Bromination aromatic, regioselectivity

Systematic studies of the selectivity of electrophilic bromine addition to ethylenic bonds are almost inexistent whereas the selectivity of electrophilic bromination of aromatic compounds has been extensively investigated (ref. 1). This surprising difference arises probably from particular features of their reaction mechanisms. Aromatic substitution exhibits only regioselectivity, which is determined by the bromine attack itself, i.e. the selectivity- and rate-determining steps are identical. 

Al-Bromosuccinimide is also a highly regioselective brominating agent at other positions, including positions a to a carbonyl group, to a C=C triple bond, and to an aromatic ring (benzylic position). When both a double and a triple bond are in the same molecule, the preferred position is a to the triple bond. ... 

In 2011, Hartwig and coworkers reported the total synthesis of taiwaniaquinol B (55, Scheme 11.9), a member of a family of diterpenoids that are derived from the abietane skeleton [36]. A key aspect of the Hartwig synthesis of taiwaniaquinol B was the use of the iridium-catalyzed borylation reaction to accomplish the C(5) functionalization of resorcinol derivative 53. This regioselectivity for the overall bromination is complementary to that which would be obtained using a standard electrophilic aromatic substitution (EAS) reaction. In the transformation of 53 to 54, a sterically controlled borylation was first accomplished, which was then followed by treatment of the boronic ester intermediate with cupric bromide to... 

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. 

Construction of the carbazole framework was achieved by slightly modifying the reaction conditions previously reported for the racemic synthesis (641,642). The reaction of the (R)-arylamine 928 with the iron complex salt 602 in air provided by concomitant oxidative cyclization the tricarbonyliron-complexed 4b,8a-dihydro-9H-carbazole (931). Demetalation of the complex 931, followed by aromatization and regioselective electrophilic bromination, afforded the 6-bromocarbazole 927, which represents a crucial precursor for the synthesis of the 6-substituted carbazole... 

Let us go back to radical brominations (cf. Section 1.7.3). The bromination of alkyl aromatics takes place completely regioselectively only the benzylic position is brominated. The intermediates are the most stable radicals that are available from alkyl aromatics, namely, benzylic radicals. Refluxing ortho-xylene reacts with 2 equiv. of bromine to give one monosubstitution... 

Regioselective, high-yield, aromatic bromination and chlorination of mesitylene, 1,3-dimethoxybenzene, 2,3-dimethylanisole, o-xylene and thiophene derivatives is observed in solid/liquid systems where solid NBS or NCS, combined with perchloric acid catalyst, is contacted at room-temperature with an organic phase (CC14 or hexane) containing the substrate737. 

Regioselectivity of aromatic bromination of co-phenylpolyoxaalkanols in aqueous solutions of SDS or CTAB are related to the concentration of the surfactant. At equal detergent/substrate ratio para bromination is preferred, and at higher surfactant concentration ortho bromination is promoted. These results are attributed to the orientation of the substrates in the micellar microenvironment which is also supported by -NMR studies1018. 

The ketone is then brominated, also with NBS, in a regioselective manner. The more conjugated enol is formed between the carbonyl group and the aromatic ring and this is attacked electrophilically by the bromine atom of the NBS (Chapter 20). 

The nucleophilicity of the aromatic system can alternatively be increased by using organometallic aromatic compounds, which also solves the problem of regioselectivity. This method was applied by Sulikowski et al., who reacted a variety of sugar lactones with aryl lithiums to afford intermediate lactols which were subsequently reduced to the C-glycosides by cyanoboro hydride [137]. For example, selective orfho-bromination of monobenzylated napthalene diol 174 affords the bromide 175 which is converted into the dianion with three equivalents of n-BuLi. Treatment with the benzylated lactone 176 afforded lactol 177 (Scheme 45, the D-dideoxygluconolactone 176 was erroneously drawn as the... 

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. 

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