Nano CuO-catalyzed C-H functionalization of 1,3-azoles with bromoarenes and bromoalkenes

Accepted Manuscript

Nano CuO Catalyzed C–H Functionalization of 1, 3-Azoles with Bromoarenes and

Bromoalkenes

Wu Zhang , Yujie Tian , Na Zhao , Yuanyuan Wang , Jia Li , Zhenghua Wang

PII:

S0040-4020(14)00599-7

10.1016/j.tet.2014.04.065

TET 25515

DOI:

Reference:

To appear in: Tetrahedron

Received Date: 26 January 2014

Revised Date: 18 April 2014

Accepted Date: 23 April 2014

Please cite this article as: Zhang W, Tian Y, Zhao N, Wang Y, Li J, Wang Z, Nano CuO Catalyzed

C–H Functionalization of 1, 3-Azoles with Bromoarenes and Bromoalkenes, Tetrahedron (2014), doi:

10.1016/j.tet.2014.04.065.

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ACCEPTED MANUSCRIPT

Nano CuO Catalyzed C–H Functionalization of 1, 3-Azoles

with Bromoarenes and Bromoalkenes

Wu Zhang,* Yujie Tian, Na Zhao, Yuanyuan Wang, Jia Li, Zhenghua Wang*

Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui

Laboratory of Molecule-Based Materials, College of Chemistry and Materials Science,

Anhui Normal University, Wuhu 241000, China. Email: zhangwu@mail.ahnu.edu.cn;

zhwang@mail.ahnu.edu.cn

Abstract:

Copper oxide catalyzed direct C–H arylation and alkenylation of aromatic

heterocycles using aryl and alkenyl bromides have been developed and has been

applied to the C-H functionalization of a variety of 1,3-azoles like benzoxazole,

benzothiazole, 1-methylbenzimidazole, and 1-methylimidazole, with moderate to

excellent yields. The best performance has been achieved in the presence of PPh₃

when average size of CuO nanoparticles is 6.5 nm. This catalyst can be recovered and

reused without significant decrease in its catalytic activity.

Keywords: CuO nanoparticles; C–H functionalization; 1, 3-azole; bromide

Graphical abstract

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1. Introduction

1, 3-Azoles as important and ubiquitous structure motifs presented in many natural

products, pharmaceutical active compounds, and organic functional materials (such as

fluorescent dyes and liquid crystals),¹have attracted great research efforts in their

syntheses and further functionalization for various applications in drug discovery and

organic synthesis.²The classical method for the preparation of this type of compounds

is the transition metal-catalyzed coupling reaction, including palladium,³rhodium,⁴

ruthenium,⁵and nickel ⁶et al. Recently, the copper facilitated synthesis of heterocycle

has attracted increasing research interests due to their relatively low cost and high

efficiency.⁷Among those, the copper-catalyzed direct C–H functionalization is

effective and straightforward and can avoid the preparation of organometallic

intermediates as coupling partners.⁸Pioneering work in this field has been performed

by Do and Daugulis in the CuI-catalyzed arylation of oxazoles,⁹by Miura in the

CuI/PPh₃catalyzed direct arylation of benzoazoles,¹⁰by You in the CuI-catalyzed

arylation of heterocycles using 1, 10-phenanthroline as ligand,¹¹and by Piguel in the

CuI-catalyzed direct alkenylation of 5-phenyloxazoles using trans-N,

N'-dimethylcyclohexane-1, 2-diamine as ligand.¹²However, the separation and

recycle of these catalyst remains a problem. Therefore, it is very necessary to develop

novel copper catalyzed system that can be easily separated and recycled after the

reactions.

Nanoparticles have emerged as high surface area heterogeneous catalysts which

increase the exposed surface area of the active component.¹³Meanwhile, their

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insolubility in reaction solvents renders them easily separable from the reaction

mixture. Recently, Copper nanoparticles have been used to catalyze the carbon-carbon

and carbon-heteroatom bond formation due to their stability and wild availability.¹⁴

Previously, we already developed CuO nanospindles-catalyzed directed arylation of

heterocycles with aryl iodides.¹⁵It is well known that the reactivity of aromatic

iodides is far superior to that of aromatic bromides. Herein we report the CuO

nanoparticles catalyzed C−H functionalization of heterocycles using aromatic

bromides.

2. Results and discussion

Our initial investigations were focused on the nanometer CuO catalyzed direct

arylation of benzoxazole 1a with bromobenzene 2a. Catalysts, bases, ligands, solvents,

reaction temperature, and reaction time were screened, and the results are summarized

in Table 1. Under our previously reported condition for the arylation of heterocycle

with aryl iodide¹⁵: the substrates were refluxed with CuO nanospindles (10 mol %) at

reflux in diglyme in the presence of K₂CO₃under stir (Table 1, entry1), no desired

product 3a was obtained. To our delight, the addition of PPh₃(30 mol %) led to the

formation of 3a in 55% yield (Table 1, entry 2). This promoted us to further

investigate the catalytical performance of the particle size and different shape of nano

CuO in the reaction.

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Table 1. Optimization of the direct arylation of benzoxazole and bromobenzene^a

1a

2a

3a

yield(%)^b

entry

1

catalyst

base

ligand

—

solvent

diglyme

DMSO

CuO nanospindles (10 mol %)

CuO (200 mesh) (10 mol %)

CuO nanoparticles (10 mol %)

CuO nanobelts (10 mol %)

K₂CO₃

Na₂CO₃

NaOAc

NEt₃

—

55

—

2

PPh₃

Phen

DMEDA

dipyridine

PPh₃

3

4

95

40

trace

85

98

34

—

5

6

CuO nanosheets (10 mol %)

CuO nanoparticles (5 mol %)

CuO nanoparticles (20 mol %)

CuO nanoparticles (10 mol %)

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21^c

22^d

23^e

24^f

—

84

73

67

—

Cs₂CO₃

K₃PO₄

K₂CO₃

—

41

78

32

trace

60

—

DMF

dioxane

toluene

diglyme

98

76

^aReaction conditions: benzoxazole (1 equiv), bromobenzene (2 equiv), base (2 equiv), CuO

b

nanoparticles (10 mol%), ligand (30 mol%), solvent (2 mL), under reflux in argon for 5h. Isolated

yields. ^c150 ^oC. ^d140 ^oC. ^e8 h. ^f3 h.

The particle size and shape is critical in this reaction, with the best performance

achieved when the CuO with 6.5 nm in average diameter was used, from which the

desired product was obtained in 95% yield (Table 1, entries 2–6)). By contrast, no

product was obtained when commercial CuO powder (about 200 mesh) was used.

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Reduing the catalyst loading from 10 to 5 mol % resulted in a decrease of the reaction

yield from 95% to 85% (Table 1, entry 7), no significant improvement in the yield

was observed when the catalyst loading was increased to 20 mol % (Table 1, entry 8).

Among several ligands investigated, including PPh₃, phen, DMEDA, and α,

α′-dipyridine, the addition of PPh₃is crucial to the copper-catalyzed arylation (Table 1,

entries 4, 9-11), which stabilize and activate the CuO nanoparticles. Both organic and

inorganic bases, including Na₂CO₃, NaOAc and NEt₃were found to promote the

reaction, with the best performance achieved from K₂CO₃(Table 1, entries 12-16).

Among various solvent studied, diglyme gave the best result (Table 1, entries 17–20).

In addition, variation of the temperature, and reaction time were also explored (Table

1, entries 21-24). The best results were obtained in diglyme at reflux for 5 h using two

equivalents of K₂CO₃as the base in the presence of CuO nanoparticles /PPh₃catalyst

system.

With this optimized reaction conditions in hand, the scope of this nano

CuO-catalyzed C–H functionalization was further investigated and the results are

summarized in Table 2. In the arylation of benzoxazole, higher yields were obtained

in the presence of electron-withdrawing groups on aryl bromides comparison to those

with electron-donating groups (Table 2, entries 1–3). Heteroaryl bromides are also

suitable for this reaction and provide the corresponding product in excellent yields

(entry 4). By contrast, no reaction was observed when aryl chloride was used for this

reaction (entry 5). Both electron-poor (entries 6-7) and electron-rich (entry 8)

benzoxazoles were efﬁciently arylated under this reaction conditions. In addition,

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heterocycles, like benzothiazole and benzimidazole also applicable for this reaction

with moderate to high yields (entries 9-15), with the lowest yields observed for the

reaction of benzothiazole with aryl bromide, which is in accordance with our previous

reported result. Imidazole can be monoarylated in 43% yield, with 35 % of the

diarylated product isolated (entry 16).

Table 2. Functionalization scope with respect to Aryl/Allyl bromides and

heterocycles^a

N

Br

N

nano CuO/ PPh₃, K₂CO₃,

diglyme, reflux

R

n

X

R

Y

n

Y

Y=C, N

n=0,1

X=O, S, NCH₃

R=H, OCH₃

time, yield

entry

heterocycle

ArX

product

h

(%)

1

2

3

4

5

6

7

8

5

95

5

79

83

92

―

59

73

76

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9

24

70

51

92

88

75

85

95

10

11

12

13

14

15

N

43

35

16

17

21

8

54

40

15

18

15

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N

19

20

21

18

24

52

46

86

N

a

The reactions were carried out using heterocycle (0.25 mmol), bromobenzene (0. 5 mmol), CuO

(0.025 mmol), base (0. 5 mmol), ligand(0. 075 mmol) in diglyme (2 mL) under reflux in argon for 5h.

^bIsolated yields.

This catalytic condition was also successfully applied to the alkenylation of

azoles with (E)-β-bromostyrene, and the results were shown in Table 2 (entries 17-21).

Both electron-rich and electron-deficient β-bromostyrene reacted with benzimidazole

to give the desired product in moderate to good yields. In general, the presence of

electron-withdrawing groups on β-bromostyrene leads to higher yields in comparison

to those with electron-donating groups. The E-isomers were obtained exclusively.

Surprisingly, a new product was separated from the reaction mixture of benzothiazole

and (E)-β-bromostyrene, and further characterization shows that it was a [2+2]

cycloaddition product. The detailed [2+2] cycloaddition process in this reaction is still

under investigation.

Table 3. Successive tests by using recycled CuO nanoparticles^a

test

1

yield

88

2

85

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3

79

^aReaction conditions: 1-methylbenzimidazole (1 equiv), bromobenzene (2 equiv), 10

mol % CuO nanoparticles, 30 mol % PPh₃, K₂CO₃(2 equiv), diglyme (2 mL), under

reflux in argon for 24h.

To test the potential applications of this reaction in industrial and pharmaceutical

areas, the reusability of the CuO nanoparticles was investigated. As shown in Table 3,

no significant decrease in the catalytic activity for the arylation of

1-methylbenzimidazole with bromobenzene was observed for the recovered CuO

nanoparticles.

To examine whether the observed catalysis is derived from CuO nanoparticles or

the leached copper species, the arylation of benzoxazole was carried out under the

optimized conditions and the catalyst was removed from the mixture by centrifugation

after 2 hours. The “catalyst-free” solution was then kept on the reaction under the

same conditions. However, no further progress of reaction was observed even after 5

hours. The leaching of the copper from the CuO nanoparticles during reaction was

examined by AAS analysis, and a slight leaching (< 1 ppm) is observed. We thus

believe that the reaction may undergo through an oxidative addition, anion

substitution, and then a reductive elimination process on the surface of the CuO

nanoparticles which was stabilized by PPh₃via a heterogeneous process. The

mechanism of the reaction is similar to our reported work.¹⁵

3. Conclusion

In conclusion, we have developed a practical and effective CuO nanoparticles

catalyzed C–H functionalization of heterocycles, such as benzoxazole, benzothiazole

and 1-methylbenzimidazole with aryl bromides and alkenyl bromides in moderate to

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excellent yields. The CuO nanoparticles catalyst can be recycled and reused without

any significant decrease in the catalytic activity.

4. Experimental section

4.1 General

All starting materials and reagents were commercially available and used without

further puriﬁcation. The CuO nanospindles, nanoparticles, nanobelts and nanosheets

were prepared according to reference.¹⁶The prepared CuO were characterized by

X-ray powder diffraction with graphite monochromatized Cu-Kα radiation (λ =

0.154060 nm) in the 2θ range from 10° to 80°. The ﬁeld-emission scanning electron

microscopy (FE-SEM) images were obtained on an S-4800 ﬁeld-emission scanning

electron microscope with an accelerating voltage of 5 kV. Brunauer-Emmett-Teller

(BET) nitrogen adsorption-desorption was measured by using a Micromeritics ASAP

2020 accelerated surface area and porosimetry system. NMR spectra were obtained at

1

25 °C on a Bruker Avance-300 at 300 MHz for H, and at 75 MHz for ¹³C NMR,

1

13

chemical shifts for H and C were both referenced to CDCl₃. High resolution mass

spectral (HRMS) data were obtained with an ionization mode of ESI on Agilent 6200

LC/MS TOF.

4.2 Catalysts characterization

The obtained CuO nanoparticles were characterized by X-ray powder diffraction

analysis (XRD). Figure 1 presents a typical XRD pattern of the as-prepared sample.

All of the detectable diffraction peaks can be indexed to (-111), (111), (-202), (202),

(-113), (-311), (220) and (-222) reflections of the monoclinic phase CuO, in good

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agreement with the standard value (JCPDS card NO. 80-1916). The mean crystalline

size of the sample, estimated from Sherrer formula, is about 6.5 nm. The morphology

of the as-synthesized CuO catalyst was studied by SEM. Figure 2a shows that the

as-prepared sample is mainly composed of aggregated spherical particles with average

diameter of about 6.5 nm, which is coincident with the result of HRTEM as shown in

Figure 2b. In addition, the results of nitrogen adsorption experiments illustrate that the

CuO catalyst has BET (Brunauer–Emmett–Teller) surface areas of 89.33 m²g^-1.

10

20

30

40

50

60

70

80

2θ (degrees)

Figure 1. XRD pattern of the prepared sample.

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Figure 2. (a) FE-SEM image of the as-prepared CuO nanoparticles; (b) HRTEM

image of the as-prepared CuO nanoparticles; (c) FE-SEM image of the

as-prepared CuO nanobelts; (d) FE-SEM image of the as-prepared CuO

nanosheets.

4.3 General procedure for CuO catalyzed arylation and alkenylation of 1, 3-azole

Under argon, 0.5 mmol of the bromobenzene or bromoalkenes were added to the

reaction mixture containing 0.25 mmol of the benzoxazole and 0.5 mmol K₂CO₃,

0.025 mmol CuO, 0. 075 mmol PPh₃, 2 mL dry diglyme was added to the reaction

vessel followed. The sealed reaction tube was stirred at 160 °C for 5-24 h. After

cooling, the reaction mixture was centrifuged to remove solid and separated the

organic phase. Then, organic phase was extracted and dried over anhydrous MgSO₄,

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and concentrated under reduced pressure after filtered. The residue was purified by

column chromatography on silica gel eluted to afford corresponding product.

4.4 Recycling procedure of the catalysts

The separated precipitates in the above procedure was washed sufficiently with

de-ionized water and ethanol for three times each, and then dried under vacuum at

50 °C for 8 h. After that the CuO nanoparticles were recovered.

4.5 Characterization data of the desired products

4.5.1 2-Phenylbenzo[d]oxazole. White solid; m.p. 102–103 °C (lit., 96-97 °C) ^[2b]; ¹H

NMR (300 MHz, CDCl₃): δ 8.27–8.25(m, 2H), 7.81–7.77(m, 1H), 7.60–7.57(m, 1H),

7.54–7.49(m, 3H), 7.38–7.33(m, 2H); ¹³C NMR (75 MHz, CDCl₃): δ 163.0, 150.8,

142.1, 131.5, 128.9, 127.6, 127.2, 125.1, 124.6, 120.0, 110.6.

4.5.2 2-(p-Tolyl)benzo[d]oxazole. White solid; m.p. 113–114 °C (lit., 114-115 °C) ^[5a]

;

¹H NMR (300 MHz, CDCl₃): δ 8.07(d, J = 7.5 Hz, 2H), 7.69–7.67(m, 1H),

7.50–7.48(m, 1H), 7.26–7.24(m, 4H), 2.36(s, 3H). ¹³C NMR (75 MHz, CDCl₃): δ

163.3, 150.7, 142.2, 142.1, 129.7, 127.6, 124.5, 124.4, 119.9, 110.5, 21.6.

4.5.3 2-(4-(trifluoromethyl)phenyl)benzo[d]oxazole. White solid; m.p. 138–139°C (lit.,

143-145 °C) ^[4d]; ¹H NMR (300 MHz, CDCl₃): δ 8.38(d, J = 7.5 Hz, 2H), 7.80–7.78(m,

3H), 7.63–7.60 (m, 1H), 7.41–7.39(m, 2H); ¹³C NMR (75 MHz, CDCl₃): δ 161.8,

151.2, 142.2, 130.8, 128.2, 126.3, 126.3, 126.2, 125.3, 122.3, 120.8, 111.2.

4.5.4 2-(pyridin-3-yl)benzo[d]oxazole. White solid; m.p. 107–109 °C (lit., 109-110 °C)

1

^[17a]; H NMR (300 MHz, CDCl₃): δ 9.44(s, 1H), 8.73(d, J =3.5 Hz, 1H), 8.46(d, J

=7.7 Hz, 1H), 7.77–7.76(m, 1H ), 7.57–7.56(m, 1H), 7.44–7.40(m, 1H), 7.36–7.35(m,

13

2H). C NMR (75 MHz, CDCl₃): δ 160.6, 152.0, 150.7, 148.7, 141.7, 134.7, 125.7,

124.9, 123.7, 123.5, 120.3, 110.7.

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4.5.5 5-chloro-2-phenylbenzo[d]oxazole. White solid; m.p. 100–102 °C (lit.,

1

104-106 °C) ^[3a]; H NMR (300 MHz, CDCl₃): δ 8.25–8.23(m, 2H), 7.75(s, 1H),

7.55–7.48(m, 4H), 7.34–7.31(m, 1H); ¹³C NMR (75 MHz, CDCl₃) δ 164.4, 149.4,

143.3, 131.9, 130.0, 129.0, 127.8, 126.7, 125.4, 120.0, 111.3.

1

4.5.6 5-chloro-2-(pyridin-3-yl)benzo[d]oxazole. White solid; m.p. 151–153°C; H

NMR (300 MHz, CDCl₃): δ 9.53(s, 1H), 8.86(d, J = 1.5 Hz, 1H), 8.57(d, J = 7.2 Hz,

1H), 7.85(s, 1H), 7.63–7.56(m, 2H), 7.46–7.43(m, 1H); ¹³C NMR (75 MHz, CDCl₃) δ

162.0, 152.4, 149.4, 148.9, 142.9, 134.9, 130.5, 126.0, 123.7, 123.1, 120.3, 111.5.

HRMS (ESI) calcd for C₁₂H₈N₂OCl ([M + H]⁺) 231.0325, found 231.0324.

4.5.7 5-methyl-2-phenylbenzo[d]oxazole White solid; m.p. 105–106°C (lit.,

105-106 °C) ^[5a]; ¹H NMR (300 MHz, CDCl₃): δ 8.27–8.26(m, 2H), 7.58–7.55(m, 4H),

7.47(d, J = 8.4 Hz, 1H) 7.18(d, J = 8.1 Hz, 1H), 2.51(s, 3H); ¹³C NMR (75 MHz,

CDCl₃) δ 163.1, 149.0, 142.3, 134.4, 131.4, 128.9, 127.5, 127.3, 126.2, 119.9, 109.9,

21.5.

4.5.8 2-Phenylbenzo[d]thiazole. White solid; m.p. 114–115 °C (lit., 111-112°C)^[2b]; ¹H

NMR (300 MHz, CDCl₃): δ 8.12–8.09(m, 3H), 7.88(d, J = 7.8 Hz, 1H), 7.52–7.48(m,

4H), 7.38(t, J = 7.8 Hz, 1H); ¹³C NMR (75 MHz, CDCl₃) δ 168.1, 154.1, 135.1, 133.6,

131.0, 129.0, 127.6, 126.3, 125.2, 123.2, 121.7.

1

4.5.9 2-(p-Tolyl)benzo[d]thiazole. White solid; m.p. 79–81 °C (lit., 80-82 °C) ^[5a]; H

NMR (300 MHz, CDCl₃): δ 8.06(d, J = 8.1 Hz, 1H), 7.99(d, J = 7.5 Hz, 2H), 7.89(d, J

= 7.5 Hz, 1H), 7.48(t, J = 6.6 Hz, 1H), 7.39–7.37(m, 1H), 7.30(d, J = 7.2 Hz, 2H),

13

2.42(s, 3H); C NMR (75 MHz, CDCl₃) δ 168.3, 154.2, 141.4, 134.9, 131.0, 129.7,

127.5, 126.2, 125.0, 123.0, 121.6, 21.5.

4.5.10 2-(pyridin-3-yl)benzo[d]thiazole. White solid; m.p. 126–127 °C (lit., 134 °C)

^[17b]; ¹H NMR (300 MHz, CDCl₃): δ 9.23(s, 1H), 8.64(d, J = 1.2 Hz, 1H), 8.27(d, J =

7.2 Hz, 1H), 8.03(d, J = 8.1 Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.44(t, J = 7.2 Hz, 1H),

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13

7.33–7.31(m, 2H); C NMR (75 MHz, CDCl₃) δ 164.5, 153.9, 151.5, 148.5, 134.9,

134.5, 129.6, 126.6, 125.7, 123.7, 123.5, 121.7.

4.5.11 1-Methyl-2-phenyl-1H-benzo[d]imidazole. White solid; m.p. 89–91 °C (lit.,

1

92-94 °C) ^[4d]; H NMR (300 MHz, CDCl₃): δ 7.86–7.82(m, 1H), 7.75–7.73(m, 2H),

7.53–7.48(m, 3H), 7.37–7.28(m, 3H), 3.80(s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ

153.7, 142.9, 136.5, 130.1, 129.8, 129.5, 128.7, 122.8, 122.5, 119.8, 109.6, 31.7.

4.5.12 1-Methyl-2-(p-tolyl)-1H-benzo[d]imidazole. White solid; m.p. 125–127 °C (lit.,

127-128 °C) ^[15]; ¹H NMR (300 MHz, CDCl₃): δ 7.84–7.81(m, 1H), 7.64(d, J = 8.1 Hz,

2H), 7.36–7.27(m, 5H), 3.80(s, 3H), 2.42(s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 153.9,

143.0, 139.9, 136.6, 129.4, 129.3, 127.3, 122.6, 122.3, 119.7, 109.6, 31.7, 21.4.

4.5.13 1-methyl-2-(4-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole. White solid;

m.p. 121–123°C (lit., 122-124 °C) ^[15]; ¹H NMR (300 MHz, CDCl₃) δ 7.93(d, J = 7.8

Hz, 2H), 7.87–7.80(m, 3H), 7.45–7.35(m, 3H), 3.91(s, 3H); ¹³C NMR (75 MHz,

CDCl₃) δ 152.1, 142.9, 136.6, 133.8, 129.8, 125.7(q, J = 3.6), 123.4, 122.8, 120.1,

109.8, 31.8.

4.5.14 1-methyl-2-(pyridin-3-yl)-1H-benzo[d]imidazole. Pale yellow solid; m.p.

142–143 °C; ¹H NMR (300 MHz, CDCl₃): δ 9.02(s, 1H), 8.76-8.74(m, 1H), 8.14(d, J

= 8.1 Hz, 1H), 7.84(d, J = 7.2 Hz, 1H), 7.51–7.31(m, 4H), 3.90(s, 3H). ¹³C NMR (75

MHz, CDCl₃) δ 150.6, 149.8, 143.0, 136.9, 136.6, 126.6, 123.6, 123.3, 122.8, 120.0,

109.8, 31.7. HRMS (ESI) calcd for C₁₃H₁₂N₃([M + H]⁺) 210.1031, found 210.1030.

4.5.15 1-methyl-2-phenyl-1H-imidazole. Light yellow oil; ^{[17c] 1}H NMR (300 MHz,

CDCl₃): δ 7.64(d, J = 6.6 Hz, 2H), 7.46–7.44(m, 3H), 7.13(s, 1H), 6.98(s, 1H), 3.75(s,

13

3H); C NMR (75 MHz, CDCl₃) δ 147.8, 130.6, 128.6, 128.6, 128.5, 128.4, 122.3,

34.5.

4.5.16 1-methyl-2,5-diphenyl-1H-imidazole. White solid; m.p. 165-166°C (lit.,

172–174°C)^[17c]; ¹H NMR (300 MHz, CDCl₃): δ 7.70(d, J = 6.6 Hz, 2H), 7.46–7.40(m,

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8H), 7.21(s, 1H), 3.68(s, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 149.4, 135.4, 130.9,

130.3, 128.8, 128.8, 128.7, 128.7,128.6, 127.9, 127.5, 33.8.

4.5.17 (E)-2-styrylbenzo[d]oxazole. Light yellow solid; m.p. 80–81 ^oC (lit., 85-86 °C)

^[2b]; ¹H NMR (300 MHz, CDCl₃): δ 7.80 (d, J = 16.4 Hz, 1H), 7.72(m, 1H), 7.61–7.52

(m, 3H), 7.42–7.33(m, 5H), 7.09 (d, J = 16.4 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃): δ

162.8, 150.4, 142.2, 139.5, 135.2, 129.8, 129.0, 127.6, 125.2, 124.5, 119.9, 114.0,

110.3.

o

4.5.18 (E)-2-styrylbenzo[d]thiazole. Light yellow solid: m.p. 106–108 C (lit.,

1

106-108 °C) ^[13]; H NMR (300 MHz, CDCl₃): δ 7.98(d, J = 7.8 Hz, 1H), 7.84(d, J =

7.8 Hz, 1H), 7.58–7.56(m, 2H), 7.49–7.37 (m, 7H). ¹³C NMR (75 MHz, CDCl₃): δ

167.0, 153.9, 137.7, 135.4, 134.4, 129.5, 129.0, 127.4, 126.3, 125.4, 123.0, 122.1,

121.5.

4.5.19 2,2'-(2,4-diphenylcyclobutane-1,3-diyl)bis(benzo[d]thiazole. Light yellow solid,

¹H NMR (300 MHz, CDCl₃): δ 8.03(d, J = 7.8 Hz, 2H), 7.77(d, J = 7.8 Hz, 2H),

7.50–7.34(m, 10H), 7.24–7.13(m, 4H)，5.16–5.08(m, 4H); ¹³C NMR (75 MHz, CDCl₃)

δ 170.1, 153.0, 138.0, 135.4, 128.3, 128.0, 126.9, 125.7, 124.6, 122.8, 121.4, 47.8,

46.3. HRMS (ESI) calcd for C₃₂H₂₂N₂S₂([M + H]⁺) 475.1302, found 475.1299.

4.5.20 (E)-1-methyl-2-styryl-1H-benzo[d]imidazole. Yellow solid; m.p. 107–109 ^oC

(lit.,114 °C)^[17d]; ¹H NMR (300 MHz, CDCl₃): δ 7.97(d, J = 15.9 Hz, 1H), 7.77 (d, J =

7.2 Hz, 1H), 7.62(d, J = 6.9 Hz, 2H), 7.43–7.29 (m, 6H), 7.10(d, J = 15.9 Hz, 1H),

13

3.85(s, 3H). C NMR (75 MHz, CDCl₃): δ 151.1, 143.1, 137.3, .136.0, 129.1, 128.9,

127.3, 122.7, 122.6, 119.3, 112.9, 109.2, 29.8.

4.5.21 (E)-1-methyl-2-(4-methylstyryl)-1H-benzo[d]imidazole. White solid; m.p.

136–139^oC; ¹H NMR (300 MHz, CDCl₃): δ 7.96(d, J = 15.9, 1H), 7.78(d, J = 6.3 Hz,

1H), 7.52(d, J = 7.8 Hz, 2H), 7.29–7.28(m, 3H), 7.21(d, J = 7.8 Hz, 2H), 7.04(d, J =

15.9, 1H), 3.82(s, 3H), 2.39(s, 3H); ¹³C NMR (75 MHz, CDCl₃): δ 151.3, 143.1,

137.3, 136.0, 133.3, 129.6, 127.2, 122.6, 122.4, 119.2, 111.9, 109.1, 29.7, 21.4.

ACCEPTED MANUSCRIPT

HRMS (ESI) calcd for C₁₇H₁₇N₂([M + H]⁺)249.1392, found 249.1388.

4.5.22 (E)-2-(4-chlorostyryl)-1-methyl-1H-benzo[d]imidazole. White solid; m.p.

1

145–146^oC; H NMR (300 MHz, CDCl₃): δ 7.91(d, J = 15.6 Hz, 1H), 7.78–7.76 (m,

1H), 7.52(d, J = 8.1 Hz, 2H), 7.36(d, J = 8.4 Hz, 2H), 7.30–7.27 (m, 3H), 7.05(d, J =

15.9 Hz, 1H), 3.84(s, 3H). ¹³C NMR (75 MHz, CDCl₃): δ 150.7, 143.0, 136.0, 135.8,

134.8, 134.4, 129.3, 129.1, 128.5, 128.4, 122.8, 122.7, 119.3, 113.4, 109.3, 29.8.

HRMS (ESI) calcd for C₁₆H₁₄N₂Cl ([M + H]⁺)269.0845, found 269.0840.

Acknowledgements

We gratefully appreciate the National Natural Science Foundation of China (NSFC

Nos. 20972002, 21171006, 21272006) for financial support.

Supplementary data

Supplementary data related to this article can be found at

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Supporting Information

Nano CuO Catalyzed C–H Functionalization of 1, 3-Azoles with

Bromoarenes and Bromoalkenes

Wu Zhang,* Yujie Tian, Na Zhao, Yuanyuan Wang, Jia Li, Zhenghua Wang*

Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Laboratory of

Molecule-Based Materials, College of Chemistry and Materials Science, Anhui Normal University,

Wuhu 241000, People’s Republic of China.

Fax: (+86)553-3883-510

E-mail: zhangwu@mail.ahnu.edu.cn; zhwang@mail.ahnu.edu.cn

Contents

¹H NMR and ¹³C NMR spectra of the desired products………………..……..S2-S22

S1

ACCEPTED MANUSCRIPT

2-Phenylbenzo[d]oxazole（¹H NMR 300 MHz, CDCl₃)

2-Phenylbenzo[d]oxazole（¹³C NMR 75 MHz, CDCl₃)

S2

ACCEPTED MANUSCRIPT

2-(p-Tolyl)benzo[d]oxazole (¹H NMR 300 MHz, CDCl₃)

2-(p-Tolyl)benzo[d]oxazole（¹³C NMR 75 MHz, CDCl₃)

S3

ACCEPTED MANUSCRIPT

2-(pyridin-3-yl)benzo[d]oxazole (¹H NMR 300 MHz, CDCl₃)

2-(pyridin-3-yl)benzo[d]oxazole (¹³C NMR 75 MHz, CDCl₃)

S4

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5-chloro-2-phenylbenzo[d]oxazole (¹H NMR 300 MHz, CDCl₃)

5-chloro-2-phenylbenzo[d]oxazole (¹³C NMR 75 MHz, CDCl₃)

S5

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5-chloro-2-(pyridin-3-yl)benzo[d]oxazole (¹H NMR 300 MHz, CDCl₃)

5-chloro-2-(pyridin-3-yl)benzo[d]oxazole (¹³C NMR 75 MHz, CDCl₃)

S6

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5-methyl-2-phenylbenzo[d]oxazole (¹H NMR 300 MHz, CDCl₃)

5-methyl-2-phenylbenzo[d]oxazole (¹³C NMR 75 MHz, CDCl₃)

S7

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2-Phenylbenzo[d]thiazole (¹H NMR 300 MHz, CDCl₃)

2-Phenylbenzo[d]thiazole (¹³C NMR 75 MHz, CDCl₃)

S8

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2-(p-Tolyl)benzo[d]thiazole (¹H NMR 300 MHz, CDCl₃)

2-(p-Tolyl)benzo[d]thiazole (¹³C NMR 75 MHz, CDCl₃)

S9

Article Doi

Nano CuO-catalyzed C-H functionalization of 1,3-azoles with bromoarenes and bromoalkenes

DOI: 10.1016/j.tet.2014.04.065

Source and publish data:

Authors:

Article abstract of DOI:10.1016/j.tet.2014.04.065

Full text of DOI:10.1016/j.tet.2014.04.065

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