Substitution reactions, with bromine

Draw all resonance forms for the intermediate formed in each of the following aromatic substitution reactions with bromine and FeBr3. If there is a choice of ortho and para products, draw the intermediate for the ortho product. 

J. F. Durana and J. D. McDonald, Infrared chemiluminescence studies of chlorine substitution reactions with brominated unsaturated hydrocarbons, J. Chem. Phys. 64 2518 (1976). 

Electronegative groups do not invariably prevent nuclear bromination, but reaction conditions must be much more severe, and the orientation of substitution may be affected by the substituent. Thus 6-nitroquinoline was brominated in sulfuric acid at 100°C to give the 8-bromo product (71) in 51% yield 8-methyl-5-nitroquinoline gave a 69% yield of the 7-bromo derivative (72) under similar conditions, whereas 7-chloroquinoline was transformed into the 5-bromo product (93%) (88CHE892) (Scheme 35). In a sealed tube reaction with bromine, 8-nitroquinoline gave a mixture... 

Arenes are unsaturated but, unlike the alkenes, they are not very reactive. Whereas alkenes commonly take part in addition reactions, arenes undergo predominantly substitution reactions, with the TT-bonds of the ring left intact. For example, bromine immediately adds to a double bond of an alkene but reacts with benzene only in the presence of a catalyst—typically, iron(III) bromide—and it does not affect the bonding in the ring. Instead, one of the bromine atoms replaces a hydrogen atom to give bromobenzene, C H Br ... 

According to K. H. Meyer, this surprising reactivity—which is also encountered amongst the enols—is explained by the fact that the OH-group activates the double bond adjacent to it and the two neighbouring double bonds of the conjugated system (Thiele s theory) are also involved in this activation. Phenol, therefore, can yield 1 2- and 1 4-substitution products with bromine, addition reactions first taking place ... 

Arylbromine(V) tetrafluorides (ArBrF4) are prepared by substitution reactions of bromine pentafluoride with ArSiF3. ArSiMe, or CdAr, in acetonitrile or pyridine solutions.131132... 

The contrasting tendencies of the two compounds toward addition vs. aromatic substitution is illustrated by their reactions with bromine ... 

Thiophene is far more reactive than benzene in electrophilic substitution reactions. Reaction with bromine in acetic acid has been calculated to be 1.76 x 109 times faster than with benzene (72IJS(C)(7)6l). This comparison should, of course, be treated with circumspection in view of the fact that the experimental conditions are not really comparable. Benzene in the absence of catalysts is scarcely attacked by bromine in acetic acid. More pertinent is the reactivity sequence for this bromination among five-membered aromatic heterocycles, the relative rates being in the order 1 (thiophene) and 120 (furan) or, for trifluoroacetylation, 1 (thiophene), 140 (furan), 5.3 xlO7 (pyrrole) (B-72MI31300, 72IJS(C)(7)6l). Among the five-membered heteroaromatics, thiophene is definitely the least reactive. 

Satake et al. have described the mechanistic aspects of the formation of 2-methoxy-277-azepine derivatives lla-d from 377-azepines lOa-d upon reaction with bromine <2003H(60)2211> (Scheme 1). Unlike the situation observed with cycloheptatrienes, delocalized azatropylium salts were not formed from the reaction of 377-azepines with bromine in the absence of an alcoholic solvent. Reaction of 12 with bromine gave 13 plus the bis-ether 14 and bromomethane. The product 14 was also observed in the reaction of 12 with NBS (0.5 equiv) with 1 equiv of 7V-bromosuccinimide (NBS) 12 afforded the succinimido-substituted derivative 15, which upon elimination of HBr in the presence of base gave the 277-azepine 16 (Scheme 2) <2003H(60)2211>. 

All these transformations are obtained in good yields and 5-bromo derivatives are often crystalline and easy to separate. By-products can be bromides or dibromides with halogen substituent at C-l and C-5, but the regioselectivity of photobromination at C-5 results from the easier formation of tertiary radicals. The a-bromination confirms the stereoselectivity of the substitution reaction with the preferential abstraction of axial H-5. 

Later, Linda and Marino84, 90, 180 were able to compare the relative reactivities of all four fundamental systems (furan, thiophene, selenophene, and pyrrole) toward bromination by molecular bromine in acetic acid. Unfortunately, the comparison could not be made on the unsubstituted rings for the following reasons first, the rates of substitution for furan and pyrrole were too high to be followed by standard kinetic techniques second, furan and pyrrole undergo ring fission and/or polymerization under the influence of the hydrobromic acid formed in the reaction finally, furan tends to give addition as well as substitution products in the reaction with bromine.1818. 

Bromine reacts with benzene in a substitution reaction (a bromine atom replaces a hydrogen atom), keeping the benzene structure intact. This ability to retain its ring structure through all sorts of chemical reactions is one of the important differences of benzene compared to alkenes and one that originally helped to define the class of aromatic compounds to which benzene belongs. 

The pattern you saw for epoxidation with peroxy-acids (more substituted alkenes react faster) is followed by bromination reactions too. The bromonium ion is a reactive intermediate, so the rate-determining step of the brominations is the bromination reaction itself. The chart shows the effect on the rate of reaction with bromine in methanol of increasing the number of alkyl substituents from none (ethylene) to four. Each additional alkene substituent produces an enormous increase in rate. The degree of branching (Me versus n-Bu versus t-Bu) within the substituents has a much smaller, negative effect (probably of steric origin) as does the geometry (E versus Z) and substitution pattern (1.1- S... 

The nucleophilic nature of the ring means that pyrrole is attacked readily by electrophiles. Reaction with bromine requires no Lewis acid and leads to substitution (confirming the aromaticity of pyrrole) at all four free positions. 

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