Efficient synthesis of benzo[g]- and benzo[h]chromene derivatives by one-pot three-component condensation of aromatic aldehydes with active methylene compounds and naphthols

Article abstract of DOI:10.1134/S1070428006120098

A convenient procedure is reported for the synthesis of benzo[g]-and benzo[h]chromene derivatives via one-pot three-component condensation of aromatic aldehydes with malononitrile or ethyl cyanoacetate and 1-or 2-naphthol in the presence of 10 mol % of ti

Full text of DOI:10.1134/S1070428006120098

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 12, pp. 1813–1815. © Pleiades Publishing, Inc., 2006.
Published in Russian in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 12, pp. 1824–1826.
Efficient Synthesis of Benzo[g]- and Benzo[h]chromene
Derivatives by One-Pot Three-Component Condensation
of Aromatic Aldehydes with Active Methylene Compounds
and Naphthols*
B. Sunil Kumara, N. Srinivasulua, R. H. Udupia, B. Rajithab, Y. Thirupathi Reddyb,
P. Narsimha Reddyb, and P. S. Kumarb
a Department of Chemistry, N.E.T. Pharmacy College, Raichur (Karnataka), India
e-mail: penthala_nr@yahoo.co.in
b Department of Chemistry, National Institute of Technology, Warangal (AP), India
Abstract—A convenient procedure is reported for the synthesis of benzo[g]- and benzo[h]chromene deriva-
tives via one-pot three-component condensation of aromatic aldehydes with malononitrile or ethyl cyano-
acetate and 1- or 2-naphthol in the presence of 10 mol % of titanium tetrachloride as catalyst. The reactions
require no solvent; they are characterized by simple experimental procedure and easy isolation and can be
performed on enlarged scale.
DOI: 10.1134/S1070428006120098
Any new procedure for the synthesis of required
compounds should fit the principle of ideal synthesis
as maximally as possible. According to Wender [1],
an ideal synthesis is that ensuring one-step preparation
of a target product in quantitative yield from readily
accessible and inexpensive starting materials; in addi-
tion, it should be environmentally safe.
phylactic, spasmodic, diuretic, antibacterial, antifun-
gal, insecticide, and anticarcinogenic activity [9], as
well as potential biodegradable agrochemicals [10],
were found among benzopyran derivatives.
Many known procedures for the synthesis of benzo-
pyran derivatives involve three-component condensa-
tion of an active methylene compound, aromatic alde-
hyde, and activated phenol in the presence of a base
[11]. However, the application of some of these
methods is limited due to poor yields and laborious
workup procedure. Titanium(IV) chloride was reported
as a good catalyst for such processes as reduction [12],
esterification [13], hydroamination [14], and others
[15]. On the other hand, there are no published data on
the synthesis of polyfunctionalized benzopyran deriva-
tives in the presence of TiCl4. In the present com-
munication we describe a general and highly effective
synthetic route to benzopyran derivatives using inex-
Benzopyran derivatives exhibit diverse pharmaco-
logical activity depending on the nature and position of
substituents in their molecules. Benzopyran system
constitutes a structural fragment of many natural
products [2] which are widely distributed in the plant
kingdom and are important due to their biological
activity [3–6]. Compounds of the benzopyran series
are used as food additives, cosmetic agents, pigments
[7], fragrant substances, optical bleachers, fluorescent
disperse dyes, and tunable laser dyes [8]. In the recent
years, compounds exhibitng anticoagulant, antiana-
Scheme 1.
OH
O
NH2
R'
TiCl4, room temperature
ArCHO
+
R'CH2CN
+
R
R
Ar
I
II
III
IVa–IVt
For Ar, R, and R', see table.
* The text was submitted by the authors in English.
1813

SUNIL KUMAR et al.
1814
Yields of benzo[g]- and benzo[h]chromenes IVa–IVt in the three-component condensation of substituted benzaldehydes,
malononitrile or ethyl cyanoacetate, and 1- or 2-naphtol
Compound no.
Ar
C6H5
R1
CN
RC6H4OH
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
Reaction time, min
Yield,a %
91
mp, °C
205 [16]
235 [16]
220 [16]
229 [11]
215 [16]
216 [11]
236 [16]
245 [11]
184 [11]
274 [16]
255 [16]
187 [16]
191 [11]
115 [16]
260 [11]
165
15
15
20
10
30
45
35
10
10
10
10
25
12
07
20
05
10
20
15
10
IVa
IVb
IVc
IVd
IVe
IVf
IVg
IVh
IVi
2-ClC6H4
3-ClC6H4
4-ClC6H4
2,4-Cl2C6H3
3-O2NC6H4
4-O2NC6H4
4-HO6H4
CN
89
CN
87
CN
91
CN
83
CN
84
CN
89
CN
92
4-MeOC6H4
C6H5
CN
90
CN
90
IVj
IVk
IVl
4-MeC6H4
4-O2NC6H4
4-MeOC6H4
2-MeOC6H4
2-ClC6H4
C6H5
CN
93
CN
75
CN
83
IVm
IVn
IVo
IVp
IVq
IVr
IVs
IVt
CN
82
CN
78
COOEt
COOEt
COOEt
COOEt
COOEt
95
4-FC6H4
88
237
2-O2NC6H4
4-MeOC6H4
2-ClC6H4
85
248
86
213
87
246
a
Yield of the isolated product.
pensive and commercially available titanium tetra-
chloride as catalyst under solvent-free conditions.
EXPERIMENTAL
The melting points were determined in open capil-
lary and are uncorrected.
According to the proposed procedure, a mixture of
aromatic aldehyde I, active methylene compound II
(malononitrile or ethyl cyanoacetate), activated phenol
III (1- or 2-naphthol), and TiCl4 (10 mol %) was
stirred at room temperature until the reaction was com-
plete (Scheme 1). The product was extracted into
appropriate solvent, the extract was dried and concen-
trated, and the residue was purified by recrystalliza-
tion. The reaction times and yields of substituted
benzochromenes IVa–IVf are given in table. It is seen
that the nature of substituent in the initial reactants
does not affect the yield of the condensation products
to a considerable extent. In all cases, the yields of
IVa–IVf were fairly high (75–95%). Some increase in
the reaction time may be noted for aromatic aldehydes
containing electron-withdrawing groups (e.g., NO2).
Ethyl 2-amino-4-phenyl-4H-benzo[g]chromene-
3-carboxylate (IVp). A mixture of 1 mol of benzalde-
hyde, 1 mol of ethyl cyanoacetate, 1 mol of 2-naph-
thol, and 0.1 mol (10 mol %) of TiCl4 was stirred for
5 min at room temperature. The progress of the reac-
tion was monitored by TLC. When the reaction was
complete, the mixture was extracted with ethyl acetate,
the extract was washed with water and dried over
anhydrous sodium sulfate, the solvent was removed,
and the residue was recrystallized from ethanol. IR
spectrum, ν, cm–1: 3404, 3296, 2989, 2938, 2904,
1671, 1615, 1525, 1402, 1306, 1219, 1072, 825, 815,
1
743. H NMR spectrum, δ, ppm: 1.41 t (3H, CH3),
4.28 q (2H, CH2), 5.64 s (1H, CH), 6.35 br.s (2H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 12 2006

EFFICIENT SYNTHESIS OF BENZO[g]- AND BENZO[h]CHROMENE DERIVATIVES
1815
2. Hatakeyama, S., Ochi, N., Numata, H., and Takanao, S.,
J. Chem Soc., Chem. Commun., 1988, p. 1202; Cingo-
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3. Kennedy, R.O. and Thornes, R.D., Coumarins: Biology,
Applications, and Mode of Action, Chichester: Wiley,
1997.
NH2), 7.10–8.08 m (11H, Harom). Mass spectrum, m/z:
346.4 [M]+, 317.4 [M – C2H5]+, 300.4 [M – C2H5 –
NH2]+. Found, %: 76.48; H 5.50; N 4.10. C22H19NO3.
Calculated, %: C 76.50; H 5.54; N 4.06. M 345.
Compounds IVa–IVo and IVq–IVt were synthe-
sized in a similar way.
Ethyl 2-amino-4-(4-fluorophenyl)-4H-benzo[g]-
chromene 3-carboxylate (IVq). IR spectrum, ν, cm–1:
3404, 3191, 2924, 2716, 2209, 1716, 1610, 1549,
4. Murray, R.D.H., Medez, J., and Brown, S.A., The
Natural Coumarins: Occurrence, Chemistry, and Bio-
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1
5. Hammad. A., El-Sayed Ali, Islam Inas, E., and
1496, 1407, 1299, 1276, 1128, 1080, 754. H NMR
Shafik, N., J. Chem. Soc. Pak., 1990, vol. 12, p. 292.
spectrum, δ, ppm: 1.33 t (3H, CH3), 3.90 q (2H, CH2),
7.42–9.74 m (10H, Harom), 7.28 br.s (2H, NH2), 9.10 s
(1H, CH). Found, %: C 72.68; H 5.01; F 5.20; N 3.89.
C22H18FNO3. Calculated, %: C 72.72; H 4.99; F 5.23;
N 3.85.
6. Samokhvalov, A.N., Vishnyakova, G.M, and Smirno-
va, T.V., Izv. Akad. Nauk SSSR, Ser. Biol., 1989, no. 1,
p. 144.
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Ed. (The Chemistry of Heterocyclic Compounds, vol.
31), New York: Wiley, 1977.
Ethyl 2-amino-4-(2-nitrophenyl)-4H-benzo[g]-
chromene-3-carboxylate (IVr). IR spectrum, ν, cm–1:
3468, 3332, 3095, 3016, 1682, 1600, 1524, 1436,
1404, 1353, 1305, 1276, 1251, 1220, 1069, 822, 721.
1H NMR spectrum, δ, ppm: 1.29 t (3H, CH3), 4.02 m
and 4.37 m (2H, CH2), 6.45 br.s (2H, NH2), 6.58 s (1H,
CH), 7.14–8.72 m (10H, Harom). Found, %: C 67.65;
H 4.68; N 7.16. C22H18N2O5. Calculated, %: C 67.69;
H 4.65; N 7.18.
8. Maeda, M., Laser Dyes, New York: Academic, 1984.
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Philadelphia: Lea & Febiger, 1989, 3rd ed.; Andre-
ani, L.L. and Lapi, E., Boll. Chim. Farm., 1960, vol. 99,
p. 583; Bonsignora, L., Loy, G., Secci, D., and Caligna-
no, A., Eur. J. Med. Chem., 1993, vol. 28, p. 517.
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El-Taweel, F.M.A.A., Heterocycles, 1987, vol. 26, 903;
Abdel Galil, F.M., Riad, B.Y., Sherif, S.M., and
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vol. 53, p. 1534.
Ethyl 2-amino-4-(4-methoxyphenyl)-4H-benzo-
[g]chromene-3-carboxylate (IVs). IR spectrum, ν,
cm–1: 3418, 3305, 3207, 2979, 2958, 2933, 2831, 1660,
1627, 1612, 1515, 1504, 1456, 1407, 1371, 1310, 1262,
1243, 1227, 1159, 1098, 1061, 805, 792. 1H NMR spec-
trum, δ, ppm: 1.20 t (3H, CH3), 3.49 s (3H, OCH3),
4.06 q (2H, CH2), 4.83 s (1H, CH), 6.36 br.s (2H,
NH2), 6.47–7.26 m (10H, Harom). Found, %: C 73.55;
H 5.66; N 3.80. C23H21NO4. Calculated, %: C 73.58;
H 5.64; N 3.73.
Ethyl 2-amino-4-(4-chlorophenyl)-4H-benzo-
[g]chromene-3-carboxylate (IVt). IR spectrum, ν,
cm–1: 3403, 3293, 2998, 2977, 2956, 1667, 1519, 1401,
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Marcantoni, E., and Sambri, L., Org. Lett., 2000, vol. 2,
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1
1221, 1074, 740. H NMR spectrum, δ, ppm: 1.29 t
13. Taber, D.F., Sheth, R.B., and Joshi, P.V., J. Org. Chem.,
(3H, CH3), 4.27 q (2H, CH2), 6.02 s (1H, CH),
6.42 br.s (2H, NH2), 6.99–8.36 m (10H, Harom). Found,
%: C 69.56; H 4.75; Cl 9.31; N 3.71. C22H18ClNO3.
Calculated, %: C 69.57; H 4.78; Cl 9.33; N 3.69.
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The authors are thankful to UGC for financial
assistance and the Director, IISC (Bangalore), for
1
recording the H NMR spectra and IICT (Hyderabad)
for mass spectral analysis.
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