Convenient synthesis of triarylmethanes and 9,10-diarylanthracenes by alkylation of arenes with aromatic aldehydes using acetyl bromide and ZnBr2/SiO2

Article abstract of DOI:10.1016/j.tetlet.2008.02.117

Reaction of electron-rich arenes with acetyl bromide and aldehydes in the presence of silica gel-supported zinc bromide was carried out in benzene to give selectively the corresponding triarylmethanes or 9,10-diarylanthracenes in high yields depending upon the ratio of an arene and an aldehyde. The mild conditions employed are especially noteworthy.

Full text of DOI:10.1016/j.tetlet.2008.02.117

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Tetrahedron Letters 49 (2008) 2537–2540
Convenient synthesis of triarylmethanes and 9,10-diarylanthracenes
by alkylation of arenes with aromatic aldehydes using acetyl
bromide and ZnBr2/SiO2
a,
a
a
b
*
Mitsuo Kodomari , Maki Nagamatsu , Megumi Akaike , Tadashi Aoyama
a Department of Applied Chemistry, Shibaura Institute of Technology, Koto-ku, Tokyo 135-8548, Japan
b College of Science and Technology, Nihon University, Chiyoda-ku, Tokyo 101-8308, Japan
Received 16 January 2008; revised 15 February 2008; accepted 21 February 2008
Available online 4 March 2008
Abstract
Reaction of electron-rich arenes with acetyl bromide and aldehydes in the presence of silica gel-supported zinc bromide was carried
out in benzene to give selectively the corresponding triarylmethanes or 9,10-diarylanthracenes in high yields depending upon the ratio of
an arene and an aldehyde. The mild conditions employed are especially noteworthy.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Triarylmethane; Anthracene; Aldehyde; Silica gel-supported zinc chloride
The acid-catalyzed Friedel–Crafts alkylation of arenes
with aromatic aldehydes has been known since 1886.1
The reaction using Lewis acid such as AlCl3 had not
received much attention until recently because of the for-
mation of many products such as triarylmethanes, triaryl-
methanol, diarylmethane, and anthracene derivatives.2
However, the analogous reaction of aldehydes has been
investigated extensively. Lewis acid-catalyzed reductive
Friedel–Crafts reaction of arenes with aromatic aldehydes
afforded exclusively the corresponding diarylmethanes.
For instance, diarylmethanes formed selectively in the reac-
tion using CaCl2,3 Sc(OTf)3/1,3-propanediol,4 and InCl3/
chloromethylsilane.5 Recently, it has been reported that
the alkylation of arenes with aldehydes using catalytic
(ZnBr2/SiO2) catalyzed alkylation of electron-rich arenes
with acetyl bromide–aromatic aldehydes gave the corre-
sponding triarylmethanes in high yields under mild condi-
tions. Triarylmethanes have attracted the attention of
chemists because of the interesting properties associated
with their derivatives.9 Although a number of methods
are available for the synthesis of triarylmethanes, most of
them are multistep process and/or require hash reaction
conditions.10 We wish to report herein a convenient and
practical method for the preparation of triarylmethanes
and 9,10-diarylanthracenes by the reaction of electron-rich
arenes with AcBr and aromatic aldehydes in the presence
of ZnBr2/SiO2. The reaction of anisole with benzaldehyde
was carried out in the presence of ZnBr2/SiO2 at room tem-
perature, but no products were obtained and anisole was
recovered. In contrast, the reaction with AcBr and benzal-
dehyde in the presence of ZnBr2/SiO2 under similar condi-
tions afforded 4,40-dimethoxytriphenylmethane 1 in high
yield.
6
7
AuCl3/3AgOTf or [Ir(COD)Cl2/SnCl4 gives triarylme-
thanes selectively. LnCl3 (Ln = Pr, Dy, Er, Sm. Yb) and
Yb(OTf)3-catalyzed alkylation of PhR (R = H, Me) with
AcCl–PhCHO also affords the corresponding triarylme-
thane.8 We found that silica gel-supported zinc bromide
Ph
OMe
+
ZnBr2/SiO2
*
CH3COBr
PhCHO
+
Corresponding author. Fax: +81 3 5859 8101.
benzene, RT
MeO
OMe
E-mail address: kodomari@sic.shibaura-it.ac.jp (M. Kodomari).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.117

2538
M. Kodomari et al. / Tetrahedron Letters 49 (2008) 2537–2540
Thus, to a mixture of anisole (4 equiv), benzaldehyde
(1 equiv), and ZnBr2/SiO2 in benzene was added drop-
as THF and dioxane the yield is very low. We next
explored the bisarylation of benzaldehyde with various are-
nes for the synthesis of triarylmethanes.12 The results are
shown in Table 1.
Electron-rich arenes such as anisole, 1,2-dimethoxy-
benzene (veratrole), 1,3,5-trimethoxybenzene, 2- and 4-
methoxytoluene, and 1-methoxynaphthalene gave the
corresponding triarylmethane in high yields (entries 1–6).
11
wise, with stirring, a solution of acetyl bromide in benzene.
After the addition, the slurry was stirred for 1 h at room
temperature, and 1 was obtained in 84% yield. Acetylani-
sole which is formed from Friedel–Crafts acylation of ani-
sole with acetyl bromide was not detected. Toluene can
also be used as a solvent, whereas in polar solvent such
Table 1
Reaction of various arenes with AcBr and benzaldehyde (PhCHO) leading to triarylmethanesa
Entry
1
Arene
Temp (°C)/time (h)
Product
Yieldb (%)
84
Ph
Anisole
rt/1
MeO
OMe
1
Ph
OMe
OMe
MeO
MeO
2
3
1,2-(MeO)2-Benzene
1,3,5-(MeO)3-Benzene
rt/1
94
71
2
Ph
OMe
OMe
OMe
rt/0.25
MeO
MeO
OMe
3
OMe
Ph
MeO
4
5
1-(MeO)-Naphthalene
2-(MeO)-Toluene
rt/1
rt/1
88
94
4
Ph
Me
Me
MeO
OMe
5
Ph
MeO
OMe
6
7
8
9
4-(MeO)-Toluene
1,2-Me2-Benzene
1,3-Me2-Benzene
1,2,3-Me3-Benzene
1-Me-Naphthalene
rt/1
90
73
72
78
97
Me
Me
6
Ph
Me
Me
Me
50/3
50/3
50/3
50/3
Me
7
Me
Me
Me
Ph
Me
Me
Me
Me
8
Ph
Me
Me
Me
Me
9
Ph
Me
10
10
a
Reaction conditions: arene (8 mmol), benzaldehyde (2 mmol), acetyl bromide (4 mmol), ZnBr2/SiO2 (0.67 g, 0.8 mmol of ZnBr2 on SiO2), benzene
(15 ml).
b
Isolated yield.

M. Kodomari et al. / Tetrahedron Letters 49 (2008) 2537–2540
2539
Table 2
reacted with benzaldehyde at 50 °C to give the triarylme-
thane 10 in 97% yield (entry 10). Heteroarenes such as 2-
methylthiophene and furane failed to give the desired trihe-
teroarylmethane under similar conditions. Next, we tested
the generality of the present reaction with veratrole varying
the aldehyde partner (Table 2). Reactions were facile with
both aromatic aldehydes having an electron-withdrawing
and an electron-donating substituent on the aromatic ring.
The yield of the product from the reaction with 4-nitro-
benzaldehyde was the same as that from the reaction with
4-methylbenzaldehyde (entries 3 and 5). In contrast to
these results, 4-methoxybenzaldehyde failed to give the
desired triarylmethane. In the literature, benzaldehyde
reacts with veratrole in the presence of sulfuric acid to give
triarylmethane 2, but 1-naphthaldehyde does not yield the
desired triarylmethane and only starting material is recov-
ered from the reaction mixture.14 In contrast, reaction of 1-
naphthaldehyde with AcBr and veratrole in the presence of
ZnBr2/SiO2 took place at room temperature to give 16 in
89% yield (entry 7). For terephthaldehyde having two alde-
hyde moieties in the same substrate, the desired product
was obtained in high yields when veratrole was used in
excess (6 equiv with respect to aldehyde) (entry 4). It has
been known that acetyl halide combines with aldehydes
to afford the adduct (a-halo ester) in the presence of Lewis
acid.15 Therefore, it can be assumed that a-halo ester is an
intermediate in the reaction of arenes with AcBr and alde-
hydes in the presence of ZnBr2/SiO2, leading to triarylme-
thanes. To test this, a-bromobenzyl acetate was allowed to
react with anisole in the presence of ZnBr2/SiO2 at room
temperature. As we hoped, the main product was tri-
arylmethane 1 (49% yield). The reaction of benzaldehyde
with acetyl bromide in the absence of anisole under the
same conditions afforded a-bromobenzyl acetate in 80%
yield. Even though we are away from realizing the exact
mechanism for the present reaction, a-halo ester may be
Reaction of veratrole (ArH) with various aldehydes leading to
triarylmethanesa
Entry
Aldehyde (ArH)
Product
Yieldb (%)
Ar
1
Benzaldehyde
94
Ar
2
Ar
Ar
Cl
2
3
4
5
6
4-Cl-Benzaldehyde
4-NO2-Benzaldehyde
4-CHO-Benzaldehyde
4-Me-Benzaldehyde
4-MeO-Benzaldehyde
97
11
Ar
Ar
O N
2
80
12
Ar
Ar
Ar
Ar
82
13
Ar
Ar
Me
81
14
Ar
Ar
MeO
Trace
15
Ar
Ar
7
1-Naphthyl-aldehyde
89
16
a
Reaction conditions: veratrole (8 mmol), aldehyde (2 mmol), acetyl
bromide (4 mmol), ZnBr2/SiO2 (0.67 g, 0.8 mmol of ZnBr2 on SiO2),
benzene (15 ml), room temperature 1 h.
b
Isolated yield.
Polymethylbenzene such as o- and m-xylene and 1,2,3-tri-
methylbenzene required a slightly elevated temperature
(50 °C) to condense effectively with benzaldehyde (entries
7–9). 1,3,5-Trimethylbenzene and 1,2,4,5-tetramethylbenz-
ene did not afford the corresponding triarylmethane, and
the diarylmethanols were obtained.13 Toluene did not react
under the same conditions, but 1-methylnaphthalene
MeO
OMe
OMe
MeO
MeO
AcBr - ZnBr2/SiO2
excess of aldehyde
77%
CHO
+
MeO
AcBr - ZnBr2/SiO2
excess of veratrole
17
Cl
OMe
OMe
MeO
MeO
OMe
OMe
MeO
MeO
AcBr - ZnBr2/SiO2
Cl
CHO
2
45%
18
Scheme 1.

2540
M. Kodomari et al. / Tetrahedron Letters 49 (2008) 2537–2540
MeO
MeO
OMe MeO
OMe
OMe
OMe
OMe
MeO
MeO
ZnBr2/SiO2
PhCHO , AcBr-
: 56%
OMe
13
MeO
OMe
OMe MeO
MeO
19
Scheme 2.
3. Hashimoto, Y.; Hirata, K.; Kagoshima, H.; Kihara, N.; Hasegawa,
M.; Saigou, K. Tetrahedron 1993, 49, 5969.
4. Tsuchimoto, T.; Tobita, K.; Hiyama, T.; Fukuzawa, S. J. Org. Chem.
1997, 62, 6997.
5. Miyai, T.; Onishi, Y.; Baba, A. Tetrahedron 1999, 55, 1017.
6. Nair, V.; Abhilash, K. G.; Vidya, N. Org. Lett. 2005, 7, 5857.
7. Poder, S.; Choudhury, J.; Roy, U. K. J. Org. Chem. 2007, 72, 3100.
8. Davydov, D. V.; Vinogradov, S. A.; Beletskaya, I. P. Izv. Akad. Nauk
SSSR, Ser. Khim. 1990, 708 (CA 113:77763).
considered as an intermediate in the reaction. Aromatic
aldehyde reacts with AcBr at first and then a-bromoaryl
acetate yielded reacts with an arene to give a triarylme-
thane.
O
Ar
O
O
Ar'H
O
+
Ar'
Ar'
Ar
Br
H
Ar
Br
9. Nair, V.; Thomas, S.; Mathew, S. C.; Abhilash, K. G. Tetrahedron
2006, 62, 6731.
When the ratio of arene:aldehyde is changed from 4:1 to
1:3, disubstituted anthracenes were obtained in good yields.
For example, the reaction of veratrole (1 equiv) with benz-
aldehyde (3 equiv) and AcBr (4 equiv) in benzene was car-
ried out in the presence of ZnBr2/SiO2 at room temperature
for 4 h to give anthracene 17 in 77% yield. It can be
assumed that diveratrylphenylmethane 2 is an intermediate
in the reaction with excess benzaldehyde, leading to 17. To
test this, the reaction of 2 with 4-chlorobenzaldehyde (ratio
1:1) was carried out under similar conditions. As we hope,
the unsymmetrically substituted anthracene 18 was
obtained in 45% yield (Scheme 1).
Furthermore, tetrakis(veratrole)adduct 13 was reacted
with benzaldehyde to afford a molecule having two anthra-
cene moieties 19 in 56% yield (Scheme 2).16 In summary, we
have developed a facile method for the synthesis of triar-
ylmethanes and 9,10-diarylanthracenes from the reaction
of electron-rich arenes with aromatic aldehydes and acetyl
bromide using ZnBr2/SiO2 under mild conditions. We
believe that the present procedure provides a useful method
for the synthesis of triarylmethanes and 9,10-diarylanthrac-
enes, which are very important compounds in pharmaceu-
tical but also in material fields.
10. (a) Raid, A.; Mouloungui, Z.; Delmas, M.; Gaset, A. Synth. Commun.
1989, 19, 3169; (b) Muthyala, R. Dyes Pigments 1994, 25, 303; (c)
Katritzky, A. R.; Toader, D. J. Org. Chem. 1997, 62, 4137.
11. Silica gel-supported zinc bromide was prepared as follows. Silica gel
(Wakogel C-200, 36.5 g) was added to a solution of zinc bromide
(60 mmol, 13.5 g) in water (100 ml), and the mixture was stirred at
room temperature for 0.5 h. The water was removed by a rotary
evaporation and the resulting reagent was then dried in vacuo
(15 mmHg) at 150 °C for 10 h. 1.2 mmol of ZnBr2 is supported on 1 g
of ZnBr2/SiO2.
12. General procedure for the synthesis of triarylmethanes: A solution of
acetyl bromide (4 mmol) in benzene (5 ml) was added dropwise to a
mixture of aromatic aldehyde (2 mmol), an arene (8 mmol) and
ZnBr2/SiO2 (0.5 g) in benzene (10 ml) at room temperature. After
addition, the suspension was stirred for 1 h at room temperature. The
reaction was quenched with water (20 ml) and silica gel was removed
by filtration. The organic layer was separated and washed with
aqueous solution of NaHCO3 and water. After evaporation of the
solvent, the crude product was purified chromatographically. Com-
pound 11 (97%); mp 193–194 °C. 1H NMR (300 MHz, CDCl3): dH
(ppm) 2.66 (6H, s, 2CH3), 6.78 (2H, d, J = 7.1 Hz, H-Ar), 6.80 (1H, s,
CH), 7.13 (2H, d, J = 7.1 Hz, H-Ar), 7.15–7.33 (5H, m, H-Ar), 7.36
(2H, t, J = 7.0 Hz, H-Ar), 7.47 (2H, t, J = 7.1 Hz, H-Ar), 7.98 (2H, d,
J = 8.0 Hz, H-Ar), 8.30 (2H, d, J = 8.3 Hz, H-Ar). HRMS (EI): calcd
for C29H24 M+ 372.1878, found 372.1872.
13. 1,3,5-Trimethylbenzene gave 2,4,6-trimethyl-a-phenylbenzenemetha-
nol in 78% yield and 1,2,4,5-tetramethylbenzene gave 2,3,5,6-tetra-
methyl-a-phenyl-benzenemethanol in 71% yield.
14. Goossens, R.; Smet, M.; Dehaen, W. Tetrahedron Lett. 2002, 43,
6605.
References and notes
15. Bigler, P.; Muhle, H.; Neuenschwander, M. S. Synthesis 1978, 593.
16. Compound 19: mp 302–304 °C. 1H NMR (300 MHz, CDCl3): dH
(ppm) 3.77 (12H, s, 4CH3), 3.79 (12H, s, 4CH3), 6.89 (4H, s, H-Ar),
7.08 (4H, s, H-Ar), 7.52–7.67 (10H, m, H-Ar), 7.78 (4H, s, H-Ar).
HRMS (TOF-CI): calcd for C54H47O8 [M+H]+ 823.3270, found
823.3267.
1. Griepentrog, H. Ber. Dtsch. Chem. Ges. 1886, 19, 1876.
2. (a) Roberts, R. M.; EI-Khawaga, A. M.; Sweeney, K. M.; EI-Zohry,
M. F. J. Org. Chem. 1987, 52, 1591; (b) Saito, S.; Ohwada, T.; Shudo,
K. J. Am. Chem. Soc. 1995, 117, 11081; (c) Olah, G. A.; Rasul, G.;
York, C.; Prakash, G. K. S. J. Am. Chem. Soc. 1995, 117, 11211.