Synthesis of substituted 2-amino-3-cyano-7,9-dimethyl-4H-pyrano[2′, 3′:4,5]thieno[2,3-b]pyridines

Article abstract of DOI:10.1023/A:1024835412937

4,6-Dimethyl-2H-thieno[2,3-b]pyridin-3-one reacts with 2-aryl-1,1- dicyanoethylenes or an aromatic aldehyde/ketone (cyclohexanone and piperidone derivatives) and malononitrile to give substituted 2-amino-3-cyano-7,9-dimethyl- 4H-pyrano[2′,3′:4,5]thieno[2,

Full text of DOI:10.1023/A:1024835412937

1380
Russian Chemical Bulletin, International Edition, Vol. 52, No. 6, pp. 1380—1385, June, 2003
Synthesis of substituted 2ꢀaminoꢀ3ꢀcyanoꢀ7,9ꢀdimethylꢀ4Hꢀ
pyrano[2´,3´:4,5]thieno[2,3ꢀb]pyridines
ꢀ
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
4,6ꢀDimethylꢀ2Hꢀthieno[2,3ꢀb]pyridinꢀ3ꢀone reacts with 2ꢀarylꢀ1,1ꢀdicyanoethylenes or
an aromatic aldehyde/ketone (cyclohexanone and piperidone derivatives) and malononitrile to
give substituted 2ꢀaminoꢀ3ꢀcyanoꢀ7,9ꢀdimethylꢀ4Hꢀpyrano[2´,3´:4,5]thieno[2,3ꢀb]pyridines.
Key words: 4,6ꢀdimethylꢀ2Hꢀthieno[2,3ꢀb]pyridinꢀ3ꢀone, 2ꢀarylꢀ1,1ꢀdicyanoethylenes,
malononitrile, threeꢀcomponent condensation.
Scheme 1
Regioꢀ and stereoselective methods for the synthesis
of substituted 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Hꢀpyrans are
under extensive development because of biological activiꢀ
ties of these compounds.1—9 2ꢀAminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ
4Hꢀpyrans fused with fragments of coumarin10 and subꢀ
stituted benzenes,11 quinolines,12 naphthalenes,13 and
pyrazolones,14,15 which exhibit anticoagulating, antiꢀ
sclerotic, anticancer, and other practically important
properties, are of the greatest interest as biologically acꢀ
tive compounds.
Earlier, it was found that 1ꢀacetylꢀ1,2ꢀdihydroꢀ3Hꢀ
indolꢀ3ꢀone and 2Hꢀbenzo[b]thiophenꢀ3ꢀone react
with 2ꢀaryl(hetaryl)ꢀ1,1ꢀdicyanoethylenes16,17 to give
2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀsubstituted 4Hꢀpyrano[3,2ꢀb]inꢀ
doles and 4Hꢀbenzo[b]thieno[3,2ꢀb]pyrans. A oneꢀstep
method for the synthesis of these compounds was develꢀ
oped. The method, which involves no preliminary synꢀ
thesis or isolation of unsaturated nitriles, is based on threeꢀ
component condensation of 1ꢀacetylꢀ1,2ꢀdihydroꢀ3Hꢀ
indolꢀ3ꢀone or 2Hꢀbenzo[b]thiophenꢀ3ꢀone with an aroꢀ
matic aldehyde and malononitrile.16,17 With the aim of
further studying the effect of the heteroatom on the direcꢀ
tion of condensation of fiveꢀmembered benzoannelated
heterocyclic ketones with 2ꢀaryl(hetaryl)ꢀ1,1ꢀdicyanoꢀ
ethylenes, we used in this reaction a new ketone, namely,
4,6ꢀdimethylꢀ2Hꢀthieno[2,3ꢀb]pyridinꢀ3ꢀone (1).
The reactions of 4,6ꢀdimethylꢀ2Hꢀthieno[2,3ꢀb]pyriꢀ
dinꢀ3ꢀone (1) with unsaturated nitriles 2 were carried out
in boiling EtOH in the presence of triethylamine for a
short period of time (Scheme 1).17 Under these condiꢀ
tions, the reactions are highly regioselective and afꢀ
ford 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ7,9ꢀdimethylꢀ4Hꢀpyraꢀ
no[2´,3´:4,5]thieno[2,3ꢀb]pyridines (3) in 53—85% yields
(Table 1, method A).
2,3: Ar = Ph (a), 4ꢀFC6H4 (b), 4ꢀClC6H4 (c),
3ꢀNO2C6H4 (d), 4ꢀMeOCOC6H4 (e)
thieno[2,3ꢀb]pyridine 1 gives enolate anion 4, which then
is involved in a Michael reaction with arylmethylideneꢀ
malononitrile 2. In basic media, Michael adduct 5 unꢀ
dergoes intramolecular cyclization into iminopyran 6
(Scheme 2). Subsequent tautomeric conversion yields
4Hꢀpyrano[3´,2´:4,5]thieno[3,2ꢀb]pyridines 3.
The direction of the reaction depends on the nature of
a substituent in arylmethylidenemalononitrile 2. For inꢀ
stance, the reaction easily occurs for
nonsubstituted phenylmethylideneꢀ
malononitrile 2a (Ar = Ph) and its
substituted analogs containing an
acceptor substituent such as a nitro
group (compound 2d) or a haloꢀ
The scheme of this process can be represented as folꢀ
lows. Initially, the reaction of triethylamine with 3ꢀoxoꢀ
gen atom (compounds 2b,c). Arylꢀ
methylidenemalononitriles 2f,g
Ar = 4ꢀMeOC6H4 (f),
3,4ꢀ(MeO)2C6H3 (g)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1306—1311, June, 2003.
1066ꢀ5285/03/5206ꢀ1380 $25.00 © 2003 Plenum Publishing Corporation

Pyrano[2´,3´:4,5]thieno[2,3ꢀb]pyridines
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 6, June, 2003
1381
Table 1. Physicochemical characteristics of compounds 3
Comꢀ
pound
3
Ar
Yield
(%)
(method)
M.p.
/°C
Found
Calculated
Molecular
formula
MS,
m/z ([M]+)
(%)
N
C
H
S
a
b
c
d
e
f
Ph
68 (A), 256—258
59 (B)
85 (A), 289—291
76 (B)
87 (A), 280—282
78 (B)
74 (A), 245—247
65 (B)
68.51
68.45
64.81
64.94
62.67
62.04
59.93
60.31
63.82
64.43
64.34
64.94
59.83
59.84
62.37
62.04
55.02
55.35
64.82
64.65
59.82
60.15
4.31
4.53
3.89
4.02
4.13
3.84
3.59
3.73
4.43
4.38
3.75
4.02
3.81
3.52
3.57
3.84
3.57
3.42
4.43
4.22
3.43
3.86
12.45
12.60
12.10
11.96
11.15
11.42
14.71
14.81
10.94
10.73
11.75
11.96
10.23
10.47
11.20
11.42
10.55
10.19
16.29
16.75
12.64
12.38
9.52
9.62
9.00
9.13
8.78
8.72
8.37
8.47
8.15
8.19
9.01
9.13
7.85
7.99
8.80
8.72
7.65
7.78
9.51
9.59
18.85
18.89
C19H15N3OS
333
351
4ꢀFC6H4
C19H14FN3OS
C19H14ClN3OS
C19H14N4O3S
C21H17N3O3S
C19H14FN3OS
C20H14F3N3OS
C19H14ClN3OS
C19H14BrN3OS
C18H14N4OS
4ꢀClC6H4
3ꢀNO2C6H4
4ꢀMeOCOC6H4
3ꢀFC6H4
368
378
60 (A), 283—285
72 (B)
391
57 (B)
61 (B)
61 (B)
69 (B)
72 (B)
53 (B)
273—275
245—247
294—296
275—277
>300
351
g
h
i
2ꢀCF3C6H4
2ꢀClC6H4
4ꢀBrC6H4
3ꢀC5H4N
401
368
411, 413
334
j
k
2ꢀC4H3S
228—230
C17H13N3OS2
339
Scheme 2
4HꢀPyrano[3´,2´:4,5]thieno[3,2ꢀb]pyridines 3 can
be obtained by a simpler method (method B) in one
step by threeꢀcomponent condensation of 3ꢀoxothieꢀ
no[2,3ꢀb]pyridine 1, malononitrile 7, and a correspondꢀ
ing aldehyde 8 (Scheme 3). In this case, the preliminary
synthesis of arylmethylidenemalononitriles 2 is unnecesꢀ
sary. Earlier, threeꢀcomponent condensation was already
used to synthesize substituted 2ꢀaminoꢀ4Hꢀpyrans. Conꢀ
densation of aldehydes, malononitrile, and ethyl acetoacꢀ
etate afforded the corresponding 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyꢀ
anoꢀ5ꢀethoxycarbonylꢀ6ꢀmethylꢀ4Hꢀpyrans.7
Scheme 3
3: Ar = 4ꢀFC6H4 (b), 4ꢀClC6H4 (c), 3ꢀFC6H4 (f), 2ꢀCF3C6H4 (g),
2ꢀClC6H4 (h), 4ꢀBrC6H4 (i), 3ꢀC5H4N (j), 2ꢀC4H3S (k)
8: Ar = 4ꢀFC6H4 (a), 4ꢀClC6H4 (b), 3ꢀFC6H4 (c), 2ꢀCF3C6H4 (d),
2ꢀClC6H4 (e), 4ꢀBrC6H4 (f), 3ꢀC5H4N (g), 2ꢀC4H3S (h)
The reaction was carried out in boiling EtOH in the
presence of triethylamine for a short period of time. Unꢀ
der these conditions, the reaction proceeds regioselectively
to give pyrans 3. Although method B provides lower
yields of the target products than method A (see Table 1),
yet the former yields, taking into account the prelimiꢀ
containing electronꢀdonor substituents (one or two alkoxy
groups) do not enter into the reaction. Probably, this is
due to a reduced electrophilicity of the Cβ atom of an
unsaturated nitrile because of the presence of the elecꢀ
tronꢀreleasing substituents.

1382
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 6, June, 2003
Shestopalov and Naumov
Scheme 4
3ꢀoxothieno[2,3ꢀb]pyridine 1 with ketone 9 and malonoꢀ
nitrile 7 in EtOH (see also Refs. 18, 19) affords, in one
step, compounds 10 in 25—86% yields (Table 2). Spiro
compounds 10 are representatives of a novel class of
heterocyclic systems, namely, piperidineꢀ4ꢀspiroꢀ and
cyclohexaneꢀ4ꢀspiroꢀ(4H )pyrano[2´,3´:4,5]thieꢀ
no[2,3ꢀb]pyridines. The suggested reaction mechanism is
similar to that shown in Scheme 2.
The structures of compounds 3 and 10 were conꢀ
firmed by data from instrumental analytical methods
(Tables 1—4).
The IR spectra of compounds 3 show absorption bands
of the deformation and stretching vibrations of the amino
group at 1647—1670 and 3239—3481 cm–1, respectively.
Absorption bands of the conjugated cyano group of the
enaminonitrile fragment in the pyran ring appear at
2198—2240 cm–1. The pattern is analogous for benzoꢀ
annelated 2ꢀaminoꢀ4Hꢀpyrans.20,21 In the IR spectra of
spiropyrans 10, absorption bands of the deformation
and stretching vibrations of the amino group appear at
1604—1656 and 3116—3460 cm–1, while absorption bands
of the conjugated cyano group of the enaminonitrile fragꢀ
ment in the pyran ring appears at 2180—2208 cm–1. The
IR spectra of compounds 10i—l contain an absorption
band at 1636—1694 cm–1 for the carbonyl group of the
acylamide fragment.
9,10: X = CH2 (a), CH—Me (b), CH—Et (c), CH—But (d),
N—Me (e), N—Et (f), N—Prn (g), N—Pri (h), N—Ac (i),
N—COOEt (j), N—COOBut (k), N—COOCH2Ph (l)
nary synthesis of unsaturated nitriles 2, are higher by
∼11—17%.
With the goal of synthesizing difficultly accessible
spiro heterocycles, we used ketones (cyclohexanone and
piperidone derivatives 9) instead of aromatic aldehydes in
these reactions (Scheme 4). It was found that heating of
Table 2. Physicochemical characteristics of compounds 10
Comꢀ
pound
10
X
Yield
(%)
M.p.
/°C
Found
Calculated
Molecular
formula
MS,
m/z ([M]+)
(%)
N
C
H
S
a
b
c
d
e
f
CH2
CH—Me
CH—Et
73
51
81
75
71
86
80
64
56
65
63
25
226—228
208—210
196—198
217—219
205—207
175—177
165—167
151—153
259—261
219—221
209—211
145—147
66.18
66.43
67.10
67.23
67.83
67.96
69.31
69.26
63.82
63.50
64.41
64.38
65.07
65.19
65.07
65.19
61.82
61.94
60.52
60.28
61.52
61.95
65.27
65.20
6.13
5.88
6.37
6.24
6.71
6.56
6.60
7.13
5.74
5.92
6.40
6.26
6.71
6.56
6.74
6.56
5.59
5.47
5.68
5.56
6.02
6.14
5.10
5.25
13.16
12.91
12.46
12.38
11.97
11.87
11.42
11.01
16.62
16.46
15.91
15.81
15.31
15.20
15.29
15.20
15.31
15.21
14.49
14.06
12.97
13.14
12.32
12.17
9.40
9.85
9.44
9.45
9.10
9.07
8.66
8.40
9.45
9.42
9.04
9.05
8.72
8.70
8.72
8.70
8.72
8.70
8.46
8.05
7.49
7.52
6.82
6.96
C18H19N3OS
C19H21N3OS
C20H23N3OS
C22H27N3OS
C18H20N4OS
C19H22N4OS
C20H24N4OS
C20H24N4OS
C19H20N4O2S
C20H22N4O3S
C22H26N4O2S
C25H24N4O3S
325
339
353
381
340
354
368
368
368
398
426
460
CH—But
N—Me
N—Et
g
h
i
N—Prn
N—Pri
N—Ac
j
N—COOEt
N—COO—But
N—COOCH2Ph
k
l

Pyrano[2´,3´:4,5]thieno[2,3ꢀb]pyridines
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 6, June, 2003
1383
Table 3. Spectral characteristics of compounds 3
Comꢀ
pound
3
1H NMR, δ
NH2
IR, ν/cm–1
H3C(9)
(s, 3 H)
H3C(7)
(s, 3 H)
H(4)
H(8)
Ar
δ(NH2)
CN
NH2
(s, 1 H) (br.s, 2 H) (s, 1 H)
a
b
2.50
2.50
2.70
2.70
4.90
4.95
6.82
6.90
7.00
7.01
7.25—7.49 (m, 5 H)
7.10—7.16, 7.30—7.35
(both m, 2 H each)
7.35 (m, 4 H)
1660
1660
2212
3300, 3352
2210 3244, 3325,
3476
2210 3240, 3330,
3474
2240 3260, 3358,
3410
2210 3278, 3325,
3398
c
2.50
2.50
2.50
2.70
2.70
2.70
4.95
5.03
5.02
6.95
6.88
6.96
7.01
7.04
7.03
1660
1670
1662
d
7.40—7.67, 8.45—8.60
(both m, 2 H each)
3.88 (s, 3 H, 4´ꢀOMe);
7.41, 7.99 (both d, 2 H each,
J = 8.17 Hz)
e*
f
2.50
2.50
2.50
2.50
2.50
2.50
2.70
2.70
2.70
2.70
2.70
2.70
4.98
5.22
5.42
4.95
5.01
3.88
6.85
6.98
6.99
6.90
6.87
7.01
7.01
7.01
7.05
7.01
7.07 (s, 1 H);
7.15—7.41 (m, 3 H)
7.41—7.71
(m, 4 H)
7.25—7.48
(m, 4 H)
7.15—7.31, 7.40—7.60
(both m, 2 H each)
7.30—7.38, 7.60—7.70 (both m, 1658
1 H each); 8.45—8.58 (m, 2 H)
6.90 (br.s, 2 H);
7.32 (br.s, 1 H)
1662
1657
1647
1661
2210 3245, 3332,
3481
2218 3247, 3321,
3468
2213 3334, 3460,
3618
2215 3239, 3320,
3448
g
h
i
j
2198
3292, 3370
k
6.50
1665
2214 3250, 3330,
3378
* ν(CO) = 1710 cm–1
.
Table 4. Spectral characteristics of compounds 10
Comꢀ
pound
10
1H NMR, δ
H3C(9) H3C(7)
IR, ν/cm–1
X(—CH2—)
NH2
H(8) δ(NH2)
CO
CN
NH2
(s, 3 H) (br.s, 2 H) (s, 1 H)
a
b
1.40—1.90
(m, 10 Н, CH2)
1.05 (s, 3 H, CHCH3);
1.45—1.80 (m, 5 H,
CHCH3, CH2);
2.52
(s, 3 H)
2.55
2.70
2.65
6.50
6.49
6.99
6.99
1654
1656
—
—
2184 3172, 3270,
3312
2184 3124, 3302,
3348
(s, 3 H)
1.90 (s, 4 H, CH2)
c
0.97 (t, 3 H, CH2CH3,
J = 1.0 Hz); 1.35—1.90 (m, 11 H,
CH2, CH2CH3, CH2)
2.50
(s, 3 H)
2.69
6.49
6.99
1644
—
2188 3176, 3312,
3418
(to be continued)

1384
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 6, June, 2003
Shestopalov and Naumov
Table 4 (continued)
Comꢀ
pound
10
1H NMR, δ
H3C(9) H3C(7)
IR, ν/cm–1
X(—CH2—)
NH2
H(8) δ(NH2)
CO
CN
NH2
(s, 3 H) (br.s, 2 H) (s, 1 H)
d*
0.90—1.00 (m, 10 H, CH,
(CH3)3C(4´)); 1.10—1.20
(m, 1 H, CH); 1.55—2.03
(m, 6 H, CH);
2.50
(s, 3 H)
2.61
6.51
6.99
1646
—
2196 3380, 3316,
3460
2.10—2.20 (m, 1 H, CH)
e**
f
1.80—1.90, 2.05—2.20 (both m, 2 H each, CH2); 2.65
2.45—2.60 (m, 8 H, H3C(1´), CH, H3C(9));
2.68—2.82 (m, 2 H, CH)
1.10 (t, 3 H, CH2CH3, J = 7.2 Hz); 1.80—1.92, 2.65
2.02—2.18 (both m, 2 H each, CH2); 2.40—2.60
(m, 7 H, 1´ꢀCH2CH3, CH,H3C (9));
6.60
6.70
7.00
7.00
1640
1638
—
—
2184 3168, 3304,
3400
2180 3116, 3296,
3412
2.80—2.90 (m, 2 H, CH)
g
0.95 (t, 3 H, CH3CH2CH2, J = 6.9 Hz); 1.55
(q, 2 H, CH2CH2CH3); 1.80—1.91, 2.00—2.15,
2.30—2.42 (all m, 2 H each, CH); 2.50—2.70
(m, 5 H, CH2CH2CH3, H3C (9));
2.65
6.62
6.99
1648
—
—
2196
2184
3198, 3344
3180, 3320
2.79—2.90 (m, 2 H, CH)
h
i
1.05 (d, 6 H, CH3CHCH3); 1.80—1.91,
2.00—2.11 (both m, 2 H each, CH); 2.50—2.58
(s, 5 H, CH, H3C (9)); 2.70—2.87
2.62
2.62
6.65
7.00
7.00
7.10
1654
1604
(m, 3 H, CH3CHCH3, CH)
1.80—2.01 (m, 4 H, CH); 2.06
(s, 3 H, 1´ꢀCOCH3); 3.20—3.38
(m, 1 H, CH); 3.48—3.68,
2.50
(s, 3 H)
1636 2184 3160, 3304,
3388
3.78—3.92 (both m, 1 H each, CH);
4.11—4.30 (m, 1 H, CH)
j
1.30 (t, 3 H, OCH2CH3,
J = 7.1 Hz); 1.85—2.05
(m, 4 H, CH); 3.35—3.50
(m, 4 H, CH); 4.10 (2 H,
q, OCH2CH3)
2.51
(s, 3 H)
2.65
6.82
7.00
1642
1680 2188 3176, 3284,
3456
k*** 1.48 (s, 9 H, (CH3)3C(4´));
1.81—2.09 (m, 4 H, CH);
3.35—3.50, 3.87—4.00
2.51
(s, 3 H)
2.65
2.68
6.75
6.84
7.00
7.01
1654
1656
1686 2188 3216, 3324,
3380
(both m, 2 H each, CH)
l
1.85—2.10 (m, 4 H, CH); 3.50
(br.s, 2 H, CH); 3.95—4.10
(m, 2 H, CH); 5.10 (s, 2 H,
COOCH2C6H5); 7.28 (s, 5 H,
COOCH2C6H5)
2.52
(s, 3 H)
1694 2208 3212, 3328,
3424
The ratio of axial/equatorial atoms is *1 : 1, **1 : 7, and ***1 : 5.
1
The H NMR data confirmed the structures of pyrꢀ
broadened singlet at δH 6.49—7.01 and of the protons of a
hydrogenated heterocycle at δH 0.90—4.10.
ans 3. Thus, along with signals for the aryl fragment at
δH 6.90—8.60, the 1H NMR spectrum shows a signal
characteristic of C(4)H as a singlet at δH 3.88—5.42. Sigꢀ
nals for the protons of an amino group appear as a broadꢀ
ened singlet at δH 6.82—6.96.
Experimental
Melting points of the products obtained were determined on
a Kofler stage. IR spectra were recorded on a Specord IRꢀ75
1
The H NMR spectra of compounds 10 contain sigꢀ
1
nals characteristic of the protons of an amino group as a
instrument (KBr pellets). H NMR spectra were recorded on a

Pyrano[2´,3´:4,5]thieno[2,3ꢀb]pyridines
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 6, June, 2003
1385
Bruker Mꢀ300 instrument. The course of the reaction was moniꢀ
tored and the purity of the products was checked by TLC on
Silufol UVꢀ254 plates.
6. J. L. Mareo, N. Martin, A. MartmezꢀGrau, C. Seoane,
A. Albert, and P. H. Cano, Tetrahedron, 1994, 50, 3509.
7. A. M. Shestopalov, Z. I. Nijazimbetova, D. H. Evans, and
M. E. Nijazimbetov, Heterocycles, 1999, 51, 1101.
8. A. M. Shestopalov, Y. M. Emeliyanova, A. A. Shestopalov,
L. A. Rodinovskaya, Z. I. Nijazimbetova, and D. H. Evans,
Org. Lett., 2002, 4, 423.
9. V. S. Velezheva, D. E. Gedz´, D. V. Gusev, A. S. Peregudov,
B. V. Lekshin, and Z. S. Klemenkova, Abstrs., Pervaya
mezhdunarodnaya konferentsiya "Khimiya i biologicheskaya
aktivnost´ azotistykh geterotsiklov i alkaloidov" [1st Int. Conf.
"Chemistry and Biological Activity of Nitrogeneous Heterocycles
and Alkaloids"] (Moscow, October 9—12, 2000), Iridiumꢀ
Press, Moscow, 2001, 1, 247 (in Russian).
Compound 1 was prepared as described earlier.22
Synthesis of compounds 3a—e (general procedure). A. Triꢀ
ethylamine (0.3 mL) was added at 40—60 °C to a solution of
equimolar amounts of compound 1 (1.79 g, 0.01 mol) and
arylmethylidenemalononitrile 2a—e (0.01 mol) in 30 mL of
EtOH. The reaction mixture was kept at 20 °C for 24 h, and the
precipitate that formed was filtered off, washed with EtOH and
hexane, and recrystallized from MeCN (see Tables 1, 3).
Synthesis of compound 3b,c,d,f—k (general procedure). B.
Triethylamine (0.3 mL) was added at 40—60 °C to a solution of
equimolar amounts of compound 1 (1.79 g, 0.01 mol), aldehyde
8a—h (0.01 mol), and malononitrile 7 (0.01 mol) in 30 mL of
EtOH. The reaction mixture was kept at 20 °C for 24 h, and the
precipitate that formed was filtered off, washed with EtOH and
hexane, and recrystallized from MeCN (see Tables 1, 3).
Synthesis of compounds 10a—l (general procedure). Triethylꢀ
amine (0.3 mL) was added at 40—60 °C to a solution of equimoꢀ
lar amounts of compound 1 (1.79 g, 0.01 mol), ketone 9a—l
(0.01 mol), and malononitrile 7 (0.01 mol) in 30 mL of EtOH.
The reaction mixture was kept at 20 °C for 24 h, and the precipiꢀ
tate that formed was filtered off, washed with EtOH and hexane,
and recrystallized from MeCN (see Tables 2, 4).
10. US Pat. 3 097 213; Ref. Zh., Khim. (Abstract Journal, Chemꢀ
istry), 1965, 12 N 257P (in Russian).
11. Eur. Pat. 758 647; Chem. Abstrs., 1997, 126, 225216v.
12. Eur. Pat. 695 547; Chem. Abstrs., 1995, 122, 23835c.
13. RF Pat. 2 125 573; Chem. Abstrs., 1999, 121, 108765j.
14. K. C. Joslhi, R. Jain, and S. Arora, J. Ind. Chem. Soc., 1988,
65, 277.
15. C. N. O’Callaghan, T. B. N. McMurry, and J. E. O’Brien,
J. Chem. Soc., Perkin Trans. 1, 1995, 417.
16. A. M. Shestopalov, O. A. Naumov, and V. N. Nesterov, Izv.
Akad. Nauk, Ser. Khim., 2003, 169 [Russ. Chem. Bull., Int.
Ed., 2003, 52, 179].
17. A. M. Shestopalov and O. A. Naumov, Izv. Akad. Nauk, Ser.
Khim., 2003, 911 [Russ. Chem. Bull., Int. Ed., 2003, 52, 961].
18. O. A. Naumov and A. M. Shestopalov, Abstrs.,
2ꢀya Molodezhnaya nauchnaya shkola po organicheskoi khimii
[2nd Junior Scientific School on Organic Chemistry]
(Ekaterinburg, May 2—6, 2000), Ekaterinburg, 2000, 134 (in
Russian).
19. O. A. Naumov and A. M. Shestopalov, Abstrs.,
3ꢀi Vserossiiskii simpozium "Strategiya i taktika organicheskogo
sinteza" [3rd AllꢀRussia Symp. "Strategy and Tactics of Orꢀ
ganic Synthesis"] (Yaroslavl´, March 3—7, 2001), Yaroslavl´,
2001, 80 (in Russian).
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Received November 11, 2002;
in revised form January 31, 2003