a,b are regiospecifically cyclocondensed with nitrogen-containing 1,2-, 1,3-, 1,4-, and 1,5-dinucleophiles [1-4]. In
the last two cases the reaction proceeds as a recyclization [3,4].
The aim of the present work was to establish unequivocally the structure of the products of
recyclization, to study the limits of its application, to investigate the effect of the ratio of starting materials on
the direction of the reaction, and to clarify the sequence of formation of intermediate compounds.
It was discovered that 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyridin-2-ones
1a,b react with an excess of diaminoethane 2a and 1,3-diaminopropane 2b nonselectively. The reaction products
are therefore not derivatives of 5-benzoyl-3-heteryl-2H-2-pyranone, as we proposed previously [3, 4], but are
6-alkylcarbamoyl-8-benzoyl-5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridines
3a,b,
7-alkylcarbamoyl-
9-benzo-yl-6-oxo-1,2,3,5-tetrahydro-2H-pyrido[1,2-a]pyrimidines 3c,d, and 1-alkyl-6-(1-alkyl-5-benzoyl-
_______
* To whom correspondence should be addressed, e-mail: bvn1967@rambler.ru.
1Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev-94, 02660, Ukraine.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 568-577, April, 2009. Original
article submitted March 16, 2009.
0009-3122/09/4504-0445©2009 Springer Science+Business Media, Inc.
445

3-ethoxy-carbonyl-2-oxo-1,2-dihydropyrid-6-yl)oxy-5-benzoyl-3-ethoxycarbonyl-2-oxo-1,2-dihydropyridines
4a,b. The latter are also formed on hydrolysis of the initial 1,2-dihydropyridin-2-ones 1a,b, occurring under the
action of water and triethylamine [3].
O
Ph
Ph
NHR
O
H2N(CH2)nNH2
EtO2C
O
EtO2C
O
O
N
O
(CH2)n
2a,b
O
+
N
H
SMe
N
R
N
O
R
2
Ph
3a–d
1a,b
4a,b
2a,b
2a,b
HS(CH2)2NH2
2a,b
5
Ph
Ph
EtO2C
O
EtO2C
O
O
O
S
N
N
N
N
(CH2)n
H
H
2
R
2
R
6
7a–d
1a, 3a,c, 4а, 6, 7а,c R = Me; 1b, 3b,d, 4b, 7b,d R = Et; 2a, 3a,b, 7a,b n = 2;
2b, 3c,d, 7c,d n = 3
The yields of compounds 3a-d and 4a,b were 39-69 and 24-49% respectively.
At the same time, at a ratio of initial reactants 1a,b and 2a,b equal to 2:1 the interaction occurs
selectively with the formation of N,N'-di(1-alkyl-5-benzoyl-3-ethoxycarbonyl-2-oxo-1,2-dihydropyrid-6-yl)-
1,2-diaminoethanes (1,3-diaminopropanes) 7a-d. These same compounds are also obtained on reaction of
dipyridyl oxides 4a,b with equimolar amounts of diaminoalkanes 2a,b. Compound 7a, under the action of a
threefold excess of diaminoalkane 2a, is recyclized into 8-benzoyl-6-methylcarbamoyl-5-oxo-1,2,3,5-
tetrahydroimidazo[1,2-a]pyridine (3a). Dipyridyl oxides 4a,b and substituted diaminoalkanes 7a-d are therefore
intermediates in the recyclization of 1,2-dihydropyridin-2-ones 1a,b into 5-oxo-1,2,3,5-tetrahydroimidazo-
[1,2-a] pyridines 3a,b and 6-oxo-1,2,3,5-tetrahydro-2H-pyrido[1,2-a]pyrimidines 3c,d.
On using 1-amino-2-mercaptoethane 5 (generated in situ from its hydrochloride and triethylamine) as a
1,4-dinucleophilic
reagent
only
di[2'-(5-benzoyl-3-ethoxycarbonyl-1-methyl-2-oxo-1,2-dihydropyrid-6-yl)-
aminoethyl] disulfide (6) was isolated from the reaction mixture. This is probably explained both by the lower
nucleophilicity of the mercapto group compared with the amino group, and by its ease of oxidation by air in the
presence of bases [5].
Like the recyclization, interaction of 1,2-dihydropyridin-2-ones 1a,b with the aromatic nitrogen-
containing 1,4-dinucleophiles o-phenylenediamine (8a) and o-aminothiophenol (8b) also takes place. The
products of this reaction were respectively, 3-alkylcarbamoyl-1-benzoyl-4-oxo-4,10-dihydrobenzo-
[4,5]imidazo[1,2-a]pyridines 9a,b, 3-alkylcarbamoyl-1-benzoyl-4-oxo-4H-benzo[4,5][1,3]thiazolo[3,2-a]pyri-
dines 9c,d and dipyridyl oxides 4a,b. The yields of compounds 9a-d and 4a,b were 57-70 and 26-32%,
respectively. The ability of o-aminothiophenol 8b, unlike 1-amino-2-mercaptoethane 5, to enter into
recyclization with 1,2-dihydropyridin-2-ones 1a,b, is, to all appearances, linked with its more rigid molecular
structure and a lower inclination towards oxidation.
The yields, melting points, and data of elemental analysis of compounds 3a-d, 6, 7a-d, and 9a-d are
13
1
given in Table 1, and the data of IR, C, and H NMR spectra in Tables 2-4. In difference to the reactions of
446

TABLE 1. Characteristics of the Synthesized Compounds
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
mp, °С*
Yield, %
69
С
H
N
S
3a
C16H15N3O3
C17H17N3O3
C17H17N3O3
C18H19N3O3
C34H32N2O9
C36H38N4O8S2
C34H34N4O8
С36Н38N4O8
С35Н36N4O8
С37Н40N4O8
C20H15N3O3
C21H17N3O3
C20H14N2O3S
C21H16N2O3S
C22H20N4O3
C23H22N4O3
C28H24N4O2
C25H20N4O3
64.37
64.64
65.60
65.58
65.73
65.58
66.64
66.45
66.43
66.66
59.88
60.15
65.32
65.17
65.83
66.04
65.45
65.61
66.25
66.45
69.74
69.56
69.89
70.18
66.02
66.29
66.75
67.01
68.22
68.03
68.62
68.64
4.98
5.09
5.58
5.50
5.32
5.50
5.68
5.89
4.99
5.26
5.59
5.33
5.22
5.47
6.02
5.85
5.84
5.66
5.92
6.03
4.31
4.38
4.56
4.77
4.15
3.89
4.42
4.28
5.03
5.19
5.72
5.51
14.30
14.13
13.61
13.50
13.74
13.50
13.15
12.91
4.86
4.57
7.93
7.79
9.07
8.94
8.65
8.56
9.02
8.74
8.50
8.38
12.13
12.17
11.85
11.69
7.48
7.73
7.29
7.44
14.30
14.42
13.97
13.92
335-337
300-303
253-256
257-259
75-77
3b
3с
63
43
39
45
61
73
69
67
62
70
63
61
57
73
77
82
69
3d
4b*2
6
8.81
8.92
185-187
220-222
155-158
215-218
123-125
283-285
272-275
250-252
241-243
232-234
210-212
214-217
210-212
7a
7b
7c
7d
9a
9b
9c
8.64
8.85
8.40
8.52
9d
11a
11b
11c
11d
75.11
74.98
70.49
70.74
5.40
5.39
5.00
4.75
12.72
12.49
13.03
13.20
_______
* Compounds 3a-d, 9a-d, 7a,b were recrystallized from DMSO, compound
4b from 2-propanol, compounds 6 and7a-d from nitromethane, compounds
11a-d from ethanol.
*2The mp of compound 4a corresponded to that given in [3].
3-cyano-5-ethoxycarbonyl-4-methyl-6-methylthio-1-phenyl-1,2-dihydropyridin-2-one with diaminoethane and
1,3-diaminopropane [6], the recyclization reaction investigated by us of compounds 1a,b into 1,6-annelated
derivatives of 3-alkylcarbonyl-5-benzoylpyridin-2-one 3a-d and 9a-d were effected with the participation of the
ethoxycarbonyl group and without elimination of the alkylamino group. This recyclization therefore has a
general character and permits the synthesis of the series of bicyclic derivatives of 3-benzoylpyridin-2-one 3a-d,
9a-d, containing an alkylcarbamoyl group in their structures.
To obtain derivatives of compound 9 suitable for establishing the structure by X-ray structural analysis
we carried out the amination of 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyridine 9a with alkylamines
10a-d. The reactions of compound 9a with a threefold excess of reactants 10a-d at 120-140oC were completed
after 10-20 min, while benzimidazo[1,2-a]pyridine 9a was completely stable to the action of a sixfold excess of
boiling aniline after 6 h. Evidently the determining factor enabling the reaction to be effected at an acceptable
rate is the high nucleophilicity of alkylamines 10a-d.
447

H2N
HX
O
NHR
O
8a,b
N
O
1a,b
4a,b
+
X
Ph
9a–d
O
NHR
O
R1 NH2
10a–d
N
X = NH
N
R1
N
Ph
H
11a–d
9а,с, 11а–d R = Me, 9b,d R = Et, 8a, 9a,b X = NH, 8b, 9c,d X = S;
10a, 11a R1 = (CH2)2OH, 10b, 11b R1 = (CH2)3OH, 10c, 11c R1 = Ph(CH2)2,
10d, 11d R1 = 2-furfuryl
It was found that the products of the amination of 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyridine
9a with alkylamines 10a-d are 1-(alkylamino)phenylmethylidene-3-methylcarbamoyl-4-oxo-1,4-dihydro-
benzo[4,5]imidazo[1,2-a]pyridines 11a-d and the reaction takes place in preparative yield (69-82%).
3-Alkylcarbamoyl-1-benzoyl-4-oxo-4H-benzo[4,5][1,3]thiazolo[3,2-a]pyridines 9c,d did not take part in similar
reactions with alkylamines 10a-d. A convincing sign of the accomplishment of this interaction is the absence
TABLE 2. IR Spectra of the Synthesized Compounds
Compound
ν, cm-1
3a
3380, 3300, 3050, 2970, 1680, 1640, 1600, 1580, 1500
3b
3c
3400, 3300, 3100, 3000, 1680, 1640, 1610, 1580, 1500, 1450, 1380, 1330
3300, 3100, 2950, 1670, 1640, 1590, 1550, 1510, 1440, 1400, 1380
3300, 3100, 3000, 1670, 1640, 1580, 1540, 1510, 1470, 1380
3100, 3000, 1720, 1680, 1610, 1530, 1450, 1400, 1370, 1320
3000, 1720, 1650, 1570, 1500, 1450, 1400, 1380, 1320
3d
4b*
6
7a
3400, 3200, 3050, 1720, 1680, 1660, 1540, 1580, 1500, 1440
3300, 3100, 3000, 1720, 1660, 1620, 1590, 1520, 1460, 1420
3400, 3200, 3000, 1720, 1660, 1580, 1520, 1450, 1370
7b
7с
7d
9a
3300, 3050, 3000, 1720, 1650, 1630, 1590, 1510, 1460, 1410
3330, 3000, 1675, 1620, 1600, 1560, 1540, 1470, 1450, 1390, 1370
3330, 3000, 1685, 1610, 1560, 1470, 1440, 1390, 1370, 1340, 1320, 1260
3350, 3000, 1670, 1615, 1560, 1490, 1460, 1420, 1380, 1330
3300, 3000, 1690, 1620, 1570, 1500, 1470, 1385, 1310
9b
9c
9d
11a
11b
11c
11d
3400, 3270, 2900, 1660, 1620, 1590, 1530, 1450, 1430, 1350, 1330, 1295
3400, 3300, 3000, 1690, 1660, 1620, 1570, 1470, 1440, 1360, 1350
3300, 3000, 2900, 1680, 1600, 1570, 1540, 1430
3350, 2900, 1690, 1660, 1620, 1560, 1470, 1440
_______
*The IR spectrum of compound 4a corresponded to that given in [3].
448

TABLE 3. 13C NMR Spectra of the Synthesized Compounds
Com-
Chemical shifts (DMSO-d6), δ, ppm
pound
3b
3c
14.8 (NCH2CH3); 33.2 (C-2); 43.1 (NCH2CH3); 43.4 (C-3); 97.7, 106.5, 127.8, 128.3,
130.7, 138.8, 146.4, 156.3; 160.3 (C=О); 162.8 (C=О); 191.3 (Ph–C=O)
18.7 (3-CH2); 26.1 (NCH3); 38.7 (C-2); 39.9 (4-CH2); 98.8, 104.6, 128.5, 128.9, 131.1,
140.0, 146.8, 155.0; 161.4 (C=О); 164.4 (C=О); 194.1 (C6H5–C=O)
7a
14.7 (ОСН2CH3); 33.4 (N CH3); 48.0 (NСН2); 60.1 (ОСН2Me); 101.5, 104.5, 128.8,
129.1, 132.0, 138.9, 148.2, 159.0, 160.2; 164.6 (C=O); 193.1 (C6H5–С=О)
9a
25.7 (NMe); 99.4, 105.6, 113.0, 116.4, 123.5, 126.8, 126.9, 128.4, 128.5, 131.2, 131.5,
138.5, 144.1, 144.9; 159.4 (C=О); 163.8 (C=О); 191.2 (C6H5–C=O)
11b
26.2 (NCH3); 32.6 (СН2); 44.3 (CH2NH); 58.4 (CH2OH); 97.3, 107.1, 116.0, 118.2,
122.9, 125.7, 128.9, 129.5, 129.8, 130.2, 131.4, 142.8, 145.0, 149.8; 161.5; 164.5 (C=О);
169.6 (C=О
11d
26.3 (NCH3); 43.2 (СН2Het); 97.5, 109.3, 111.4, 116.0, 118.2, 123.2, 125.8, 129.2, 129.5,
129.7, 129.8, 131.6, 142.6, 144.1, 145.4, 149.3, 149.8, 161.6; 164.4 (C=О); 169.4 (C=О)
from the 13C NMR spectra of the extremely characteristic signals of the carbonyl group carbon atom of the
13
benzoyl fragment which, in the C NMR spectra of 1,6-annelated derivatives of 5-alkylcarbamoyl-3-benzoyl-
pyridin-2-one 3b,c, 9a, are observed in the region of 191.2-194.1 ppm.
TABLE 4. 1H NMR Spectra of the Synthesized Compounds
Com-
pound
Chemical shifts (DMSO-d6) δ, ppm (SSCS, J, Hz)*
1
2
3a
2.75 (3Н, d, J = 4.2, NНCH3); 3.91 (2H, m, Н-2); 4.14 (2H, t, J = 9.3, Н-3);
7.52 (5Н, m, C6H5); 8.31 (1Н, s, Н-7); 8.90 (1Н, br. s, NНMe); 9.39 (1Н, br. s, 1-NH)
3b
3c
3d
1.08 (3Н, t, J = 7.2, NНCH2CH3); 3.21 (2Н, m, NНCH2CH3); 3.92 (2H, m, Н-2);
4.13 (2H, t, J = 9.0, Н-3); 7.52 (5Н, m, C6H5); 8.32 (1Н, s, Н-7); 9.02 (1Н, br. s, NНEt);
9.37 (1Н, br. s, 1-NH)
2.04 (2Н, m, Н-3); 2.75 (3Н, d, J = 4.5, NНCH3); 3.52 (2H, m, Н-2); 3.99 (2H, m, Н-4);
7.39-7.65 (5Н, m, C6H5); 8.31 (1Н, s, Н-8); 8.92 (1Н, q, J = 4.5, NНMe);
10.88 (1Н, br. s, 1-NH)
1.07 (3Н, t, J = 6.6, NCH2CH3); 2.06 (2Н, m, Н-3); 3.47 (2H, m, NCH2CH3);
3.53 (2H, m, Н-2); 3.98 (2H, m, Н-4); 7.40-7.61 (5Н, m, C6H5); 8.32 (1Н, s, Н-8);
9.05 (1Н, br. t, NНСН2СН3); 10.87 (1Н, br. s, 1-NH)
4b*2
6
1.28 (12H, m, 4СН2CH3), 4.18 (4H, q, J = 7.1, 2NСН2Mе),
4.37 (4H, q, J = 6.4, 2OСН2Me), 7.52-7.65 (10H, m, 2C6H5), 8.17 (2H, s, 4-2Н)
1.30 (6Н, t, J = 6.6, 2ОСН2CH3); 2.96 (4Н, t, J= 6.0, 2СН2S); 3.59 (6Н, s, 2NCH3);
3.85 (4Н, m, 2СН2 ); 4.26 (4H, q, J = 6.6, 2ОСН2Mе); 7.45-7.54 (5Н, m, C6H5);
8.44 (2Н, s, 4-2Н); 10.70 (2Н, s, 2NH)
7a
1.15 (6H, t, J = 6.9, 2OСН2CH3); 3.40 (6H, s, 2NCH3); 3.65 (4H, br. s, 2NСН2);
4.07 (4H, q, J = 6.9, 2OСН2Me); 7.45-7.56 (10H, m, 2C6H5); 8.04 (2H, s, 2Н-4);
9.34 (2H, s, 2NH)
7b
1.14 (12H, m, 4СН2CH3); 3.46 (4Н, br. s, 2NСН2); 4.05 (8H, m, 4СН2Me);
7.48-7.57 (10H, m, 2C6H5); 8.05 (2H, s, 2Н-4); 8.76 (2H, s, 2NH)
7с
1.15 (6H, t, J = 7.2, 2OСН2CH3); 2.03 (2H, t, J = 6.6, CH2); 3.21 (4H, m, 2NCH2);
3.43 (6H, s, 2NCH3); 4.08 (4H, q, J = 7.2, OСН2Me); 7.44-7.61 (10H, m, 2C6H5);
8.08 (2H, s, 2Н-4); 9.43 (2H, s, 2NH)
7d
9a
1.16 (12H, m, 4СН2CH3); 1.99 (2H, t, J = 6.3, CH2); 3.17 (4H, m, 2NCH2);
4.08 (8H, m, 4СН2Me); 7.48-7.62 (10H, m, 2C6H5); 8.02 (2H, s, 2Н-4); 8.89 (2H, s, 2 NH)
2.85 (3Н, d, J = 3.6, NНCH3); 7.48 (1Н, m, НAr); 7.63-7.69 (6Н, m, НAr);
7.84 (1Н, m, Н-9); 8.68 (1Н, s, Н-2); 8.70 (1Н, m, Н-6); 9.00 (1Н, br. s, NНMe);
13.71 (1Н, s, 10-NH)
9b
1.16 (3Н, t, J = 6.3, NНCH2CH3); 3.36 (2Н, m, NНCH2CH3); 7.49 (1Н, m, НAr);
7.62-7.76 (6Н, m, НAr); 7.88 (1Н, m, Н-9); 8.69 (1Н, s, Н-2); 8.71 (1Н, m, Н-6);
9.11 (1Н, br. s, NНEt); 13.73 (1Н, s, 10-NH)
449

TABLE 4 (continued)
1
2
9c
2.87 (3Н, d, J = 2.7, NНCH3); 7.66 (7Н, m, НAr); 8.23 (1Н, m, Н-9); 8.74 (1Н, s, Н-2);
9.02 (1Н, br. s, NНMe); 9.20 (1Н, m, H-6)
9d
1.18 (3Н, t, J = 6.6, NНCH2CH3); 3.34 (2Н, m, NНCH2CH3); 7.68-7.83 (7Н, m, НAr);
8.26 (1Н, m, Н-9); 8.78 (1Н, s, Н-2); 9.15 (1Н, br. s, NНEt); 9.24 (1Н, m, H-6)
11a
2.79 (3Н, d, J = 4.2, NНCH3); 3.51 (2Н, br. s, СН2); 3.67 (2Н, br. s, СН2);
5.25 (1Н, br. s, ОН); 7.37-7.82 (8Н, m, НAr); 7.98 (1Н, s, Н-2); 8.54 (1Н, d, J = 7.8, Н-6);
9.00 (1Н, q, J = 4.2, NНMе); 12.82 (1Н, br. s, NH)
11b
11c
11d
1.85 (2Н, t, J = 6.3, СН2); 2.80 (3Н, d, J = 4.2, NНCH3); 3.50-3.61 (4Н, m, 2СН2);
4.62 (1Н, t, J = 4.8, ОН); 7.36-7.80 (8Н, m, НAr); 7.98 (1Н, s, Н-2);
8.54 (1Н, d, J = 7.8, Н-6); 9.00 (1Н, q, J = 4.2, NНMе); 12.74 (1Н, br. s, NH)
2.78 (3Н, d, J = 4.8, NНCH3); 2.99 (2Н, t, J = 6.0, CH2Ph); 3.69 (2Н, m, СH2NH);
7.23-7.52 (13Н, m, НAr); 7.93 (1Н, s, Н-2); 8.52 (1Н, d, J = 7.5, Н-6);
8.96 (1Н, q, J = 4.8, NНMе); 12.64 (1Н, t, J = 6.6, NH
2.80 (3Н, d, J = 4.5, NНCH3); 4.69 (2Н, d, J = 4.5, СН2Het); 6.37 (1Н, m, Het);
6.44 (1Н, m, Het); 7.36-7.73 (9Н, m, НAr); 8.01 (1Н, s, Н-2); 8.52 (1Н, d, J = 7.5, Н-6);
8.95 (1Н, q, J = 4.5, NНMе); 12.85 (1Н, br. t, NH)
_______
* The 1H NMR spectrum of compound 4a corresponded to that given in
[3], the 1H NMR spectrum of compound 6 was recorded in CDCl3.
The structure of compound 11c was investigated by X-ray structural analysis (Table 5 and Fig. 1). An
interesting special feature of its molecular structure is the formation of the fairly stable intramolecular hydrogen
bonds N–H···N and N–H···O, closing the six-membered rings N(4)C(14)C(8)C(7)N(2)H(4) and N(3)C(10–
12)O(2)H(3).
Fig. 1. General form of the molecule of 3-methylcarbamoyl-4-oxo-1-(2-phenylethylamino)
phenylmethylidene-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyridine 11c.
On the basis of the experimental data the following scheme may be proposed for the mechanism of
recyclization of dihydropyridin-2-ones 1a,b into bicyclic derivatives of benzimidazole 9a,b. It is probable that the
first stages of the reaction are the hydrolysis and amination of dihydropyridin-2-ones 1a,b, respectively, into
compounds 4a,b and intermediates 12a,b. It should be mentioned that the latter, in all appearances, may also be
450

Table 5. Main Bond Lengths in Compound 11c
Bond
C(1)–N(2)
l, Å
Bond
C(7)–C(8)
l, Å
1.328(2)
1.400(3)
1.363(3)
1.376(2)
1.377(2)
1.3597(19)
1.338(2)
1.399(2)
1.391(2)
1.353(2)
1.386(2)
1.321(2)
1.419(3)
1.357(3)
1.368(2)
C(1)–C(2)
C(2)–C(3)
C(3)–N(1)
N(1)–N(2)
N(3)–N(4)
C(6)–N(3)
C(6)–C(7)
C(8)–N(5)
C(8)–N(4)
C(9)–N(5)
C(9)–C(10)
C(10)–C(11)
C(11)–N(4)
obtained directly on amination of dihydropyridin-2-ones 1a,b with o-phenylenediamine 8a [1]. The intermediate
products 12a,b are possibly subject to intramolecular nucleophilic attack by the free amino group of the
o-phenylenediamine fragment at the endocyclic N atom, being converted in this way into benzimidazole derivatives
13a,b. The latter, to all appearances, are transformed into the bicyclic heterocompounds 9a,b through the
conformation of 14a,b most advantageous for intramolecular cyclization. Evidently, the recyclizations of
dihydropyridin-2-ones 1a,b into 5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridines 3a,b, 6-oxo-1,2,3,5-tetrahydro-
2H-pyrido[1,2-a]pyrimidines 3c,d and 4-oxo-4H-benzo[4,5][1,3]thiazolo[3,2-a]pyridines 9c,d are brought about in a
similar manner.
It is known that substituted benzo[4,5]imidazo[1,2-a]pyridines and benzo[4,5][1,3]thiazolo[3,2-a]pyridines
display fungicidal [7, 8], antimicrobial [9], antitumor [8, 10], antiviral [11], and antibacterial [8] properties. As a
result of the investigations carried out by us new possibilities have been found for the synthesis and functionalization
of 1,6-annelated derivatives of 3-alkylcarbamoyl-5-benzoylpyridin-2-ones 3a-d, 9a-d which are promising
biologically active compounds.
O
Ph
EtO
–
O
OH
8a
H
4a,b
1a,b
N
O
N
R
–MeSH
H2N
12a,b
O
Ph
O
Ph
EtO
O
N
H
O
O
R
O
9a,b
NH
N
NH
N
OEt
–EtOH
NH
R
14a,b
13a,b
12 −14 a R = Me, b R = Et
451

EXPERIMENTAL
1
13
The H and C NMR spectra were recorded on a Varian-300 instrument (300 and 75 MHz respectively),
internal standard was TMS. The IR spectra were recorded on a UR-20 instrument in KBr disks.
X-Ray structural investigation of a monocrystal of 11c, grown in ethanol, with linear dimensions
0.48×0.28×0.12 mm was carried out at room temperature on a Bruker Smart Apex II diffractometer (λMoKα
radiation, graphite monochromator, θmax = 26.56o, segment of sphere -11 ≤ h ≤ 16, -13 ≤ k ≤ 15, -17 ≤ l ≤ 17). In all
14214 reflections were collected, of which 4436 were symmetrically independent (R-factor averaging 0.034).
Crystals of compound 11c: C28H24N4O2, M = 448.51, monoclinic, space group P21/n (No. 14), a = 13.2132 (10),
b = 12.6692(9), c = 14.7662(13) Å, β = 111.446(3)o, V = 2300.7(3) Å3, Z = 4, dcalc = 1.295, µ = 0.084 mm-1,
F(000) = 944. The structure was solved by the direct method and refined by least squares in a full matrix anisotropic
approximation using the SHELXS97 and SHELXL97 programs [12, 13]. The atoms of the phenyl rings C(23-29),
and also atoms C(21) and C(22) and the protons associated with them, were randomized in the two positions A and B
with populations 55 and 45% respectively. All the hydrogen atoms linked with carbon atoms were positioned
geometrically, and the H(N) atoms participating in the formation of hydrogen bonds were shown objectively and
refined isotropically. In the refinement 2666 reflections with I > 2σ(I) were used (364 parameters being refined,
number of reflections per parameter 7.32, the weighting scheme used was ω = 1/[σ2(F02) + (0.1P)2], where P =(F02 +
2Fc2)/3). An absorption correction was introduced according to the SADABS program (ratio of minimum to
maximum correction Tmin/Tmax = 0.85). The final values of the divergence factors were R1(F2) 0.0955, Rw(F2) 0.1679,
GOOF 0.995 for all reflections and R1(F2) 0.0492, Rw(F2) 0.1331, GooF 0.993 for reflections with I > 2σ(I). The
residual electron density from the Fourier difference series after the last ring of refining was 0.25 and -0.18 e/Å3. A
complete set of the X-ray structural data for compound 11c has been deposited in the Cambridge structural data bank
(CCDC 6839232).
6-Alkylcarbamoyl-8-benzoyl-5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridines 3a,b, 7-Alkylcarba-
moyl-9-benzoyl-6-oxo-1,2,3,5-tetrahydro-2H-pyrido[1,2-a]pyrimidines 3c,d, 3-Alkylcarbamoyl-1-benzoyl-
4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyridines 9a,b, 3-Alkylcarbamoyl-1-benzoyl-4-oxo-4H-benzo-
[4,5][1,3]thiazolo[3,2-a]pyridines 9c,d. A solution of 1,2-dihydropyridin-2-one 1a,b (1 mmol) and amine 2a,b
(1.5 mmol) or amine 8a,b (1.0 mmol) in 2-propanol (4 ml) was boiled for 2-6 h, cooled, and the precipitate of
compounds 3a-d, 9a-d filtered off. Dipyridyl oxides 4a,b were isolated on evaporating the filtrate.
1-Alkyl-6-(1-alkyl-5-benzoyl-3-ethoxycarbonyl-2-oxo-1,2-dihydropyrid-6-yl)oxy-5-benzoyl-3-ethoxy-
carbonyl-2-oxo-1,2-dihydropyridines 4a,b were obtained by the method of [3].
N,N'-Di(1-alkyl-5-benzoyl-3-ethoxycarbonyl-2-oxo-1,2-dihydropyrid-6-yl)-1,2-diaminoethane (1,3-di-
aminopropane) 7a-d. A solution of amine 2a,b (0.5 mmol) in 2-propanol (3 ml) was added dropwise with stirring to
a solution of 1,2-dihydropyridin-2-one 1a,b (dipyridyl oxide 4a,b) (1 mmol) in 2-propanol (3 ml). The reaction mass
was maintained at 20oC for 3 h and the solid compound 7a-d filtered off.
Recyclization of N,N'-Di(1-alkyl-5-benzoyl-3-ethoxycarbonyl-2-oxo-1,2-dihydropyrid-6-yl)-1,2-di-
aminoethane (7a) into 8-Benzoyl-6-methylcarbamoyl-5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridine (3a). A
solution of compound 7a (0.626 g, 1 mmol) and diaminoethane 2a (0.18 g, 3 mmol) in 2-propanol (4 ml) was boiled
for 5 h, cooled, and solid compound 3a was filtered off. Yield was 0.559 g, 81%).
Di[2'-(5-benzoyl-3-ethoxycarbonyl-1-methyl-2-oxo-1,2-dihydropyrid-6-yl)aminoethyl] Disulfide (6). A
solution of 1,2-dihydropyridin-2-one 1a (0.331 g, 1 mmol), 1-amino-2-mercaptoethane hydrochloride (0.170 g, 1.5
mmol), and triethylamine (0.152 g, 1.5 mmol) in 2-propanol (4 ml) was boiled for 3 h, cooled, and solid compound 6
was filtered off.
Amination of 4-Oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyridine (9a) with Alkylamines 10. A
mixture of compound 9a (0.345 g, 1 mmol) and alkylamine 10 (3 mmol) was maintained at 120-140oC for
10-20 min, cooled, boiled with 2-propanol (3 ml), cooled, and solid compound 11 was filtered off.
452

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