One-pot aromatic bromination–rearrangement catalyzed by GaCl 3

Reaction of monoalkylbenzenes with bromine in the presence of a catalytic amount of GaCl 3 (5 mol %) initially gives o/p -bromination products, which are converted into mixtures containing considerable amounts of the m -brominated products. Notably, the bromination of dimethyl-, trimethyl-, and tetramethylbenzenes gives dibromo-and/or tribromoarenes, which are converted into monobromoarenes.


Introduction
The bromination of aromatic compounds has been conducted using halogenating reagents such as Br 2 and HOBr in the presence or absence of catalysts. 1These methods convert monoalkylbenzenes into o/p-brominated products.Since the m-derivatives are formed in small amounts, their preparations in general employ multistep processes. 2A previous report that Al 2 Cl 6 -water catalyst promotes the isomerization of bromoarenes 3 led us to study one-pot catalytic procedures for the o/p-bromination of monoalkylbenzenes followed by isomerization to give mixtures containing the m-derivatives. 4We now show that GaCl 3 5,6,7 catalyzes such To a solution of hexylbenzene and GaCl 3 (5 mol %) in methylcyclohexane was added an equimolar amount of bromine, and the mixture was stirred at room temperature for 12 h giving the bromohexylbenzenes o-1, m-1, and p-1 in 18%, 38%, and 15% yields, respectively (Table 1, entry 3).The structures were determined by comparison with the authentic samples prepared separately (see Experimental Section).Benzyl bromination proceeded in the absence of the catalyst, and 1 was not detected.The use of FeCl 3 (3.6 mol %) exhibited normal orientations, giving o-1 (20%) and p-1 (78%).Such aromatic bromination isomerization could also be carried out with AlCl 3 (5 mol %), although the reaction was sometimes not reproducible, probably because of the insolubility of AlCl 3 in this solvent.The bromination using GaCl 3 is rapid, and o- Determined by 1 H-NMR.b The reaction was conducted for 5 min.
Polymethylbenzenes exhibit interesting behaviors: polybrominated products are initially formed, which are converted into monobromides.Reaction of m-xylene for 1 min gives the 4,6dibrominated 4,6-3 as the major product, and the monobromide 2 predominates after 12 h (Table 2).Such a phenomenon has not been reported before.Bromination of m-xylene with AlCl 3 under the same conditions for 1 min gives 4-2 predominantly, which is the usual orientation.
Similar tendencies are observed in the bromination of p-xylene with GaCl 3 (Table 3).The reaction for 5 min gives 2,5-dibrominated 5 predominantly, which is converted into 2brominated 4 after 12 h.In this case, AlCl 3 also shows somewhat related isomerization behaviors, although less prominently than with GaCl 3 .Based on bromine, as determined by 1 H-NMR.
Bromination of 1,2,3-and 1,3,5-trimethylbenzene with GaCl 3 initially gives considerable amounts of dibromo-and tribromoarenes, which are converted into monobromoarenes (Table 4).It should be noted that 5-bromo-1,2,3-trimethylbenzene can be prepared in one step from the corresponding hydrocarbon.The previous preparation of this compound employed a multistep process. 8Reactions of both 1,2,3,4-tetramethyl-and 1,2,4,5-tetramethylbenzene with GaCl 3 give initially equal amounts of monobromides and dibromides, which are converted into the monobromides after 12 h (Table 4).Thus, the second and/or the third brominations are faster than the first bromination in the reactions catalyzed by GaCl 3 .It seems that the bromide group behaves as an activating group in the electrophilic substitution.We propose that the interaction of GaCl 3 with Br, as well as the C-H bonds of neighboring methyl groups, promote such polybromination.Previously, we reported aromatic substitution reactions which involve interactions between GaCl 3 and C-H bonds. 5The monobrominated arenes obtained here are the thermodynamically controlled products, because of the lower numbers of o-interactions between the bromide and the methyl group.

Table 1 .
1 and p-1 are obtained in 5 min in 23% and 42% yields, respectively, with a very small amount of m-1 (entry 4).When the mixture is stirred for 12 h at room temperature, p-1 decreases and m-1 increases.Bromination of several alkylbenzenes catalyzed by GaCl 3 is shown in Table1.In the Bromination of alkylbenzenes catalyzed by GaCl 3 case of neopentylbenzene and isobutylbenzene, larger amounts of the m-derivatives are obtained, which may be a result of steric reasons (entries 6 and 7).The different o/p ratio of toluene and ethylbenzene may also be explained analogously (entries 1 and 2): a methyl group behaves as a considerably smaller group than an ethyl group in this reaction.

Table 4 .
Bromination of tri-and tetramethylbenzenes b Not detected by GC-MS.