Palladium-catalyzed direct C2-arylation of azoles with aromatic triazenes

Article abstract of DOI:10.1039/c9ob01883b

A highly efficient palladium-catalyzed arylation of azoles at the C2-position using 1-aryltriazenes as aryl reagents was developed. Azoles including oxazoles, thiazoles, imidazoles, 1,3,4-oxadiazoles, and oxazolines could react with 1-aryltriazenes smoothly to generate the corresponding products in good to excellent yields, and various substitution patterns were tolerated toward the reaction.

Full text of DOI:10.1039/c9ob01883b

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Palladium-catalyzed direct C2-arylation of azoles
with aromatic triazenes†
Cite this: Org. Biomol. Chem., 2019,
17, 9209
Can Liu,‡a,b Zhiming Wang, ‡a Lei Wang,
*
a,b,c Pinhua Li b,c and
Yicheng Zhang*b,c
Received 27th August 2019,
Accepted 2nd October 2019
A highly efficient palladium-catalyzed arylation of azoles at the C2-position using 1-aryltriazenes as aryl
reagents was developed. Azoles including oxazoles, thiazoles, imidazoles, 1,3,4-oxadiazoles, and oxazo-
lines could react with 1-aryltriazenes smoothly to generate the corresponding products in good to excel-
lent yields, and various substitution patterns were tolerated toward the reaction.
DOI: 10.1039/c9ob01883b
rsc.li/obc
tion,13 aromatic trifluoromethylation,14 CO insertion (carbony-
lative) and N2 extrusion,15 and C2-arylation of indoles.16
Introduction
2-Aryl substituted azoles are ubiquitous features in both However, the application of 1-aryltriazenes in the reaction of
natural products and synthetic chemicals, and they are impor- direct C–H arylation of azoles is still unexplored. As part of our
tant structural units that play significant roles as functional program directed towards the development of transition-metal-
materials, pharmaceuticals and bioactive compounds.1 Among catalyzed C–H bond activation and our ongoing interest in the
their synthetic strategies, the transition-metal-catalyzed direct C–H bond functionalization of azoles,8a,17 herein, we introduce
C–H bond arylation of azoles represents an efficient, economi- 1-aryltriazenes as a readily available and effective arylating
cal, and potential alternative method, which has recently source for heteroaromatic C–H functionalization. In this
received particular attention.2 In the past few years, great pro- paper, a palladium-catalyzed direct arylation of azoles at the
gress has been achieved in the direct C–C bond formation of C2-position with 3,3-diethyl-1-aryltriazenes is described. A
azoles via C–H activation using various arylation reagents, wide range of azoles, including oxazoles, thiazoles, imidazoles,
such as aryl halides,3 arylmesylates,4 aryltriflates,5 organosili- 1,3,4-oxadiazoles, and oxazolines could react with 3,3-diethyl-
cons,6 organoboranes,7 sodium arylsulfinates,8 and so on. 1-aryltriazenes smoothly to generate the corresponding pro-
Despite having achieved remarkable progress in this field, the ducts in good to excellent yields (Scheme 1).
development of new efficient synthetic methods for the syn-
thesis of 2-aryl substituted azoles from readily available and
simple aryl sources is highly desirable considering both scien-
tific and practical significance.
Results and discussion
Our initial investigation was carried out by examining the reac-
tion of benzoxazole (1a) with 3,3-diethyl-1-(p-tolyl)triazene (2a)
in the presence of Pd(PPh3)4 and CuI in DMF, and the C2-ary-
lation product, 2-(p-tolyl)benzoxazole (3a), was isolated in 38%
yield (Table 1, entry 1). It is worth noting that when 3,3-
diethyl-1-(p-tolyl)triazene was used instead of p-tolyldiazonium
tetrafluoroborate, as a precursor of 3,3-diethyl-1-(p-tolyl)tria-
zene, only a 13% yield of the desired product 3a was obtained
Aromatic triazenes are very useful and versatile intermedi-
ates in organic synthesis, which can be easily transformed into
various functional groups after treatment with the corres-
ponding reagents.9 In addition, they are efficient electrophilic
partners in transition-metal-catalyzed carbon–carbon cross-
coupling reactions, such as the Heck-type reaction,10 Suzuki-
type reaction,11 Hiyama-type reaction,12 aromatic fluorina-
aAdvanced Research Institute and Department of Chemistry, Taizhou University,
Taizhou, Zhejiang 318000, P. R. China. E-mail: leiwang@tzc.edu.cn
bDepartment of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000,
P. R. China. E-mail: lbqzhych@163.com
cState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c9ob01883b
Scheme 1 Pd-Catalyzed C-2 arylation of azoles with aromatic
‡These authors contributed equally to this work.
triazenes.
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Table 1 Optimization of the reaction conditionsa
TMEDA and Bipy, in the model reaction, generating the
desired product in less yields (Table 1, entry 9). In addition,
the Pd-catalyst and CuI are essential in the model reaction and
no desired product was formed in the absence of Pd(OAc)2 or
CuI (Table 1, entries 10 and 11). Other additives, such as CuBr,
CuCl, Cu2O, CuBr2, AgI, DDQ (2,3-dichloro-5,6-dicyano-1,4-
benzoquinone), K2S2O8, TBHP (tert-butyl hydroperoxide),
CF3CO2H, CF3SO3H and BF3·Et2O, were examined as additives
for this direct C2-arylation reaction, and 1.5 equiv. of CuI dis-
played the highest reactivity. CuBr, CuCl, CuBr2 and AgI were
no longer the effective additives in the reaction, and Cu2O,
DDQ, K2S2O8, TBHP, CF3CO2H, CF3SO3H and BF3·Et2O were
ineffective in the reaction (Table 1, entries 7, 12–22). The effect
of the solvent on the reaction was also investigated. Among the
tested solvents, DMF (N,N-dimethylformamide) was the most
suitable reaction medium for the model reaction. DMAC (N,N-
dimethylacetamide), NMP (N-methyl-2-pyrrolidone), DMSO
(dimethyl sulfoxide), EtOH and MeCN were inferior and gener-
ated the desired product 3a in 57, 43, 55, 12 and 18% yields,
respectively (Table 1, entries 23–27). Unfortunately, trace
amounts of products or no desired products were observed
when the reactions were carried out in CH3CO2H, toluene,
DCE (1,2-dichloroethane) and 1,4-dioxane (Table 1, entries
28–31). In addition, the reaction time and temperature were
also optimized, and the results are summarized in Table 1
(entry 32).
Under the optimized reaction conditions (10 mol% of Pd
(OAc)2, 1.5 equiv. of CuI, DMF as the solvent at 130 °C for
12 h), the scope of the palladium catalyzed direct C2-arylation
of azoles with 3,3-diethyl-1-aryltriazenes was investigated. The
results are summarized in Scheme 2. As can be seen from
Scheme 2, most of the benzoxazoles, both with electron-donat-
ing substituents, such as Me, tert-Bu, and MeO groups, and
electron-withdrawing groups, such as F, Cl and Br, on the
benzene rings, could react smoothly with 3,3-diethyl-1-(p-tolyl)
triazene (2a) to give the corresponding products (3a–3j) in
good to excellent yields (Scheme 2). Simple oxazoles, such as
ethyl oxazole-5-carboxylate, and 1,3,4-oxadiazoles, with various
substituents (Ph, 4-MePh, and 4-ClPh) at the 2-positions of
their heterocyclic rings were also employed for the reaction
Entry Pd catalyst
Additive
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
Pd(PPh)4
Pd2(dba)3
PdCl2
CuI (2.0 eq.)
CuI (2.0 eq.)
CuI (2.0 eq.)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
38
35
53
50
Pd(CH3CN)2Cl2 CuI (2.0 eq.)
Pd(PPh3)2Cl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
—
CuI (2.0 eq.)
CuI (2.0 eq.)
CuI (1.5 eq.)
CuI (1.0 eq.)
CuI (0.2 eq.)
CuI (1.5 eq.)
—
CuBr (1.5 eq.)
CuCl (1.5 eq.)
Cu2O (1.5 eq.)
CuBr2 (1.5 eq.)
AgI (1.5 eq.)
DDQ (1.5 eq.)
K2S2O8 (1.5 eq.)
TBHP (1.5 eq.)
48
83, 63c
81
64
9
10d, 24e, 27f
N. R.
N. R.
28
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
31
N. R.
19
37
Trace
Trace
Trace
N. R.
N. R.
Trace
57
43
55
12
18
CF3CO2H (1.5 eq.) DMF
CF3SO3H (1.5 eq.) DMF
BF3·Et2O (1.5 eq.)
CuI (1.5 eq.)
CuI (1.5 eq.)
CuI (1.5 eq.)
CuI (1.5 eq.)
CuI (1.5 eq.)
CuI (1.5 eq.)
CuI (1.5 eq.)
CuI (1.5 eq.)
CuI (1.5 eq.)
CuI (1.5 eq.)
DMF
DMAC
NMP
DMSO
EtOH
MeCN
AcOH
Toluene Trace
DCE NR
Dioxane NR
DMF
82g, 64h
81i, 56j
Trace
a Reaction conditions: 1a (0.50 mmol), 2a (0.75 mmol), Pd catalyst
(10 mol%), additive (1.5–2.0 eq.), solvent (3.0 mL), 130 °C for 12 h.
b Isolated yield based on 1a. c Pd(OAc)2 (5 mol%) was added. d N,N′-
Dimethylethylenediamine (DMEDA, 0.20 mmol) was used. e N,N,N′,N′-
Tetramethylethylenediamine (TMEDA, 0.20 mmol) was used. f 2,2′-
Bipyridyl (Bipy, 0.20 mmol) was used. g Reaction for 24 h. h Reaction
for 6 h. i Reaction at 140 °C. j Reaction at 120 °C.
under the present reaction conditions. This interesting pre- with 3,3-diethyl-1-aryltriazenes under the optimized reaction
liminary result encouraged us to optimize the reaction con- conditions, and the corresponding products were obtained in
ditions on the basis of a palladium catalyst, additive and good yields (Scheme 2, 3k–3o). In addition, benzothiazole,
solvent, and the results are summarized in Table 1. For the 6-aminobenzothiazole, thiazole, 4-methylthiazole, 4,5-di-
choice of palladium sources, comparable product yields methylthiazole, and 2-(4-methylthiazol-5-yl)ethanol could also
were obtained when Pd2(dba)3, PdCl2, Pd(CH3CN)2Cl2, undergo direct C2-arylation with 2a under the present
Pd(PPh3)2Cl2, or Pd(OAc)2 was used as the Pd catalyst instead reaction conditions, providing the corresponding products
of Pd(PPh3)4. It was obvious that Pd(OAc)2 was the most (Scheme 2, 3p–3u) in 55–83% yields. To our delight,
effective catalyst among the tested Pd-catalysts for the reaction, N-methylbenzimidazole reacted with 2a to generate the desired
and 10 mol% loading was the best choice (Table 1, entries product 3v in 57% yield. On the other hand, the reactions
2–6). Furthermore, when 1.5 equivalents of CuI were used, the between benzoxazole (1a) and various 3,3-diethyl-1-aryltria-
yield of compound 3a decreased slightly from 83% to 81%. zenes were investigated. 3,3-Diethyl-1-phenyltriazene was suc-
But, when 1.0 equivalent of CuI was employed, the yield of cessfully reacted with 1a to give the corresponding product
compound 3a dramatically decreased (Table 1, entries 7 and (3w) in 83% yield (Scheme 2). 3,3-Diethyl-1-aryltriazenes with
8). However, a substoichiometric amount of CuI of 0.2 equiv. different functional groups, including electron-donating
was used with a combination of N,N-ligands, such as DMEDA, groups and electron-withdrawing ones on the aromatic rings,
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position of the benzene rings reacted with 1a to give the
desired products in 81–90% yields (Scheme 2, 3a and 3x–3aa).
Meanwhile, 3,3-diethyl-1-aryltriazenes with an electron-with-
drawing group (fluoro or chloro) at the para-position of the
benzene rings reacted with 1a, generating the corresponding
products in 58% and 68% yields, respectively (Scheme 2, 3ab
and 3ac). Further investigation indicated that disubstituted
3,3-diethyl-1-aryltriazenes bearing electron-rich functional
groups (methyl) could react with 1a to form the corresponding
products in high yields, ignoring their positions on the
benzene rings (Scheme 2, 3af–3ah). It is important to note that
the meta- or ortho-position effect in aryltriazenes is not
obvious in the formation of 3ad and 3ae (Scheme 2, 3ad and
3ae vs. 3a and 3af–3ah). However, aryltriazenes with an elec-
tron-withrawing group, including a CN, NO2 or CO2Et group
on the benzene rings, exhibited no reactivity in the reaction
under the present conditions. No product was detected and
the starting materials were recovered unchanged.
In order to expand the reaction scope, nonaromatic hetero-
cyclic compounds were examined. Notably, 4,5-dihydrooxa-
zoles including 4,4-dimethyl-4,5-dihydrooxazole, 4-phenyl-4,5-
dihydrooxazole, and 4-benzyl-4,5-dihydrooxazole, could also
react smoothly with 3,3-diethyl-1-aryltriazenes to generate the
desired products in 79%, 87%, 70%, 79%, and 77% yields,
respectively (Scheme 3, 4a–e).
Additionally, free (NH)-imidazole was employed for reac-
tions with 3,3-diethyl-1-aryltriazenes under the standard reac-
tion conditions, and the corresponding diarylated products
were obtained in 60%, 57% and 55% yields, respectively
(Scheme 4, 5a–c). However, when 1-acetylimidazole was used
as one of the substrates in the reaction, the corresponding dia-
rylated product 5b was obtained in 51% yield (Scheme 5).
Although the exact mechanism of this reaction is not clear
at present, a possible pathway is proposed as shown in
Scheme 6 on the basis of our observation and literature
reports.18 The 3,3-diethyl-1-aryltriazene (2) undergoes an oxi-
dative addition onto Pd(0), which is reduced from a Pd(OAc)2
precursor to form intermediate A.15 The ensuing extrusion of
N2 from the obtained A generates the arylpalladium species
B.16 On the other hand, an electrophilic attack of CuI on the
benzoxazole (1a) C–H bond produces intermediate C,18a at
Scheme 2 Palladium-catalyzed direct C2-arylation of azoles with 3,3-
diethyl-1-aryltriazenes [reaction conditions:
1
(0.50 mmol),
2
(0.75 mmol), Pd(OAc)2 (0.05 mmol), CuI (0.75 mmol), DMF (3.0 mL),
130 °C, 12 h; isolate yield of the product].
were tolerated, and reacted with 1a to produce the corres-
ponding products in good to excellent yields. 3,3-Diethyl-1-
aryltriazenes with an electron-donating group, such as a
Scheme 3 The reactions of 4,5-dihydrooxazole with 3,3-diethyl-1-
methyl, ethyl, iso-propyl, methoxy, or ethoxy group at the para- aryltriazenes.
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process and 3,3-diethyl-1-aryltriazenes as coupling species in
other reactions are currently under way in our laboratory.
Experimental section
General remarks
All 1H NMR and 13C NMR spectra were recorded on a 400 MHz
Bruker FT-NMR spectrometer (400 MHz or 100 MHz, respect-
ively). All chemical shifts are given as δ values (ppm) with
reference to tetramethylsilane (TMS) as an internal standard.
The peak patterns are indicated as follows: s, singlet; d,
doublet; t, triplet; q, quartet; h, heptet, and m, multiplet. The
coupling constants, J, are reported in Hertz (Hz). The chemi-
cals and solvents were purchased from commercial suppliers
either from Aldrich, USA or Shanghai Chemical Company,
China. The products were purified by flash chromatography on
100–200 mesh silica gel, SiO2.
Scheme 4 The diarylation of free (NH)-imidazole with 3,3-diethyl-1-
aryltriazenes (1 : 2 = 1 : 3).
Typical procedure for the synthesis of 3,3-diethyl-1-
aryltriazenes9e
Scheme 5 The diarylation of 1-acetylimidazole with 3,3-diethyl-1-(p-
tolyl)triazene (1 : 2 = 1 : 3).
A solution of a primary arylamine (3.0 mmol) in HCl (aq.,
37%, 1.5 mL) was cooled in an ice-bath while a solution of
NaNO2 (228 mg, 3.3 mmol) in cold water (6.0 mL) was added
dropwise. The resulting solution of the diazonium salt was
stirred at 0 °C for 30 min and then added to a solution of di-
ethylamine (1.10 g, 15.0 mmol) and K2CO3 (7.46 g, 54.0 mmol)
in acetonitrile/water (v : v = 1 : 2, 15.0 mL) by one portion. The
reaction mixture was allowed to warm to room temperature
and stirred for 30 min. The aqueous phase was extracted with
ethyl acetate (3 × 10.0 mL). The organic phase was washed
twice with brine, dried with MgSO4, and concentrated under
reduced pressure. The crude product was purified by flash
column chromatography over silica gel giving the corres-
ponding 3,3-diethyl-1-aryltriazene.
Typical procedure for the palladium-catalyzed C-2 arylation of
azoles with 3,3-diethyl-1-aryltriazenes
Scheme 6 Proposed reaction mechanism.
A 10 mL sealable reaction tube with a Teflon-coated cap
equipped with a magnetic stir bar was charged with azole (1,
0.50 mmol), Pd(OAc)2 (0.05 mmol), CuI (0.75 mmol) and DMF
(3.0 mL), and then 3,3-diethyl-1-aryltriazene (2, 0.75 mmol)
was added using a syringe. The reaction mixture was stirred at
130 °C for 12 h. After the reaction was completed, the reaction
mixture was cooled to room temperature, quenched with
water, and extracted with ethyl acetate (2 × 7.0 mL). The
organic phase was dried over MgSO4, filtered, and concen-
trated under reduced pressure to yield the crude product,
which was further purified by flash chromatography on silica
gel with ethyl acetate/petroleum ether (v : v = 20 : 1 → 2 : 1) to
provide the corresponding product (3, 4 or 5).
which Cu/Pd exchange occurs to form the Pd(II) species D.18f
Finally, the reductive elimination of D furnishes the desired
product 2-aryl benzoxazole (3) and regenerates Pd(II) for the
next run.
Conclusions
In summary, we have developed a new and highly efficient
method for palladium-catalyzed direct C–H bond arylation of
azoles at the C2-position using 3,3-diethyl-1-aryltriazenes as
the arylating reagents. Various azoles including oxazoles, thia-
zoles and 1,3,4-oxadiazoles, and especially nonaromatic oxazo-
lines and free (NH)-imidazoles, could react smoothly with 3,3-
Characterization data for the products
2-(p-Tolyl)benzo[d]oxazole (3a).8a Colorless solid. 1H NMR
diethyl-1-aryltriazenes to give the corresponding products in (400 MHz, CDCl3): δ 8.13 (d, J = 8.1 Hz, 2H), 7.76–7.74 (m, 1H),
good to excellent yields. Further mechanistic studies of this 7.56–7.53 (m, 1H), 7.35–7.29 (m, 4H), 2.41 (s, 3H); 13C NMR
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(100 MHz, CDCl3): δ 163.3, 150.7, 142.2, 142.0, 129.6, 127.6, 1H), 7.18 (d, J = 8.0 Hz, 2H), 4.31 (q, J = 7.1 Hz, 2H), 2.31 (s,
124.8, 124.4, 124.4, 119.8, 110.4, 21.6.
3H), 1.31 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
5-Methyl-2-(p-tolyl)benzo[d]oxazole (3b).8a Colorless solid. δ 164.4, 157.8, 142.0, 141.9, 135.2, 129.5, 127.1, 123.6, 61.3,
1H NMR (400 MHz, CDCl3): δ 8.11 (d, J = 8.0 Hz, 2H), 7.53 (s, 21.5, 14.2.
1H), 7.41 (d, J = 8.2 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.12 (d, J =
Ethyl
2-(4-methoxyphenyl)oxazole-5-carboxylate
(3l).22
8.2 Hz, 1H), 2.47 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz, Colorless solid. 1H NMR (400 MHz, CDCl3): δ 8.07 (d, J =
CDCl3): δ 163.4, 148.9, 142.4, 141.8, 134.2, 129.6, 127.5, 125.9, 8.4 Hz, 2H), 7.79 (s, 1H), 6.97 (d, J = 8.5 Hz, 2H), 4.39 (q, J =
124.6, 119.9, 109.8, 21.6, 21.5.
7.1 Hz, 2H), 3.85 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H); 13C NMR
6-Methyl-2-(p-tolyl)benzo[d]oxazole (3c).8a Colorless solid. (100 MHz, CDCl3): δ 164.3, 162.3, 157.9, 141.7, 135.4, 129.0,
1H NMR (400 MHz, CDCl3): δ 8.10 (d, J = 8.0 Hz, 2H), 7.61 (d, 119.0, 114.2, 61.3, 55.4, 14.2.
J = 8.0 Hz, 1H), 7.34 (s, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.13 (d, J =
2-Phenyl-5-(p-tolyl)-1,3,4-oxadiazole (3m).8a Colorless solid.
8.0 Hz, 1H), 2.48 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz, 1H NMR (400 MHz, CDCl3): δ 8.13–8.11 (m, 2H), 8.01 (d, J =
CDCl3): δ 162.8, 150.9, 141.7, 140.0, 135.2, 129.5, 127.4, 125.6, 8.0 Hz, 2H), 7.52–7.51 (m, 3H), 7.31 (d, J = 8.0 Hz, 2H), 2.42 (s,
124.6, 119.1, 110.6, 21.7, 21.5.
3H); 13C NMR (100 MHz, CDCl3): δ 164.6, 164.2, 142.2, 131.5,
4-Methyl-2-(p-tolyl)benzo[d]oxazole (3d).19 Colorless solid. 129.7, 129.0, 126.8, 124.0, 121.1, 21.6.
1H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.0 Hz, 2H), 7.37 (d,
2,5-Di(p-tolyl)-1,3,4-oxadiazole (3n).8a Colorless solid. 1H
J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.20 (t, J = 7.8 Hz, 1H), NMR (400 MHz, CDCl3): δ 8.01 (d, J = 7.9 Hz, 4H), 7.32 (d, J =
7.11 (d, J = 7.4 Hz, 1H), 2.66 (s, 3H), 2.41 (s, 3H); 13C NMR 7.9 Hz, 4H), 2.43 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 164.4,
(100 MHz, CDCl3): δ 162.5, 150.4, 141.7, 141.5, 130.4, 129.5, 142.1, 129.7, 126.8, 121.2, 21.6.
127.5, 124.9, 124.7, 124.5, 107.7, 21.6, 16.5.
2-(4-Chlorophenyl)-5-(p-tolyl)-1,3,4-oxadiazole (3o).8a Colorless
5-(tert-Butyl)-2-(p-tolyl)benzo[d]oxazole (3e).8a Colorless solid. 1H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 8.5 Hz, 2H),
solid. 1H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 7.9 Hz, 2H), 8.00 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 8.5 Hz, 2H), 7.32 (d, J =
7.81 (s, 1H), 7.49 (d, J = 8.5 Hz, 1H), 7.41 (d, J = 8.5 Hz, 1H), 8.0 Hz, 2H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 164.8,
7.32 (d, J = 7.9 Hz, 2H), 2.43 (s, 3H), 1.42 (s, 9H); 13C NMR 163.4, 142.4, 137.8, 129.74, 129.4, 128.1, 126.8, 122.5, 120.9,
(100 MHz, CDCl3): δ 163.4, 148.7, 148.0, 142.1, 141.8, 129.6, 21.6.
127.5, 124.6, 122.5, 116.3, 109.5, 34.9, 31.7, 21.6.
2-(p-Tolyl)benzo[d]thiazole (3p).8a Colorless solid. 1H NMR
5-Methoxy-2-(p-tolyl)benzo[d]oxazole (3f).20 Colorless solid. (400 MHz, CDCl3): δ 8.05 (d, J = 8.3 Hz, 1H), 7.97 (d, J = 7.7 Hz,
1H NMR (400 MHz, CDCl3): δ 8.11 (d, J = 8.0 Hz, 2H), 7.43 (d, 2H), 7.87 (d, J = 7.9 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.35 (t, J =
J = 8.8 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 2.4 Hz, 1H), 7.5 Hz, 1H), 7.28 (d, J = 7.7 Hz, 2H), 2.41 (s, 3H); 13C NMR
6.92 (dd, J = 8.8, 2.4 Hz, 1H), 3.86 (s, 3H), 2.42 (s, 3H); 13C (100 MHz, CDCl3): δ 168.2, 154.2, 141.4, 135.0, 131.0, 129.7,
NMR (100 MHz, CDCl3): δ 164.0, 157.3, 145.3, 143.0, 141.9, 127.5, 126.2, 125.0, 123.0, 121.5, 21.5.
129.6, 127.4, 124.5, 113.3, 110.5, 102.8, 55.9, 21.6.
2-(p-Tolyl)benzo[d]thiazol-6-amine (3q). Colorless solid. 1H
5-Fluoro-2-(p-tolyl)benzo[d]oxazole (3g).20 Colorless solid. NMR (400 MHz, CDCl3): δ 7.92 (d, J = 7.9 Hz, 2H), 7.83 (d, J =
1H NMR (400 MHz, CDCl3): δ 8.11 (d, J = 8.1 Hz, 2H), 7.49–7.45 8.7 Hz, 1H), 7.27 (d, J = 7.9 Hz, 2H), 7.12 (d, J = 2.1 Hz, 1H),
(m, 1H), 7.43–7.41 (m, 1H), 7.71 (d, J = 8.1 Hz, 2H), 7.07–7.02 6.84 (dd, J = 7.9, 2.1 Hz, 1H), 3.85 (s, 2H), 2.42 (s, 3H); 13C
(m, 1H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 165.0, NMR (100 MHz, CDCl3): δ 164.0, 147.6, 144.4, 140.5, 136.7,
160.1 (d, J = 238.7 Hz), 147.0 (d, J = 1.3 Hz), 143.0 (d, J = 13.2 131.3, 129.6, 127.0, 123.5, 115.6, 105.7, 21.4. HRMS (ESI) ([M +
Hz), 142.4, 129.7, 127.6, 124.1, 112.4 (d, J = 26.2 Hz), 110.7 (d, H]+) Calcd for [C14H13N2S]+: 241.0799, found: 241.0797.
J = 10.1 Hz), 106.2 (d, J = 25.5 Hz), 21.6.
2-(p-Tolyl)thiazole (3r).8a Colorless solid. 1H NMR
6-Chloro-2-(p-tolyl)benzo[d]oxazole (3h).8a Colorless solid. (400 MHz, CDCl3): δ 8.85 (d, J = 8.0 Hz, 2H), 7.82 (d, J = 3.2 Hz,
1H NMR (400 MHz, CDCl3): δ 8.10 (d, J = 8.2 Hz, 2H), 7.64 (d, 1H), 7.26 (d, J = 3.2 Hz, 1H), 7.23 (d, J = 8.0 Hz, 2H), 2.38 (s,
J = 8.5 Hz, 1H), 7.56 (d, J = 1.6 Hz, 1H), 7.33–7.30 (m, 3H), 2.43 3H); 13C NMR (100 MHz, CDCl3): δ 168.5, 143.4, 140.1, 130.9,
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 164.0, 151.0, 142.4, 129.6, 126.4, 118.2, 21.3.
141.0, 130.4, 129.7, 127.6, 125.1, 123.9, 120.3, 111.1, 21.6.
4-Methyl-2-(p-tolyl)thiazole (3s).8a Colorless solid. 1H NMR
5-Chloro-2-(p-tolyl)benzo[d]oxazole (3i).8a Colorless solid. (400 MHz, CDCl3): δ 7.81 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz,
1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.0 Hz, 2H), 7.71 (d, 2H), 6.81 (s, 1H), 2.49 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz,
J = 1.8 Hz, 1H), 7.45 (d, J = 8.6 Hz, 1H), 7.32–7.25 (m, 3H), 2.43 CDCl3): δ 167.7, 153.6, 139.9, 131.1, 129.5, 126.3, 112.9, 21.3,
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 164.6, 149.3, 143.3, 17.2.
142.5, 129.9, 129.7, 127.7, 125.0, 123.9, 119.8, 111.1, 21.6.
4,5-Dimethyl-2-(p-tolyl)thiazole (3t).8a Colorless solid. 1H
5-Bromo-2-(p-tolyl)benzo[d]oxazole (3j).21 Colorless solid. 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.0 Hz, 2H), 7.17 (d, J =
NMR (400 MHz, CDCl3): δ 8.15 (d, J = 8.1 Hz, 2H), 7.77–7.75 8.0 Hz, 2H), 2.35 (s, 3H), 2.34 (s, 3H), 2.33 (s, 3H); 13C NMR
(m, 1H), 7.58–7.56 (m, 1H), 7.35–7.32 (m, 3H), 2.44 (s, 3H); 13
C
(100 MHz, CDCl3): δ 163.4, 148.9, 139.3, 131.2, 129.3, 125.9,
NMR (100 MHz, CDCl3): δ 163.3, 150.7, 142.2, 142.1, 129.6, 125.8, 21.2, 14.7, 11.3.
127.6, 124.9, 124.5, 124.4, 119.9, 110.5, 21.6.
2-(4-Methyl-2-(p-tolyl)thiazol-5-yl)ethanol (3u). Colorless
Ethyl 2-(p-tolyl)oxazole-5-carboxylate (3k).17c Colorless solid. solid. 1H NMR (400 MHz, CDCl3): δ 7.75 (d, J = 7.9 Hz, 2H),
1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 8.0 Hz, 2H), 7.72 (s, 7.20 (d, J = 7.9 Hz, 2H), 3.84 (t, J = 6.2 Hz, 2H), 2.99 (t, J =
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6.2 Hz, 2H), 2.39 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz,
2-(m-Tolyl)benzo[d]oxazole (3ae).8a Colorless solid. H NMR
CDCl3): δ 164.9, 149.8, 139.8, 131.1, 129.5, 127.5, 126.1, 63.0, (400 MHz, CDCl3): δ 8.09 (s, 1H), 8.04 (d, J = 7.6 Hz, 1H),
29.9, 21.3, 15.1. HRMS (ESI) ([M + H]+) Calcd for [C13H16NO2]+: 7.78–7.75 (m, 1H), 7.57–7.55 (m, 1H), 7.40 (t, J = 7.6 Hz, 1H),
234.0953, found: 234.0951.
7.35–7.32 (m, 3H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3):
1-Methyl-2-(p-tolyl)-1H-benzo[d]imidazole (3v).7a Colorless δ 163.2, 150.7, 142.1, 138.7, 132.3, 128.8, 128.2, 127.0, 125.0,
1
solid. H NMR (400 MHz, CDCl3): δ 7.83–7.81 (m, 1H), 7.66 (d, 124.7, 124.5, 119.9, 110.5, 21.3.
J = 7.9 Hz, 2H), 7.40–7.37 (m, 1H), 7.34–7.28 (m, 4H), 3.86 (s,
2-(3,4-Dimethylphenyl)benzo[d]oxazole (3af).23 Colorless
3H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.9, 143.0, solid; 1H NMR (400 MHz, CDCl3): δ 8.03 (s, 1H), 7.96 (d, J =
139.8, 136.6, 129.4, 129.3, 127.3, 122.6, 122.3, 119.7, 109.5, 7.8 Hz, 1H), 7.76–7.73 (m, 1H), 7.55–7.53 (m, 1H), 7.34–7.29
31.6, 21.4.
(m, 2H), 7.25 (d, J = 7.7 Hz, 1H), 2.34 (s, 3H), 2.31 (s, 3H); 13C
2-Phenylbenzo[d]oxazole (3w).8a Colorless solid. 1H NMR NMR (100 MHz, CDCl3): δ 163.4, 150.6, 142.2, 140.7, 137.3,
(400 MHz, CDCl3): δ 8.18–8.16 (m, 2H), 7.70–7.68 (m, 1H), 130.1, 128.6, 125.1, 124.7, 124.6, 124.4, 119.7, 110.4, 19.9, 19.6.
7.50–7.48 (m, 1H), 7.44–7.42 (m, 3H), 7.27–7.25 (m, 2H); 13C
2-(3,5-Dimethylphenyl)benzo[d]oxazole (3ag).19 Colorless
1
NMR (100 MHz, CDCl3): δ 163.0, 150.8, 142.1, 131.5, 128.9, solid. H NMR (400 MHz, CDCl3): δ 7.88 (s, 2H), 7.77–7.75 (m,
127.6, 127.2, 125.1, 124.5, 120.0, 110.5.
1H), 7.57–7.55 (m, 1H), 7.34–7.32 (m, 2H), 7.15 (s, 1H), 2.40 (s,
2-(4-Ethylphenyl)benzo[d]oxazole (3x).23 Colorless solid. 1H 6H); 13C NMR (100 MHz, CDCl3): δ 163.4, 150.7, 142.1, 138.6,
NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.2 Hz, 2H), 7.77–7.75 133.3, 126.9, 125.4, 124.9, 124.5, 119.9, 110.5, 21.2.
(m, 1H), 7.57–7.55 (m, 1H), 7.35–7.32 (m, 4H), 2.72 (q, J =
2-(2,4-Dimethylphenyl)benzo[d]oxazole (3ah).3m Colorless
7.6 Hz, 2H), 1.28 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, solid. 1H NMR (400 MHz, CDCl3): δ 8.11 (d, J = 8.3 Hz, 1H),
CDCl3): δ 163.3, 150.7, 148.2, 142.2, 128.4, 127.7, 124.8, 124.6, 7.83–7.81 (m, 1H), 7.61–7.58 (m, 1H), 7.38–7.36 (m, 2H),
124.4, 119.8, 110.5, 28.9, 15.2.
7.18–7.16 (m, 2H), 2.81 (s, 3H), 2.41 (s, 3H); 13C NMR
2-(4-iso-Propylphenyl)benzo[d]oxazole (3y).24 Colorless solid. (100 MHz, CDCl3): δ 163.6, 150.2, 142.2, 141.2, 138.7, 132.5,
1H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.2 Hz, 2H), 7.77–7.75 129.9, 126.8, 124.7, 124.2, 123.4, 119.9, 110.3, 22.1, 21.3.
(m, 1H), 7.56–7.54 (m, 1H), 7.36 (d, J = 8.2 Hz, 2H), 7.33–7.31
4,4-Dimethyl-2-(p-tolyl)-2-oxazoline (4a).3r Colorless solid.
(m, 2H), 2.97 (h, J = 6.9 Hz, 1H), 1.28 (d, J = 6.9 Hz, 6H); 13C 1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 8.0 Hz, 2H), 7.19 (d, J
NMR (100 MHz, CDCl3): δ 163.2, 152.8, 150.7, 142.2, 127.7, = 8.0 Hz, 2H), 4.08 (s, 2H), 2.37 (s, 3H), 1.37 (s, 6H); 13C NMR
127.0, 124.8, 124.7, 124.4, 119.8, 110.4, 34.2, 23.7.
(100 MHz, CDCl3): δ 162.1, 141.4, 128.9, 128.1, 125.1, 78.9,
2-(4-Methoxyphenyl)benzo[d]oxazole (3z).8a Colorless solid. 67.4, 28.3, 21.4.
1H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.7 Hz, 2H), 7.74–7.71
2-(4-Methoxyphenyl)-4,4-dimethyl-2-oxazoline (4b).3r Colorless
(m, 1H), 7.53–7.51 (m, 1H), 7.33–7.27 (m, 2H), 7.99 (d, J = solid. 1H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 8.5 Hz, 2H),
8.7 Hz, 2H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 163.1, 6.88 (d, J = 8.5 Hz, 2H), 4.05 (s, 2H), 3.80 (s, 3H), 1.35 (s, 6H);
162.2, 150.6, 142.2, 129.29, 124.5, 124.3, 119.6, 119.5, 114.3, 13C NMR (100 MHz, CDCl3): δ 161.8, 161.7, 129.8, 120.4, 113.5,
110.3, 55.3.
78.9, 67.3, 55.2, 28.3.
2-(4-Ethoxyphenyl)benzo[d]oxazole (3aa).24 Colorless solid.
2-(4-Chlorophenyl)-4,4-dimethyl-2-oxazoline (4c).25 Colorless
1H NMR (400 MHz, CDCl3): δ 8.16 (d, J = 8.8 Hz, 2H), 7.74–7.71 solid. 1H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 8.3 Hz, 2H),
(m, 1H), 7.54–7.52 (m, 1H), 7.33–7.27 (m, 2H), 6.99 (d, J = 7.38 (d, J = 8.3 Hz, 2H), 4.12 (s, 2H), 1.39 (s, 6H); 13C NMR
8.8 Hz, 2H), 4.08 (q, J = 7.0 Hz, 2H), 1.43 (t, J = 7.0 Hz, 3H); 13
C
(100 MHz, CDCl3): δ 161.2, 137.3, 129.6, 128.5, 126.5, 79.2,
NMR (100 MHz, CDCl3): δ 163.2, 161.7, 150.6, 142.3, 129.3, 67.7, 28.4.
124.5, 124.3, 119.5, 119.4, 114.7, 110.3, 63.6, 14.7.
2-(p-Tolyl)-4-phenyl-2-oxazoline (4d).26 Colorless solid. 1H
2-(4-Fluorophenyl)benzo[d]oxazole (3ab).8a Colorless solid. NMR (400 MHz, CDCl3): δ 7.96 (d, J = 7.9 Hz, 2H), 7.40–7.30
1H NMR (400 MHz, CDCl3): δ 8.25–8.22 (m, 2H), 7.76–7.74 (m, (m, 5H), 7.27 (d, J = 7.9 Hz, 2H), 5.39 (t, J = 9.1 Hz, 1H), 4.80 (t,
1H), 7.56–7.54 (m, 1H), 7.35–7.33 (m, 2H), 7.21–7.17 (m, 2H); J = 9.2 Hz, 1H), 4.28 (t, J = 8.2 Hz, 1H), 2.43 (s, 3H); 13C NMR
13C NMR (100 MHz, CDCl3): δ 164.8 (d, J = 251.2 Hz), 162.1, (100 MHz, CDCl3): δ 164.8, 142.5, 141.9, 129.0, 128.7, 128.4,
150.8, 142.1, 129.8 (d, J = 8.8 Hz), 125.1, 124.6, 123.5 (d, J = 127.5, 126.7, 124.7, 74.7, 70.0, 21.5.
3.2 Hz), 120.0, 116.1 (d, J = 22.1 Hz), 110.5.
2-(p-Tolyl)-4-benzyl-2-oxazoline (4e). Colorless solid. 1H
2-(4-Chlorophenyl)benzo[d]oxazole (3ac).8a Colorless solid. NMR (400 MHz, CDCl3): δ 7.85 (d, J = 7.9 Hz, 2H), 7.34–7.22
1H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 8.5 Hz, 2H), 7.79–7.77 (m, 7H), 4.62–4.55 (m, 1H), 4.34 (t, J = 8.9 Hz, 1H), 4.15 (t, J =
(m, 1H), 7.60–7.58 (m, 1H), 7.51 (d, J = 8.5 Hz, 2H), 7.40–7.35 7.9 Hz, 1H), 3.27 (dd, J = 13.7, 4.8 Hz, 1H), 2.74 (dd, J = 13.6,
(m, 2H); 13C NMR (100 MHz, CDCl3): δ 162.1, 150.8, 142.0, 9.1 Hz, 1H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 164.1,
137.8, 129.3, 128.8, 125.7, 125.3, 124.7, 120.1, 110.6.
141.7, 138.0, 129.2, 129.0, 128.5, 128.2, 126.5, 124.9, 71.7, 67.8,
2-(o-Tolyl)benzo[d]oxazole (3ad).8a Colorless solid. 1H NMR 41.8, 21.5. HRMS (ESI) ([M + H]+) Calcd for [C17H18NO]+:
(400 MHz, CDCl3): δ 8.17 (d, J = 7.3 Hz, 1H), 7.82–7.78 (m, 1H), 252.1388, found: 252.1387.
7.60–7.56 (m, 1H), 7.42–7.39 (m, 1H), 7.37–7.32 (m, 4H), 2.81
1,2-Di(p-tolyl)-1H-benzo[d]imidazole (5a).27 Colorless solid.
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 163.4, 150.3, 142.2, 1H NMR (400 MHz, CDCl3): δ 7.87 (d, J = 8.0 Hz, 1H), 7.47 (d, J
138.8, 131.8, 130.9, 129.9, 126.3, 126.0, 125.0, 124.3, 120.1, = 8.0 Hz, 2H), 7.33–7.28 (m, 3H), 7.24–7.18 (m, 4H), 7.11 (d, J =
110.5, 22.1.
7.9 Hz, 2H), 2.45 (s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz,
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CDCl3): δ 152.6, 142.9, 139.5, 138.5, 137.4, 134.5, 130.4, 129.3,
129.0, 127.2, 127.1, 123.0, 122.7, 119.6, 110.4, 21.3, 21.2.
1,2-Di(p-tolyl)-1H-imidazole (5b). Colorless solid. 1H NMR
(400 MHz, CDCl3): δ 7.29 (d, J = 8.0 Hz, 2H), 7.22–7.18 (m, 3H),
7.11–7.09 (m, 3H), 7.06 (d, J = 7.9 Hz, 2H), 2.39 (s, 3H), 2.31 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 146.8, 138.1, 138.0, 136.2,
129.9, 128.8, 128.7, 128.4, 127.6, 125.6, 122.8, 21.2, 21.1.
HRMS (ESI) ([M + H]+) Calcd. for [C17H17N2]+: 249.1392, found:
249.1393.
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1,2-Diphenyl-1H-imidazole (5c).27 Colorless solid. 1H NMR
(400 MHz, CDCl3): δ 7.40–7.38 (m, 5H), 7.26–7.21 (m, 6H), 7.16
(s, 1H); 13C NMR (100 MHz, CDCl3): δ 146.7, 138.5, 130.3,
129.4, 129.0, 128.5, 128.3, 128.1, 128.1, 125.8, 122.8.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We gratefully acknowledge the National Natural Science
Foundation of China (21772062 and 21572078).
Notes and references
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