Atmospheric CO2 promoted synthesis of N-containing heterocycles over B(C6F5)3 catalyst

Article abstract of DOI:10.1039/c6nj01721e

B(C₆F₅)₃ combined with atmospheric CO₂ was found to be highly effective for the cyclization of ortho-substituted aniline derivatives with N,N-dimethylformamide (DMF), and a series of N-containing heterocycles including benzothiazoles, benzimidazoles, quinazolinone and benzoxazole were obtained in good to excellent yields.

Full text of DOI:10.1039/c6nj01721e

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DOI: 10.1039/C6NJ01721E
NJC
PAPER
Atmospheric CO2 Promoted Synthesis of N-Containing
Heterocycles over B(C F ) Catalyst
6
5 3
Received 00th January 20xx,
Accepted 00th January 20xx
Xiang Gao, Bo Yu, Qingqing Mei, Zhenzhen Yang, Yanfei Zhao, Hongye Zhang, Leiduan Hao, Zhimin
Liu*
DOI: 10.1039/x0xx00000x
6 5 3 2
B(C F ) combined with atmospheric CO was found to be highly effective for the cyclization of ortho-substituted aniline
www.rsc.org/
derivatives with N,N-dimethylformamide (DMF), and a series of N-containing heterocycles including benzothiazoles,
benzomidazoles, quinazolinone and benzoxazole were obtained in good to excellent yields.
9
10
11
aniline derivatives with carboxylic acids, nitriles and esters,1
or the oxidative cyclization of the substrates with aldehydes
and alcohols in the presence of oxidants. Recently, the
synthesis of benzimidazoles via the reaction of 1,2-
arylenediamines with N,N-dimethylformamide (DMF) was
2
1
. Introduction
13
Since CO2 emission has caused serious environmental
problems, the capture and utilization of CO have drawn much
attention in recent years. As an abundant, nontoxic, easily
available, and renewable carbon source, CO can be widely
applied in many areas such as food, separation, chemical
reaction, material processing and fabrication, and so on.
Recently, the CO -promoted reactions have been reported,
showing promising potentials for applications of CO . For
example, Kleij et al. reported a CO -based method for efficient
and highly selective formation of cyclic cis-diol scaffolds.
Jiang’s group found that the side reaction in the oxidative
cross-coupling of sulfides could be suppressed efficiently in the
presence of CO2. Wang et al. reported a CO -mediated
metathesis reaction of amines with N,N-dimethylformamide to
various formamides. Our group applied CO as a cocatalyst
combined with a task-specific ionic liquid to realize the
efficient hydration of propargylic alcohols to α-hydroxy
2
1
reported, however, highly acidic reaction medium was
2
14
required.
The synthesis of N-containing heterocyclic
compounds from o-phenylenediamines and N-substituted
formamide was also reported using zinc catalyst in the
2
15
2
presence of poly(methylhydrosiloxane). Most of the reported
2
protocols suffered from one or more drawbacks such as metal-
based or toxic catalyst systems, strong oxidising or caustic
reagents, hazardous solvents, poor yield and low selectivity.
Therefore, exploring simple, green, efficient catalytic systems
is still highly desirable.
Herein, we present an efficient protocol for the synthesis of
N-containing heterocycles, which was realized by CO2-
promoted cyclization of ortho-substituted aniline derivatives
2
3
4
2
5
2
(
including
anthranilamide
dimethylformamide (DMF) over B(C F ) catalyst under mild
2-aminothiophenols,
o-phenylenediamines,
6
and 2-aminophenol)
with N,N-
ketones. As a promotor or cocatalyst, CO could be easily
separated from the reaction solution, thus showing promising
applications.
N-containing heterocyclic compounds are generally
biocompatible, which could be widely used as pharmaceutical
and agrochemical agents. The scaffolds of benzazoles, such as
2
6
5 3
conditions. A series of N-containing heterocycles including
benzothiazoles, benzomidazoles, quinazolinone and
benzoxazole were obtained in good to excellent yields. The
reaction mechanism was explored in details.
7
benzothiazoles,
benzimidazoles,
quinazolinones
and
benzoxazoles, are typical N-containing heterocycles that are
extensively used as antiviral, antibacterial, anticancer,
2
. Experimental section
2.1 Materials
antihistaminic,
antitubercular,
antihypertensive,
anti-
8
inflammatory agents and plant growth regulators. The general
protocols for the synthesis of these N-containing heterocycles
are based on the condensation reaction of ortho-substituted
CO (99.99%) was provided by Beijing Analytical Instrument
2
Company. 2-Aminothiophenol (98%) and 2-amino-4-
chlorothiophenol (97%) were purchased from J&K Scientific
Ltd. 2-Amino-4-methoxybenzenethiol (98%), 2-amino-5-
nitrobenzenethiol (98%) were purchased from Beijing Kaida
Technology
Development
Co.,
Ltd.
2-Amino-5-
methylbenzenethiol, 2-amino-5-methoxybenzenethiol, 2-
amino-5-ethoxybenzenethiol, 2-amino-5-fluorobenzenethiol,
2
-amino-5-chlorobenzenethiol
and
2-amino-5-
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1
bromobenzenethiol were synthesized according to the 1h: 6-chlorobenzothiazole: H NMR (400 MHz, DMSO) δ 9.47
View Article Online
DOI: 10.1039/C6NJ01721E
[S1-6]
reported
procedures.
Different
kinds
of
o- (s, 1H), 8.19 (dd, J = 16.2, 5.2 Hz, 2H), 7.54 (dd, J = 8.6, 1.9 Hz,
phenylenediamines and hydrosilanes were purchased from 1H); C NMR (100 MHz, DMSO) δ 159.10, 154.47, 132.93,
1
3
J&K Scientific Ltd and Alfa Aesar. The deuterated solvents 131.49, 126.11, 124.48, 122.96.
1
(
DMSO-d6, C D , CDCl3, DMF-d7) were obtained from 1i: 5-bromobenzothiazole: H NMR (400 MHz, DMSO) δ 9.40 (s,
6
6
Cambridge Isotope Laboratories, Inc. All chemicals were of 1H), 8.47 (d, J = 1.8 Hz, 1H), 8.03 (d, J = 8.7 Hz, 1H), 7.69 (dd, J
13
analytical grade and used as received.
= 8.7, 1.9 Hz, 1H); C NMR (100 MHz, DMSO) δ 157.79, 152.57,
1
1
1
36.22, 129.83, 125.55, 125.03, 118.73.
j: 5-nitrobenzothiazole: H NMR (400 MHz, DMSO) δ 9.72 (s,
2
.2 Typical procedure for the cyclization of ortho-substituted
1
aniline derivatives with CO2
H), 9.24 (d, J = 1.9 Hz, 1H), 8.38 – 8.32 (m, 1H), 8.27 (d, J = 9.0
13
In a typical experiment, 2-aminothiophenol (0.5 mmol, 0.0626 Hz, 1H); C NMR (100 MHz, DMSO) δ 163.59, 157.13, 145.18,
g), B(C F ) (5 mol%, 0.0128 g), Et SiH (2 mmol, 0.1764 g), 134.99, 124.02, 121.82, 120.20.
6
5 3
2
2
1
DMF (1 mL) were loaded in a 10 mL flask equipped with a 2a: benzimidazole: H NMR (400 MHz, DMSO) δ 12.47 (s, 1H),
magnetic stirrer. The air in the reactor was replaced by CO2. 8.22 (s, 1H), 7.59 (s, 2H), 7.19 (dd, J = 5.9, 3.1 Hz, 2H); C NMR
13
The CO pressure was kept at 0.1 MPa using a balloon. The (100 MHz, DMSO) δ 142.37, 122.15.
2
1
reaction mixture was stirred at 120 °C for 24 h. Finally, the 2b: 6-methylbenzimidazole: H NMR (400 MHz, DMSO) δ
reaction mixture was cooled down in ice-water, and the 12.30 (s, 1H), 8.12 (s, 1H), 7.46 (d, J = 8.2 Hz, 1H), 7.36 (s, 1H),
1
13
product yields were determined by H NMR using pyrazine as 7.00 (d, J = 8.2 Hz, 1H), 2.41 (s, 3H); C NMR (100 MHz, DMSO)
the internal standard of the crude mixture. The pure products δ 139.44, 136.43, 135.37, 131.80, 123.43, 114.54, 113.84,
were obtained via column chromatography separation and 20.68.
1
13
1
characterized by NMR. H NMR (400 MHz) and C NMR (100 2c: 7-methylbenzimidazole: H NMR (400 MHz, DMSO) δ 12.41
MHz) analysis was carried out on a Bruker Avance 400 HD (s, 1H), 8.15 (s, 1H), 7.37 (d, J = 7.9 Hz, 1H), 7.06 (t, J = 7.6 Hz,
Ⅲ
13
spectrometer with DMSO-d6 as the solvent at ambient 1H), 6.96 (d, J = 7.2 Hz, 1H); C NMR (101 MHz, DMSO) δ
temperature. The NMR spectra of the products were given in 141.72, 137.96, 132.02, 129.16, 122.41, 122.14, 113.11, 17.21.
1
Supporting Information (Figure S3-S33).
2d: 5, 6-dimethylbenzimidazole: H NMR (400 MHz, DMSO) δ
1
13
2.23 (s, 1H), 8.07 (s, 1H), 7.36 (s, 2H), 2.30 (s, 6H); C NMR
100 MHz, DMSO) δ 140.51, 136.20, 129.61, 114.81, 19.44.
a: benzothiazole: H NMR (400 MHz, DMSO) δ 9.41 (s, 1H), 2e: 6-methoxybenzimidazole: H NMR (400 MHz, DMSO) δ
.12 (dd, J = 8.1, 2.8 Hz, 2H), 7.48 (m, 2H); C NMR (100 MHz, 12.28 (s, 1H), 8.10 (s, 1H), 7.46 (s, 1H), 7.08 (d, J = 2.0 Hz, 1H),
2.3 NMR spectral data of the products
(
1
1
1
13
8
13
DMSO) δ 156.26, 153.50, 134.03, 126.50, 125.80, 123.48, 6.81 (dd, J = 8.7, 2.3 Hz, 1H), 3.78 (s, 3H); C NMR (101 MHz,
1
22.79.
DMSO) δ 156.05, 141.92, 138.41, 133.94, 116.77, 111.82,
1
1
b: 5-methylbenzothiazole: H NMR (400 MHz, DMSO) δ 9.29 97.91, 55.87.
1
(
s, 1H), 8.04-7.84 (m, 2H), 7.33 (d, J = 7.8 Hz, 1H), 2.43 (s, 3H); 2f: 5-fluorobenzimidazole: H NMR (400 MHz, DMSO) δ 12.81
1
3
C NMR (100 MHz, DMSO) δ 155.24, 151.71, 135.62, 134.19, (s, 1H), 8.38 (s, 1H), 7.63 (dd, J = 8.5, 4.9 Hz, 1H), 7.47 (d, J =
28.13, 123.00, 122.35, 21.44.
1
3
1
1
9
7
7.8 Hz, 1H), 7.04 (td, J = 9.7, 1.9 Hz, 1H); C NMR (100 MHz,
1
c: 5-methoxybenzothiazole: H NMR (400 MHz, DMSO) δ DMSO) δ 159.46, 157.12, 143.01, 115.70, 109.74, 109.49,
.18 (s, 1H), 7.96 (d, J = 8.9 Hz, 1H), 7.72 (d, J = 2.5 Hz, 1H), 100.93 (CH).
13
1
.13 (dd, J = 8.9, 2.5 Hz, 1H), 3.84 (s, 3H); C NMR (100 MHz, 2g: 5-chlorobenzimidazole: H NMR (400 MHz, DMSO) δ 12.61
DMSO) δ 157.97, 153.78, 148.01, 135.53, 123.89, 116.15, (s, 1H), 8.27 (s, 1H), 7.65 (s, 1H), 7.60 (d, J = 8.5 Hz, 1H), 7.21
1
3
1
1
8
05.20, 56.17.
(dd, J = 8.5, J = 1.8 Hz, 1H); C NMR (100 MHz, DMSO) δ
1
d: 6-methoxybenzothiazole: H NMR (400 MHz, DMSO) δ 143.46, 139.29, 136.62, 126.19, 122.04, 116.39, 115.22.
.34 (s, 1H), 7.87 (s, 1H), 7.04 (d, J = 8.6 Hz, 1H), 6.62 (d, J = 8.4 2h: 5, 6-dichlorobenzimidazole: H NMR (400 MHz, DMSO) δ
Hz, 1H), 3.75 (s, 3H); C NMR (100 MHz, DMSO) δ 162.07, 12.72 (s, 1H), 8.34 (s, 1H), 7.86 (s, 2H); C NMR (100 MHz,
1
1
3
13
1
61.37, 140.89, 137.85, 115.79, 110.49, 108.09, 56.07.
DMSO) δ 145.2, 138.2, 124.8, 117.2.
1
1
1
e: 5-ethoxybenzothiazole: H NMR (400 MHz, DMSO) δ 9.18 2i: 5-bromobenzimidazole: H NMR (400 MHz, DMSO) δ 12.70
(
s, 1H), 7.95 (d, J = 8.9 Hz, 1H), 7.69 (d, J = 2.4 Hz, 1H), 7.11 (dd, (s, 1H), 8.31 (s, 1H), 7.83 (s, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.32 (d,
1
3
J = 8.9, 2.5 Hz, 1H), 4.09 (q, J = 7.0 Hz, 2H), 1.36 (t, J = 7.0 Hz, J = 8.3 Hz, 1H); C NMR (100 MHz, DMSO) δ 143.69, 125.05,
1
3
3
1
1
1
H); C NMR (100 MHz, DMSO) δ 157.19, 153.69, 147.92, 114.50.
35.51, 123.88, 116.43, 105.77, 64.15, 15.08. 2j: 5-nitrobenzimidazole: H NMR (400 MHz, DMSO) δ 8.55 (s,
f: 5-fluorobenzothiazole: H NMR (400 MHz, DMSO) δ 9.37 (s, 1H), 8.51 (d, J = 2.1 Hz, 1H), 8.11 (dd, J = 8.9, 2.2 Hz, 1H), 7.76
1
1
1
3
13
H), 8.26 – 8.01 (m, 2H), 7.42 (td, J = 9.0, 2.6 Hz, 1H); C NMR (d, J = 8.9 Hz, 1H); C NMR (100 MHz, DMSO) δ 146.26, 142.15,
(
100 MHz, DMSO) δ 161.59, 159.17, 156.87, 156.84, 150.40, 117.10.
1
1
1
1
=
1
35.46, 135.35, 124.77, 124.67, 115.38, 115.13, 109.30, 109.03. 2k: 5-trifluoromethylbenzimidazole: H NMR (400 MHz, DMSO)
1
g: 5-chlorobenzothiazole: H NMR (400 MHz, DMSO) δ 9.42 (s, δ 12.89 (s, 1H), 8.45 (s, 1H), 7.97 (s, 1H), 7.78 (d, J = 8.4 Hz, 1H),
13
H), 8.34 (d, J = 2.0 Hz, 1H), 8.09 (d, J = 8.7 Hz, 1H), 7.58 (dd, J 7.49 (dd, J = 8.5, 1.1 Hz, 1H); C NMR (100 MHz, DMSO) δ
13
8.7, 2.1 Hz, 1H); C NMR (100 MHz, DMSO) δ 157.81, 152.31, 144.27, 128.67, 125.97, 123.27, 122.27, 121.95, 120.57, 118.03.
35.74, 130.57, 127.16, 124.67, 122.66.
2
| J. Name., 2012, 00, 1-3
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1
2
l: methyl benzimidazole-5-carboxylate: H NMR (400 MHz, conditions (Table 1, entry 3). The above results indicated that
View Article Online
DOI: 10.1039/C6NJ01721E
DMSO) δ 12.77 (s, 1H), 8.40 (s, 1H), 8.23 (s, 1H), 7.84 (dd, J = DMF involved the synthesis of the product, and CO greatly
2
13
8
(
2
.5, 1.3 Hz, 1H), 7.67 (d, J = 8.5 Hz, 1H), 3.86 (s, 3H). C NMR promoted the reaction (Table 1, entries 2 vs. 3). Then the
100 MHz, DMSO) δ 167.28, 145.07, 123.72, 123.39, 52.39. influence of the catalyst amount was tested, and
m: etheyl benzimidazole-5-carboxylate: H NMR (400 MHz, benzothiazole could be obtained in good yields even with 1
1
DMSO) δ 11.73 (s, 1H), 8.43 (s, 1H), 8.24 (s, 1H), 7.84 (dd, J = mol% B(C F ) (Table 1, entry 5), demonstrating that B(C F )
6 5 3
6
5 3
8
2
1
6
2
1
7
.5, J = 1.3 Hz, 1H), 7.68 (d, J = 8.5 Hz, 1H), 4.31 (q, J = 7.1 Hz, combined with atmospheric CO was highly efficient for this
2
H), 1.32 (t, J = 7.1 Hz, 3H); C NMR (100 MHz, DMSO) δ reaction. The influences of reaction temperature and time
66.51, 144.82, 141.22, 138.44, 123.80, 123.18, 117.77, 115.12, were also investigated. It was indicated that the yields of
13
0.69, 14.45.
benzothiazole decreased obviously as decreasing the
1
n: 5-benzoylbenzimidazole: H NMR (400 MHz, DMSO) δ temperature (Table 1, entries 3 vs. 6, 7) or shortening the time
2.91 (s, 1H), 8.49 (s, 1H), 8.04 (s, 1H), 7.83 – 7.65 (m, 4H), (Table 1, entries 3 vs. 8-10), and the optimal conditions were
.59 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2H); C NMR (100 120 C and 24 h.
13
MHz, DMSO) δ 195.34, 155.18, 144.37, 137.73, 133.67, 131.51,
1
30.49, 129.02, 127.88, 123.41, 109.43, 107.55.
a
1
Table 1. The cyclization of 2-aminothiophenol with DMF under different conditions
2
o: N-methylbenzimidazole: H NMR (400 MHz, DMSO) δ 8.19
(
s, 1H), 7.68 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.24 (dd,
1
3
J = 14.3, 7.7 Hz, 2H), 3.82 (s, 3H); C NMR (100 MHz, DMSO) δ
1
43.95, 142.74, 134.03, 121.68, 120.88, 118.71, 109.57, 30.06
1
2
p: N-phenylbenzimidazole: H NMR (400 MHz, DMSO) δ 8.08
o
b
b
Entry
Cats/mol%
T/ C
t/h
Conv. [%]
Yield [%]
(
s, 1H), 7.89 – 7.87 (m, 1H), 7.53 – 7.41 (m, 6H), 7.30 (dd, J =
13
c
9
1
1
2
1
1
.1, J =5.4 Hz, 2H); C NMR (100 MHz, DMSO) δ 142.73,
35.25, 132.70, 129.06, 127.12, 123.08, 122.81, 121.92, 119.47,
09.54.
1
5
5
5
3
1
5
5
5
5
5
120
120
120
120
120
100
80
24
24
24
24
24
24
24
18
12
6
0
26
>99
99
76
51
30
98
69
15
0
d
2
23
99
92
73
50
26
90
66
10
3
4
1
q: 4-azabenzimidazole: H NMR (400 MHz, DMSO) δ 12.78 (s,
H), 8.45 (s, 1H), 8.35 (dd, J = 4.7, 1.3 Hz, 1H), 8.02 (dd, J = 8.0,
1
3
5
.3 Hz, 1H), 7.23 (dd, J = 8.0, 4.7 Hz, 1H); C NMR (100 MHz,
DMSO) δ 151.50, 144.37, 144.17, 131.09, 124.41, 118.19.
6
1
2
1
=
1
2
1
r: 5-azabenzimidazole: H NMR (400 MHz, DMSO) δ 12.86 (s,
7
H), 8.95 (s, 1H), 8.40 (s, 1H), 8.30 (d, J = 5.5 Hz, 1H), 7.59 (d, J
8
120
120
120
13
5.4 Hz, 1H); C NMR (100 MHz, DMSO) δ 144.63, 141.61,
9
41.32, 140.12, 138.06, 109.80.
1
10
s: 5-azabenzimidazole: H NMR (400 MHz, DMSO) δ 12.51 (s,
H), 8.47 (s, 1H), 8.11 (s, 2H), 8.00 (dd, J = 6.3, 3.3 Hz, 2H), 7.37
a
Reaction conditions: 2-aminothiophenol (0.5 mmol), B(C
dd, J = 6.4, 3.2 Hz, 2H); C NMR (100 MHz, DMSO) δ146.95, mmol), DMF (1 mL), CO (0.1 MPa), 120 C, 24 h; determined by H NMR (DMSO-
6
F
)
5 3
(5 mol%), Et
2
SiH
2
(2
13
o
b
1
(
2
c
1
3
1
32.01, 130.18, 129.16, 128.25, 123.79.
a: quinazolinone benzoxazole: H NMR (400 MHz, DMSO) δ
2.24 (s, 1H), 8.25 – 7.98 (m, 2H), 7.81 (t, J = 7.6 Hz, 1H), 7.66
d
6
, 400 MHz) using pyrazine as an internal standard; only CO
DMF; only DMF (1 mL), without CO .
2
(0.1 MPa), without
d
1
2
1
3
Based on the above results, the substituted 2-
aminothiophenols with electron donating and electron
withdrawing groups were tested to react with DMF in the
(d, J = 8.1 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H); C NMR (100 MHz,
DMSO) δ 161.19, 149.24, 145.84, 134.77, 127.69, 127.20,
1
4
7
2
1
26.30, 123.11.
1
presence of atmospheric CO and Et SiH over B(C F ) catalyst.
2 2 2 6 5 3
a: benzoxazole: H NMR (400 MHz, DMSO) δ 8.71 (s, 1H),
.86 – 7.71 (m, 1H), 7.71 – 7.56 (m, 1H), 7.33 (td, J = 7.0, 1.4 Hz,
As shown in Scheme 1, all the substituted substrates could be
converted to corresponding benzothiazoles, and excellent
product yields were gained in most cases. Though the
reactivities of the substrates with electron donating groups
were lower than those with electron withdrawing groups, high
product yields could be obtained as reaction time prolonged to
13
H); C NMR (101 MHz, DMSO) δ 153.75, 149.26, 139.60,
25.21, 124.22, 119.88, 110.72.
3
. Results and discussion
4
0 h (Scheme 1, 1b-e). The derivatives with electron
In our initial experiments, the cyclization of 2-
withdrawing groups including -F, -Cl and -Br displayed
relatively high reactivities, and corresponding products were
achieved in high yields (Scheme 1, 1f-i). Even for the substrate
aminothiophenol catalysed by B(C F ) as a model reaction was
6
5 3
carried out, and the results are listed in Table 1. The cyclization
reaction did not occur in the presence of atmospheric CO2
without DMF, while it could proceed in the presence of DMF
with strong electron withdrawing -NO group, corresponding
2
product, 5-nitrobenzothiazole, was obtained in a yield of 68%
within 40 h (Scheme 1, 1j). In addition, 4-substituent 2-
aminothiophenols were also tolerated in this reaction, though
without CO , producing benzothiazole in a yield of 23% (Table
2
1
, entries 1-2). Excitingly, the coexistence of atmospheric CO2
and DMF significantly improved the reaction activity, affording
benzothiazole in an excellent yield of 99% under the similar
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less reactive than 5-substituent substrates, probably due to
electronic and steric effects (Scheme 1, 1d, 1h vs. 1c, 1g).
View Article Online
DOI: 10.1039/C6NJ01721E
Scheme 1. Synthesis of various benzothiazoles. Reaction conditions: Reactant (0.5
o
mmol), B(C
6
F
5
)
3
(5 mol%), Et
2
SiH
2
(2.5 mmol), DMF (1 mL), CO
2
(0.1 MPa), 120 C, 24 h;
a
1
Reaction time: 40 h. The yields were determined by H NMR (DMSO-d
6
, 400 MHz)
using pyrazine as an internal standard. Isolated yields were in the bracket.
Encouraged by the great success in the reactions of 2-
aminothiophenols with DMF to various benzothiazoles, we
applied B(C F ) in catalysing the cycloaddition of diverse o-
6
5 3
phenylenediamines with DMF. Using Et SiH as the silane, Scheme 2. Synthesis of benzimidazoles. Reaction conditions: Reactant (0.5 mmol),
2
2
o
B(C
6
F
5
)
3
(5 mol%), (EtO)
3
SiH (5 mmol), DMF (1 mL), CO
2
(0.1 MPa), 120 C, 24 h. The
benzimidazole was obtained in a poor yield of 15% under
atmospheric CO2 pressure at 120 C for 24 h, while
triethoxysilane ((EtO) SiH) afforded a product yield of 99%
1
o
Yields were determined by H NMR (DMSO-d
standard. Isolated yields were in the bracket.
6
, 400 MHz) using pyrazine as an internal
3
under the same other conditions. Hence, (EtO) SiH instead of
3
Inspired by the above results, we further explored the
cyclization of less reactive but more challenging substrates
with DMF catalysed by B(C F ) in the presence of CO . To our
delight, anthranilamide bearing an amide group gave rise to 4-
quinazolinone in a yield of 99% despite the less-nucleophilic
ability of the amide group for the condensation step (Scheme
Et SiH was used in the cyclization of o-phenylenediamines
2
2
with DMF. As shown in Scheme 2, B(C F ) combined with
6
5 3
6
5 3
2
atmospheric CO was very effective for catalysing DMF to react
2
with all the tested o-phenylenediamines, affording the
corresponding products in excellent yields in most cases. For
example, substituents on phenyl ring of diamines with
disparate electronic properties had no obvious bias on the
formation of products (Scheme 2, 2a-k). Ortho- and bis-
substituents on the benzene moiety showed no obvious
influence on the reaction outcome (Scheme 2, 2c-d, 2h). It was
noteworthy that both ester and ketone functionalities
remained intact after reaction, which was important for the
production of these kinds of benzimidazoles (Scheme 2, 2l-n).
In addition, the N-methyl and phenyl substituted diamines
could give rise to 2o and 2p smoothly despite the increased
steric hindrance for the cyclization. As examples of diamines
containing N-heteroatoms, 2,3- and 3,4-diaminopyridine were
also amenable to this protocol (Scheme 2, 2q-r). Interestingly,
o-phenylenediamine containing an extended conjugated
system could proceed successfully as well, and the
corresponding product 2s was obtained in a yield of 94%.
3
, equation 1). In addition, the inert substrate 2-aminophenol
could also be cyclized with DMF, producing 4a in a yield of 42%.
As the CO pressure was increased to 1 MPa, benzoxazole was
2
obtained in a yield of 70% (Scheme 3, equation 2). These
findings indicated that the B(C F ) -CO catalytic system was
6
5 3
2
highly efficient for the synthesis of N-containing heterocycles.
Scheme 3. Synthesis of quinazolinone and benzoxazole. Reaction conditions: Reactant
o
(
2
0.5 mmol), B(C
4 h. The Yields were determined by H NMR (DMSO-d
6
F
5
)
3
(5 mol%), (EtO)
3
SiH (5 mmol), DMF (1 mL), CO
2
(0.1 MPa), 120 C,
1
6
, 400 MHz) using pyrazine as an
a
2
internal standard. CO pressure was 1 MPa.
To explore the possible reaction mechanism, a series of
experiments were conducted. First, the interaction of B(C F )
6
5 3
4
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ARTICLE
1
13
11
19
with DMF was examined by H, C, B and F NMR analyses, of DMF, which may further react with CO and silane to form the
2
View Article Online
1
DOI: 10.1039/C6NJ01721E
as shown in Figure S1. From the H NMR spectra of DMF and trimethylamine product and drove the reaction to the right, thus
its mixture with B(C F ) , it was found that the signals of H greatly promoting the reaction. Then the intramolecular
6
5 3
atoms from CH (1, 2) and CHO (3) of DMF in the mixture nucleophilic cyclization of A and dehydration reaction of B
3
shifted downfield from δ 2.14 to 2.68, δ 2.45 to 2.71 and δ took place successively, thus yielding product C.
7
.74 to 8.37, respectively; meanwhile, the signals of C atoms
from CH (1, 2) and CHO (3) of DMF in the mixture shifted
3
downfield from δ 30.30 to 34.17, δ 34.92 to 38.74 and δ
1
61.51 to 165.55, respectively. Moreover, the B atom in
B(C F ) showed an upfield shift from δ 14.64 to -0.36 after
6
5 3
19
interaction with DMF. The F NMR signals assigning to F (1, 2,
3
1
) atoms in B(C F ) shifted upfield from -160.35, -144.30, -
6 5 3
28.92 ppm to -162.22, -155.10, -133.01 ppm, respectively , as
B(C F ) mixed with DMF. All these shifts demonstrated the
6
5 3
strong electrostatic interaction between DMF and B(C F ) , Scheme 5. Possible reaction pathway.
6
5 3
suggesting that DMF was activated by B(C F ) . The C-N bond
6
5 3
of DMF was weaken, making it more favorable to break, thus
1
5
easily releasing the -CHO building block for reaction.
4. Conclusions
In summary, B(C F ) combined with atmospheric CO was
The cyclization of 2-aminothiophenol with DMF in the
presence of atmospheric CO and Et SiH catalyzed by B(C F )
6
5 3
2
2
2
2
6 5 3
found to be highly effective for the cyclization of various kinds
of ortho-substituted aniline derivatives with DMF, and a series
of N-containing heterocycles including benzothiazoles,
benzomidazoles, quinazolinone and benzoxazole were
obtained in good to excellent yields. This work presented a
new metal-free catalytic system for the production of N-
containing heterocyclic compounds, also opened a new way
was conducted at 120
examined by GC-MS analysis. A new small peak appeared at t =
.333 s with the molecular ion (M+) peak of 45 (Figure S2),
C for 15h, and the reaction solution was
1
attributing to dimethylamine (m/z=45), which suggested that DMF
reacted with 2-aminothiophenol to form a formylated
intermediate and release dimethylamine as the leaving group of
DMF. Another small peak appeared at t=1.325 s (see Figure S2),
assigning to trimethylamine, implying that the intermediate
for the utilization of CO in green chemical processes.
2
dimethylamine further reacted with CO and silane catalyzed by
2
B(C F5)3, forming trimethylamine, which drove the cyclization
6
Acknowledgements
We thank the National Natural Science Foundation of China
reaction to the right, thus greatly promoting the reaction
.
To further probe the role of CO in this cyclization reaction,
2
(No. 21125314, 21403252, 21533011, 21503239) for the
isotope-labeling experiments were performed, as shown in
13
13
financial support.
Scheme 4. Using CO2, C-labelled benzothiazole was not
detected, while non-labelled product was obtained in 99%
yield. Using [D ]-DMF instead of DMF, D-labelled benzothiazole
was obtained in 99% yield. From these results, it can be
concluded that DMF served as the formylation reagent, while
7
Notes and references
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, 14-16
reports,
a possible mechanism was proposed, as shown
in Scheme 5. Firstly, DMF was activated by B(C F ) via
6
5 3
electrostatic interaction, thus making the nucleophilic attack of
substrates much easier to form formylated intermediate A.
Simultaneously, dimethylamine was released as the leaving group
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New Journal of Chemistry
View Article Online
DOI: 10.1039/C6NJ01721E
Graphic Abstract
CO
2
gas greatly promoted the cyclization of various o-substituted anilines with
N,N-dimethylformamide, producing N-containing heterocycles in high yields.