Niobium Pentachloride Mediated (Hetero)aromatic Aldehyde Friedel-Crafts Hydroxyalkylation with Arenes: An Efficient Strategy to Synthesize Triarylmethanes

Article abstract of DOI:10.1055/s-0037-1610727

Niobium pentachloride is an efficient and useful Lewis acid to conduct Friedel-Crafts hydroxyalkylation between arenes and (hetero)aromatic aldehydes, to generate triarylmethanes. This practical methodology offers several advantages, such as short reaction time, mild experimental conditions, and excellent yields.

Full text of DOI:10.1055/s-0037-1610727

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–I
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S. M. M. Rodrigues et al.
Paper
Synthesis
Niobium Pentachloride Mediated (Hetero)aromatic Aldehyde
Friedel–Crafts Hydroxyalkylation with Arenes: An Efficient Strategy
to Synthesize Triarylmethanes
Shirley M. M. Rodrigues*
Daniel Previdi
R
O
NbCl5 (1 equiv.)
DCM, rt
Giovanni S. Baviera
Alexandre A. Matias
Paulo M. Donate
H
X
R
X
X
R = H, F, NO2, CH3, CF3, OCH3 X = various
Departamento de Química, Faculdade de Filosofia, Ciências e
Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901,
Ribeirão Preto, Brazil
24 examples up to 99% yield
shirleymma@yahoo.com.br
This paper is dedicated to Professor Mauricio Gomes Constantino
on the occasion of his 75th birthday.
Received: 27.06.2019
Accepted after revision: 08.08.2019
Published online: 29.08.2019
tion,21 Mannich reactions,22 multicomponent reactions,23
and Diels–Alder reactions,24 among others.25
As part of our interest in developing new synthetic
methodologies, we report an efficient and simple procedure
to obtain triarylmethanes through Friedel–Crafts-type hy-
droxyalkylation mediated by NbCl5 under mild conditions.
First, we optimized the experimental conditions by us-
ing benzaldehyde as the common substrate. Different
arenes were screened in the presence of various amounts of
NbCl5, using several kinds of solvents, at room temperature.
One equivalent of NbCl5 and dichloromethane as solvent
provided the best results. Although the aldehyde was com-
pletely converted within a few hours, we routinely added
saturated aqueous sodium carbonate solution after 24
hours to quench the reactions (Table 1).
Toluene (2a) was the first arene we used under these
conditions (Table 1, entry 1), but the reaction with benzal-
dehyde (1a) did not produce any compound 3a, and we
completely recovered benzaldehyde. On the other hand, the
reaction between benzaldehyde (1a) and xylenes 2b–d re-
sulted in the desired triarylmethanes 3b–d (Table 1, entries
2–4) in good yields (59–66%). The fact that xylenes possess
two electron-donating methyl groups and are thus more
nucleophilic arenes than toluene explains the results. These
reactions furnished only one regioisomeric product in
which the methyne group attached to the aryl carbon is lo-
cated at the para position relative to an electron-donating
methyl group (Table 1, entries 2 and 3). In the case of p-xy-
lene (2d), the para position is blocked, so the carbonyl
group was added at the ortho position (Table 1, entry 4). Re-
action of benzaldehyde (1a) with anisole (2e) produced
compound 3e in 58% yield (Table 1, entry 5). When we used
1,4-dimethoxybenzene (2f), the reaction afforded the de-
sired compound 3f in 75% yield (Table 1, entry 6). Further-
more, the reaction between a more electron-rich arene
DOI: 10.1055/s-0037-1610727; Art ID: ss-2019-m0349-op
Abstract Niobium pentachloride is an efficient and useful Lewis acid
to conduct Friedel–Crafts hydroxyalkylation between arenes and (hete-
ro)aromatic aldehydes, to generate triarylmethanes. This practical
methodology offers several advantages, such as short reaction time,
mild experimental conditions, and excellent yields.
Keywords triarylmethanes, niobium pentachloride, Friedel–Crafts hy-
droxyalkylation, carbocations, (hetero)aromatic aldehydes
Triarylmethanes are well-known substructures in sev-
eral areas including dyes,1 photochromic agents,2 materials
science,3 and medicinal chemistry (acting as anticancer,4
antitubercular,5 and antifungal agents6), among other
fields.7 Due to the importance of triarylmethane com-
pounds, considerable attention has been given to the devel-
opment of different and efficient methods to synthesize
these compounds.7
Friedel–Crafts hydroxyalkylation is a common strategy
to prepare triarylmethanes.7 Various Lewis or protic acids,
such as AuCl3/AgOTf,8 Yb(OTf)3,9 AlCl3,10 BF3·H2O,11 FeCl3,12
ZrOCl2,13 TfOH,14 [Ir(COD)Cl]2–SnCl4,6,15 ZnBr2/SiO2,16 and
FeCl3/Ac2O,17 have been employed.7 However, these meth-
ods have disadvantages: they demand the use of superacids
and corrosive acids as well as additives like co-oxidants or
co-catalysts, experimental conditions are harsh, reaction
times are long, and yields are low.
In this context, the use of niobium(V) chloride (NbCl5)
offers many advantages: it is easy to handle and can act as
an excellent acid system for numerous reactions under mild
conditions, including allylic halide synthesis,18 intramolec-
ular alkene hydrofunctionalization,19 benzylic alcohol nu-
cleophilic substitution reactions,20 dithioacetal deprotec-
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
S. M. M. Rodrigues et al.
Paper
Synthesis
such as 1,2,4-trimethoxybenzene (2g) and benzaldehyde
(1a) gave the triarylmethane 3g in 90% yield (Table 1, entry
7).
To work around this issue, we performed the reaction
under the same conditions, but used 4-nitrobenzaldehyde
(4a) as electrophile. As expected, the reaction between 4a
and toluene (2a) produced the desired triarylmethane 5a in
moderate yield (67%) (Table 1, entry 8). In addition, the re-
actions with 4-nitrobenzaldehyde (4a) and xylenes 2b–d
furnished the corresponding triarylmethanes 5b–d in high-
er yields (72–77%) (Table 1, entries 9–11) than the corre-
sponding reactions employing benzaldehyde (1a) as sub-
strate (Table 1, entries 2–4).
Table 1 Reactions of Benzaldehyde (1a) and 4-Nitrobenzaldehyde (4a) with Several Arenesa
R
O
NbCl5 (1 equiv.)
H
DCM, rt
R
arene 2a–g
(2.2 equiv.)
(arene)
(arene)
1a R = H
3a–g R = H
4a R = NO2
5a–g R = NO2
Reactions with benzaldehyde (1a)
Reactions with 4-nitrobenzaldehyde (4a)
Entry
Arene
Triarylmethane 3 (Yield)b
Entry
Arene
Triarylmethane 5 (Yield)b
NO2
1
8
2a
2a
3a (no reaction)
5a (67%; p,p′/p,o′ 69:31)c
NO2
2
9
2b
2b
3b (66%)
5b (77%)
NO2
3
10
2c
2c
3c (59%)
5c (72%)
NO2
4
11
2d
2d
3d (62%)
5d (75%)
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

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S. M. M. Rodrigues et al.
Paper
Synthesis
Table 1 (continued)
Reactions with benzaldehyde (1a)
Reactions with 4-nitrobenzaldehyde (4a)
Entry
Arene
Triarylmethane 3 (Yield)b
Entry
Arene
Triarylmethane 5 (Yield)b
NO2
OMe
OMe
5
12
2e
2e
MeO
OMe
3e (58%; p,p′/p,o′ 83:17)c
MeO
OMe
5e (72%; p,p′/p,o′ 87:13)c
NO2
OMe
OMe
MeO
OMe
OMe
MeO
OMe
6
13
OMe
OMe
2f
2f
MeO
MeO
5f (85%)
OMe
NO2
3f (75%)
OMe
OMe
OMe
OMe
MeO
OMe
OMe
MeO
OMe
OMe
7
14
MeO
MeO
MeO
OMe
MeO
OMe
2g
2g
MeO
3g (90%)
MeO
5g (98%)
a Reaction conditions: arene (2.2 mmol), aldehyde (1.0 mmol), NbCl5 (1.0 mmol), DCM (5 mL), room temperature, 24 h.
b Isolated yield.
c Ratio determined by NMR spectroscopy.
The reaction between 4-nitrobenzaldehyde (4a) and
anisole (2e) led to the expected triarylmethane 5e in very
good yield (72%) (Table 1, entry 12). When we used 1,4-di-
methoxybenzene (2f), the reaction proceeded very well and
gave compound 5f in excellent yield (85%) (Table 1, entry
13). Likewise, when the reaction was conducted with elec-
tron-rich arenes like 1,2,4-trimethoxybenzene (2g) and 4-
nitrobenzaldehyde (4a), the triarylmethane 5g emerged in
very high yield (98%).
Table 2 Reactions of 2g with 4a in the Presence of Different Amounts
of NbCl5
a
NO2
O
NbCl5
MeO
MeO
OMe
OMe
H
DCM, rt
1,2,4-trimethoxybenzene (2g)
(2.2 equiv.)
O2N
MeO
OMe
4a
At this point, we decided to verify whether the high
yields obtained in the previous reactions could be main-
tained even at lower NbCl5 concentrations, mainly by using
a highly electrophilic aldehyde, such as 4-nitrobenzalde-
hyde (4a), and a very nucleophilic arene, like 1,2,4-trime-
thoxybenzene (2g) (Table 2). The reactions between 4a and
2g with fewer equivalents of NbCl5 produced low yields of
triarylmethane 5g (Table 2, entries 2 and 3). We also per-
formed the control reaction without NbCl5, but the desired
product was not obtained (Table 2, entry 4), which demon-
strates that the presence of 1 equivalent of NbCl5 is import-
ant in this type of reaction.
5g
Entry
Equivalents of NbCl5
Yield (%)b of triarylmethane 5g
1
2
3
4
1.0
0.5
0.1
0
98
75
24
0
a Reaction conditions: arene 2g (2.2 mmol), aldehyde 4a (1.0 mmol), DCM
(5 mL), room temperature, 24 h.
b Isolated yield.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

D
S. M. M. Rodrigues et al.
Paper
Synthesis
With these results in hand, we fixed NbCl5 at 1 equiva-
lent and 1,2,4-trimethoxybenzene (2g) as starting arene,
and studied the generality of the reaction through experi-
ments carried out with different aldehydes as electrophiles
(Table 3). When we applied the experimental conditions to
3-nitrobenzaldehyde and 2-nitrobenzaldehyde, the reac-
tions produced the corresponding triarylmethanes 7a and
7b in very high yields (98% and 95%, respectively). Benzal-
dehyde derivatives bearing an electron-withdrawing group
(CF3, Cl, Br, or F) at the para position also afforded the de-
sired triarylmethanes 7c–f in very high yields (96–99%) (Ta-
ble 3).
use of NbCl5, which is important because diaryl(het-
eroaryl)methanes are essential structural moieties in natu-
ral products, biologically active molecules, and synthetic
materials.26
In contrast, the reactions with other aromatic and ali-
phatic aldehydes, including cinnamaldehyde, phenylacetal-
dehyde, valeraldehyde, and octanal, did not give the desired
triarylmethanes, probably because carbocations that were
not at the benzylic position originated in the medium. To
guarantee the success of this methodology, the resulting
carbocation needs to be simultaneously stabilized by the
mesomeric effect of the oxygen atom and the phenyl group.
In summary, we have developed a simple and straight-
forward method to synthesize triarylmethanes by Friedel–
Crafts hydroxyalkylation by means of a practical protocol
based on niobium pentachloride. The results clearly
demonstrate an excellent tolerance to the various types of
functional groups, where both aromatic aldehydes with
electron-donating and electron-withdrawing groups react
well to produce triarylmethanes in excellent yields.
Table 3 Scope of the Reaction of 1,2,4-Trimethoxybenzene (2g) with
Respect to the Aldehydea
OMe
MeO
MeO
R
OMe
OMe
O
NbCl5 (1 equiv.)
DCM, rt
+
R
H
MeO
MeO
OMe
OMe
R
2g
6a–k
OMe
OMe
7a–k
All solvents were obtained from commercial sources and were puri-
fied according to standard procedures. Melting points were deter-
mined on a Reichert Kofler block apparatus, with a non-calibrated
thermometer, installed under a Bristoline microscope. NMR spectros-
copy was performed on a Bruker DPX-300, Bruker DRX-400, or Bruker
DRX-500 instrument, operating at 300, 400, or 500 MHz for 1H and at
75, 100, or 125 MHz for 13C, respectively. TMS was used as internal
standard. The chemical shifts are reported in ppm (); coupling con-
stants (J) are given in hertz (Hz). The following abbreviations are em-
ployed to designate chemical shift multiplicities: s = singlet, br s =
broad singlet, d = doublet, dd = double doublet, t = triplet, dt = double
triplet, m = multiplet. Mass spectra were recorded on a Shimadzu
GC/MS QP-2010 spectrometer (Shimadzu Corporation, Kyoto, Japan)
fitted with an electron-impact ionization (EI) source operating at 70
eV. GC analyses were conducted on a Shimadzu GC-2010 Plus instru-
ment equipped with a fused silica capillary column (Restek Rtx-5,
30 m length × 0.25 mm i.d.) operating at temperatures ranging from
100 to 310 °C at 5 °C/min. High-resolution electrospray ionization
mass spectra (HRESIMS) were measured on a micrOTOF-Q II (Bruker
Daltonics) spectrometer. IR spectra were recorded on a Perkin Elmer
Spectrum RX I FTIR system, in KBr pellets or plates. All reactions were
MeO
MeO
MeO
MeO
OMe
OMe
MeO
OMe
MeO
OMe
7a–i
7a
7b
7c
7j (91%)b
R = 3-NO2
R = 2-NO2
R = 4-CF3
R = 4-Cl
(98%)b
(95%)b
(97%)b
(99%)b
(96%)b
(98%)b
(93%)b
(95%)b
(98%)b
N
MeO
OMe
OMe
7d
7e
7f
R = 4-Br
MeO
OMe
R = 4-F
MeO
7k (90%)b
7g
7h
7i
R = 4-CH3
R = 4-OMe
R = 3,4,5-(OMe)3
a Reaction conditions: arene 2g (2.2 mmol), aldehyde 6a–k (1.0 mmol),
NbCl5 (1.0 mmol), DCM (5 mL), room temperature, 24 h.
b Isolated yield.
monitored by TLC on pre-coated aluminum sheets (silica gel 60 F254
)
as the stationary phase.
Condensation Reaction of Aldehydes with Arenes in the Presence
of NbCl5 as Acid Catalyst; General Procedure
Furthermore, when we employed benzaldehydes bear-
ing an electron-donating substituent [4-CH3, 4-OCH3, or
3,4,5-(OMe)3], the reaction provided very good yields (7g–i,
93–98%) (Table 3). Similarly, 2-naphthaldehyde reacted
with 1,2,4-trimethoxybenzene (2g) to produce the triaryl-
methane 7j in 91% yield. The reaction between pyridine-4-
carbaldehyde and 2g under the same reaction conditions
afforded the corresponding diaryl(heteroaryl)methane 7k
in high yield (90%) (Table 3). The latter reaction attests to
the great versatility of the methodology developed with the
A suspension of aldehyde (1 mmol) and NbCl5 (1 mmol) in DCM (5
mL) was stirred at 0 °C. Then, arene (2.2 mmol) was added. The reac-
tion was allowed to reach room temperature. The end of the reaction
was monitored via TLC. Next, the reaction mixture was quenched
with saturated Na2CO3 solution (15 mL) and extracted with Et2O
(3 × 20 mL). The organic layer was washed with brine, dried over an-
hydrous MgSO4, filtered, and concentrated. The residue was purified
by flash column chromatography (silica gel; hexane–EtOAc, 9.5:0.5 to
8:2 v/v) to afford the pure compounds. All obtained products were
characterized by their spectroscopic data [1H, 13C, and 19F NMR, IR, MS
(EI)].
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

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S. M. M. Rodrigues et al.
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Synthesis
1,1′-(Phenylmethanediyl)bis(2,4-dimethylbenzene) (3b)
1,1′-(Phenylmethanediyl)bis(2,5-dimethoxybenzene) (3f)
Pale yellow oil; yield: 198 mg (66%).
Pale yellow, viscous oil; yield: 273 mg (75%).
IR: 3054, 2927, 2852, 1712, 1266, 739 cm–1
.
IR: 2950, 2832, 1590, 1493, 1219, 1049, 801, 709 cm–1
.
1H NMR (300 MHz, CDCl3):  = 2.12 (s, 6 H), 2.28 (s, 6 H), 5.61 (s, 1 H),
6.62 (d, J = 7.80 Hz, 2 H), 6.87 (d, J = 7.80 Hz, 2 H), 6.97 (s, 2 H), 7.02 (d,
J = 7.96 Hz, 2 H), 7.18–7.24 (m, 3 H).
13C NMR (100 MHz CDCl3):  = 19.5 (2 CH3), 20.9 (2 CH3), 49.9
(CH),126.0 (CH), 126.3 (2 CH), 128.2 (2 CH), 129.1 (2 CH), 129.7 (2
CH), 131.2 (2 CH),135.6 (2 C), 136.3 (2 C), 139.1 (2 C), 143.2 (C).
1H NMR (400 MHz, CDCl3):  = 3.69 (s, 6 H), 3.72 (s, 6 H), 6.23 (s, 1 H),
6.52 (d, J = 3.03 Hz, 2 H), 6.78 (dd, J = 8.85, 2.53 Hz, 2 H), 6.85 (d, J =
8.59 Hz, 2 H), 7.16 (d, J = 7.33 Hz, 2 H), 7.23 (t, J = 7.33 Hz, 1 H), 7.31
(d, J = 7.33 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 43.5 (CH), 55.4 (2 CH3O), 56.4 (2
CH3O), 110.7 (2 CH), 111.9 (2 CH), 117.2 (2 CH), 125.8 (CH), 127.9 (2
CH), 129.2 (2 CH), 133.9 (2 C), 143.3 (C), 151.6 (2 C), 157.3 (2 C).
MS (EI): m/z (%) = 300 (80) [M+], 285 (100), 223 (15), 207 (19), 193
(28), 179 (51), 165 (21), 91 (6), 77 (5).
MS (EI): m/z (%) = 364 (100) [M+], 333 (24), 241 (11), 213 (17), 151
(13), 121 (30).
1,1′-(Phenylmethanediyl)bis(3,4-dimethylbenzene) (3c)
1,1′-(Phenylmethanediyl)bis(2,4,5-trimethoxybenzene) (3g)
White solid; mp 123–124 °C (Lit.27 126–127 °C); yield: 382 mg (90%).
Pale yellow oil; yield: 177 mg (59%).
IR: 3056, 2925, 2853, 1713, 1266, 739 cm–1
.
IR: 2956, 1512, 1204, 1037, 816, 707 cm–1
.
1H NMR (300 MHz, CDCl3):  = 2.19 (s, 6 H), 2.22 (s, 6 H), 5.41 (s, 1 H),
6.82 (d, J = 7.41 Hz, 2 H), 6.91 (s, 2 H), 7.03 (d, J = 7.64 Hz, 2 H), 7.11 (d,
J = 7.41 Hz, 2 H), 7.18–7.24 (m, 3 H).
13C NMR (75 MHz, CDCl3):  = 19.3 (2 CH3), 19.8 (2 CH3), 56.2 (CH),
126.0 (CH), 126.8 (2 CH), 128.2 (2 CH), 129.4 (2 CH), 129.5 (2 CH),
130.7 (2 CH), 134.3 (2 C), 136.3 (2 C), 141.6 (2 C), 144.5 (C).
1H NMR (300 MHz, CDCl3):  = 3.63 (s, 6 H), 3.66 (s, 6 H), 3.88 (s, 6 H),
6.08 (s, 1 H), 6.43 (s, 2 H), 6.54 (s, 2 H), 7.04–7.06 (d, J = 7.02 Hz, 2 H),
7.14–7.24 (m, 3 H).
13C NMR (100 MHz, CDCl3):  = 42.5 (CH), 55.9 (2 CH3O), 56.6 (2
CH3O), 56.9 (2 CH3O), 98.4 (2 CH), 114.6 (2 CH), 124.5 (C), 125.7 (CH),
127.8 (2 CH), 128.9 (2 CH), 142.7 (2 C), 144.2 (2 C), 148.0 (2 C), 151.5
(2 C).
MS (EI): m/z (%) = 300 (45) [M+], 285 (100), 223 (13), 207 (11), 193
(17), 179 (19), 165 (13), 91 (3), 77 (3).
MS (EI): m/z (%) = 424 (100) [M+], 393 (67), 347 (14), 241 (10), 181
(29), 151 (23), 91 (15).
1,1′-(Phenylmethanediyl)bis(2,5-dimethylbenzene) (3d)
Pale yellow solid; mp 80–82 °C; yield: 186 mg (62%).
1,1′-[(4-Nitrophenyl)methanediyl]bis(4-methylbenzene) (5a)
IR: 3056, 2932, 2836, 1712, 1266, 738 cm–1
.
Yellow oil; yield: 213 mg (67%); ratio of isomers p,p′ (5a)/p,o′ (5a′) =
69:31.
1H NMR (400 MHz, CDCl3):  = 2.11 (s, 6 H), 2.20 (s, 6 H), 5.63 (s, 1 H),
6.54 (s, 2 H), 6.95 (d, J = 7.58 Hz, 2 H), 7.02 (d, J = 7.08 Hz, 2 H), 7.04 (d,
J = 7.08 Hz, 2 H), 7.18–7.22 (m, 1 H), 7.25–7.29 (m, 2 H).
IR: 2927, 1712, 1347, 1267, 748 cm–1
.
13C NMR (100 MHz, CDCl3):  = 19.2 (2 CH3), 21.2 (2 CH3), 50.5 (CH),
126.1 (CH), 126.9 (2 CH), 128.2 (2 CH), 129.8 (2 CH), 129.9 (2 CH),
130.1 (2 CH), 133.4 (2 C), 134.9 (2 C), 141.8 (2 C), 142.9 (C).
MS (EI): m/z (%) = 300 (70) [M+], 285 (100), 223 (7), 207 (17), 193 (30),
179 (69), 165 (21), 91 (6), 77 (5).
Major Isomer
1H NMR (500 MHz, CDCl3):  = 2.33 (s, 6 H), 5.55 (s, 1 H), 6.97 (d, J =
7.91 Hz, 4 H), 7.12 (d, J = 7.91 Hz, 4 H), 7.27 (d, J = 8.69 Hz, 2 H), 8.12
(d, J = 8.69 Hz, 2 H).
13C NMR (125 MHz, CDCl3):  = 21.0 (2 CH3), 55.9 (CH), 123.5 (2 CH),
129.1 (4 CH), 129.3 (4 CH), 130.2 (2 CH), 136.5 (2 C), 139.6 (2 C), 146.5
(C), 152.1 (C).
1,1′-(Phenylmethanediyl)bis(4-methoxybenzene) (3e)
Pale yellow oil; yield: 176 mg (58%); ratio of isomers p,p′ (3e)/p,o′
(3e′) = 83:17.
MS (EI): m/z (%) = 317 (78) [M+], 302 (100), 256 (10), 239 (10), 226
(11), 195 (39), 179 (44), 165 (37), 152 (9), 107 (12).
IR: 2915, 1598, 1493, 1260, 809, 746, 699 cm–1
.
Minor Isomer
Major Isomer
1H NMR (500 MHz, CDCl3):  = 2.20 (s, 3 H), 2.34 (s, 3 H), 5.71 (s, 1 H),
6.75 (d, J = 7.52 Hz, 1 H), 6.91 (d, J = 8.04 Hz, 2 H), 7.12–7.15 (m, 4 H),
7.20 (d, J = 8.82 Hz, 2 H), 7.23–7.26 (m, 1 H), 8.13 (d, J = 8.82 Hz, 2 H).
13C NMR (125 MHz, CDCl3):  = 19.8 (CH3), 21.0 (CH3), 53.0 (CH), 123.5
(2 CH), 126.1 (CH), 126.9 (CH), 129.2 (CH), 129.4 (2 CH), 129.5 (2 CH),
130.3 (2 CH), 130.7 (CH), 136.5 (2 C), 138.8 (C), 141.0 (C), 146.6 (C),
151.6 (C).
1H NMR (300 MHz, CDCl3):  = 3.78 (s, 6 H), 5.45 (s, 1 H), 6.82 (d, J =
8.66 Hz, 4 H), 7.02 (d, J = 8.66 Hz, 4 H), 7.09–7.11 (m, 2 H), 7.16–7.23
(m, 2 H), 7.27–7.30 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 48.7 (CH), 55.2 (2 CH3O), 113.6 (2 CH),
126.1 (CH), 128.2 (2 CH), 129.3 (2 CH), 130.3 (2 CH), 136.5 (2 C), 144.6
(2 C), 158.7 (2 C).
MS (EI): m/z (%) = 304 (100) [M+], 289 (6), 273 (58), 227 (85), 197 (30),
181 (17), 153 (21), 113 (11).
MS (EI): m/z (%) = 317 (84) [M+], 302 (100), 256 (10), 239 (9), 226 (16),
195 (27), 179 (54), 165 (37), 152 (10), 107 (9).
Minor Isomer
1,1′-[(4-Nitrophenyl)methanediyl]bis(2,4-dimethylbenzene) (5b)
MS (EI): m/z (%) = 304 (100) [M+], 289 (32), 273 (34), 227 (29), 197
(26), 165 (21), 121 (49), 91 (23).
Pale yellow solid; mp 134–137 °C; yield: 265 mg (77%).
IR: 3066, 2974, 2917, 1519, 1342, 812, 744 cm–1
.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

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S. M. M. Rodrigues et al.
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Synthesis
1H NMR (300 MHz, CDCl3):  = 2.12 (s, 6 H), 2.30 (s, 6 H), 5.70 (s, 1 H),
6.55 (d, J = 7.80 Hz, 2 H), 6.90 (d, J = 7.80 Hz, 2 H), 7.01 (s, 2 H), 7.19 (d,
J = 8.74 Hz, 2 H), 8.12 (d, J = 8.74 Hz, 2 H).
13C NMR (75 MHz, CDCl3):  = 19.5 (2 CH3), 20.9 (2 CH3), 49.7 (CH),
123.5 (2 CH), 126.7 (2 CH), 129.0 (2 CH), 130.4 (2 CH), 131.5 (2 CH),
136.2 (2 C), 136.4 (2 C), 137.6 (2 C), 146.5 (C), 151.4 (C).
1,1′-[(4-Nitrophenyl)methanediyl]bis(2,5-dimethoxybenzene)
(5f)
Yellow solid; mp 135–137 °C; yield: 348 mg (85%).
IR: 2937, 2832, 1516, 1495, 1345, 1217, 1045, 834, 709 cm–1
.
1H NMR (300 MHz, CDCl3):  = 3.64 (s, 6 H), 3.67 (s, 6 H), 6.18 (s, 1 H),
6.37 (d, J = 2.96 Hz, 2 H), 6.75 (dd, J = 8.89, 2.96 Hz, 2 H), 6.82 (d, J =
8.74 Hz, 2 H), 7.22 (d, J = 8.89 Hz, 2 H), 8.10 (d, J = 8.74 Hz, 2 H).
13C NMR (75 MHz, CDCl3):  = 43.8 (CH), 55.5 (2 CH3O), 56.3 (2 CH3O),
111.3 (2 CH), 111.9 (2 CH), 117.3 (2 CH), 123.3 (2 CH), 129.9 (2 CH),
132.0 (C), 146.3 (2 C), 151.5 (2 C), 151.9 (C), 153.5 (2 C).
MS (EI): m/z (%) = 345 (74) [M+], 330 (100), 240 (12), 222 (34), 207
(20), 193 (44), 178 (40), 165 (9).
1,1′-[(4-Nitrophenyl)methanediyl]bis(3,4-dimethylbenzene) (5c)
Yellow oil; yield: 248 mg (72%).
IR: 3056, 2929, 1712, 1267, 738 cm–1
MS (EI): m/z (%) = 409 (100) [M+], 378 (6), 258 (13), 241 (8), 151 (15),
121 (42).
.
1H NMR (400 MHz, CDCl3):  = 2.20 (s, 6 H), 2.24 (s, 6 H), 5.49 (s, 1 H),
6.79 (d, J = 7.58 Hz, 2 H), 6.87 (s, 2 H), 7.06 (d, J = 7.58 Hz, 2 H), 7.28 (d,
J = 8.72 Hz, 2 H), 8.12 (d, J = 8.72 Hz, 2 H).
1,1′-[(4-Nitrophenyl)methanediyl]bis(2,4,5-trimethoxybenzene)
(5g)
13C NMR (100 MHz, CDCl3):  = 19.3 (2 CH3), 19.8 (2 CH3), 56.0 (CH),
123.5 (2 CH), 126.6 (2 CH), 129.8 (2 CH), 130.2 (2 CH), 130.5 (2 CH),
135.1 (2 C), 136.8 (2 C), 140.0 (2 C), 146.4 (C), 152.3 (C).
MS (EI): m/z (%) = 345 (46) [M+], 330 (100), 222 (21), 207 (17), 193
(19), 178 (15), 165 (5).
Orange solid; mp 60–61 °C; yield: 460 mg (98%).
IR: 3001, 2936, 1512, 1203, 1033, 887, 742 cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.65 (s, 6 H), 3.68 (s, 6 H), 3.90 (s, 6 H),
6.11 (s, 1 H), 6.39 (s, 2 H), 6.56 (s, 2 H), 7.20 (d, J = 8.66 Hz, 2 H), 8.10
(d, J = 8.66 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 43.0 (CH), 56.0 (2 CH3O), 56.5 (2
CH3O), 56.7 (2 CH3O), 98.1 (2 CH), 114.5 (2 CH), 122.3 (2 C), 123.1 (2
CH), 129.5 (2 CH), 142.8 (2 C), 146.1 (C), 148.6 (2 C), 151.5 (2 C), 152.8
(C).
MS (EI): m/z (%) = 469 (100) [M+], 438 (48), 181 (21), 151 (27).
HRESIMS: m/z calcd for C25H27NNaO8 [M + Na]+: 492.1634; found:
1,1′-[(4-Nitrophenyl)methanediyl]bis(2,5-dimethylbenzene) (5d)
Yellow solid; mp 103–106 °C; yield: 259 mg (75%).
IR: 3076, 2972, 2917, 1518, 1346, 813, 737 cm–1
.
1H NMR (300 MHz, CDCl3):  = 2.11 (s, 6 H), 2.21 (s, 6 H), 5.72 (s, 1 H),
6.46 (br s, 2 H), 6.98 (d, J = 7.80 Hz, 2 H), 7.08 (d, J = 7.80 Hz, 2 H), 7.20
(d, J = 8.59 Hz, 2 H), 8.14 (d, J = 8.59 Hz, 2 H).
492.1628.
13C NMR (75 MHz, CDCl3):  = 19.1 (2 CH3), 21.2 (2 CH3), 50.3 (CH),
123.5 (2 CH), 127.6 (2 CH), 129.7 (CH), 129.8 (CH), 130.5 (2 CH), 130.6
(2 CH), 133.3 (2 C), 135.5 (2 C), 140.3 (2 C), 146.6 (C), 151.2 (C).
1,1′-[(3-Nitrophenyl)methanediyl]bis(2,4,5-trimethoxybenzene)
(7a)
Yellow solid; mp 101–104 °C (Lit.28 117 °C); yield: 459 mg (98%).
MS (EI): m/z (%) = 345 (93) [M+], 330 (100), 240 (12), 222 (69), 207
IR: 2963, 1512, 1201, 1034, 815, 763, 668 cm–1
.
(27), 193 (68), 178 (59), 165 (12).
1H NMR (400 MHz, CDCl3):  = 3.65 (s, 6 H), 3.68 (s, 6 H), 3.91 (s, 6 H),
6.12 (s, 1 H), 6.40 (s, 2 H), 6.58 (s, 2 H), 7.37–7.39 (m, 1 H), 7.40 (t, J =
6.82 Hz, 1 H), 7.92 (br s, 1 H), 8.00 (dt, J = 6.82, 2.52 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 42.7 (CH), 56.1 (2 CH3O), 56.6 (2
CH3O), 56.8 (2 CH3O), 98.1 (2 CH), 114.6 (2 CH), 120.9 (C), 122.4 (2 C),
123.6 (CH), 128.6 (CH), 134.9 (CH), 142.8 (CH), 147.0 (2 C), 148.2 (2
C), 148.7 (2 C), 151.6 (C).
1,1′-[(4-Nitrophenyl)methanediyl]bis(4-methoxybenzene) (5e)
Yellow oil; yield: 251 mg (72%); ratio of isomers p,p′ (5e)/p,o′ (5e′) =
87:13.
IR: 3056, 2921, 1712, 1266, 738 cm–1
.
Major Isomer
1H NMR (400 MHz, CDCl3):  = 3.79 (s, 6 H), 5.53 (s, 1 H), 6.84 (d, J =
8.46 Hz, 4 H), 6.99 (d, J = 8.46 Hz, 4 H), 7.26 (d, J = 8.59 Hz, 2 H), 8.13
(d, J = 8.59 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 48.9 (CH), 55.3 (2 CH3O), 114.0 (4 CH),
123.5 (2 CH), 130.1 (2 CH), 130.2 (4 CH), 134.8 (2 C), 146.4 (C), 152.4
(2 C), 158.4 (C).
MS (EI): m/z (%) = 469 (100) [M+], 438 (37), 181 (35), 151 (28).
HRESIMS: m/z calcd for C25H27NNaO8 [M + Na]+: 492.1634; found:
492.1625.
1,1′-[(2-Nitrophenyl)methanediyl]bis(2,4,5-trimethoxybenzene)
(7b)
MS (EI): m/z (%) = 349 (98) [M+], 334 (4), 318 (59), 227 (100), 121 (4),
Orange solid; mp 134–135 °C; yield: 446 mg (95%).
91 (2).
IR: 3004, 2935, 2835, 1511, 1463, 1202, 1033, 851, 737 cm–1
.
1H NMR (400 MHz, CDCl3):  = 3.62 (s, 6 H), 3.68 (s, 6 H), 3.88 (s, 6 H),
6.35 (s, 1 H), 6.54 (s, 2 H), 6.55 (s, 2 H), 7.07 (dd, J = 7.83, 1.26 Hz, 1 H),
7.34 (dt, J = 7.83, 7.83, 1.39 Hz, 1 H), 7.44 (dt, J = 7.83, 7.83, 1.26 Hz, 1
H).
13C NMR (100 MHz, CDCl3):  = 38.9 (CH), 56.0 (2 CH3O), 56.7 (2
CH3O), 56.8 (2 CH3O), 98.3 (2 CH), 114.3 (2 CH), 122.3 (2 C), 124.4
(CH), 126.8 (CH), 131.1 (CH), 131.9 (CH), 139.0 (2 C), 142.7 (2 C),
148.6 (2 C), 149.8 (C), 151.7 (C).
Minor Isomer
13C NMR (100 MHz, CDCl3):  = 55.0 (CH3O), 55.3 (CH3O), 55.5 (CH),
113.9 (2 CH), 120.4 (CH), 123.3 (2 CH), 128.5 (2 CH), 129.9 (1 CH),
130.0 (CH), 130.4 (2 CH), 131.3 (CH), 134.2 (2 C), 146.3 (C), 156.9 (2
C), 158.3 (C).
MS (EI): m/z (%) = 349 (100) [M+], 334 (28), 318 (28), 227 (32), 121
(63), 91 (13).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

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S. M. M. Rodrigues et al.
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Synthesis
MS (EI): m/z (%) = 469 (26) [M+], 421 (100), 406 (23), 256 (39), 242
1,1′-[(4-Fluorophenyl)methanediyl]bis(2,4,5-trimethoxyben-
(36), 232 (20), 195 (43), 168 (35).
zene) (7f)
HRESIMS: m/z calcd for C25H27NNaO8 [M + Na]+: 492.1634; found:
White solid; mp 100–101 °C; yield: 433 mg (98%).
IR: 2956, 1508, 1320, 1204, 1038, 884, 764 cm–1
.
492.1610.
1H NMR (300 MHz, CDCl3):  = 3.64 (s, 6 H), 3.66 (s, 6 H), 3.88 (s, 6 H),
6.05 (s, 1 H), 6.41 (s, 2 H), 6.55 (s, 2 H), 6.89–6.95 (m, 2 H), 6.99–7.04
(m, 2 H).
13C NMR (125 MHz, CDCl3):  = 41.8 (CH), 55.9 (2 CH3O), 56.5 (2
CH3O), 56.6 (2 CH3O), 98.3 (2 CH), 114.4 (d, JCF = 21.1 Hz, 2 CH), 114.6
(2 CH), 124.1 (2 C), 130.2 (d, JCF = 7.7 Hz, 2 CH), 139.9 (d, JCF = 2.9 Hz,
C), 142.6 (2 C), 148.1 (2 C), 151.4 (2 C), 160.9 (d, JCF = 243 Hz, C).
1,1′-{[4-(Trifluoromethyl)phenyl]methanediyl}bis(2,4,5-trime-
thoxybenzene) (7c)
Pale yellow solid; mp 50–51 °C; yield: 478 mg (97%).
IR: 2937, 1510, 1324, 1206, 1035, 887, 768 cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.65 (s, 6 H), 3.67 (s, 6 H), 3.89 (s, 6 H),
6.11 (s, 1 H), 6.41 (s, 2 H), 6.58 (s, 2 H), 7.17 (d, J = 7.78 Hz, 2 H), 7.50
(d, J = 7.78 Hz, 2 H).
19F NMR (471 MHz, CDCl3):  = –118.7.
13C NMR (125 MHz, CDCl3):  = 42.7 (CH), 56.1 (2 CH3O), 56.7 (4
CH3O), 98.5 (2 CH), 114.9 (2 CH), 123.3 (2 C), 124.4 (q, JCF = 271 Hz,
CF3), 124.8 (q, JCF = 3.84 Hz, 2 CHCCF3), 128.2 (q, JCF = 32.6 Hz, CCF3),
129.2 (2 CH), 142.9 (2 C), 148.5 (2 C), 148.8 (C), 151.7 (2 C).
MS (EI): m/z (%) = 442 (100) [M+], 411 (70), 347 (7), 181 (17), 151 (20),
109 (20).
HRESIMS: m/z calcd for C25H27FNaO6 [M + Na]+: 465.1689; found:
465.1680.
19F NMR (471 MHz, CDCl3):  = –63.24.
MS (EI): m/z (%) = 492 (100) [M+], 461 (16), 347 (10), 181 (21), 151
1,1′-[(4-Methylphenyl)methanediyl]bis(2,4,5-trimethoxyben-
(27), 69 (5).
zene) (7g)
White solid; mp 134–137 °C (Lit.29 142–143 °C); yield: 408 mg (93%).
HRESIMS: m/z calcd for C26H27F3NaO6 [M + Na]+: 515.1657; found:
IR: 2918, 1512, 1200, 1037, 854, 760 cm–1
.
515.1643.
1H NMR (400 MHz, CDCl3):  = 2.30 (s, 3 H), 3.64 (s, 6 H), 3.66 (s, 6 H),
3.88 (s, 6 H), 6.04 (s, 1 H), 6.44 (s, 2 H), 6.54 (s, 2 H), 6.93 (d, J = 7.96
Hz, 2 H), 7.04 (d, J = 7.96 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 21.0 (CH3), 42.1 (CH), 56.1 (2 CH3O),
56.7 (2 CH3O), 57.0 (2 CH3O), 98.5 (2 CH), 114.7 (2 CH), 125.0 (2 C),
128.7 (2 CH), 128.9 (2 CH), 135.1 (C), 141.0 (C), 142.7 (2 C), 148.0 (2
C), 151.6 (2 C).
1,1′-[(4-Chlorophenyl)methanediyl]bis(2,4,5-trimethoxyben-
zene) (7d)
White solid; mp 157–159 °C (Lit.27 168–169 °C); yield: 454 mg (99%).
IR: 2932, 1513, 1450, 1203, 1036, 886, 761 cm–1
.
1H NMR (300 MHz, CDCl3):  = 3.64 (s, 6 H), 3.67 (s, 6 H), 3.89 (s, 6 H),
6.02 (s, 1 H), 6.39 (s, 2 H), 6.54 (s, 2 H), 6.98 (d, J = 8.42 Hz, 2 H), 7.21
(d, J = 8.42 Hz, 2 H).
MS (EI): m/z (%) = 438 (100) [M+], 407 (83), 347 (9), 181 (19), 151 (17),
13C NMR (100 MHz, CDCl3):  = 42.1 (CH), 56.0 (2 CH3O), 56.7 (2
CH3O), 56.8 (2 CH3O), 98.3 (2 CH), 114.5 (2 CH), 123.8 (2 C), 128.0 (2
CH), 130.3 (2 CH), 131.4 (C), 142.8 (C), 143.0 (2 C), 148.2 (2 C), 151.5
(2 C).
105 (24).
HRESIMS: m/z calcd for C26H30NaO6 [M + Na]+: 461.1940; found:
461.1930.
MS (EI): m/z (%) = 458 (100) [M+], 427 (72), 181 (25), 151 (30), 125
1,1′-[(4-Methoxyphenyl)methanediyl]bis(2,4,5-trimethoxyben-
(17).
zene) (7h)
White solid; mp 125–130 °C (Lit.29 131 °C); yield: 432 mg (95%).
HRESIMS: m/z calcd for C25H27ClNaO6 [M + Na]+: 481.1394; found:
IR: 2960, 1507, 1205, 1029, 880, 815, 764 cm–1
.
481.1370.
1H NMR (400 MHz, CDCl3):  = 3.64 (s, 6 H), 3.66 (s, 6 H), 3.78 (s, 3 H),
3.88 (s, 6 H), 6.02 (s, 1 H), 6.42 (s, 2 H), 6.54 (s, 2 H), 6.79 (d, J = 8.59
Hz, 2 H), 6.96 (d, J = 8.59 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 41.7 (CH), 55.1 (CH3O), 56.1 (2 CH3O),
56.7 (2 CH3O), 57.1 (2 CH3O), 98.6 (2 CH), 113.3 (2 CH), 114.6 (2 CH),
125.0 (C), 129.9 (2 CH), 136.3 (2 C), 142.8 (2 C), 148.0 (2 C), 151.6 (2
C), 157.6 (C).
1,1′-[(4-Bromophenyl)methanediyl]bis(2,4,5-trimethoxyben-
zene) (7e)
Orange solid; mp 137–138 °C (Lit.29 141 °C); yield: 483 mg (96%).
IR: 2933, 1511, 1451, 1200, 1035, 884, 761 cm–1
.
1H NMR (400 MHz, CDCl3):  = 3.64 (s, 6 H), 3.67 (s, 6 H), 3.88 (s, 6 H),
6.01 (s, 1 H), 6.40 (s, 2 H), 6.54 (s, 2 H), 6.92 (d, J = 8.47 Hz, 2 H), 7.35
(d, J = 8.47 Hz, 2 H).
MS (EI): m/z (%) = 454 (94) [M+], 423 (100), 347 (6), 271 (10), 181 (14),
13C NMR (100 MHz, CDCl3):  = 42.1 (CH), 56.1 (2 CH3O), 58.7 (2
CH3O), 58.8 (2 CH3O), 98.3 (2 CH), 114.6 (2 CH), 119.5 (C), 123.7 (2 C),
130.7 (2 CH), 131.0 (2 CH), 142.8 (C), 143.5 (2 C), 148.3 (2 C), 151.6 (2
C).
151 (12), 121 (37).
HRESIMS: m/z calcd for C26H30NaO7 [M + Na]+: 477.1889; found:
477.1882.
MS (EI): m/z (%) = 504 (100) [M+], 502 (98), 473 (63), 471 (62), 347
1,1′-[(3,4,5-Trimethoxyphenyl)methanediyl]bis(2,4,5-trimethoxy-
(16), 208 (12), 181 (37), 151 (40).
benzene) (7i)
Yellow solid; mp 103–104 °C (Lit.27 97–99 °C); yield: 504 mg (98%).
HRESIMS: m/z calcd for C25H27BrNaO6 [M + Na]+: 525.0889; found:
525.0873.
IR: 3002, 2935, 2834, 1588, 1512, 1454, 1205, 1126, 1031, 880, 763
cm–1
.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

H
S. M. M. Rodrigues et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3):  = 3.65 (s, 6 H), 3.70 (s, 6 H), 3.71 (s, 6 H),
3.82 (s, 3 H), 3.89 (s, 6 H), 6.01 (s, 1 H), 6.28 (s, 2 H), 6.54 (s, 2 H), 6.55
(s, 2 H).
13C NMR (100 MHz, CDCl3):  = 42.6 (CH), 56.0 (4 CH3O), 56.8 (2
CH3O), 57.1 (2 CH3O), 60.8 (CH3O), 98.4 (2 CH), 106.4 (2 CH), 114.5 (2
CH), 124.5 (2 C), 136.1 (C), 139.8 (C), 142.7 (2 C), 148.1 (2 C), 151.6 (2
C), 152.8 (2 C).
Central de Espectrometria de Massas de Micromoléculas Orgânicas
(CEMMO) of the Faculty of Pharmaceutical Sciences of Ribeirão Preto,
University of São Paulo for assistance and access to the mass spec-
trometry facility.
Supporting Information
MS (EI): m/z (%) = 514 (100) [M+], 483 (92), 347 (12), 331 (18), 181
(38), 151 (14).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610727.
S
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o
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HRESIMS: m/z calcd for C28H34NaO9 [M + Na]+: 537.2101; found:
537.2093.
References
2-[Bis(2,4,5-trimethoxyphenyl)methyl]naphthalene (7j)
(1) Muthyala, R.; Katritzky, A. R.; Lan, X. Dyes Pigm. 1994, 25, 303.
(2) (a) Baptista, M. S.; Indig, G. L. J. Phys. Chem. B 1998, 102, 4678.
(b) Irie, M. J. Am. Chem. Soc. 1983, 105, 2078.
White solid; mp 155–159 °C; yield: 432 mg (91%).
IR: 2962, 1512, 1196, 1034, 878, 818, 762 cm–1
.
(3) (a) Noack, A.; Schröder, A.; Hartmann, H. Angew. Chem. Int. Ed.
2001, 40, 3008. (b) Strekowski, L.; Lee, H.; Lin, S. Y.; Czarny, A.;
Deeveer, D. V. J. Org. Chem. 2000, 65, 7703.
(4) Lewis, M. R.; Goland, P. P. Cancer Res. 1952, 12, 130.
(5) Parai, M. K.; Panda, G.; Chaturvedi, V.; Manju, Y. K.; Sinha, S.
Bioorg. Med. Chem. Lett. 2008, 18, 289.
(6) Podder, S.; Choudhury, J.; Roy, U. K.; Roy, S. J. Org. Chem. 2007,
72, 3100.
(7) For reviews on the synthesis and application of triarylmeth-
anes, see: (a) Nair, V.; Thomas, S.; Mathew, S. C.; Abhilash, K. G.
Tetrahedron 2006, 62, 6731. (b) Mondal, S.; Panda, G. RSC Adv.
2014, 4, 28317.
(8) (a) Nair, V.; Abhilash, K. G.; Vidya, N. Org. Lett. 2005, 7, 5857.
(b) Nair, V.; Vidya, N.; Abhilash, K. G. Synthesis 2006, 3647.
(9) Genovese, S.; Epifano, F.; Pelucchini, C.; Curini, M. Eur. J. Org.
Chem. 2009, 1132.
(10) Wang, X.; Wang, Y.; Du, D. M.; Xu, J. J. Mol. Catal. A: Chem. 2006,
255, 31.
1H NMR (300 MHz, CDCl3):  = 3.61 (s, 6 H), 3.67 (s, 6 H), 3.90 (s, 6 H),
6.24 (s, 1 H), 6.47 (s, 2 H), 6.57 (s, 2 H), 7.25–7.28 (m, 1 H), 7.35 (br s, 1
H), 7.39–7.42 (m, 2 H), 7.67–7.81 (m, 3 H).
13C NMR (75 MHz, CDCl3):  = 42.7 (CH), 56.1 (2 CH3O), 56.8 (2 CH3O),
57.0 (2 CH3O), 98.7 (2 CH), 115.0 (2 CH), 124.5 (2 C), 125.1 (CH), 125.6
(CH), 126.9 (CH), 127.4 (CH), 127.5 (CH), 127.9 (CH), 128.3 (CH), 132.1
(C), 133.5 (C), 142.0 (C), 142.9 (2 C), 148.3 (2 C), 151.8 (2 C).
MS (EI): m/z (%) = 474 (100) [M+], 443 (76), 347 (7), 181 (14), 151 (12),
141 (22).
HRESIMS: m/z calcd for C29H30NaO6 [M + Na]+: 497.1940; found:
497.1929.
4-[Bis(2,4,5-trimethoxyphenyl)methyl]pyridine (7k)
Yellow solid; mp 94–95 °C; yield: 382 mg (90%).
IR: 2957, 2935, 1595, 1512, 1451, 1317, 1204, 1038, 890, 765 cm–1
.
1H NMR (400 MHz, CDCl3):  = 3.65 (s, 6 H), 3.68 (s, 6 H), 3.90 (s, 6 H),
6.02 (s, 1 H), 6.40 (s, 2 H), 6.55 (s, 2 H), 6.97–6.98 (m, 2 H), 8.45–8.46
(m, 2 H).
(11) Prakash, G. K. S.; Panja, C.; Shakhmin, A.; Shah, E.; Mathew, T.;
Olah, G. A. J. Org. Chem. 2009, 74, 8659.
(12) Li, H.; Yang, J.; Liu, Y.; Li, Y. J. Org. Chem. 2009, 74, 6797.
(13) Pasha, M. A.; Nagashree, S. Int. J. Res. Chem. Environ. 2013, 3, 54.
(14) (a) Wilsdorf, M.; Leichnitz, D.; Reissig, H.-U. Org. Lett. 2013, 15,
2494. (b) Saito, S.; Ohwada, T.; Shudo, K. J. Org. Chem. 1996, 61,
8089.
(15) Choudhury, J.; Podder, S.; Roy, S. J. Am. Chem. Soc. 2005, 127,
6162.
(16) Kodomari, M.; Nagamatsu, M.; Akaike, M.; Aoyama, T. Tetrahe-
dron Lett. 2008, 49, 2537.
13C NMR (100 MHz, CDCl3):  = 42.4 (CH), 56.1 (2 CH3O), 56.6 (2
CH3O), 56.7 (2 CH3O), 98.1 (2 CH), 114.5 (2 CH), 122.2 (2 C), 124.2 (2
CH), 142.8 (2 C), 148.6 (2 C), 149.3 (2 CH), 151.6 (2 C), 153.9 (C).
MS (EI): m/z (%) = 425 (100) [M+], 394 (39), 347 (19), 181 (31), 151
(25).
HRESIMS: m/z calcd for C24H28NO6 [M + H]+: 426.1917; found:
426.1905.
(17) Li, Z. X.; Duan, Z.; Kang, J. X.; Wang, H. Q.; Yu, L. J.; Wu, Y. J. Tet-
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Mansuy, V.; Petit, M.; Amatore, M. Org. Lett. 2017, 19, 2062.
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Funding Information
The authors thank Fundação de Amparo à Pesquisa do Estado de São
Paulo (FAPESP, grants 2016/04896-7 and 2018/24680-4), Coorde-
nação de Aperfeiçoamento de Pessoal de Nível Superior Brasil
(CAPES), and Conselho Nacional de Desenvolvimento Científico e Tec-
nológico (CNPq) for financial support and fellowships.
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0-4)
(21) Kirihara, M.; Noguchi, T.; Okajima, N.; Naito, S.; Ishizuka, Y.;
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Acknowledgment
The generous gift of niobium pentachloride samples by CBMM (Com-
panhia Brasileira de Metalurgia e Mineração) is gratefully acknowl-
edged. The authors thank Prof. Dr. Norberto Peporine Lopes from
(23) (a) Siqueira, M. S.; Silva-Filho, L. C. Tetrahedron Lett. 2016, 57,
5050. (b) Santos, W. H.; Silva-Filho, L. C. Synthesis 2012, 44,
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© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

I
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© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I