Aniline selective bromination

Finally we mention in this section the non-catalytic selective bromination of aniline by the application of a zeolite pre-loaded with Bt2 as a slow release reagent (ref. 27). Aniline, dissolved in CCI4 was treated with Br2 adsorbed onto various zeolites and zeolite CaA was found to be most selective for monosubstitution (92%). The addition of organic bases improved the performance, probably due to scavenging of HBr. Also the toluidines could be monobrominated with this system with >95% selectivity. 

The direct bromination of aniline and phenol derivatives in solution results in polybromination to give a complex mixture. But bromination by gas-solid and solid-solid reactions proceeds more efficiently and selectively. Bromination by gas-solid reaction can be accomplished through a very simple procedure. For example, the powdered crystalline aniline 13 and Br2 were placed in... 

Kamikawa et al. chose the first option to generate the benthocyanin skeleton [91]. To begin with, 100 and aniline 126 are transformed into o-nitrodi-phenylamine 127 by intermolecular N-arylation. Reduction of the nitro group and selective bromination produces 128, and this time an intramolecular Buch-wald-Hartwig reaction is used to derive a mixture of the desired phenazine 129 and the elimination product 130. The fundamental problem with this approach relates to the selective introduction of the halogen substituent that is required for the intramolecular N-arylation. 

Recently, several selective bromination reagents for reactive aromatic amines have been developed, for example, 2,4,4,6-tetrabromocyclohexa-2,5-dienone (35), iV-bromosuccinimide-dimethylformamide (36), and hexabro-mocyclopentadiene (37). Although molecular bromine is too reactive to perform selective bromination (mono- versus polybromination), the combined used of bromine and zeolites X and Y has been reported to be applicable to the selective bromination of halobenzenes and alkylbenzenes (38). This zeolite method, however, was not successful in the selective bromination of highly active aromatic compounds. Bromine preadsorbed on zeolite 5A (Ca type) was found to monobrominate aniline in carbon tetrachloride with excellent regioselectivity (91-93% para selectivity) in the presence of organic base, pyridine or 2,6-lutidine (Table XII) (39). The preadsorption of bromine on zeolite 5A is necessary for selective bromination, because the inverse procedure of adding bromine to aniline that had been adsorbed on zeolite beforehand caused a nonselective reaction. 

Bromination of Aromatic Compounds. Phenols, anilines, and other electron-rich aromatic corrqiounds can be monobromi-nated using NBS in DMF with higher yields and higher levels of para selectivity than with Br2 iV-TrimethyIsilylanilines and aromatic ethers are also selectively brominated by NBS in CHCI3 or ecu. A-Substituted pyrroles are brominated with NBS in THF to afford 2-bromopyrroles (1 equiv) or 2,5-dibromopyrroles (2 equiv) with high selectivity, whereas bromination with Br2 affords the thermodynamically more stable 3-bromopyrroles. The use of NBS in DMF also achieves the controlled bromination of imidazole and nitroimidazole. Thiophenes are also selectively brominated in the 2-position using NBS in acetic acid-chloroform. ... 

A wide variety of aromatic compounds can be brominated. Highly reactive ones, such as anilines and phenols, may undergo bromination at all activated positions. More selective reagents such as pyridinium bromide perbromide or tetraalkylammonium tribromides can be used in such cases.18 Moderately reactive compounds such as anilides, haloaromatics, and hydrocarbons can be readily brominated and the usual directing effects control the regiochemistry. Use of Lewis acid catalysts permits bromination of rings with deactivating substituents, such as nitro and cyano. 

Benzene, toluene, ethylbenzene and chlorobenzene have been shown to be suitable substrates under these conditions, and the reaction rates are 50 to 70 times faster than for uncatalysed reactions. This reaction can be further enhanced by use of methanol as a co-catalyst, which allows bromination of anilines in quantitative yield with complete selectivity for the para- isomer [54],... 

Kinetic results on the chlorination of aniline by A-chloro-3-methyl-2,6-diphenylpiperi-din-4-one (3) suggest that the protonated reagent is reactive and that the initial site of attack is at the amino nitrogen. The effects of substituents in the aniline have been analysed but product studies were not reported. Zinc bromide supported on acid-activated montmorillonite K-10 or mesoporous silica (100 A) has been demonstrated to be a fast, selective catalyst for the regioselective para-bromination of activated and mildly deactivated aromatics in hydrocarbon solvents at 25 °C. For example, bromobenzene yields around 90% of dibromobenzenes with an ortholpara ratio of 0.12. 

Poly(4-vinylpyridine)-supported bromate in nonaqueous solution has been used in the bromination of aromatic compounds with potassium bromide <2005SC1947>. This bromination method is simple, efficient, mild, and selective for methoxyarenes, anilines, and phenols. 

Bromination of aniline in homogeneous solution immediately proceeds to tribromina-tion. Using bromine adsorbed on 5A zeolite leads to a selective monobromination mostly at the para position146. 

In bromination of anilines, the ortholpara ratio is significantly increased in presence of cetyltrimethylammonium bromide (CTAB) but is not altered with a symmetrical ammonium salt (TBAB). Surprisingly, increasing steric hindrance in the ortho position by N-alkylation has resulted with higher ortho-selectivity. This phenomenon is linked to the orientation of the aniline at the surface of the micellar aggregates1017. 

Such high selectivity induced by bromine on zeolite 5 A may be explainable by the idea that bromine is first activated to form Br with a OH site on zeolite SA, and thus the most active and less hindered para position of the aniline nucleus has dominant access to the Br that is located near a pore window of the zeolite, as an aniline molecule is too large to enter the pores of zeolite SA. It is interesting that the presence of organic bases such as pyridine or 2,6-lutidine not only improved the conversion, owing to neutralization of the generated HBr, but also increased the para-bromination selectivity. 

It may be mentioned that the concept of choosing a derivative with a particular detector in mind is quite frequently employed in residue analysis. And with the development of more diversified selective detectors, we are sure to see more of it. Thiophosphoryl derivatives of phenols for the flame photometric detector (59), nitrophenyl derivatives of amines and thiols (60) and brominated anilines for the EC detector (61), chloro-acetylated phenols for the microcoulometric detector (62), and many other examples (63) would be worth mentioning. The selectivity of a chemical reaction combined with the selectivity of a gas chromatographic detector can provide superior analytical eflBciency. 

Bromination of anilines. Good selectivity (p-bromination) is observed with KBr and sodium perborate in HOAc at room temperature. 

Bromination of Aromatic Compounds. Phenols, anilines, and other electron-rich aromatic compounds can be monobromi-nated using NBS in DMF with higher yields and higher levels of para selectivity than with Br2 M-Trimethylsilylanilines and aro-... 

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