Acylation and cyclodehydration of benzofuran-, benzothiophene-, and indolyl-3-acetic acid arylamides. Synthesis of novel benzofuro[2,3-c]-, benzothieno[2,3-c], and indolo[2,3-c]pyrilium and pyridine derivatives

Article abstract of DOI:10.1023/B:COHC.0000033542.86752.27

The acylation of benzo[b]furan-, benzo[b]thiophene, and indolyl-3-acetic acid arylamides using acetic anhydride in the presence of 70% perchloric acid occurs at the α-position of the heterocycle to give 2-acetylbenzo[b]furan- , 2-acetylbenzo[b]thiophene,

Full text of DOI:10.1023/B:COHC.0000033542.86752.27

Chemistry of Heterocyclic Compounds, Vol. 40, No. 4, 2004
ACYLATION AND CYCLODEHYDRATION
OF BENZOFURAN-, BENZOTHIOPHENE-, AND
INDOLYL-3-ACETIC ACID ARYLAMIDES.
SYNTHESIS OF NOVEL BENZOFURO[2,3-c]-,
BENZOTHIENO[2,3-c], AND INDOLO[2,3-c]-
PYRILIUM AND PYRIDINE DERIVATIVES
S. V. Tolkunov, V. S. Tolkunov, and V. I. Dulenko
The acylation of benzo[b]furan-, benzo[b]thiophene, and indolyl-3-acetic acid arylamides using acetic
anhydride in the presence of 70% perchloric acid occurs at the α-position of the heterocycle to give
2-acetylbenzo[b]furan-, 2-acetylbenzo[b]thiophene, and 2-acetylindolyl-3-acetic acid arylamides.
Depending on the amount of perchloric used in the reaction they undergo cyclodehydration to
3-arylamino-1-methylhetero[2,3-c]pyrilium salts and to N-aryl-1-methyl-3(2H)hetero[2,3-c]pyridones.
Keywords: 2-acetylbenzo[b]thiophene-3-acetic acid arylamides, 2-acetylbenzo[b]furan-3-acetic acid
arylamides, 2-acetylindolyl-3-acetic acid arylamides, 3-arylamino-1-methylhetero[2,3-c]pyrilium,
N-aryl-1-methyl-3(2H)hetero[2,3-c]pyridones, cyclodehydration.
o-Acylation and subsequent dehydration of β-oxoalkyl derivatives of aromatic and heterocyclic systems
give condensed pyrilium salts [1]. This reaction has been used by us previously in the benzofuran,
benzothiophene, and indole series [2-4]. The acylation and cyclodehydration of benzofuran-, benzothiophene-,
and indolyl-3-acetic acid arylamides has not been studied previously. This reaction is of interest since the amides
described above have two reactive nucleophilic centers (CO and NH) and hence acylation-cyclodehydration can
occur by two routes to yield pyrilium salts and pyridine bases.
We have studied the acylation of the arylamides of the benzo[b]furan-3-acetic acid 1a-e,
benzo[b]thiophene-3-acetic acids 2a,b, and indolyl-3-acetic acids 3a-c in the system acetic anhydride–70%
perchloric acid with different perchloric acid content. The acylation takes place at the α-position of the
heterocycle. The intermediately formed 2-acetylheteryl-3-acetic acid arylamides 4-6 are cyclodehydrated to the
corresponding 3-arylamino-1-methylpyrilium perchlorates 7-9. We have found that the yields of the pyrilium
salts 7-9 depend on the amount of perchloric acid taken in the reaction. The maximal yields for the pyrilium salt
(90%) are observed with a two fold excess of perchloric acid. It was interesting to find that the NH group in the
3-arylaminopyrilium salts is not acylated, even upon prolonged holding of compounds 7-9 in the acylating
mixture.
__________________________________________________________________________________________
L. M. Litvinenko Institute of Physical Organic and Carbon Chemistry, National Academy of Sciences of
Ukraine, Donetsk 83114; e-mail: tolkunov@uvika.dn.ua. Translated from Khimiya Geterotsiklicheskikh
Soedinenii, No. 4, pp. 577-585, April, 2004. Original article submitted March 1, 2001.
0009-3122/04/4004-0481©2004 Plenum Publishing Corporation
481

CH2CONHAr
Ac2O
HClO4
R
X
1a–e, 2a,b, 3a–c
NHAr
Ac2O
+
R
4a–e, 5a,b, 6a–c
O
_
X
HClO4
ClO4
Me
7a–e, 8a,b, 9a–c
HClO4
O
CH2CONHAr
ArNH2
R
R
O
O
X
X
Me
Me
10a–c
4a–e, 5a,b, 6a–c
AcOH, TEA
O
R
N
Ar
X
Me
11a–e, 12a,b, 13a–c
1, 4 Х = О, R = 6-Me; a Ar = Ph, b Ar = 4-MeC6H4, c Ar = 4-ClC6H4, d Ar = 4-BrC6H4,
e Ar = 4-CH3OC6H4; 2, 5, X = S, R = 5-Me, a Ar = 4-MeC6H4, b Ar = 4-MeOC6H4;
3, 6, 9 X = NH, R = H; a Ar = Ph; b Ar = 4-MeC6H4; c Ar = 4-MeOC6H4; 7, 11 X = O,
R = 7-Me, a Ar = Ph, b Ar = 4-MeC6H4, c Ar = 4-ClC6H4, d Ar = 4-BrC6H4,
e Ar = 4-CH2OC6H4; 8, 12 X = S, R = 6-Me, a Ar = 4-MeC6H4, b Ar = 4-MeOC6H4;
10 a X = O, R = 7-Me, b X = S, R = 6-Me, c X = NH, R = H; 13 X = NH, R = H; a Ar = Ph,
b Ar = 4-MeC6H4, c Ar = 4-MeOC6H4
In contrast to the acylation of the benzo[b]furan-3-acetic acid arylamides 1a-e and the
benzo[b]thiophene-3-acetic acid arylamides 2a,b that of the indolyl-3-acetic acid arylamides occurs with
significant tarring. Since we could not prepare the corresponding pyrilium salts in the pure state, we carried out
an alternative method for their synthesis consisting of the cyclization of the 2-acetylindolyl-3-acetic acid
arylamides 6a-c in a mixture of acetic anhydride and 70% perchloric acid. The 2-acetylheteryl-3-acetic acid
arylamides 4-6 were prepared by the reaction of the 1-methylhetero[2,3-c]pyrones 10a-c with anilines in DMF.
Cyclodehydration of the keto amides 4a-e, 5a,b, 6a-c in an acylating mixture with an excess of 70% perchloric
acid gave the corresponding pyrilium salts 7a-e, 8a,b, 9a-c in greater than 90% yield. The pyrilium perchlorates
7-9 synthesized by this method were identical to the pyrilium salts obtained by the acylation of the benzofuran-
and benzothiophene-3-acetic acid arylamides. The structure of the 3-arylamino-1-methylpyrilium perchlorates
7-9 was confirmed using elemental analytical analysis and from their 1H NMR spectra (Tables 1 and 2).
A study of the cyclodehydration of the keto amides 4a-e, 5a,b, 6a-c in the acylating mixture with an
equivalent amount of 70% perchloric acid showed that, along with the pyrilium salts 7a-e, 8a,b, 9a-c, the
reaction mixture contained the corresponding N-aryl-1-methyl-3(2H)hetero[2,3-c]pyridones 11-13. Thus a
chromatographic investigation of the composition of the reaction mixture (after separation of the pyrilium salt)
showed that the product of cyclodehydration of the 2-acetyl-6-methyl-(4-methylphenyl)amide of benzo[b]furan-
3-acetic acid (4b) using 70% perchloric acid in acetic anhydride gave both the pyrilium salt 7b (yield 40%)
482

TABLE 1. Characteristics of the Compounds Synthesized
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
Yield, %
(method)
mp, °С
Rf
С
Н
Hal
5
N
6
S
7
1
1a
1b
1c
1d
1e
2a
2b
2
3
4
8
9
10
C17H15NO2
C18H17NO2
C17H14ClNO2
C17H14BrNO2
C18H17NO3
C18H17NOS
C18H 17NO2S
76.80
76.96
5.79
5.70
—
—
5.32
5.28
—
—
—
—
—
159-160
149-150
—
—
75 (A),
77 (B)
77.28
77.40
6.21
6.13
5.15
5.01
76 (A),
76 (B)
68.00
68.12
4.62 11.65 4.55
4.71 11.83 4.67
172-173 0.55
70 (A),
75(B)
59.15
59.32
4.29 23.38 4.21
4.10 23.21 4.07
180-181
173-174
—
—
76 (A),
75 (B)
73.00
73.20
5.67
5.80
—
—
—
4.59
4.74
67 (A),
68 (B)
73.05
73.19
5.70
5.80
4.51 10.69 157-158 0.75
4.74 10.85
65 (A)
67 (B)
69.62
69.43
5.67
5.50
4.61 10.56 171-172
4.50 10.30
—
63 (A),
69 (B)
3a
3b
3c
4a
4b
4c
4d
4e
C16H14N2O
C17H16N2O
C17H16N2O2
C19H17NO3
C20H19NO3
C19H16ClNO3
C19H16BrNO3
C20H19NO4
77.56
76.78
77.38
77.25
72.65
72.84
74.37
74.25
74.86
74.75
66.85
66.77
58.95
59.08
71.36
71.20
5.57
5.64
6.21
6.10
5.67
5.75
5.63
5.58
—
—
—
—
—
11.31
11.19
10.69
10.60
9.83
9.99
4.41
4.56
—
—
—
—
—
—
—
—
186-187
187-188
184-185
187-188
173
—
—
75 (B)
80 (B)
78 (B)
88
—
—
5.83
5.96
4.21
4.36
0.81
95
4.63 10.45 4.17
4.72 10.37 4.10
4.12 20.56 3.67
4.18 20.69 3.63
5.56
5.68
175-176 0.64
192-193 0.57
80
83
—
4.25
4.15
193
205-206 0.86
198-200
0.93
93
5a
5b
6a
6b
6c
7a
C20H19NO2S
C20H19NO3S
C18H16N2O2
C19H18N2O2
C19H18N2O3
C19H16ClNO6
71.28
71.19
67.81
67.97
73.81
73.96
74.40
74.49
70.65
70.79
58.51
58.55
5.53
5.68
5.35
5.42
5.67
5.52
6.02
5.92
5.74
5.63
4.24
4.14
4.21
4.15
4.10
3.96
9.42
9.58
9.03
9.14
8.78
8.69
3.45
3.59
9.36
9.50
9.26
9.07
—
—
—
—
80
87
95
98
93
90
—
—
—
—
—
235-237 0.42
229-230 0.43
224-225
—
—
9.11
9.10
224-225
(with dec.)
7b
7c
7d
7e
8a
C20H18ClNO6
C19H15Cl2NO6
59.43
59.49
4.58
4.49
8.69
8.78
3.57
3.47
—
—
—
—
240
(with dec.)
227-228
(with dec.)
—
—
—
—
—
86
83
90
85
90
53.67
53.79
3.68 16.63 3.44
3.56 16.71 3.30
C19H15BrClNO6 48.56
48.69
3.37 17.13 3.14
3.23 17.05 2.99
248-249
(with dec.)
C20H18ClNO7
57.34
57.22
4.48
4.32
8.35
8.44
3.28
3.34
223-224
(with dec.)
C20H18ClNO5S
57.32
57.21
4.48
4.32
8.38
8.44
3.25
4.34
7.58
7.64
7.28
7.36
—
240
(with dec.)
8b
9a
C20H18ClNO6S
C18H15ClN2O5
55.23
55.11
4.02
4.16
8.21
8.13
3.15
3.21
232-233
(with dec.)
—
—
97
80
57.55
57.69
4.17
4.03
9.33
9.46
7.51
7.47
235
(with dec.)
483

TABLE 1 (continued)
1
2
3
4
5
6
7
8
9
10
90
96
9b
C19H17ClN2O5
C19H17ClN2O6
58.76
58.69
4.52
4.41
8.98
9.12
7.13
7.20
—
—
254-255
(with dec.)
—
—
9c
56.29
56.38
4.15
4.23
8.91
8.76
7.10
6.92
233-234
(with dec.)
10a
10b
10c
10d
10e
11a
11b
C19H15NO2
C20H17NO2
C19H14ClNO2
C19H14BrNO2
C20H17NO3
C20H17NOS
C20H17NO2S
78.73
78.87
79.25
79.19
70.33
70.48
61.83
61.97
75.37
75.22
75.06
75.20
71.45
71.62
5.35
5.23
5.47
5.65
—
4.66
4.84
4.57
4.62
—
—
—
192-193 0.36
193-194 0.33
226-227 0.45
229-230 0.38
191-192 0.31
100
100
100
100
100
100
100
—
4.23 10.78 4.45
4.36 10.95 4.33
3.98 21.61 3.68
3.83 21.70 3.80
5.51
5.37
5.49
5.36
—
—
—
4.27
4.39
4.52
4.38 10.04
4.31
4.18
—
9.95
214-215
—
5.04
5.11
9.42
9.56
254-255 0.27
(with dec.)
12a
12b
12c
C18H14N2O
C19H16N2O
C19H16N2O2
78.65
78.81
5.27
5.14
—
—
—
10.34
10.21
—
—
—
—
284-285
(with dec.)
—
100
100
100
79.26
79.14
5.68
5.59
9.56
9.71
290
(with dec.)
0.41
75.14
74.98
5.47
5.30
9.18
9.20
288-289 0.32
(with dec.)
13a
13b
C13H10O3
72.78
72.89
67.71
67.80
4.63
4.71
4.44
4.38
—
—
—
160
0.50
100
100
C13H10O2S
—
13.85 187-188 0.44
13.92
together with 16.5% of the starting keto amide 4b and 26% of the 1,7-dimethyl-2-N-(4-methylphenyl)-
3(2H)benzofuro[2,3-c]pyridone (11b). The alternative direction of cyclodehydration of the keto amides 4-6 is
achieved by heating them in acetic acid in the presence of triethylamine. In this way the N-aryl-1-methyl-
3(2H)hetero[2,3-c]pyridones 11-13 are formed in good yields.
EXPERIMENTAL
1H NMR spectra were taken on a Gemini-200 instrument (200 MHz) using DMSO-d6 as solvent and
TMS as internal standard. Monitoring of the purity of the products obtained was carried out using TLC on
Silufol UV-254 plates and the system toluene–ethanol (4:1). Analysis of the reaction products was performed by
HPLC on a Laboratory pristroje chromatograph (Prague) with an RIDK-102 differential refractometer detector
and 3 × 150 mm column using Separon C18 stationary phase and methanol–water (7:3) mobile phase.
The parameters for the compounds synthesized are given in Tables 1 and 2.
6-Methylbenzo[b]furan-3-acetic acid and 5-methylbenzo[b]thiophene-3-acetic acids were prepared by
the methods [5, 6].
Preparation of the Arylamides (1a-e, 2a,b, 3a-c) (General Method). A. Pyridine (1 ml) and the
corresponding arylamine (0.01 mol) were added with cooling to a benzene solution (20 ml) of the
6-methylbenzo[b]furan-3-acetic acid chloride or 5-methylbenzo[b]thiophene-3-acetic acid chloride which had
been obtained from the corresponding acid (0.01 mol) and PCl5 by the standard method. The product was held at
room temperature for 4 h. The precipitate was filtered off and washed with aqueous alcohol and hexane.
Crystallization from isopropanol gave the arylamides 1a-e, 2a,b.
484

TABLE 2. 1H NMR Spectra of Compounds Synthesized
Chemical shift, δ, ppm (spin spin coupling, J, Hz)
Com-
pound
R, substituent
in Ar (3H, s)
(3Н, s)
CH3
CH2
NH
Н arom. in Het
Н arom. in Ar
(3Н, s)
(2Н, s)
(NH in Het); (1Н, s)
1
2
3
4
5
6
7
1a
2.41 (6-СН3)
—
3.73
7.08 ( 1Н, d, J = 8.0, 5-Н); 7.37 (1Н, s, 2-Н);
7.54 (1Н, d, J = 8.0, 4-Н); 7.81 (2Н, s, 7-Н)
7.00 (1Н, t, J = 8.0, 4'-Н);
7.28 (2Н, t, J = 8.0, 3',5'-Н);
7.60 (2Н, d, J = 8.0, 2',6'-Н)
10.12
1b
1c
1d
1e
2a
2b
2.20 (4'-СН3);
2.42 (6-СН3)
—
—
—
—
—
—
3.71
3.72
3.72
3.68
3.86
3.85
7.14 ( 1Н, d, J = 8.0, 5-Н); 7.36 (1Н, s, 2-Н);
7.56 (1Н, d, J = 8.0, 4-Н); 7.80 (1Н, s, 7-Н)
7.04 (2Н, d, J = 8.0, 3',5'-Н);
7.52 (2Н, d, J = 8.0, 2',6'-Н)
10.06
10.37
10.41
10.12
10.14
10.11
2.42 (6-СН3)
7.08 (1Н, d, J = 8.0, 5-Н); 7.36 (1Н, s, 2-Н);
7.60 (1Н, d, J = 8.0, 4-Н); 7.81 (1Н, s, 7-Н)
7.34 (2Н, d, J = 8.0, 2',6'-Н);
7.61 (2Н, d, J = 8.0, 3',5'-Н)
2.40 (6-СН3)
7.08 (1Н, d, J = 8.0, 5-Н); 7.37 (1Н, s, 2-Н);
7.57 (1Н, d, J = 8.0, 4-Н); 7.81 (1Н, s, 7-Н)
7.08 (1Н, d, J = 8.0, 5-Н); 7.36 (1H, s, 2-Н);
7.54 (1Н, d, J = 8.0, 4-Н); 7.80 (1Н, s, 7-Н)
7.52 (2Н, d, J = 8.0, 2',6'-Н);
7.54 (2Н, d, J = 8.0, 3',5'-Н)
6.87 (2Н, d, J = 8.9, 3',5'-Н);
7.51 (2Н, d, J = 8.9, 2',6'-Н)
2.41 (6-СН3);
3.71 (4'-OСН3)
2.23 (4'-СН3);
2.42 (5-СН3)
7.20 (1Н, d, J = 8.2, 6-Н); 7.53 (1Н, s, 2-Н);
7.69 (1Н, s, 4-Н); 7.83 (1Н, d, J = 8.2, 7-Н)
7.09 (2Н, d, J = 8.2, 3',5'-Н);
7.48 (2Н, d, J = 8.2, 2',6'-Н)
2.43 (5-СН3);
3.71 (4'-OСН3)
7.21 ( 1Н, d, J = 8.2, 6-Н); 7.53 (1Н, s, 2-Н);
7.70 (1Н, s, 4-Н); 7.85 (1Н, d, J = 8.2, 7-Н)
6.88 (2Н, d, J = 8.6, 3',5'-Н);
7.51 (2Н, d, J = 8.6, 2',6'-Н)

TABLE 2 (continued)
1
2
3
4
5
6
7
3a
—
—
3.69
6.98 (1Н, t, J = 7.5, 6-Н); 7.07 ( 1Н, t, J = 7.5, 5-Н);
7.24 (1Н, d, J = 2.0, 2-Н); 7.36 (1Н, d, J = 8.0, 7-Н);
7.62 (1Н, d, J = 8.0, 4-Н)
7.10 (1Н, t, J = 8.0, 4'-Н);
7.30 (2Н, t, J = 8.0, 3',5'-Н);
7.56 (2Н, d, J = 8.0, 2',6'-Н)
9.95
(10.92)
3b
3c
4a
2.20 (4'-СН3)
3.70 (4'-OСН3)
2.46 (6-СН3)
—
—
3.69
3.69
4.19
6.98 (1Н, t, J = 7.5, 6-Н); 7.07 ( 1Н, t, J = 7.5, 5-Н);
7.24 (1Н, d, J = 2.0, 2-Н); 7.36 (1Н, d, J = 8.0, 7-Н);
7.62 (1Н, d, J = 8.0, 4-Н)
7.09 (2Н, d, J = 8.4, 3',5'-Н);
7.53 (2Н, d, J = 8.4, 2',6'-Н)
9.95
(10.92)
6.98 (1Н, t, J = 7.5, 6-Н); 7.07 (1Н, t, J = 7.5, 5-Н);
7,24 (1Н, d, J = 2.0, 2-Н); 7.35 (1Н, d, J = 8.0, 7-Н);
7.61 (1Н, d, J = 8.0, 4-Н)
6.85 (2Н, d, J = 9.0, 3',5'-Н);
7.51 (2Н, d, J = 9.0, 2',6'-Н)
9.93
(10.90)
2.57
7.17 (1Н, d, J = 8.0, 5-Н); 7.47 (1Н, s, 7-Н);
7.68 (1Н, d, J = 8.0, 4-Н)
7.02 (1H, t, J = 8.0, 4'-Н);
7.27 (2Н, t, J = 8.0, 3',5'-H);
7.57 (2H, d, J = 8.0, 2',6'-H)
10.16
4b
4c
4d
4e
5a
5b
2.20 (4'-СН3);
2.42 (6-СН3)
2.53
2.56
2.57
2.57
2.61
2.61
4.15
4.12
4.12
4.14
4.36
4.32
7.14 ( 1Н, d, J = 8.0, 5-Н); 7.45 (1Н, s, 7-Н);
7.66 (1Н, d, J = 8.0, 4-Н)
7.04 (2Н, d, J = 8.0, 3',5'-Н);
7.42 (2Н, d, J = 8.0, 2',6'-Н)
10.06
10.37
10.20
9.95
2.45 (6-СН3)
7.18 (1Н, d, J = 8.1, 5-Н); 7.36 (1Н, s, 7-Н);
7.70 (1Н, d, J = 8.1, 4-Н)
7.34 (2Н, d, J = 8.0, 2',6'-Н);
7.61 (2Н, d, J = 8.0, 3',5'-Н)
2.45 (6-СН3)
7.16 (1Н, d, J = 8.1, 5-Н); 7.40 (1Н, s, 7-Н);
7.70 (1Н, d, J = 8.1, 4-Н)
7.34 (2Н, d, J = 8.0, 2',6'-Н);
7.55 (2Н, d, J = 8.0, 3',5'-Н)
2.48 (6-СН3);
3.71 (4'-OCH3)
2.22 (4'-СН3);
2.43 (5-СН3)
7.16 (1Н, d, J = 8.1, 5-Н); 7.44 (1Н, s, 7-Н);
7.66 (1Н, d, J = 8.1, 4-Н)
7.38 ( 1Н, d, J = 8.3, 6-Н); 7.86 (1Н, d, J = 8.3, 7-Н);
7.92 (2Н, s, 4-Н)
6.82 (2Н, d, J = 8,9, 3',5'-Н);
7.46 (2Н, d, J = 8.9, 2',6'-Н)
7.08 (2Н, d, J = 8.0, 3',5'-Н);
7.46 (2Н, d, J = 8.0, 2',6'-Н)
10.19
10.15
2.43 (5-СН3);
3.70 (4'-OСН3)
7.37 ( 1Н, d, J = 8.4, 6-Н); 7.84 (1Н, d, J = 8.4, 7-Н);
7.90 (1Н, s, 4-Н)
6.86 (2Н, d, J = 8.8, 3',5'-Н);
7.44 (2Н, d, J = 8.8, 2',6'-Н)

TABLE 2 (continued)
1
2
3
4
5
6
7
6a
—
2.63
4.18
7.04 (1Н, t, J = 8.0, 6-Н); 7.24 (1Н, t, J = 8.0, 5-Н);
7.46 (1Н, d, J = 8.0, 7-Н); 7.75 (1Н, d, J = 8.0, 4-Н)
7.10 (1Н, t, J = 8.0, 4'-Н);
7.30 (2Н, t, J = 8.0, 3',5'-Н);
7.56 (2Н, d, J = 8.0, 2',6'-Н)
10.07,
(10.64)
6b
6c
7b
7c
7e
8a
8b
9a
2.22 (4'-СН3)
2.63
2.63
2.74
2.79
2.74
2.81
2.75
2.91
4.18
4.16
—
7.06 (1Н, t, J = 8.0, 6-Н); 7.28 (1Н, t, J = 8.0, 5-Н);
7.46 (1Н, d, J = 8.0, 7-Н); 7.75 (1Н, d, J = 8.0, 4-Н)
7.08 (2Н, d, J = 8.0, 3',5'-Н);
7.46 (2Н, d, J = 8.0, 2',6'-Н)
10.07,
(10.64)
3.70 (4'-OСН3)
7.07 (1Н, t, J = 8.0, 6-Н); 7.29 (1Н, t, J = 8.0, 5-Н);
7.45 (1Н, d, J = 8.0, 7-Н); 7.75 (1Н, d, J = 8.0, 4-Н)
6.85 (2Н, d, J = 8.7, 3',5'-Н);
7.48 (2Н, d, J = 8.7, 2',6'-Н)
10.03
(11.62)
2.35 (4'-СН3);
2.50 (7-СН3)
7.45 (1Н, d, J = 8.0, 6-Н); 7.48 (1Н, s, 8-Н);
7.58 (1Н, s, 4-Н); 8.29 (1Н, d, J = 8.0, 5-Н)
7.34 (2Н, d, J = 8.0, 3',5'-Н);
7.45 (2Н, d, J = 8.0, 2',6'-Н)
12.23
12.38
12.19
12.38
12.25
2.54 (7-СН3)
—
7.40 (1Н, d, J = 8.0, 6-Н); 7.61 (2Н, m, 4,8-Н);
8.34 (1Н, d, J = 8.0, 5-Н)
7.36 (1Н, d, J = 8.0, 6-Н); 7.47 (1H, s, 8-Н); 7.60 (1Н, s, 4-Н);
8.31 (1Н, d, J = 8.0, 5-Н)
7.61 (4Н, m, 2',3',5',6'-Н)
2.52 (7-СН3);
3.80 (4'-ОСН3)
—
7.10 (2Н, d, J = 8.8, 3',5'-Н);
7.49 (2Н, d, J = 8.8, 2',6'-Н)
2.41 (4'-СН3);
2.52 (6-СН3)
—
7.49 (1Н, d, J = 8.0, 7-Н); 7.75 (1Н, s, 4-H);
8.07 (1Н, d, J = 8.0, 8-Н); 8.44 (1Н, s, 5-Н)
7.40 (2Н, d, 3',5'-Н J = 8.0);
7.54 (2Н, d, J = 8.0, 2',6'-Н)
2.46 (6- СН3);
3.81 (4'-ОСН3)
—
7.46 (1Н, d, J = 8.0, 7-Н); 7.70 (1Н, s, 4-Н);
8.00 (1Н, d, J = 8.0, 8-Н); 8.36 (1Н, s, 5-Н)
7.21 (1Н, t, J = 8.0, 7-Н); 7.31 (1Н, d, J = 8.0, 8-Н);
7.60 (1Н, s, 4-Н); 7.73 (1Н, t, J = 8.0, 6-Н);
8.31 (1Н, d, J = 7.8, 5-Н)
7.10 (2Н, d, J = 8.6, 3',5'-H);
7.50 (2Н, d, J = 8.6, 2',6'-Н)
7.45–7.53 (5H, m, 2',3',4',5',6-H)
—
—
11.56
(11.85)
9b
2.34 (4'-СН3)
2.86
—
7.21 (1Н, t, J = 8.0, 7-Н); 7.49 (1Н, d, J = 8.0, 8-Н);
7.56 (1Н, s, 4-Н); 7.74 (1Н, t, J = 8.0, 6-Н);
8.31 (1Н, d, J = 7.8, 5-Н)
7.29 (2Н, d, J = 8.6, 3',5'-Н);
7.42 (2Н, d, J = 8.6, 2',6'-Н)
11.59
(11.90)

TABLE 2 (continued)
1
2
3
4
5
6
7
—
10a
10b
11a
11b
11c
11d
11e
12a
12b
13b
2.42 (7-СН3)
2.40 (6-СН3)
2.48 (7-СН3)
2.42
2.40
2.12
2.10
2.10
2.11
2.09
2.08
2.12
2.14
—
—
—
—
—
—
—
—
—
—
6.56 (1Н, s, 4-H); 7.50 (1Н, s, 8-Н);
7.61 (1H, d, J = 8.2, 6-H); 7.93 (1Н, d, J = 8.2, 5-H)
—
6.78 (1Н, s, 4-H); 7.42 (1Н, d, J = 8.2, 7-Н);
7.63 (1H, d, J = 8.2, 8-H); 7.96 (1Н, s, 5-H)
—
—
6.74 (1Н, s, 4-Н); 7.14 (1Н, d, J = 8.0, 6-Н); 7.59 (1Н, s, 8-H);
7.88 (1Н, d, J = 8.0, 5-Н)
7.24-7.55 (5H, m, 2',3',4',5',6'-H)
—
2.39 (4'-СН3);
2.47 (7-СН3)
2.46 (7-СН3)
6.80 (1Н, s, 4-Н); 7.19 (1Н, s, 8-H);
7.34 (1Н, d, J = 8.0, 6-Н); 7.94 ( 1Н, d, J = 8.0, 5-Н)
6.82 (1Н, s, 4-Н); 7.17 (1Н, d, J = 8.0, 6-Н); 7.39 (1Н, s, 8-Н);
7.95 (1Н, d, J = 8.0, 5-Н)
7.16 (2Н, d, J = 8.0, 3',5'-Н);
7.34 (2Н, d, J = 8.0, 2',6'-Н)
7.37 (2Н, d, J = 8.6, 3',5'-Н);
7.61 (2Н, d, J = 8.6, 2',6'-Н)
—
—
2.47 (7-СН3)
6.83 (1Н, s, 4-Н); 7.18 (1Н, d, J = 8.0, 6-Н); 7.39 (1Н, s, 8-Н)
7.95 (1Н, d, J = 8.0, 5-Н)
7.31 (2Н, d, J = 7.5, 3',5'-Н);
7.75 (2Н, d, J = 7.5, 2',6'-Н)
—
2.45 (7-СН3);
3.81 (4'-ОСН3)
2.38 (4'-СН3);
2.42 (6-СН3)
6.79 (1Н, s, 4-Н); 7.16 (1Н, d, J = 7.8, 6-Н); 7.37 (1Н, s, 8-Н);
7.94 ( 1Н, d, J = 7.8, 5-Н)
7.10 (1Н, s, 4-Н); 7.38 (1Н, d, J = 8.0, 7-H);
7.72 (1Н, d, J = 8.0, 8-Н); 8.02 (1Н, s, 5-Н)
7.06 (2Н, d, J = 8.4, 3',5'-Н);
7.20 (2Н, d, J = 8.4, 2',6'-Н)
7.15 (2Н, d, J = 8.0, 3',5'-Н);
7.33 (2Н, d, J = 8.0, 2',6'-Н)
—
—
2.43 (6-СН3);
3.82 (4'-ОСН3)
7.03 (1Н, s, 4-Н); 7.42 (1Н, d, J = 8.0, 7-Н);
7.76 (1Н, d, J = 8.0, 8-Н); 8.04 (1Н, s, J = 8.0, 5-Н)
7.10 (2Н, d, J = 8.8, 3',5'-Н);
7.22 (2Н, d, J = 8.8, 2',6'-Н )
—
2.36 (4'-СН3)
6.82 (1Н, s, 4-Н); 7.00 (1Н, t, J = 8.0, 7-Н);
7.25 (1Н, d, J = 8.0, 8-Н); 7.44 (1Н, t, J = 8.0, 6-Н);
7.87 (1Н, d, J = 8.0, 5-Н)
7.10 (2Н, d, J = 8.0, 3',5'-Н);
7.29 (2Н, d, J = 8.0, 2',6'-Н)
(10.41)
13c
3.84 (4'-ОСН3)
2.20
—
6.87 (1Н, s, 4-Н ); 7.03 (1Н, t, J = 7.6, 7-Н);
7.29 (1Н, d, J = 8.0, 8-Н); 7.48 (1Н, t, J = 7.6, 6-Н);
8.02 (1Н, d, J = 8.0, 5-Н)
7.08 (2Н, d, J = 8.8, 3',5'-Н);
7.20 (2Н, d, J = 8.8, 2',6'-Н)
(10.53)

B. Carbonyldiimidazole (1.62 g, 0.01 mol) was added to a solution of the corresponding heteryl-3-acetic
acid (0.01 mol) in anhydrous dioxane. The solution was stirred for 1.5 h at room temperature and the arylamine
(0.01 mol) was added. The mixture was stirred for 4 h and poured into a 5% aqueous solution of NaHCO3
(50 ml). The precipitated crystals were filtered off, washed with water, and crystallized from isopropanol to give
the arylamides 1a-e, 2a,b, 3a-c.
Preparation of the Pyrilium Salts (7a-e, 8a,b, 9a-c) (General Method). Perchloric acid (70%, 2 ml)
was added with cooling to a solution of the arylamides 1a-e, 2a,b or the corresponding keto amide 4-6
(0.01 mol) in acetic anhydride (10 ml). The mixture was held at room temperature for 2 h. The precipitate
formed was filtered off, washed with acetic acid and then water, dried, and crystallized from acetic acid to give
the pyrilium salts 7a-e, 8a,b, 9a-c.
1,7-Dimethylbenzofuro[2,3-c]-3-pyrone (10a) was prepared from 1,7-dimethyl-3-hydroxybenzofuro-
[2,3-c]pyrilium fluoroborate [7] by a method similar to that for 10c [8].
1,6-Dimethylbenzothieno[2,3-c]-3-pyrone
(10b)
was
prepared
from
1,6-dimethyl-3-
hydroxybenzothieno[2,3-c]pyrilium fluoroborate [7] by a method similar to that for 10c [8].
Preparation of 2-Acetylheteryl-3-acetic Acid Arylamides (4a-e, 5a,b, 6a-c) (General Method). The
arylamine (0.15 mol) was added to a solution of the pyrone 10a (0.01 mol) in isopropanol (for pyrones 10b,c in
DMF). The mixture was refluxed for 0.5 h (for 10b,c refluxed for 2 h), cooled, and poured into water. The
precipitate formed was filtered off, washed with water, and dried to give the arylamides 4a-e, 5a,b, 6a-c.
Compounds 4a-e were crystallized from isopropanol and 5a,b, 6a-c were crystallized from aqueous DMF.
Preparation of N-Aryl-1-methyl-3(2H)hetero[2,3-c]pyrid-3-ones (11a-e, 12a,b, 13a-c) (General
Method). Triethylamine (0.05 mol) was added to a solution of the 2-acetylheteryl-3-acetic acid arylamides 4a-e,
5a,b, 6a-c (0.01 mol) in acetic acid. The mixture was refluxed for 1.5 h, cooled, poured into water, and a
solution of ammonia was added to pH ≥ 7. The precipitate was filtered off, washed with water, dried, and
crystallized from alcohol to give the pyridones 11a-e, 12a,b, 13a-c.
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1.
2.
3.
4.
5.
6.
7.
8.
Y. P. Stradyn', Khim. Geterotsikl. Soedin., 1412 (1981).
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V. I. Dulenko and S. V. Tolkunov, Khim. Geterotsikl. Soedin., 889 (1987).
B. B. Dey and Y. Sankaranarayanan, J. Indian Chem. Soc., 687 (1934).
F. Sauter and F. Ecker, Monats. Chem., 99, 610 (1968).
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489