Preparation of triaryl- and triheteroarylmethanes under ytterbium triflate catalysis and solvent-free conditions

Article abstract of DOI:10.1002/ejoc.200801115

Triaryl- and triheteroarylmethanes have been synthesized in very good yield under solvent-free conditions from differently substituted aldehydes and 2-methylfuran or methoxybenzene in the presence of Yb(OTf)₃ as catalyst. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.

Full text of DOI:10.1002/ejoc.200801115

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200801115
Preparation of Triaryl- and Triheteroarylmethanes under Ytterbium Triflate
Catalysis and Solvent-Free Conditions
Salvatore Genovese,*[a] Francesco Epifano,[a] Caroline Pelucchini,[b] and Massimo Curini[b]
Keywords: Triarylmethanes / Triheteroarylmethanes / Ytterbium / Activated arenes / Condensation reactions
Triaryl- and triheteroarylmethanes have been synthesized in
very good yield under solvent-free conditions from dif-
ferently substituted aldehydes and 2-methylfuran or meth-
oxybenzene in the presence of Yb(OTf)3 as catalyst.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
workup procedures with low selectivities and co-occurrence
of several side reactions, which makes chromatography for
the purification of the adducts necessary.[11,12]
Introduction
During the last 15 years, rare earth metal triflates have
been found to be unique Lewis acids in that they are water-
tolerant reusable catalysts and can effectively promote sev-
eral carbon–carbon and carbon–heteroatom bond-forma-
tion reactions in high yield.[1,2] In continuation of our ongo-
ing studies aimed at developing mild and practical proto-
cols for the synthesis of useful building blocks and/or biolo-
gically active compounds by using Yb(OTf)3 as a catalyst
and employing water as solvent or solvent-free conditions,
it was speculated that this lanthanide salt, which has re-
cently been shown to catalyse a variety of valuable and
good yielding C–C bond-forming reactions;[3] might be
ideal for effecting the condensation of aldehydes with acti-
vated arenes in the synthesis of triaryl- and triheteroaryl-
methanes. These compounds have been used as protective
groups,[4] photochromic agents,[5] and dyes[6] and have been
extensively used as key intermediates in synthetic, medici-
nal, and industrial chemistry.[7] Ring-hydroxylated triaryl-
methanes have been also reported to exhibit antitumor and
antioxidant activities.[8] Moreover diheteroarylmethanes are
of interest to the food industry as natural components of
certain food and beverage items as well as flavour agents in
coffee.[9] Despite their importance, the synthesis of triaryl-
and triheteroarylmethanes has received to date little atten-
tion. Although a number of methods for the synthesis of
triarylmethanes are available, most of them suffer major or
minor limitations in that they are multi-step processes, re-
quire harsh reaction conditions[10] with low yields, tedious
Results and Discussion
Herein, we wish to report that, by the appropriate choice
of the reaction conditions, ytterbium triflate can be conve-
niently used for the preparation of triaryl- and trihetero-
arylmethanes in high yield. Thus, reaction of 2-methylfuran
with benzaldehyde in the presence of Yb(OTf)3 under sol-
vent-free conditions (Scheme 1) was used as model. The re-
action was carried out at room temperature for 4 h by using
commercially available benzaldehydes (1 mmol) and 2-
methylfuran (1 mmol) in the presence of Yb(OTf)3 hydrate
(1mol-% based on the aldehyde) as catalyst.
Scheme 1.
After the addition of 1  NaOH to precipitate YbIII as
the corresponding hydroxide, the desired product was ob-
tained in 98% yield after filtration and extraction with Et2O
(3ϫ5 mL). On the basis of the above-cited result, a variety
of substituted benzaldehydes were investigated for the cata-
lytic activity of Yb(OTf)3. As shown in Table 1 the desired
triaryl- and triheteroarylmethanes were selectively obtained
in excellent yield.
On the basis of these results, we decided to explore the
use of methoxybenzene as starting material in place of 2-
methylfuran, by performing the reaction under the same
conditions as described above.
[a] Dipartimento di Scienze del Farmaco, Università “G. D’An-
nunzio di Chieti-Pescara”,
Via dei Vestini 31, 66013 Chieti Scalo (CH), Italy
E-mail: sgenovese@unich.it
[b] Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di
Chimica Organica, Università degli Studi di Perugia
Via del Liceo 1, 06123 Perugia, Italy
Fax: +39-075-58551116
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 1132–1135

Triaryl- and Triheteroarylmethanes
Table 1. Yb(OTf)3-catalyzed formation of trietheroarylmethanes by
reaction of 2-methylfuran with substituted benzaldehydes.
In this case, too, the corresponding adducts were ob-
tained in very good yield (Table 2). It is important to note
that the adducts were regioselectively obtained, having the
new carbon–carbon bond in para position of the methoxy-
1
benzene ring as determined by H NMR analysis. To this
respect it may be supposed that the linkage of the unsubsti-
tuted benzene moiety occurred in para position of both ani-
sole rings due to steric hindrance of the methoxy group.
Table 2. Yb(OTf)3-catalyzed formation of trietheroarylmethanes by
reaction of methoxybenzene with substituted benzaldehydes.
[a] Yields of pure isolated products, characterized by GC-MS, IR,
1H NMR and 13C NMR data. The degree of purity of each product
listed in Table 1 was analyzed by GC/MS.
From every reaction the catalyst was recovered by pre-
cipitation as Yb(OH)3, filtration and transformation into
the triflate as already described.[13] Recycled in this way, the
catalyst could be reused several times without any signifi-
cant loss of activity.
[a] Yields of pure isolated products, characterized by GC-MS, IR,
1H NMR and 13C NMR data. The degree of purity of each product
listed in Table 1 was analyzed by GC/MS.
Eur. J. Org. Chem. 2009, 1132–1135
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Salvatore Genovese, F. Epifano, C. Pelucchini, M. Curini
SHORT COMMUNICATION
C17H15NO4 (297.31): calcd. C 68.68, H 5.09, N 4.71, O 21.5; found
C 68.60, H 5.01, N 4.67, O 21.49.
The same reaction was also performed by using other
metal triflates from the lanthanide series (e.g. lanthanum
and europium), but the results were by far worse than with
Yb(OTf)3.
From a mechanistic point of view, it could be hypothe-
sized that YbIII, due to its high oxophilicity, coordinates the
oxygen atom of the aldehyde, thereby enhancing the electro-
philicity of the carbonyl group and thus facilitating the at-
tack of the π-electron-rich arene.
5-[(4-Chlorophenyl)(5-methyl-2-furyl)methyl]-2-methylfuran (3): Pale
yellow solid; m.p. 95–100 °C. 1H NNR (200 MHz, CDCl3; Me4Si):
δ = 2.27 (2 s, 6 H, CH3), 5.89 (s, 1 H, Ar3CH), 7.18–7.37 (m, 8 H,
aromatic H) ppm. 13C NMR (200 MHz, CDCl3; Me4Si): δ = 13.35,
48.39, 104.59, 105.02, 129.08, 131.65, 132.21, 135.73, 147.45,
151.33 ppm. C17H15ClO2 (286.76): calcd. C 71.21, H 5.27, Cl 12.36,
O 11.1; found C 71.17, H 5.23, Cl 12.32, O 11.11. MS: m/z (%) =
286 (100) [M+], 51 (9), 75 (8), 89 (6), 102 (2), 115 (10), 128 (5), 141
(12), 162 (5), 175 (100), 189 (6), 208 (49), 229 (8), 243 (48), 271
(15).
Conclusions
2-Methyl-5-{(5-methyl-2-furyl)[4-(trifluoromethyl)phenyl]methyl}-
furan (4): Pale yellow solid; m.p. 91–96 °C. 1H NMR: see ref.[15]
13C NMR: see ref.[15] C18H15F3O2 (320.31): calcd. C 67.50, H 4.72,
F 17.79, O 9.9; found C 67.47, H 4.66, F 17.75, O 9.94.
In this manuscript we have demonstrated that electron-
rich aromatic system undergo an efficient condensation re-
action with several differently substituted benzaldehydes
under the catalysis of Yb(OTf)3 hydrate by means of an
easy and environmentally sound method. The simple
workup procedure, mild reaction conditions and high yields
make our methodology a valid contribution to the existing
processes in the field of triaryl- and trietheroarylmethane
synthesis. Moreover, this protocol introduces a pratical and
viable technology of solvent-free reactions. Further investi-
gations to broaden the scope of this technology are in pro-
gress in our laboratories. It is reasonable to expect that the
present work will find such use in the synthesis of the title
compounds, which are very valuable building blocks in
many respects.
2-Methyl-5-[(5-methyl-2-furyl)(2-nitrophenyl)methyl]furan (5): Pale
yellow solid; m.p. 89–91 °C. 1H NMR: see ref.[14] 13C NMR: see
ref.[14] C17H15NO4 (297.31): calcd. C 68.68, H 5.09, N 4.71, O 21.5;
found C 68.62, H 5.03, N 4.67, O 21.48.
2-Methyl-5-[(5-methyl-2-furyl)(3-nitrophenyl)methyl]furan (6): Yel-
low solid; m.p. 95–96 °C. 1H NMR: see ref.[14] 13C NMR: see ref.[14]
C17H15NO4 (297.31): calcd. C 68.68, H 5.09, N 4.71, O 21.5; found
C 68.62, H 5.03, N 4.67, O 21.48.
5-[(4-Fluorophenyl)(5-methyl-2-furyl)methyl]-2-methylfuran (7): Pale
1
yellow solid; m.p. 90–93 °C. H NMR (200 MHz, CDCl3; Me4Si):
δ = 2.27 (2 s, 6 H, CH3), 5.92 (s, 1 H, Ar3CH), 7.01–7.94 (m, 8 H,
aromatic H) ppm. 13C NMR (200 MHz, CDCl3; Me4Si): δ = 13.35,
48.39, 104.59, 105.02, 110.01–110.71 (d, J = 28 Hz, o-CH), 132.61–
132.88 (d, J = 3.2 Hz, p-C), 134.74–134.91 (d, J = 7.2 Hz, m-CH),
147.45, 151.33, 160.25–160.75–166.75 (d, J = 6 Hz, CF) ppm.
C17H15FO2 (270.30): calcd. C 75.54, H 5.59, F 7.03, O 11.8; found
C 75.50, H 5.55, F 7.00, O 11.81. MS: m/z (%) = 270 (100) [M+],
51 (7), 65(4), 77 (6), 95 (7), 107 (10), 120 (6), 133 (14), 146 (17),
159 (12), 175 (12), 189 (10), 213 (15), 227 (55), 241 (1), 255 (19).
Experimental Section
Synthesis of Trietheroarylmethanes. Typical Procedure: A mixture
of benzaldehyde (1.0 mmol) and 2-methylfuran or methoxybenzene
(2.0 mmol) was vigorously stirred with [Yb(H2O)n](OTf)3
(0.01 mmol) at room temperature for 4 h. 1  NaOH (2 mL) was
added, the white precipitate filtered, and the resulting solution ex-
tracted with Et2O (3ϫ2 mL). The collected organic phases were
dried with anhydrous Na2SO4, and the solvent was evaporated to
dryness to give the desired trietheroarylmethanes in pure form. The
degree of purity of each product listed in Table 1 was analyzed by
GC/MS with a Hewlett Packard 6890 gas chromatograph equipped
with a 12.5 mmϫ0.25 mm MetSil column couplet to HP Chem
Station Software. The carrier gas was helium at a pressure of
3.5 kg/cm2, and the column temperature was programmed from 50
to 270 °C at 10 °C/min. The chromatogram was obtained by using
a reporting integrator. Mass spectra were obtained from a GC-
MS system operating in the EI mode at 70eV, equipped with a
12.5 mmϫ0.25 mm MetSil column and an HP5973 Mass Selective
Detector, by using the same chromatographic conditions reported
above. The column was connected to the mass spectrometer in-
source through an open-split interface heated at 250 °C. 1H and
13C NMR spectra were recorded by using the same general pro-
cedure as already reported in ref.[17]
2-[(1,1Ј-Biphenyl-4-yl)(5-methyl-2-furyl)methyl]-5-methylfuran (8):
Orange solid; m.p. 99–103 °C. 1H NMR (200 MHz, CDCl3;
Me4Si): δ = 2.29 (2 s, 6 H, CH3), 5.93 (s, 1 H, Ar3CH), 7.28–7.63
(m, 8 H, aromatic H) ppm. 13C NMR (200 MHz, CDCl3; Me4Si):
δ = 13.35, 48.39, 104.57, 105.01, 126.97, 127.45, 128.66, 129.74,
136.40, 139.64, 139.94, 147.45, 151.3 ppm. C23H20O2 (328.41):
calcd. C 84.12, H 6.14, O 9.74; found C 84.09, H 6.10, O 9.71. MS:
m/z (%) = 328 (100) [M+], 51 (3), 77 (6), 91 (7), 103 (2), 115 (5),
131 (3), 152 (13), 175 (55), 189 (5), 202 (17), 215 (10), 228 (9), 243
(34), 270 (11), 285 (66), 313 (10).
1-Methoxy-4-[(4-methoxyphenyl)(phenyl)methyl]benzene (9): White
1
solid; m.p. 95–100 °C. H NMR: see ref.[16] 13C NMR: see ref.[16]
C21H20O2 (304.39): calcd. C 82.86, H 6.62, O 10.51; found C 82.83,
H 6.59, O 10.48.
1-[Bis(4-methoxyphenyl)methyl]-4-nitrobenzene (10): Pale yellow so-
lid; m.p. 90–93 °C. 1H NMR: see ref.[16] 13C NMR: see ref.[16]
C21H19NO4 (349.39): calcd. C 72.19, H 5.48, N 4.01, O 18.32;
found C 72.16, H 5.43, N 3.97, O 18.39.
1-[Bis(4-methoxyphenyl)methyl]-4-chlorobenzene (11): Pale yellow
solid; m.p. 89–91 °C. 1H NMR: see ref.[16] 13C NMR: see ref.[16]
C21H19ClO2 (338.83): calcd. C 74.44, H 5.65, Cl 10.46, O 9.44;
found C 74.40, H 5.62, Cl 10.42, O 9.41.
2-Methyl-5-[(5-methyl-2-furyl)(phenyl)methyl]furan (1): Yellow so-
lid; m.p. 95–100 °C. 1H NMR: see ref.[12] 13C NMR: see ref.[12]
C17H16O2 (252.31): calcd. C 80.93, H 6.39, O 12.68; found C80.88,
H 6.35, O 12.62.
1-[Bis(4-methoxyphenyl)methyl]-4-(trifluoromethyl)benzene
Whie solid; m.p. 97–100 °C. H NMR (200 MHz, CDCl3; Me4Si):
δ = 3.87 (2 s, 6 H, CH3), 5.40 (s, 1 H, Ar3CH), 6.82–8.12 (m, 8 H,
(12):
1
2-Methyl-5-[(5-methyl-2-furyl)(4-nitrophenyl)methyl]furan (2): Yel-
low solid; m.p. 89–91 °C. 1H NMR: see ref.[14] 13C NMR: see ref.[14]
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 1132–1135

Triaryl- and Triheteroarylmethanes
aromatic H). 13C NMR (200 MHz, CDCl3; Me4Si): δ = 54.82,
55.76, 113.56–120.69–127.83–134.96 (q, J = 285.02 Hz, CF3)
vese, M. C. Marcotullio, O. Rosati, Org. Lett. 2005, 7, 1331; i)
M. Curini, F. Epifano, S. Genovese, Tetrahedron Lett. 2006, 47,
4697; j) M. Curini, F. Epifano, S. Genovese, Tetrahedron Lett.
2007, 48, 2717.
114.04, 124.73–124.90–125.08–125.25 (q,
126.67–129.39–130.08–130.79 (q, J = 28.4 Hz, CCF3), 129.59,
130.25–130.32–130.39–130.46 (q, 2.8 Hz, m-CH) 138.15,
J = 6.8 Hz, o-CH)
[4] T. W.Greene, P. G. M. Wust, Protective Groups in Organic Syn-
thesis, 3rd ed., Wiley, New York, 1999, p. 150.
[5] a) R. Aldag, Photochromism based on dissociation processes” in
Photochromism: Molecules and Systems (Eds.: H. Dürr, H.
Bouas-Laurent), Elsevier, London, 1990; b) M. Irie, J. Am.
Chem. Soc. 1983, 105, 2078.
[6] a) P. Rys, H. Zollinger, Fundamentals of the Chemistry and Ap-
plication of Dyes, Wiley-Interscience, New York, 1972; b) R.
Muthyala, A. R. Katritzky, X. Lan, Dyes Pigm. 1994, 25, 303.
[7] a) M. S. Shchepinov, V. A. Korshun, Chem. Soc. Rev. 2003,
32,170; b) D. F. Duxbury, Chem. Rev. 1993, 93, 381; c) R.
Schnitzer, F. Hawking, Experimental Chemotherapy, Academic
Press, New York, 1963, vol. 1.
J
=
149.15, 157.99 ppm. C22H19F3O2 (372.39): calcd. C 70.96, H 5.14,
F 15.31, O 8.59; found C 70.93, H 5.11, F 15.28, O 8.53. MS: m/z
(%) = 372 (70) [M+], 53 (6), 77 (4), 95 (3), 115 (3), 131 (4), 145 (7),
159 (5), 175 (10), 195 (3), 215 (6), 235 (22), 249 (7), 263 (9), 277
(41), 305 (15), 320 (90).
1-[Bis(4-methoxyphenyl)methyl]-3-nitrobenzene (13): Pale yellow so-
lid; m.p. 90–93 °C. 1H NMR: see ref.[16] 13C NMR: see ref.[16]
C21H19NO4 (349.39): calcd. C 72.19, H 5.48, N 4.01, O 18.32;
found C 72.16, H 5.44, N 3.97, O 18.29.
1-[Bis(4-methoxyphenyl)methyl]-4-fluorobenzene (14): Yellow solid;
[8] N. Mibu, K. Sumoto, Chem. Pharm. Bull. 2000, 48, 1810.
[9] A. R. Katritzky, L. Xie, W. Fan, J. Org. Chem. 1993, 58, 4376.
[10] For reviews, see: a) G. Dyker, Angew. Chem. 2000, 112, 4407;
Angew. Chem. Int. Ed. 2000, 39, 4237; b) A. S. K. Hashmi, Gold
Bull. 2003, 36, 3; c) A. S. K. Hashmi, Gold Bull. 2004, 37, 51;
d) A. Arcadi, S. D. Guiseppe, Curr. Org. Chem. 2004, 8, 795;
e) A. Hoffmann-Röder, N. Krause, Org. Biomol. Chem. 2005,
3, 387; f) A. S. K. Hashmi, Chem. Rew. 2007, 107, 3180–3211;
g) A. S. K. Hashmi, L. Schwarz, P. Rubenbauer, M. C. Blanco,
Adv. Synth. Catal. 2006, 348, 705–708.
1
m.p. 89–90 °C. H NMR (200 MHz, CDCl3; Me4Si): δ = 3.82 (2 s,
6 H, CH3), 5.34 (s, 1 H, Ar3CH), 6.85–8.01 (m, 8 H, aromatic H)
ppm. 13C NMR (200 MHz, CDCl3; Me4Si): δ = 54.82, 55.71,
114.04, 114.45–115.15 (d, J = 28 Hz, o-CH), 129.59, 130.41–130.59
(d, J = 7.2 Hz, m-CH) 135.79, 139.25–139.32 (d, J = 2 Hz, p-C)
157.99, 157.65–164.15 (d, J = 260 Hz, CF) ppm. C21H19FO2
(322.38): calcd. C 78.24, H 5.94, F 5.89, O 9.93; found: C 78.20, H
5.91, F 5.86, O 9.90. MS: m/z (%) = 322 (100) [M+], 53 (6), 77(5),
95 (8), 120 (7), 133 (10), 146 (16), 156 (11), 178 (74), 185 (36), 189
(15), 213 (15), 227 (45), 255 (33), 270 (80).
[11] Z. Li, Z. Duan, J. Koung, H. Yu, Tetrahedron 2008, 64, 1924–
1930 and references cited herein.
[12] N. Vijay, K. G. Abhilash, N. Vidya, Org. Lett. 2005, 7, 5857–
5859 and references cited herein.
[1] S. Kobayashi, M. Sugiura, H. Kitagawa, W. L. Lam, Chem.
Rev. 2002, 102, 2227.
[13] M. Fieser, Reagents for Organic Synthesis, Wiley-Interscience,
New York, 1989, vol. 14, p. 188.
[2] S. Kobayashi, Chem. Lett. 1991, 2187.
[14] a) S. C. Cagieva, T. A. Sukhova, D. V. Savinov, V. A. Tuskaev,
K. A. Lyssenko, N. M. Bravaya, N. Belokon, B. M. Bulychew,
Russ. Chem. Bull. Int. Ed. 2006, 55, 1794–1802.
[3] a) M. Curini, F. Epifano, M. C. Marcotullio, O. Rosati, Tetra-
hedron Lett. 2001, 42, 3193; b) M. Curini, F. Epifano, M. C.
Marcotullio, O. Rosati, Heterocycles 2001, 55, 1599; c) M. Cur-
ini, F. Epifano, M. C. Marcotullio, O. Rosati, Eur. J. Org.
[15] N. Vijay, K. G. Abhilash, Synthesis 2006, 3647–3653 and refer-
ences cited herein.
Chem. 2002, 1562; d) M. Curini, F. Epifano, F. Maltese, O. [16] S. Podder, U. K. Roy, S. J. Roy, J. Org. Chem. 2007, 72, 3103–
Rosati, Tetrahedron Lett. 2002, 43, 4895; e) M. Curini, F. Epi-
fano, F. Maltese, O. Rosati, Synlett 2003, 552; f) M. Curini, F.
Epifano, M. C. Marcotullio, F. Maltese, Eur. J. Org. Chem.
2003, 1631; g) Curini, F. Epifano, F. Montanari, O. Rosati, S.
Taccone, Synlett 2004, 1832; h) M. Curini, F. Epifano, S. Geno-
3105 and references cited herein.
[17] P. Ceccherelli, M. Curini, M. C. Marcotullio, O. Rosati, E.
Wenkert, J. Org. Chem. 1991, 56, 7065.
Received: November 11, 2008
Published Online: January 29, 2009
Eur. J. Org. Chem. 2009, 1132–1135
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