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Synthesis 2013; 45(4): 501-506
DOI: 10.1055/s-0032-1317957
paper
© Georg Thieme Verlag Stuttgart · New York

Copper-Catalyzed Synthesis of 2-Arylbenzoxazoles in Tetrabutylammonium Bromide

Md Ashif Ali
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India   Fax: +91(361)2690762   Email: tpunni@iitg.ernet.in
,
Mamta Suri
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India   Fax: +91(361)2690762   Email: tpunni@iitg.ernet.in
,
Tharmalingam Punniyamurthy*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India   Fax: +91(361)2690762   Email: tpunni@iitg.ernet.in
› Author Affiliations
Further Information

Publication History

Received: 16 October 2012

Accepted after revision: 07 December 2012

Publication Date:
10 January 2013 (online)

 
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Abstract

Copper-catalyzed synthesis of 2-arylbenzoxazoles from 1-bromo-2-iodobenzenes and benzamides in tetrabutylammonium bromide is described.


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Key words

2-arylbenzoxazoles - heterocycles - copper - catalysis - tetrabutylammonium bromide

Benzoxazole is an important structural motif found in many compounds that exhibit interesting biological, medicinal, and material properties (Figure [1]).[1] [2] [3] For example, benzoxazole derivatives are characterized as 5-HT3 receptor agonist,[ 2a ] HIV reverse transcriptase inhibitor L-697,661,[ 2b ] peroxisome proliferator-activated receptor γ antagonist JTP-426467,[ 2c ] anticancer agent NSC-693638,[ 2d ] orexin-1 receptor antagonist SB-334867,[ 2e ] estrogen receptor-β agonist ERB-041,[ 2f ] and Rho kinase inhibitors.[ 2g ] In addition, compounds with benzoxazole core structures are well known to exhibit antimicrobial,[ 3a ] antibacterial,[ 3b ] and anti-inflammatory[ 3c ] activities, and are used to treat immune diseases,[ 3d ] cerebral ischemia,[ 3e ] and duchenne muscular dystrophy.[ 3f ] Benzoxazoles are also used as fluorescent whitening dyes.[ 3g ]

Zoom Image
Figure 1 Examples of biologically active benzoxazoles

Traditionally, the synthesis of benzoxazole has been carried out from o-aminophenols by condensation either with carboxylic acids[ 4 ] or aldehydes, followed by oxidative cyclization.[ 5 ] However, these methods are often limited by the unavailability of suitably substituted substrate precursors and sometimes by the requirement of strong acids and elevated temperatures. Some of these limitations have been overcome by the recent developments in coupling and C–H functionalization reactions utilizing transition metal catalysis that function under relatively milder conditions (Scheme [1]).[6] [7]

Zoom Image
Scheme 1 Modern methods for benzoxazole synthesis

Copper- and iron-catalyzed cyclization of 2-haloanilides via intramolecular C–O cross-coupling has been shown.[6c] [d] [e] [f] , [7a] [b] The copper-based catalytic system has also been studied for domino C–N and C–O cross-coupling reactions of 1,2-dihalobenzenes with arylamides.[6a] [b] More recently, bisaryloxime ethers and arylanilides have been converted into benzoxazoles by use of copper(II) triflate that functions by a C–H functionalization process.[6g] [7c] [d] These reactions have been carried out in organic solvents or water.

The use of molten salts for organic synthesis has been an active topic because of their excellent thermal stability and low vapor pressure.[ 8 ] Tetrabutylammonium bromide is often used as an additive and reaction medium for organic synthesis.[ 9 ] Herein, we report the synthesis of 2-arylbenzoxazoles from 1-bromo-2-iodobenzenes and arylamides in the presence of copper(I) iodide in tetrabutylammonium bromide. The latter plays a dual role, as reaction medium as well as to facilitate the formation of the copper(II) oxide nanoparticles that act as the catalyst.[10] [11] The procedure does not require a volatile organic medium or the addition of external chelating ligands, and provides the target products in moderate to good yield.

First, the reaction conditions were optimized by employing 4-methoxybenzamide and 1-bromo-2-iodobenzene as model substrates (Table [1]). The reaction occurred to afford the target molecule, 2-(4-methoxyphenyl)benzoxazole, in 65% yield when a mixture of the substrates, copper(I) iodide (10 mol%), potassium hydroxide (2.5 equiv), and tetrabutylammonium bromide (2 equiv) was stirred at 110 °C under air. Decreasing the amount of catalyst (5 mol%) or the temperature (100 °C) led to the formation of the target product in 45% yield. The reaction with potassium hydroxide was superior to that with cesium carbonate or potassium carbonate as base. A control experiment in which the reaction was carried out in the absence of copper(I) iodide confirmed that the target molecule was not formed and the starting material was recovered intact.

Table 1 Optimization of the Reaction Conditionsa

Entry

Base (equiv)

Yield (%)b

1

KOH (2)

51

2

KOH (2.5)

65

3

Cs2CO3 (2.5)

17

4

K2CO3(2.5)

22

5c

KOH (2.5)

45

6d

KOH (2.5)

45

7e

KOH (2.5)

n.d.f

a Reagents and conditions: 4-methoxybenzamide (1.0 mmol), 1-bromo-2-iodobenzene (1.0 mmol), CuI (10 mol%), TBAB (2.0 mmol), 110 °C, 24 h, air.

b Isolated yield.

c Reaction was carried out at 100 °C.

d Reaction was carried out with 5 mol% catalyst.

e Without CuI.

f Not determined.

Next, the scope of the procedure was studied for the reactions of a series of substituted benzamides and 1-bromo-2-iodobenzenes (Table [2]). The reactions of 1-bromo-2-iodobenzene with benzamide and 2-methyl-, 3-chloro-, 3-methyl-, 4-bromo-, 4-chloro-, 4-methoxy-, and 4-methyl-substituted benzamides provided benzoxazoles 2a–h in 53–75% yield. Similarly, the reactions of benzamide with 1-bromo-2-iodobenzene substituted with 5-isopropyl, 5-methoxy, and 5-methyl groups gave benzoxazoles 2i–k in 43–68% yield. Likewise, 1-bromo-2-iodo-5-isopropylbenzene reacted with 4-bromo-, 4-methoxy-, and 4-methyl-substituted benzamides to afford the target products 2l–n in 56–71% yield. In addition, 1-bromo-2-iodo-5-meth­oxybenzene and 1-bromo-2-iodo-5-methylbenzene reacted with 4-bromo, 4-methoxy, and 4-methyl-substituted benzamides to provide benzoxazoles 2o–r in 49–65% yield. However, the reaction does not proceed with aliphatic amides such as propanamide under these conditions, and the starting material was recovered intact.

Table 2 Reaction of 1-Bromo-2-iodobenzenes with Amidesa

Entry

R1

R2

Product

Yield (%)b

 1

H

H

2a

61

 2

H

2-Me

2b

75

 3

H

3-Cl

2c

57

 4

H

3-Me

2d

67

 5

H

4-Br

2e

55

 6

H

4-Cl

2f

53

 7

H

4-OMe

2g

65

 8

H

4-Me

2h

60

 9

5-i-Pr

H

2i

68

10

5-OMe

H

2j

43

11

5-Me

H

2k

56

12

5-i-Pr

4-Br

2l

56

13

5-i-Pr

4-OMe

2m

62

14

5-i-Pr

4-Me

2n

71

15

5-OMe

4-Me

2o

49

16

5-Me

4-Br

2p

50

17

5-Me

4-OMe

2q

63

18

5-Me

4-Me

2r

65

a Reaction conditions: Benzamide (1.0 mmol), 1-bromo-2-iodobenzene (1.0 mmol), CuI (10 mol%), KOH (2.5 mmol), TBAB (2.0 mmol), 110 °C, 24 h, air.

b Isolated yield.

Zoom Image
Figure 2 TEM and powder X-ray analyses of the isolated copper(II) oxide nanoparticles

To reveal the nature of the active catalyst, the catalyst was isolated after the reaction, and characterized by powder X-ray and transmission electron microscopy (TEM) analyses (Figure [2]). The observed results suggest that copper(I) iodide undergoes reaction with potassium hydroxide to give copper(II) oxide nanoparticles[ 10 ] that catalyze the reaction (Scheme [2]).

In summary, the synthesis of 2-arylbenzoxazoles by using copper catalysis in tetrabutylammonium bromide has been described. Tetrabutylammonium bromide plays a dual role, as a reaction medium as well as stabilizer of the active copper(II) oxide nanoparticles that are formed during the reaction.[10] [11] The active catalyst has been isolated and characterized by TEM and powder X-ray analysis to be copper(II) oxide nanoparticles.

Zoom Image
Scheme 2

CuI, aryl halides, and amides were purchased from Aldrich and used without further purification. The column chromatography was performed with Rankem silica gel (60–120 mesh). NMR spectra (400 MHz for 1H and 100 MHz for 13C) were recorded using a DRX-400 Varian spectrometer and CDCl3 as solvent with TMS as an internal standard. Chemical shifts (δ) are reported in ppm and spin-spin coupling constants (J) are given in Hz. Melting points were determined by using a Buchi B-540 melting point apparatus and are uncorrected. FT-IR spectra were recorded on a Perkin-Elmer­ IR spectrometer. Elemental analyses were recorded by using a Perkin Elmer CHNS analyzer.


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2-Arylbenzoxazoles; General Procedure

A mixture of the amide (1.0 mmol), the 1-bromo-2-iodobenzene (1.0 mmol), CuI (10 mol%), KOH (2.5 mmol), and TBAB (2.0 mmol) was stirred at 110 °C under air. The progress of the reaction was monitored by TLC. Upon completion of the reaction, the mixture was cooled to r.t. and then diluted with EtOAc (10 mL). The resulting soln was washed with H2O (2 × 10 mL). Drying (Na2SO4) and evaporation of the solvent gave a residue that was purified by column chromatography (silica gel, EtOAc–hexane, 1:99 to 10:90).


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2-Phenylbenzoxazole (2a)[ 6c ]

Colorless solid; yield: 0.119 g (61%); mp 101–102 °C (Lit.[ 6c ] 101–102 °C).

IR (KBr): 3060, 2961, 1616, 1552, 1472, 1447, 1344, 1241, 1196, 1052, 1022, 942 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.26–8.23 (m, 2 H), 7.78–7.75 (m, 1 H), 7.58–7.55 (m, 1 H), 7.53–7.50 (m, 3 H), 7.36–7.32 (m, 2 H).

13C NMR (100 MHz, CDCl3): δ = 162.9, 150.7, 142.1, 131.4, 128.8, 127.6, 127.1, 125.1, 124.5, 120.0, 110.6.

Anal. Calcd for C13H9NO: C, 79.98; H, 4.65; N, 7.17. Found: C, 80.05; H, 4.68; N, 7.12.


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2-(2-Methylphenyl)benzoxazole (2b)[ 6g ]

Yellow solid; yield: 0.157 g (75%); mp 63–64 °C (Lit.[ 6g ] 63–65 °C).

IR (KBr): 2950, 1614, 1547, 1485, 1451, 1262, 1240, 1205, 1145, 1108, 1028, 920 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.17 (d, J = 7.6 Hz, 1 H), 7.80–7.78 (m, 1 H), 7.59–7.56 (m, 1 H), 7.40–7.31 (m, 5 H), 2.80 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 163.4, 150.3, 142.2, 138.9, 131.9, 130.9, 130.0, 126.3, 126.1, 125.1, 124.4, 120.2, 110.5, 22.4.

Anal. Calcd for C14H11NO: C, 80.36; H, 5.30; N, 6.69. Found: C, 80.41; H, 5.28; N, 6.65.


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2-(3-Chlorophenyl)benzoxazole (2c)[ 7c ]

Colorless solid; yield: 0.131 g (57%); mp 122–123 °C (Lit.[ 7c ] 122 °C).

IR (KBr): 2961, 1638, 1616, 1549, 1465, 1452, 1433, 1261, 1240, 1073, 1049, 928 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.24 (t, J = 2.0 Hz, 1 H), 8.14–8.11 (m, 1 H), 7.78–7.75 (m, 1 H), 7.59–7.56 (m, 1 H), 7.50–7.42 (m, 2 H), 7.38–7.35 (m, 2 H).

13C NMR (100 MHz, CDCl3): δ = 161.8, 151.0, 142.1, 135.3, 131.6, 130.4, 129.1, 127.8, 125.8, 125.7, 125.0, 120.4, 110.9.

Anal. Calcd for C13H8ClNO: C, 67.99; H, 3.51; N, 6.10. Found: C, 68.06; H, 3.48; N, 6.14.


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2-(3-Methylphenyl)benzoxazole (2d)[ 12a ]

Yellow solid; yield: 0.14 g (67%); mp 80–81 °C (Lit.[ 12a ] 79–80 °C).

IR (KBr): 2962, 1718, 1618, 1552, 1487, 1453, 1261, 1245, 1093, 1020, 919 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.09 (s, 1 H), 8.05 (d, J = 7.6 Hz, 1 H), 7.77–7.74 (m, 1 H), 7.58–7.56 (m, 1 H), 7.40 (t, J = 8.0 Hz, 1 H), 7.36–7.31 (m, 3 H), 2.44 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 163.4, 150.9, 142.3, 138.9, 132.5, 129.0, 128.3, 127.2, 125.2, 124.9, 124.7, 120.1, 110.7, 21.5.

Anal. Calcd for C14H11NO: C, 80.36; H, 5.30; N, 6.69. Found: C, 80.43; H, 5.32; N, 6.73.


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2-(4-Bromophenyl)benzoxazole (2e)[ 6c ]

Colorless solid; yield: 0.151 g (55%); mp 156–157 °C (Lit.[ 6c ] 157–158 °C).

IR (KBr): 2924, 1615, 1592, 1547, 1484, 1452, 1400, 1342, 1294, 1261, 1244, 1176, 1107, 1069, 1052, 1009 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.12–8.09 (m, 2 H), 7.76–7.74 (m, 1 H), 7.67–7.64 (m, 2 H), 7.57–7.55 (m, 1 H), 7.36–7.34 (m, 2 H).

13C NMR (100 MHz, CDCl3): δ = 162.3, 150.9, 142.2, 132.4, 129.2, 126.4, 126.3, 125.6, 124.9, 120.3, 110.8.

Anal. Calcd for C13H8BrNO: C, 56.96; H, 2.94; N, 5.11. Found: C, 56.90; H, 2.91; N, 5.07.


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2-(4-Chlorophenyl)benzoxazole (2f)[ 6g ]

Colorless solid; yield: 0.122 g (53%); mp 151–152 °C (Lit.[ 6g ] 152–153 °C).

IR (KBr): 1635, 1617, 1484, 1452, 1405, 1244, 1091, 1055, 1011, 925 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.19–8.16 (m, 2 H), 7.76–7.74 (m, 1 H), 7.57–7.55 (m, 1 H), 7.50–7.47 (m, 2 H), 7.37–7.34 (m, 2 H).

13C NMR (100 MHz, CDCl3): δ = 162.1, 150.8, 142.1, 137.8, 129.3, 128.9, 125.7, 125.4, 124.8, 120.2, 110.7.

Anal. Calcd for C13H8ClNO: C, 67.99; H, 3.51; N, 6.10. Found: C, 67.94; H, 3.53; N, 6.06.


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2-(4-Methoxyphenyl)benzoxazole (2g)[ 6c ]

Colorless solid; yield: 0.146 g (65%); mp 97–98 °C (Lit.[ 6c ] 97–98 °C).

IR (KBr): 2958, 2924, 2853, 1618, 1605, 1504, 1471, 1454, 1421, 1257, 1243, 1188, 1169, 1019 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.19 (dd, J = 1.6, 6.8 Hz, 2 H), 7.73–7.71 (m, 1 H), 7.55–7.52 (m, 1 H), 7.32–7.29 (m, 2 H), 7.02 (dd, J = 2.0, 6.8 Hz, 2 H), 3.87 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 163.3, 162.4, 150.8, 142.4, 129.5, 124.7, 124.5, 119.8, 119.7, 114.5, 110.5, 55.5.

Anal. Calcd for C14H11NO2: C, 74.65; H, 4.92; N, 6.22. Found: C, 74.72; H, 4.94; N, 6.18.


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2-(4-Methylphenyl)benzoxazole (2h)[ 7a ]

Colorless solid; yield: 0.126 g (60%); mp 115–116 °C (Lit.[ 7a ] 116 °C).

IR (KBr): 2961, 2917, 1635, 1622, 1500, 1450, 1407, 1259, 1243, 1172, 1108, 1054, 1015 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.14 (dd, J = 2.0, 6.8 Hz, 2 H), 7.75–7.73 (m, 1 H), 7.57–7.54 (m, 1 H), 7.34–7.30 (m, 4 H), 2.42 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 163.5, 150.9, 142.4, 142.2, 129.8, 127.8, 125.0, 124.7, 124.6, 120.0, 110.7, 21.8.

Anal. Calcd for C14H11NO: C, 80.36; H, 5.30; N, 6.69. Found: C, 80.32; H, 5.33; N, 6.64.


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6-Isopropyl-2-phenylbenzoxazole (2i)

Yellow liquid; yield: 0.159 g (68%).

IR (neat): 2962, 1622, 1555, 1484, 1450, 1432, 1323, 1260, 1096, 1052, 1024, 923 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.24–8.20 (m, 2 H), 7.67 (d, J = 8.0 Hz, 1 H), 7.54–7.47 (m, 3 H), 7.44 (d, J = 1.6 Hz, 1 H), 7.23 (dd, J = 1.6, 8.0 Hz, 1 H), 3.08–3.01 (m, 1 H), 1.32 (d, J = 6.8 Hz, 6 H).

13C NMR (100 MHz, CDCl3): δ = 162.8, 151.2, 147.1, 140.3, 131.4, 129.0, 127.6, 123.6, 119.6, 108.2, 34.6, 24.5.

Anal. Calcd for C16H15NO: C, 80.98; H, 6.37; N, 5.90. Found: C, 81.06; H, 6.39; N, 5.86.


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6-Methoxy-2-phenylbenzoxazole (2j)[ 12b ]

Gray solid; yield: 0.097 g (43%); mp 76–77 °C (Lit.[ 12b ] 75–76 °C).

IR (KBr): 2961, 1619, 1555, 1487, 1449, 1433, 1347, 1321, 1144, 1128, 1097, 1052, 1022, 920 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.20–8.17 (m, 2 H), 7.63 (d, J = 8.8 Hz, 1 H), 7.50–7.48 (m, 3 H), 7.10 (d, J = 2.4 Hz, 1 H), 6.96 (dd, J = 2.4, 8.8 Hz, 1 H), 3.87 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 162.4, 158.5, 151.8, 136.1, 131.2, 129.0, 127.5, 127.4, 120.2, 113.0, 95.6, 56.1.

Anal. Calcd for C14H11NO2: C, 74.65; H, 4.92; N, 6.22. Found: C, 74.70; H, 4.90; N, 6.25.


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6-Methyl-2-phenylbenzoxazole (2k)[ 7a ]

Colorless solid; yield: 0.117 g (56%); mp 92–93 °C (Lit.[ 7a ] 93 °C).

IR (KBr): 3054, 2961, 2917, 2857, 1626, 1615, 1552, 1476, 1448, 1336, 1261, 1097, 1072, 1050, 1020 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.23–8.21 (m, 2 H), 7.63 (d, J = 8.0 Hz, 1 H), 7.52–7.49 (m, 3 H), 7.37 (d, J = 0.8 Hz, 1 H), 7.16 (d, J = 7.6 Hz, 1 H), 2.49 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 162.7, 151.2, 140.1, 135.7, 131.4, 129.0, 127.6, 125.9, 119.5, 110.9, 21.9.

Anal. Calcd for C14H11NO: C, 80.36; H, 5.30; N, 6.69. Found: C, 80.30; H, 5.27; N, 6.74.


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2-(4-Bromophenyl)-6-isopropylbenzoxazole (2l)

Gray solid; yield: 0.177 g (56%); mp 101–102 °C.

IR (KBr): 2960, 2923, 2868, 1721, 1635, 1614, 1591, 1546, 1479, 1432, 1397, 1261, 1102, 1067, 1045 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.09–8.06 (m, 2 H), 7.66–7.62 (m, 3 H), 7.42 (t, J = 0.8 Hz, 1 H), 7.24–7.21 (m, 1 H), 3.06–3.01 (m, 1 H), 1.31 (d, J = 7.2 Hz, 6 H).

13C NMR (100 MHz, CDCl3): δ = 162.0, 151.3, 147.5, 140.3, 132.4, 129.0, 126.5, 126.1, 123.9, 119.7, 108.3, 34.7, 24.5.

Anal. Calcd for C16H14BrNO: C, 60.78; H, 4.46; N, 4.43. Found: C, 60.83; H, 4.48; N, 4.40.


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6-Isopropyl-2-(4-methoxyphenyl)benzoxazole (2m)

Yellow solid; yield: 0.166 g (62%); mp 47–48 °C.

IR (KBr): 2956, 1618, 1579, 1557, 1455, 1434, 1420, 1382, 1363, 1318, 1305, 1251, 1183, 1170, 1128, 1116, 1061, 1051, 1029, 937, 920 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.17 (dd, J = 1.6, 6.8 Hz, 2 H), 7.62 (d, J = 8.4 Hz, 1 H), 7.40 (d, J = 1.2 Hz, 1 H), 7.20 (dd, J = 1.6, 8.4 Hz, 1 H), 7.01 (dd, J = 2.0, 6.8 Hz, 2 H), 3.87 (s, 3 H), 3.07–3.00 (m, 1 H), 1.31 (d, J = 6.8 Hz, 6 H).

13C NMR (100 MHz, CDCl3): δ = 162.9, 162.3, 151.1, 146.5, 140.5, 129.3, 123.4, 120.1, 119.2, 114.4, 108.0, 55.4, 34.5, 24.5.

Anal. Calcd for C17H17NO2: C, 76.38; H, 6.41; N, 5.24. Found: C, 76.44; H, 6.38; N, 5.28.


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6-Isopropyl-2-(4-methylphenyl)benzoxazole (2n)

Yellow solid; yield: 0.178 g (71%); mp 51–52 °C.

IR (KBr): 2947, 1619, 1499, 1482, 1431, 1320, 1258, 1179, 1094, 1050, 1014, 938, 922 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.12–8.09 (m, 2 H), 7.65 (d, J = 7.6 Hz, 1 H), 7.42 (t, J = 0.8 Hz, 1 H), 7.31 (d, J = 8.0 Hz, 2 H), 7.22 (dd, J = 1.6, 8.0 Hz, 1 H), 3.08–3.01 (m, 1 H), 2.42 (s, 3 H), 1.31 (d, J = 7.2 Hz, 6 H).

13C NMR (100 MHz, CDCl3): δ = 163.1, 151.2, 146.8, 141.9, 140.4, 129.7, 127.5, 124.8, 123.5, 119.4, 108.1, 34.6, 24.5, 21.7.

Anal. Calcd for C17H17NO: C, 81.24; H, 6.82; N, 5.57. Found: C, 81.31; H, 6.84; N, 5.52.


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6-Methoxy-2-(4-methylphenyl)benzoxazole (2o)

Gray solid; yield: 0.117 g (49%); mp 83–84 °C.

IR (KBr): 2961, 1627, 1503, 1487, 1462, 1410, 1433, 1347, 1261, 1214, 1143, 1126, 1096, 1019 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.08 (d, J = 8.4 Hz, 2 H), 7.61 (d, J = 8.8 Hz, 1 H), 7.30 (d, J = 8.0 Hz, 2 H), 7.09 (d, J = 2.4 Hz, 1 H), 6.94 (dd, J = 2.4, 8.4 Hz, 1 H), 3.86 (s, 3 H), 2.41 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 162.7, 158.3, 151.7, 141.7, 136.1, 129.8, 127.4, 124.8, 120.0, 112.8, 95.6, 56.1, 21.8.

Anal. Calcd for C15H13NO2: C, 75.30; H, 5.48; N, 5.85. Found: C, 75.25; H, 5.45; N, 5.82.


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2-(4-Bromophenyl)-6-methylbenzoxazole (2p)

Colorless solid; yield: 0.144 g (50%); mp 157–158 °C.

IR (KBr): 1636, 1478, 1396, 1261, 1245, 1147, 1097, 1049, 1005 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.08–8.05 (m, 2 H), 7.64–7.60 (m, 3 H), 7.35 (s, 1 H), 7.17 (d, J = 8.0 Hz, 1 H), 2.49 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 161.8, 151.2, 140.0, 136.1, 132.3, 129.0, 126.4, 126.2, 119.6, 111.0, 22.0.

Anal. Calcd for C14H10BrNO: C, 58.36; H, 3.50; N, 4.86. Found: C, 58.31; H, 3.48; N, 4.81.


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2-(4-Methoxyphenyl)-6-methylbenzoxazole (2q)[ 12c ]

Yellow solid; yield: 0.151 g (63%); mp 91–92 °C (Lit.[ 12c ] 90–91°C).

IR (KBr): 2918, 1619, 1604, 1504, 1457, 1437, 1420, 1336, 1321, 1305, 1288, 1260, 1248, 1185, 1176, 1121, 1059, 1024, 941, 920 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.16 (dd, J = 2.0, 6.8 Hz, 2 H), 7.59 (d, J = 8.0 Hz, 1 H), 7.34 (d, J = 0.8 Hz, 1 H), 7.13 (d, J = 8.0 Hz, 1 H), 7.01 (dd, J = 2.0, 6.8 Hz, 2 H), 3.87 (s, 3 H), 2.48 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 162.9, 162.3, 151.1, 140.2, 135.2, 129.4, 125.8, 120.1, 119.1, 114.5, 110.8, 55.6, 21.9.

Anal. Calcd for C15H13NO2: C, 75.30; H, 5.48; N, 5.85. Found: C, 75.34; H, 5.50; N, 5.88.


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6-Methyl-2-(4-methylphenyl)benzoxazole (2r)[ 12c ]

Yellow solid; yield: 0.145 g (65%); mp 102–103 °C (Lit.10c 103–104 °C).

IR (KBr): 3050, 2924, 1619, 1555, 1500, 1479, 1408, 1335, 1250, 1173, 1116, 1053, 1015, 940, 925 cm–1.

1H NMR (400 MHz, CDCl3): δ = 8.11 (d, J = 8.0 Hz, 2 H), 7.61 (d, J = 8.4 Hz, 1 H), 7.35 (s, 1 H), 7.31 (d, J = 8.0 Hz, 2 H), 7.14 (d, J = 8.0 Hz, 1 H), 2.48 (s, 3 H), 2.41 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 163.0, 151.1, 141.9, 140.1, 135.4, 129.8, 127.6, 125.8, 124.7, 119.3, 110.8, 22.0, 21.8.

Anal. Calcd for C15H13NO: C, 80.69; H, 5.87; N, 6.27. Found: C, 80.75; H, 5.89; N, 6.30.


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Acknowledgment

This work was supported by the Department of Science and Technology, New Delhi, and the Council of Scientific and Industrial Research, New Delhi.

Supporting Information

    for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/ejournals/toc/synthesis.
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Figure 1 Examples of biologically active benzoxazoles
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Scheme 1 Modern methods for benzoxazole synthesis
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Figure 2 TEM and powder X-ray analyses of the isolated copper(II) oxide nanoparticles
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Scheme 2