Condensed pyridine bases. Synthesis and reactions of benzofuro[2,3-c] indeno[2,1-e]-, benzothieno[2,3-c]indeno[2,1-e]-, benzofuro-[3,2-c]indeno[2,1-e] - and thieno[2,3:4′,5′]-thieno[3,2-c]indeno[2,1-e]pyridines

Article abstract of DOI:10.1007/s10593-005-0158-8

Condensation of hetarene carboxaldehydes with phthalide gave 2-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 2-(3-hydroxy-1-oxoinden-2-yl)-5- ethylthieno[2,3-b]thiophene. Starting from hetaryl acetic acids gave 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 3-(3-hydroxy-1-oxoinden-2-yl) benzo[b]thiophene. Acylation of 3-hydroxy-1-oxoinden-2-yl-substituted heterocycles using acetic anhydride in the presence of 70% HClO₄ leads to the formation of pentacyclic pyrilium salts. Pentacyclic indenopyridines are prepared by treating the pyrilium salts with ammonia. The reaction of the carbonyl group in the indenopyridines with hydroxylamine, hydrazine hydrate, and in reduction using NaBH₄ has been studied.

Full text of DOI:10.1007/s10593-005-0158-8

Chemistry of Heterocyclic Compounds, Vol. 41, No. 3, 2005
CONDENSED PYRIDINE BASES. SYNTHESIS
AND REACTIONS OF BENZOFURO[2,3-c]INDENO[2,1-e]-,
BENZOTHIENO[2,3-c]INDENO[2,1-e]-, BENZOFURO-
[3,2-c]INDENO[2,1-e]- AND THIENO[2,3:4',5']-
THIENO[3,2-c]INDENO[2,1-e]PYRIDINES
S. V. Tolkunov, A. I. Khyzhan, S. Yu. Suikov, and V. I. Dulenko
Condensation of hetarene carboxaldehydes with phthalide gave 2-(3-hydroxy-1-oxoinden-2-
yl)benzo[b]furan and 2-(3-hydroxy-1-oxoinden-2-yl)-5-ethylthieno[2,3-b]thiophene. Starting from
hetaryl acetic acids gave 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 3-(3-hydroxy-1-oxoinden-2-
yl)benzo[b]thiophene. Acylation of 3-hydroxy-1-oxoinden-2-yl-substituted heterocycles using acetic
anhydride in the presence of 70% HClO4 leads to the formation of pentacyclic pyrilium salts.
Pentacyclic indenopyridines are prepared by treating the pyrilium salts with ammonia. The reaction of
the carbonyl group in the indenopyridines with hydroxylamine, hydrazine hydrate, and in reduction
using NaBH4 has been studied.
Keywords: benzo[b]thiophene, benzo[b]furan, indeno[2,1-e]pyridines, pyrilium salts, thieno[2,3-b]-
thiophene, condensation.
The natural alkaloids harmine and harmane, which contain condensed indole and pyridine rings and
ellipticine, which contains an indole and isoquinoline rings together with their synthetic analogs [1] are of
interest from both a theoretical and a practical viewpoint.
By means of an acid catalyzed heterocyclization we were able to synthesize benzothieno- and
benzofuro[2,3-c]pyrilium salts and the oxygen and sulphur analogs of β-carbolines [2, 3] based on them.
Exchange of the indole nucleus for benzo[b]thiophene and benzo[b]furan in the tricyclic and tetracyclic analogs
of the β-carbolines gives rise to a number of specific chemical and biological properties [4, 5]. Special interest in
the study of biological activity can arise in the pentacyclic derivatives of benzothieno[2,3-c]- and benzofuro[2,3-
c]pyridines containing an indene ring since it is known that a series of natural alkaloids contain an
indenopyridine structural fragment [6-8]. We have based our synthesis of the pentacyclic pyridine bases on the
use of a previously developed approach, according to which the corresponding pyrilium salt [9] is employed as
the key intermediate. The latter were prepared by the acylation of the (3-hydroxy-1-oxoinden-2-yl)-substituted
heterocycles 1-4.
Compounds 1-4 were made using two methods. The first involves the condensation of the hetarene
carboxaldehydes 5, 6 with phthalide 7 [10]. Using this method (Scheme 1), 2-formylbenzo[b]furan (5) and
_________________________________________________________________________________________
L. M. Litvinenko Institute of Physical-organic Chemistry and Coal Chemistry, National Academy of
Sciences of Ukraine, Donetsk 83114, e-mail: tolkunov@uvika.dn.ua. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 3, pp. 435-443, March, 2005. Original article submitted July 23, 2001;
revision submitted June 2, 2004.
0009-3122/05/4103-0379©2005 Springer Science+Business Media, Inc.
379

Scheme 1
O
O
CHO
O
5
O
O
1
HO
+
7
O
Et
S
S
Et
S
S
CHO
6
HO
2
5-ethyl-2-formylthieno[2,3-b]thiophene (6) gave good yields of 2-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan (1)
and 5-ethyl-2-(3-hydroxy-1-oxoinden-2-yl)thieno[2,3-b]thiophene (2). The reaction occurs readily when
refluxing a mixture of the starting materials in the presence of sodium methylate.
The synthesis of 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan (3) and -benzo[b]thiophene (4) were
performed by successive reactions of the corresponding hetaryl acetic acids to 3-(benzo[b]furyl-3-
methylene)phthalide (8) and 3-(benzo[b]thienyl-3-methylene)phthalide (9) and then their recyclization to the
indenones 3, 4 with sodium methylate using the method in [11] (Scheme 2). Attempts to prepare compounds 3
and 4 by condensation of benzo[b]furan(2H)-3-one and benzo[b]thiophen(2H)-3-one with 1,3-indanedione were
unsuccessful. In contrast to a similar reaction with dimedone [5], there occurs in this case a condensation
involving the methylene group of the benzo[b]furan(2H)-3-one and benzo[b]thiophen(2H)-3-one and not the
indanedione.
Scheme 2
O
O
H
O
O
CH2COOH
C
+
X
X
8, 9
O
MeONa
O
O
O
OH
+
H2C
O
X
X
3, 4
3, 8 X = O; 4, 9 X = S
The IR spectra of compounds 1-4 show a group of absorption bands for the C=O bond at 1680,
1660 cm-1 and C=C at 1640 and 1620 cm-1. This shows that the indicated compounds exist in the enol form. The
1H NMR spectra also only show bands for the absorption of the corresponding enol form.
380

Acylation of compounds 1-4 using acetic anhydride in the presence of 70% perchloric acid gives the
indenopyrilium pentacyclic salts 10-13, the IR spectra of which show absorption bands for the pyrilium and
aromatic rings at 1505-1640 cm-1 together with absorption for a carbonyl group at 1710 cm-1 (Scheme 3).
Scheme 3
O
Me
O
Me
Me
O
H2O
_
+
ClO4
N
HO
O
14
NH3
O
10
O
18
Me
+
Me
_
+
_
O
MeCO ClO4
NH3
N
ClO4
1–4
Et
S
S
11
O
O
19
O
O
H2O
_
ClO4
+
O
X
OH
O
Me
Me
15a,b
NH3
12, 13
O
N
16, 17
12, 15a, 16 X = O; 13, 15b, 17 X = S
Me
The presence of an oxo group in the pyrilium salts 10, 12, 13 destabilizes them, as a result of which they
are readily hydrolyzed in aqueous alcoholic solutions to the corresponding 3(2)-acetyl-2(3)-(inden-2-yl)-
benzo[b]furan or -benzo[b]thiophene (14, 15).
1
The H NMR spectra of compounds 14, 15 show a double set of signals for the methyl groups
corresponding to the enol and keto form. According to the ratio of integrated intensities of the methyl group
signals and also the signal for the CH proton of the keto form (5.92 ppm) it is evident that compounds 14, 15
contain up to 30% of the keto form.
The target heteroindeno[2,1-e]pyridines 16-19 were prepared by treating the pyrilium salts 10-13 or the
tricarbonyl compounds 14, 15 with aqueous alcoholic ammonia solution.
381

1
Some features of the H NMR spectra of the pyrilium salts 12, 13 and the corresponding pyridine bases
16, 17 should be noted. The observed low field shift of the 11-H aromatic proton signal to 9.4 ppm, as in the
case of an analogously constructed tetracyclic pyridine base [5], is related to its structural characteristics.
Calculation of compounds 16, 17 using the AM1 (MOPAC 6.0) method shows that the distance between H-11
and the C=O group is 2.19 Å for X = O and 2.12 Å for X = S. Because it is placed at a small distance from the
CO group and is fixed by the overall rigidity of the molecule the H-11 proton must experience the marked low
1
field shift via magnetic anisotropy. A similar effect is absent in the H NMR spectra of compounds 10, 18,
isomers of compounds 12, 16. Calculation shows the presence of significant steric hindrances in the starting
molecules 16, 17, in particular towards the products of reaction at the carbonyl group. On this basis it can be
proposed that the reactivity of the carbonyl group in the indenopyridines 16, 17 will be lowered [5].
With the aim of checking these ideas we carried out reactions at the oxo group of 6-methyl-12-
oxobenzothieno[2,3-c]indeno[2,1-e]pyridine (17) using hydroxylamine, hydrazine hydrate, and sodium
borohydride (Scheme 4).
Scheme 4
R1
Me
R2
N
,
NH2OH, N2H4, [H]
NH2OH, N2H4 [H]
18
17
N
R1
Me
20–22
R2
23, 25, 26
Me
N
NH2OH
19
R1
R2
24
20, 23, 24 R1 – R2 = NOH; 21 R1 = R2 = H, 22, 26 R1 = OH, R2 = H, 25 R1–R2 = N–NH2
When refluxing compound 17 with hydroxylamine hydrochloride in acetic acid for 20 h, the starting
indenopyridine 17 is always present in the reaction mixture. The yield of the oxime 20 does not exceed 50%.
The indenopyridine does not react with hydrazine hydrate in alcohol and acetic acid even after refluxing for
20 h. Prolonged heating of the indenopyridine 17 with hydrazine hydrate in ethylene glycol leads to reduction of
the C=O group to give the 6-methyl-(12H)-benzothieno[2,3-c]indeno[2,1-e]pyridine (21). Reduction of 17 with
sodium borohydride gives a high yield of the corresponding hydroxy derivative 22. In contrast, 6-methyl-12-
oxobenzofuro[3,2-c]indeno[2,1-e]pyridine (18) and 8-ethyl-6-methylthieno[2,3:4',5']thieno[3,2-c]indeno[2,1-e]-
pyridine (19) react with hydroxylamine after 1 h under these conditions to give the corresponding oximes 23, 24.
Heating the indenopyridine 18 with hydrazine hydrate in alcohol gave the hydrazone 25. Attention was paid to a
1
number of features of their H NMR spectra. In place of the expected single signal to low field for the amino
group there were observed two exchangeable signals of intensity 1H at 8.60 and 8.80 ppm which were markedly
different in half width. With increase in temperature (18-50°C) the broadened signal at 8.60 ppm reacted more
strongly and shifted by 0.15 ppm to high field whereas the signal at 8.80 ppm shifted by 0.05 ppm. While there
is good agreement in the integrated intensities of the aliphatic and aromatic parts of the spectrum, the aromatic
region shows multiplets at 8.0 and 8.3 ppm for 0.5H which are assigned to the H-1 proton and are due to the
existence of a mixture of geometric isomers which differ in the position of the amino group relative to
382

TABLE 1. Characteristics of the Compounds Synthesized
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °С Yield, %
С
Н
Cl
—
—
—
—
—
—
N
S
1
C17H10O3
77.78
77.86
65.55
65.36
77.31
77.86
73.67
73.36
77.62
77.86
73.49
73.36
58.62
59.01
52.48
52.24
59.26
59.01
56.81
56.65
75.78
74.99
74.80
74.99
71.58
71.23
80.15
79.99
75.80
75.72
79.86
79.99
68.55
68.03
72.31
72.13
79.55
79.41
75.28
75.22
76.18
75.99
84.35
65.12
76.38
76.24
79.55
79.43
3.94
3.84
4.04
3.87
3.48
3.84
3.35
3.62
4.15
3.84
3.74
3.62
3.00
2.87
3.17
2.97
2.27
2.87
2.84
2.75
3.76
3.97
3.81
3.97
3.81
3.78
4.02
3.89
3.41
3.68
3.53
3.89
4.06
3.91
3.97
3.82
4.25
4.56
4.43
4.32
4.23
4.03
4.20
4.03
4.21
4.38
4.25
4.56
—
—
—
—
—
—
—
—
—
—
—
—
—
—
174
200
140
166
272
272
260
220
235
223
190
167
178
224
200
280
218
307
185
190
330
138
243
190
71
41
80
77
38
40
84
83
92
94
74
54
63
90
91
89
86
64
83
85
71
88
70
50
2
C17H12O2S2
C17H10O3
20.24
20.53
—
3
4
C17H10O2S
C17H10O3
11.60
11.52
—
8
9
C17H10O2S
C19H11ClO7
C19H13ClO6S2
C19H11ClO7
C19H11ClO6S
C19H12O4
11.15
11.52
—
10
11
12
13
14
15a
15b
16
17
18
19
20
21
22
23
24
25
26
9.34
9.14
8.39
8.12
9.41
9.14
8.47
8.80
14.67
14.64
—
7.74
7.94
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
C19H12O4
—
C19H12O3S
C19H11NO2
C19H11NO2S
C19H11NO2
C19H13NOS2
C19H12N2OS
C19H13NS
10.28
10.01
—
4.67
4.91
4.55
4.65
4.67
4.91
4.34
4.18
9.02
8.85
5.02
4.87
4.51
4.62
9.51
9.33
10.88
10.64
—
19.04
19.12
10.37
10.13
11.34
11.16
10.47
10.57
C19H13NOS
C19H12N2O2
C19H14N2OS2
C19H13N3O
C19H13NO2
—
7.82
7.99
14.12
14.04
5.05
4.87
18.47
18.30
—
—
the C=N bond [12]. In addition, in the anti isomer (NH2 8.8, H-1 8.0 ppm) the protons of the amino group can
interact with the electron pair of the benzofuran oxygen atom to form an intramolecular hydrogen bond. The
calculated distances between these atoms are fully in agreement with this possibility. The temperature
experiment and the absence of spin-spin coupling between the protons in the NH2 in a 2M COSY experiment
confirm our interpretation.
Reduction of the indenopyridine 18 with sodium borohydride gives 12-hydroxybenzofuro-6-methyl-
[3,2-c]indeno[2,1-e]pyridine (26). Attempts to carry out a Beckmann reaction with the oximes 23, 24 in PPA at
140°C gave the starting oximes.
383

TABLE 2. Spectroscopic Characteristics of Compounds 1-4, 8-26
1Н NMR spectrum, δ, ppm (J, Hz)
IR spectrum,
Com-
ν, cm-1,
СН3 (3Н, s),
(С2Н5)
(3Н, t, 2Н, q)
pound
Н arom and other protons
С=О and С=С
1
1
2
3
4
1680, 1640, 1620,
1530
7.10 (1Н, s, Н-3'); 7.16-7.23 (2Н, m, H-5',6');
7.40-7.61 (6Н, m)
—
2
1660, 1650, 1625,
1570
6.80 (1Н, s, H-4'); 7.00 (1Н, s, H-3');
7.45-7.62 (4Н, m)
(1.34, 2.90,
J = 7.0)
3
1680, 1550
7.32-7.41 (2Н, m, H-5' and H-6');
—
7.52 (1Н, s, H-2'); 7.55-7.78 (6Н, m)
4
1710-1640, 1580
7.32-7.41 (2Н, m, H-5',6'); 7.41-7.53 (3Н, m,
H-4',5,6); 7.61 (1Н, s, H-2');
—
7.71-8.08 (3Н, m, H-4,7',7)
8
1770, 1700, 1610,
1570
7.12 (1Н, s, H-2'); 7.46-8.07 (7Н, m);
8.14 (1Н, d, J = 8.0, H-4); 8.27 (1Н, s, СН=)
—
—
9
1750, 1640, 1450
7.37 (1Н, s, H-2'); 7.46-8.07 (7Н, m);
8.29 (1Н, s, СН=); 8.33 (1Н, d, J = 8.0, H-4)
10
11
1710, 1580, 1500,
1450
7.30-7.78 (7Н, m); 8.10 (1Н, d, J = 8.0, H-1)
2.98
1710, 1610, 1580
7.36 (1Н, t, J = 7.9, 3-Н); 7.39 (1Н, s, H-7);
7.52-7.62 (2Н, m, H-2,4); 7.70 (1Н, d, J = 8.0,
H-1)
2.98, (1.36,
3.00, J = 7.5)
12
13
14
1715, 1610, 1580
1715, 1610, 1580
7.20-7.60 (6Н, m); 8.05 (1Н, d, J = 8.0, H-1);
9.30 (1Н, d, J = 8.0, H-11)
7.40-7.70 (6Н, m); 8.05 (1Н, d, J = 8.0, H-1);
9.40 (1Н, d, J = 8.0, H-11)
2.75
2.70
1700, 1690, 1650,
1615
5.51 (HO- enol in exchange with H2O);
5.76 (1H, CH enol form); 7.40-8.20 (8H, m)
2.30
(keto form);
2.40 (enol
form)
15b
1700, 1690, 1650,
1615
5.20 (HO-enol in exchange with H2O);
5.96 (1H, CH enol form); 7.40-8.20 (8H, m)
2.41
(keto form);
2.43 (enol
form)
16
17
18
1710, 1605, 1590,
1560
7.20-7.60 (6Н, m); 8.0 (1Н, d, J = 8.0, H-1);
9.30 (1Н, d, J = 8.0, H-11)
2.75
2.70
2.98
1700, 1605-1560
7.40-7.70 (6Н, m); 8.05 (1Н, d, J = 8.0, H-1);
9.40 (1Н, d, J = 8.0, H-11)
1710, 1635, 1605,
1585, 1570
7.40-7.61 (4Н, m, H-2,3,8,9); 7.76 (1H, J = 8.0,
H-4); 7.94 (1H, J = 8.0, H-7); 8.09 (1H, J = 8.0,
H-10); 8.39 (1H, d, J = 8.0, H-1)
19
20
1705, 1610, 1575,
1550
7.36 (1H, t, J = 7.9, H-3); 7.39 (1H, s, H-7);
7.52–7.62 (2H, m, H-2,4); 7.71 (1H, d, J = 8.0,
H-1)
2.98 (1.36,
3.00, J = 7.5)
1660 (C=NOH),
1615, 1590
7.42-7.80 (4Н, m, H-2,3,9,10); 8.17 (1Н, d,
J = 8.0, H-8); 8.43 (1Н, d, J = 8.0, H-4);
8.50 (1Н, d, J = 8.0, H-1); 9.83 (1Н, d, J = 8.0,
H-11); 13.1 (1Н, s, HON= )
2.83
2.87
2.83
21
22
1620, 1590, 1570
4.19 (2Н, s, 12-СН2); 7.42–7.64 (5Н, m,
H-2,3,4,9,10); 7.65 (1Н, d, J = 7.8, H-8);
8.18 (1Н, d, J = 7.8, H-11); 8.24 (1Н, d,
J = 7.8, H-1)
3400 (С–ОН), 1620, 3.40 (OН in exchange with Н2О); 6.00 (1Н, s,
1585, 1550
СН–ОН); 7.15-8.20 (7Н, m); 8.91 (1Н, d,
J = 8.0, H-1)
384

TABLE 2 (continued)
1
2
3
4
23
1670 (C=NOH),
1620, 1585, 1550
7.40-7.60 (4Н, m, H-2,3,8,9); 7.78 (1Н, d, J = 8.0, 2.99
H-4); 7.90 (1Н, d, J = 7.8, H-7); 8.10 (1Н, d,
J = 7.8, H-10); 8.38 (1Н, d, J = 8.0, H-1);
13.1 (1Н, s, HON=)
24
25
1670 (C=NOH),
1610, 1599, 1550
7.40 (1Н, s, H-7); 7.40-7.53 (2Н, m, H-2,3);
7.82 (1Н, d, J = 8.0, H-4); 8.27 (1Н, d, J = 8.0,
H-1); 12.91 (1Н, s, HON=)
2.96
(1.25, 3.25,
J = 7.5)
3350 (NH2), 1650,
1620, 1585, 1550
7.45-7.65 (5Н, m, H-2,3,4,8,9); 7.78 (1Н, d,
J = 8.0, H-7); 8.13 (1Н, d, J = 8.0, H-1);
syn isomer: 8.30 (1Н, d, J = 8.0, H-1);
8.60 (2Н, s, NH2); anti isomer: 8.00 (1Н, d,
J = 8.0, H-1); 8.80 (2Н, s, NH2)
3.04
26
3400 (ОН), 1615,
1590, 1550
3.40 (OН in exchange with Н2О); 6.00 (1Н, s,
СН–О); 7.40-8.20 (8Н, m)
2.99
EXPERIMENTAL
1
IR spectra were taken on a UR-20 instrument using KBr and H NMR spectra on a Gemini-200
instrument (200 MHz) with TMS internal standard and DMSO-d6 solvent. Elemental analytical data for the
compounds synthesized agreed with those calculated. The characteristics of the compounds prepared are given in
Tables 1 and 2.
2-(3-Hydroxy-1-oxoinden-2-yl)benzo[b]furan (1) and 5-Ethyl-2-(3-hydroxy-1-oxoinden-2-yl)thieno-
[2,3-b]thiophene (2) (General Method). A mixture of 2-formylbenzo[b]furan 5 or 2-formyl-5-ethylthieno-
[2,3-b]thiophene (6) (0.1 mol), phthalide 7 (14.7 g, 0.11 mol), sodium methylate (prepared from sodium (7 g,
0.3 mol) and methanol (100 ml)), and ethyl acetate (8.8 ml) was refluxed for 2 h. Water (500 ml) was added to
the solution which was then filtered and acidified with hydrochloric acid to pH 1.0. The precipitate was filtered
off and recrystallized from acetonitrile.
3-(3'-Benzo[b]furyl-3-methylene)phthalide (8) and 3-(Benzo[b]thienyl-3-methylene)phthalide (9).
Triethylamine (10.5 ml, 0.075 mol) was added slowly to a mixture of the benzofuran-3- or benzothiophen-3-
acetic acids (0.025 mol) and phthalic anhydride (3.75 g, 0.025 mol) in acetic anhydride (16 ml) and the mixture
was heated for 1 h at 100°C. The reaction product was cooled and poured into a mixture of ice (30 g) and
hydrochloric acid (10 ml). The precipitate was filtered off and crystallized from acetonitrile.
3-(3-Hydroxy-1-oxoinden-2-yl)benzo[b]furan (3) and 3-(3-Hydroxy-1-oxoinden-2-yl)benzo-
[b]thiophene (4) (General Method). A mixture of compound 8 or 9 (0.1 mol) and sodium methylate (prepared
from sodium (3.7 g, 0.16 mol) and methanol (100 ml)) was refluxed for 2 h. Methanol was evaporated off in
vacuo and the residue was dissolved in water and acidified to pH 1.0. The product was filtered off, washed with
water, and crystallized from acetonitrile.
6-Methyl-12-oxobenzofuro[3,2-c]indeno[2,1-e]pyrilium (10), 8-Ethyl-6-methylthieno[2,3:4',5']-
thieno[3,2-c]indeno[2,1-e]pyrilium (11), and 6-Methyl-12-oxobenzofuro(benzothieno)[2,3-c]indeno[2,1-e]-
pyrilium (12, 13) Perchlorate Salts (General Method). Perchloric acid (0.5 ml, 70%) was added to a
suspension of the hetaryliden-1-one 1-4 (0.005 mol) in acetic anhydride (5 ml). The mixture became warm and
the starting compounds 1-4 dissolved. The reaction mixture was held for 1 h at room temperature and the
precipitated pyrilium salt was filtered off, washed with isopropanol and ether, and crystallized from acetic acid.
3-Acetyl-2-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan (14), 2-Acetyl-3-(3-hydroxy-1-oxoinden-2-
yl)benzo[b]furan (15a), and 2-Acetyl-3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]thiophene (15b) (General
Method). A suspension of the corresponding pyrilium salt 10, 12, 13 (0.005 mol) in 70% aqueous alcohol
385

(50 ml) was heated to the salt dissolving. It was filtered and the product was precipitated with water. For
purification, the product was dissolved in a 5% solution of NaHCO3, filtered, and precipitated using
hydrochloric acid. It was crystallized from alcohol.
Indenopyridines 16-19 (General Method). Concentrated ammonia solution (10 ml) was added to a
suspension of the perchlorates 10-13 (0.005 mol) in methanol (20 ml). The mixture was refluxed for 0.5 h,
cooled, water (20 ml) was added, and the precipitate was filtered off and crystallized from DMF.
12-Hydroximino-6-methylbenzothieno[2,3-c]indeno[2,1-e]pyridine
(20),
12-Hydroximino-6-
methylbenzofuro[3,2-c]indeno[2,1-e]pyridine (23), and 8-Ethyl-11-hydroximino-6-methylthieno-
[2,3:4',5']thieno[3,2-c]indeno[2,1-e]pyridine (24) (General Method). A mixture of the indenopyridine 17, 18,
or 19 (0.005 mol) and hydroxylamine hydrochloride (1.4 g, 0.02 mol) in acetic acid (40 ml) was refluxed for 1 h
for compounds 18 and 19 or for 20 h for compound 17. Sodium acetate (1.64 g, 0.02 mol) was added to the
reaction mixture and heating was continued for a further 0.5 h. The product was cooled and the precipitate was
filtered off, washed with water, and crystallized from DMF.
6-Methyl-(12H)-benzothieno[2,3-c]indeno[2,1-e]pyridine (21) (General Method). Hydrazine hydrate
(5 ml, 85%) was added to a suspension of the indenopyridine 17 (1.5 g, 0.005 mol) in ethylene glycol (40 ml)
and the mixture was refluxed for 15 h. After cooling, the precipitate was filtered off, washed with water, and
crystallized from alcohol.
6-Methyl-12-oxobenzofuro[3,2-c]indeno[2,1-e]pyridine Hydrazone (25). Hydrazine hydrate (5 ml,
85%) was added to a suspension of the indenopyridine 18 (1.43 g, 0.005 mol) in methanol (100 ml) and the
mixture was refluxed for 3 h. After cooling, the precipitate was filtered off, washed with water, and crystallized
from DMSO.
12-Hydroxy-6-methyl-(12H)-benzothieno[2,3-c]indeno[2,1-e]pyridine (22) and 12-Hydroxy-6-
methyl-(12H)-benzofuro[3,2-c]indeno[2,1-e]pyridine (26) (General Method). Sodium borohydride (0.19 g,
0.005 mol) was added in small portions to a suspension of the indenopyridine 17 or 18 (1.50 g, 0.005 mol) in
methanol (20 ml). The mixture obtained was stirred for 3 h and left overnight. It was diluted with water (20 ml)
and the precipitate formed was filtered off, washed with water, and crystallized from acetone.
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