Aromatic Bromination in Concentrated Nitric Acid

Action of bromine in concentrated nitric acid allows carrying out monoand polybromination of moderately deactivated aromatic compounds. 4-Chloronitrobenzene and isophthalic acid turnes into 3-bromo-4-chloronitrobenzene and 5-bromoisophthalic acid at reaction with bromine in concentrated nitric acid at 20 ̊C whereas in absence of bromine in the same conditions 4-chloro-1, 3-dinitrobenzene and 5-nitroisophthalic acid are formed accordingly. Presence of bromine in concentrated nitric acid changes nitrating capacity to brominating one. Terephthalic acid and phthalic anhydride at heating with bromine in concentrated nitric acid can be transformed to appropriating tetrabromo substituted compounds.


Introduction
Aromatic compounds with bromine atom in the ring are of great value in organic chemistry.Bromine is introduced into the aromatic ring as to give desired properties to the final product as, especially, to attain the required reactivity for further syntheses connected with exchange of bromine for various groups.The principal method of bromine introduction into aromatic molecules is electrophilic bromination.It easily proceeds when activating electron-donating substituents are present in the ring but when deactivating electron-withdrawing substituents are present special methods are required [1].
Earlier we have described bromination of strongly deactivated aromatic compounds by action of bromine in concentrated sulfuric acid in the presence of nitric acid [2] and have discussed competition of bromination and nitration in this media [3].As participation of nitric acid is of critical importance we have carried out interaction of deactivated aromatics with bromine in pure nitric acid without sulfuric acid.It has appeared that moderately deactivated aromatic compounds which are easily nitrated with concentrated nitric acid are only brominated if concentrated nitric acid contains bromine.Possibility to use treatment with bromine in concentrated nitric acid for synthesis mono-and polybromo substituted aromatics is considered in the present work.

Reagents and Analytics
Bromine, 99% nitric acid and aromatic substrates were obtained from commercial suppliers and were used without further purification. 1Н and 13 C NMR spectra were determined in DMSO-d6 on a Jeol ECX-400 NMR spectrometer, the chemical shifts were reported in δ ppm relative to TMS as internal standard.Correctness of signals reference in 1 Н and 13 C NMR spectra in addition proved to be true the analysis of two-dimentional spectroscopy HETCOR { 1 H- 13 C}.Element analyses are made on the FlashEA 1112HT.Mass spectra were registered on MX-1320 mass spectrometer.IR spectra were recorded on a Perkin-Elmer-598 spectrometer in KBr pellets.Reactions and purity of the formed products were monitored by TLC on Silufol UV-254 plates.The melting points were measured using Boetius apparatus and were uncorrected.
In the same conditions but without bromine 4-chloro-1,3-dinitrobenzene 3 was a single product in yield 98%, identical to standard sample.
In concentrated H 2 SO 4 in the presence HNO 3 4-chloronitobezene 1 gives directly 5-bromo-4-chloro-1,3-dinitrobenzene 4 by nitration at first and following bromination of 4-chloro-1,3-dinitrobenzene [2].Dinitrobenzene 3 and other dinitrobenzenes are not brominated with system Br 2 /HNO 3 .The fact that compound 1 is brominated with system Br 2 /HNO 3 and is nitrated with system Br 2 /H 2 SO 4 -HNO 3 is caused evidently by less nitrating capacity of the first system.Nitric acid exists in sulfuric acid with concenration of 90% and more completely as nitronium cation.Content of nitronium cation in pure nitric acid observed by Raman and IR spectra is about several percents (~3% molar) owing to self-dehydration: , and it strongly decreases with the addition of 5% water [8].Nitronium cation is the attacking electrophilic species at aromatic nitration of 4-chloronitobezene both in concentrated sulfuric acid and in 85% -95% nitric acid also [9].
Since bromination in absence of nitric acid does not take place apparently that interaction of bromine with nitronium cation is a key stage in generation of brominating agent.Electron transfer from bromine to nitronium- cation gives brominating species which exceeds an initial nitronium cation on electrophility, and, possible, closed by structure to bromonium cation.Generated brominating agent is so more active than nitrating one that bromination proceed with much greater rate than nitration.Therefore bromination takes place instead of nitration when bromine is present in concentrated nitric acid.
Preparative possibilities of bromination in concentrated nitric acid are demonstrated on an example of benzene dicarboxylic acids.Isophtalic acid 5 turns to 5-bromoisophthalic acid 6 in mild conditions.Compound 6 was isolated after stirring 5 in concentrated nitric acid containing excess of bromine at 20˚C for 1 hours in yield 55%.After 22 hours 4,5-dibromoisophthalic acid 7 was obtained in yield 65%. Treatment of isophthalic acid 5 with concentrated nitric acid at 20˚C in absence of bromine gives 5-nitroisophthalic acid 8 in high yield (Scheme 2).Isophtalic acid 5 is comparable with 4-chloronitobezene 1 on easiness of bromination and suppression of nitration.
5-Bromoisophthalic acid 6 is of commercial significance as intermediate.The main method for its preparation is bromination of isophthalic acid 5 in oleum at a heat.For example acid 5 is heated with bromine in 10% oleum in sealed tube at 130˚C for 22 hours [10] or in 20% oleum at 102˚C -107˚C for 6 h in the presence of 2% -3% of iodine as catalyst [11].That strongly contrasts with described above process in concentrated nitric acid at room temperature.
Long heating of isophthalic acid 5 with bromine in concentrated HNO 3 at 55˚C -60˚C does not lead to introduction into the ring more than two bromine atoms.Terephthalic acid 9 unlike acid 5 is completely brominated in concentrated HNO 3 .Heating of terephthalic acid 9 with bromine in concentrated HNO 3 at 50˚C -55˚C for 12 hours gives tetrabromoterephthalic acid 10 in yield 65% (Scheme 3).Earlier this compound was synthesized by bromination of terephthalic acid in 20 % oleum at presence of iodine at 125˚C during 76 hours [12].By means of the given method it is possible to introduce four atoms of bromine into molecule of phthalic anhydride.Interaction of phthalic anhydride 11 with bromine in concentrated nitric acid at 50˚C -65˚C for 22 hours yields 79% of 3,4,5,6-tetrabromophthalic anhydride 12 (Scheme 4).In absence of bromine phthalic anhydride is nitrated to mixture of 3-nitro and 4-nitro derivatives [13].Proposed in literature methods for manufacture of tetrabromophthalic anhydride 12 used as flame retarder [14] consists in bromination of phthalic anhydride in strong oleum combined with sulfur dioxide oxidation process [15] [16].
Accumulation of four carboxylic groups so deactivates benzene ring that prevents bromination in nitric acid.Pyromellitic acid 13 does not changed at interaction with bromine in concentrated HNO 3 .Bromination is possible to carry out with system Br 2 /H 2 SO 4 -HNO 3 .Pyromellitic acid 13 turns into 3-bromopyromellitic 14 under stirring in concentrated H 2 SO 4 containing bromine and HNO 3 at 75˚C for 15 hours in yield 90% (Scheme 5).earlier by bromination of 1,2,4,5-tetramethylbenzene and following oxidation of methyl groups with potassium permanganate [17].

Conclusion
Thus action of bromine in concentrated nitric acid can be a method for introduction bromine atoms in the ring of moderately deactivated aromatic compounds at rather mild conditions.Brominating agent generated in concentrated nitric acid significantly exceeds on electrophility nitrating agent because of bromination proceeds much more quickly.Presence of bromine in concentrated nitric acid completely suppresses nitrating capacity of the media in relation to moderately deactivated compounds.Strongly deactivated compounds do not react in the given media.Action of bromine in concentrated sulfuric acid in presence of nitric acid is necessary at this case [3].

Scheme 1 .
Scheme 1.Reactions of 4-chloronitobezene with bromine in concentrated nitric acid and in concentrated sulfuric acid in the presence of nitric acid.
Scheme 2. Reactions of isophthalic acid in concentrated nitric acid in the presence and in the absence of bromine.Scheme 4. Reactions of phthalic anhydride with bromine in concentrated nitric acid.Scheme 5. Reaction of pyromellitic acid in concentrated sulfuric acid in the presence of nitric acid.