Efficient and facile synthesis of 3-amino-1-aryl-9h-fluorene-2,4- dicarbonitrile under solvent-free conditions

Article abstract of DOI:10.1080/00397910902779298

A versatile and efficient route to 3-amino-1-aryl-9H-fluorene-2,4- dicarbonitrile via multicomponent reactions of 1-indanone, aromatic aldehydes, and malononitrile under solvent-free conditions using NaOH as the catalyst is described. This method provides

Full text of DOI:10.1080/00397910902779298

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Efficient and Facile Synthesis
of 3-Amino-1-aryl-9H-
fluorene-2,4-dicarbonitrile
Under Solvent-Free Conditions
Liangce Rong a b , Hongxia Han a , Hong Jiang b
Shujiang Tu a b
&
a College of Chemistry and Chemical Engineering,
Xuzhou Normal University, Xuzhou, China
b Key Laboratory of Biotechnology for Medicinal
Plant, Xuzhou, Jiangsu, China
Version of record first published: 04 Sep 2009
To cite this article: Liangce Rong, Hongxia Han, Hong Jiang & Shujiang Tu (2009):
Efficient and Facile Synthesis of 3-Amino-1-aryl-9H-fluorene-2,4-dicarbonitrile Under
Solvent-Free Conditions, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 39:19, 3493-3499
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Synthetic Communications1, 39: 3493–3499, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902779298
Efficient and Facile Synthesis of 3-Amino-1-
aryl-9H-fluorene-2,4-dicarbonitrile Under
Solvent-Free Conditions
Liangce Rong,1,2 Hongxia Han,1 Hong Jiang,2 and Shujiang Tu1,2
1College of Chemistry and Chemical Engineering, Xuzhou Normal
University, Xuzhou, China
2Key Laboratory of Biotechnology for Medicinal Plant,
Xuzhou, Jiangsu, China
Abstract: A versatile and efficient route to 3-amino-1-aryl-9H-fluorene-2,4-
dicarbonitrile via multicomponent reactions of 1-indanone, aromatic aldehydes,
and malononitrile under solvent-free conditions using NaOH as the catalyst
is described. This method provides several advantages over alternative procedures
such as mild, solvent-free conditions at ambient temperature and direct isolation
of the products in good yields.
Keywords: Fluorene, grinding, multicomponent reactions, solvent-free, synthesis
In this new century, green chemistry has become a major driving force for
organic chemists to develop environmentally benign routes to a myriad of
materials.[1] One of the green synthetic methods, solvent-free organic
synthesis, has garnered much attention from organic chemists. This
method has many advantanges, such as high efficiency and selectivity,
easy separation and purification, and mild reaction conditions, and these
benefit industry as well as the environment.[2]
Multicomponent reactions, an important class of organic tandem
reactions, are one-pot processes with at least three components that form
Received April 28, 2008.
Address correspondence to Liangce Rong, College of Chemistry and Chemical
Engineering, Xuzhou Normal University, Xuzhou, China. E-mail: lcrong2005@
yahoo.com
3493

3494
L. Rong et al.
Scheme 1. The reaction of 1-indanone, aromatic aldehydes, and malononitrile
under solvent-free conditions.
a single product, which incorporates most or even all of the starting
materials.[3] The huge interest for such multicomponent reactions during
the recent years has been oriented toward developing combinatorial
chemistry procedures because of the high efficiency and convenience of
these reactions in comparison with multistage procedures.
In recent years, we have synthesized several compounds using this
technique.[4] Herein, we report the preparation of 3-amino-1-aryl-9H-
fluorene-2,4-dicarbonitrile derivatives under solvent-free conditions.
Fluorene and fluorene derivatives are important compounds and have
different types of biological activities, such as anti-inflammatory[5] and
antitumor activites.[6] The literature reports that the tetrahydrobenzo[a]-
fluorine compounds also inhibit bone loss or bone resorption.[7] Recently,
we found an efficient and facile method to synthesize this compound by a
multicomponent reaction under solvent-free conditions. 1-Indanone 1, aro-
matic aldehydes 2, and malononitrile 3 were blended together in a mortar
and ground at room temperature (Scheme 1). The reaction completed
within a very short time (1–3min), and a series of 3-amino-1-aryl-9H-
fluorene-2,4-dicarbonitrile derivatives could be gained with good yields.
The results of the reaction are listed in Table 1. The structures of the
Table 1. Synthetic results of compounds 4
Entry
Ar
Time (min)
Product
Yield (%)
Mp (ꢀC)
1
2
3
4
5
6
7
8
9
10
4-CH3C6H4
4-CH3OC6H4
3,4-(CH3O)2C6H3
4-FC6H4
4-BrC6H4
4-ClC6H4
2-ClC6H4
3-ClC6H4
2,4-Cl2C6H3
3,4-Cl2C6H3
2
2
3
2
3
2
2
2
1
1
4a
4b
4c
4d
4e
4f
81
80
75
82
78
83
80
76
87
77
269–270
215–217
219–221
266–268
246–248
259–260
293–294
263–265
265–267
277–279
4g
4h
4i
4j

3-Amino-1-aryl-9H-fluorene-2,4-dicarbonitrile
3495
Scheme 2. Plausible mechanism of 3-amino-1-aryl-9H-fluorene-2,4-dicarbonitrile
formation.
products were confirmed on the basis of infrared (IR), 1H NMR
spectroscopic data, and elemental analysis, and the formation of com-
pound 4 could be explained by a possible mechanism presented in Scheme 2.
In conclusion, we have developed a rapid and highly efficient method
for the synthesis of 3-amino-1-aryl-9H-fluorene-2,4-dicarbonitrile via the
reaction of different aromatic aldehydes, 1-indanone, and malononitrile
under solvent-free conditions. Particularly valuable features of this
method include the greater yields of the products, mild reaction condi-
tions, and reduced environmental impact, which make it a useful and
attractive process for the synthesis of these important compounds.
EXPERIMENTAL
General Procedure
Melting points were uncorrected. IR spectra were recorded on a Tensor
1
27 spectrometer in KBr. H NMR spectra were obtained in dimethyl-
sulfoxide (DMSO)-d6 solution with Me4Si as internal standard using a
Bruker 400-MHz spectrometer. Elemental analyses were carried out
using a Perkin-Elmer 240 II analyzer.
General Procedure for the Syntheses of 3-Amino-1-aryl-9H-
fluorene-2,4-dicarbonitrile
The general procedure is as follows: 1-indanone 1 (2 mmol), aromatic
aldehyde 2 (2 mmol), malononitrile 3 (5 mmol), and NaOH (0.2 g) were

3496
L. Rong et al.
added to a mortar. The mixture was ground with a pestle at room
temperature. The reaction was completed within 1–3 min, and the reac-
tion mixture was poured into water. The product was filtered, dried,
and recrystallized from 95% ethanol.
Data
3-Amino-1-p-tolyl-9H-fluorene-2,4-dicarbonitrile (4a)
Mp: 269–270ꢀC. IR (KBr) v: 3470, 3372, 3234, 3036, 2894, 2208, 1632,
1564, 1516, 1476, 1447, 1398, 1376, 1305, 1267, 1186, 1155, 1100, 826,
1
758, 726 cmꢁ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 2.42 (3H, s,
CH3), 3.70 (2H, s, CH2), 6.73 (2H, s, NH2), 7.38 (2H, d, J ¼ 8.0 Hz,
ArH), 7.48 (2H, d, J ¼ 8.0 Hz, ArH), 7.53 (2H, t, J ¼ 7.2 Hz, ArH),
7.63 (1H, d, J ¼ 6.8 Hz, ArH), 8.35 (1H, d, J ¼ 7.6 Hz, ArH). Anal. calcd.
for C22H15N3: C, 82.22; H, 4.70; N, 13.08. Found: C, 82.40; H, 4.63; N,
13.01.
3-Amino-1-(4-methoxyphenyl)-9H-fluorene-2,4-dicarbonitrile (4b)
Mp: 215–217ꢀC; IR (KBr) v: 3469, 3346, 3232, 2931, 2836, 2215, 2180,
1638, 1610, 1546, 1513, 1460, 1394, 1305, 1277, 1253, 1175, 1104, 1032,
;
829, 755, 723 cmꢁ1 1H NMR (400 MHz, DMSO-d6) (d, ppm): 3.72
(2H, s, CH2), 3.81 (3H, s, CH3O), 6.71 (2H, s, NH2), 6.96 (2H, d,
J ¼ 8.4 Hz, ArH), 7.12 (2H, d, J ¼ 8.4 Hz, ArH), 7.33 (2H, d, J ¼ 8.0 Hz,
Hz, ArH), 7.64 (1H, d, J ¼ 6.8 Hz, ArH), 8.35 (1H, d, J ¼ 7.6 Hz, ArH).
Anal. calcd. for C22H15N3O: C, 78.32; H, 4.48; N, 12.46. Found: C,
78.48; H, 4.55; N, 12.26.
3-Amino-1-(3,4-dimethoxyphenyl)-9H-fluorene-2,4-dicarbonitrile (4c)
Mp: 219–221ꢀC; IR (KBr) v: 3480, 3355, 3234, 2939, 2852, 2211,
2182, 1638, 1570, 1544, 1519, 1451, 1421, 1308, 1258, 1240, 1157, 1136,
;
1022, 811, 758, 721 cmꢁ1 1H NMR (400 MHz, DMSO-d6) (d, ppm):
3.77 (2H, s, CH2), 3.81 (3H, s, OCH3), 3.85 (3H, s, OCH3), 6.71
(2H, s, NH2), 7.20 (1H, s, ArH), 7.52 (2H, t, J ¼ 8.0 Hz, ArH), 7.58
(1H, d, J ¼ 8.0 Hz, ArH), 7.65 (1H, d, J ¼ 6.8 Hz, ArH), 8.23 (1H, d,
J ¼ 8.4 Hz, ArH), 8.36 (1H, d, J ¼ 8.0 Hz, ArH). Anal. calcd. for
C23H17N3O2: C, 75.19; H, 4.66. N, 11.44. Found: C, 75.38; H, 4.60; N,
11.38.

3-Amino-1-aryl-9H-fluorene-2,4-dicarbonitrile
3497
3-Amino-1-(4-fluorophenyl)-9H-fluorene-2,4-dicarbonitrile (4d)
Mp: 266–268ꢀC (lit.[8] 264–266ꢀC); IR (KBr) v: 3458, 3364, 3250, 2942,
2817, 2211, 1641, 1602, 1561, 1541, 1513, 1475, 1456, 1304, 1228, 1157,
;
1100, 844, 756, 720 cmꢁ1 1H NMR (400 MHz, DMSO-d6) (d, ppm):
3.71 (2H, s, CH2), 6.79 (2H, s, NH2), 7.42 (2H, t, J ¼ 8.8 Hz, ArH),
7.54 (2H, dd J ¼ 7.2 Hz, J ¼ 8.8 Hz, ArH), 7.65 ꢂ 7.68 (3H, m, ArH),
8.36 (1H, d, J ¼ 8.0 Hz, ArH). Anal. calcd. for C21H12FN3: C, 77.53;
H, 3.72; N, 12.92. Found: C, 77.72; H, 3.65; N, 12.83.
3-Amino-1-(4-bromophenyl)-9H-fluorene-2,4-dicarbonitrile (4e)
Mp: 246–248ꢀC (lit.[8] 257–259ꢀC); IR (KBr) v: 3464, 3361, 3230, 2928,
2840, 2218, 1633, 1575, 1559, 1494, 1476, 1449, 1394, 1375, 1303, 1264,
1
1156, 1078, 1010, 830, 755, 720 cmꢁ1; H NMR (400 MHz, DMSO-d6)
(d, ppm): 3.71 (2H, s, CH2), 6.82 (2H, s, NH2), 7.53 (2H, t, J ¼ 7.2 Hz,
ArH), 7.56 (2H, d, J ¼ 8.4 Hz, ArH), 7.64 (1H, d, J ¼ 6.8 Hz, ArH),
7.78 (2H, d, J ¼ 8.4 Hz, ArH), 8.36 (1H, d, J ¼ 7.2 Hz, ArH). Anal. calcd.
for C21H12BrN3: C, 65.30; H, 3.13; N, 10.88. Found: C, 65.48; H, 3.05; N,
10.76.
3-Amino-1-(4-chlorophenyl)-9H-fluorene-2,4-dicarbonitrile (4f)
Mp: 259–260ꢀC (lit.[8] 275–277ꢀC); IR (KBr) v: 3464, 3361, 3229, 2938, 2842,
2217, 1633, 1576, 1560, 1493, 1477, 1449, 1393, 1374, 1302, 1263, 1155,
;
1078, 1010, 830, 755, 720 cmꢁ1 1H NMR (400MHz, DMSO-d6) (d,
ppm): 3.70 (2H, s, CH2), 6.81 (2H, s, NH2), 7.52 (2H, t, J ¼ 6.8 Hz, ArH),
7.56 (2H, d, J ¼ 8.4 Hz, ArH), 7.63 (1H, d, J ¼ 7.2 Hz, ArH), 7.78 (2H, d,
J ¼ 8.4 Hz, ArH), 8.36 (1H, d, J ¼ 6.8 Hz, ArH). Anal. calcd. for
C21H12ClN3: C, 73.79; H, 3.54; N, 12.29. Found: C, 73.58; H, 3.61; N, 12.40.
3-Amino-1-(2-chlorophenyl)-9H-fluorene-2,4-dicarbonitrile (4g)
Mp: 293–294ꢀC; IR (KBr) v: 3404, 3358, 3250, 2841, 2821, 2212, 2181,
1621, 1597, 1570, 1542, 1521, 1507, 1488, 1447, 1436, 1398, 1308, 1267,
1156, 1101, 785, 753, 720 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6)
(d, ppm): 3.54 (2H, dd, J1 ¼ 22.4 Hz, J2 ¼ 22.4 Hz, CH2), 6.88 (2H,
s, NH2), 7.51–7.61 (5H, m, ArH), 7.64 (1H, d, J ¼ 7.2 Hz, ArH), 7.71
(1H, d, J ¼ 7.6 Hz, ArH), 8.37 (1H, d, J ¼ 7.6 Hz, ArH). Anal. calcd.
for C21H12ClN3: C, 73.79; H, 3.54; N, 12.29. Found: C, 73.56; H, 3.63;
N, 12.38.

3498
L. Rong et al.
3-Amino-1-(3-chlorophenyl)-9H-fluorene-2,4-dicarbonitrile (4h)
Mp: 263–265ꢀC; IR (KBr) v: 3462, 3356, 3237, 2941, 2837, 2213, 1635,
1561, 1542, 1501, 1487, 1474, 1448, 1307, 1266, 1259, 1101, 801, 748,
1
723 cmꢁ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 3.72 (2H, s, CH2),
6.81 (2H, s, NH2), 7.52 (1H, d, J ¼ 7.2 Hz, ArH), 7.57 (2H, d, J ¼ 8.0 Hz,
ArH), 7.62 (2H, d, J ¼ 6.8 Hz, ArH), 7.66 (1H, d, J ¼ 6.8 Hz, ArH),
7.72 (1H, s, ArH), 8.37 (1H, d, J ¼ 6.8 Hz, ArH). Anal. calcd. for
C21H12ClN3: C, 73.79; H, 3.54; N, 12.29. Found: C, 73.90; H, 3.48; N
12.20.
3-Amino-1-(2,4-dichlorophenyl)-9H-fluorene-2,4-dicarbonitrile (4i)
Mp: 265–267ꢀC (lit.[8] 267–269ꢀC); IR (KBr) n: 3467, 3363, 3242, 2216,
1714, 1635, 1572, 1560, 1485, 1444, 1382, 1306, 1262, 1100, 801, 751,
717 cmꢁ1;1H NMR (400 MHz, DMSO-d6) (d, ppm): 3.56 (2H, s, CH2),
6.91 (2H, s, NH2), 7.51–7.61 (5H, m, ArH), 7.92 (1H, d, J ¼ 2.0 Hz,
ArH), 8.34 (1H, d, J ¼ 7.2 Hz, ArH). Anal. calcd. for C21H11Cl2N3: C,
67.04; H, 2.95; N, 11.17. Found: C, 67.22; H, 2.88; N, 11.09.
3-Amino-1-(3,4-dichlorophenyl)-9H-fluorene-2,4-dicarbonitrile (4j)
Mp: 277–279ꢀC; IR (KBr) n: 3456, 3361, 3251, 2890, 2202, 1640, 1601,
1564, 1514, 1476, 1451, 1303, 1226, 1154, 842, 756 cmꢁ1;1H NMR
(400 MHz, DMSO-d6) (d, ppm): 3.71 (2H, s, CH2), 6.76 (2H, s, NH2),
7.36–7.66 (6H, m, ArH), 8.36 (1H, d, J ¼ 7.2 Hz, ArH). Anal. calcd. for
C21H11Cl2N3: C, 67.04; H, 2.95; N, 11.17. Found: C, 67.20; H, 2.90; N,
11.11.
ACKNOWLEDGMENTS
We thank the Natural Science Foundation of Jiangsu Education Depart-
ment (No. 08KJB150017) and the PeiYu Foundation (No. 07PYL06) of
Xuzhou Normal University for financial support.
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