One-step synthesis of 5-acetyl-2-amino-4-aryl-3-cyano-4H-pyrano[3,2-b] indoles. Molecular and crystal structure of 5-acetyl-2-amino-4-(4′-chloro- 3′-nitrophenyl)-3-cyano-4H-pyrano[3,2-b]indole

Article abstract of DOI:10.1023/A:1022468903806

A one-step procedure was developed for the synthesis of 5-acetyl-2-amino-4-aryl-3-cyano-4H-pyrano[3,2-b]indoles involving the three-component reaction of 1-acetylindol-3(2H)-one with aromatic aldehydes and malononitrile in ethanol in the presence of triethylamine as the catalyst. The structure of 5-acetyl-2-amino-4-(4′-chloro-34′-nitrophenyl)-3-cyano- 4H-pyrano[3,2-b]indole was established by X-ray diffraction analysis.

Full text of DOI:10.1023/A:1022468903806

Russian Chemical Bulletin, International Edition, Vol. 52, No. 1, pp. 179—186, January, 2003
179
Oneꢀstep synthesis of 5ꢀacetylꢀ2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ
4Hꢀpyrano[3,2ꢀb]indoles. Molecular and crystal structure of 5ꢀacetylꢀ
2ꢀaminoꢀ4ꢀ(4´ꢀchloroꢀ3´ꢀnitrophenyl)ꢀ3ꢀcyanoꢀ4Hꢀpyrano[3,2ꢀb]indole
A. M. Shestopalov,a O. A. Naumov,a and V. N. Nesterovb
aN. 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
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5085. Eꢀmail: vlad@kremlin.nmhu.edu
A oneꢀstep procedure was developed for the synthesis of 5ꢀacetylꢀ2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ
4Hꢀpyrano[3,2ꢀb]indoles involving the threeꢀcomponent reaction of 1ꢀacetylindolꢀ3(2H )ꢀone
with aromatic aldehydes and malononitrile in ethanol in the presence of triethylamine as the
catalyst. The structure of 5ꢀacetylꢀ2ꢀaminoꢀ4ꢀ(4´ꢀchloroꢀ3´ꢀnitrophenyl)ꢀ3ꢀcyanoꢀ4Hꢀ
pyrano[3,2ꢀb]indole was established by Xꢀray diffraction analysis.
Key words: 1ꢀacetylindolꢀ3(2H )ꢀone, 5ꢀacetylꢀ2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Hꢀpyraꢀ
no[3,2ꢀb]indoles, threeꢀcomponent reaction, Xꢀray diffraction analysis.
Substituted 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Hꢀpyrans exꢀ
hibit biological activities, which gave impetus to the exꢀ
tensive development of regioꢀ and stereoselective proceꢀ
dures for the synthesis of these compounds.1—9 From this
viewpoint, 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Hꢀpyrans annelated
with fragments of coumarin,10 substituted benzenes,11
quinolines,12 naphthalene,13 and pyrazolone,14,15 which
exhibit anticoagulant, antisclerotic, antitumor activities,
and other practically important properties, are of most
interest. Of particular interest are pyrans annelated with
another biologically active molecule, viz., indole.9,16 The
latter compounds were prepared by condensation of
1ꢀacetylindolꢀ3(2H )ꢀone (1) with aromatic aldehydes folꢀ
lowed by the reactions of the resulting 1ꢀacetylꢀ2ꢀarylꢀ
ideneꢀ1Hꢀindolꢀ3ꢀones with malononitrile.
EtOH in the presence of Et3N over a short period of
time.18 Under these conditions, the reactions proceeded
with high regioselectivity to give 5ꢀacetylꢀ2ꢀaminoꢀ4ꢀarylꢀ
3ꢀcyanoꢀ4Hꢀpyrano[3,2ꢀb]indoles 2a—j in good yields
(Scheme 1, Tables 1 and 2, method A).
Scheme 1
With the aim of developing simpler procedures for the
synthesis of substituted pyrano[3,2ꢀb]indoles 2, we studꢀ
ied the reactions of 1ꢀacetylindolꢀ3(2H)ꢀone (1) with unꢀ
saturated nitriles 3 and investigated the threeꢀcomponent
reaction of compound 1, aromatic aldehydes 4, and
malononitrile 5. Earlier, products of the reaction of
indolone 1 with malononitrile 5 have been erroneously
assigned the structures of acyclic Michael adducts.17 Later
on, their structures were corrected.16 To reliably establish
the structures of these products, we studied these comꢀ
pounds by various physicochemical methods, including
Xꢀray diffraction analysis.
2,3: R = Ph (a), 2ꢀFC6H4 (b), 3ꢀFC6H4 (c), 4ꢀFC6H4 (d),
2ꢀClC6H4 (e), 4ꢀClC6H4 (f), 3ꢀBrC6H4 (g), 2ꢀNO2C6H4 (h),
3ꢀpyridyl (i), 2ꢀC4H2SBrꢀ5 (j)
The reactions of 1ꢀacetylindolꢀ3(2H )ꢀone (1) with
unsaturated nitriles 3a—j were carried out on heating in
Initially, treatment of 1ꢀacetylindolꢀ3(2H )ꢀone (1)
with triethylamine affords enolate anion 6 (Scheme 2),
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 169—175, January, 2003.
1066ꢀ5285/03/5201ꢀ179 $25.00 © 2003 Plenum Publishing Corporation

180
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
Shestopalov et al.
Table 1. Physicochemical characteristics and massꢀspectrometric data for compounds 2a—w
Comꢀ
pound
R
M.p./°C
Yield (%)
(method)
Found
Calculated
Molecular
formula
MS,
m/z ([M]+)
(%)
C
H
N
2a
2b
2c
2d
2e
2f
Ph
313—315
285—287
280—282
276—278
294—296
260—262
273—275
263—265
268—269
59 (A)
80 (B)
73.06
72.95
4.87
4.56
11.43
12.77
C20H15N3O2
329
2ꢀFC6H4
3ꢀFC6H4
4ꢀFC6H4
2ꢀClC6H4
4ꢀClC6H4
3ꢀBrC6H4
2ꢀNO2C6H4
51 (A)
68.91
69.16
4.31
4.03
12.45
12.10
C20H14FN3O2
C20H14FN3O2
C20H14FN3O2
C20H14ClN3O2
C20H14ClN3O2
C20H14BrN3O2
C20H14N4O4
347
347
347
364
364
408
374
330
56 (A)
69.34
69.16
3.75
4.03
11.75
12.10
76 (A)
69 (B)
68.81
69.16
3.89
4.03
12.50
12.10
63 (A)
66.37
66.02
3.57
3.85
11.20
11.55
90 (A)
73 (B)
65.85
66.02
3.57
3.85
11.90
11.55
2g
2h
2i
71 (A)
59 (A)
91 (A)
58.65
58.82
3.45
3.43
10.34
10.29
64.52
64.17
4.02
3.74
14.62
14.97
68.84
69.09
3.96
4.24
17.32
16.97
C19H14N4O2
2j
257—259
271—273
279—281
271—273
257—259
291—293
255—257
268—270
274—276
18 (A)
26 (B)
52.52
52.17
3.18
2.90
10.49
10.14
C18H12BrN3O2S
C21H14F3N3O2
C20H14ClN3O2
C20H13Cl2N3O2
C20H13Cl2N3O2
C20H14BrN3O2
C20H14BrN3O2
C20H13BrFN3O2
C20H14N4O4
414
397
364
397
397
408
408
426
374
409
330
2k
2l
2ꢀCF3C6H4
3ꢀClC6H4
44 (B)
57 (B)
67 (B)
81 (B)
54 (B)
82 (B)
46 (B)
61 (B)
95 (B)
55 (B)
63.83
63.48
3.81
3.53
10.23
10.58
65.67
66.02
4.13
3.85
11.15
11.55
2m
2n
2o
2p
2q
2r
2s
2t
2,3ꢀCl2C6H3
2,4ꢀCl2C6H3
2ꢀBrC6H4
60.28
60.45
2.99
3.27
10.18
10.58
60.10
60.45
3.56
3.27
10.23
10.58
58.47
58.82
3.71
3.43
9.89
10.29
4ꢀBrC6H4
58.77
58.82
3.48
3.43
10.31
10.29
5ꢀBrꢀ2ꢀFꢀC6H3
3ꢀNO2C6H4
56.52
56.34
3.33
3.05
10.86
9.86
63.82
64.17
3.46
3.74
14.62
14.97
4ꢀClꢀ3ꢀNO2ꢀC6H3 266—268
251—253
58.93
58.75
3.04
3.18
13.36
13.71
C20H13ClN4O4
C19H14N4O2
68.87
69.09
4.19
4.24
16.86
16.97
2u
269—271
295—297
67 (B)
64.83
64.48
4.16
3.88
12.19
12.54
C18H13N3O2S
335
2v
72 (B)
72 (B)
64.31
64.48
3.60
3.88
12.89
12.54
C18H13N3O2S
C22H17N3O4
335
387
2w
4ꢀMeOOCC6H4
273—275
67.87
68.22
4.69
4.39
10.50
10.85

Oneꢀstep synthesis of 4Hꢀpyrano[3,2ꢀb]indoles
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
181
Table 2. Spectroscopic characteristics of compounds 2a—w*
Comꢀ
pound
1H NMR, δ (J/Hz)
IR, ν/cm–1
COMe
H(4)
NH2
H arom.
δ(NH2) CO CN
NH2
(s, 3 H) (s, 1 H) (br.s, 2 H)
2a
2b
2.48
2.58
5.24
5.62
6.78
6.75
7.02—7.10 (m, 2 H); 7.21—7.45 (m, 5 H); 7.61 (d,
1 H, H(9), J = 8.6); 8.08 (d, 1 H, H(6), J = 7.8)
1665
1668
1687 2220 3216, 3250,
3324, 3378
6.90—6.95 (m, 1 H); 7.05—7.12 (m, 2 H); 7.20—7.25
(m, 1 H); 7.38 (t, 2 H, J = 5.5); 7.61 (d, 1 H, H(9),
J = 8.6); 7.98 (d, 1 H, H(6), J = 7.8)
1695 2218 3210, 3248,
3321, 3375
2c
2d
2e
2.58
2.52
2.50
5.35
5.31
5.75
6.78
6.89
6.72
6.90—6.69 (m, 3 H); 7.29—7.40 (m, 3 H); 7.61 (d,
1 H, H(9), J = 8.6); 8.00 (d, 1 H, H(6), J = 7.8)
1665
1667
1664
1697 2217 3218, 3250,
3332, 3380
7.00—7.18 (m, 4 H); 7.33—7.49 (m, 2 H); 7.59 (d,
1 H, H(9), J = 8.6); 8.01 (d, 1 H, H(6), J = 7.8)
1700 2221 3218, 3258,
3323, 3390
6.90 (s, 1 H); 7.11—7.20 (m, 2 H);
7.35—7.40 (m, 3 H); 7.60 (d, 1 H, H(9), J = 8.6);
7.98 (d, 1 H, H(6), J = 7.8)
1702 2220 3208, 3246,
3320, 3380
2f
2.4
5.28
5.28
6.15
6.83
6.79
6.80
7.03—7.10 (m, 2 H); 7.25—7.41 (m, 4 H); 7.60 (d,
1 H, H(9), J = 8.6); 7.98 (d, 1 H, H(6), J = 7.8)
1667
1662
1669
1695 2219 3220, 3250,
3322, 3387
2g
2h
2.52
2.58
7.03 (d, 1 H, J = 8.3); 7.20—7.42 (m, 5 H); 7.61 (d,
1 H, H(9), J = 8.6); 7.98 (d, 1 H, H(6), J = 7.8)
1691 2208 3219, 3251,
3330, 3393
7.12 (d, 1 H, J = 7.76); 7.33—7.42 (m, 3 H);
7.50—7.63 (m, 2 H); 7.80 (d, 1 H, H(9), J =8.6);
7.95 (d, 1 H, H(6), J = 7.8)
1700 2218 3210, 3240,
3320, 3420
2i
2.58
5.31
6.80
7.23—7.45 (m, 4 H); 7.60 (d, 1 H, H(9), J = 8.6);
7.92 (d, 1 H, H(6), J = 7.8);
1666
1696 2215 3215, 3252,
3338, 3370
8.30—8.45 (m, 2 H, H(6), H(2))
2j
2.67
2.58
2.52
2.58
2.40
5.60
5.78
5.28
5.85
5.72
6.72
6.78
6.80
6.88
6.80
6.90—7.10, 7.25—7.48 (both m, 2 H each); 7.58 (d,
1 H, H(9), J = 8.6); 7.98 (d, 1 H, H(6), J = 7.8)
1660
1666
1663
1663
1664
1700 2210 3210, 3240,
3322, 3400
2k
2l
7.03 (d, 1 H, J = 7.1); 7.40—7.49 (m, 4 H);
7.60—7.70 (m, 2 Н); 7.83 (d, 1 H, H(6), J = 7.8)
1694 2208 3216, 3250,
3325, 3380
7.00—7.08 (m, 2 H); 7.19—7.42 (m, 4 H); 7.60 (d,
1 H, H(9), J = 8.6); 7.98 (d, 1 H, H(6), J = 7.8)
1694 2215 3210, 3250,
3335, 3388
2m
2n
7.15—7.21 (m, 1 H); 7.32—7.42 (m, 4 H); 7.61 (d,
1 H, H(9), J = 8.6); 7.90 (d, 1 H, H(6), J = 7.8)
1699 2218 3210, 3248,
3323, 3378
6.90—6.97, 7.19—7.25 (both m, 1 H each);
7.31—7.45 (m, 3 H); 7.60 (d, 1 H, H(9), J = 8.6);
7.85 (d, 1 H, H(6), J = 7.8)
1704 2224 3208, 3232,
3328, 3360
2o
2p
2q
2r
2s
2t
2.55
2.50
2.62
2.51
2.60
2.53
5.76
5.25
5.58
5.50
5.38
5.27
6.78
6.78
6.90
6.98
7.00
6.87
6.86 (d, 1 H, J = 7.7); 7.13—7.62 (m, 6 H);
7.98 (d, 1 H, H(6), J = 7.7)
1664
1670
1665
1665
1663
1698 2217, 3212, 3248,
3325, 3380
7.00—7.08 (m, 2 H); 7.35—7.44 (m, 4 H); 7.60 (d,
1 H, H(9), J = 8.6); 7.98 (d, 1 H, H(6), J = 7.8)
1690 2210 3250, 3310,
3320, 3370
7.02—7.12 (m, 2 H); 7.35—7.44 (m, 3 H); 7.62 (d,
1 H, H(9), J = 8.6); 7.90 (d, 1 H, H(6), J = 7.8)
1695 2217 3205, 3223,
3242, 3390
7.38—7.64 (m, 5 H); 7.89 (s, 1 H); 7.95 (d, 1 H,
H(9), J = 8.6); 8.10 (d, 1 H, H(6), J = 7.8)
1690 2215 3210, 3250,
3338, 3360
7.35—7.43, 7.63—7.72 (both m, 3 H each);
7.90 (d, 1 H, H(6), J = 7.8)
1696 2220 3215, 3248,
3325, 3395
7.06 (br.s, 2 H, H(2), H(5)); 7.48 (t, 2 H, H(7),
H(8), J = 7.1); 7.61 (d, 1 H, H(9), J = 8.6); 7.93 (d,
1 H, H(6), J = 7.8); 8.45 (br.s, 2 H, H(3), H(5))
1660
1665
1702 2202 3190, 3240,
3320, 3340
1700 2214 3215, 3250,
2u
2.52
5.43
6.75
6.84 (d, 1 H, H(4), J = 5.0); 7.08 (s, 1 H, H(2));
7.30—7.40 (m, 3 H, H(5), H(8), H(7)); 7.59 (d, 1 H,
H(9), J = 8.6); 8.08 (d, 1 H, H(6), J = 7.8)
3330, 3378
(to be continued)

182
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
Shestopalov et al.
Table 2 (continued)
Comꢀ
pound
1H NMR, δ (J/Hz)
H arom.
IR, ν/cm–1
δ(NH2) CO CN
COMe
H(4)
NH2
NH2
(s, 3 H) (s, 1 H) (br.s, 2 H)
2v
2.62
2.53
5.64
5.38
6.68
7.11
6.90 (c, 2 H); 7.22 (c, 1 H); 7.29—7.42 (m, 2 H);
7.60 (d, 1 H, H(9), J = 8.6);
8.03 (d, 1 H, H(6), J = 7.8)
1663
1680
1697 2218 3215, 3245,
3332, 3378
2w
3.83 (s, 3 Н, 4'ꢀCOOMe); 7.14—7.23 (m, 2 H);
7.38—7.49 (m, 2 Н, H(8), H(7)); 7.62 (d, 1 H, H(9),
J = 8.6); 7.92 (m, 2 H); 8.00 (d, 1 H, H(6), J = 7.8)
1700, 2215 3200, 3240,
1670
3320, 3440
* The assignments of the signals for H(9) and H(6) were made based on the experimental data published earlier.19
Scheme 2
which is involved in the Michael reaction with arylꢀ
idenemalononitriles 3. In a basic medium, Michael adꢀ
ducts 7 undergo intramolecular cyclization to give iminoꢀ
pyrans 8. The tautomeric transformation of the latter comꢀ
pounds gives rise to 5ꢀacetylꢀ2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ
4Hꢀpyrano[3,2ꢀb]indoles 2.
The direction of the reaction depends on the nature of
the aryl substituent in arylidenemalononitrile 3. For exꢀ
ample, unsubstituted benzylidenemalononitrile 3a, its subꢀ
stituted analogs containing the nitro group (3h) or haloꢀ
gen atom (3b—g), and derivatives of pyridine (3i) and
thiophene (3j) aldehydes are readily involved in these
reactions. The reactions with arylidenemalononitriles conꢀ
taining one or two alkoxy groups do not proceed at all.
Most likely, this fact is associated with a decrease in the
electrophilicity of the Cβ atom of unsaturated nitrile due
to the presence of electronꢀreleasing substituents.
Pyrans 2 can be prepared according to a simpler oneꢀ
step procedure (without the preliminary synthesis of
arylidenemalononitriles 3), viz., by the threeꢀcomponent
reaction of acetylindolꢀ3(2H )ꢀone 1, malononitrile 5,
and the corresponding aldehyde 4 (Scheme 3, see Table 1,
method B). This reaction has been used earlier for the
synthesis of substituted 2ꢀaminoꢀ4Hꢀpyrans. For example,
condensation of aldehydes, malononitrile, and ethyl acꢀ
etoacetate afforded 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ5ꢀethoxyꢀ
carbonylꢀ6ꢀmethylꢀ4Hꢀpyrans.7
The reaction was carried out on heating in EtOH in
the presence of Et3N over a short period of time. Under
these conditions, the reaction proceeded regioselectively
to form pyrans 2. The latter method gives the target prodꢀ
ucts in lower yields than those obtained according to the
method A. However, taking into account the prelimiꢀ
nary synthesis of unsaturated nitriles 2, these yields are
∼10—15% higher.
Some compounds, in particular, annelated pyran 2t
(R = 4ꢀpyridyl), can be prepared only according to the
method B. Thus, in attempting to prepare unsaturated
nitrile 3 (R = 4ꢀpyridyl) from pyridineꢀ4ꢀcarbaldehyde
(4n) and malononitrile (5), we obtained substituted cycloꢀ
hexene 9 7 (Scheme 4).

Oneꢀstep synthesis of 4Hꢀpyrano[3,2ꢀb]indoles
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
183
Scheme 3
Scheme 4
The structures of compounds 2a—w were confirmed
by physicochemical and spectroscopic methods (see
Tables 1 and 2).
According to the Cambridge Structural Database, data
on the structures of systems containing the annelated
2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Hꢀpyran or 1ꢀacetylindole
fragments analogous to compounds 2 are lacking in the
literature.
Xꢀray diffraction analysis of compound 2s (Fig. 1,
Tables 3 and 4) showed that the substituted 4Hꢀpyran
heterocycle adopts a strongly flattened chair conforꢀ
R = Ph (4a, 2a); 4ꢀFC6H4 (4b, 2d); 4ꢀClC6H4 (4c, 2f);
2ꢀC4H2SBrꢀ5 (4d, 2j); 2ꢀCF3C6H4 (4e, 2k); 3ꢀClC6H4 (4f, 2l);
2,3ꢀCl2C6H3 (4g, 2m); 2,4ꢀCl2C6H3 (4h, 2n);
2ꢀBrC6H4 (4i, 2o); 4ꢀBrC6H4 (4j, 2p); 5ꢀBrꢀ2ꢀFC6H3 (4k, 2q);
3ꢀNO2C6H4 (4l, 2r); 4ꢀClꢀ3ꢀNO2C6H3 (4m, 2s);
4ꢀpyridyl (4n, 2t); 3ꢀC4H3S (4o, 2u); 2ꢀC4H3S (4p, 2v);
4ꢀMeOOCC6H4 (4q, 2w)
Cl(1)
O(3)
C(4´)
N(15)
O(4)
C(5´)
C(3´)
C(2´)
C(6´)
C(1´)
C(11)
O(2)
C(10)
C(4)
C(6)
C(5A)
N(14)
C(7)
N(5)
C(13)
C(4A)
C(3)
C(8)
C(1A)
C(9A)
C(2)
C(9)
O(1)
N(12)
Fig. 1. Molecular structure of 5ꢀacetylꢀ2ꢀaminoꢀ4ꢀ(4´ꢀchloroꢀ3´ꢀnitrophenyl)ꢀ3ꢀcyanoꢀ4Hꢀpyrano[3,2ꢀb]indole (2s).

184
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
Shestopalov et al.
Table 3. Bond lengths (d) in the structure of 2s
and the Ph substituent (C(5A)...C(9A)) are small (6.4 and
4.2°, respectively), which is indicative of a flattening of
the tricyclic fragment as a whole. The twist of the
pseudoaxial aryl substituent with respect to the planar
fragment of the pyran ring is 82.5°. The rotation of the
nitro group with respect to the Ph ring by 44.2° is caused
by the presence of the Cl atom at the adjacent atom
(nonbonded Cl(1)...O(3) distance (2.926(4) Å) is smaller
than the sum of the van der Waals radii of the atoms22). It
should be noted that the aryl substituent is twisted due to
the presence of the nitro group toward the plane of the
heterocycle, i.e., it is in the anti orientation relative to the
H atom at the C(4) atom. The observed spatial arrangeꢀ
ment of the acetyl group gives rise to the O(2)...H(4A)
nonbonded interaction, which can be considered23,24 as
an intramolecular contact (C(4)...O(2), 2.771(4) Å;
C(4)—H(4A), 1.0 Å; O(2)...H(4A), 2.42 Å;
C(4)—H(4A)...O(2) angle, 101°). As can be seen from
Table 3, there is a noticeable redistribution of the bond
lengths in the planar N(12)—C(2)=C(3)—C(13)≡N(14)
fragment, which is attributable to conjugation. The reꢀ
maining geometric parameters of the compounds under
study have the expected values.25 In the crystal, molꢀ
ecules 2s are linked in infinite chains through the interꢀ
molecular hydrogen bonds N(12)—H(12A)...N(14)
(1.5 – x, 3.5 – y, –z) (N(12)...N(14), 3.101(4) Å;
N(12)—H(12A), 0.88 Å; H(12A)...N(14), 2.27 Å;
Bond
d/Å
Bond
d/Å
Cl(1)—C(4´)
O(1)—C(1A)
O(1)—C(2)
1.727(3)
1.374(3)
1.376(4)
1.215(4)
1.218(4)
1.208(4)
1.389(4)
1.418(4)
1.424(4)
1.330(4)
1.149(4)
1.467(4)
1.333(4)
1.429(4)
1.361(4)
1.417(4)
1.516(4)
1.488(4)
C(4)—C(1´)
C(5A)—C(6)
C(5A)—C(9A)
C(6)—C(7)
C(7)—C(8)
C(8)—C(9)
C(9)—C(9A)
C(10)—C(11)
C(1´)—C(6´)
C(1´)—C(2´)
C(2´)—C(3´)
C(3´)—C(4´)
C(4´)—C(5´)
C(5´)—C(6´)
O(1W)—C(1W)
C(1W)—C(2W)
C(1W)—C(3W)
1.527(4)
1.386(5)
1.406(4)
1.370(5)
1.389(5)
1.376(5)
1.388(4)
1.490(5)
1.382(4)
1.389(4)
1.391(4)
1.371(5)
1.383(5)
1.381(4)
1.173(6)
1.468(7)
1.478(7)
O(2)—C(10)
O(3)—N(15)
O(4)—N(15)
N(5)—C(10)
N(5)—C(4A)
N(5)—C(5A)
N(12)—C(2)
N(14)—C(13)
N(15)—C(3´)
C(1A)—C(4A)
C(1A)—C(9A)
C(2)—C(3)
C(3)—C(13)
C(3)—C(4)
C(4)—C(4A)
mation. The O(1) and C(4) atoms deviate from the
C(2)—C(3)—C(1A)—C(4A) plane (within 0.011 Å) in
opposite directions by –0.042 and 0.028 Å, respecꢀ
tively. The folding angles along the C(1A)...C(2) and
C(3)...C(4A) lines are rather small (3.4 and 1.9°, respecꢀ
tively). The conformation of this ring can be represented
as a flattened sofa with the O(1) atom deviating from the
plane through the five atoms of the ring (planar to within
0.011 Å) by –0.032 Å. It should be noted that the heteroꢀ
cycles in substituted 4Hꢀpyrans studied earlier3,20,21 are
less flattened and adopt boat conformations with a more
pronounced folding. Both the dihedral angle between the
planar pyrrole heterocycle and the planar fragment of the
pyran ring and the dihedral angle between the pyrrole ring
N(12)—H(12A)...N(14)
angle,
158°)
and
N(12)—H(12B)...O(2) (x, 1 + y, z) (N(12)...O(2),
2.966(4) Å; N(12)—H(12B), 0.88 Å; H(12B)...O(2),
2.10 Å; N(12)—H(12B)...O(2) angle, 166°). It should be
noted that the O atom of the acetone molecule of solvaꢀ
tion forms a rather weak intermolecular hydrogen bond
with the pyran molecule, viz., C(11)—H(11C)...O(1W)
(1 – x, y, 0.5 – z) (C(11)...O(1W), 3.271(4) Å;
Table 4. Bond angles (ω) in the structure of 2s
Angle
ω/deg
Angle
ω/deg
Angle
ω/deg
C(1A)—O(1)—C(2)
C(10)—N(5)—C(4A)
C(10)—N(5)—C(5A)
C(4A)—N(5)—C(5A)
O(4)—N(15)—O(3)
O(4)—N(15)—C(3´)
O(3)—N(15)—C(3´)
C(4A)—C(1A)—O(1)
C(4A)—C(1A)—C(9A)
O(1)—C(1A)—C(9A)
N(12)—C(2)—C(3)
N(12)—C(2)—O(1)
C(3)—C(2)—O(1)
115.3(2)
122.0(3)
129.1(3)
107.3(2)
124.3(3)
117.8(3)
117.9(3)
126.0(3)
110.9(3)
123.0(3)
127.2(3)
110.8(3)
122.0(3)
117.6(3)
126.0(3)
116.3(2)
106.2(2)
C(4A)—C(4)—C(1´)
C(3)—C(4)—C(1´)
C(1A)—C(4A)—N(5)
C(1A)—C(4A)—C(4)
N(5)—C(4A)—C(4)
C(6)—C(5A)—C(9A)
C(6)—C(5A)—N(5)
C(9A)—C(5A)—N(5)
C(7)—C(6)—C(5A)
C(6)—C(7)—C(8)
112.2(2)
111.0(2)
108.2(3)
124.2(3)
127.1(3)
120.1(3)
132.1(3)
107.8(3)
118.4(3)
121.9(3)
120.4(3)
118.7(3)
120.6(3)
133.5(3)
105.7(3)
119.3(3)
121.7(3)
N(5)—C(10)—C(11)
N(14)—C(13)—C(3)
C(6´)—C(1´)—C(2´)
C(6´)—C(1´)—C(4)
C(2´)—C(1´)—C(4)
C(1´)—C(2´)—C(3´)
C(4´)—C(3´)—C(2´)
C(4´)—C(3´)—N(15)
C(2´)—C(3´)—N(15)
C(3´)—C(4´)—C(5´)
C(3´)—C(4´)—Cl(1)
C(5´)—C(4´)—Cl(1)
C(6´)—C(5´)—C(4´)
C(5´)—C(6´)—C(1´)
O(1W)—C(1W)—C(2W)
O(1W)—C(1W)—C(3W)
C(2W)—C(1W)—C(3W)
119.0(3)
177.1(3)
118.6(3)
121.0(3)
120.4(3)
119.6(3)
121.4(3)
122.1(3)
116.5(3)
119.1(3)
122.4(3)
118.4(3)
119.9(3)
121.4(3)
120.9(6)
122.2(6)
116.9(5)
C(9)—C(8)—C(7)
C(8)—C(9)—C(9A)
C(9)—C(9A)—C(5A)
C(9)—C(9A)—C(1A)
C(5A)—C(9A)—C(1A)
O(2)—C(10)—N(5)
O(2)—C(10)—C(11)
C(2)—C(3)—C(13)
C(2)—C(3)—C(4)
C(13)—C(3)—C(4)
C(4A)—C(4)—C(3)

Oneꢀstep synthesis of 4Hꢀpyrano[3,2ꢀb]indoles
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
185
Xꢀray diffraction study of compound 2s. Colorless crystals of
compound 2s were prepared by slow crystallization from acꢀ
etone during two days. Crystals of 2s (C20H13ClN4O4•C3H6O)
are monoclinic, at –80 °C: a = 23.77(3) Å, b = 8.877(6) Å,
C(11)—H(11C), 0.98 Å; H(11C)...O(1W), 2.31 Å;
C(11)—H(11C)...O(1W) angle, 166°).
Apparently, intramolecular contacts are formed in
Michael adducts 7 (see Scheme 2), whose subsequent
cyclization affords one of two possible isomers containing
the Ph substituent in the axial position.
c = 23.09(2) Å, β = 117.23(6)°, V = 4332(7) Å3, Z = 8, dcalc
=
1.432 g cm–3, space group C2/c. The unit cell parameters and
intensities of 3509 reflections were measured on an automated
fourꢀcircle Siemens P3/PC diffractometer (λ(MоꢀКα) radiaꢀ
tion, graphite monochromator, θ/2θ scan technique, θmax = 27°).
The structure was solved by direct methods and refined by the
fullꢀmatrix leastꢀsquare method with anisotropic thermal paꢀ
rameters for all nonhydrogen atoms. The positions of the H atoms
were calculated geometrically and refined using the riding model.
The final values of the reliability factors were as follows:
R1 = 0.057 based on 2381 independent reflections with I > 2σ(I )
and wR2 = 0.146 based on 3382 independent reflections. All
calculations were carried out with the use of the SHELXLꢀ97
program package. The bond lengths and bond angles are given in
Tables 3 and 4, respectively. The coordinates and isotropic
equivalent thermal parameters of the nonhydrogen atoms were
deposited with the Cambridge Structural Database.
The IR spectra of annelated pyrans are characterized
by the presence of bending and stretching absorption bands
of the amino group at 1660—1680 and 3190—3440 cm–1
,
respectively. The conjugated cyano group of the enaminoꢀ
nitrile fragment of the pyran ring is manifested in the
region of 2202—2221 cm–1. The absorption band of the
carbonyl group of the Nꢀacetyl fragment has a somewhat
higher frequency (1687—1702 cm–1) than the expected
value. This shift is, apparently, associated with the deviaꢀ
tion of the acetyl group from the plane of the indole
system and disruption of conjugation with the N atom (as
was demonstrated by Xꢀray diffraction analysis of comꢀ
pound 2s).
1
The H NMR spectroscopic data for the compounds
under consideration are also not contradictory with the
structures of annelated pyrans 2. Thus, the 1H NMR specꢀ
tra have signals for the protons of the acetyl substituent
(δ 2.48—2.67), aryl substituents, and indole fragment
(δ 6.90—8.45) along with the characteristic signal for the
H(4) proton (δ 5.24—6.15), which is shifted downfield by
1.0—1.2 ppm compared to that observed in the spectra
of nonannelated 2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanopyrans.7 The
slightly broadened signal for the protons of the amino
group (δ 6.68—7.11) is also characteristic.
References
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Experimental
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Synthesis of 5ꢀacetylꢀ2ꢀaminoꢀ4ꢀarylꢀ3ꢀcyanoꢀ4Hꢀpyraꢀ
no[3,2ꢀb]indoles 2 (general procedure). A. К Triethylamine
(0.3 mL) was added to a solution of equimolar amounts of
compound 1 26 (1.75 g, 0.01 mol) and arylidenemalononitrile
3a—j in EtOH (30 mL) at 40—60 °C. The reaction mixture was
kept at 20 °C for 24 h. The precipitate that formed was filtered
off, washed with EtOH and hexane, and recrystallized from
MeCN. The characteristics of compounds 2a—j are given in
Tables 1 and 2.
B. Triethylamine (0.3 mL) was added to a solution of
equimolar amounts of compound 1 (1.75 g, 0.01 mol), aldehyde
4a—q, and malononitrile 5 (0.66 g, 0.01 mol) in EtOH (30 mL)
at 40—60 °C. The reaction mixture was kept and treated as
described above. The characteristics of compounds 2a,d,f,j—w
are given in Tables 1 and 2.
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Received May 17, 2002;
in revised form September 25, 2002