Bromination of hydrocarbons with CBr4, initiated by light-emitting diode irradiation

The bromination of hydrocarbons with CBr4 as a bromine source, induced by light-emitting diode (LED) irradiation, has been developed. Monobromides were synthesized with high efficiency without the need for any additives, catalysts, heating, or inert conditions. Action and absorption spectra suggest that CBr4 absorbs light to give active species for the bromination. The generation of CHBr3 was confirmed by NMR spectroscopy and GC–MS spectrometry analysis, indicating that the present bromination involves the homolytic cleavage of a C–Br bond in CBr4 followed by radical abstraction of a hydrogen atom from a hydrocarbon.


Introduction
Bromination reactions of organic compounds are fundamental reactions for providing a wide variety of organic precursors for industrial materials [1][2][3][4][5][6][7][8]. Generally, the bromination of saturated hydrocarbons proceeds through radical abstraction of hydrogen atoms and trapping with bromide, whereas the bromination reactions of aromatic and unsaturated hydrocarbons are induced by electrophilic addition of bromine and/or a cationic bromide. Combinations of N-bromosuccinimide (NBS) with azobisisobutyronitrile or benzoyl peroxide as radical initiators are typical conditions for Wohl-Ziegler bromination [9][10][11][12] and are widely used for the bromination of benzylic and allylic positions, despite the need for heating and the generation of equimolar amounts of waste. To avoid these drawbacks, several efforts have been focused on benzylic bromination using Br 2 or bromide salts as highly efficient bromine sources [13][14][15][16][17]. However, the direct bromination of non-activated C-H bonds is still a challenging task. Although Br 2 [13], CBr 4 [18][19][20], R 4 NBr [21,22] and LiBr [23] have been reported to serve as bromine sources for the bromination of saturated hydrocarbons, these reactions exhibit low selectivity or reactivity. Efficient bromination using Br 2 as a bromine source combined with a stoichiometric base [24], an excess of MnO 2 [25], or a catalytic amount of Li 2 MnO 3 [26] has been reported to give high reactivity and selectivity. The combination of CBr 4 with a copper catalyst at high temperature also achieves effective bromination of hydrocarbons [27]. We have focused on CBr 4 , which is solid and easy to handle, as a bromine source. CBr 4 has been used in organic synthesis to give useful bromide-containing precursors. For instance, alkyl alcohols can be converted to alkyl bromides in the presence of CBr 4 and triphenylphosphine; this is known as the Appel reaction [28]. This combination can also be used to transform aldehydes into dibromoalkenes, which are useful precursors for the Corey-Fuchs reaction [29], to obtain terminal alkynes. Although CBr 4 has been used for various bromination reactions including radical brominations, these reactions need further additives to proceed. Here, we disclose the efficient bromination of saturated hydrocarbons, using CBr 4 as a bromine source without any additives, through radical reactions induced by irradiation with light from commonly used light-emitting diodes (LEDs) [30]. In this reaction, additives, catalysts, heating, and inert reaction conditions are all unnecessary.

Results and Discussion
First, the bromination of cyclohexane under LED irradiation was investigated using 1.0 mL of cyclohexane with 0.20 mmol CBr 4 ( Table 1). The desired monobrominated product was obtained in 77% yield, based on CBr 4 , after 2 h, and no dibromide was observed ( To investigate the wavelength dependency of the present reaction, the action spectrum of the bromination of cyclohexane in the presence of CBr 4 was obtained by plotting the apparent quantum efficiency against wavelength (Figure 1, red line) [31]. It was found that the present reaction was promoted by irradiation with ultraviolet (UV) light and deactivated under visiblelight (>475 nm) irradiation. CBr 4 shows strong absorption in the UV region (Figure 1, blue line), and this overlaps with the  above-mentioned action spectrum. The activation of CBr 4 is therefore considered to be induced by photo-irradiation, initiating the reaction. Although other light sources could also activate CBr 4 , we adopted LED light due to safety, mildness, and availability. We have confirmed that fluorescent room light could also promote the reaction.
A plausible mechanism for the present bromination is illustrated in Scheme 1. First, photo-irradiation generates a bromine radical and a CBr 3 radical (Scheme 1, reaction 1), which abstracts a hydrogen atom from the substrate to form CHBr 3 (Scheme 1, reaction 2). Finally, the radical species derived from the substrate reacts with the bromine radical or CBr 4 to afford the brominated product (Scheme 1, reactions 3 and 4). Additionally, the in situ generated CHBr 3 releases a bromine radical upon LED irradiation, thus serving as a bromine source (Scheme 1, reaction 5). Alternatively the radical species derived from the substrate abstracts a bromine atom from CHBr 3 (Scheme 1, reaction 6).  To examine the above hypothesis, the bromination of cyclohexane was monitored using 13 C NMR spectroscopy ( Figure 2). CBr 4 (0.50 mmol) dissolved in cyclohexane (0.10 mL) and CDCl 3 (0.40 mL) was observed at −29.7 ppm (Figure 2a). After stirring a reaction mixture of CBr 4 (0.50 mmol) and cyclohexane (0.10 mL) under LED irradiation for 24 h, peaks assigned to bromocyclohexane (53.4, 37.6, 25.9, and 25.1 ppm) and another strong peak at 9.6 ppm appeared (Figure 2c). The latter peak was found to be consistent with the peak of CHBr 3 (0.50 mmol) dissolved in cyclohexane (0.10 mL) and CDCl 3 (0.40 mL) (Figure 2b). Additionally, the generation of CHBr 3 in the present bromination was confirmed by 1 H NMR spectroscopy and GC-MS spectrometry. These results support the reaction pathway described above, although the chemical species after the second bromination was not assigned at this point.

Conclusion
In conclusion, we have developed a method for the hydrocarbon bromination induced by LED irradiation using CBr 4 as a bromine source. The present reaction system did not require any additives, catalysts, heating, or inert conditions, and is therefore an extremely simple procedure. An action spectrum and NMR measurements showed that the LED irradiation activates CBr 4 to generate bromine radicals, which initiate the bromination reaction. Further elucidation of the detailed mechanism and the use of LED irradiation in other reaction systems are under investigation in our laboratory.

Experimental General information
All commercially available compounds were purchased and used as received. Cyclohexane, cyclooctane, n-hexane, and toluene were purchased from Wako Pure Chemical Industries and used as received. 1 H (400 MHz) and 13 C (100 MHz) NMR spectra were recorded using a JEOL JNM-LA400 spectrometer. Proton chemical shifts are reported relative to residual solvent peak of CDCl 3 at δ 7.26 ppm. Carbon chemical shifts are reported relative to CDCl 3 at δ 77.00 ppm. Gas chromatographic analysis was conducted with Shimadzu GC-2014 equipped with FID detector. The chemical yields were determined using dodecane as an internal standard. The NMR data of all brominated products match those reported.
General procedure for the bromination induced by LED irradiation A reaction tube was charged with CBr 4 (66.33 mg, 0.20 mmol) and a hydrocarbon (1.0 mL). The reaction mixture was stirred under white LED (7 W) irradiation. To this was added dodecane (45.2 μL, 0.20 mmol) and the yield was determined by GC analysis with dodecane as an internal standard.