Synthesis of indenes via aluminum chloride-promoted tandem Friedel-Crafts alkylation of arenes and cinnamaldehydes

Article abstract of DOI:10.1016/j.molcata.2014.04.027

A series of substituted indenes were synthesized from arenes and cinnamaldehydes via aluminum chloride-promoted tandem Friedel-Crafts alkylation. The scope and limitation of the tandem reaction were explored. A plausible reaction mechanism is also discuss

Full text of DOI:10.1016/j.molcata.2014.04.027

Journal of Molecular Catalysis A: Chemical 391 (2014) 168–174
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Synthesis of indenes via aluminum chloride-promoted tandem
Friedel–Crafts alkylation of arenes and cinnamaldehydes
Haiouani Kheira, Pingfan Li, Jiaxi Xu∗
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology,
Beijing 100029, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of substituted indenes were synthesized from arenes and cinnamaldehydes via aluminum
chloride-promoted tandem Friedel–Crafts alkylation. The scope and limitation of the tandem reaction
were explored. A plausible reaction mechanism is also discussed. This approach provides a convenient
method for the synthesis of indene derivatives using a readily available and low cost Lewis acid and
starting materials.
Received 21 January 2014
Received in revised form 11 April 2014
Accepted 18 April 2014
Available online 28 April 2014
© 2014 Elsevier B.V. All rights reserved.
Keywords:
Arene
Aluminum chloride
Indene
Friedel–Crafts alkylation
Tandem reaction
Cascade reaction
1. Introduction
of research groups as well [6]. We have also reported tandem
Friedel–Crafts acylation and alkylation of arenes with acyl chlo-
Tandem reactions usually show higher efficiency and conve-
nience than corresponding multi-step reaction sequences. Thus,
they have attracted much attention recently, and have been used
widely in synthetic organic chemistry [1]. Friedel–Crafts alkyl-
ation is a classical method for the preparation of alkyl arenes
despite limitations like multiple alkylation and rearrangement
[2]. Tandem Friedel–Crafts reactions, if well designed, could
streamline many otherwise difficult synthesis of arene deriva-
tives. An early example of tandem Friedel–Crafts alkylation is
anhydrous aluminum chloride (AlCl3) catalyzed synthesis of triph-
enylmethane from benzaldehyde and benzene [3]. Similarly,
benzaldehyde was reacted with benzene or toluene to gener-
ate triphenylmethane or phenylditolylmethane, respectively, in
the presence of acetyl chloride and Lewis acids, including LnCl3
(Ln = Pr, Dy, Er, Sm, Yb) and Yb(OTf)3 [4]. Recently, we found
both aromatic and aliphatic aldehydes reacted with electron-
rich arenes in tandem Friedel–Crafts alkylation pathways to
afford 1,1,1-triarylalkanes or 1,1-diarylalkanes in the presence
of anhydrous AlCl3 under solvent-free conditions [5]. Strong
protic acid-catalyzed tandem Friedel–Crafts reactions of arenes
with aromatic aldehydes have been investigated by a number
rides or ␣,␤-unsaturated acyl chlorides to give 1,1-diaryl-1-alkenes
or indanone derivatives, respectively, in good yields in the pres-
ence of anhydrous AlCl3 [7]. Tandem reactions of ␣,␤-unsaturated
acyl chlorides with phenols produced dihydrocoumarins [8]. A
Cu(OTf)2-catalyzed tandem Friedel–Crafts alkylation/cyclization
process was used to synthesize dihydroindenes [9]. Indenoindene-
fused ␣-methylene-␥-butyrolactones were prepared via a tan-
dem intra- and intermolecular Friedel–Crafts reaction [10].
The trifluoroacetic acid-mediated tandem Friedel–Crafts alkyl-
ation/cyclization/hydrogen transfer sequence gave an efficient
method to prepare flavylium derivatives from chalcones and
phenols [11]. The trifluoromethanesulfonic acid (TfOH) catalyzed
tandem Friedel–Crafts acylation and alkylation of arenes and
4,4,4-trifluoro/3-(trifluoromethyl)crotonic acids gave rise to tri-
fluoromethylated dihydrochalcones and indanones [12]. We have
also realized the synthesis of dihydrochalcones via AlCl3-promoted
tandem Friedel–Crafts acylation and alkylation of arenes with ␣,␤-
unsaturated acyl chlorides [13].
Indene derivatives represent a very important class of carbo-
cyclic compounds with interesting biological activities to serve as
drug candidates [14]. They have attracted much attention as lig-
ands in tailored metallocene complexes, especially for Group 4
metallocene catalysts for olefin polymerization [15]. Consequently,
many approaches toward the synthesis of indene ring systems
have been developed. The most important methods include
∗
Corresponding author. Tel.: +86 10 6443 5565; fax: +86 10 6443 5565.
E-mail address: jxxu@mail.buct.edu.cn (J. Xu).
http://dx.doi.org/10.1016/j.molcata.2014.04.027
1381-1169/© 2014 Elsevier B.V. All rights reserved.

H. Kheira et al. / Journal of Molecular Catalysis A: Chemical 391 (2014) 168–174
169
acid-catalyzed cyclodehydration of phenyl-substituted allylic
alcohols [16], cyclization of phenyl-substituted propynes [17],
ring expansion of substituted cyclopropenes [18], addition of
organometallic reagents to 1-indanone followed by dehydration
[19], cyclization of chalcones [20] or ␤-arylalkyl carbonyl com-
pounds [21], and many transition-metal catalyzed protocols [22].
As a continuation of our studies on tandem Friedel–Crafts alkyl-
ation [5,7,13], we initiated a study for the reaction between arenes
and cinnamaldehydes under the catalysis of Lewis acids to prepare
indene derivatives. Herein, we report a facile synthesis of substi-
tuted indenes via AlCl3-promoted tandem Friedel–Crafts alkylation
of arenes with cinnamaldehydes. A plausible reaction mechanism
is also discussed.
2.2.4. 1,3-Bis(4-methoxyphenyl)indene (4b)
Colorless oil; yield: 66 mg (20%). 1H NMR (400 MHz, CDCl3): ı
7.45 (d, J = 7.9 Hz, 2H, ArH), 7.35 (d, J = 8.3 Hz, 1H, ArH), 7.11 (d,
J = 7.3 Hz, 2H, ArH), 7.07 (d, J = 6.9 Hz, 1H, ArH), 7.02 (d, J = 7.7 Hz, 2H,
ArH), 6.83 (d, J = 8.0 Hz, 2H, ArH), 6.77–6.64 (m, 2H, ArH), 6.29 (d,
J = 10.7 Hz, 1H, CH), 4.47 (d, J = 10.7 Hz, 1H, CH), 3.65 (s, 3H, CH3O),
3.57 (s, 3H, CH3O). 13C NMR (100 MHz, CDCl3): ı 159.4, 158.6, 143.8,
143.4, 135.6, 134.6, 131.6, 129.0, 128.7, 127.7, 126.7, 125.6, 124.3,
121.1, 120.6, 114.3, 114.2, 114.1, 114.0, 110.8, 55.6, 55.4, 54.6. IR
(ꢀmax, cm−1) 831, 1031, 1480, 1608, 3059. HRMS (ESI) calcd for
C23H21O2 m/z: 329.1536 [M+H]+; found 329.1541.
2.2.5. 5-Methyl-3-phenyl-1H-indene (3ca) and
7-methyl-3-phenyl-1H-indene (3cb) and
6-methyl-3-phenyl-1H-indene (3cc)
2. Experimental
Light yellow oil; yield: 228 mg (71%). 1H NMR (400 MHz, CDCl3):
ı 7.50–7.46 (m, 3H, ArH), 7.41–7.36 (m, 5H, ArH), 7.40–7.30 (m, 5H,
ArH), 7.29–7.22 (m, 5H, ArH), 7.18–7.16 (m, 2H, ArH), 7.13–7.11 (m,
2H, ArH), 7.07–7.04 (m, 2H, ArH), 6.54 (t, J = 2.0 Hz, 1H, CH), 6.51 (t,
J = 2.0 Hz, 1H, CH), 6.48 (t, J = 2.0 Hz, 1H, CH), 3.48 (d, J = 2.0 Hz, 2H,
CH2), 3.44 (d, J = 2.0 Hz, 2H, CH2), 3.37 (d, J = 2.0 Hz, 2H, CH2), 2.41
(s, 9H, 3CH3). 13C NMR (100 MHz, CDCl3): ı 145.1, 145.08, 145.05,
141.8, 141.7, 141.4, 141.3, 141.25, 141.23, 138.1, 138.0, 135.7, 135.6,
134.5, 134.4, 129.7, 129.3, 129.2, 128.4, 128.3, 128.2, 127.6, 127.5,
127.4, 126.8, 126.5, 126.0, 125.9, 125.6, 125.5, 124.9, 124.8, 124.7,
124.5, 124.0, 123.7, 120.9, 120.0, 119.9, 118.1, 118.07, 118.04, 37.9,
37.7, 36.9, 21.5, 21.3, 21.2. IR (ꢀmax, cm−1) 830, 1365, 1466, 1600,
3050. HRMS (ESI) calcd for C16H14 m/z: 207.1168 [M+H]+; found
207.1170.
2.1. General methods
1H NMR and 13C NMR spectra were recorded on a Bruker 400
(400 MHz) spectrometer in CDCl3 with TMS as an internal standard.
IR spectra were obtained on a Nicolet AVATAR 330 FTIR spec-
trometer. HRMS spectra were recorded with an LC/MSD TOF mass
spectrometer. TLC analysis was performed on glass pre-coated sil-
ica gel YT257–85 (10–40 ␮m) plates. Spots were visualized with UV
light or iodine. Column chromatography was performed on silica
gel zcx II (200–300 mesh) with petroleum ether and ethyl acetate
as the eluent.
2.2. General procedure for AlCl3-promoted tandem Friedel–Crafts
alkylation of arenes with cinnamaldehydes
2.2.6. 4,7-Dimethyl-3-phenyl-1H-indene (3d)
Light yellow oil; yield: 219 mg (60%). 1H NMR (400 MHz, CDCl3):
ı 7.53–7.50 (m, 2H, ArH), 7.45–7.42 (m, 2H, ArH), 7.37–7.35 (m, 2H,
ArH), 7.33–7.31 (m, 1H, ArH), 6.65 (t, J = 2.0 Hz, 1H, CH), 3.56 (d,
J = 2.0 Hz, 2H, CH2), 2.46 (s, 3H, CH3), 2.39 (s, 3H, CH3). 13C NMR
(101 MHz, CDCl3): ı 144.4, 142.9, 142.6, 136.5, 135.1, 132.8, 130.7,
129.4, 129.0, 128.8, 126.9, 126.8, 120.2, 118.9, 38.7, 21.6, 21.6. IR
(ꢀmax, cm−1) 834, 1360, 1480, 1610, 3050. HRMS (ESI) calcd for
To a mixture of anhydrous aluminum chloride (0.53 g, 4 mmol)
and arene (2 mL) was added a solution of cinnamaldehyde (0.13 g,
1 mmol) in the same arene (1 mL) dropwise under reflux. The result-
ing mixture was kept stirring for 5 h under reflux. After cooling
to room temperature and addition of water (10 mL), the resulting
mixture was extracted with chloroform (10 mL × 3). The combined
organic solution was dried over Na2SO4. After evaporation of the
solvent, the residue was purified on silica gel column with a mix-
ture of petroleum ether (60–90 ◦C fraction) and ethyl acetate (15:1,
v/v) as eluent to afford the desired product.
C
17H17 m/z: 221.1325 [M+H]+; found 221.1332.
2.2.7. 5-Fluoro-3-phenyl-1H-indene (3ea) and
7-fluoro-3-phenyl-1H-indene (3eb)
Light yellow oil; yield: 132 mg (63%). 1H NMR (400 MHz, CDCl3):
ı 7.57–7.51 (m, 6H, ArH), 7.39 (dd, J = 8.4, 3.6 Hz, 2H, ArH), 7.32–7.30
(m, 2H, ArH), 7.26–7.22 (m, 2H, ArH), 7.12 (dd, J = 14.5, 5.8 Hz, 4H,
ArH), 6.59 (t, J = 2.1 Hz, 1H, CH), 6.53 (t, J = 2.1 Hz, 1H, CH), 3.50 (d,
J = 1.8 Hz, 2H, CH2) 3.49 (d, J = 1.8 Hz, 2H, CH2). 13C NMR (100 MHz,
CDCl3): ı 164.2, 163.6, 144.7, 144.6, 144.2, 144.1, 143.5, 143.4,
130.1, 130.0, 129.3, 129.2, 126.3, 126.2, 125.1, 125.0, 124.3, 124.2,
123.4, 123.3,120.2, 120.1,115.6, 115.4, 114.7, 114.6, 114.5, 114.3,
38.2, 38.1. IR (ꢀmax, cm−1) 758, 1271, 1486, 1662, 3461. HRMS (ESI)
calcd for C15H12F m/z: 211.0918 [M+H]+; found 211.0923.
2.2.1. 3-Phenylindene (3a) [23]
Light yellow oil; yield: 149 mg (78%). 1H NMR (400 MHz, CDCl3):
ı 7.60 (dd, J = 9.9, 2.8 Hz, 3H, ArH), 7.54 (d, J = 7.3 Hz, 1H, ArH), 7.45
(t, J = 7.5 Hz, 2H, ArH), 7.39–7.24 (m, 3H, ArH), 6.58 (t, J = 2.0 Hz, 1H,
CH), 3.51 (d, J = 2.0 Hz, 2H, CH2).
2.2.2. 1,3-Diphenylindene (4a) [24]
Colorless oil; yield: 24 mg (9%). 1H NMR (400 MHz, CDCl3): ı 7.64
(d, J = 7.1 Hz, 2H, ArH), 7.59 (d, J = 7.5 Hz, 1H, ArH), 7.44 (t, J = 7.4 Hz,
2H, ArH), 7.36 (dd, J = 10.5, 4.2 Hz, 1H, ArH), 7.32–7.24 (m, 4H, ArH),
7.22–7.15 (m, 4H, ArH), 6.62 (d, J = 2.0 Hz, 1H, CH), 4.68 (d, J = 2.0 Hz,
1H, CH).
2.2.8. 5-Chloro-3-phenyl-1H-indene (3fa) and
7-chloro-3-phenyl-1H-indene (3fb)
Light yellow oil; yield: 165 mg (73%). 1H NMR (400 MHz, CDCl3):
ı 7.53–7.51 (m, 6H, ArH), 7.42–7.43 (m, 2H, ArH), 7.35–7.31 (m, 4H,
ArH), 7.28–7.25 (m, 4H, ArH), 6.60 (t, J = 2.1 Hz, 1H, CH), 6.57 (t,
J = 2.1 Hz, 1H, CH), 3.51 (d, J = 2.1 Hz, 2H, CH2), 3.50 (d, J = 2.1 Hz,
2H, CH2). 13C NMR (100 MHz, CDCl3): ı 134.65, 143.60, 133.5,
133.4, 131.3, 131.2, 130.8, 130.7, 130.5, 130.3, 128.8, 128.7, 127.9,
127.7, 126.7, 126.6, 125.26 125.22, 124.8, 124.08, 124.02, 123.2,
119.09, 119.07, 37.22, 37.20. IR (ꢀmax, cm−1) 747, 1265, 1489, 1663,
3435. HRMS (ESI) calcd for C15H12Cl m/z: 227.0622 [M+H]+; found
227.0624.
2.2.3. 5-Methoxy-3-phenyl-1H-indene (3ba)
Light yellow oil; yield: 148 mg (67%). 1H NMR (400 MHz, CDCl3):
ı 7.66–7.63 (m, 2H, ArH), 7.57 (s, 1H, ArH), 7.43 (d, J = 4.0 Hz, 2H,
ArH), 7.28 (s, 1H, ArH), 7.04–7.02 (m, 2H, ArH), 6.69 (t, J = 2.1 Hz,
1H, CH), 3.92 (s, 3H, CH3O), 3.54 (d, J = 2.1 Hz, 2H, CH2). 13C NMR
(101 MHz, CDCl3): ı = 158.2, 147.9, 133.3, 129.1, 129.1, 128.7, 128.4,
127.5, 112.9, 112.5, 112.4, 112.4, 110.6, 54.2, 39.3. IR (ꢀmax, cm−1
)
818, 1030, 1470, 1604, 3049. HRMS (ESI) calcd for C16H15O m/z:
223.1117 [M+H]+; found 223.1120.

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H. Kheira et al. / Journal of Molecular Catalysis A: Chemical 391 (2014) 168–174
2.2.9. 5-Bromo-3-phenyl-1H-indene (3ga) and
7-bromo-3-phenyl-1H-indene (3gb)
1489, 1605, 3054. HRMS (ESI) calcd for C15H11Cl2 m/z: 261.0232
[M+H]+; found 261.0232.
Light yellow oil; yield: 164 mg (61%). 1H NMR (400 MHz, CDCl3):
ı 7.66–7.60 (m, 4H, ArH), 7.48–7.51 (m, 4H, ArH), 7.48–7.41 (m,
3H, ArH), 7.40–7.35 (m, 3H, ArH), 6.66 (t, J = 2.1 Hz, 1H, CH), 6.65
(t, J = 2.1 Hz, 1H, CH), 3.57 (d, J = 1.8 Hz, 2H, CH2), 3.56 (d, J = 1.8 Hz,
2H, CH2). 13C NMR (100 MHz, CDCl3): ı 144.7, 144.6, 144.1, 143.9,
143.5, 143.4, 130.7, 130.6, 129.4, 129.3, 126.4 126.3, 125.2, 125.1,
2.2.15. 5,6-Dichloro-3-(4-chlorophenyl)-1H-indene (3k)
Light yellow oil; yield: 354 mg (68%). 1H NMR (400 MHz, CDCl3):
ı 7.55–749 (m, 1H, ArH), 7.42–7.35 (m, 2H, ArH), 7.29–7.27 (m, 1H,
ArH), 7.22–7.15 (m, 2H, ArH), 6.46 (t, J = 2.0 Hz, 1H, CH), 3.37 (d,
J = 2.0 Hz, 2H, CH2). 13C NMR (100 MHz, CDCl3): ı 144.7, 143.16,
143.14, 136.2, 132.38, 132.36, 131.6, 130.7, 129.6, 127.1, 126.5,
125.4, 124.4, 120.0, 38.4. IR (ꢀmax, cm−1) 680, 766, 1460, 1665,
3050. HRMS (ESI) calcd for C15H10Cl3 m/z: 294.9843 [M+H]+; found
294.9846.
124.3, 124.2, 121.6, 121.5, 120.1, 120.0, 38.3, 38.1. IR (ꢀmax, cm−1
)
754, 1029, 1468, 1653, 3444. HRMS (ESI) calcd for C15H12Br m/z:
271.0117 [M+H]+; found 271.0120.
2.2.10. 5,6-Dichloro-3-phenyl-1H-indene (3h)
Light yellow oil; yield: 208 mg (80%). 1H NMR (400 MHz, CDCl3):
ı 7.68 (d, J = 1.9 Hz, 1H, ArH), 7.52 (dd, J = 12.3, 7.6 Hz, 3H, ArH),
7.47–7.41 (m, 1H, ArH), 7.37–7.33 (m, 1H, ArH), 7.26 (dd, J = 6.5,
5.2 Hz, 1H, ArH), 6.59 (t, J = 2.1 Hz, 1H, CH), 3.50 (d, J = 2.1 Hz, 2H,
CH2). 13C NMR (100 MHz, CDCl3): ı 144.5, 142.9, 142.8, 136.1, 132.1,
131.4, 130.4, 130.3, 129.4, 126.9, 126.2, 125.2, 124.2, 119.8, 38.2. IR
(ꢀmax, cm−1) 765, 1244, 1468, 1665, 3350. HRMS (ESI) calcd for
2.2.16. 6-Chloro-1,3-bis(3,4-dichlorophenyl)-1H-indene (4k)
Light yellow oil; yield: 80 mg (7%). 1H NMR (400 MHz, CDCl3): ı
7.46–7.42 (m, 2H, ArH), 7.33 (s, 1H, ArH), 7.31–7.26 (m, 2H, ArH),
7.26 (s, 1H, ArH), 7.21 (s, 1H, ArH), 7.16–7.14 (m, 2H, ArH), 6.62 (d,
J = 2.0 Hz, 1H, CH), 4.68 (d, J = 2.0 Hz, 1H, CH). 13C NMR (100 MHz,
CDCl3): ı 148.0, 143.4, 142.3, 139.5, 136.2, 135.3, 133.0, 132.2,
131.1, 130.8, 129.8, 129.7, 127.5, 127.1, 126.5, 126.3, 125.6, 125.1,
124.6, 120.6, 54.5. IR (ꢀmax, cm−1) 680, 750, 1468, 1605, 3350. HRMS
(ESI) calcd for C21H12Cl5 m/z: 438.9376 [M+H]+; found 438.9380.
C
15H11Cl2 m/z: 261.0232 [M+H]+; found 261.0235.
2.2.11. 1,3-Bis(3,4-dichlorophenyl)-1H-indene (4h)
Colorless oil; yield: 40 mg (10%). 1H NMR (400 MHz, CDCl3): ı
7.72 (d, J = 1.7 Hz, 1H, ArH), 7.51 (t, J = 6.7 Hz, 2H, ArH), 7.46 (dd,
J = 8.2, 1.8 Hz, 1H, ArH), 7.33 (dd, J = 10.0, 5.3 Hz, 2H, ArH), 7.21–7.27
(m, 3H, ArH), 6.98 (dd, J = 8.2, 1.8 Hz, 1H, ArH), 6.56 (d, J = 2.0 Hz,
1H, CH), 4.62 (d, J = 2.0 Hz, 1H, CH). 13C NMR (100 MHz, CDCl3): ı
147.9, 143.3, 142.2, 139.3, 136.0, 135.1, 132.9, 132.7, 132.0, 130.7,
2.2.17. 5,6-Dichloro-3-(4-methoxyphenyl)-1H-indene (3l)
Colorless oil; yield: 223 mg (77%). 1H NMR (400 MHz, CDCl3): ı
7.52 (d, J = 3.1 Hz, 1H, ArH), 7.37 (s, 2H, ArH), 7.23 (d, J = 4.1 Hz, 1H,
ArH), 6.98 (dd, J = 8.3, 1.9 Hz, 2H, ArH), 6.64 (t, J = 2.1 Hz, 1H, CH),
3.87 (s, 1H, CH3O), 3.49 (d, J = 2.1 Hz, 2H, CH2). 13C NMR (101 MHz,
CDCl3): ı 159.2, 148.9, 134.3, 130.1, 130.1, 129.8, 129.4, 128.5,
113.9, 113.5, 113.4, 111.6, 55.3, 40.3. IR (ꢀmax, cm−1) 822, 1030,
129.7, 129.5, 127.3, 126.9, 126.4, 124.4, 120.5, 54.3. IR (ꢀmax, cm−1
)
754, 1029, 1468, 1653, 3444. HRMS (ESI) calcd for C21H13Cl4 m/z:
1470, 1664, 3110. HRMS (ESI) calcd for C16H13
Cl2O m/z: 291.0338
404.9766 [M+H]+; found 404.9768.
[M+H]+; found 291.0340.
2.2.12. 3-(4-Chlorophenyl)-1H-indene (3i)
3. Results and discussion
Colorless oil; yield: 176 mg (78%). 1H NMR (400 MHz, CDCl3): ı
7.59 (dd, J = 7.5, 2.7 Hz, 1H), 7.53–7.51 (m, 1H, ArH), 7.46–7.42 (m,
1H, ArH), 7.37–7.35 (m, 1H, ArH), 7.34–7.29 (m, 1H, ArH), 7.26–7.21
(m, 1H, ArH), 6.57 (t, J = 2.1 Hz, 1H, CH), 3.49 (d, J = 2.1 Hz, 2H, CH2).
13C NMR (100 MHz, CDCl3): ı 145.2, 144.8, 143.9, 136.2, 130.9,
For our new approach toward indene derivatives via tandem
Friedel–Crafts alkylation of arenes and cinnamaldehydes under the
catalysis of Lewis acids, we optimized the reaction conditions using
benzene (1a) and cinnamaldehyde (2a) as model starting materials.
These results are summarized in Table 1.
128.6, 127.7, 127.6, 126.2, 124.9, 124.1, 120.3, 38.2. IR (ꢀmax, cm−1
)
640, 767, 1446, 1600, 3050. HRMS (ESI) calcd for C15H12Cl m/z:
Lewis acids such as BF3·OEt2, ZnCl2, and FeCl3·6H2O and protic
acid H2NSO3H were ineffective for our desired reaction (Table 1,
entries 1–5). However, when anhydrous FeCl3 or AlCl3 was used,
the desired product was obtained (Table 1, entries 7 and 8). Treat-
ment of cinnamaldehyde (2a) in benzene with AlCl3 in a molar
ratio 1:1.3 of substrate 2a:AlCl3 (benzene in excess) at room
temperature gave rise to a mixture of 3-phenylindene (3a) and
1,3-diphenylindene (4a) in low yields (Table 1, entry 8). Increas-
ing the amount of benzene resulted in yield improvement of
3-phenylindene (3a) slightly (Table 1, entries 9 and 10). The both
yields of 3a and 4a increased significantly with an increase of the
AlCl3 loading (Table 1, entry 11). When the reaction was conducted
at 50 ◦C for 10 h, the yield of the product 3a further increased to
60%, while the yield of the product 4a decreased to 10%, showing
a better selectivity (Table 1, entry 12). Further elevating the reac-
tion temperature and shortening the reaction time improved both
yields and selectivity (Table 1, entries 11–13). However, extending
the reaction time resulted in a decrease in selectivity under reflux-
ing conditions (Table 1, entries 14 and 15). The products 3a and
4a were obtained in 78% and 9%, respectively, when the reaction
was performed under reflux for 5 h (Table 1, entry 15). The optimal
reaction conditions are as following: a solution of cinnamaldehyde
(1a) (1 mmol) in benzene (1 mL) was added dropwise to a suspen-
sion of anhydrous AlCl3 (4 mmol) in benzene (2 mL) under reflux,
and the reaction mixture was further refluxed for 5 h.
227.0622 [M+H]+; found 227.0622.
2.2.13. 6-Chloro-1,3-diphenyl-1H-indene (4i)
Colorless oil; yield: 30 mg (10%). 1H NMR (400 MHz, CDCl3):
ı 7.69–7.66 (m, 1H, ArH), 7.55 (d, J = 8.1 Hz, 2H, ArH), 7.43 (dd,
J = 8.3, 2.4 Hz, 2H, ArH), 7.36–7.32 (m, 3H, ArH), 7.25–7.20 (m, 3H,
ArH), 6.98–6.95 (m, 2H, ArH), 6.58 (d, J = 2.1 Hz, 1H, CH), 4.63 (d,
J = 2.1 Hz, 1H, CH). 13C NMR (100 MHz, CDCl3): ı 149.6, 142.8, 140.7,
138.3, 136.2, 134.6, 130.9, 130.8, 130.0, 129.6, 129.4, 128.1, 127.6,
127.3, 126.9, 126.3, 125.3, 124.9, 123.2, 121.4, 54.2. IR (ꢀmax, cm−1
)
822, 1031, 1469, 1663, 3367. HRMS (ESI) calcd for C21H16Cl m/z:
303.0935 [M+H]+; found 303.0938.
2.2.14. 5-Chloro-3-(4-chlorophenyl)-1H-indene (3ja) and
7-chloro-3-(4-chlorophenyl)-1H-indene (3jb)
Colorless oil; yield: 221 mg (85%). 1H NMR (400 MHz, CDCl3): ı
7.52–7.50 (m, 2H, ArH), 7.47–7.45 (m, 2H, ArH), 7.42–7.38 (m, 4H,
ArH), 7.37–7.32 (m, 2H, ArH), 7.32–7.26 (m, 2H, ArH), 7.25–7.07 (m,
2H, ArH), 6.64–6.57 (m, 2H, ArH), 6.56 (t, J = 2.1 Hz, 1H, CH), 6.54 (t,
J = 2.1 Hz, 1H, CH), 3.46 (d, J = 2.1 Hz, 2H, CH2), 3.45 (d, J = 2.1 Hz,
2H, CH2). 13C NMR (101 MHz, CDCl3): ı 146.4, 146.3, 143.5, 143.4,
142.8, 142.7, 142.0, 141.9, 133.0, 132.0, 131.5, 129.9, 129, 128.9,
128.8, 127.7, 127.7, 127.3, 126.5, 126.4, 125.8, 125.7, 125.1, 125.0,
124.7, 124.6, 120.9, 120.8, 38.08, 38.07. IR (ꢀmax, cm−1) 694, 820,

H. Kheira et al. / Journal of Molecular Catalysis A: Chemical 391 (2014) 168–174
171
Table 1
Tandem Friedel–Crafts reaction of benzene (1a) and cinnamaldehyde (2a).a
Ph
Ph
Lewis acid
CHO
+
+
Ph
benzene
Ph
1a
2a
3a
4a
.
Entry
Lewis acid
Loading (mmol)
Benzene (mL)
Reaction temp. (◦C)
Reaction time (h)
Yield (%)b
3a
4a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
BF3·OEt2
ZnCl2
ZnCl2
H2NSO3H
FeCl3·6H2O
FeCl3
FeCl3
AlCl3
AlCl3
AlCl3
4
4
4
4
4
4
4
1.3
1.3
1.3
4
4
4
1
1
1
1
1
1
1
1
1.5
2
2
2
2
2
2
25–30
25–30
Reflux
Reflux
25–30
25–30
Reflux
25–30
25–30
25–30
25–30
50
24
12
12
12
24
12
12
15
15
15
12
10
1
0
0
0
0
Trace
0
Trace
9
14
9
14
15
47
60
18
53
78
Trace
0
Trace
Trace
5
8
9
9
15
10
2
5
9
AlCl3
AlCl3
AlCl3
AlCl3
Reflux
Reflux
Reflux
4
4
3
5
AlCl3
a
A solution of cinnamaldehyde (0.13 g, 1 mmol) in benzene (1 mL) was added to a suspension of Lewis acid in benzene.
Isolated yield.
b
Table 2
Synthesis of substituted indenes from arenes and cinnamaldehydes.a
R1
R2
R2
R1
AlCl3
CHO
+
+
+
benzene
R1
R2
R2
2a
1a
4
R1
3xa
3xb
R1
.
Entry
Starting materials
Products
Yieldb (%)
3
4
Ph
Ph
Ph
+
1
2
1a + 2a
78
67
9
3a
4a
C6H4(OMe)-p
Ph
MeO
+
1b + 2a
20
C6H4(OMe)-p
3ba
4b
Ph
Ph
Ph
+
+
3
4
1c + 2a
1d + 2a
71 (3ca:3cb:3cc 1.00:0.78:0.76)c
Trace
Trace
3cc
3ca
3cb
60

172
H. Kheira et al. / Journal of Molecular Catalysis A: Chemical 391 (2014) 168–174
Table 2 (Continued)
Entry
Starting materials
Products
Yieldb (%)
3
4
Ph
Ph
F
+
5
6
7
1e + 2a
63 (3ea:3eb 1:1) c
73 (3fa:3fb 1:1) c
61 (3ga:3gb 1:1) c
Trace
F
3eb
3ea
3fa
3ga
Ph
Ph
Cl
Br
+
+
1f + 2a
Trace
Trace
Cl
3fb
Ph
Ph
1g + 2a
Br
3gb
8
9
1h + 2a
1a + 2b
80
78
10
10
C6H4Cl-p
C6H4Cl-p
Cl
+
10
11
1f + 2b
85 (3ja:3jb 1:1) c
Trace
Cl
3ja
3jb
1f + 2b
1h + 2c
68
77
7
12
Trace
a
A solution of a cinnamaldehyde (1 mmol) in an arene (1 mL) was added in a suspension of AlCl3 (0.53 g, 4 mmol) in the same arene (2 mL) under refluxing. The resulting
solution was further stirred under refluxing for 5 h.
b
Isolated yield.
c
Determined by 1H NMR spectrum.
After successful optimization of the reaction conditions, we
subsequently studied the scope of the reaction by examining vari-
ous substituted benzenes and cinnamaldehydes. These results are
presented in Table 2. Substituted benzenes and cinnamaldehy-
des can produce both 3-arylindenes 3 and 1,3-diarylindenes 4,
with 3 as major products. Our extension of substrate scope started
with examining different arenes. Anisole (1b) with a strongly
electron-donating methoxy group on the benzene ring provided
both products 3ba and 4b in yields of 67% and 20%, respectively,
possibly due to its high electrophilicity (Table 2, entry 2). However,
toluene (1c) gave rise to a mixture of isomeric 5-/7-/6-methyl-
3-phenylindenes (3ca, 3cb, and 3cc in ratio of 1.00:0.78:0.76)
possibly due to its high reactivity with an electron-donating methyl
group on the benzene ring (Table 2, entry 3). The results indicate
that toluene was alkylated on its ortho, para, and meta positions
although anisole was alkylated on its para-position only. The
difference in the regioselectivity is attributed to the different sub-
stituents (methyl and methoxy). Methoxy is a more electron-rich

H. Kheira et al. / Journal of Molecular Catalysis A: Chemical 391 (2014) 168–174
173
AlCl3
H
AlCl3
AlCl3
O
HO+
O
O
-
H+
- HOAlCl3
AlCl3
- H+
- H+
Ph
Ph
Ph
Ph
Ph
H
2a
Ph
Ph
Ph
H
H+
Path A
3a
6
Ph
Ph
Ph
H
5
- H+
+ H+
Ph
Ph
H
Ph
- H+
Ph
Path B
Ph
Ph
7
8
OPh
Ph
O
+OH2
- H2O
Ph
Ph
O OH
O+
+
+ H+
O2
H2O
-H+
Ph
Ph
Ph
Ph
9
H
+OH
Ph
Ph
Ph
PhO+
PhO
Ph
OH
OH
+ H+
OH
-PhOH
+ H+
- H+
- H2O
Ph
Ph
Ph
10
4a
11
Scheme 1. Proposed mechanism for AlCl3-promoted tandem Friedel–Crafts alkylation of arenes with cinnamaldehydes.
group than methyl and shows good direction in the alkylation step.
Treatment of 2a with p-xylene (1d) produced the corresponding
indene product 3d only in a yield of 60% (Table 2, entry 4). As
for the reactions of various halobenzenes 1e–g, pairs of different
regiomeric indene derivatives 3e–g were obtained in good yields
varying from 61% to 73%, regardless of the halogen substitution, in
1:1 ratio because both ortho and para alkylation occurred (Table 2,
entries 5–7). The regiomeric ratios were determined by 1H NMR
spectral analysis. Even the reaction of o-dichlorobenzene (1h) and
cinnamaldehyde (2a) produced both products 3h and 4h in 80% and
10% yields, respectively (Table 2, entry 8).
We then investigated the generality of different cinnamaldehy-
des 2 in the current tandem reaction. 4-Chlorocinnamaldehyde (2b)
was reacted with benzene under the optimized conditions to pro-
duce both products 3i and 4i in yields of 78% and 10%, respectively
(Table 2, entry 9). However, when 2b was reacted with chloroben-
zene (1f), two regiomeric indene derivatives 3ja and 3jb generated
in 85% yield in a ratio of 1:1 and no product 4j was observed (Table 2,
entry 10). When 2b was reacted with o-dichlorobenzene (1h) it pro-
duced both products 3k and 4k in 68% and 7% yields, respectively
(Table 2, entry 11). The reaction of 4-methoxycinnamaldehyde (2c)
and o-dichlorobenzene (1h) gave rise to 3l as sole product in a yield
of 77% (Table 2, entry 12).
A plausible mechanism of the tandem reaction is proposed in
Scheme 1. The oxygen atom of the carbonyl group in cinnamalde-
hyde first coordinates with AlCl3, which initiates a Friedel–Crafts
alkylation with benzene and subsequent deoxygenation to gen-
erate 1,3-diphenylallylium (5). The subsequent reaction can take
place in two distinct pathways (Path A and Path B). In Path A, 1,3-
diphenylallylium (5) undergoes an intramolecular Friedel–Crafts
alkylation to directly afford 1-phenylindene (6), which further iso-
merizes to the better conjugated and more stable 3-phenylindene
(3a) under the acidic reaction conditions. Alternatively, in Path B,
1,3-diphenylallylium (5) can undergo a competitive intermolec-
ular Friedel–Crafts alkylation with another molecule of benzene
to yield 1,3,3-triphenylpropene (7), which would then undergo
another intramolecular Friedel–Crafts alkylation to generate 1,3-
diphenylindane (8) under acidic conditions. 1,3-Diphenylindane
(8) could then be oxidized in the presence of air to afford perox-
ide 9, which undergoes a rearrangement to generate phenol and
protonated indanone 10, similar to the mechanism for the clas-
sical preparation of phenol and acetone from isopropylbenzene
via oxygen oxidation. The protonated indanone 10 further par-
ticipates in another intermolecular Friedel–Crafts alkylation with
benzene to give 1,3-diphenylindan-1-ol (11), which undergoes an
elimination of water to produce 1,3-diphenylindene (4a). Since the
intramolecular reaction of 1,3-diphenylallylium (5) proceeds faster
than the intermolecular version, product 3a generates in preference
to 4a.
4. Conclusion
In summary, the reaction between cinnamaldehydes and
arenes under Lewis acid conditions was investigated. This tan-
dem Friedel–Crafts alkylation process can generate substituted
indene derivatives in good yields in the presence of anhy-
drous AlCl3. The scope and limitation of the tandem reaction
were studied. The intermolecular Friedel–Crafts alkylation of
cinnamaldehydes and arenes, deoxygenation, and subsequent
intramolecular Friedel–Crafts alkylation generated 3-arylindene
derivatives. Competitively, the intermediates of the intermolecu-
lar Friedel–Crafts alkylation underwent a further intermolecular
Friedel–Crafts alkylation with a second molecule of arene fol-
lowed by an intramolecular Friedel–Crafts alkylation, air oxidation,
rearrangement, another intermolecular Friedel–Crafts alkylation,
and acidic elimination to gave rise to 1,3-diarylindene derivatives.

174
H. Kheira et al. / Journal of Molecular Catalysis A: Chemical 391 (2014) 168–174
The current method features the use of easily available starting
materials in one-pot tandem reaction to synthesize a series of
indene derivatives using aluminum chloride, a readily available and
low cost Lewis acid.
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