A convenient synthesis of 2-amino-3-cyano-4-aryl-1,4,5,6-tetrahydrobenzo[h] chromenes derivatives using KF-Al2O3 as catalyst

Article abstract of DOI:10.1081/SCC-200030542

A series of new 2-amino-3-cyano-4-aryl-1,4,5,6-tetrahydrobenzo[h]chromenes derivatives were synthesized by the reaction of malononitrile with 2-arylmethylidene-3, 4-dihydro-1(2H)-naphthalenone in N,N-dimethylformamide (DMF) at 80°C catalyzed by KF-Al₂O₃. The structure of the product was confirmed by x-ray analysis.

Full text of DOI:10.1081/SCC-200030542

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A Convenient Synthesis of
2‐Amino‐3‐cyano‐4‐aryl‐1,4,5,6‐te
Derivatives Using KF‐Al2O3 as
Catalyst
Xiang‐shan Wang a b c , Zhao‐sen Zeng a , Da‐qing
Shi a c , Xian‐yong Wei b & Zhi‐min Zong b
a Department of Chemistry , Xuzhou Normal
University , Xuzhou Jiangsu, 221116, China
b School of Chemical Engineering , China
University of Mining and Technology , Xuzhou
Jiangsu, China
c The Key Laboratory of Biotechnology on Medical
Plant , Xuzhou Jiangsu, China
Published online: 10 Jan 2011.
To cite this article: Xiang‐shan Wang , Zhao‐sen Zeng , Da‐qing Shi ,
Xian‐yong Wei & Zhi‐min Zong (2004) A Convenient Synthesis of
2‐Amino‐3‐cyano‐4‐aryl‐1,4,5,6‐tetrahydrobenzo[h]chromenes Derivatives Using
KF‐Al2O3 as Catalyst, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:18, 3265-3271, DOI: 10.1081/
SCC-200030542
To link to this article: http://dx.doi.org/10.1081/SCC-200030542
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 18, pp. 3265–3271, 2004
A Convenient Synthesis of 2-
Amino-3-cyano-4-aryl-1,4,5,6-
tetrahydrobenzo[h]chromenes
Derivatives Using KF-Al2O3 as Catalyst
1
1,3
Xiang-shan Wang,1,2,3, Zhao-sen Zeng, Da-qing Shi,
*
Xian-yong Wei,2 and Zhi-min Zong2
1Department of Chemistry, Xuzhou Normal University,
Xuzhou Jiangsu, China
2School of Chemical Engineering, China University of Mining
and Technology, Xuzhou Jiangsu, China
3The Key Laboratory of Biotechnology on Medical Plant,
Xuzhou Jiangsu, China
ABSTRACT
A series of new 2-amino-3-cyano-4-aryl-1,4,5,6-tetrahydrobenzo[h]chromenes
derivatives were synthesized by the reaction of malononitrile with 2-aryl-
methylidene-3, 4-dihydro-1(2H)-naphthalenone in N,N-dimethylformamide
(DMF) at 808C catalyzed by KF-Al2O3. The structure of the product was
confirmed by x-ray analysis.
*
Correspondence: Xiang-shan Wang, Department of Chemistry, Xuzhou Normal
University, Xuzhou Jiangsu 221116, China; E-mail: xswang1974@yahoo.com.
3265
DOI: 10.1081/SCC-200030542
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3266
Wang et al.
Key Words: Benzo[h]chromene; Malononitrile; KF-Al2O3; Synthesis.
The synthesis of chromenes and their derivatives is of high interest in
organic chemistry. In particular, 2-aminochromenes constitute the basic struc-
ture of natural products possessing biological and pharmacological activi-
ties,[1,2] such as antijuvenile hormones,[3] antiallergenics,[4] and anticancer
agents.[5] The utility of fluoride salts as a potential base in a variety of
synthetic reactions has been recognized in recent years.[6] However, low solu-
bility of fluoride salts in ordinary solvents hampers their wide application in
organic synthesis. On the other hand, there has been increasing use of inor-
ganic solid supports as catalysts for many years,[7] resulting in higher selectiv-
ity, milder reaction conditions, and easier work-up. In particular, potassium
fluoride coated with alumina (KF-alumina) has been a versatile solid-
supported reagent used for Knoevenagel reaction,[8] Henry reaction,[9]
Darzens reaction,[10] Witting reaction,[11] alkylation,[12] elimination,[10] and
any other reactions.[13] In our previous paper,[14] we reported the reaction of
2-arylmethylidene-3,4-dihydro-1(2H)-naphthalenone with malononitrile at
room temperature, with 3-aryl propionitrile derivatives being obtained. As an
extension of the study, this paper reports on the synthesis of a new series of
2-amino-3-cyano-4-aryl-1,4,5,6-tetrahydrobenzo[h]chromenes
using KF-Al2O3 as catalyst.
derivatives
When 2-arylmethylidene-3, 4-dihydro-1(2H)-naphthalenone (1), malono-
nitrile (2), and KF/Al2O3 were kept at 808C for 3ꢀ6 hr in DMF (Sch. 1), the
desired 2-amino-3-cyano-4-aryl-1,4,5,6-tetrahydrobenzo[h]chromenes deri-
vatives (3) were obtained in good yields (Table 1). The structure of 3a was
confirmed by X-ray analysis.a The structure of the product 3a was shown in
Fig. 1.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
Infrared (IR) spectra were recorded on a FT IR-8101 spectrometer (Shimadzu
1
Scientific Instrument Corporation of Japan). H nuclear magnetic resonance
(NMR) spectra were measured on an Inova-400 spectrometer (Varian Inc.,
USA) using tetramethylsilane (TMS) as internal standard. Microanalyses
aX-Ray crystallography for 3a: Empirical formula C21H18N2O2, Fw ¼ 330.37,
˚
˚
T ¼ 296(2) K, monoclinic, space group P2(1)/c, a ¼ 6.478(1) A, b ¼ 25.557(5) A,
3
˚
˚
c ¼ 10.549(2) A, a ¼ 908, b ¼ 96.75(2)8, g ¼ 908, V ¼ 1734.4(5) A , Z ¼ 4,
Dc ¼ 1.265 Mg/m , l(MoKa) ¼ 0.71073 A, m ¼ 0.08 mm21, F(000) ¼ 696. 1.598,
3
˚
u , 25.258, R ¼ 0.0367, wR ¼ 0.0854. S ¼ 0.891, Largest diff. peak and hole: 0.148
23
˚
and 20.111 e. A
.

Synthesis of Chromenes and Their Derivatives
3267
Scheme 1.
were carried out using a Carlo Erba 1110 analyzer (Carlo Erba Inc., Italy).
X-ray diffraction was measured on a Siemens P4 diffractometer (Brucker
Company, Germany).
General Procedure for Preparation of KF-Al2O3
To a solution of KF (58 g) in water (100 mL) was added Al2O3 (100 g)
with stirring. The mixture was stirred for 3 hr at 808C, then the solvent was
evaporated and the solid was dried for 4 hr at 1208C to give KF-Al2O3.
General Procedure for Synthesis 2-Amino-3-cyano-4-aryl-
1,4,5,6-tetrahydrobenzo[h]chromenes 3
A dry 100-mL flask was charged with 2-arylmethylidene-3, 4-dihydro-
1(2H)-naphthalenone (1) (5 mmol), malononitrile (2) (5 mmol), KF/Al2O3,
and DMF (20 mL). The mixture was stirred at 808C for 3–6 hr then cooled
to room temperature. The solid material was filtered off and washed with
DMF. The filterate was poured into 200 mL of water. The yellow solid was
Table 1. Yields of the products.
Entry
Ar
R
Yield (%)
3a
3b
3c
3d
3e
3f
4-CH3OC6H4
C6H5
H
92
90
87
94
90
89
86
92
H
4-CH3C6H4
4-ClC6H4
H
H
3-NO2C6H4
2,4-Cl2C6H3
4-CH3C6H4
4-ClC6H4
H
H
3g
3h
CH3
CH3

3268
Wang et al.
Figure 1. X-ray crystal structure of 3a.
filtered off and then washed with water. The crude solid was purified by
recrystallization from 95% EtOH to give (3).
3a: mp 1838C–1848C; IR (KBr, n, cm21): 3427, 3325, 3066, 2933, 2898,
2192, 1698, 1639, 1588, 1470, 1420, 1274, 1090, 840, 765; 1H NMR
(DMSO-d6, d, ppm): 1.83–2.18(m, 2H, CH2), 2.57–2.76 (m, 2H, CH2),
3.74 (s, 3H, OCH3), 4.02 (s, 1H, CH), 6.75–7.51(m, 10H, NH2 þ ArH);
(Found: C, 76.28; H, 5.60; N, 8.35. C21H18N2O2 requires C, 76.34; H, 5.49;
N, 8.48%).
3b: mp 2018C–2038C; IR (KBr, n, cm21): 3455, 3303, 3045, 2909, 2827,
2191, 1699, 1648, 1598, 1504, 1415, 1376, 1321, 1270, 1137, 1107, 1013,
763; 1H NMR (CDCl3, d, ppm): 2.04–2.20(m, 2H, CH2), 2.63–2.84 (m, 2H,
CH2), 4.09(s, 1H, CH), 4.55(s, 2H, NH2), 7.11–7.54 (m, 9H, ArH).
(Found: C, 79.80; H, 5.49; N, 9.27. C20H16N2O requires C, 79.98; H, 5.37;
N, 9.33%).
3c: mp 1668C–1688C; IR (KBr, n, cm21): 3429, 3276, 3026, 2937, 2828,
2183, 1692, 1649, 1598, 1407, 1356, 1321, 1282, 1145, 1095, 1036, 802, 771,
736; 1H NMR (CDCl3, d, ppm): 2.06–2.19 (m, 2H, CH2), 2.32 (s, 3H, CH3),
2.63–2.78 (m, 2H, CH2), 4.04 (s, 1H, CH), 4.52 (s, 2H, NH2), 7.10–7.46

Synthesis of Chromenes and Their Derivatives
3269
(m, 8H, ArH). (Found: C, 80.11; H, 5.99; N, 8.77. C21H18N2O requires C,
80.23; H, 5.77; N, 8.91%).
3d: mp 1758C–1778C; IR (KBr, n, cm21): 3404, 3310, 3010, 2952,
2877, 2827, 2191, 1692, 1649, 1605, 1504, 1414, 1254, 1172, 1095, 1028,
1
845, 802, 763; H NMR (CDCl3, d, ppm): 1.96–2.24 (m, 2H, CH2), 2.69–
2.87 (m, 2H, CH2), 4.26 (s, 1H, CH), 4.70 (s, 2H, NH2), 7.14–7.46 (m, 8H,
ArH). (Found: C, 71.69; H, 4.61; N, 8.30. C20H15ClN2O requires C, 71.75; H,
4.52; N, 8.37%).
3e: mp 1768C–1778C; IR (KBr, n, cm21): 3447, 3318, 2920, 2850, 2191,
1649, 1590, 1488, 1379, 1289, 1180, 1079, 888, 814, 755; 1H NMR (CDCl3, d,
ppm): 2.01–2.21 (m, 2H, CH2), 2.63–2.84 (m, 2H, CH2), 4.08 (s, 1H, CH),
4.61 (s, 2H, NH2), 7.13–8.16 (m, 8H, ArH). (Found: C, 69.44; H, 4.50; N,
12.15. C20H15N3O3 requires C, 69.56; H, 4.38; N, 12.17%).
3f: mp 2118C–2128C; IR (KBr, n, cm21): 3436, 3279, 3025, 2928, 2834,
2191, 1691, 1641, 1605, 1539, 1415, 1356, 1270, 1137, 1095, 771; 1H NMR
(CDCl3, d, ppm): 1.95–2.26 (m, 2H, CH2), 2.63–2.82 (m, 2H, CH2),
4.63 (s, 2H, NH2), 4.78 (s, 1H, CH), 7.12–7.47 (m, 7H, ArH). (Found: C,
64.92; H, 3.99; N, 7.42. C20H14Cl2N2O requires C, 65.06; H, 3.82; N, 7.59%).
3g: mp 2048C–2068C; IR (KBr, n, cm21): 3455, 3310, 3018, 2936, 2818,
2183, 1692, 1633, 1590, 1488, 1406, 1356, 1312, 1270, 1087, 1013, 845, 771;
1H NMR (CDCl3, d, ppm): 2.05–2.19 (m, 2H, CH2), 2.32 (s, 6H, 2CH3),
2.62–2.78 (m, 2H, CH2), 4.03 (s, 1H, CH), 4.52 (s, 2H, NH2), 6.94–
7.36 (m, 7H, ArH). (Found: C, 80.27; H, 6.20; N, 8.44. C22H20N2O requires
C, 80.46; H, 6.14; N, 8.53%).
3h: mp 2008C–2028C; IR (KBr, n, cm21): 3435, 3318, 3045, 2936, 2818,
1
2183, 1679, 1633, 1590, 1497, 1415, 1340, 1270, 1137, 1107, 824; H NMR
(CDCl3, d, ppm): 1.96–2.18 (m, 2H, CH2), 2.33 (s, 3H, CH3), 2.63–
2.80 (m, 2H, CH2), 4.07 (s, 1H, CH), 4.56 (s, 2H, NH2), 6.95–7.36 (m, 7H,
ArH). (Found: C, 72.20; H, 4.93; N, 8.01. C21H17ClN2O requires C, 72.31; H,
4.91; N, 8.03%).
ACKNOWLEDGMENTS
We are grateful to the Foundation of the Surpassing Project of Jiangsu
Province and the Natural Science Foundation of the Education Committee
of Jiangsu Province for financial support.
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Received in Japan March 31, 2004