Direct C-N coupling of imidazoles and benzylic compounds via iron-catalyzed oxidative activation of C-H bonds

Article abstract of DOI:10.1021/jo201253m

Iron-catalyzed direct C-N bond formation between imidazoles and benzylic hydrocarbons is described. The reaction utilizes an inexpensive iron catalyst-oxidant system that is suitable for the coupling of a range of benzylic C-H bonds with various imidazoles.

Full text of DOI:10.1021/jo201253m

NOTE
pubs.acs.org/joc
Direct CꢀN Coupling of Imidazoles and Benzylic Compounds via
Iron-Catalyzed Oxidative Activation of CꢀH Bonds
Qinqin Xia,† Wanzhi Chen,*,† and Huayu Qiu*,‡
†Department of Chemistry, Zhejiang University, Xixi Campus, Hangzhou 310028, P. R. China
‡College of Materials, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 310036, P. R. China
S Supporting Information
b
ABSTRACT: Iron-catalyzed direct CꢀN bond formation
between imidazoles and benzylic hydrocarbons is described.
The reaction utilizes an inexpensive iron catalystꢀoxidant
system that is suitable for the coupling of a range of benzylic
CꢀH bonds with various imidazoles.
he imidazole derivatives have attracted much attention for
their wide applications as enzyme inhibitors,1 drugs,2 and
Benzimidazole (1a) and diphenylmethane (2a) were selected
as the model substrates to test suitable reaction conditions
(Table 1). When FeCl3 was used as the catalyst and di-tert-butyl
peroxide (DTBP) as the oxidant in dichloroethane (DCE) at
80 °C, 3a was obtained in 13% yield (Table 1, entry 1). Although
copper salts are often used as catalysts for oxidative coupling
reactions,12 less than 5% yield of 3a was observed using Cu-
(OTf)2 and CuBr as catalysts (entries 3 and 4). DDQ, BQ, and
hyperiodine compounds are well-known oxidants in oxidative
CꢀH activation and functionalization;13 however, they are not
effective (entries 5ꢀ8). The reaction is also sensitive to solvents,
and no product was obtained in DMSO and methanol (entries 9
and 10). When the reaction was carried out in chlorobenzene at
120 °C, the yield was increased to 62% (entry 13). Further
increase of the temperature to 135 °C resulted in a lower yield of
41% (entry 14). The use of FeCl2 instead of FeCl3 as the catalyst
could increase the yield to 70% (entry 15). Furthermore, we
found that 10 mol % of FeCl2 was the best choice for the reaction
(entries 16ꢀ18). In each run of the coupling reactions, benzo-
phenone was found to be the major side product. A large excess
of diarylmethanes could significantly improve the conversion of
imidazole derivatives, therefore, 6ꢀ10 equivalents of benzylic
hydrocarbons were used.
Under the optimized conditions, the coupling of a variety of
benzylic hydrocarbons with benzoimidazole was investigated
(Table 2). A few diarylmethanes bearing either electron-with-
drawing or electron-donating groups could react, and the corre-
sponding products were provided in moderate to good yields
(Table 2, entries 1ꢀ6, 8, and 9). However, strong electron-
withdrawing groups considerably lower the yield (entry 7). The
reaction is assumed to proceed via methylenyl cation intermedi-
ate generated by oxidation of the CꢀH bond, and thus, the
electron-withdrawing group would destabilize the proposed
intermediate (Scheme 1). The less activated 2j and 2k also
T
polymers.3 They have also been broadly used as the precursors of
N-heterocyclic carbenes (NHC)4 and ionic liquids.5 It is known
that N-alkylation and N-arylation of imidazoles are among the
most important methods for the synthesis of imidazole deriva-
tives. Nucleophilic substitution with alkyl halides is one of the
most classical methods for the N-alkylation of imidazoles.
However, this method suffers from use of alkyl halides and
strong bases. Thus, a more efficient method for construction of
imidazole derivatives is highly desired. In recent years, great
progress has been made in transition-metal-catalyzed oxida-
tive coupling of CꢀH and NꢀH bonds with CꢀH bonds to
form CꢀC6 and CꢀN7 bonds. For example, the oxidative
coupling reactions between benzylic CꢀH bonds and sp3, sp2,
or sp CꢀH bonds have been reported.6c,d,j,k This strategy is an
efficient and straightforward method to synthesize benzylic
derivatives. Transition-metal-catalyzed CꢀH amination using
nitrene derivatives as the nitrogen source is the most widely
developed and impactful method to form CꢀN bonds.8 Recently,
amidation of the benzylic sp3 CꢀH bonds with unmodified
sulfonamides or carboxamides have been realized by using transi-
tion-metal salts as the catalysts.7eꢀi This strategy is an important
method for the synthesis of valuable nitrogen-containing com-
pounds without the need of a prefunctionalized starting material.
However, the known benzylic CꢀH amination methods typically
require nitrogen sources bearing powerful electron-withdrawing
groups such as sulfonamides and carboxamides. As early as 1993,
Hanefeld et al. had reported the direct oxidative CꢀN coupling
reaction of indazoles and benzotriazoles with di- and triphenyl-
methane derivatives. However, the desired products were obtained
in less than 10% yields.9 The direct conversion of benzylic CꢀH
bonds into CꢀN bonds using imidazoles as the nitrogen sources
remains the great challenge. Iron is one of the most abundant
and inexpensive metals on earth10 and is an efficient catalyst for
CꢀN cross-coupling reactions.11 Herein, we present a direct iron-
catalyzed N-alkylation of imidazoles with benzylic hydrocarbons.
Received: June 17, 2011
Published: July 29, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo201253m J. Org. Chem. 2011, 76, 7577–7582
|

The Journal of Organic Chemistry
NOTE
Table 1. Optimization of Reaction Conditionsa
Scheme 1. Possible Mechanism of Oxidative CꢀN Coupling
entry
cat.
FeCl3
oxidant
DTBP
solvent
T (°C)
yield (%)
1
2
DCE
80
80
13
FeCl2 4H2O
DTBP
DTBP
DTBP
DDQ
DCE
trace
trace
trace
trace
trace
N.D.b
trace
N.D.
N.D.
trace
28
3
3
Cu(OTf)2
CuBr
DCE
80
4
DCE
80
5
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl2
FeCl2
FeCl2
DCE
80
6
PhI(OAc)2
BQ
DCE
80
7
DCE
80
8
TBHP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DCE
80
The reaction is assumed to proceed via diphenylmethane
radical generated from the H abstraction of diphenylmethane by
a di-tert-butyl peroxide molecule in the presence of FeCl2
(Scheme 1). The radical could be further oxidized to benzyl
cation through a single-electron transfer process assisted by
Fe(III) ion.6d Finally, nucleophilic reaction of benzimidazole
with the benzyl cation would form the product 3a.
9
CH3OH
DMSO
Toluene
C6H5Cl
C6H5Cl
C6H5Cl
C6H5Cl
C6H5Cl
C6H5Cl
C6H5Cl
60
10
11
12
13
14
15
16c
17d
18
80
80
100
120
135
120
120
120
120
62
41
70
In summary, FeCl2-catalyzed amination of benzylic CꢀH
bonds leading to imidazole derivatives is presented. Benzylic
hydrocarbons are more easily available and environmentally
friendly than alkyl halides. The inexpensive and readily available
catalystꢀoxidant system is of practical interest for N-alkylation of
imidazoles.
72
47
N.D.
a Reaction conditions: 1a (0.5 mmol), 2a (3.0 mmol), catalyst (0.1
mmol), oxidant (1.0 mmol), 1.0 M 1a in solvent, 24 h, under N2. b Not
detected by TLC c FeCl2 (0.05 mmol). d FeCl2 (0.025 mmol).
’ EXPERIMENTAL SECTION
reacted with benzimidazole leading to R-aminated products
(entries 10 and 11). Direct N-alkylation of 1a with ethylbenzene
and propylbenzene were also successful, but the yields are low
(entries 12 and 13). Moreover, benzimidazole could also react
with primary benzylic CꢀH bonds (entries 14ꢀ17). The
amination reactions of p-xylene and mesitylene with benzimida-
zole only yielded monoaminated products. Again, 4-chloroto-
luene bearing an electron-withdrawing group showed lower
activity toward oxidative CꢀH activation.
General Procedure for the Synthesis of Products 3 or 4:
Synthesis of 1-Benzhydryl-1H-benz[d]imidazole (3a)14. An
oven-dried Schlenk tube equipped with a magnetic stir bar was charged
with 1a (59 mg, 0.5 mmol), FeCl2 (6.4 mg, 0.05 mmol), and 2a (504 mg,
3.0 mmol). The tube was evacuated and refilled with N2, and this process
was repeated three times. Then ditert-butyl peroxide (146 mg, 1.0
mmol) in chlorobenzene (0.5 mL) was added. The resulting mixture was
stirred at 120 °C for 24 h. After cooling to room temperature, the solvent
was removed under reduced pressure. The residue was purified by
column chromatography eluting with ethyl acetate/petroleum (1:2):
white solid; yield 72%; 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.0
Hz, 1H), 7.59 (s, 1H), 7.35ꢀ7.34 (m, 6H), 7.27ꢀ7.24 (m, 1H),
7.19ꢀ7.12 (m, 6H), 6.73 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
144.1, 142.6, 138.1, 134.1, 129.0, 128.5, 128.2, 122.9, 122.4, 120.4,
110.7, 63.6.
1-(Phenyl(p-tolyl)methyl)-1H-benz[d]imidazole (3b): white
solid; yield 63%; mp 115ꢀ117 °C; 1H NMR (400 MHz, CDCl3) δ 7.81
(d, J = 8.0 Hz, 1H), 7.60 (s, 1H), 7.34ꢀ7.11 (m, 10H), 7.03 (d, J = 8.0
Hz, 2H), 6.70 (s, 1H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
144.1, 142.6, 138.3, 135.1, 134.1, 129.7, 128.9, 128.3, 128.2, 128.1, 122.9,
122.3, 120.4, 110.8, 63.4, 21.1; HRMS (TOF MS EI+) m/z calcd for
C21H18N2 298.1470, found 298.1471.
The dehydrogenative coupling of various imidazoles and a
benzylic sp3 CꢀH bond was also examined under the reaction
conditions used above (Table 3). Benzoimidazole 1b having two
methyl groups at its 5- and 6-positions shows relatively lower
activity compared to 1a (Table 3, entry 1). Unexpectedly,
2-substituted 1cꢀg having either electron-withdrawing or elec-
tron-donating groups display higher activities than benzoimida-
zole itself (entries 2ꢀ6). The oxidative coupling of diphenyl-
methane and imidazoles bearing a electron-withdrawing group at
the 4 or 5 position also proceeded well (entries 7 and 9). The
reaction of 4-nitro-1H-imidazole would afford 4g in 70% yield,
and its structure was confirmed by NOE measurement (entry 7).
Trace amount of its regioisomer 1-benzhydryl-5-nitro-1H-imi-
dazole (4g0) was also observed from NMR analysis. 4,5-Diphenyl-
1H-imidazole reacted with diphenylmethane to afford the corre-
sponding product in relatively lower yield (entry 8) probably due
to large steric hindrance. Interestingly, the coupling of 4,
5-dicyano-1H-imidazole with diphenylmethane gave 4i in almost
quantitative yield (entry 9). However, imidazole is totally unreac-
tive, and imidazole was recovered after reaction (entry 10).
1-(Phenyl(o-tolyl)methyl)-1H-benz[d]imidazole (3c): white
solid; yield 64%; mp 106ꢀ108 °C; 1H NMR (400 MHz, CDCl3) δ 7.85
(d, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.37ꢀ7.35 (m, 3H), 7.30ꢀ7.26 (m,
3H), 7.21ꢀ7.18 (m, 1H), 7.14ꢀ7.11 (m, 4H), 6.88 (s, 1H), 6.76 (d, J =
7.6 Hz, 1H), 2.22 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 144.0, 142.6,
137.5, 136.4, 136.3, 134.0, 131.0, 129.0, 128.5, 128.5, 128.2, 127.8, 126.5,
123.0, 122.5, 120.4, 110.5, 60.7, 19.1; HRMS (TOF MS EI+) m/z calcd
for C21H18N2 298.1470, found 298.1466.
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NOTE
Table 2. Reactions of Benzimidazole with Various Benzylic Hydrocarbonsa
a Reaction conditions: 1a (0.5 mmol), 2 (3.0 mmol), FeCl2 (0.05 mmol), DTBP (1.0 mmol), 1a 1.0 M in C6H5Cl, 120 °C, 24 h, under N2. b 2 (5.0
mmol), 36 h. c Toluene (2 mL), 36 h.
1-(Phenyl(m-tolyl)methyl)-1H-benz[d]imidazole (3d): White
solid; yield 60%; Mp 118ꢀ120 °C; 1H NMR (400 MHz, CDCl3) δ 7.84
(d, J = 8.0 Hz, 1H), 7.62 (s, 1H), 7.37ꢀ7.35 (m, 3H), 7.29ꢀ7.14 (m, 7H),
7.00 (s, 1H), 6.94 (d, J = 7.2 Hz, 1H), 6.72 (s, 1H), 2.31 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 144.0, 142.6, 138.8, 138.2, 138.0, 134.1, 129.3, 128.9,
128.8, 128.4, 128.1, 125.3, 122.9, 122.3, 120.3, 110.7, 63.6, 21.4; HRMS
(TOF MS EI+) m/z calcd for C21H18N2: 298.1470, found 298.1469.
1-((4-Chlorophenyl)(phenyl)methyl)-1H-benz[d]imidazole
7.20ꢀ7.10 (m, 4H), 7.06 (d, J = 8.4 Hz, 2H), 6.72 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 144.1, 142.3, 137.6, 136.7, 134.4, 133.9, 129.4,
129.2, 129.1, 128.8, 128.2, 123.1, 122.5, 120.5, 110.6, 63.0; HRMS (TOF
MS EI+) m/z calcd for C20H15ClN2 318.0924, found 318.0921.
1-((4-Fluorophenyl)(phenyl)methyl)-1H-benz[d]imidazole
(3f): light yellow oil; yield 90%; 1H NMR (400 MHz, CDCl3) δ 7.81 (d,
J = 7.6 Hz, 1H), 7.57 (s, 1H), 7.33 (s, 3H), 7.24 (t, J = 7.6 Hz, 1H),
7.18ꢀ7.00 (m, 8H), 6.72 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 162.5
(d, JCꢀF = 247.2 Hz), 144.1, 142.4, 137.8, 133.9 (d, JCꢀF = 3.1 Hz), 130.0,
129.9 (d, JCꢀF = 8.4 Hz), 129.1, 128.7, 128.0, 123.1, 122.5, 120.5, 116.0
1
(3e): yellow solid; yield 69%; mp 119ꢀ120 °C; H NMR (400 MHz,
CDCl3) δ 7.83 (d, J = 8.4 Hz, 1H), 7.59 (s, 1H), 7.37ꢀ7.25 (m, 6H),
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NOTE
Table 3. Reactions of Various Imidazoles with
Diphenylmethanea
123.7 (q, JCꢀF = 270.6 Hz), 123.2, 122.7, 120.6, 110.5; HRMS (TOF MS
EI+) m/z calcd for C21H15F3N2 352.1187, found 352.1188.
1-((4-tert-Butylphenyl)(phenyl)methyl)-1H-benz[d]imida-
zole (3h): white solid; yield 54%; mp 123ꢀ125 °C; 1H NMR
(400 MHz, CDCl3) δ 7.85 (d, J = 8.0 Hz, 1H), 7.64 (s, 1H), 7.40ꢀ
7.35 (m, 5H), 7.28ꢀ7.09 (m, 7H), 6.74 (s, 1H), 1.33 (s, 9H); 13C
NMR (100 MHz, CDCl3) δ 151.6, 144.2, 142.7, 138.4, 135.0, 134.1,
128.9, 128.3, 128.0, 128.0, 125.9, 122.8, 122.3, 120.4, 110.8, 63.3,
34.6, 31.2; HRMS (TOF MS EI+) m/z calcd for C24H24N2 340.1939,
found 340.1938.
1-(Biphenyl-4-yl(phenyl)methyl)-1H-benz[d]imidazole (3i):15
white solid; yield 83%; 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 7.6 Hz,
1H), 7.69 (s, 1H), 7.61ꢀ7.58 (m, 4H), 7.47ꢀ7.37 (m, 6H), 7.30ꢀ7.21 (m,
7H), 6.81 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 142.6, 141.4, 140.1,
138.0, 137.0, 129.1, 128.8, 128.6, 128.5, 128.2, 127.7, 127.1, 123.0, 122.4,
120.4, 110.8, 63.3.
1-(1,2,3,4-Tetrahydronaphthalen-1-yl)-1H-benz[d]imidazole
(3j): light yellow oil; yield 53%; 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J =
8.0 Hz, 1H), 7.68 (s, 1H), 7.31ꢀ7.24 (m, 5H), 7.11 (t, J = 8.0 Hz, 1H), 6.93
(d, J = 7.6 Hz, 1H), 5.68 (t, J = 6.2 Hz, 1H), 3.02ꢀ2.93 (m, 2H), 2.33ꢀ2.26
(m, 2H), 1.93ꢀ1.88 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 144.0,
142.9, 137.8, 133.4, 133.1, 129.5, 128.8, 128.3, 126.7, 122.7, 122.1, 120.5,
110.4, 54.5, 30.1, 29.0, 19.9; HRMS (TOF MS EI+) m/zcalcd for C17H16N2
248.1313, found 248.1311.
1-(2,3-Dihydro-1H-inden-1-yl)-1H-benz[d]imidazole (3k):
light yellow oil; yield 52%; H NMR (400 MHz, CDCl3) δ 7.83 (d,
1
J = 8.0 Hz, 1H), 7.77 (s, 1H), 7.41ꢀ7.33 (m, 2H), 7.30ꢀ7.18 (m, 4H),
7.11 (d, J = 7.2 Hz,1H), 5.97 (t, J = 7.2 Hz, 1H), 3.18ꢀ3.15 (m, 1H),
3.10ꢀ3.04 (m, 1H), 2.76ꢀ2.72 (m, 1H), 2.37ꢀ2.31 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 144.1, 141.0, 140.7, 133.6, 129.0, 128.1, 125.9,
122.8, 122.2, 120.3, 110.6, 55.2, 21.6; HRMS (TOF MS EI+) m/z calcd
for C16H14N2 234.1157, found 234.1151.
1-(1-Phenylethyl)-1H-benz[d]imidazole (3l):16 white solid;
yield 31%; 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.82 (d, J = 8.4
Hz, 1H), 7.34ꢀ7.24 (m, 4H), 7.20ꢀ7.19 (m, 4H), 5.65ꢀ5.61 (m, 1H),
2.01 (d, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 144.1, 141.0,
140.7, 133.6, 129.0, 128.1, 125.9, 122.8, 122.2, 120.3, 110.6, 55.2, 21.6.
1-(1-Phenylpropyl)-1H-benz[d]imidazole (3m): light yellow
oil; yield 31%; 1H NMR (400 MHz, CDCl3) δ 8.12 (s, 1H), 7.82 (d, J =
7.6 Hz, 1H), 7.36ꢀ7.21 (m, 8H), 5.31 (t, J = 7.6 Hz, 1H), 2.49ꢀ2.37 (m,
2H), 1.01 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 143.9,
141.1, 139.5, 133.7, 128.9, 128.1, 126.5, 122.8, 122.2, 120.3, 110.5, 61.7,
27.9, 11.2; HRMS (TOF MS EI+) m/z calcd for C16H16N2 236.1313,
found 236.1316.
1-(3,5-Dimethylbenzyl)-1H-benz[d]imidazole (3n):17 white
solid; yield 41%; 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H),
7.86ꢀ7.84 (m, 1H), 7.34ꢀ7.27 (m, 3H), 6.96 (s, 1H), 6.82 (s, 2H),
5.28 (s, 2H), 2.28 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 143.9,
143.2, 138.7, 135.3, 134.0, 129.9, 124.9, 123.0, 122.1, 120.3, 110.0,
48.7, 21.2.
1-(4-Methylbenzyl)-1H-benz[d]imidazole (3o):17 white solid;
1
yield 32%; H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H), 7.84 (d, J =
8.0 Hz, 1H), 7.33ꢀ7.26 (m, 3H), 7.16 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 8.0
Hz, 2H), 5.31 (s, 2H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
143.9, 143.1, 138.1, 133.9, 132.3, 129.6, 127.1, 123.0, 122.2, 120.3, 110.0,
48.6, 21.1.
a Reaction conditions: 1 (0.5 mmol), 2a (3.0 mmol), FeCl2 (0.05 mmol),
DTBP (1.0 mmol), 1 1.0 M in C6H5Cl, 120 °C, 24 h, under N2.
(d, JCꢀF = 21.8 Hz), 115.9, 110.7, 62.9; HRMS (TOF MS EI+) m/z calcd
for C20H15FN2 302.1219, found 302.1212.
1-(Phenyl(4-(trifluoromethyl)phenyl)methyl)-1H-benz[d]-
1-(4-Chlorobenzyl)-1H-benz[d]imidazole (3p):17 light yellow
1
oil; yield 23%; H NMR (400 MHz, CDCl3) δ 7.95 (s, 1H), 7.84
(d, J = 7.2 Hz, 1H), 7.32ꢀ7.25 (m, 5H), 7.11 (d, J = 8.0 Hz, 2H), 5.33
(s, 2H); 13C NMR (100 MHz, CDCl3) δ 143.9, 143.1, 134.1, 133.9,
133.7, 129.2, 128.3, 123.2, 122.4, 120.5, 109.9, 48.1.
1
imidazole (3g): light yellow oil; yield 23%; H NMR (400 MHz,
CDCl3) δ 7.84 (d, J = 8.0 Hz, 1H), 7.62 (s, 1H), 7.60 (d, J = 5.2 Hz, 2H),
7.39 (t, J = 3.2 Hz, 3H), 7.40ꢀ7.10 (m, 7H), 6.79 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 144.0, 142.3, 142.2, 137.0, 126.2, 133.8, 130.7 (q,
JCꢀF = 32.5 Hz), 129.3, 129.0, 128.5, 128.3, 126.0 (q, JCꢀF = 3.5 Hz),
1-Benzyl-1H-benz[d]imidazole (3q):17 white solid; yield 45%;
1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H),
7.35ꢀ7.26 (m, 6H), 7.18 (d, J = 6.4 Hz, 2H), 5.34 (s, 2H); 13C NMR
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NOTE
(100 MHz, CDCl3) δ 143.9, 143.2, 135.4, 133.9, 129.0, 128.2, 127.0,
123.1, 122.2, 120.4, 110.0, 48.8.
1-Benzhydryl-1H-imidazole-4,5-dicarbonitrile (4i): white
solid; yield 95%; mp 128ꢀ130 °C; 1H NMR (400 MHz, CDCl3)
δ 7.47ꢀ7.43 (m, 7H), 7.15ꢀ7.13 (m, 4H), 6.74 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 141.0, 135.5, 129.7, 129.6, 128.0, 123.6, 112.8,
111.5, 107.6, 66.5; HRMS (TOF MS EI+) m/z calcd for C18H12N4
284.1062, found 284.1065.
1-Benzhydryl-5,6-dimethyl-1H-benz[d]imidazole(4a):white
solid; yield 48%; mp 253ꢀ255 °C; 1H NMR (400 MHz, CDCl3) δ 7.55
(s, 1H), 7.46 (s, 1H), 7.33ꢀ7.31 (m, 6H), 7.11ꢀ7.09 (m, 4H), 6.89 (s,
1H), 6.67 (s, 1H), 2.31 (s, 3H), 2.24 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 142.6, 141.8, 138.3, 132.6, 132.1, 131.3, 128.9, 128.4, 128.2,
120.3, 110.7, 63.3, 20.5, 20.2; HRMS (TOF MS EI+) m/z calcd for
C22H20N2 312.1626, found 312.1625.
1-Benzhydryl-2-methyl-1H-benz[d]imidazole (4b): Yellow
solid; yield 83%; Mp 141ꢀ142 °C; 1H NMR (400 MHz, CDCl3) δ 7.70
(d, J = 8.0 Hz, 1H), 7.34ꢀ7.13 (m, 11H), 6.95 (t, J = 7.8 Hz, 1H), 6.87 (s,
1H), 6.59 (d, J = 8.0 Hz, 1H), 2.53 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 152.3, 142.4, 137.7, 135.0, 128.8, 128.3, 128.2, 122.1, 121.8,
119.0, 111.8, 63.1, 15.1; HRMS (TOF MS EI+) m/z calcd for C21H18N2
298.1470, found 298.1475.
1-Benzhydryl-2-chloro-1H-benz[d]imidazole (4c): white solid;
yield 80%; mp 135ꢀ137 °C; 1H NMR (400 MHz, CDCl3) δ 7.71
(d, J = 8.4 Hz, 1H), 7.36ꢀ6.98 (m, 13H), 6.60 (d, J = 8.4 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 141.9, 141.3, 137.0, 134.7, 128.8, 128.4, 128.2,
123.0, 122.5, 119.5, 112.2, 63.9; HRMS (TOF MS EI+) m/z calcd for
C20H15ClN2 318.0924, found 318.0928.
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra for
S
b
3aꢀq and 4aꢀi. This material is available free of charge via the
Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: chenwzz@zju.edu.cn; hyqiu@hznu.edu.cn.
’ ACKNOWLEDGMENT
The project is supported by Natural Science Foundation of
China (20872129 and 21072170), RFDP Foundation (20080-
3350011), and the Fundamental Research Fund for the Central
Universities (2010QNA3004).
1-Benzhydryl-2-phenyl-1H-benz[d]imidazole (4d): white
1
solid; yield 84%; mp 184ꢀ186 °C; H NMR (400 MHz, CDCl3) δ
’ REFERENCES
7.87 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 7.2 Hz, 2H), 7.51ꢀ7.46 (m, 3H),
7.34ꢀ7.33 (m, 6H), 7.26ꢀ7.16 (m, 5H), 7.04ꢀ7.01 (m, 2H), 6.87 (d,
J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 154.9, 143.5, 138.3,
134.8, 130.6, 129.9, 129.6, 128.7, 128.1, 128.0, 122.6, 122.2, 120.0, 113.4,
63.7; HRMS (TOF MS EI+) m/z calcd for C26H20N2 360.1626, found
360.1621.
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7.90 (d, J = 8.4 Hz, 1H), 7.37ꢀ7.28 (m, 7H), 7.19ꢀ7.11 (m, 6H), 6.78 (d,
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=
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1-Benzhydryl-2-isopropyl-1H-benz[d]imidazole (4f): yel-
low solid; yield 71%; mp 173ꢀ175 °C; 1H NMR (400 MHz, CDCl3)
δ 7.78 (d, J = 8.0 Hz, 1H), 7.35ꢀ7.16 (m, 11H), 7.00 (s, 1H), 6.93 (t, J =
7.6 Hz, 1H), 6.58 (d, J = 8.4 Hz, 1H), 3.27 (m, 1H), 1.39 (d, J = 6.4 Hz,
6H); 13C NMR (100 MHz, CDCl3) δ 160.5, 142.8, 138.1, 134.8, 128.8,
128.1, 121.9, 121.5, 119.4, 112.3, 62.3, 27.0, 21.9; HRMS (TOF MS EI+)
m/z calcd for C23H22N2 326.1783, found 326.1786.
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1-Benzhydryl-4-nitro-1H-imidazole (4g): light yellow oil;
1
yield 70%; H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 1.6 Hz, 1H),
7.41ꢀ7.40 (m, 7H), 7.15ꢀ7.13 (m, 4H), 6.63 (s, 1H); 1H NMR
(400 MHz, DMSO-d6) δ 8.31 (s, 1H), 7.92 (s, 1H), 7.43ꢀ7.39 (m,
6H), 7.24 (d, J = 7.2 Hz, 4H), 7.03 (s, 1H) ;13C NMR (100 MHz,
CDCl3) δ 147.8, 137.1, 136.2, 129.3, 129.1, 127.9, 119.6, 66.3; HRMS
(TOF MS EI+) m/z calcd for C16H13N3O2 279.1008, found 279.1005.
1-Benzhydryl-5-nitro-1H-imidazole (4g0): light yellow oil;
1
yield <5%; H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H), 7.49 (s,
1H), 7.44ꢀ7.35 (m, 7H), 7.18 (d, J = 7.2 Hz, 4H); 13C NMR (100 MHz,
DMSO-d6) δ 142.1, 139.2, 138.1, 134.4, 129.4, 128.9, 128.5, 64.7;
HRMS (TOF MS EI+) m/z calcd for C16H13N3O2 279.1008, found
279.1010.
1-Benzhydryl-4,5-diphenyl-1H-imidazole (4h): white solid;
yield 48%; mp 133ꢀ135 °C; 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J =
7.2 Hz, 2H), 7.43ꢀ7.33 (m, 10H), 7.22ꢀ7.13 (m, 5H), 7.05ꢀ7.04 (m,
3H), 6.23(s, 1H); 13C NMR (100 MHz, CDCl3) δ 139.2, 138.0, 136.4,
134.4, 131.1, 130.6, 129.2, 128.9, 128.8, 128.8, 128.2, 128.1, 128.1, 126.4,
126.3, 62.9; HRMS (TOF MS EI+) m/z calcd for C28H22N2 386.1783,
found 386.1790.
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The Journal of Organic Chemistry
NOTE
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’ NOTE ADDED AFTER ASAP PUBLICATION
Scheme 1 was corrected and reposted August 22, 2011.
7582
dx.doi.org/10.1021/jo201253m |J. Org. Chem. 2011, 76, 7577–7582