Reaction of 6-methoxybenzo[b]furan-3(2H)-one and benzo[b]thiophen-3(2H) -one with 2-aryl-1,1-dicyanoethylenes as a convenient synthetic route to substituted 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]furans and 2-amino-4-aryl-3-cyano-4H-benzothieno[3,2-b]pyrans

Article abstract of DOI:10.1023/A:1024468813689

The reactions of 6-methoxybenzo[b]furan-3(2H)-one with 2-aryl-1,1- dicyanoethylenes and malononitrile or with aromatic aldehyde and two moles of malononitrile afford 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]furans. The reactions of benzo[b]thiophen-3(2H)-one with 2-aryl-1,1-dicyanoethylenes or with aromatic aldehyde and one mole of malononitrile produce 2-amino-4-aryl-3-cyano-4H-benzothieno[3,2-b]pyrans.

Full text of DOI:10.1023/A:1024468813689

Russian Chemical Bulletin, International Edition, Vol. 52, No. 4, pp. 961—968, April, 2003
961
Reaction of 6ꢀmethoxybenzo[b]furanꢀ3(2Н )ꢀone and
benzo[b]thiophenꢀ3(2Н )ꢀone with 2ꢀarylꢀ1,1ꢀdicyanoethylenes
as a convenient synthetic route to substituted
2ꢀaminoꢀ4ꢀarylꢀ1,3ꢀdicyanoꢀ7ꢀmethoxydibenzo[b,d]furans
and 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Нꢀbenzothieno[3,2ꢀb]pyrans
ꢀ
A. M. Shestopalov and O. A. Naumov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: shchem@dol.ru
The reactions of 6ꢀmethoxybenzo[b]furanꢀ3(2Н )ꢀone with 2ꢀarylꢀ1,1ꢀdicyanoethylenes
and malononitrile or with aromatic aldehyde and two moles of malononitrile afford 2ꢀaminoꢀ
4ꢀarylꢀ1,3ꢀdicyanoꢀ7ꢀmethoxydibenzo[b,d]furans. The reactions of benzo[b]thiophenꢀ3(2Н )ꢀ
one with 2ꢀarylꢀ1,1ꢀdicyanoethylenes or with aromatic aldehyde and one mole of malononitrile
produce 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Нꢀbenzothieno[3,2ꢀb]pyrans.
Key words: 6ꢀmethoxybenzo[b]furanꢀ3(2Н )ꢀone, 6ꢀmethoxyꢀ2ꢀ[(4ꢀaryl)methylidene]ꢀ
1ꢀbenzofuranꢀ3(2Н )ꢀone, 2ꢀaminoꢀ4ꢀarylꢀ1,3ꢀdicyanoꢀ7ꢀmethoxydibenzo[b,d]furan, benꢀ
zo[b]thiophenꢀ3(2Н )ꢀone, 2ꢀ[(4ꢀaryl)methylidene]ꢀ1ꢀbenzothiophenꢀ3(2Н )ꢀone, 2ꢀaminoꢀ
4ꢀarylꢀ3ꢀcyanoꢀ4Нꢀbenzothieno[3,2ꢀb]pyran, threeꢀcomponent condensation.
The reactions of 1ꢀacetylꢀ1,2ꢀdihydroindolꢀ3(2Н )ꢀ
one with 2ꢀaryl(hetaryl)ꢀ1,1ꢀdicyanoethylenes have preꢀ
viously been shown1,2 to afford 5ꢀacetylꢀ2ꢀaminoꢀ4ꢀarylꢀ
3ꢀcyanoꢀ4,5ꢀdihydropyrano[3,2ꢀb]indoles. The method of
oneꢀpot synthesis of substituted pyrano[3,2ꢀb]indoles
(without preliminary preparation and isolation of unsatꢀ
urated nitriles) by the threeꢀcomponent condensation
of 1ꢀacetylindolꢀ3(2H )ꢀone, aromatic aldehyde, and
malononitrile was developed.3 In continuation of the studꢀ
ies of heterocyclic ketones with 2ꢀaryl(hetaryl)ꢀ1,1ꢀ
dicyanoethylenes, we studied the reaction of 6ꢀmethoxyꢀ
benzo[b]furanꢀ3(2H )ꢀone (1), which is the oxygen anaꢀ
log of 3ꢀoxoindole, with arylmethylidenemalononitriles
2a—h. It turned out that this reaction afforded 2ꢀaminoꢀ
4ꢀarylꢀ1,3ꢀdicyanoꢀ7ꢀmethoxydibenzo[b,d]furans 3a—h
instead of the expected 2ꢀaminoꢀ4ꢀaryl(hetaryl)ꢀ3ꢀcyanoꢀ
7ꢀmethoxyꢀ4Нꢀpyran[3,2ꢀb]benzofurans 4 (method A,
Scheme 1).
Scheme 1
2, 3
a
b
c
d
e
f
g
h
Ar
Ph
4ꢀFC6H4 2ꢀClC6H4 4ꢀClC6H4 2ꢀBrC6H4 3ꢀBrC6H4
3ꢀpy
3ꢀThienyl
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 911—917, April, 2003.
1066ꢀ5285/03/5204ꢀ961 $25.00 © 2003 Plenum Publishing Corporation

962
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Shestopalov and Naumov
Scheme 2
Primarily formed Michael adducts 5 undergo
Aromatic aldehyde ArCHO 10 is formed in the reacꢀ
tions of benzofuranone 1 with arylmethylidenemalonoꢀ
nitriles 2i,j (Ar = 2ꢀFC6H4 (i), 4ꢀBrC6H4 (j)), indicating
the different reaction course (Scheme 3).
It is known5 that the condensation of malononitrile 6
and aromatic aldehydes 10 (Knoevenagel reaction) is reꢀ
versible. Therefore, the reaction mixture (a solution in
96% EtOH) can contain both compounds 1, 2 and comꢀ
pounds 6, 10. Probably, malononitrile 6 is condensed
with 6ꢀmethoxybenzofuranꢀ3(2H )ꢀone (1) to form unꢀ
saturated dinitrile 11, which reacts with arylmethylꢀ
idenemalononitrile 2 in the Michael reaction. The further
1,2ꢀelimination of a molecule of malononitrile 6 to
form 2ꢀ[(4ꢀaryl)methylidene]ꢀ6ꢀmethoxyꢀ1ꢀbenzofuranꢀ
3(2Н )ꢀones 7 (Scheme 2). Compounds 7a—c were isoꢀ
lated and characterized (Tables 1 and 2). The reaction
of malononitrile 6 (2 mol) with intermediate 7 afꢀ
fords adduct 8, which undergoes ring closure via the
Thorpe—Ziegler reaction to form imine 9. The subseꢀ
quent tautomeric transformation and dehydrocyanation
afford benzofuran 3. The reaction mixture also contains
compounds 7a,b (Ar = 4ꢀFC6H4 (a), 4ꢀClC6H4 (b)),
which were isolated.
Table 1. Physicochemical characteristics of compounds 7a—c
Compound
7
Ar
Yield
(%)
M.p.
/°C
Found
Calculated
Molecular
formula
MS,
m/z ([M]+)
(%)
H
С
a
b
c
4ꢀFС6H4
4ꢀСlС6H4
2ꢀThienyl
76
87
73
173—175
166—168
187—189
70.81
71.11
66.85
67.03
65.24
65.10
3.98
4.10
3.54
3.87
4.05
3.90
С16H11FO3
С16H11ClO3
С14H10O2S
270
286
258
Table 2. Spectroscopic characteristics of compounds 7a—c*
Comꢀ
pound 7
1H NMR, δ (J/Hz)
OCH3 (s, 3 H) H(5), H(7) (m, 2 H) —CH= (s, 1 H) H(4) (d, 1 Н)
IR,
ν(СО)/cm–1
Ar
a
b
c
3.90
3.95
3.94
6.80—6.90
6.80—6.90
6.80—6.90
7.10
7.10
–**
7.69 (J = 1.3)
7.70 (J = 1.3)
7.80 (J = 1.1)
7.31 (t, 2 H, Н(6´), Н(2´), J = 8.8);
8.01 (t, 2 H, Н(5´), Н(3´), J = 8.8)
7.55 (d, 2 H, Н(6´), Н(2´), J = 8.4); 1703
7.98 (d, 2 H, Н(5´), Н(3´), J = 8.4)
7.11—7.20 (m, 2 H, 2ꢀCH=, Ar);
7.60—7.65 (m, 2 H, Ar)
1710
1696
* The signals were assigned according to the experimental data.4
** Superimposed on the signals of the substituent.

4HꢀBenzothieno[3,2ꢀb]pyrans
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
963
Scheme 3
with malononitrile 6 (2 mol) in EtOH (method B,
Scheme 4).
Scheme 4
Ar = 4ꢀFC6H4 (3b, 7a), 4ꢀClC6H4 (3d, 7b)
Since the Michael adducts 8 are generated in the reacꢀ
tion with arylmethylidenemalononitrile 2, it is reasonable
to assume that 2ꢀaminoꢀ3ꢀcyanodibenzofurans 3 can be
synthesized without preliminary synthesis of 2ꢀarylꢀ
methylideneꢀ6ꢀmethoxyꢀ1ꢀbenzofuranꢀ3(2Н )ꢀone 7 or
arylmethylidenemalononitriles 2 by the threeꢀcomponent
condensation of 6ꢀmethoxybenzo[b]furanꢀ3(2H )ꢀone (1),
the corresponding aldehyde 10, and malononitrile 6. Inꢀ
deed, the reaction of 6ꢀmethoxybenzo[b]furanꢀ3(2H )ꢀ
one (1) with malononitrile 6 (2 mol) and aldehyde 10
(1 mol) in EtOH in the presence of Et3N affords diꢀ
benzofurans 3 (method С, Scheme 5) in approximately
the same yields as in method А (Tables 3 and 4).
transformation of intermediate 8 into dibenzofuran 3 proꢀ
ceeds similarly to Scheme 1. In this case, aromatic aldeꢀ
hydes 10 remain in excess. They were isolated in the pure
state or characterized as arylmethylidenemalononitriles
2i,j due to the addition of malononitrile 6 to the filtrate.
The scheme of the reaction can be attributed, most
likely, to the Bell—Evans—Polanyi (BEP) rules, which
were presented for the pair of carbonyl compounds: cycloꢀ
hexanone and benzaldehyde in the reaction with thioꢀ
semicarbazide.6 Since arylmethylidenemalononitrile 2,
like benzaldehyde thiosemicarbazone, in protic solvents
exists in the kinetic equilibrium with the initial comꢀ
pounds, we can assume that arylmethylidenemalonoꢀ
nitrile 2 is thermodynamically unstable and is formed via
the kinetically controlled reaction route. By analogy beꢀ
tween cyclohexanone thiosemicarbazone and intermediꢀ
ate 11 (although it does not completely correspond
to cyclohexanone thiosemicarbazone because has the
annelated aromatic cycle), it can be assumed that comꢀ
pound 11 is thermodynamically stable and its reaction is
thermodynamically controlled and irreversible. Therefore,
the reactions of benzofuranone 1 with arylmethylideneꢀ
malononitriles 2 afford aromatic aldehydes. In both cases
(see Schemes 2 and 3), the reactions are accompanied by
the elimination of HCN, are irreversible, and afford
dibenzofurans 3.
We mentioned that the direction of the process is afꢀ
fected by the nature of a substituent in arylmethylideneꢀ
malononitrile 2. For example, unsubstituted benzylideneꢀ
malononitrile 2a and arylmethylidenemalononitriles conꢀ
taining electronꢀwithdrawing substituents, such as the niꢀ
tro group (compound 2l) and halogen atoms (compounds
2b—f,i,j,l,o and heterocyclic derivatives 2g,h,p,q), readily
enter into this reaction. Arylmethylidenemalononitriles 2
containing electronꢀreleasing substituents (one or two
alkoxy groups, dialkylamino groups) do not react.
The experimental results were used to develop simpler
methods for the synthesis of substituted dibenzofurans 3.
Taking into account Scheme 2, we purposefully obtained
compounds 3 by the stepꢀbyꢀstep synthesis with prelimiꢀ
nary isolation of intermediate 7 followed by its reaction
Scheme 5
3, 10: Ar = 4ꢀFC6H4 (3b, 10a), 2ꢀClC6H4 (3c, 10b),
4ꢀClC6H4 (3d, 10c), 3ꢀpy (3g, 10d), 2ꢀFC6H4 (3i, 10e),
4ꢀBrC6H4 (3j, 10f), 3ꢀNO2C6H4 (3k, 10g), 3ꢀFC6H4 (3l, 10h),
2ꢀCF3C6H4 (3m, 10i), 2,3ꢀCl2C6H3 (3n, 10j),
2ꢀFꢀ5ꢀBrC6H3 (3o, 10k), 4ꢀpy (3p, 10l), 2ꢀthienyl (3q, 10m),
4ꢀMeOOCC6H4 (3r, 10n)
Unlike 6ꢀmethoxybenzo[b]furanꢀ3(2H )ꢀone (1), the
reactions of benzo[b]thiophenꢀ3(2H )ꢀone (12) with
arylmethylidenemalononitriles 2a,b,l under similar conꢀ
ditions (heating of equimolar amounts of compounds 12
and 2 in EtOH in the presence of Et3N) occur differꢀ
ently and afford 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Нꢀbenzothieꢀ
no[3,2ꢀb]pyrans 13a—c (method А, Scheme 6) in high
yields (Tables 5 and 6).
The scheme of this reaction can include transformaꢀ
tions similar to those described previously3 for the reacꢀ
tions of 1ꢀacetylindolꢀ3(2H )ꢀone with 2ꢀaryl(hetaryl)ꢀ
1,1ꢀdicyanoethylenes 2: Michael adduct 14 is primarily
formed and then undergoes intramolecular ring closure to
form aminopyran 13.
According to the scheme described above, 2ꢀaminoꢀ
4ꢀarylꢀ3ꢀcyanoꢀ4Нꢀbenzothieno[3,2ꢀb]pyrans 13b,c were
prepared by the stepꢀbyꢀstep synthesis with preliminary
isolation of the corresponding 2ꢀarylmethylideneꢀ1ꢀ
benzothiophenꢀ3(2Н )ꢀone 15a,b (Tables 7 and 8) folꢀ
lowed by its reaction with malononitrile 6 in EtOH
(method В, Scheme 7).

964
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Shestopalov and Naumov
Table 3. Physicochemical characteristics of compounds 3a—r
Compound
3
Ar
Yield
(%)
M.p.
/°C
Found
Calculated
Molecular
formula
MS,
m/z ([M]+)
(%)
(method)
С
H
N
a
b
C6H5
42 (A)
293—295
275—277
74.69
74.34
70.29
70.59
3.55
3.83
3.22
3.36
12.74
12.39
12.50
12.11
C21H12N3O2
339
357
4ꢀFC6H4
34 (A),
51 (B),
43 (C)
36 (A),
31 (C)
46 (A),
36 (B),
42(C)
C21H12FN3O2
c
d
2ꢀClC6H4
4ꢀClC6H4
248—250
308—310
67.82
67.47
67.77
67.47
2.93
3.21
3.49
3.21
11.59
11.24
11.64
11.24
C21H12ClN3O2
C21H12ClN3O2
374
374
e
f
2ꢀBrC6H4
3ꢀBrC6H4
3ꢀpy
42 (A)
318—320
266—268
318—320
292—294
245—247
305—307
207—209
287—289
270—272
276—278
258—260
304—306
263—265
313—315
59.94
60.29
60.64
60.29
70.94
70.59
66.44
66.09
70.24
70.59
59.99
60.29
65.28
65.63
70.94
70.59
65.21
64.86
61.62
60.92
58.15
57.80
70.24
70.59
65.74
66.09
69.24
69.52
2.59
2.87
3.15
2.87
3.81
3.53
2.91
3.19
3.64
3.36
2.73
2.87
2.99
3.13
3.08
3.36
3.23
2.95
2.99
2.70
2.24
2.52
3.39
3.53
3.47
3.19
3.98
3.78
9.70
10.05
10.40
10.05
16.12
16.47
12.52
12.17
11.36
11.76
9.65
10.05
14.23
14.58
11.76
11.76
10.72
10.32
10.67
10.32
9.98
C21H12BrN3O2
C21H12BrN3O2
C20H12N4O2
418
418
340
345
357
418
384
357
407
407
436
340
345
397
47 (A)
g
h
i
47 (A),
41 (C)
40 (A)
3ꢀThienyl
2ꢀFC6H4
C19H11N3O2S
C21H12FN3O2
C21H12BrN3O2
C21H12N4O4
46 (C)
47 (C)
51 (C)
39 (C)
41 (C)
32 (C)
56 (C)
49 (C)
j
4ꢀBrC6H4
3ꢀNO2C6H4
3ꢀFC6H4
k
l
C21H12FN3O2
C22H12F3N3O2
C21H11Cl2N3O2
C21H11FBrN3O2
C20H12N4O2
m
n
o
p
q
r
2ꢀCF3C6H4
2,3ꢀCl2C6H3
2ꢀFꢀ5ꢀBrC6H3
4ꢀpy
9.63
16.07
16.47
11.82
12.17
10.93
10.58
2ꢀThienyl
4ꢀMeOOCC6H4
56 (B),
54 (C)
43 (C)
C19H11N3O2S
C23H15N3O4
Since the Michael adducts 15 are generated in the
reaction with arylmethylidenemalononitrile 2, it seems
reasonable that 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Нꢀbenzoꢀ
thieno[3,2ꢀb]pyrans 13 can be prepared by a simpler
method, viz., in one step, without preliminary synthesis
of 2ꢀarylmethylideneꢀ1ꢀbenzothiophenꢀ3(2Н )ꢀone 15 or
Scheme 6
13: Ar = Ph (a), 4ꢀClC6H4 (b), 4ꢀBrC6H4 (c)

4HꢀBenzothieno[3,2ꢀb]pyrans
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
965
Table 4. Spectroscopic characteristics of compounds 3a—r
Comꢀ
pound 3
1H NMR, δ (J/Hz)
NH2
IR, ν/cm–1
OCH3
Ar
δ(NH2)
ν(CN)
ν(NH2)
a
b
c
d
e
f
3.88
(m, 3 H)
3.87
(br.s, 3 Н) (br.s, 2 Н)
3.88 6.51
(br.s, 3 Н) (br.s, 2 Н)
3.88 6.60
(br.s, 3 Н) (br.s, 2 Н)
6.41
(br.s, 2 Н)
6.57
7.04, 7.20 (both s, 1 H each, Ar);
7.60—7.67 (m, 5 H, Ar); 8.10 (s, 1 H, Ar)
7.03—7.08 (m, 2 H, Ar); 7.27—7.58 (m, 3 H, Ar);
7.75 (br.s, 1 Н, Ar), 8.10 (d, 1 H, Ar, J = 8.6)
6.96—7.39 (m, 2 H, Ar); 7.39—7.69 (m, 4 H, Ar);
8.10 (s, 1 H, Ar)
7.13—7.41 (m, 5 Н, Ar); 7.71 (s, 1 H, Ar);
8.03—8.13 (m, 1 Н, Ar)
6.68 (s, 1 H, Ar); 7.78—7.87 (m, 5 H, Ar);
8.12 (d, 1 H, Ar, J = 7.6)
1630
2220
3240, 3350, 3465
3260, 3360, 3480
3242, 3360, 3460
3250, 3360, 3460
3230, 3320, 3460
3240, 3370, 3445
1638
1637
1635
1635
1632
2220
2221
2220
2222
2220
3.74—3.98
(m, 3 H)
3.90
6.51
(br.s, 2 Н)
6.47
7.08 (d, 1 H, Н(5´), J = 7.8);
(m, 3 H)
(br.s, 2 Н)
7.19—7.31 (m, 4 H, Ar); 7.80 (s, 1 H, Ar);
8.10 (d, 1 H, Ar, J = 7.8)
g
h
3.90
6.52
7.05 (d, 1 H, Ar, J = 8.9); 7.20 (s, 2 H, Ar);
7.65 (s, 1 H, Ar); 8.10 (t, 1 H, C(4´)H, J = 5.1);
8.82 (s, 1 H, C(6´)); 8.88 (s, 1 H, C(2´))
7.10 (d, 1 H, H(4´), J = 5.2);
1625
1632
2220
2220
3220, 3340, 3400
3240, 3350, 3462
(br.s, 3 Н) (br.s, 2 Н)
3.90
6.47
(br.s, 3 Н) (br.s, 2 Н)
7.31—7.40 (m, 2 Н, Ar); 7.85 (s, 1 Н, Ar);
8.00—8.08 (m, 2 Н, Ar)
i
3.89
(br.s, 3 Н) (br.s, 2 Н)
3.90 6.49
(br.s, 3 Н) (br.s, 2 Н)
3.88 6.52
(br.s, 3 Н) (br.s, 2 Н)
6.48
7.03—7.63 (m, 6 H, Ar);
8.09 (s, 1 H, Ar)
7.00—7.10, 7.60—7.80 (both m, 3 H each, Ar);
8.09 (s, 1 H, Ar)
7.01—7.20 (m, 3 Н, Ar); 7.69 (d, 2 Н, Ar, J = 8.96); 1630
8.15—8.41 (m, 2 Н, Ar);
1623
1635
2220
2230
2220
3240, 3360, 3460
3240, 3360, 3440
3240, 3360, 3460
j
k
8.82 (s, 1 H, H(6´)); 8.88 (s, 1 H, H(2´))
l
3.89
6.41
7.05 (m, 1 H, Ar); 7.22 (s, 1 H, Ar);
7.30—7.55 (m, 3 H, Ar); 7.60—7.70 (m, 1 H, Ar);
8.10 (d, 1 H, Н(6´), J = 7.8)
1633
2230
3240, 3370, 3460
(br.s, 3 Н) (br.s, 2 Н)
m
n
o
p
q
r
3.88
(br.s, 3 Н) (br.s, 2 Н)
3.90 6.51
(br.s, 3 Н) (br.s, 2 Н)
3.86 6.53
(br.s, 3 Н) (br.s, 2 Н)
3.89 6.46
(br.s, 3 Н) (br.s, 2 Н)
3.89 6.54
(br.s, 3 Н) (br.s, 2 Н)
3.73 6.47
(br.s, 3 Н) (br.s, 2 Н)
6.50
7.03—7.18 (m, 3 Н, Ar); 7.55 (s, 1 Н, Ar);
7.82—8.10 (m, 3 Н, Ar)
6.95—7.20 (m, 3 H, Ar); 7.60—7.80 (m, 2 H, Ar);
8.10 (s, 1 H, Ar)
6.92—7.22, 7.32—7.63 (both m, 2 H each, Ar);
7.89, 8.10 (both s, 1 H each, Ar)
7.02—7.42 (m, 2 H, Ar); 7.61 (s, 1 H, Ar); 8.10
(t, 2 H, Ar, J = 5.0); 8.71, 8.85 (both s, 1 H each, Ar)
7.07 (d, 2 H, Ar, J = 4.7); 7.33 (s, 2 H, Ar);
7.97—8.05 (m, 2 H, Ar)
1640
1624
1630
1632
1638
1632
2220
2216
2230
2220
2220
2208
3240, 3360, 3462
3264, 3376, 3464
3240, 3360, 3440
3180, 3320, 3410
3220, 3370, 3470
3384, 3712, 3752
3.88 (br.s, 3 Н, COOCH3); 6.64 (s, 1 H, Ar);
6.93 (br.s, 1 Н, Ar); 7.38 (s, 1 H, Ar);
7.52—7.61, 8.00—8.10 (both m, 2 H each, Ar)
Scheme 7
arylmethylidenemalononitriles 2, by the threeꢀcomponent
condensation of benzo[b]thiophenꢀ3(2H )ꢀone (12), the
corresponding aldehyde 10, and malononitrile 6. In fact,
heating of compound 12 with malononitrile 6 (1 mol) in
EtOH in the presence of Et3N produces 2ꢀaminoꢀ4ꢀ
arylꢀ4Hꢀ[1]benzothieno[3,2ꢀb]pyranꢀ3ꢀcarbonitriles 13
(method С, Scheme 8). The relative yields of these
compounds with various substituents are presented in
Table 5. The structures of compounds 3 and 13 were
15: Ar = 4ꢀClC6H4 (a), 4ꢀBrC6H4 (b)

966
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Shestopalov and Naumov
Table 5. Physicochemical characteristics of compounds 13a—f
Comꢀ
pound
13
Ar
Yield
(%)
(method)
M.p.
/°C
Found
Calculated
Molecular
formula
MS,
m/z ([M]+)
(%)
N
С
H
S
a
b
Ph
28 (A)
218—220
280—282
69.51
71.03
63.67
63.81
4.31
3.97
3.13
3.27
9.45
9.20
8.15
8.27
10.52
10.54
9.48
C18H12N2OS
304
339
4ꢀClC6H4 18 (A),
20 (В),
C18H11ClN2OS
9.46
31 (С)
c
4ꢀBrC6H4 21 (A),
38 (B),
275—277
56.02
56.41
2.57
2.89
7.55
7.31
8.39
8.37
C18H11BrN2OS
383
48 (C)
d
e
f
2ꢀFC6H4
3ꢀpy
36 (С)
18 (С)
219—221
264—266
248—250
67.81
67.07
66.82
66.87
61.82
61.91
3.89
3.44
3.43
3.63
3.43
3.25
8.30
8.69
13.90
13.76
8.94
9.93
9.95
10.51
10.50
20.65
20.66
C18H11FN2OS
C17H11N3OS
C16H10N2OS2
322
305
310
2ꢀThienyl 33 (С)
9.03
Table 6. Spectroscopic characteristics of compounds 13a—f
Comꢀ
pound 13
1H NMR, δ (J/Hz)
2ꢀNH2 (br.s, 2 H)
IR, ν/cm–1
H(4) (s, 1 H)
Ar
δ(NH2) ν(CN)
ν(NH2)
a
b
5.06
5.08
7.08
7.11
7.38—8.12 (m, 9 H)
1654
1654
2226 3233, 3312, 3365
2225 3216, 3245, 3430
7.35 (t, 2 H, J = 8.14); 7.48—7.55
(m, 4 Н); 7.86—8.00 (m, 2 Н)
7.25 (d, 1 H, J = 7.14); 7.44—7.62
(m, 5 H); 7.62—7.73 (m, 1 H);
7.88 (d, 1 H, J = 8.45)
c
d
5.07
5.08
7.08
7.10
1656
2224 3240, 3320, 3472
2224 3215, 3247, 3428
7.35—7.42 (m, 3 H); 7.54 (s, 1 H);
7.75 (t, 2 H, J = 10.55);
1655
7.96—8.01 (m, 2 H)
e
f
4.95
4.95
7.08
7.10
7.30 (br.s, 2 H); 7.46—7.73 (m, 4 H);
7.90—8.12 (m, 2 H)
7.41 (s, 1 H); 7.54 (d, 1 H, J = 7.14);
7.75—7.96 (m, 3 H); 8.19—8.38 (m, 2 H)
1656
1655
2227 3215, 3270, 3370
2225 3218, 3253, 3382
Table 7. Physicochemical characteristics of compounds 15a,b
Compound
15
R
Yield
(%)
M.p.
/°C
Found
Calculated
Molecular
formula
MS,
m/z ([M]+)
(%)
H
С
a
b
4ꢀClС6H4
4ꢀBrС6H4
46
57
165—167
180—182
65.91
66.05
56.85
56.80
3.48
3.33
2.84
2.86
С15H9ClOS
С15H9BrOS
273
317

4HꢀBenzothieno[3,2ꢀb]pyrans
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
967
Table 8. Spectroscopic characteristics of compounds 15a,b
a singlet (δ 4.95—5.07) along with the signals from
the protons of the benzothiophene and aryl fragments
(δ 7.30—8.68). The signals of the protons of the amino
group appear as a singlet at δ 7.08—7.10.
It is most probable that the differences in the reactivity
of compounds 1 and 12 are related to the different elecꢀ
trophilicities of the C atom in position 3. It is most likely
that in benzofuranone 1 the electrophilicity of the C atom
in the carbonyl group is higher than that in benzoꢀ
thiophenone 12. Therefore, compound 1 primarily enters
into the Knoevenagel reaction and then undergoes transꢀ
formation into dibenzofuran 3.
Comꢀ
pound 15
1H NMR, δ (J/Hz)
IR,
ν(СО)/cm–1
—CH=
(s, 1 H)
Ar
Thus, the study of the reactions of 6ꢀmethoxybenꢀ
zo[b]furanꢀ3(2Н )ꢀone (1) and benzo[b]thiophenꢀ3(2Н )ꢀ
one (12) with malononitrile and aldehydes allowed us
to develop the regioselective methods for the syntheꢀ
sis of 2ꢀaminoꢀ4ꢀarylꢀ1,3ꢀdicyanoꢀ7ꢀmethoxydibenꢀ
zo[b,d]furans 3 and 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Нꢀbenzoꢀ
thieno[3,2ꢀb]pyrans 13, respectively.
a
b
6.61
7.11 (d, 1 Н, J = 7.35);
7.31—7.53 (m, 5 H);
7.83 (t, 2 H, Н(2´),
Н(6´), J = 8.4)
7.70 (d, 1 H, J = 7.75);
7.38—7.50 (m, 3 H);
7.85—7.98 (m, 2 H)
1676
1682
6.63
Experimental
confirmed by the data of physicochemical analyses (see
Tables 3—6).
Melting points of the synthesized compounds were deterꢀ
mined on a Koffler stage. IR spectra of the compounds were
recorded on a Specord IRꢀ75 instrument in pellets with KBr.
1Н NMR spectra were detected on a Bruker Мꢀ300 instrument.
The reaction course and purity of products were monitored by
TLC on the Silufol UVꢀ254 plates.
Scheme 8
Compounds 1 10 and 12 11 were synthesized according to
previously described procedures.
13: Ar = 4ꢀClC6H4 (b), 2ꢀFC6H4 (d), 3ꢀpy (e), 2ꢀthienyl (f)
Synthesis of compounds 7a—c (general procedure). A soluꢀ
tion of equimolar amounts of compound 1 (1.64 g, 0.01 mol)
and aldehyde 10a—c (0.01 mol) in EtOH (30 mL) was added at
40—60 °С by Et3N (0.3 mL). The reaction mixture was stored
for 24 h at 20 °С. A precipitate that formed was filtered off and
washed with EtOH and hexane (see Tables 1 and 2).
Synthesis of compounds 3a—h (general procedure). А. A soꢀ
lution of equimolar amounts of compound 1 (1.64 g, 0.01 mol)
and arylmethylidenemalononitrile 2a—h (0.01 mol) in EtOH
(30 mL) was added at 40—60 °С by Et3N (0.3 mL). The reaction
mixture was refluxed with stirring for 30 min and then stored for
24 h at 20 °С. A precipitate was filtered off and washed with
EtOH and hexane (see Tables 3 and 4).
Synthesis of compounds 3b,d (general procedure). В. A soluꢀ
tion of equimolar amounts of compound 7a,b (0.01 mol) and
malononitrile 6 (0.01 mol) in EtOH (30 mL) was added at
40—60 °С by Et3N (0.3 mL). The reaction mixture was refluxed
with stirring for 30 min and then stored for 24 h at 20 °С. A
precipitate was filtered off and washed with EtOH and hexane
(see Tables 3 and 4).
Synthesis of compounds 3b—d,g,i—r (general procedure).
C. A solution of equimolar amounts of compound 1 (1.64 g,
0.01 mol), aldehyde 10a—n (0.01 mol), and malononitrile 6
(0.01 mol) in EtOH (30 mL) was added at 40—60 °С by Et3N
(0.3 mL). The reaction mixture was refluxed with stirring
for 30 min and then stored for 24 h at 20 °С. A precipiꢀ
tate was filtered off and washed with EtOH and hexane (see
Tables 3 and 4).
The IR spectra of compounds 3 are characterized by
the absorption bands of deformation and stretching
vibrations of the amino group at 1623—1650 and
3180—3460 cm–1, respectively. The absorption bands
of vibrations of the conjugated cyano groups in the
enaminonitrile fragment of the aniline cycle appear at
1
2208—2230 cm–1. The Н NMR spectroscopic data do
not contradict the structure of annelated anilines 3. For
example, along with signals of the protons of the methoxy
group (δ 3.74—3.98) and aryl substituent (δ 6.68—8.85),
the Н NMR spectrum contains the characteristic modꢀ
erately broadened signal from the protons of the amino
group at δ 6.41—6.60.
The IR spectra of compounds 13 manifest absorption
bands of deformation and stretching vibrations of the
amino group at 1654—1655 and 3215—3472 cm–1, reꢀ
spectively. The absorption bands of the conjugated cyano
groups of the enaminonitrile fragment in the pyran cycle
are detected in the 2224—2227 cm–1 interval. A similar
pattern is observed in the IR spectra of benzannelated
2ꢀaminoꢀ4Нꢀpyrans.7—9
The 1Н NMR spectroscopic data agree with the strucꢀ
ture of annelated pyrans 13. For example, the H NMR
spectrum contains the characteristic signal of С(4)Н as
1
1

968
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Shestopalov and Naumov
Synthesis of compounds 13a—c (general procedure). А. A soꢀ
azotistykh geterotsiklov i alkanov" [Abstrs. 1st Intern. Conf.
"Chemistry and Biological Activity of Nitrogenꢀcontaining
Geterocycles and Alkaloid] (Moscow, October 9—12, 2000),
Iridium Press, Moscow, 2001, 1, 247 (in Russian).
2. V. S. Velezheva, K. V. Nevskii, and N. N. Suvorov, Khim.
Geterotsikl. Soedin., 1985, 230 [Chem. Heterocycl. Compd.,
1985, 21, 235 (Engl. Transl.)].
lution of equimolar amounts of compound 1 (1.50 g, 0.01 mol)
and arylmethylidenemalononitrile 2a,b,e (0.01 mol) in EtOH
(30 mL) was added at 40—60 °С by Et3N (0.3 mL). The reaction
mixture was stored for 24 h at 20 °С. A precipitate was filtered
off, washed with EtOH and hexane, and recrystallized from
MeCN (see Tables 5 and 6).
Synthesis of compounds 13b,f (general procedure). В. A soluꢀ
tion of equimolar amounts of compound 15a,b (0.01 mol) and
malononitrile 6 (0.01 mol) in EtOH (30 mL) was added at
40—60 °С by Et3N (0.3 mL). The reaction mixture was stored
for 24 h at 20 °С. A precipitate was filtered off, washed with EtOH
and hexane, and recrystallized from MeCN (see Tables 5 and 6).
Synthesis of compounds 13b,d,e,f (general procedure). С.
A solution of equimolar amounts of compound 1 (1.50 g,
0.01 mol), aldehyde 10c,f,d,m (0.01 mol), and malononitrile 6
(0.01 mol) in EtOH (30 mL) was added at 40—60 °С by Et3N
(0.3 mL). The reaction mixture was stored for 24 h at 20 °С.
A precipitate was filtered off, washed with EtOH and hexane,
and recrystallized from MeCN (see Tables 5 and 6).
3. O. Naumov and A. Shestopalov, Abstrs. 7th Blue Danube
Symp. on Heterocyclic Chemistry (Eger, Hungary, 1998), Eger,
1998, 124.
4. C. J. Adams and L. Main, Tetrahedron, 1991, 47, 4979.
5. Yu. A. Sharanin, V. K. Promonenkov, and V. P. Litvinov,
Malononitril, Itogi nauki i tekhniki, Ser. Organicheskaya
khimiya [Malononitrile, Advances in Science and Technology,
Ser. Organic Chemistry], VINITI, Moscow, 1991, 20, Part 1,
239 pp. (in Russian).
6. M. Dewar and R. Doherti, Teoriya vozmushchenii
molekulyarnykh orbitalei v organicheskoi khimii [Perturbation
Theory of Molecular Orbitals in Organic Chemistry], Mir,
Moscow, 1977, 273 pp. (Russ. Transl.).
Synthesis of compounds 15a,b (general procedure). A soluꢀ
tion of equimolar amounts of compound 12 (1.50 g, 0.01 mol)
and aldehyde 10a,b (0.01 mol) in EtOH (30 mL) was added at
40—60 °С by Et3N (0.3 mL). The reaction mixture was stored
for 24 h at 20 °С. A precipitate was filtered off and washed with
EtOH and hexane (see Tables 7 and 8).
7. Yu. A. Sharanin, V. K. Promonenkov, and L. G. Sharanina,
Zh. Org. Khim., 1982, 18, 625 [J. Org. Chem. USSR, 1982, 18,
544 (Engl. Transl.)].
8. Yu. A. Sharanin, L. N. Shcherbina, L. G. Sharanina, and
V. V. Puzanova, Zh. Org. Khim., 1983, 19, 164 [J. Org. Chem.
USSR, 1983, 19, 150 (Engl. Transl.)].
9. M. S. Chauhan and I. W. J. Still, Can. J. Chem., 1975,
53, 2880.
10. A. Blom and J. Tambor, Ber., 1905, 38, 3590.
11. C. Hansch and H. G. Lindwell, J. Org. Chem., 1945, 10, 383.
References
1. V. S. Velezheva, D. E. Gedz´, D. V. Gusev, A. S. Peregudov,
B. V. Lekshin, and Z. S. Klemenkova, Tez. dokl.
1ꢀi Mezhdunar. konf. "Khimiya i biologicheskaya aktivnost´
Received October 2, 2002;
in revised form December 19, 2002