Electrophilic nitration of aromatics is a fundamental reaction in the preparation of intermediates of many compounds including pharmaceuticals, dyestuffs, explosives, pesticides, and so on.1 The mechanistic and synthetic aspects of nitration chemistry have been studied over these years. However, many traditional processes suffer from serious disadvantages, including low selectivity for the desired product and the requirement for large quantities of mineral or Lewis acids as activators.2 Major efforts are therefore being made to develop processes with lower environmental impact.
Among a number of efforts on developing alternative methodologies, the combined use of nitrogen dioxide and molecular oxygen in the place of the classical nitric acidsulfuric system appears to be the most attractive and promising.3 Suzuki has reported that nitrogen dioxide is activated to react with a wide variety of nonactivated and moderately activated aromatic substrates to afford the corresponding nitro compounds in good yields.4 We have reported that 1-nitronaphthalene, naphthonitriles and methylated benzonitriles could be smoothly nitrated in the presence of zeolites by the combined action of nitrogen dioxide and molecular oxygen.5 The use of solid acid catalysts is a very attractive alternative to improve regioselectivity because of the case of separation, recyclability of the catalysts.6 4,4'-Dibromo-2-nitrobiphenyl is an important fine chemical with a constantly increasing world market owing to its usefulness as synthetic intermediates.7 The present work deals with an efficient and high-selective preparation of the nitrated 4,4'-dibromobiphenyl with a nitrogen dioxide/ molecular oxygen process.
Regents and Apparatus
Zeolites were purchased from New Materials Research Center of Tianjin in China. Melting points were determined on a WRS-2 apparatus and uncorrected. 1H NMR and 13C NMR spectra were recorded on a Agilent VNMRS- 600MHz spectrometer (at 600 and 151MHz, respectively) with TMS as internal standard. Chemical shifts (δ) were expressed and coupling constants J were given in Hz. Infrared (IR) spectra were recorded on a Thermo Nicolet 67 Fourier transform (FT)-IR spectrometer as KBr pellets. High resolution mass spectra (HRMS) data were obtained using a Waters ACQUITY UP mass spectrometer with ESI source. TLC was performed with silica gel GF254 percolated on class plates, and spots were visualized with UV. Shimadzu GC-2014C (WONDACAP-1 df=1.5 μm× 0.53mm I.D×30 m) was utilized to determine product isomer compositions with 4-nitrotoluene as internal standard. The injector and flame ionization detector were set at 280 ℃. The GC column was operated from 140 to 250 ℃ at a rate of 10 ℃/min, and held the final temperature for 3 min. All other chemicals were analytical grade without any further purification.
Typical Experimental Procedure for Zeolite Cationexchange
The standard procedure for cation-exchange involved stirring a supplied commercial zeolite (2.50 g) in a refluxing aqueous solution of the corresponding metal chloride (0.2 mol/L, 50 mL) for 24 h. The solid was filtrated, washed with deionized water until halide-free and dried at 110 ℃ for 6 h, and then calcined in air at 550 ℃ for 6 h.
Nitrate Progress with Nitrogen Dioxide/molecular Oxygen
Quantitative 4,4'-dibromobiphenyl, nitrogen dioxide, zeolite, and dichloromethane were placed in a flask. Oxygen was passed into the system to replace air, and a balloon filled with oxygen was connected. The mixture was stirred at a certain temperature and progress of the reaction was monitored by TLC with pure petroleum ether as eluent. The Rf values of 4,4'-dibromobiphenyl and 4,4'-Dibromo- 2-nitrobiphenyl are 0.75 and 0.31, respectively.
When the reaction was complete, excess nitrogen dioxide was removed by blowing air into the solution and collected in a cold trap for reuse. The zeolite was removed by filtration and the filter liquor was washed with water, 5% aqueous solution of sodium bicarbonate followed by water. The organic phase separated was dried with anhydrous sodium sulfate, and concentrated under reduced pressure to give a yellow solid residue. The product was analyzed by GC. The yellow solid with further purification was analyzed. The used zeolite was recovered by washing and calcination.
Yellow solid mp 125.1−125.8 ℃ (lit.8 mp 125−126 ℃) IR (KBr) ν = 1535 (NO2), 785 (C−Br) cm−1. 1HNMR (CDCl3, 600 MHz) δ 8.02 (s), 7.55 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 7.14 (d, J = 8.2 Hz, 2H). 13CNMR (DMSO, 151MHz) δ 152.37, 138.91, 138.32, 136.56, 136.15, 134.87, 133.02, 129.90, 125.26, 124.36. HRMS (ESI) for C12H7Br2NO2 calcd 364.8844 found 364.8841.
RESULTS AND DISCUSSION
From Table 1, nitration of 4,4'-dibromobiphenyl 1 with traditional nitric acid and nitrosulfuric acids gave a mixture of 4,4'-dibromo-2-nitrobiphenyl 2 and 4,4'-dibromo- 3-nitrobiphenyl 3 in the isomer ratio of 2.5 and 3.8 (Entries 1 and 2 in Table 1) in yield of 70 and 38%, respectively. Dinitrated products were predominant in nitrosulfuric acids process. However, reaction could be mildly conducted at the combined action of nitrogen dioxide and molecular oxygen. When the amount of nitrogen dioxide increasing, the reaction towards good mononitrated yield in high region-selection up to a ratio of 6.0−9.0 above in 2 to 3 (Entries 5−7 in Table 1) and 4,4'-dibromo-2-nitrobiphenyl 2 was efficiently formed in over 70% yield.
Table 1.aThe data in parentheses meant a molar ratio of nitrogen dioxide to 4,4'-dibromobiphenyl.bThere action was carried out in dichloromethane (5.0 mL) using 1 (1.0 mmol), 95% nitric acid (2.0 mmol).cThe reaction was conducted in dichloromethane (5.0 mL) using 1 (1.0 mmol), 95% nitric acid (1.5 mmol) and 98% sulfuric acid (1.5 mmol).
It was also found that catalysts played an important role in improvement of the reaction. Smith and his coworkers had reported that halobenzenes could be nitrated with nitrogen dioxide and molecular oxygen in the presence of zeolite HBEA catalyst can give products of nitration, in which the para-nitro isomer predominates over the orthoisomer. 9 While Suzuki group had reported that ZSM-5 appeared to be better catalytic selective characteristics.10 In the recent work of the Chun J Shi, superior selectivity for production of 4,4'-dibromo-2-nitrobiphenyl was achieved at low conversion catalyzed by HBEA-500 with nitric acid/acetic anhydride as nitration agent.11 In the hope of improving the selectivity of 4,4'-dibromo-2-nitrobiphenyl in the nitrogen dioxide and molecular oxygen system, hydrogen and its metal ions exchanged BEA and ZSM-5 zeolites were employed. Zeolites facilitated the reaction and gave a high yield as compared with no catalysts. Among H+, Co2+, Mg2+, Fe3+ and La3+ modified zeolites, FeZSM- 5 was observed to give the most excellent yield of 90% with 84% 4,4'-dibromo-2-nitrobiphenyl selectivity (Entries 6-13 in Table 2). The activity of the zeolites may be due to the existence of strong acid sites and metal cations, which could easily prompt the production of NO2+ that appeared to play a positive role in attaining a higher 2 : 3 isomer ratio (Scheme 3).
Table 2.aAll reactions were carried out in dichloromethane (5 mL) using substrate 1 (1.0 mmol ), liquid NO2 (6.0 mmol) and catalyst (0.2 g). Oxygen was passed into the system to replace air, and a balloon filled with oxygen was connected. The mixture was stirred at 5 ℃.bZeolites were calcined at 550℃ for 2 h in air prior to use.cDetermined by GC.dA combined yield of 2 and 3 based on consumed 1 was given.eCalculated from GC peak areas, excluding other isomers and byproducts.fConducted in the air atmosphere.g1,2-dichloroethane was used as the solvent.
As considering the prospects for applications, the optimization scale up procedures were investigated. The represented results were summarized in Table 3. From Table 3, the similar yields and isomers ratio had been achieved.
Table 3.aThe mixture was stirred at 5 ℃ for 12 h.bThe ratio in parentheses meant a molar amount in nitrogen dioxide to 4,4'-dibromobiphenyl.
FeZSM-5 could be reused by simple filtration with a little loss of original activity (Table 4). Even after four times usage there was few observed change in nitration selectivity and yield.
Table 4.aAll conditions were the same to Table 3 (Entry 1).
Nitration of 4,4'-dibromobiphenyl with nitrogen dioxide/ molecular oxygen system in the presence of zeolites could show excellent selectivity in high yield. Moreover, 4,4'-dibromo-2-nitrobiphenyl could be efficiently prepared using environmentally economic process.