Facile synthesis of nonsymmetrical heteroaryl-substituted triarylmethanes: Via the FeCl3·6H2O-catalyzed two-step Friedel-Crafts-type reaction

Article abstract of DOI:10.1039/c6ob01638c

The FeCl₃·6H₂O-catalyzed three-component aza-Friedel-Crafts reaction of aromatic/heteroaromatic compounds, aromatic aldehydes and tert-butyl carbamate was reported. The subsequent Friedel-Crafts-type alkylation of the resulting tert-

Full text of DOI:10.1039/c6ob01638c

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Organic & Biomolecular Chemistry
ARTICLE
Facile synthesis of nonsymmetrical heteroaryl-substituted
triarylmethanes via FeCl3⋅6H2O-catalyzed two-steps Friedel-Crafts-
type reaction
Received 00th January 20xx,
Accepted 00th January 20xx
S. Ruengsangtongkul, P. Taprasert, U. Sirion and J. Jaratjaroonphong∗
DOI: 10.1039/x0xx00000x
FeCl3⋅6H2O-catalyzed three-component aza-Friedel-Crafts reaction of aromatic/heteroaromatic compounds, aromatic
aldehydes and tert-butyl carbamate was reported. The subsequent Friedel-Crafts-type alkylation of the resulting tert-butyl
diarylmethyl carbamate with heteroaromatic compounds under “open-flask” at room temperature was also performed.
The two-steps reaction was especially useful for the synthesis of functionalized nonsymmetrical heteroaryl-substituted
triarylmethanes in good yields under an air atmosphere at room temperature.
www.rsc.org/
Introduction
Triarylmethanes (TRAMs) are useful compounds which have
been widely applied in diverse areas of chemistry such as
medicinal chemistry, the dye industry and materials science.1-3
Particularly, triarylmethane derivatives containing indole,
furan and thiophene skeletons have been shown to be
powerful pharmaceuticals with diverse biological activities (Fig
1).2a,b,e,g,h Although convenient methods for the construction of
symmetrical TRAMs have gained much attention in past
decades,4-5 the development of methods for the synthesis of
nonsymmetrical heteroaryl-substituted TRAMs remain a great
challenge.6-10 Among the existing methods, Lewis acids or
Brønsted acid-catalyzed Friedel-Crafts arylation reaction of
nonsymmetrical diarylmethyl alcohol, sulfonamides, sulfones
and phosphates represents one of the most straightforward
way to afford
a variety of nonsymmetrical heteroaryl-
Fig 1 Examples of biological active heteroaryl-substituted TRAMs.
substituted TRAMs.1a,11 However, most of the examples
reported to date are limited to reactions of indole or aromatic
benzene substrates. Furthermore, there are disadvantages
such as the use of expensive and corrosive reagents, high
catalyst loading, elevated temperature, long duration, low
yields of products and special care for moisture/air sensitive
reagents.6-11 Recently, our groups reported Bi(OTf)3-catalyzed
aza-Friedel-Crafts reaction of electron-rich arenes, aldehydes
which could be used as an alternative alkylating agent to react
with 2-methylfuran
in the presence of Bi(OTf)3 giving
nonsymmetrical furyl-substituted triarylmethanes.12 To the
best of our knowledge, the synthetic approach for
nonsymmetrical heteroaryl-substituted triarylmethanes using
secondary benzylic carbamate is almost undeveloped. Only the
and tert-butyl or benzyl carbamate leading to
a direct
reaction
of
tert-butyl
and
benzyl
phenyl(2,4,5-
synthesis of tert-butyl and benzyl diarylmethyl carbamates
trimethoxyphenyl)methyl carbamates with 2-methylfuran has
been reported.12 In addition, the cleavage of the N-Boc and N-
Cbz protective group are competition reaction under Lewis
acids or Brønsted acid conditions.13-14
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Scheme 1 Metal-Catalyzed one-pot, three component aza-Friedel-Crafts reaction and sebsequent Friedel-Crafts-type reaction of the resulting diarylmethyl carbamates for
the synthesis of nonsymmetrical heteroaryl-substituted TRAMs.
In the past decade, the commercially available, inexpensive, the synthesis of nonsymmetrical diarylindolylmethanes
15-16
and environmentally friendly FeCl3
has been proposed as through a FeCl3-catalyzed three-component aza-Friedel-Crafts
an excellent potential catalyst for the Friedel-Crafts-type reaction of indole, aldehyde, and tertiary aromatic amines in
alkylation approaches to synthesize nonsymmetrical TRAMs. In one-pot.20 The reaction is well established, but the substrate
an early pioneering example, Wu and co-workers scope is strictly limited to the indole and tertiary aromatic
demonstrated that FeCl3 can serve as an effective catalyst for amine substrates and the reaction are proceeded at elevated
the synthesis of nonsymmetrical TRAMs via sequential double temperature (100
arylation of different arenes to geminal diacetate generated in FeCl3 6H2O as an efficient catalyst for a one-pot, three
situ from aldehyde and acetic anhydride in the presence of component aza-Friedel-Crafts reaction of electron-rich
FeCl3 at 80
C.17 Later on, Kim reported the synthesis of aromatic/hetero-aromatic compounds, aromatic aldehydes
nonsymmetrical indolyl-substituted TRAMs via FeCl3 6H2O and tert-butyl carbamate. The subsequent Friedel-Crafts-type
catalyzed regioselective arylation of -amido sulfones leading alkylation of the resulting tert-butyl diarylmethyl carbamates
°C). Herein, we report the first use of
⋅
°
⋅
α
to nonsymmetrical diarylsulfones which undergo further with heteroaromatic compounds under “open-flask” at room
Friedel-Crafts alkylation with indole derivatives.18 However, temperature was also performed. The advantage of the
only moderate yields (46-60%) of nonsymmetrical indolyl- present procedure is that it is a mild, facile, and efficient
substituted TRAMs were obtained after the reaction was method for the synthesis of functionalized nonsymmetrical
carried out in the presence of 20 mol% of FeCl3⋅6H2O at room heteroaryl-substituted TRAMs in two-steps. Moreover, the
temperature for 12 h in the second step. Recently, Kim and co- whole process is atom economic due to the fact that the tert-
workers found that the reaction of electron-rich arenes butyl carbamate is incorporated into the first step and is then
(except 1,3,5-trimethoxybenzene) with sulfonamidessulfones recovered in the second one (Scheme 1). Compared to the
or N-sulfonyl aldimines using FeCl3
proceeded according to a double Friedel-Crafts reaction to give toxicity. The Friedel-Crafts-type reaction of tert-butyl diaryl
symmetrical triarylmethanes due to the intrinsic instability of carbamate employing FeCl3 6H2O as catalyst also gave the
⋅ ⋅6H2O is much cheaper and has lower
6H2O as catalyst generally Bi(OTf)3 catalyst,12 FeCl3
⋅
the intermediate benzylic sulfonamide derivatives. Only the product in higher yields and with shorter reaction times.
reaction of 1,3,5-trimethoxybenzene with N-sulfonyl aldimines Moreover, the present synthetic procedure has the advantage
could proceed to the formation of the mono Friedel-Crafts of affording
a
nonsymmetrical heteroaryl-substituted
product.19 Alternatively, Wang developed a new strategy for triarylmethane core with high structural diversity under mild
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Table 2 Synthesis of tert-butyl diarylmethyl carbamates with various substratesa
Table 1 Optimization of the three-component aza-Friedel-Crafts reactiona
Entry
FeCl3⋅6H2O
Solvent
Time (h)
4a, yieldb (%)
(mol%)
10
10
10
10
10
5
1
2
3
4
5
6
7
8
9
10
Toluene
DCE
2
2
90
91
CH3NO2
CH3OH
H2O
2
81
2
72
2
35
86 (91)c
Toluene
DCE
2
5
2
92
2.5
2.5
0
Toluene
DCE
2
59
2
80
d
-
DCE
48
a
Reaction conditions: 1a (1 mmol), 2a (1.1 mmol), 3a (1 mmol),
b
FeCl3⋅6H2O, solvent (1 mL), room temperature. Isolated yield of
analytical pure products. The reaction using Bi(OTf)3 (5 mol%) instead
of FeCl3⋅6H2O. d No reaction based on TLC analysis.
c
a Reaction conditions: 1 (1 mmol), 2 (1.1 mmol), 3 (1 mmol), FeCl3⋅6H2O
(0.05 mmol), DCE (1 mL), room temperature. Isolated yields. The
b
c
reaction conditions under an air atmosphere at room
temperature.
d
reaction was carried in DCE at 80 °C for 2 h. The reaction was carried
in toluene at rt for 2 h.
Results and Discussion
Table 3 Optimization of Friedel-Crafts reaction of diarylmethyl carbamatea
Initially, an optimized FeCl3
component aza-Friedel-Crafts reaction of 1,3,5-trimethoxy-
benzene (1a), benzaldehyde (2a) and tert-butyl carbamate (
⋅6H2O-catalyzed, one-pot, three
3)
was examined in various solvents under air atmosphere. The
results are listed in Table 1. As anticipated, the reaction in the
presence of FeCl3⋅6H2O (10 mol%) afforded the tert-butyl
diarylcarbamate 4a in high yield at room temperature in non-
polar and weakly polar solvents such as toluene and
dichloroethane (DCE) (entries 1-2). A slightly lower yield was
obtained when employing polar aprotic and polar protic
solvents such as CH3NO2 and CH3OH (entries 3-4). The reaction
was also performed in water as a reaction medium (entry 5)
which has advantages from environmental and safety
standpoints.21 However, lower product yield was obtained.
From the solvent effect study, it was determined that toluene
and DCE were the solvents of choice. Next, the quantity of the
catalyst in toluene and DCE was optimized. A best yield of 4a
Entry Catalyst
mol%
Time (h)
6a, yieldb (%)
1
2
3
4
FeCl3⋅6H2O
FeCl3⋅6H2O
10
5
4
93
4
70
6912
Bi(OTf)3
10
-
24
24
c
-
-
a
Reaction conditions: 4h (0.5 mmol), 2-methylfuran (0.5 mmol),
FeCl3⋅6H2O, DCE (1 mL), room temperature. b Isolated yield of analytical
pure products. c No reaction based on TLC analysis.
was obtained in the using 5 mol % FeCl3⋅6H2O in DCE (entry 7
in Table 1). Compared to Bi(OTf)3 (5 mol%) as catalyst in
heteroaromatic compounds, aromatic aldehydes and tert-butyl
toluene, an inexpensive and environmentally friendly
carbamate. The experimental results are summarized in Table
FeCl3
⋅
control reaction in the absence of FeCl3
6H2O gave the product in comparable yield (entry 5). A
6H2O gave no products
2. While 1,3,5-trimethoxybenzene could react with
combination of aromatic aldehyde and tert-butyl carbamate in
the presence of 5 mol % FeCl3 6H2O under the optimized
a
⋅
and the starting materials were recovered (entry 10).
⋅
With the optimized reaction conditions in hand (Table 1,
entry 7), the scope and generality of the reaction was further
investigated with an array of electron-rich aromatic and
reaction condition to furnish the desired products 4a-f as a
sole product in high yields, heating was needed in the case of
2-pyridine carbaldehyde to accelerate the reaction rate and to
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Table 4 Synthesis of nonsymmetrical heteroaryl-substituted TRAMS with various substratesa
a Reaction conditions: 1 (0.5 mmol), 4 (0.5 mmol), FeCl3⋅6H2O (0.05 mmol), DCE (1 mL), room temperature. b Isolated yields. c The reaction was carried in DCE for 24 h.
increase the yield of the product 4g. The less steric hindered The aromatic aldehydes bearing electron-withdrawing
electron-rich arene, 1,2,4-trimethoxybenzene, gave a slightly substituents on the phenyl ring also reacted smoothly with 2-
lower yield of the desired product 4h and symmetrical methylfuran at room temperature to furnish compound 4j in
triarylmethane 5h was observed as a minor product via a 76 % yield. Moreover, the steric hindered N-heteroaromatic
double Friedel-Crafts reaction which could be due to the compound, N-Boc pyrrole, proved to be effective, leading to
intrinsic instability of the benzylic carbamate 4h. In the case of the selective formation of 4m in moderate yield.
1,2,4-trimethoxybenzene, however, toluene is found to be the
solvent of choice in terms of yield and selectivity of the carbamate
product. Not only 1,2,4-trimethoxybenzene, but also FeCl3 6H2O-catalyzed Friedel-Crafts-type reaction under “open-
Subsequently, the transformation of tert-butyl diarylmethyl
4
to functionalized nonsymmetrical TRAMs via
⋅
heteroaromatic nucleophiles like 2-methylfuran or 2-methyl- flask” and mild conditions was investigated. Our initial
and 2-ethylthiophene were equally good to satisfactory in investigations employing diarylmethyl carbamate 4h and 2-
toluene to afford the desired products 4i, 4k and 4l in good methylfuran as model substrates in combination with 10 mol
yields, along with a small amount of side products 5i and 5l
.
% FeCl3
⋅
6H2O as catalyst focused on the evaluation of the
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Table 5 Friedel-Crafts reaction of diarylmethyl carbamate 4aa
efficiency of the catalyst. The results are listed in Table 3.
Gratifyingly, the Friedel-Crafts reaction of 2-methylfuran using
4h as an alkylating agent in DCE at room temperature was very
effective, leading to the selective formation of the
corresponding nonsymmetrical triarylmethane 6a in high yield
(entry 1). Decreasing the catalyst loading to
5 mol %
FeCl3⋅6H2O gave a slightly lower yield of 6a (entry 2). In
comparison to the reaction in the presence of 10 mol %
Bi(OTf)3 (entry 3) which has been reported by our group,12 the
reaction employing 10 mol % FeCl3⋅6H2O gave a higher yield of
nonsymmetrical TRAMs and with a shorter reaction time (six
times). Furthermore, FeCl3
lower toxicity
⋅6H2O is much cheaper and has
The scope and generality of the synthesis strategy of
nonsymmetrical TRAMs bearing hetetroaryl substituents were
further investigated with an array of diarylmethyl carbamates
Entry
Catalyst
mol%
Time (h)
Product, yieldb (%)
4 and heteroaromatic compounds using 10 mol % FeCl3⋅6H2O
in DCE under “open-flask” at room temperature.
6t
5i
1
2
3
4
5
5
6
7
FeCl3⋅6H2O
FeCl3
10
10
10
10
40
10
20
-
24
24
24
24
24
24
24
24
53
12
34
20
31
41
33
22
trace
27
12
39
22
34
Representative results are illustrated in Table 4. The use of
diarylmethyl carbamate 4h containing 2,4,5-trimethoxyphenyl
Bi(OTf)3
ring could react smoothly with 2-alkylfurans, indole derivatives
and the less reactive 2-alkylthiophenes to give nonsymmetrical
In(OTf)3
In(OTf)3
I2
I2
-
TRAMs 6a-b
other hand, the reaction of N-Boc pyrrole with 4h gave only a
moderate yield of the desired product 6e and compound was
, 6f-g and 6c-d in good to excellent yields. On the
c
c
-
-
7
a
obtained as a side-product in 44% yield via a double arylation
at C-2 and C-5 positions of the pyrrole ring. The Friedel-Crafts
reaction of diarylmethyl carbamate containing heteroaromatic
Reaction conditions: 4a (0.5 mmol), 2-methylfuran (0.5 mmol),
FeCl3⋅6H2O, DCE (1 mL), room temperature. b Isolated yield of analytical
pure products. c No reaction based on TLC analysis.
substitutents such as 5-methylfuran
(4i and 4j), 5-
methylthiophene (4k) and N-Boc pyrrole (4m) in the Ar1 ring
formation of compound
alkylation. The formation of the desired product
explained by addition of heteroarenes such as indole to the
reactive intermediate which is generated by Iron(III) ion
catalysed tert-buyl carbamate elimination of III and followed
by aromatization of VI
4
through an aza-Friedel-Crafts-type
with the different heteroaromatic compound in the presence
6
could be
of 10 mol % FeCl3
⋅
good at affording
6H2O in DCE at room temperature were also
collection of nonsymmetrical
a
V
di(heteroaryl)aryl-methanes 6h-s in good to excellent yields. In
the case of 5-methylfurylaryl carbamates 4i and 4j with N-Boc
pyrrole, only the mono Friedel-Crafts alkylation products 6l
and 6m were obtained in 68% and 56%, respectively.
.
Interestingly, the reaction of FeCl3⋅6H2O (10 mol %) with a
Conclusions
mixture of 4a and 2-methylfuran in DCE at room temperature
gave moderate yield of the desired product 6t. Unexpectedly,
bis(furyl)methane 5i and 1,3,5-trimethoxybenzene were
isolated in 22% and 33% yields, respectively (Table 5, entry 1).
The reaction of 4a with 2-methylfuran in the presence of
various Lewis acids such as Bi(OTf)3 and In(OTf)3 as well as
molecular iodine were also investigated. The results are shown
In conclusion, we have demonstrated a mild, facile, atom
economical and efficient method for the synthesis of
functionalized nonsymmetrical heteroaryl-substituted TRAMs
via two-steps Friedel-Crafts-type reaction catalyzed by
FeCl3
FeCl3
⋅
⋅
6H2O in DCE under “open-flask” at room temperature.
6H2O is shown to be an efficient catalyst for a one-pot,
three component aza-Friedel-Crafts reaction of aromatic/
heteroaromatic compounds, aromatic aldehydes and tert-butyl
carbamate in the first step leading to the tert-butyl
diarylmethyl carbamates which could react smoothly with a
variety of heteroaromatic compounds at room temperature by
in Table
5 (entries 2-6). In all case, the mixture of
unsymmetrical TRAMs product 6t and side-product 5i were
also observed. The formation of 5i could be obtained through
an unusual loss of 1,3,5-trimethoxybenzene under these
condition.11d
On the basis of literature information18-19 and our finding,12
association with 10 mol % of FeCl3⋅6H2O to afford the
functionalized nonsymmetrical heteroaryl-substituted TRAMs
in good to excellent yields. The advantages of the present
method are the use of mild reaction conditions with an
inexpensive commercially available catalyst at low loadings to
yield a simple and environmentally friendly synthesis under an
air atmosphere. Moreover, the whole process is atom
a plausible mechanism for the formation of compounds
4
and
6
is depicted in Scheme 2. The first step is the formation of
activated N-Boc imine I, which is formed by the Iron(III) ion
catalyzed condensation of the aldehyde and tert-butyl
carbamate. The nucleophilic addition of heteroaromatic
compound attacks the resulting imine
I leading to the
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Scheme 2 Plausible reaction mechanism.
economic due to the fact that the tert-butyl carbamate is was purified by radial chromatography (SiO2, 100% hexane to 30%
incorporated into the first step and is then recovered in the EtOAc/hexane as eluent) to give the corresponding α-branched
second one. The further development of asymmetric reactions amines 4 and/or triarylmethanes 5.
is ongoing and will be reported in due course.
Spectral data of compounds 4a-f, 4h, 4i, 4k, 4l, 5h, 5i, 5k, 5l were
in agreement with our previous reported.12
Experimental Section
tert-Butyl
pyridin-2-yl(2,4,6-trimethoxyphenyl)methylcarba-
mate (4g). White solid; m.p. 124-126 oC; yield 324.4 mg (87%). 1H
NMR (400 MHz, CDCl3): δ 8.50 (d, J = 4.6 Hz, 1H), 7.54 (t, J = 7.6 Hz,
1H), 7.22 (d, J = 7.9 Hz, 1H), 7.06 (br t, J = 5.9 Hz, 1H), 6.63 (d, J =
9.7 Hz, 1H), 6.30 (d, J = 9.7 Hz, 1H), 6.15 (s, 2H), 3.81 (s, 3H), 3.75 (s,
6H), 1.48 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 161.8, 160.6, 158.7,
155.8, 148.4, 135.8, 121.0, 120.7, 111.2, 91.3, 78.9, 55.9, 55.2, 49.6,
28.5; IR (film): νmax 3455 (N-H), 2974, 2937, 2840, 1715, 1608, 1592,
1496, 1456, 1333, 1226, 1205, 1171, 1155, 1119, 1043, 1020, 951,
814, 770 cm-1; HRMS (ESI-TOF) calcd for C20H27N2O5 [M+H]+
375.1920, found 375.1921.
General Methods
NMR spectra were recorded on BRUKER AVANC (400 MHz). 1H
NMR spectra were recorded at 400 MHz. Chemical shifts are
reported in parts per million (ppm) from tetramethylsilane with the
solvent resonance as the internal standard (deuterochloroform: δ
7.26 ppm). 13C NMR spectra were recorded at 100 MHz with
complete proton decoupling. Chemical shifts are reported in parts
per million (ppm) from tetramethylsilane with the solvent
resonance as the internal standard (deuterochloroform: δ 77.0
ppm). High-resolution mass spectra (HRMS) data were obtained
with a Finnigan MAT 95. Infrared spectra were determined on a
PERKIN ELMER FT/IR-2000S spectrophotometer and are reported in
wave number (cm-1). Radial chromatography on a Chromatotron
was performe using Merck silica gel 60 PF254 with CaSO4 1/2 H2O [E.
Merck, Darmstadt, Germany] and was activated by heating in an
oven at 80 °C for 45 min. Thin layer chromatography (TLC) was
performed with Merck silica gel 60 PF254 aluminium plate [E. Merck,
Darmstadt, Germany]. Melting points were measured using a
Melting point apparatus (Griffin) and are uncorrected. All chemicals
for synthesis were purchased from commercial sources and used
without further purification.
tert-butyl (5-methylfuran-2-yl)(4-nitrophenyl)methylcarbamate
1
(4j). Yellow oil; yield 252.6 mg (76 %). H NMR (400 MHz, CDCl3): δ
8.20 (d, J = 8.3 Hz, 2H), 7.51 (d, J = 8.3 Hz, 2H), 6.00 (br s, 1H), 5.94
(br s, 1H), 5.90 (br d, J = 1.0 Hz, 1H), 5.45 (br s, 1H), 2.25 (s, 3H),
1.45 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 154.9, 153.0, 150.5,
147.9, 147.6, 127.8, 123.8, 109.0, 106.5, 80.6, 52.9, 28.4, 13.5; IR
(film): νmax 3406 (N-H), 1715, 1521, 1349, 1244, 1166, 1022, 857,
788 cm-1; HRMS (ESI-TOF) calcd for C17H20N2O5Na [M+Na]+
355.1270, found 355.1272.
tert-Butyl 2-((tert-butoxycarbonylamino)(phenyl)methyl)-1H-
pyrrole-1-carboxylate (4m). Pale yellow oil; yield 175.6 mg (47%).
1H NMR (400 MHz, CDCl3): δ 7.90 (d, J = 8.6 Hz, 1H), 7.30-7.13 (m,
5H), 6.40 (d, J = 8.6 Hz, 1H), 6.25 (br s, 1H), 6.16 (br t, J = 3.2 Hz, 1H),
5.78 (br s, 1H), 1.49 (s, 9H), 1.40 (s, 9H); 13C NMR (100 MHz, CDCl3):
δ 155.3, 149.0, 141.7, 128.2, 127.0, 126.6, 122.6, 114.3, 110.0, 84.2,
79.6, 52.4, 28.5, 27.8; IR (film): νmax 3433 (N-H), 1740, 1716, 1490,
1369, 1335, 1166, 1045, 847, 701 cm-1; HRMS (ESI-TOF) calcd for
C21H28N2O4Na [M+Na]+ 395.1947, found 395.1946.
General procedure for the synthesis of diarylmethyl carbamate 4
To a dichloroethane solution (1 mL) of electron-rich arene (1.0
mmol), freshly distilled aldehyde (1.1 mmol), and tert-butyl
carbamate (1.0 mmol) in
a test-tube open to air at room
temperature was added FeCl3∙6H2O (0.05 mmol). After the reaction
was stirred until completion (TLC analysis), the reaction mixture was
quenched with aqueous NaHCO3 (10 mL) and extracted with CH2Cl2
(2 x 10 mL). The combined organic layer was washed with brine (10
mL), dried over anhydrous Na2SO4 and filtered. The filtrate was
evaporated (aspirator then vacuo) to give a crude product, which
General procedure for the synthesis of nonsymmetrical
triarylmethane 6
To a dichloroethane solution (2 mL) of diarylmethyl carbamate
4 (0.5 mmol) and heteroaromatic compound (0.5 mmol) in a test-
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tube open to air at room temperature was added FeCl3∙6H2O (0.05
3-(Phenyl(2,4,5-trimethoxyphenyl)methyl)-1H-indole (6f). Pink
mmol). After the reaction was stirred until completion (TLC solid; m.p. 164-165 oC; yield 173.7 mg (93%). 1H NMR (400 MHz,
analysis), the reaction mixture was quenched with distilled water CDCl3): δ 8.08 (br s, 1H), 7.35-7.25 (m, 7H), 7.20 (t, J = 7.5 Hz, 1H),
(10 mL) and extracted with EtOAc (2 x 10 mL). The combined 7.03 (t, J = 7.5 Hz, 1H), 6.70 (s, 1H), 6.64 (s, 1H), 6.59 (s, 1H), 6.10 (s,
organic layer were washed with water (10 mL) and saturated 1H), 3.94 (s, 3H), 3.78 (s, 3H), 3.64 (s, 3H); 13C NMR (100 MHz,
aqueous NaCl (10 mL), dried over anhydrous Na2SO4 and filtered. CDCl3): δ 151.3, 148.1, 144.3, 142.9, 136.8, 128.8, 128.0, 127.0,
The filtrate was evaporated (aspirator then vacuo) to give a crude 125.9, 124.5, 124.0, 122.1, 121.8, 119.9, 119.5, 119.1, 114.6, 111.0,
product, which was purified by radial chromatography (SiO2, 100% 98.3, 56.9, 56.6, 56.1, 40.9; IR (film): νmax 3411, 3369, 2958, 2941,
hexane to 50% EtOAc/hexane as eluent) to give the corresponding 2832, 1509, 1456, 1397, 1316, 1205, 1178, 1035, 742, 702 cm-1;
unsymmetrical triarylmethanes 6.
Spectral data of compounds 6a and 5i were in agreement with 396.1579.
our previous reported.12
5-Methoxy-3-(phenyl(2,4,5-trimethoxyphenyl)methyl)-1H-in-
dole (6g). Purple solid; m.p. 140-142 oC; yield 193.7 mg (96%). 1H
HRMS (ESI-TOF) calcd for C24H23NO3Na [M+Na]+ 396.1576, found
2-Ethyl-5-(phenyl(2,4,5-trimethoxyphenyl)methyl)furan (6b). NMR (400 MHz, CDCl3): δ 7.87 (br s, 1H), 7.30-7.19 (m, 6H), 6.83
Brown solid; m.p. 51-53 oC; yield 167.4 mg (95%). 1H NMR (400 (dd, J = 2.4, 8.7 Hz, 1H), 6.68 (d, J = 2.2 Hz, 1H), 6.64 (s, 1H), 6.59 (s,
MHz, CDCl3): δ 7.32-7.29 (m, 2H), 7.25-7.19 (m, 3H), 6.65 (s, 1H), 2H), 5.32 (s, 1H), 3.91 (s, 3H), 3.75 (s, 3H), 3.70 (s, 3H), 3.62 (s, 3H);
6.58 (s, 1H), 5.92 (d, J = 2.8 Hz, 1H), 5.82 (s, 1H), 5.78 (d, J = 2.8 Hz, 13C NMR (100 MHz, CDCl3): δ 153.6, 151.3, 148.0, 144.1, 142.9,
1H), 3.91 (s, 3H), 3.76 (s, 3H), 3.75 (s, 3H), 2.64 (q, J = 7.5 Hz, 2H), 131.9, 128.8, 128.0, 127.6, 125.9, 124.6, 124.3, 119.4, 114.4, 111.9,
1.23 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 157.0, 154.9, 111.6, 102.1, 98.2, 57.0, 56.6, 56.1, 55.8, 41.8; IR (film): νmax 3354,
151.2, 148.4, 143.0, 142.4, 128.5, 128.1, 126.2, 122.4, 114.8, 108.6, 2936, 2830, 1583, 1508, 1485, 1453, 1438, 1396, 1319, 1265, 1205,
104.4, 98.1, 56.7, 56.6, 56.1, 43.1, 21.4, 12.3; IR (film): νmax 2970, 1172, 1109, 1031, 831, 734, 701 cm-1; HRMS (ESI-TOF) calcd for
2936, 2848, 2832, 1610, 1560, 1509, 1464, 1397, 1317, 1209, 1180,
1111, 1036, 982, 876, 739, 701 cm-1; HRMS (ESI-TOF) calcd for
C22H24O4Na [M+Na]+ 375.1572, found 375.1579.
C
25H25NO4Na [M+Na]+ 426.1681, found 426.1697.
2-Ethyl-5-((5-methylfuran-2-yl)(phenyl)methyl)furan
(6h).
1
Yellow oil; yield 127.5 mg (96%). H NMR (400 MHz, CDCl3): δ 7.42-
2-Methyl-5-(phenyl(2,4,5-trimethoxyphenyl)methylthiophene
7.31 (m, 5H), 5.96 (br d, J = 3.4 Hz, 4H), 5.45 (s, 1H), 2.69 (q, J = 7.5
(6c). White solid; m.p. 98-100 oC; yield 124.3 mg (70%). 1H NMR Hz, 2H), 2.33 (s, 3H), 1.28 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz,
(400 MHz, CDCl3): δ 7.32-7.22 (m, 5H), 6.69 (s, 1H), 5.58 (br d, J = CDCl3): δ 157.2, 153.0, 152.7, 151.4, 140.1, 128.4, 127.0, 108.2,
3.0 Hz, 1H), 6.56 (s,1H), 6.46 (d, J = 3.0 Hz, 1H), 5.98 (s, 1H), 3.91 (s, 108.0, 106.1, 104.4, 45.2, 21.4, 13.6, 12.2; IR (film): νmax 2973, 2922,
3H), 3.75 (s, 3H), 3.73 (s, 3H), 2.44 (s, 3H); 13C NMR (100 MHz, 2880, 1603, 1558, 1496, 1453, 1219, 1184, 1075, 1058, 1021, 964,
CDCl3): δ 151.2, 148.6, 145.7, 144.2, 143.1, 138.6, 128.7, 128.2 , 954, 778, 731, 699 cm-1; HRMS (ESI-TOF) calcd for C18H18O2Na
126.4, 125.9, 124.5, 124.4, 114.4, 98.2, 56.9, 56.8, 56.2, 44.5, 15.4; [M+Na]+ 289.1204, found 289.1205.
IR (film): νmax 2933, 2848, 1608, 1600, 1509, 1463, 1453, 1316,
2-Ethyl-5-((5-methylfuran-2-yl)(4-nitrophenyl)methyl)furan (6i).
1
1396, 1247, 1207, 1178, 1103, 1036, 979, 740, 701 cm-1; HRMS (ESI- Brown oil; yield 122.9 mg (79%). H NMR (400 MHz, CDCl3): δ 8.20
TOF) calcd for C21H22O3SNa [M+Na]+ 377.1187, found 377.1190.
(d, J = 8.6 Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H), 5.96 (d, J = 3.3 Hz, 2H),
5.94 (d, J = 4.1 Hz, 2H), 5.46 (s, 1H), 2.62 (q, J = 7.5 Hz, 2H), 2.27 (s,
2-Ethyl-5-(phenyl(2,4,5-trimethoxyphenyl)methylthiophene
(6d). Brown solid; m.p. 84-85 oC; yield 140.2 mg (76%). 1H NMR (400 3H), 1.22 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 157.9,
MHz, CDCl3): δ 7.34-7.25 (m, 5H), 6.74 (s, 1H), 6.64 (d, J = 3.2 Hz, 152.1, 151.1, 150.9, 147.6, 147.1, 129.4, 123.8, 108.9, 108.7, 106.3,
1H), 6.58 (s, 1H), 6.52 (d, J = 3.2 Hz, 1H), 6.03 (s, 1H), 3.92 (s, 3H), 104.7, 44.9, 21.4, 13.6, 12.2; IR (film): νmax 2974, 2938, 2880, 1717,
3.77 (s, 3H), 3.76 (s, 3H), 2.82 (q, J = 7.5 Hz, 2H), 1.31 (t, J = 7.5 Hz, 1605, 1560, 1520, 1348, 1217, 1182, 1110, 1016, 860, 782, 735
3H); 13C NMR (100 MHz, CDCl3): δ 151.1, 148.5, 146.2, 145.3, 144.2, cm-1; HRMS (ESI-TOF) calcd for C18H17NO4Na [M+Na]+ 334.1055,
143.0, 128.7, 128.1, 126.3, 125.7, 124.3, 122.5, 114.2, 98.0, 56.8, found 334.1053.
56.7, 56.1, 44.4, 23.5, 15.8; IR (film): νmax 2964, 2933, 2848, 2832,
2-((5-Ethylthiophen-2-yl)(phenyl)methyl)-5-methylfuran
(6j).
1
1609, 1600, 1508, 1461, 1453, 1396, 1317, 1246, 1207, 1178, 1103, Yellow oil; yield 127.1 mg (90%). H NMR (400 MHz, CDCl3): δ 7.37-
1036, 979, 739, 701 cm-1; HRMS (ESI-TOF) calcd for C22H24O3SNa 7.28 (m, 5H), 6.62 (d, J = 3.3 Hz, 1H), 6.60 (d, J = 3.3 Hz, 1H), 5.96 (d,
[M+Na]+ 391.1344, found 391.1346.
J = 2.8 Hz, 1H), 5.92 (br s, 1H), 5.53 (s, 1H), 2.80 (q, J = 7.5 Hz, 2H),
tert-Butyl 2-(phenyl(2,4,5-trimethoxyphenyl)methyl)-1H-pyr- 2.28 (s, 3H), 1.29 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
role-1-carboxylate (6e). Brown solid; m.p. 85-86 oC; yield 93.2 mg 154.4, 151.6, 146.7, 142.8, 142.0, 128.5, 128.4, 127.0, 125.4, 122.7,
1
(44%). H NMR (400 MHz, CDCl3): δ 7.34-7.25 (m, 5H), 6.74 (s, 1H), 108.5, 106.1, 46.5, 23.5, 15.8, 13.7; IR (film): νmax 2966, 2924, 1634,
6.64 (d, J = 3.2 Hz, 1H), 6.58 (s, 1H), 6.52 (d, J = 3.2 Hz, 1H), 6.03 (s, 1494, 1452, 1219, 1022, 785, 699 cm-1; HRMS (ESI-TOF) calcd for
1H), 3.92 (s, 3H), 3.77 (s, 3H), 3.76 (s, 3H), 2.82 (q, J = 7.5 Hz, 2H), C18H18OSNa [M+Na]+ 305.0976, found 304.2592.
1.31 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 151.1, 148.5,
2-((5-ethylthiophen-2-yl)(4-nitrophenyl)methyl)-5-methylfuran
146.2, 145.3, 144.2, 143.0, 128.7, 128.1, 126.3, 125.7, 124.3, 122.5, (6k). Brown oil; yield 121.2 mg (74%). 1H NMR (400 MHz, CDCl3): δ
114.2, 98.0, 56.8, 56.7, 56.1, 44.4, 23.5, 15.8; IR (film): νmax 2964, 8.19 (d, J = 8.6 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 6.64 (d, J = 3.0 Hz,
2933, 2848, 2832, 1609, 1600, 1508, 1461, 1453, 1396, 1317, 1246, 1H), 6.60 (d, J = 3.0 Hz, 1H), 6.00 (d, J = 2.9 Hz, 1H), 5.94 (br s, 1H),
1207, 1178, 1103, 1036, 979, 739, 701 cm-1; HRMS (ESI-TOF) calcd 5.62 (s, 1H), 2.81 (q, J = 7.5 Hz, 2H), 2.28 (s, 3H), 1.29 (t, J = 7.5 Hz,
for C22H24O3SNa [M+Na]+ 391.1344, found 391.1346.
3H); 13C NMR (100 MHz, CDCl3): δ 152.7, 152.3, 147.6, 147.0, 140.7,
129.3, 126.0, 123.8, 122.9, 109.2, 106.3, 46.2, 23.5, 15.8, 13.7; IR
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(film): νmax 2970, 2931, 2874, 1717, 1640, 1598, 1520, 1446, 1347, NMR (400 MHz, CDCl3): δ 8.18 (d, J = 8.6 Hz, 2H), 8.13 (br s, 1H),
1266, 1218, 1109, 1022, 858, 839, 807, 737, 703 cm-1; HRMS (ESI- 7.46 (d, J = 8.6 Hz, 2H), 7.23 (dd, J = 5.3, 8.7 Hz, 1H), 7.08 (dd, J =
TOF) calcd for C18H17NO3SNa [M+Na]+ 350.0827, found 350.0824.
9.5, 2.1 Hz, 1H), 6.83 (td, J = 8.4, 1.9 Hz, 1H), 6.81 (br s, 1H), 5.92 (br
tert-Butyl 2-((5-methylfuran-2-yl)(phenyl)methyl)-1H-pyrrole-1- d, J = 2.1 Hz, 1H), 5.88 (d, J = 3.0 Hz, 1H), 5.68 (s, 1H), 2.28 (s, 3H);
carboxylate (6l). Yellow oil; yield 114.7 mg (68%). 1H NMR (400 13C NMR (100 MHz, CDCl3): δ 158.9 (1J = 234.0 Hz), 153.4, 150.9,
MHz, CDCl3): δ 7.33-7.25 (m, 4H), 7.16 (d, J = 7.4 Hz, 2H), 6.10 (br t, J 136.2 (3J = 13.0 Hz), 129.3, 124.5 (4J = 3.0 Hz), 123.6, 122.9, 119.7 (3J
= 2.0 Hz, 1H), 6.02 (s, 1H), 5.88 (br s, 1H), 5.71 (br d, J = 1.9 Hz, 1H), = 10.0 Hz), 114.6, 108.1, 107.2 (2J = 16.0 Hz), 106.4, 97.6 (2J = 25.0
5.64 (br d, J = 1.9 Hz, 1H), 2.27 (s, 3H), 1.46 (s, 9H); 13C NMR (100 Hz), 41.4, 13.3; IR (film): νmax 3342, 2924, 2853, 1714, 1626, 1598,
MHz, CDCl3): δ 154.8, 151.0, 149.4, 141.2, 134.9, 128.8, 128.2, 1520, 1450, 1347, 1216, 1141, 1108, 1015, 952, 848, 736 cm-1;
126.7, 122.2, 114.5, 109.8, 108.3, 106.1, 83.9, 44.5, 27.8, 13.7; IR HRMS (ESI-TOF) calcd for C20H15FN2O3Na [M+Na]+ 373.0964, found
(film): νmax 2980, 2922, 1743, 1561, 1453, 1488, 1405, 1370, 1331, 373.0960.
1161, 1117, 1063, 1022, 848, 778, 728, 699 cm-1; HRMS (ESI-TOF)
calcd for C21H23NO3Na [M+Na]+ 360.1576, found 360.1574.
3-((5-Methylthiophen-2-yl)(phenyl)methyl)-1H-indole (6r). Red
oil; yield 142.8 mg (94%). 1H NMR (400 MHz, CDCl3): δ 8.00 (br s,
tert-Butyl 2-((5-methylfuran-2-yl)(4-nitrophenyl)methyl)-1H- 1H), 7.40-7.24 (m, 7H), 7.20 (t, J = 7.6 Hz, 1H), 7.05 (t, J = 7.6 Hz,
pyrrole-1-carboxylate (6m). Brown oil; yield 107.2 mg (56%). 1H 1H), 6.83 (s, 1H), 6.58 (br s, 2H), 5.82 (s, 1H), 2.44 (s, 3H); 13C NMR
NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.2 Hz, 2H), 7.33 (d, J = 8.2 Hz, (100 MHz, CDCl3): δ 145.7, 144.0, 138.4, 136.6, 128.4, 128.3, 126.8,
2H), 6.17 (s, 1H), 6.14 (t, J = 3.2 Hz, 1H), 5.90 (br d, J = 1.81 Hz, 1H), 126.5, 125.3, 124.5, 123.5, 122.1, 119.9, 114.7, 111.1, 44.2, 15.3; IR
5.79 (br s, 1H), 5.70 (br d, J = 2.7 Hz, 1H), 2.27 (s, 3H), 1.46 (s, 9H); (film): νmax 3418, 2917, 2858, 1618, 1560, 1493, 1456, 1417, 1338,
13C NMR (100 MHz, CDCl3): δ 152.7, 151.6, 148.8, 148.6, 146.6, 1220, 1095, 800, 740, 700 cm-1. HRMS (ESI-TOF) calcd for C20H16NS+
133.3, 129.4, 123.3, 122.2, 114.5, 109.8, 108.7, 106.0, 83.9, 44.0, [M-H]+ 302.0998, found 302.1006.
27.7, 13.5; IR (film): νmax 2924, 2851, 1740, 1522, 1370, 1347, 1157,
1120, 849, 733 cm-1; HRMS (ESI-TOF) calcd for C21H22N2O5Na carboxylate (6s). Red solid; m.p. 80-82 C; yield 133.7 mg (72%). H
[M+Na]+ 405.1426, found 405.1423.
NMR (400 MHz, CDCl3): δ 7.95 (br s, 1H), 7.39-7.34 (m, 3H), 7.30-
tert-Butyl
2-((1H-indol-3-yl)(phenyl)methyl)-1H-pyrrole-1-
o
1
3-((5-Methylfuran-2-yl)(phenyl)methyl)-1H-indol (6n). Red oil; 7.26 (m, 2H), 7.23-7.17 (m, 4H), 6.54 (br s, 1H), 6.26 (br s, 1H), 6.07
1
yield 122.2 mg (85%). H NMR (400 MHz, CDCl3): δ 8.02 (br s, 1H), (t, J = 3.2 Hz, 1H), 5.68 (s, 1H), 1.34 (s, 9H); 13C NMR (100 MHz,
7.43-7.25 (m, 7H), 7.20 (t, J = 7.4 Hz, 1H), 7.06 (t, J = 7.4 Hz, 1H), CDCl3): δ 149.7, 143.5, 136.9, 136.6, 128.8), 128.1, 127.0, 126.2,
6.80 (s, 1H), 5.90 (br d, J = 2.5 Hz, 1H), 5.85 (d, J = 2.5 Hz, 1H), 5.65 123.4, 122.0, 121.9, 119.8, 119.3, 114.7, 111.1, 119.8, 83.7, 41.9,
(s, 1H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 155.1, 151.2, 27.7; IR (film): νmax 3418, 2980, 1733, 1489, 1456, 1403, 1370, 1330,
142.2, 136.6, 128.6, 128.4, 126.9, 126.6, 123.4, 122.1, 119.7, 119.5, 1160, 1117, 1063, 1012, 847, 739 cm-1; HRMS (ESI-TOF) calcd for :
117.8, 111.2, 108.2, 106.0, 42.8, 13.8; IR (film): νmax 3417, 3059, C24H24N2O2Na [M+Na]+ 395.1735, found 395.1732.
3027, 2921, 1602, 1561, 1494, 1456, 1416, 1338, 1218, 1095, 1021,
2-Methyl-5-(phenyl(2,4,6-trimethoxyphenyl)methyl)furan (6t).
o
963, 783, 741, 700 cm-1; HRMS (ESI-TOF) calcd for C20H17NONa White solid; m.p. 78-80 C; yield 89.8 mg (53%). 1H NMR (400 MHz,
[M+Na]+ 310.1208, found 310.1209.
CDCl3): δ 7.24-7.21 (m, 4H), 7.18-7.13 (m, 1H), 6.16 (s, 2H), 5.96 (s,
5-Methoxy-3-((5-methylfuran-2-yl)(phenyl)methyl)-1H-indole
1H), 5.87 (br d, J = 2.6 Hz, 1H), 5.80 (br d, J = 2.6 Hz, 1H), 3.82 (s,
(6o). Brown solid; m.p. 90-92 oC; yield 137.6 mg (87%). 1H NMR (400 3H), 3.66 (s, 6H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.2,
MHz, CDCl3): δ 7.92 (br s, 1H), 7.35-7.29 (br m, 5H), 7.29-7.21 (br m, 159.2, 155.2, 149.9, 143.1, 128.5, 127.6, 125.6, 112.2, 107.4, 106.0,
2H), 6.84 (br d, J = 8.8 Hz, 1H), 6.79 (br d, J = 8.6 Hz, 2H), 5.87 (d, J = 91.8, 55.9, 55.3, 39.7, 13.7; IR (film): νmax 2938, 2838, 1606, 1590,
16.2 Hz, 2H),5.58 (s, 1H), 3.75 (s, 3H), 2.28 (s, 3H); 13C NMR (100 1494, 1455, 1417, 1223, 1204, 1149, 1116, 1059, 812, 699 cm-1;
MHz, CDCl3): 155.0, 153.8, 151.1, 142.1, 131.6, 128.5, 128.3, 127.2, HRMS (ESI) calcd for C21H22O4Na [M+Na]+ 361.1416, found
126.5, 124.0, 117.4, 112.2, 111.7, 108.1, 105.9, 101.6, 55.8, 29.7, 361.1417.
13.7; IR (film): νmax 3419, 2940, 2831, 1705, 1625, 1584, 1487, 1455,
tert-Butyl 2,5-bis(phenyl(2,4,5-trimethoxyphenyl)methyl)-1H-
1216, 1171, 1051, 1022, 787, 724, 700 cm-1; HRMS (ESI-TOF) calcd pyrrole-1-carboxylate (7). Pale yellow oil; yield 75.0 mg (44%). 1H
for C21H19NO2Na [M+Na]+ 340.1313, found 340.1314.
NMR (400 MHz, CDCl3): δ 7.29-7.24 (m, 4H), 7.20-7.16 (m, 2H), 7.14-
7.10 (m, 4H), 6.53 (s, 1H), 6.50 (s, 1H), 6.36 (s, 1H), 6.32 (s, 1H), 6.25
6-Fluoro-3-((5-methylfuran-2-yl)(phenyl)methyl)-1H-indole
(6p). Red oil; yield 131.6 mg (86%). 1H NMR (400 MHz, CDCl3): δ (s, 1H), 6.19 (s, 1H), 5.36 (d, J = 14.7 Hz, 2H), 3.88 (s, 3H), 3.87 (s,
8.00 (br s, 1H), 7.34-7.27 (m, 6H), 7.04 (dd, J = 9.6, 1.7 Hz, 1H), 6.82 3H), 3.71 (s, 3H), 3.70 (s, 3H), 3.67 (s, 6H), 1.01 (s, 3H), 0.96 (s, 6H);
(td, J = 9.2, 2.2 Hz, 1H), 6.77 (s, 1H), 5.92 (br d, J = 2.6 Hz, 1H), 5.84 13C NMR (100 MHz, CDCl3): 151.4, 150.0, 148.3, 143.5, 143.4, 143.1,
(d, J = 2.6 Hz, 1H), 5.60 (s, 1H), 2.29 (s, 3H); 13C NMR (100 MHz, 137.4, 137.3, 129.2, 129.1, 128.1, 128.0, 126.2, 126.1, 124.6, 124.4,
CDCl3): δ 160.0 (1J = 263.0 Hz), 154.9, 151.3, 142.0, 136.5 (4J = 13.0 114.2, 113.9, 112.2, 111.8, 98.5, 83.4, 57.0, 56.9, 56.7, 56.6, 56.32,
Hz), 128.5, 128.4, 126.7, 123.6, 123.5, 120.5 (3J = 10.0 Hz), 117.9, 56.29, 43.4, 43.2, 28.3, 26.8, 26.7; IR (film): νmax 3104.1, 3026, 3001,
108.3 (2J = 22.0 Hz), 108.2, 106.1, 97.4 (2J = 22.0 Hz), 42.8, 13.7; IR 2936, 2832, 1610, 1561, 1509, 1464, 1453, 1438, 1397, 1316, 1210,
(film): νmax 3426, 3063, 3028, 2922, 1627, 1559, 1497, 1456, 1342, 1036, 701 cm-1; HRMS (ESI-TOF) calcd for C41H45NO8Na [M+Na]+
1251, 1217, 1140, 1022, 952, 837, 803, 738, 724, 700 cm-1; HRMS 702.3043, found 702.3042.
(ESI-TOF) calcd for C20H16FNONa [M+Na]+ 328.1114, found
328.1113.
Acknowledgements
6-Fluoro-3-((5-methylfuran-2-yl)(4-nitrophenyl)methyl)-1H-
o
1
indole (6q). Brown solid; m.p. 174-176 C; yield 108.6 mg (62%). H
8 | J. Name., 2012, 00, 1-3
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Chem., 2004, 1584; (m) A. R. Katritzky and D. Toader, J. Org.
Chem., 1997, 62, 4137.
(a) M. Nambo and C. M. Crudden, ACS Catal., 2015, 5, 4734;
(b) F.-L. Sun, X.-J. Gu, Q. Zheng, Q.-L. He and S. L. You, Eur. J.
Org. Chem., 2010, 47; (c) Q. Kang, Z.-A. Zhao and S.-L. You, J.
Am. Chem. Soc., 2007, 129, 1484.
Financial support from the Center of Excellence for Innovation in
Chemistry (PERCH-CIC), Office of Higher Education Commission,
Ministry of Education and by a Research Grant from Burapha
University through the National Research Council of Thailand (Grant
no. Grant no. 21/2556 and 90/2557) are gratefully acknowledged.
Special thanks to Prof. Dr. Ron Beckett, Faculty of Science, Burapha
University for kindly proof-reading the English manuscript.
6
7
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OB-ART-07-2016-001638
Table of Content
A mild, facile, atom economical and efficient method was described for the synthesis of functionalized nonsymmetrical
heteroaryl-substituted triarylmethanes from electron-rich aromatic/heteroaromatic compounds, aromatic aldehydes and
tert-butyl carbamate via two-steps Friedel-Crafts-type reaction catalyzed by FeCl3⋅6H2O under “open-flask” at room
temperature.
R1
H
N
H
Ar3
FeCl3 6H2O
(10 mol%)
H
Ar1
H
X
FeCl3 6H2O
(5 mol%)
2
or
R1
R
+
NHBoc
Ar2
Ar3
3
R
Ar2CHO
+
Ar1
air, rt
Ar1
21 examples
MeO
Ar2
air, rt
X
H2NBoc
- H2NBoc
H
R2
OMe
X = O, S, NBoc
MeO