One-step synthesis of substituted 2-amino-5,6,7,8-tetrahydro-4H-benzo[b] pyrans. Molecular and crystal structure of 2-amino-3-(2-methoxyethoxycarbonyl)- 4-(2-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-benzo[b]pyran

Article abstract of DOI:10.1023/A:1024721710597

Substituted 2-aminobenzo[b]pyrans were synthesized by three-component condensation of aromatic aldehydes, cyanoacetic acid derivatives, and cyclic 1,3-diketones. The molecular and crystal structure of 2-amino-3-(2- methoxyethoxycarbonyl)-4-(2-nitrophenyl)

Full text of DOI:10.1023/A:1024721710597

1164
Russian Chemical Bulletin, International Edition, Vol. 52, No. 5, pp. 1164—1171, May, 2003
Oneꢀstep synthesis of substituted 2ꢀaminoꢀ5,6,7,8ꢀtetrahydroꢀ
4Hꢀbenzo[b]pyrans. Molecular and crystal structure
of 2ꢀaminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ4ꢀ(2ꢀnitrophenyl)ꢀ5ꢀoxoꢀ
5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran
a
b
A. M. Shestopalov,a Yu. M. Emelianova, and V. N. Nesterov
ꢀ
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
Substituted 2ꢀaminobenzo[b]pyrans were synthesized by threeꢀcomponent condensation
of aromatic aldehydes, cyanoacetic acid derivatives, and cyclic 1,3ꢀdiketones. The molecular
and crystal structure of 2ꢀaminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ4ꢀ(2ꢀnitrophenyl)ꢀ5ꢀoxoꢀ
5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran was established by Xꢀray diffraction analysis.
Key words: pyran, 1,3ꢀcyclohexanedione, dimedone, benzopyran, Xꢀray diffraction analysis.
Substituted 2ꢀaminoꢀ4Hꢀbenzo[b]pyrans attract attenꢀ
tion because they can be used as drugs, immunomoduꢀ
lators,1 and analogs of natural products2 and other
important compounds. In addition, 2ꢀaminoꢀ4Hꢀbenꢀ
zo[b]pyrans are used in the synthesis of difficultly accesꢀ
sible annelated heterocycles.3
simple oneꢀstep process in which the generation of prodꢀ
uct 1 (see Scheme 1) can take simultaneously two pathꢀ
ways (A and B), viz., the reaction of unsaturated nitrile 2
with dicarbonyl compound 3 (path A) and the reaction
of cyanoacetic acid derivative 5 with intermediate 6
(path B).
Earlier,4—7 benzannelated 2ꢀaminoꢀ4Hꢀpyrans 1
(Scheme 1) have been synthesized in two steps. The first
step consists in preparing arylmethylenemalononitriles 2.
However, the synthesis and isolation of the latter are someꢀ
times impossible8 and are occasionally associated with a
particular danger because these compounds are strong
lacrimators and are similar in toxicity to the known war
gas, oꢀchlorobenzylidenemalononitrile (CS).9 The secꢀ
ond step involves the reaction of the resulting unsaturated
nitriles 2 with the corresponding diketones 3. Earlier,
2ꢀaminoꢀ3ꢀcyanoꢀ4,7,7ꢀtrimethylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetraꢀ
hydroꢀ4Hꢀbenzo[b]pyran has been synthesized without
the preisolation of unsaturated nitrile.10 We have also reꢀ
ported the oneꢀstep synthesis of substituted 2ꢀaminoꢀ4Hꢀ
benzo[b]pyrans.11
With the aim of simplifying these procedures and makꢀ
ing them safe, in the present study we examined the possiꢀ
bility of the oneꢀstep synthesis of benzopyrans 1 without
the preliminary synthesis of arylmethylenemalononitriles 2
by threeꢀcomponent condensation of aldehydes 4, deꢀ
rivatives of cyanoacetic acid 5, and cyclic 1,3ꢀdiketones
3a,b, which we have developed earlier for the synthesis of
spiroꢀ4ꢀ(piperidinoꢀ4)ꢀ2H,4Hꢀpyrano[2,3ꢀc]pyrazoles.12
The advantage of this method is that it is based on the
Under the same conditions, the reactions afforded
many various 2ꢀaminoꢀ4Hꢀpyrans (see the Experimental
section). For their synthesis, we used available aldehydes
containing structural fragments of natural compounds and
pharmaceuticals.13 In addition to malononitrile, we used
methyl, ethyl, isopropyl, tertꢀbutyl, 2ꢀmethoxyethyl, and
benzyl cyanoacetates as methyleneꢀactive nitriles. In none
of the reactions under study, was transesterification obꢀ
served in spite of the fact that the reactions were carried
out in EtOH.
Earlier, 5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyrans have
been synthesized with the use of cyclic 1,3ꢀdiketones.4—7
In one study,14 cyclohexanone (7) was proposed as a carꢀ
bonyl compound for the synthesis of 4Hꢀbenzo[b]pyrans
(Scheme 2). We repeated this experiment and found out
that structure 8 has been erroneously assigned to the prodꢀ
uct with m.p. 247—250 °C, which has been prepared by
refluxing a mixture of unsaturated nitrile 2 (Ar = Ph,
Z = CN) and cyclohexanone (7) in EtOH in the presence
of Et3N as the catalyst.14 In reality, the reactions perꢀ
formed under these conditions afforded substituted hexaꢀ
hydronaphthalenes 9, which are generally synthesized by
the reactions of unsaturated nitriles 2 with cyclohexylꢀ
idenemalononitrile (10).15
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1103—1109, May, 2003.
1066ꢀ5285/03/5205ꢀ1164 $25.00 © 2003 Plenum Publishing Corporation

Oneꢀstep synthesis of 2ꢀaminoꢀ4Hꢀbenzo[b]pyrans
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 5, May, 2003
1165
Scheme 1
Scheme 2
pyrans 1a,b,j—r. The absorption bands of the carbonyl
groups are observed at 1704—1670 cm–1
.
The 1H NMR spectra of compounds 1a—z have charꢀ
acteristic signals for the protons of the amino group. Due
to hydrogen bonding, these signals in the spectra of pyrꢀ
ans 1c—i,s—z containing the
carboxyl group at position 3
of the pyran ring are shifted
downfield (δ 7.37—7.64)
compared to those in the
spectra of pyrans 1a,b,j—r
(δ 6.47—7.12)16 containing
the cyano group at position 3.
1: Ar = 4ꢀOBunꢀ3ꢀOMeC6H3 (a), 5ꢀMeꢀ2ꢀfuryl (b), 4ꢀClC6H4 (c),
2ꢀthienyl (d), 2,4ꢀF2C6H3 (e, t), 2ꢀNO2C6H4 (f, j),
3ꢀNO2C6H4 (g, k, w), 4ꢀNO2C6H4 (h, l, x), 4ꢀpyridyl (i, y),
2,4,5ꢀ(OMe)3ꢀC6H2 (m), 4ꢀOPrꢀ3ꢀOMeC6H3 (n),
3,4ꢀ(—OCH2O—)ꢀ2ꢀClC6H2 (o), 4ꢀ(OCH2C(O)NH2)C6H4 (p),
4ꢀ(Nꢀmorpholinyl)ꢀC6H4 (q),
In the spectra of pyrans 1f—h,j—l, the chemical shift δ of
the signal for the proton of the C(4)H group sharply deꢀ
creases (Table 1) as the position of the nitro group in the
benzene ring changes from the ortho to meta and para
positions. This is, apparently, attributable to an intramoꢀ
lecular contact between the H atom at C(4) and one of
the O atoms of the nitro group in the ortho position of the
phenyl substituent (C(4)H...O=N(O)C6H4). This conꢀ
4ꢀ(OCH2CH2ꢀ(Nꢀmorpholinyl))ꢀ3ꢀOMeC6H3 (r), 2ꢀFC6H4 (s),
4ꢀCOOMeC6H4 (u, v, z);
Z = CN (a, b, j—r), COOMe (c, d, s), COOEt (e, t),
COOCH2CH2OMe (f—i, w—y), COOPri (u), COOBut (v),
COOCH2Ph (z)
R = H (1a—i, 3a), Me (1j—z, 3b)
Table 1. Chemical shifts (δ) of the signals for the protons of the
main fragments of 2ꢀaminobenzo[b]pyrans 1f—h,j—l
We prepared 2ꢀaminoꢀ4Hꢀbenzo[b]pyrans as stable
analytically pure colorless powders, which can be recrysꢀ
tallized from EtOH or MeCN. The structures of all comꢀ
pounds were confirmed by IR and 1H NMR spectroscopy
and elemental analysis (see the Experimental section).
The IR spectra of the aminopyrans synthesized have a
series of stretching absorption bands of the amino group
(3455—3184 cm–1) and an intense bending band of this
group (1674—1650 cm–1). The high intensity of the abꢀ
sorption band at 2204—2188 cm–1 confirms the presence
of the cyano group conjugated with the amino group in
Comꢀ
Position of
δ
pound NO2 group
С(4)H С(6)H2 С(7)H2 С(8)H2 NH2
1f
orthoꢀ
metaꢀ
paraꢀ
orthoꢀ
metaꢀ
paraꢀ
5.41
4.68
4.67
4.96
4.43
4.38
2.22
2.29
2.29
2.11
2.21
2.19
1.86
1.93
1.92
—
—
—
2.58 7.64
2.66 7.61
2.65 7.61
2.50 7.06
2.55 7.13
2.54 7.12
1g
1h
1j
1k
1l

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Russ.Chem.Bull., Int.Ed., Vol. 52, No. 5, May, 2003
Shestopalov et al.
tact was detected by Xꢀray diffraction analysis. In addiꢀ
tion, δH of all groups of the benzopyran ring in the spectra
of pyrans 1f,j containing the nitro group in the ortho posiꢀ
tion (and, presumably, having the C(4)H...O=N(O)C6H4
hydrogen bond) differ from those in the spectra of pyrans
1g,h,k,l containing the nitro group in the meta or para
positions.
According to the results of Xꢀray diffraction analysis
of compound 1f, the reaction afforded only the synperiꢀ
planar (sp) isomer of two possible isomers, viz., the sp and
antiperiplanar (ap) isomers. Earlier, we have observed the
formation of only sp isomers for substituted 4ꢀ(2ꢀnitroꢀ
phenyl)ꢀ1,4ꢀdihydropyridines,17,18 4ꢀ(2ꢀnitrophenyl)ꢀ4Hꢀ
thiopyrans,19 and 4ꢀ(2ꢀnitrophenyl)ꢀ4,5ꢀdihydrothioꢀ
phenes.20 The sp isomers are, apparently, stabilized by
an intramolecular contact C(4)H...O=N(O). This asꢀ
sumption is to some extent supported by the absence
of atroposelectivity in the 2ꢀaminoꢀ3ꢀethoxycarbonylꢀ
4ꢀ(3ꢀfluorophenyl)ꢀ7,7ꢀdimethylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetraꢀ
hydroꢀ4Hꢀbenzo[b]pyran molecules, which exist (accordꢀ
ing to the Xꢀray diffraction data) as a mixture of the sp
and ap isomers in a ratio of 2 : 1.16
The heterocycle in molecule 1f, like those in the subꢀ
stituted 4Hꢀpyrans studied earlier,16,21,22 adopts a flatꢀ
tened boat conformation with the O(1) and C(4) atoms
deviating from the plane (to within 0.016 Å) passing
through the remaining four atoms of the ring by 0.119 and
0.158 Å, respectively. The foldings along the O(1)...C(4),
The overall view of molecule 1f is shown in Fig. 1. The
bond lengths and bond angles are given in Tables 2 and 3,
respectively. The atomic numbering scheme used in Fig. 1
differs from that assumed in the text.
C(19)
C(14)
C(13)
O(7)
O(4)
N(2)
C(15)
C(16)
C(18)
C(17)
C(12)
C(11)
O(3)
O(6)
O(2)
C(6)
C(4)
C(7)
C(5)
C(3)
C(1)
C(8)
O(5)
C(9)
C(10)
C(2)
O(1)
N(1)
Fig 1. Overall view of the 2ꢀaminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ4ꢀ(2ꢀnitrophenyl)ꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran
molecule (1f).

Oneꢀstep synthesis of 2ꢀaminoꢀ4Hꢀbenzo[b]pyrans
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 5, May, 2003
1167
Table 2. Bond lengths (d) in the 2ꢀaminoꢀ3ꢀ(2ꢀmethoxyꢀ
ethoxycarbonyl)ꢀ4ꢀ(2ꢀnitrophenyl)ꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ
4Hꢀbenzo[b]pyran molecule (1f)
(3.035(3) Å) and C(5)...C(16) (3.124(3) Å) whose lengths
are smaller than twice the van der Waals radius of the
C atom.23 The rotation of the nitro group with respect to
the benzene ring (dihedral angle is 54.0°) is noticeably
larger than that observed in substituted 4ꢀ(oꢀnitrophenyl)ꢀ
1,4ꢀdihydropyridines (the corresponding dihedral angles
are in the range of 31.6—44.1°).17,18 The orthoꢀnitrophenyl
substituent in the molecule under consideration, like those
in substituted 1,4ꢀdihydropyridines,17,18 is in the synperiꢀ
planar orientation with respect to the H(4a) atom reꢀ
sulting in the shortened nonbonded O(3)...C(4) conꢀ
tact (3.079(3) Å). According to the published data,24,25
this contact can be considered as an C—H...O hydroꢀ
gen bond (C(4)—H(4a), 0.98 Å; H(4a)...O(3), 2.37 Å;
C(4)—H(4a)...O(3), 128°).
As can be seen from Fig. 1, the carbonyl group is in
the cis orientation with respect to the C(2)=C(3) bond,
which leads to the formation of the strong intramolecuꢀ
lar N(1)—H(1a)...O(5) hydrogen bond between this
group and the amino group (N(1)...O(5), 2.691(2) Å;
N(1)—H(1a), 0.86 Å; H(1a)...O(5), 2.09 Å;
N(1)—H(1a)...O(5), 127°) and causes flattening of this
fragment. This molecular structure is responsible for the
redistribution of the bond lengths compared to the stanꢀ
dard values26 and facilitates conjugation of the amino and
carbonyl groups with the C(2)=C(3) double bond.
Bond
d/Å
Bond
d/Å
O(1)—C(2)
O(1)—C(10)
O(2)—C(6)
O(3)—N(2)
O(4)—N(2)
O(5)—C(1)
O(6)—C(1)
O(6)—C(17)
O(7)—C(18)
O(7)—C(19)
N(1)—C(2)
N(2)—C(12)
C(1)—C(3)
C(2)—C(3)
C(3)—C(4)
1.370(2)
1.375(2)
1.215(2)
1.211(2)
1.225(2)
1.225(2)
1.344(2)
1.439(2)
1.408(3)
1.427(3)
1.333(2)
1.469(2)
1.445(2)
1.362(2)
1.520(2)
C(4)—C(5)
1.514(2)
1.535(2)
1.332(3)
1.475(3)
1.509(3)
1.496(4)
1.497(4)
1.492(3)
1.388(2)
1.392(2)
1.388(2)
1.371(3)
1.381(3)
1.384(3)
1.486(4)
C(4)—C(11)
C(5)—C(10)
C(5)—C(6)
C(6)—C(7)
C(7)—C(8)
C(8)—C(9)
C(9)—C(10)
C(11)—C(16)
C(11)—C(12)
C(12)—C(13)
C(13)—C(14)
C(14)—C(15)
C(15)—C(16)
C(17)—C(18)
C(2)...C(10), and C(3)...C(5) lines are characterized by
rather small angles (13.0, 9.8, and 10.4°, respectively).
The cyclohexenone ring adopts a distorted halfꢀchair
conformation with the C(7) and C(8) atoms deviating
from the plane of the remaining atoms (planar to within
0.019 Å) in opposite directions by –0.156 and 0.493 Å,
respectively. The dihedral angle between the bottom of
the boat of the heterocycle and the plane of the fused
ring is 9.4°.
The pseudoaxial orthoꢀnitrophenyl substituent is virꢀ
tually perpendicular to the planar fragment of the pyran
ring (dihedral angle between these fragments is 87.1°).
Earlier, we have found an analogous orientation of this
substituent in substituted 4ꢀ(oꢀnitrophenyl)ꢀ1,4ꢀdihydroꢀ
pyridine.17 This orientation results, apparently, from the
forced intramolecular nonbonded contacts C(3)...C(16)
In the crystals, molecules 1f are linked in dimers by
the intermolecular N(1)—H(1b)...O(7) hydrogen bonds
(1 – х, 2 – y, –z) (N(1)...O(7), 2.958(3) Å; N(1)—H(1b),
0.86 Å; H(1b)...O(7), 2.13 Å; N(1)—H(1b)...O(7), 160°).
Experimental
The melting points were measured on a Kofler stage. The IR
spectra were recorded on a Perkin—Elmer 577 instrument in
KBr pellets (1 : 200). The 1H NMR spectra were measured on a
Table 3. Bond angles (ω) in the 2ꢀaminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ4ꢀ(2ꢀnitrophenyl)ꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ
4Hꢀbenzo[b]pyran molecule (1f)
Angle
ω/deg
Angle
ω/deg
Angle
ω/deg
C(2)—O(1)—C(10)
C(1)—O(6)—C(17)
C(18)—O(7)—C(19)
O(3)—N(2)—O(4)
O(3)—N(2)—C(12)
O(4)—N(2)—C(12)
O(5)—C(1)—O(6)
O(5)—C(1)—C(3)
O(6)—C(1)—C(3)
N(1)—C(2)—C(3)
N(1)—C(2)—O(1)
C(3)—C(2)—O(1)
C(2)—C(3)—C(1)
C(2)—C(3)—C(4)
118.52(14)
117.74(16)
113.1(2)
C(1)—C(3)—C(4)
C(5)—C(4)—C(3)
C(5)—C(4)—C(11)
C(3)—C(4)—C(11)
C(10)—C(5)—C(6)
C(10)—C(5)—C(4)
C(6)—C(5)—C(4)
O(2)—C(6)—C(5)
O(2)—C(6)—C(7)
C(5)—C(6)—C(7)
C(8)—C(7)—C(6)
C(7)—C(8)—C(9)
C(10)—C(9)—C(8)
C(5)—C(10)—O(1)
120.61(15)
109.46(14)
109.65(13)
112.61(13)
118.92(16)
122.50(16)
118.52(16)
120.69(17)
122.34(19)
116.91(19)
112.7(2)
C(5)—C(10)—C(9)
O(1)—C(10)—C(9)
C(16)—C(11)—C(12) 115.61(15)
C(16)—C(11)—C(4)
C(12)—C(11)—C(4)
C(13)—C(12)—C(11) 123.15(17)
C(13)—C(12)—N(2)
C(11)—C(12)—N(2)
C(14)—C(13)—C(12) 119.24(18)
C(13)—C(14)—C(15) 119.46(17)
C(14)—C(15)—C(16) 120.25(18)
C(15)—C(16)—C(11) 122.16(17)
126.34(18)
110.67(16)
123.53(16)
118.88(15)
117.56(16)
121.55(17)
126.87(18)
111.57(15)
127.95(18)
109.60(16)
122.45(16)
117.68(16)
121.69(16)
119.57(15)
124.78(15)
114.47(16)
122.37(15)
112.4(2)
110.90(19)
122.97(16)
O(6)—C(17)—C(18)
O(7)—C(18)—C(17)
108.62(19)
109.3(2)

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Shestopalov et al.
Bruker ACꢀ300 spectrometer (300 MHz) in DMSOꢀd6 with
respect to Me4Si.
C19H20N2O7. Calculated (%): C, 58.76; H, 5.19; N, 7.21. IR,
ν/cm–1: 3404, 3280 (N—H); 1692, 1688 (C=O); 1670 (δ(NH2)).
1H NMR, δ: 1.86 (m, 2 H, C(7)H2); 2.22 (m, 2 H, C(6)H2);
2.58 (t, 2 H, C(8)H2, J = 6.4 Hz); 3.07 (s, 3 H, OMe); 3.29 (t,
2 H, CH2OMe, J = 4.0 Hz); 3.88 and 4.00 (both m, 1 H each,
COOCH2); 5.41 (s, 1 H, C(4)H); 7.30 and 7.54 (both t, 1 H each,
C(4´)H, C(5´)H, J = 8.0 Hz); 7.32 and 7.74 (both d, 1 H each,
C(3´)H, C(6´)H, J = 8.0 Hz); 7.64 (br.s, 2 H, NH2).
2ꢀAminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ4ꢀ(3ꢀnitrophenyl)ꢀ5ꢀ
oxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1g). The yield was
84%, m.p. 155 °C. Found (%): C, 58.78; H, 5.26; N, 7.31.
C19H20N2O7. Calculated (%): C, 58.76; H, 5.19; N, 7.21. IR,
ν/cm–1: 3392, 3272 (N—H); 1696 (C=O); 1636 (δ(NH2)).
1H NMR, δ: 1.93 (m, 2 H, C(7)H2); 2.29 (m, 2 H, C(6)H2);
2.66 (m, 2 H, C(8)H2); 3.17 (s, 3 H, OMe); 3.41 (m, 2 H,
CH2OMe); 4.04 (m, 2 H, COOCH2); 4.68 (s, 1 H, C(4)H); 7.52
(t, 1 H, C(5´)H, J = 9.0 Hz); 7.61 (m, 3 H, C6H4, NH2); 7.97
(m, 2 H, C6H4).
2ꢀAminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ4ꢀ(4ꢀnitrophenyl)ꢀ5ꢀ
oxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1h). The yield was
72%, m.p. 171 °C. Found (%): C, 58.74; H, 5.30; N, 7.18.
C19H20N2O7. Calculated (%): C, 58.76; H, 5.19; N, 7.21. IR,
ν/cm–1: 3456, 3328 (N—H); 1688 (C=O); 1656 (δ(NH2)).
1H NMR, δ: 1.92 (m, 2 H, C(7)H2); 2.29 (m, 2 H, C(6)H2);
2.65 (m, 2 H, C(8)H2); 3.23 (s, 3 H, OMe); 3.45 (m, 2 H,
CH2OMe); 4.05 (t, 2 H, COOCH2, J = 5.9 Hz); 4.67 (s, 1 H,
C(4)H); 7.44 and 8.08 (both d, 2 H each, C6H4, J = 9.9 Hz);
7.61 (br.s, 2 H, NH2).
2ꢀAminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ5ꢀoxoꢀ4ꢀ(3ꢀpyridyl)ꢀ
5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1i). The yield was 61%,
m.p. 153—154 °C. Found (%): C, 62.66; H, 5.84; N, 8.09.
C18H20N2O5. Calculated (%): C, 62.78; H, 5.85; N, 8.13. IR,
ν/cm–1: 3400, 3264 (N—H); 1688 (C=O); 1664 (δ(NH2)).
1H NMR, δ: 1.97 (m, 2 H, C(7)H2); 2.29 (m, 2 H, C(6)H2);
2.63 (m, 2 H, C(8)H2); 3.23 (s, 3 H, OMe); 3.42 (m, 2 H,
CH2OMe); 4.04 (m, 2 H, COOCH2); 4.52 (s, 1 H, C(4)H); 7.14
and 8.32 (both d, 2 H each, C5H4N, J = 6.7 Hz); 7.57
(s, 2 H, NH2).
2ꢀAminoꢀ4ꢀarylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenꢀ
zo[b]pyrans (1a—z) (general procedure). Triethylamine (0.5 mL)
was added to a solution of aromatic aldehyde 4 (10 mmol),
malononitrile (or cyanoacetic ester) 5 (10 mmol), and 1,3ꢀdiꢀ
ketone 3 (10 mmol) in EtOH (25 mL) and the reaction mixture
was refluxed for 10 min. The precipitate that formed was filꢀ
tered off, washed with EtOH and hexane, and recrystallized
from EtOH.
2ꢀAminoꢀ4ꢀ(2ꢀbutoxyꢀ3ꢀmethoxyphenyl)ꢀ3ꢀcyanoꢀ5ꢀoxoꢀ
5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1a). The yield was 85%,
m.p. 196—197 °C. Found (%): C, 68.51; H, 6.55; N, 7.51.
C21H24N2O4. Calculated (%): C, 68.46; H, 6.57; N, 7.60. IR,
ν/cm–1: 3356, 3184 (N—H); 2194 (CN); 1680 (C=O); 1654
(δ(NH2)). 1H NMR, δ: 0.99 (t, 3 H, O(CH2)3CH3, J = 8.9 Hz);
1.48 (q, 2 H, O(CH2)2CH2CH3, J = 8.9 Hz); 1.73 (m, 2 H,
OCH2CH2Et); 1.98 (m, 2 H, C(7)H2); 2.29 (t, 2 H, C(6)H2, J =
8.9 Hz); 2.62 (m, 2 H, C(8)H2); 3.78 (s, 3 H, OMe); 3.91 (t,
2 H, OCH2, J = 7.2 Hz); 4.17 (s, 1 H, C(4)H); 6.62 and 6.79
(both d, 1 H each, C6H3, J = 10.0 Hz); 6.71 (s, 3 H, NH2, C6H3).
2ꢀAminoꢀ3ꢀcyanoꢀ4ꢀ(5ꢀmethylfuryl)ꢀ5ꢀoxoꢀ5,6,7,8ꢀ
tetrahydroꢀ4Hꢀbenzo[b]pyran (1b). The yield was 83%,
m.p. 204—205 °C. Found (%): C, 66.69; H, 5.11; N, 10.35.
C15H14N2O3. Calculated (%): C, 66.66; H, 5.22; N, 10.36. IR,
ν/cm–1: 3375, 3320, 3210 (N—H); 2204 (CN); 1675 (C=O);
1
1655 (δ(NH2)). H NMR, δ: 1.95 (m, 2 H, C(7)H2); 2.18 (s,
3 H, Me); 2.32 (t, 2 H, C(6)H2, J = 6.7 Hz); 2.59 (t, 2 H,
C(8)H2, J = 7.0 Hz); 4.26 (s, 1 H, C(4)H); 5.89 (m, 2 H,
C(3´)H, C(4´)H); 6.92 (br.s, 2 H, NH2).
2ꢀAminoꢀ4ꢀ(4ꢀchlorophenyl)ꢀ3ꢀmethoxycarbonylꢀ5ꢀoxoꢀ
5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1c). The yield was 69%,
m.p. 196—197 °C. Found (%): C, 61.45; H, 4.93; N, 4.30.
C17H16ClNO4. Calculated (%): C, 61.36; H, 4.85; N, 4.21. IR,
ν/cm–1: 3455, 3330 (N—H); 1690 (C=O); 1655 (δ(NH2)).
1H NMR, δ: 1.91 (m, 2 H, C(7)H2); 2.28 (m, 2 H, C(6)H2);
2.61 (t, 2 H, C(8)H2, J = 6.6 Hz); 3.52 (s, 3 H, OMe); 4.57 (s,
1 H, C(4)H); 7.17 and 7.25 (both d, 2 H each, C6H4, J =
7.7 Hz); 7.47 (br.s, 2 H, NH2).
2ꢀAminoꢀ3ꢀmethoxycarbonylꢀ5ꢀoxoꢀ4ꢀ(2ꢀthienyl)ꢀ5,6,7,8ꢀ
tetrahydroꢀ4Hꢀbenzo[b]pyran (1d). The yield was 69%,
m.p. 196—197 °C. Found (%): C, 59.05; H, 4.87; N, 4.62.
C15H15NO4S. Calculated (%): C, 59.00; H, 4.95; N, 4.59. IR,
ν/cm–1: 3410, 3305 (N—H); 1690, 1660 (C=O); 1650 (δ(NH2)).
1H NMR, δ: 1.97 (m, 2 H, C(7)H2); 2.36 (m, 2 H, C(6)H2);
2.61 (t, 2 H, C(8)H2, J = 6.7 Hz); 3.51 (s, 3 H, OMe); 4.90 (s,
1 H, C(4)H); 6.73 (d, 1 H, C(3´)H, J = 2.8 Hz); 6.84 (m,
1 H, C(4´)H); 7.17 (d, 1 H, C(5´)H, J = 6.0 Hz); 7.46
(br.s, 2 H, NH2).
2ꢀAminoꢀ4ꢀ(2,4ꢀdifluorophenyl)ꢀ3ꢀethoxycarbonylꢀ5ꢀoxoꢀ
5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1e). The yield was 80%,
m.p. 186—187 °C. Found (%): C, 61.79; H, 4.80; N, 4.00.
C18H17F2NO4. Calculated (%): C, 61.89; H, 4.90; N, 4.01. IR,
ν/cm–1: 3412, 3296 (N—H); 1694 (C=O); 1654 (δ(NH2)).
1H NMR, δ: 1.12 (t, 3 H, CH2CH3, J = 8.9 Hz); 1.97 (m, 2 H,
C(7)H2); 2.26 (m, 2 H, C(6)H2); 2.62 (t, 2 H, C(8)H2, J =
7.0 Hz); 3.97 (q, 2 H, OCH2, J = 8.9 Hz); 4.69 (s, 1 H, C(4)H);
6.78 (m, 2 H, C6H3); 7.19 (m, 1 H, C6H3); 7.39 (br.s, 2 H, NH2).
2ꢀAminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ4ꢀ(2ꢀnitrophenyl)ꢀ5ꢀ
oxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1f). The yield was
78%, m.p. 135 °C. Found (%): C, 58.80; H, 5.29; N, 7.17.
2ꢀAminoꢀ3ꢀcyanoꢀ7,7ꢀdimethylꢀ4ꢀ(2ꢀnitrophenyl)ꢀ5ꢀoxoꢀ
5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1j). The yield was 77%,
m.p. 257 °C (decomp.). Found (%): C, 63.73; H, 5.00; N, 12.36.
C18H17N3O4. Calculated (%): C, 63.71; H, 5.05; N, 12.38. IR,
ν/cm–1: 3472, 3336, 3256 (N—H); 2192 (CN); 1688 (C=O);
1
1664 (δ(NH2)). H NMR, δ: 0.90 and 1.03 (both s, 3 H each,
C(7)Me2); 2.11 (m, 2 H, C(6)H2); 2.50* (m, 2 H, C(8)H2); 4.96
(s, 1 H, C(4)H); 7.06 (br.s, 2 H, NH2); 7.35 and 7.82 (both d,
1 H each, C(3´)H, C(6´)H, J = 7.6 Hz); 7.42 and 7.65 (both t,
1 H each, C(4´)H, C(5´)H, J = 7.6 Hz).
2ꢀAminoꢀ3ꢀcyanoꢀ7,7ꢀdimethylꢀ4ꢀ(3ꢀnitrophenyl)ꢀ5ꢀoxoꢀ
5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1k). The yield was 89%,
m.p. 223—224 °C. Found (%): C, 63.78; H, 5.03; N, 12.47.
C18H17N3O4. Calculated (%): C, 63.71; H, 5.05; N, 12.38. IR,
ν/cm–1: 3432, 3336, 3200 (N—H); 2184 (CN); 1680 (C=O);
1
1664 (δ(NH2)). H NMR, δ: 0.96 and 1.07 (both s, 3 H each,
C(7)Me2); 2.21 (m, 2 H, C(6)H2); 2.55 (s, 2 H, C(8)H2); 4.43
(s, 1 H, C(4)H); 7.13 (s, 2 H, NH2); 7.66 (m, 2 H, C6H4); 7.97
(s, 1 H, C(2´)H); 8.09 (d, 1 H, C6H4, J = 9.0 Hz).
* The signals for the protons of the C(8)H2 methylene group in
the spectra of compounds 1j,m—q,s,u,w overlap with the signal
for the protons of DMSOꢀd6.

Oneꢀstep synthesis of 2ꢀaminoꢀ4Hꢀbenzo[b]pyrans
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 5, May, 2003
1169
2ꢀAminoꢀ3ꢀcyanoꢀ7,7ꢀdimethylꢀ4ꢀ(4ꢀnitrophenyl)ꢀ5ꢀ
oxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1l). The yield was
82%, m.p. 143 °C. Found (%): C, 63.73; H, 5.11; N, 12.44.
C18H17N3O4. Calculated (%): C, 63.71; H, 5.05; N, 12.38. IR,
ν/cm–1: 3392, 3328, 3216 (N—H); 2192 (CN); 1684 (C=O);
2ꢀAminoꢀ3ꢀcyanoꢀ4ꢀ[3ꢀmethoxyꢀ4ꢀ(2ꢀmorpholinoꢀ
ethoxy)phenyl]ꢀ7,7ꢀdimethylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀ
benzo[b]pyran (1r). The yield was 67%, m.p. 169—170 °C.
Found (%): C, 66.11; H, 6.81; N, 9.34. C25H31N3O5. Calcuꢀ
lated (%): C, 66.21; H, 6.89; N, 9.26. IR, ν/cm–1: 3332 (N—H);
2192 (CN); 1688 (C=O); 1674 (δ(NH2)). 1H NMR, δ: 1.01 and
1.09 (both s, 3 H each, C(7)Me2); 2.16 (m, 2 H, C(6)H2); 2.49
(s, 2 H, C(8)H2); 2.69 (t, 2 H, C6H3—OCH2CH2N, J = 5.0 Hz);
3.10* (m, 4 H, CH2—N—CH2); 3.58 (m, 4 H, CH2—O—CH2);
3.77 (s, 3 H, OMe); 4.02 (t, 2 H, PhOCH2CH2N, J = 5.0 Hz);
4.12 (s, 1 H, C(4)H); 6.62 and 6.81 (both d, 1 H each, C(5´)H,
C(6´)H, J = 10.5 Hz); 6.68 (s, 3 H, NH2, C(2´)H).
1
1656 (δ(NH2)). H NMR, δ: 0.96 and 1.05 (both s, 3 H each,
C(7)Me2); 2.19 (m, 2 H, C(6)H2); 2.54 (m, 2 H, C(8)H2); 4.38
(s, 1 H, C(4)H); 7.12 (s, 2 H, NH2); 7.45 and 8.17 (both d,
2 H each, C6H4, J = 8.8 Hz).
2ꢀAminoꢀ3ꢀcyanoꢀ4ꢀ(2,4,5ꢀtrimethoxyphenyl)ꢀ7,7ꢀdimethylꢀ
5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1m). The yield was
83%, m.p. 111—112 °C. Found (%): C, 65.64; H, 6.23; N, 7.27.
C21H24N2O5. Calculated (%): C, 65.61; H, 6.29; N, 7.29. IR,
ν/cm–1: 3344, 3192 (N—H); 2196 (CN); 1688 (C=O); 1662
(δ(NH2)). 1H NMR, δ: 1.03 and 1.12 (both s, 3 H each,
C(7)Me2); 2.14 (m, 2 H, C(6)H2); 2.50 (s, 2 H, C(8)H2); 3.19
(s, 3 H, C(2´)OMe); 3.29 (s, 6 H, C(4´)OMe, C(5´)OMe); 4.39
(s, 1 H, C(4)H); 6.47 (br.s, 2 H, NH2); 6.53 and 6.57 (both s,
1 H each, C6H2).
2ꢀAminoꢀ3ꢀcyanoꢀ4ꢀ(3ꢀmethoxyꢀ4ꢀpropoxyphenyl)ꢀ7,7ꢀdiꢀ
methylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1n). The
yield was 77%, m.p. 157—158 °C. Found (%): C, 69.07; H, 6.87;
N, 7.33. C22H26N2O4. Calculated (%): C, 69.09; H, 6.85;
N, 7.32. IR, ν/cm–1: 3340, 3190 (N—H); 2200 (CN); 1680
(C=O); 1650 (δ(NH2)). 1H NMR, δ: 1.02 (t, 3 H, O(CH2)2CH3,
J = 8.3 Hz); 1.02 and 1.09 (both s, 3 H each, C(7)Me2); 1.76 (q,
2 H, CH2CH3, J = 8.3 Hz); 2.16 (m, 2 H, C(6)H2); 2.49 (s, 2 H,
C(8)H2); 3.77 (s, 3 H, OMe); 3.87 (t, 2 H, OCH2, J = 8.9 Hz);
4.12 (s, 1 H, C(4)H); 6.63 and 6.78 (both d, 1 H each, C(5´)H,
C(6´)H, J = 10.0 Hz); 6.68 (s, 3 H, NH2, C(2´)H).
2ꢀAminoꢀ4ꢀ(2ꢀfluorophenyl)ꢀ3ꢀmethoxycarbonylꢀ7,7ꢀdiꢀ
methylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1s). The
yield was 59%, m.p. 201—202 °C. Found (%): C, 65.95; H, 5.94;
N, 4.18. C19H20FNO4. Calculated (%): C, 66.08; H, 5.84;
N, 4.06. IR, ν/cm–1: 3428, 3312 (N—H); 1696, 1670 (C=O);
1
1656 (δ(NH2)). H NMR, δ: 0.89 and 1.04 (both s, 3 H each,
C(7)Me2); 2.16 (m, 2 H, C(6)H2); 2.49 (m, 2 H, C(8)H2); 3.48
(s, 3 H, OMe); 4.68 (s, 1 H, C(4)H); 7.08 (m, 4 H, C6H4); 7.49
(br.s, 2 H, NH2).
2ꢀAminoꢀ4ꢀ(2,4ꢀdifluorophenyl)ꢀ3ꢀethoxycarbonylꢀ7,7ꢀdiꢀ
methylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1t). The
yield was 72%, m.p. 204—205 °C. Found (%): C, 63.56; H, 5.57;
N, 3.78. C20H21F2NO4. Calculated (%): C, 63.65; H, 5.61;
N, 3.71. IR, ν/cm–1: 3424, 3312 (N—H); 1694, 1670 (C=O);
1
1656 (δ(NH2)). H NMR, δ: 0.96 and 1.09 (both s, 3 H each,
C(7)Me2); 1.11 (t, 3 H, CH2CH3, J = 8.0 Hz); 2.13 (m, 2 H,
C(6)H2); 2.47 (m, 2 H, C(8)H2); 3.94 (q, 2 H, OCH2CH3, J =
8.0 Hz); 4.67 (s, 1 H, C(4)H); 6.77 (m, 2 H, C6H3); 7.17 (m,
1 H, C6H3); 7.39 (br.s, 2 H, NH2).
2ꢀAminoꢀ4ꢀ(2ꢀchloroꢀ3,4ꢀmethylenedioxyphenyl)ꢀ3ꢀcyanoꢀ
7,7ꢀdimethylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1o).
The yield was 93%, m.p. 255 °C (decomp.). Found (%): C, 61.10;
H, 4.71; N, 7.53. C19H17ClN2O4. Calculated (%): C, 61.22;
H, 4.59; N, 7.51. IR, ν/cm–1: 3332, 3256, 3212 (N—H); 2188
2ꢀAminoꢀ3ꢀisopropyloxycarbonylꢀ4ꢀ(4ꢀmethoxycarboꢀ
nylphenyl)ꢀ7,7ꢀdimethylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀ
benzo[b]pyran (1u). The yield was 81%, m.p. 195—196 °C.
Found (%): C, 66.70; H, 6.61; N, 3.42. C23H27NO6. Calcuꢀ
lated (%): C, 66.81; H, 6.58; N, 3.39. IR, ν/cm–1: 3412, 3300
1
(CN); 1688 (C=O); 1670 (δ(NH2)). H NMR, δ: 1.02 and 1.06
1
(both s, 3 H each, C(7)Me2); 2.17 (m, 2 H, C(6)H2); 2.51 (s,
2 H, C(8)H2); 4.62 (s, 1 H, C(4)H); 6.01 (d, 2 H, OCH2O, J =
1.1 Hz); 6.64 (s, 1 H, C(5´)H); 6.80 (br.s, 2 H, NH2); 6.91 (s,
1 H, C(6´)H).
(N—H); 1688 (C=O); 1664 (δ(NH2)). H NMR, δ: 0.91 and
1.21 (both d, 3 H each, OCH(CH3)2, J = 6.6 Hz); 0.92 and 1.09
(both s, 3 H each, C(7)Me2); 2.13 (m, 2 H, C(6)H2); 2.48 (m,
2 H, C(8)H2); 3.82 (s, 3 H, OMe); 4.53 (s, 1 H, C(4)H); 4.79
(m, 1 H, OCHMe2); 7.26 and 7.78 (both d, 2 H each, C6H4, J =
9.4 Hz); 7.43 (br.s, 2 H, NH2).
2ꢀAminoꢀ4ꢀ(4ꢀcarbamoylmethoxy)phenylꢀ3ꢀcyanoꢀ7,7ꢀdiꢀ
methylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1p). The
yield was 89%, m.p. 201—202 °C. Found (%): C, 65.35; H, 5.63;
N, 11.50. C20H21N3O4. Calculated (%): C, 65.38; H, 5.76;
N, 11.44. IR, ν/cm–1: 3380, 3324, 3192 (N—H); 2194 (CN);
1682 (C=O); 1650 (δ(NH2)). 1H NMR, δ: 1.01 and 1.10 (both s,
3 H each, C(7)Me2); 2.15 (m, 2 H, C(6)H2); 2.49 (s, 2 H,
C(8)H2); 4.16 (s, 1 H, C(4)H); 4.33 (s, 2 H, OCH2); 6.68 (br.s,
2 H, C(2)NH2); 6.84 and 7.09 (both d, 2 H each, C6H4, J =
10.2 Hz); 7.22 (br.s, 2 H, C(O)NH2).
2ꢀAminoꢀ3ꢀcyanoꢀ7,7ꢀdimethylꢀ4ꢀ(4ꢀmorpholinophenyl)ꢀ5ꢀ
oxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1q). The yield was
79%, m.p. 226 °C (decomp.). Found (%): C, 69.70; H, 6.63;
N, 10.96. C22H25N3O4. Calculated (%): C, 69.63; H, 6.64;
N, 11.07. IR, ν/cm–1: 3450, 3308, 3200 (N—H); 2200 (CN);
1686 (C=O); 1664 (δ(NH2)). 1H NMR, δ: 1.01 and 1.11
(both s, 3 H each, C(7)Me2); 2.15 (m, 2 H, C(6)H2); 2.49 (s,
2 H, C(8)H2); 3.09 (m, 4 H, CH2—N—CH2); 3.74 (m, 4 H,
CH2—O—CH2); 4.11 (s, 1 H, C(4)H); 6.60 (s, 2 H, NH2); 6.79
and 7.03 (both d, 2 H each, C6H4).
2ꢀAminoꢀ3ꢀtertꢀbutoxycarbonylꢀ4ꢀ(4ꢀmethoxycarboꢀ
nylphenyl)ꢀ7,7ꢀdimethylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀ
benzo[b]pyran (1v). The yield was 59%, m.p. 207—208 °C.
Found (%): C, 67.44; H, 6.90; N, 3.21. C24H29NO6. Calcuꢀ
lated (%): C, 67.43; H, 6.84; N, 3.28. IR, ν/cm–1: 3436, 3320
1
(N—H); 1690, 1682 (C=O); 1668 (δ(NH2)). H NMR, δ: 0.91
and 1.08 (both s, 3 H each, C(7)Me2); 1.28 (s, 9 H, OCMe3);
2.12 (m, 2 H, C(6)H2); 2.48 (m, 2 H, C(8)H2); 3.82 (s, 3 H,
OMe); 4.49 (s, 1 H, C(4)H); 7.26 and 7.79 (both d, 2 H each,
C6H4, J = 9.4 Hz); 7.37 (br.s, 2 H, NH2).
2ꢀAminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ7,7ꢀdimethylꢀ4ꢀ(3ꢀ
nitrophenyl)ꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1w).
The yield was 93%, m.p. 116 °C. Found (%): C, 60.62; H, 5.72;
* The signals for the protons of the methylene groups in the
spectra of compounds 1r,x overlap with the signal for the proꢀ
tons of water present in DMSOꢀd6, which was used in NMR
spectroscopic studies.

1170
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Shestopalov et al.
N, 6.84. C21H24N2O7. Calculated (%): C, 60.57; H, 5.81;
N, 6.73. IR, ν/cm–1: 3392, 3288 (N—H); 1692 (C=O); 1664
(δ(NH2)). 1H NMR, δ: 0.93 and 1.06 (both s, 3 H each,
C(7)Me2); 2.19 (m, 2 H, C(6)H2); 2.56 (m, 2 H, C(8)H2); 3.18
(s, 3 H, OMe); 3.42 (m, 2 H, CH2OMe); 4.03 (m, 2 H,
COOCH2); 4.65 (s, 1 H, C(4)H); 7.52 (t, 1 H, C(5´)H, J =
10.3 Hz); 7.61 (br.s, 3 H, NH2, C(2´)H); 7.98 (m, 2 H,
C(4´)H, C(6´)H).
2ꢀAminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ7,7ꢀdimethylꢀ4ꢀ(4ꢀ
nitrophenyl)ꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1x).
The yield was 80%, m.p. 183 °C. Found (%): C, 60.51; H, 5.68;
N, 6.85. C21H24N2O7. Calculated (%): C, 60.57; H, 5.81;
N, 6.73. IR, ν/cm–1: 3376, 3256 (N—H); 1696 (C=O); 1656
(δ(NH2)). 1H NMR, δ: 0.92 and 1.07 (both s, 3 H each,
C(7)Me2); 2.19 (m, 2 H, C(6)H2); 2.55 (m, 2 H, C(8)H2); 3.20
(s, 3 H, OMe); 3.44 (m, 2 H, CH2OMe); 4.04 (t, 2 H, COOCH2,
J = 4.0 Hz); 4.64 (s, 1 H, C(4)H); 7.43 and 8.08 (both d,
2 H each, C6H4, J = 9.5 Hz); 7.60 (br.s, 2 H, NH2).
diffractometer (λꢀMoꢀKα radiation, graphite monochromator,
θ/2θ scanning technique, θmaх = 27°).
The structure was solved by direct methods and refined by
the fullꢀmatrix leastꢀsquares method with anisotropic thermal
parameters for nonohydrogen atoms. The positions of the
H atoms were calculated geometrically and refined using
the riding model. The final reliability factors were as folꢀ
lows: R1 = 0.054 based on 3090 independent reflections and
wR2 = 0.1479 based on 4007 reflections. All calculations were
carried out with the use of the SHELXL97 program package.28
The atomic coordinates and isotropic equivalent thermal paꢀ
rameters of the nonhydrogen atoms were deposited with the
Cambridge Structural Database.
References
1. Eur. Pat. 695547; Chem. Abstrs., 1995, 122, 23835c.
2. Khimicheskaya entsiklopediya [Chemical Encyclopedia],
Rossiiskaya Entsiklopediya, Moscow, 1998, 5, 200 (in
Russian).
3. C. N. O´Callaghan, T. B. H. McMurry, and J. E. O´Brien,
J. Chem. Soc., Perkin Trans. 1, 1995, 4, 417.
4. Z. Rappoport and D. Ladkani, J. Chem. Soc., Perkin Trans. 1,
1974, 2595.
5. Yu. A. Sharanin, V. K. Promonenkov, and L. G. Sharanina,
Zh. Org. Khim., 1982, 18, 625 [J. Org. Chem. USSR, 1982, 18
(Engl. Transl.)].
2ꢀAminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ7,7ꢀdimethylꢀ5ꢀoxoꢀ
4ꢀ(4ꢀpyridyl)ꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1y). The
yield was 61%, m.p. 156—157 °C. Found (%): C, 64.51; H, 6.61;
N, 7.55. C20H24N2O5. Calculated (%): C, 64.50; H, 6.50;
N, 7.52. IR, ν/cm–1: 3384, 3256 (N—H); 1690, 1675 (C=O);
1
1660 (δ(NH2)). H NMR, δ: 0.94 and 1.09 (both s, 3 H each,
C(7)Me2); 2.15 (m, 2 H, C(6)H2); 2.50 (m, 2 H, C(8)H2); 3.25
(s, 3 H, OMe); 3.42 (m, 2 H, OCH2); 4.03 (m, 2 H, OCH2);
4.49 (s, 1 H, C(4)H); 7.12 and 8.33 (both d, 2 H each, C5H4N,
J = 5.0 Hz); 7.57 (br.s, 2 H, NH2).
2ꢀAminoꢀ3ꢀbenzyloxycarbonylꢀ4ꢀ(4ꢀmethoxycarboꢀ
nylphenyl)ꢀ7,7ꢀdimethylꢀ5ꢀoxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀ
benzo[b]pyran (1z). The yield was 87%, m.p. 193 °C. Found (%):
C, 70.15; H, 5.97; N, 2.96. C27H27NO6. Calculated (%):
C, 70.27; H, 5.90; N, 3.04. IR, ν/cm–1: 3400, 3292 (N—H);
6. 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 (Engl. Transl.)].
7. A. S. Polyanskaya, R. I. Bodina, V. Yu. Shchadrin, and N. I.
Aboskalova, Zh. Org. Khim., 1984, 20, 2481 [J. Org. Chem.
USSR, 1984, 20 (Engl. Transl.)].
1
1692, 1670 (C=O); 1652 (δ(NH2)). H NMR, δ: 0.90 and 1.09
(both s, 3 H each, C(7)Me2); 2.12 (m, 2 H, C(6)H2); 2.49 (m,
2 H, C(8)H2); 3.83 (s, 3 H, OMe); 4.60 (s, 1 H, C(4)H); 4.97
(m, 2 H, OCH2); 7.04 (m, 2 H, C6H5); 7.22 (m, 5 H, C6H5
(3 H), C6H4 (2 H)); 7.56 (br.s, 2 H, NH2); 7.74 (d, 2 H, C6H4,
J = 10.4 Hz).
8. A. M. Shestopalov, Z. I. Niazimbetova, D. H. Evans, and
M. E. Nijazimbetov, Heterocycles, 1999, 51, 1101.
9. F. Freeman, Chem. Rev., 1980, 80, 329.
10. V. D. Dyachenko, S. G. Krivokolysko, and V. P. Litvinov,
Zh. Org. Khim., 1998, 34, 750 [Russ. J. Org. Chem., 1998, 34
(Engl. Transl.)].
11. Yu. M. Emel´yanova, Tez. dokl. II Mezhd. molodezhnoi conf.
"Aktual´nye tendentsii v organicheskom sinteze na poroge novoi
ery" [Abstrs. of Papers, IId International Conf. of Young Scholꢀ
ars "Modern Trends in Organic Synthesis on the Eve of New
Era"] (St. Petersburg, June 28—30, 1999), St. Petersburg,
1999, p. 24a (in Russian).
12. A. M. Shestopalov, Yu. M. Emelianova, A. A. Shestopalov,
L. A. Rodinovskaya, Z. I. Niazimbetova, and D. H. Evans,
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15. Yu. A. Sharanin, V. K. Promonenkov, and V. P. Litvinov, in
Malononitril. 1. Itogi nauki i tekhniki, Ser. Organicheskaya
khimiya [Malononitrile. P. 1, Advances in Science and Techꢀ
nology: Ser. Organic Chemistry], VINITI, Moscow, 1991,
20(1), 239 pp. (in Russian).
2ꢀAminoꢀ1,3,3ꢀtricyanoꢀ4ꢀphenylꢀ3,4,4a,5,6,7ꢀhexahydroꢀ
naphthalene (9). A mixture of equimolar amounts (10 mmol) of
cyclohexanone (7) and phenylmethylenemalononitrile was reꢀ
fluxed in EtOH (10 mL) in the presence of a catalytic amount of
Et3N (2 drops) for 10 min. The precipitate that formed was
filtered off and recrystallized from EtOH. The yield was 24%,
m.p. 259—261 °C (cf. lit. data27: m.p. 260—265 °C). Found (%):
C, 75.93; H, 5.35; N, 18.55. C19H16N4. Calculated (%): C, 75.98;
H, 5.37; N, 18.65. IR, ν/cm–1: 3424, 3340, 3256, 3232 (N—H);
2212 (CN); 1650 (δ(NH2)). 1H NMR, δ: 0.92 (m, 1 H, C(4a)H);
1.50 (m, 2 H, C(5)H2); 1.73 and 2.11 (both m, 1 H each,
C(6)H2); 2.21 and 2.78 (both m, 1 H each, C(7)H2); 3.31 (d,
1 H, C(4)H, J = 11.7 Hz); 5.78 (s, 1 H, C(8)H); 7.07 (s, 2 H,
NH2); 7.46 (m, 5 H, C6H5).
Xꢀray diffraction analysis of compound 1f. Colorless crystals
of 2ꢀaminoꢀ3ꢀ(2ꢀmethoxyethoxycarbonyl)ꢀ4ꢀ(2ꢀnitrophenyl)ꢀ5ꢀ
oxoꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀbenzo[b]pyran (1f) (C19H20N2O7)
belong to the monoclinic system, at 25 °C: a = 8.455(2),
b = 8.916(2), c = 24.670(5) Å, β = 96.93(2)°, V = 1846.1(6) Å3,
dcalc = 1.397 g cm–3, Z = 4, space group P21/n.
The unit cell parameters and intensities of 4278 reflecꢀ
tions were measured on an automated fourꢀcircle Siemens
16. L. G. Sharanina, V. N. Nesterov, G. V. Klokol, L. A.
Rodinovskaya, V. E. Shklover, Yu. A. Sharanin, Yu. T.

Oneꢀstep synthesis of 2ꢀaminoꢀ4Hꢀbenzo[b]pyrans
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 5, May, 2003
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Struchkov, and V. K. Promonenkov, Zh. Org. Khim., 1986,
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[Chem. Heterocycl. Compd., 1997, 33 (Engl. Transl.)].
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Sharanin, A. M. Shestopalov, and L. A. Rodinovskaya, Acta
Crystallogr., Sect. C, 1985, 41, 1191.
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Litvinov, Khim. Geterotsikl. Soedin., 1991, 205 [Chem.
Heterocycl. Compd., 1991, 27 (Engl. Transl.)].
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100, 7384.
24. L. BerkovitchꢀYellin and L. Leiserowitz, Acta Crystallogr.,
Sect. B, 1984, 40, 159.
19. V. N. Nesterov, A. M. Shestopalov, and L. A. Rodinovskaya,
25. G. R. Desiraju, Acc. Chem. Res., 1991, 29, 290.
26. F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G.
Orpen, and R. Taylor, J. Chem. Soc., Perkin Trans. 2, 1987, 1.
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1973, 104, 447.
Tez.
dokl.,
Natsional´naya
kristallokhimicheskaya
konferentsiya [Abstrs. of Papers, AllꢀRussian CrystalꢀChemiꢀ
cal Conference], (Chernogolovka, May 24—29, 1998),
Chernogolovka, 1998, Uꢀ40 (in Russian).
20. A. V. Samet, A. M. Shestopalov, V. N. Nesterov, and V. V.
Semenov, Synthesis, 1997, 6, 623.
21. G. V. Klokol, L. G. Sharanina, V. N. Nesterov, V. E.
Shklover, Yu. A. Sharanin, and Yu. T. Struchkov, Zh. Org.
Khim., 1987, 23, 412 [J. Org. Chem. USSR, 1987, 23 (Engl.
Transl.)].
28. G. M. Sheldrick, SHELXL97. Program for the Refinement of
Crystal Structure, Göttingen University, Göttingen (Gerꢀ
many), 1997.
Received June 20, 2002;
in revised form January 16, 2003