Aerobic oxidative bromination of arenes using an ionic liquid as both the catalyst and the solvent

Accepted Manuscript Aerobic Oxidative Bromination of Arenes Using an Ionic Liquid as both the Catalyst and the Solvent Yun-Lai Ren, Binyu Wang, Xin-Zhe Tian, Shuang Zhao, Jianji Wang PII: DOI: Reference:

S0040-4039(15)30191-X http://dx.doi.org/10.1016/j.tetlet.2015.09.150 TETL 46822

To appear in:

Tetrahedron Letters

Received Date: Revised Date: Accepted Date:

3 August 2015 27 September 2015 30 September 2015

Please cite this article as: Ren, Y-L., Wang, B., Tian, X-Z., Zhao, S., Wang, J., Aerobic Oxidative Bromination of Arenes Using an Ionic Liquid as both the Catalyst and the Solvent, Tetrahedron Letters (2015), doi: http://dx.doi.org/ 10.1016/j.tetlet.2015.09.150

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Aerobic Oxidative Bromination of Arenes Using an Ionic Liquid as both the Catalyst and the Solvent Yun-Lai Ren, Binyu Wang, Xin-Zhe Tian, Shuang Zhao, Jianji Wang* School of Chemical Engineering & Pharmaceutics, Henan University of Science and Technology, Luoyang, Henan 471003, P. R. China. School of Chemistry and chemical Engineering, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan 453007, P. R. China.

ABSTRACT A method for the bromination of alkoxy-substituted benzenes and naphthalines was developed by using the residual oxygen in the reaction tube as the oxidant, and [Bmim]NO3 (1-butyl-3-methylimidazolium nitrate) ionic liquid as both the catalyst and the solvent. No other reagent apart from the ionic liquid and molecular bromine was used in the reactions, and basically all the bromine atoms in the bromine source were transferred to the bromination products, showing that the presented protocol is highly atom economic and practical.

Keywords: Bromination Arenes Ionic liquid Catalysis.

* Corresponding author. Tel.: 86-379-64232156 ; Fax: 86-379-64210415. E-mail address: [email protected] (J. Wang).

Bromination of arenes is an important chemical transformation1 because the resulting products often serve as the electrophilic coupling partner for the cross-coupling reactions to synthesize various classes of organic compounds.2 Therefore, considerable effort has been devoted to the development of various effective

brominating

reagent

systems,

e.g.

bromide

salts/oxidant,3

N-bromosuccinimide4 as well as other fantastic and expensive bromonium equivalents.5 By all appearances, the use of bromide salts as the brominating reagent leads to low atom economy due to the fact that metal elements in bromide salts cannot transfer to the bromination product. The reactions using the bromonium equivalents such as N-bromosuccinimide also suffer from the inherent disadvantages including low atom economy and expensive brominating reagent. Another alternative brominating reagent is the inexpensive and readily available molecular bromine.6 However, the classical bromination methods with molecular bromine suffer from poor atom economy: up to 50% bromine atoms is transferred to the bromination product and the resulting HBr by-product not only wastes raw material, but also pollutes the environment. One of the effective solutions to this situation is the oxidative strategy where the resulting HBr by-product is in-situ oxidated to reactive bromine species in the presence of oxidant.7 From the environmental and economic perspectives, molecular oxygen (especially in its diluted form, air) is the most ideal oxidizer,8 which prompts chemists to develop various aerobic methods for the bromination of arenes using Fe2O3/zeolite,8 CeO2 nanoparticles,9 copper salts,10 9-mesityl-10-methylacridinium ion,11 sodium nitrite,12 2

RuCl3·xH2O,13 H5PMo10V2O4014 or NH4VO315 as the catalyst. In a previous work, we have developed an aerobic method for the iodination with nitrogen dioxide as the catalyst and acetonitrile as the solvent.[12b] Considering the fact that the use of toxic nitrogen dioxide catalyst and the evaporable solvent is easy to lead to environmental pollution, our attention is turned to developing a more clean procedure for the aerobic bromination of arenes by using ionic liquid as both the catalyst and solvent, and the results are herein reported. Compared with the previous procedure for the ionic liquid or sodium nitrite-catalyzed aerobic bromination of arenes,[7a,7b,3a] the notable advantage of this procedure is the absence of corrosive acid condition. Bromination of methoxybenzene was selected as a model reaction to initiate our investigation. As shown in Table 1 (entry 1), bromination of methoxybenzene gave 4-bromoanisole in 44% yield in the case of 0.5 equiv. Br2 and 1.5 mL acetonitrile solvent. Subsequently, various reaction conditions including reaction temperature, time and solvent were changed to increase the yield, but these attempts were unsuccessful because 50% of bromine atoms in the molecular bromine was theoretically converted to the unreactive Br- ion.16 In order to obtain a higher yield, we tried to add a catalytic amount of [Bmim]NO3 to catalyze the oxidation of the resulting unreactive Br- ion to reactive bromine species (Table 1, entries 3-5). For example, an addition of 10 mol% [Bmim]NO3 increased the yield from 44% to 90%. The residual oxygen in the reaction tube seemed to play a role of the oxidizing reagent. Indeed, the removal of oxygen from the reaction system led to a remarkable decrease in the yield (Table 1, entries 7,10). Since [Bmim]NO3 is often regarded to be a greener

3

solvent,17 acetonitrile was replaced by this ionic liquid as the solvent. The results shown in Table 1 (entry 6) revealed that [Bmim]NO3 was an effective solvent, and 86% yield was obtained by using this ionic liquid as the solvent. After discovering a suitable catalyst and solvent, we optimized other reaction conditions such as the loading of brominating reagent, the reaction temperature and time. It was shown that 0.5 equiv. Br2 was sufficient for the complete monobromination of methoxybenzene, and an increase of the brominating source loading amount led to a decrease of the monobromination yield due to the increase of dibromination by-product yield. The reaction required at a temperature as high as 80 o

C, and the yield of the desired product was decreased to 81% in the case of 60 oC.

Under the optimal condition, the monobromination of methoxybenzene occurred at the p-position related to the methoxy group with excellent selectivities (Scheme 1), and only small amount of ortho-bromination product was observed. Such an excellent regioselectivity was also observed in previous literatures16 where NaNO2-catalyzed bromination

of

arenes

was

investigated.

The

main

by-products

were

2,4-dibromoanisole (<2% yield) from the dibromination as well as 2-bromoanisole from the ortho-bromination. Another by-product was from the nitration of the benzene ring. A variety of representative phenyl rings were tested to examine the scope and limitation of the new bromination method. As seen from Table 2, many phenyl rings with alkoxy group underwent the bromination in moderate to high yields with excellent selectivities. Although the bromination of toluene often gives benzyl bromide in previous literature, 18 no benzyl bromide product was observed under our 4

experimental condition (Table 2, entries 2,4,5). Benzene, alkylbenzenes and several electron withdrawing group-substituted benzenes were less reactive (Table 2, entries 13,14,15). These results reveal that the scope of the presented bromination method was limited to more electron-rich phenyl rings in the case of the bromination of phenyl rings. Surprisingly, the benzene ring with amino group gave the bromination product in lower yield (Table 2, entry 12) although amino groups are also stronger electron-donating group. This result can be rationalized by assuming that the bromination reaction is incompatible with the alkaline character of amino groups. Indeed, the bromination of methoxybenzene gave the bromination product in poor yield in the presence of alkaline substances (Table 1, entry 11). We tried to examine the reaction with isobutylbenzene, phenylamine and phenol as the substrate, but the desired bromination products were obtained in low yields. Alkoxy group-substituted naphthalenes are also a kind of good substrates for the bromination, but naphthalene without activating group was not smoothly converted into α-bromonaphthalene (Table 2, entry 16). Bromination of 1-methoxynaphthalene occurred at the 4-position, while 2-ethoxynaphthalene was brominated at its 1-position (Table 2, entries 17, 18). The same site-selectivity was also reported in previous literatures19 where the electrophilic substitution of naphthalene rings was examined. Next, the bromination of several disubstituted or trisubstituted benzenes was investigated to extend the scope of the presented bromination method. As seen from Table 2, a series of ortho-, meta- and para-substituted alkoxybenzenes were brominated in moderate to high yields (Table 2, entries 3-8). The bromination occurred selectively at para-position of alkoxy group in the case of ortho- and meta-substituted alkoxybenzenes (Table 2, entries 3, 4), while para-substituted alkoxybenzene underwent ortho-bromination related to alkoxy group (Table 2, entry

5

5). The present procedure for bromination also allowed 1,2,3-trimethoxybenzene to be brominated with high selectivity (Table 2, entry 8). Interestingly, the bromination selectively occurred at the alkoxy-substituted benzene ring in the coexistence of alkoxy and alkyl benzene rings (Scheme 2). 1-Alkoxynaphthalene was preferentially brominated over naphthalene without substituted

group.

When

the

alkoxy-substituted

benzene

encountered

the

alkoxy-substituted naphthalene, the latter was selectively brominated. This offers an opportunity to the selective bromination of one alkoxy-substituted benzene or naphthalene ring in the case of the substrate containing two aromatic rings. For example, when benzyl phenyl ethers were employed as the substrates (Table 2, entries 9-11), only phenyl rings bonded to oxygen were functionalizated and no bromination occurred at the phenyl side of the benzyloxy moiety. Subsequently, our investigation was focused on the recycling of the catalyst with bromination of methoxybenzene as a model reaction. At the end of the reaction, the desired product was extracted with diethyl ether (3 × 5 mL). After the organic layer containing the product was separated, the recovered [Bmim]NO3 catalyst could be reused for seven times without a significant change relative to the catalytic activity (see Table S4 in the supporting information ). Finally, we were lost in thought about the reaction mechanism. It is known that molecular bromine is more reactive towards electron-rich aromatic compounds,6 which was also confirmed by the following experimental result: methoxybenzene was reacted with 0.5 equiv. molecular bromine to give 4-bromoanisole in 44% yield in the absence of catalyst (Table 1, entry 1). Thus it is reasonable to assume that the bromination starts with the reaction between benzene ring and molecular bromine to give the bromination product and HBr (Scheme 3).6 The resulting HBr is then

6

oxidated by the residual oxygen in the reaction tube to give reactive molecular bromine21 where [Bmim]NO3 possibly plays a role of catalyst precursor (Scheme 3). Indeed, bromination of methoxybenzene with HBr as the brominating reagent smoothly proceeded (Table 1, entry 7), while the bromination did not occur in the absence of [Bmim]NO3 (Table 1, entry 2). At the present stage, we can not confirm the real catalytic species, but it is possible that the real catalytic species was formed from the NO3- anion of [Bmim]NO3 because the bromination did not occur in some ionic liquids without NO3- anion (Table 1, entries 8,9). It is also possible that NO2/NO or NO+/NO pair served for the catalytic cycle upon the basis of previous literatures.20,21 In conclusion, a new procedure for the bromination of alkoxy-substituted benzenes and naphthalines was developed by using the residual oxygen in the reaction tube as the oxidant, and [Bmim]NO3 ionic liquid as both the catalyst and solvent. The presented method for the bromination has a highly atom economic character since basically all the atoms in the brominating reagent could be transferred to the bromination product. No other reagent apart from the ionic liquid and molecular bromine was used in the reactions, which suggests that the presented protocol is practical. The presented method allowed a series of alkoxy-substituted benzenes and naphthalines to be smoothly brominated in moderate to high yields with excellent selectivities. Compared with the previous procedure for ionic liquid or sodium nitrite-catalyzed aerobic bromination of arenes, [7a,7b,3a] the notable advantage of this procedure is that the corrosive acid is absent. Preliminary mechanistic investigation suggests that the bromination possibly starts with the reaction between benzene ring

7

and molecular bromine to give the bromination product and HBr. Then the resulting HBr is oxidated by the residual oxygen in the reaction tube to give reactive molecular bromine where [Bmim]NO3 possibly plays a role of catalyst precursor. Acknowledgments This work is sponsored by the Program for Science＆Technology Innovation Talents in Universities of Henan Province (Grant No.15HASTIT004) and the National Natural Science Foundation of China (Grant No. 21002023). Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:

.

References and notes 1 (a) Fujita, M.; Leveque, J.-M.; Komatsu, N.; Takahide, K. Ultrason Sonochem. 2015, 27, 247-251; (b) Schade, M.; Franzka, S.; Cappuccio, F.; Volker, P.; Angelika, H.; Nils, H. Appl. Surf. Sci. 2015, 336, 85-88; (c) Lyalin, B. V.; Petrosyan, V. A. Russ. J. Electrochem. 2013, 49, 497–529; (d) Kandepi, V. V. K. M.; Narender, N. Synthesis-Stuttgart 2012, 44, 15–26; (e) Zhang, G. F.; Wang, Y.; Ding, C. R.; Liu, R. H.; Liang, X. M. Chin. J. Org. Chem. 2011, 31, 804–813; (f) Andrievsky, A. M.; Gorelik, M. V. Russian Chem. Rev. 2011, 80, 421–428. 2 (a) Yang, Q. L.; Quan, Z. J.; Wu, S.; Du, B. X.; Wang, M. M.; Li, P. D.; Zhang, Y. P.; Wang, X. C. Tetrahedron 2015, 71, 6124-6134; (b) Zhao, J. J.; Li, P.; Xia C. G.; Li, F. W. Chem. Commun. 2014, 50, 4751-4754; (c) Zemtsova, M. N.; Kulemina, S. V.; Rybakov, V. B.; Klimochkin, Y. N. Russ. J. Org. Chem. 2015, 51, 636-639; (d) Pena-Lopez, M.; Sarandeses, L. A.; Sestelo, J. P. Eur. J. Org. Chem. 2013, 2545–2554; (e) Sore, H. F.; Galloway, W. R. J. D.; Spring, D. R. Chem. Soc. Rev. 2012, 41, 1845–1866; (f) Li, H. B.; Seechurn, C. C. C. J.; Colacot, T. J. ACS Catal. 2012, 2, 1147–1164. 3 (a) Delia, T. J.; Hood, R. J. Aust. J. Chem. 2015, 68, 254-255; (b) Kumar, L.; Mahajan, T.; Agarwal, D. D. Ind. Eng. Chem. Res. 2014, 53, 8321-8321; (c) Bhattacharya, M.; Cluff, D. B.; 8

Das, S. Inorg. Chem. Acta 2014, 423, 238-241; (d) Delia, T. J.; Hood, R. J. Aust. J. Chem. 2014, 68, 254-255; (e) Dey, R. R.; Dhar, S. S. Chinese Chem. Lett. 2013, 24, 866–868; (f) Naresh, M.; Kumar, M. A.; Reddy, M. M.; Swamy, P.; Nanubolu, J. B.; Narender, N. Synthesis-Stuttgart 2013, 45, 1497–1504; (g) Das, P. J.; Sarkar, S. Indian J. Chem. Section B 2013, 52, 802–806; (h) Boruah, J. J.; Das, S. P.; Borah, R.; Gogoi, S. R.; Islam, N. S. Polyhedron 2013, 52, 246–254; (i) Zhang, Q.; Gong, S. W.; Liu, L. J.; Yin, H. D. Process Saf. Environ. 2013, 91, 86–91. 4 (a) Hou, J. P.; Li, Z. J.; Jia, X.-D.; Liu, Z.-Q. Synthetic Commun. 2014, 44, 181-187; (b) Schmidt, V. A.; Quinn, R. K.; Brusoe, A. T.; Alexanian, E. J. J. Am. Chem. Soc. 2014, 136, 14389–14392; (c) Mohan, R. B.; Reddy, N. C. G. Synthetic Commun. 2013, 43, 2603–2614; (d) Li, B.; Gao, L. F.; Bian, F. L.; Yu, W. Tetrahedron Lett. 2013, 54, 1063–1066; (e) Ma, X. T.; Tian, S. K. Adv. Synth. Catal. 2013, 355, 337–340; (f) Vrazic, D.; Jereb, M.; Laali, K. K.; Stavber, S. Molecules 2013, 18, 74–96; (g) Schroder, N.; Wencel-Delord, J.; Glorius, F. J. Am. Chem. Soc. 2012, 134, 8298–8301; (h) Zhang, R.; Huang, L.; Zhang, Y. F.; Chen, X. R.; Xing, W. H.; Huang, J. Catal. Lett. 2012, 142, 378–383; (i) Aoki, S.; Matsuo, Y.; Ogura, S.; Ohwada, H.; Hisamatsu, Y.; Moromizato, S.; Shiro, M.; Kitamura, M. Inorg. Chem. 2011, 50, 806–818. 5 (a) Sivey, J. D.; Bickley, M. A.; Victor, D. A. Environ. Sci. Technol. 2015, 49, 4937–4945; (b) de Almeida, L. S.; de Mattos, M. C. S.; Esteves, P. M. Synlett 2013, 24, 603–606; (c) Albadi, J.; Tajik, H.; Keshavarz, M.; Abedini, M. Monatsh Chem. 2013, 144, 179–181; (d) Sandtorv, A. H.; Bjorsvik, H. R. Adv. Synth. Catal. 2013, 355, 499–507; (e) Rayala, R.; Wnuk, S. F. Tetrahedron Lett. 2012, 53, 3333–3336; (f) Ghorbani-Vaghei, R.; Shahbazi, H.; Veisi, H. Tetrahedron Lett. 2012, 53, 2325–2327. 6 (a) Li, H.-J.; Wu, Y.-C.; Dai, J.-H.; Yan, S.; Cheng, R. J.; Qiao, Y. Y. Molecules 2014, 19, 3401-3416; (b) Thais, D.-A.; Jaime, M.-F.; Javier, R.-L.; Mello, R.; Acerete, R.; Asensioa, G.; González-Núñez, M. E. RSC Adv. 2014, 4, 51016-51021; (c) Kumar, L.; Mahajan, T.; Sharma, V.; Agarwal, D. D. Ind. Eng. Chem. Res. 2011, 50, 705–712; (d) Kong, J.; Galabov, B.; Koleva, G.; Zou, J. J.; Schaefer, H. F.; Schleyer, P. V. Angew. Chem. Int. Ed. 2011, 50, 6809–6813; (e) Mokhtary, M.; Lakouraj, M. M. Chinese Chem. Lett. 2011, 22, 13–17; (f) Kumar, L.; Mahajan, T.; Agarwal, D. D. Green Chem. 2011, 13, 2187–2196. 7 (a) Song, S.; Sun, X.; Li, X. W.; Yuan, Y. Z.; Jiao, N. Org. Lett. 2015, 17, 2886–2889; (b) Wang, J.; Chen, S.-B.; Wang, S.-G.; Li, J.-H. Aust. J. Chem. 2014, 68, 513-517; (c) Prebil, R.; Laali, K. 9

K.; Stavber, S. Org. Lett. 2013, 15, 2108–2111; (d) Kasradze, V. G.; Ignatyeva, I. B.; Khusnutdinov, R. A.; Suponitskii, K. Y.; Antipin, M. Y.; Yunusov, M. S. Chem. Heterocycl. Com. 2012, 48, 1018–1027; (e) Khosravi, K.; Kazemi, S. Chinese Chem. Lett. 2012, 23, 387–390; (f) Koini, E. N.; Avlonitis, N.; Calogeropoulou, T. Synlett 2011, 11, 1537–1542. 8 (a) Liu, J. M.; Zhang, Yi, X. H.; Liu, C.; Liu, R.; Zhang, H.; Zhuo, K. L; Lei, A. W. Angew. Chem. Int. Ed. 2015, 54, 1261–1265; (b) Shi, Z. Z.; Zhang, C.; Tang, C. H.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3381–3430; (c) Nishina, Y.; Takami, K. Green Chem. 2012, 14, 2380–2383. 9 Leyva-Perez, A.; Combita-Merchan, D.; Cabrero-Antonino, J. R.; Al-Resayes, S. I.; Corma, A. ACS Catal. 2013, 3, 250–258. 10 (a) Mo, S. Y.; Zhu, M.; Shen, Z. M. Org. Biomol. Chem. 2013, 11, 2756–2760; (b) Liu, A. H.; Ma, R.; Zhang, M.; He, L. N. Catal. Today 2012, 194, 38–43; (c) Liu, A. H.; He, L. N.; Hua, F.; Yang, Z. Z.; Huang, C. B.; Yu, B.; Li, B. Adv. Synth. Catal. 2011, 353, 3187–3195. 11 Ohkubo, K.; Mizushima, K.; Iwata, R.; Fukuzumi, S. Chem. Sci. 2011, 2, 715–722. 12 (a) Xu, L.; Wang, Y.; Wen, X.; Ding, C. R.; Zhang, G. F.; Liang, X. M. Synlett, 2011, 2265–2269; (b) Ren, Y.-L.; Shang, H. T.; Wang, J. J.; Tian, X. Z.; Zhao, S.; Wang, Q.; Li, F. W.; Adv. Synth. Catal., 2013, 355, 3437–3442. 13 Limberg, C.; Teles, J. H. Adv. Synth. Catal., 2001, 343, 447–449. 14 Neumann, R.; Assael, I. J. Chem. Soc. Chem. Commun., 1988, 1285–1287. 15 Kikushima, K.; Moriuchi, T.; Hirao, T. Tetrahedron Lett. 2010, 51, 340–342. 16 Zhang, G. F.; Liu, R. H.; Xu, Q.; Ma, L. X.; Liang, X. M. Adv. Synth. Catal. 2006, 348, 862–866. 17 Li, Z. L.; Li, G. L.; Jiang, L. H.; Li, J. L.; Sun, G. Q.; Xia, C. G.; Li, F. W. Angew. Chem. Int. Ed. 2015, 54, 1494–1498. 18 Ling, X. G.; Xiong, Y.; Zhang, S. T.; Huang, R. F.; Zhang, X. H. Chinese Chem. Lett. 2013, 24, 45–48. 19 (a) Okamoto, K.; Watanabe, M.; Murai, M.; Hatano, R.; Ohe, K. Chem. Commun. 2012, 48, 3127–3129; (b) Zhou, C. Y.; Li, J.; Peddibhotla, S.; Romo, D. Org. Lett. 2010, 12, 2104–2107; (c) Wan, S.; Wang, S. R.; Lu, W. J.; J. Org. Chem. 2006, 71, 4349–4352. 20 Liu, R.; Liang, X.; Dong, C.; Hu, X.; J. Am. Chem. Soc. 2004, 126, 4112–4113. 21 Holan, M.; Jahn, U. Org. Lett. 2014, 16, 58–61. 10

22 General experimental procedure for the bromination: 1 mL [Bmim]NO3, 0.5 mmol substrate and 0.25 mmol Br2 were added to a dried 45 mL tube equipped with a magnetic stirring (note: the air in the tube was not removed). Then the reaction tube was sealed to perform the reaction at 80 oC for 24 h. Once the reaction time was reached, the mixture was cooled to room temperature and 3 mL water was added. Then the desired product was extracted with CH2Cl2 (3 × 10 mL). GC analysis of the mixture provided the GC yield of the product. The product in another parallel experiment was purified by column chromatography, and identified by 1

H-NMR and 13C-NMR.

11

MeO

Residual air in the reaction tube MeO

+ Br2 0.5 equiv

[Bmim]NO3 80 oC, 24 h

Br +

MeO 86%

Br

Br < 2% MeO Br <3%

Scheme 1 Bromination of methoxybenzene with [Bmim]NO3 as the catalyst and solvent.

12

1mL [Bmim]NO3

0.5 equiv Br2

+ Me

MeO

1mL [Bmim]NO3

OMe MeO

+

1mL [Bmim]NO3

OMe +

0.5 equiv Br2

MeO

Br Br

MeO

1mL [Bmim]NO3

Br 2% OMe

Br +

MeO 5%

65% Br OMe

Br +

1mL [Bmim]NO3

0.5 equiv Br2

Me

90%

0.5 equiv Br2

Br trace

81%

1% O

Cl

+

0.5 equiv Br2

+ Cl

+

MeO

O

90% Br Br

78%

Scheme 2 Several competition reactions between different aromatic rings.

13

MeO

+ Br2

HBr + 1 O2 4

MeO

Br + HBr

Catalytic species from [Bmim]NO3

1 Br + 1 H O 2 2 2 2

Scheme 3 Considerations on the mechanistic pathway.

14

Table 1 Bromination of methoxybenzene a MeO

+ 0.5Br2

Catalyst Solvent, 80 oC, 24 h

MeO

Br

Entry

Catalyst

Solventc

Bromine source

Conversion (%)b

Yield (%)b

1

-

Acetonitrile

Br2

51

44

2

-

Acetonitrile

HBr

0

0

3

[Bmim]NO3 (2 mol%) [Bmim]NO3 (5 mol%) [Bmim]NO3 (10 mol%)

Acetonitrile

Br2

72

68

Acetonitrile

Br2

84

86

Acetonitrile

Br2

98

90

6

-

[Bmim]NO3

Br2

97

86

7

-

[Bmim]NO3

HBr

99

90

8

-

[Bmim]Cl

HBr

0

0

9

-

[Bmim]BF4

HBr

0

0

10d

-

[Bmim]NO3

HBr

61

53

11e

-

[Bmim]NO3

Br2

33

18

4 5

a

Reaction conditions: 0.5 mmol methoxybenzene, 0.25 mmol Br2 or 0.5 mmol HBr, 80 oC, 24 h,

the air in the tube was not removed. b

Determined by GC with 1,2,4,5-tetramethylbenzene as an internal standard.

c

1.5 mL.

d

The air inside the tube was replaced with N2 gas by six vacuum/gas cycles.

e

0.25 mmol NaCO 3 was added.

15

Table 2 Bromination of various substituted benzenes and naphthalines a [Bmim]NO3

ArH + 0.5 Br2

ArBr

80 oC, 24 h

Residual air in the reaction tube

Entry

Substrate

Product

1

MeO

MeO

2

3

4

GC yield (%)b Isolated yield (%)

O

70

87

72

83

53

Br

81

68

Me

64

61

72

-

80

77

97

80

78

72

76

60

Br 86

70

40

33

6

-

trace

-

6

-

13

-

Br

O

MeO

MeO

H3C

Br

H3C

MeO

MeO Me

5

86

Br

MeO

Me

Me

MeO Br

6

MeO MeO

7

MeO

MeO

MeO OMe

MeO

MeO

10 11

OMe

MeO

MeO

O

9

Br

MeO

MeO

8

Br

MeO

Br

O

Br

O NC

O NC

O

O

F

F

12

N

N

Br Br

13

Me

Me

14

Cl

Cl

15

Br

Br

Br Br

Br

Br

16

16

OMe

OMe

17

98

80

87

85

Br

18

a

OEt

Br

OEt

Reaction conditions: 0.5 mmol methoxybenzene, 0.25 mmol Br2, 1 mL [Bmim]NO3, 80 oC, 24 h,

the air in the tube was not removed. b

Determined by GC with an internal standard.

17

Graphical Abstract

Aerobic Oxidative Bromination of Arenes Using an Ionic Liquid as both the Catalyst and the Solvent Yun-Lai Ren, Binyu Wang, Xin-Zhe Tian, Shuang Zhao, Jianji Wang*

Ar H + 0.5 Br2

[Bmim]NO3

Ar

Br

A method for the bromination of alkoxy-substituted benzenes and naphthalines was developed by using the residual oxygen in the reaction tube as the oxidant, and [Bmim]NO3 (1-butyl-3-methylimidazolium nitrate) ionic liquid as both the catalyst and solvent. No other reagent apart from the ionic liquid and molecular bromine was used in the reactions, and basically all the bromine atoms in bromine source were transferred to the bromination products, showing that the presented protocol is highly atom economic and clean.

18

Research Highlights ► Greener and readily available ionic liquid was used as both the solvent and

catalyst. ► The reaction is highly atom-economic and practical. ► Clean and inexpensive air was used as the oxidant.

19