Bromobenzenes, substituted

N-Alkylanilines.1 Treatment of bromobenzene substituted in the meta position by electron-attracting groups [OCH3, Cl, N(CH3)2] with sodium amide generates a benzyne derivative which reacts with a primary aliphatic amine to give the corresponding... 

Methyl iodide ethyl bromide ethyl iodide, higher alkyl halides, chloroform, iodoform, carbon tetrachloride, chlorobenzene, bromobenzene, iodobenzene, benzyl chloride (and nuclear substituted derivatives)... 

Nitration using this reagent was first investigated, by Francis. He showed that benzene and some of its homologues bromobenzene, benzonitrile, benzoyl chloride, benzaldehyde and some related compounds, and phenol were mono-nitrated in solutions of benzoyl nitrate in carbon tetrachloride anilines would not react cleanly and a series of naphthols yielded dinitro compounds. Further work on the orientation of substitution associated this reagent with higher proportions of o-substitution than that brought about by nitric acid this point is discussed below ( 5.3.4). 

Chlorine or bromine react with benzene in the presence of carriers, such as ferric halides, aluminum halides, or transition metal halides, to give substitution products such as chlorobenzene or bromobenzene [108-86-17, C H Br occasionally para-disubstitution products are formed. Chlorobenzene [108-90-7] ... 

Bromination has been shown not to exhibit a primary kinetic isotope effect in the case of benzene, bromobenzene, toluene, or methoxybenzene. There are several examples of substrates which do show significant isotope effects, including substituted anisoles, JV,iV-dimethylanilines, and 1,3,5-trialkylbenzenes. The observation of isotope effects in highly substituted systems seems to be the result of steric factors that can operate in two ways. There may be resistance to the bromine taking up a position coplanar with adjacent substituents in the aromatization step. This would favor return of the ff-complex to reactants. In addition, the steric bulk of several substituents may hinder solvent or other base from assisting in the proton removal. Either factor would allow deprotonation to become rate-controlling. 

A similar substitution reaction occurs with other strong bases. Treatment of bromobenzene with potassium amide (KNH2) in liquid Nhh solvent, for instance, gives aniline. Curiously, though, when bromobenzene labeled with radioactive 14C at the Cl position is used, the substitution product has equal amounts of the label at both Cl and C2, implying the presence of a symmetrical reaction intermediate in which Cl and C2 are equivalent. 

The present method of preparation of 4,4 -dimethyl-l,l -biphenyl is that described by McKillop, Elsom, and Taylor 15 It has the particular advantages of high yield and manipulative simplicity and is, moreover, applicable to the synthesis of a variety of symmetrically substituted biaryls 3,3 - and 4,4 -Disubstituted and 3,3, 4,4 -tetrasubstituted 1,1 -biphenyls are readily piepared, but the reaction fails when applied to the synthesis of 2,2 -disubstituted-l,T biphenyls The submitters have effected the following conversions by the above procedure (starting aromatic bromide, product biphenyl, % yield) bromobenzene, biphenyl, 85,1 -bromo-4-methoxybenzene, 4,4 -dimethoxy-l, 1 -biphenyl, 99, 1 bromo 3 methylbenzene, 3,3 dimethyl-1,l -biphenyl, 85 4-bromo-l,2-dimethylbenzene, 3,3, 4,4 -tetramethyl-l,l -biphenyl, 76, l-bromo-4-chlorobenzene, 4,4 -dichloro-l,l -biphenyl, 73, l-bromo-4-fluorobenzene, 4,4 -difluoro-l,l -biphenyl, 73... 

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 ... 

A further difficulty in the case of fluoro-, chloro- and bromobenzenes is that with them apparently no choice of the 8 values seems to be reconcilable with the observed order of ease of substitution at the various positions unsubstituted benzene > para > ortho > meta. Both the inductive and the resonance effects are seen to leave the charge on the w-position practically unchanged, and approximately equal to 1.00c, while the observed order demands a considerably smaller value. As in the case of naphthalene, however, we shall find later that this discrepancy can apparently be explained by taking into account the polarization of the molecule by the attacking group. 

Such reactions appear to be rather general in scope, since an aryl example, the substitution for bromine in bromobenzene, and for halogen in a normal alkyl halide has also been observed (21). 

One 7i-bond of an aromatic ring can be converted to a cyclohexadiene 1,2-diol by reaction with enzymes associated with P. putida A variety of substituted aromatic compounds can be oxidized, including bromobenzene, chlorobenzene, " and toluene. In these latter cases, introduction of the hydroxyl groups generates a chiral molecule that can be used as a template for asymmetric syntheses. " ... 

For dihydrodiols derived from substituted benzenes, the key to their significance lies in the availability of two adjacent chiral centers with an established absolute stereochemistry. The dihydrodiol from benzene is, of conrse, the meso compound, although enantiomers produced by subsequent reaction with a chiral reagent are readily separated. There are useful reviews containing nnmerous applications (Carless 1992 Ribbons et al. 1989), many of which involve, in addition, the nse of di-flnoro-, di-chloro-, or di-bromobenzene-2,3-dihydrodiols. 

Several optimization studies have been carried out under these phosphine-free conditions. The reaction of bromobenzene and styrene was studied using Pd(OAc)2 as the catalyst, and potassium phosphate and (V,(V-dimethylacetamide (DMA) were found to be the best base and solvent. Under these conditions, the Pd content can be reduced to as low as 0.025 mol %.142 The reaction of substituted bromobenzenes with methyl a-acetamidoacrylate has also been studied carefully, since the products are potential precursors of modified amino acids. Good results were obtained using either N, (V-diisopropylethylamine or NaOAc as the base. 

Besides benzyl chloride, methyl- and/or chlorine-substituted benzyl chlorides, phenethyl chloride, etc. are also successfully employed to give 2 -diaralkylaminofluorans in excellent yield. However, aryl halides such as chlorobenzene and bromobenzene hardly enable the reaction, though aryl iodides such as iodobenzene give 2 -diarylaminofluorans in low yield. 

Witte, F., Urbanik, E., Zetzsch, C. (1986) Temperature dependence of the rate constants for the addition of OH to benzene and to some mono substituted aromatics (aniline, bromobenzene, and nitrobenzene) and the unimolecular decay of the adducts. Kinetics into a quasi-equilibrium. J. Phys. Chem. 90, 3251-3259. 

Aryl halides can also be reduced by tin hydrides76,77, although these reactions always require initiators because the stronger C—X bonds in aryl halides are less reactive than the C—X bonds in alkyl halides. In fact, a series of meta- and para-substituted bromobenzenes, where X is either meta- or para-CH3O-, C=N, Cl, F, CF3, CH3, Bu-f or 2,6-dichloro, have been reduced by tributyltin deuteride (equation 60). It is worth noting that the more reactive bromide is reduced selectively in the presence of the less reactive chloride and fluoride groups (equation 61). 

Bromobenzenes are converted into the corresponding chloro compounds on reaction with aqueous sodium hypochlorite in the presence of tetra-n-buty lammoni um hydrogen sulphate [40]. The reaction is pH dependent. At pH > 10, the bromobenzenes are effectively inert, but over the pH range 7.5-9, conversion occurs into the chlorobenzenes without any side reactions and the reaction appears to be light-induced. At more acidic levels (pH 4-5), bromobenzene is converted quantitatively into chlorobenzene within one hour. No reaction occurs in the absence of the catalyst and yields from light and dark reactions are comparable. Side reactions are observed, however, with substituted bromobenzenes under these low pH conditions. 

Lund and coworkers [131] pioneered the use of aromatic anion radicals as mediators in a study of the catalytic reduction of bromobenzene by the electrogenerated anion radical of chrysene. Other early investigations involved the catalytic reduction of 1-bromo- and 1-chlorobutane by the anion radicals of trans-stilhene and anthracene [132], of 1-chlorohexane and 6-chloro-l-hexene by the naphthalene anion radical [133], and of 1-chlorooctane by the phenanthrene anion radical [134]. Simonet and coworkers [135] pointed out that a catalytically formed alkyl radical can react with an aromatic anion radical to form an alkylated aromatic hydrocarbon. Additional, comparatively recent work has centered on electron transfer between aromatic anion radicals and l,2-dichloro-l,2-diphenylethane [136], on reductive coupling of tert-butyl bromide with azobenzene, quinoxaline, and anthracene [137], and on the reactions of aromatic anion radicals with substituted benzyl chlorides [138], with... 

Nickel(O) triphenylphosphine can be used to couple aryl halides and alkenes to synthesize substituted olefins [149], 1,2-bis[(di-2-propylphosphino)benzene]nick-el(0) can be used to couple aryl halides [150], and l,2-bis[(diphenylphos-phino)ethane]nickel(0) can be used to prepare benzoic acid from bromobenzene in the presence of carbon dioxide [151]. 

This reaction sequence illustrates how the rates of many base-catalyzed reactions can be enhanced greatly by substitution of dimethylsulfoxide for the usual hydroxylic solvents. Other examples of the enhanced reactivity of anions in dimethylsulfoxide are found in Wolff-Kishner reductions and Cope elimination reactions. The present reaction illustrates the generation of an aryne intermediate from bromobenzene. ... 

The method of electrochemical initiation of these reactions has some limitations, the main limitation being that the probability of substitution of a leaving group by a nucleophile depends on the nature of the substrate. Let us compare two reactions similar in the solvent employed (DMSO) and the nucleophile used (Bu4NSPh), but different in the chosen substrates (4-bromobenzophenone or bromobenzene)... 

Pinson and Saveant 1978, Swartz and Stenzel 1984). On electrochemical initiation (Hg cathode), 4-bromobenzophenone gives rise to 4-(phenylthio)benzophenone in the 80% yield, whereas bromoben-zene yields diphenyldisulfide with the yield of only 10% and unsubstituted benzene with the yield of more than 95%. In the bromobenzene case, this means that the substitution is a minor reaction, whereas the main ronte is ordinary debromination. According to Swartz and Stenzel (1984), the substrate anion-radicals are initially formed in the preelectrode space. Stability of these anion-radicals are different. The less stable anion-radicals of bromobenzene do not have enough time to go into the catholyte pool. They give rise to the phenyl radicals in the vicinity of the cathode. The phenyl radicals are instantly reduced into the phenyl anions. They tear protons from the solvent and yield benzene. 

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