Ethylbenzene radical bromination

In 1994, the free-radical bromination of toluene (and other alkylaro-matics) in sc C02 was reported (Tanko and Blackert, 1994 Tanko et al., 1994). Product yields were similar to those obtained with conventional solvents. The relative reactivity of the secondary hydrogens of ethylbenzene versus the primary hydrogens of toluene on a per hydrogen basis, r(2°/l°), were assessed via competition experiments and (a) did not vary with pressure, (b) were nearly identical to what is observed in conventional solvents. 

As a result, an alkyl benzene undergoes selective bromination at the weak benzylic C—H bond under radical conditions to form a benzylic halide. For example, radical bromination of ethylbenzene using either Br2 (in the presence of light or heat) or A/-bromosuccinimide (NBS, in the presence of light or peroxides) forms a benzylic bromide as the sole product. 

The mechanism for halogenation at the benzylic position resembles other radical halogenation reactions, and so it involves initiation, propagation, and termination. Mechanism 18.10 illustrates the radical bromination of ethylbenzene using Bt2 (h or A). 

FIGURE 13.76 The thermal or photochemical decomposition of bromine in ethylbenzene leads to 1-bromo-l-phenylethane through radical bromination at the henzylic position. 

Important differences are seen when the reactions of the other halogens are compared to bromination. In the case of chlorination, although the same chain mechanism is operative as for bromination, there is a key difference in the greatly diminished selectivity of the chlorination. For example, the pri sec selectivity in 2,3-dimethylbutane for chlorination is 1 3.6 in typical solvents. Because of the greater reactivity of the chlorine atom, abstractions of primary, secondary, and tertiary hydrogens are all exothermic. As a result of this exothermicity, the stability of the product radical has less influence on the activation energy. In terms of Hammond s postulate (Section 4.4.2), the transition state would be expected to be more reactant-like. As an example of the low selectivity, ethylbenzene is chlorinated at both the methyl and the methylene positions, despite the much greater stability of the benzyl radical ... 

Benzyl chloride undergoes further chlorination to give di- and tri-chloro derivatives, though it is possible to control the extent of chlorination by restricting the amount of chlorine used. As indicated above, it is easier to mono-brominate than it is to mono-chlorinate. The particular stabilization conferred on the benzylic radical by resonance is underlined by the reaction of ethylbenzene with halogens. 

Direct bromination of toluene and ethylbenzene form the corresponding benzyl bromides in high yield. The observed selectivity in SC-CO2 is similar to that observed in conventional organic solvents. Also, SC-CO2 is an effective alternative to carbon tetrachloride for use in the classical Ziegler bromination with N-bromosuccinimide. Reaction yields are high, side products are minimized, and bromine-atom selectivities are observed. Thus, SC-CO2 must be useful as a viable, environmentally benign substitute for many of the solvents typically used for free-radical reactions (Tanko and Blackert, 1994). 

Substrates that carry a replaceable benzylic hydrogen atom, or a similar hydrogen that gives rise to a stabilized radical, can be selectively chlorinated or brominated. Ethylbenzene leads to only... 

The stability of free radicals is reflected in their ease of formation. Toluene, which forms a benzyl radical, reacts with bromine 64,000 times faster than does ethane, which forms a primary alkyl radical. Ethylbenzene, which forms a secondary benzylic radical, reacts 1 million times faster than ethane. 

A further useful application of SC-CO2 as a reaction medium is the free-radical side-chain bromination of alkylaromatics, replacing conventional solvents such as tetra-chloromethane or chlorofluorohydrocarbons having no abstractable hydrogen atoms [920]. For example, bromination of ethylbenzene in SC-CO2 at 40 °C and 22.9 MPa yields 95 cmol/mol (1-bromoethyl)benzene, with practically the same regioselectivity as obtained in conventional tetrachloromethane as the solvent. Even the classical Wohl-Ziegler bromination of benzylic or allylic substrates using A-bromosuccinimide (NBS) can be conducted in SC-CO2 [920]. Irradiation of a solution of toluene, NBS, and AIBN (as initiator) in SC-CO2 at 40 °C and 17.0 MPa for 4 hours gave (bromomethyl)-... 

Entry 1 is a chlorination at a stereogenic tertiary center and proceeds with complete racemization. In Entry 2, a tertiary radical is generated by loss of C=0, again with complete racemization. In Entry 3, an a-methylbenzyl radical is generated by a fragmentation and the product is again racemic. Entry 4 involves a benzylic bromination by NBS. The chirality of the reactant results from enantiospecific isotopic labeling of ethylbenzene. The product, which is formed via an a-methylbenzyl radical intermediate, is racemic. 

Like radical side-chain bromination, side-chain chlorination by S02C12 and a peroxide occurs mainly on the a-carbon atom ethylbenzene gives mainly (l-chloroethyl)benzene cumol gives 90% of the a- and 10% of the /9-chloro product. Chlorine enters the jS-position of terf-butylbenzene. o- and p-Nitro-toluene cannot be converted into the corresponding benzyl chlorides by S02C12 and a peroxide.419... 

In order to demonstrate that uncomplexed bromine atoms act as chain propagators, toluene and ethylbenzene were photobromina-ted in a competition study at pressures of 75 to 423 bar and at 40 °C. Over the entire pressure range, the reactivity of the benzylic secondary C-H bond in ethylbenzene was found to be about 30 times greater than that of the corresponding primary C-H bond in toluene. The analogous value for the reactivity in CCI4 at 40 °C is 36. The bromine atoms in SC-CO2 are therefore particularly free. It would be important to determine quantum yields (chain lengths) at various pressures to learn more about mechanistic aspects and other details of the reaction. Local solvent structures on model free-radical reactions in SC-CO2 have been analyzed in some detail. [33]... 

Table IX. 1 gives the data on the relative rates of hydrocarbon oxidation obtained in the mixed oxidation of two hydrocarbons (usually the second hydrocarbon is ethylbenzene). For comparison, the relative reactivity for radicals and bromine atoms is also given in this table.

Halogenation of a larger alkyl side chain is highly regioselective, as illustrated by the halogenation of ethylbenzene. When treated with NBS, the only monobromo organic product formed is 1-bromo-l-phenylethane.This regioselectivity is dictated by the resonance stabilization of the benzylic radical intermediate. The mechanism of radical bro-mination at a benzylic position is identical to that for allylic bromination (Section 8.6A). 

As you should be able to deduce from Problem 13.27, abstraction of hydrogen is especially easy at the a position of ethylbenzene. This abstraction occurs easily because of the resonance stabilization of the henzylic radical (Rg. 13.74). Because bromine will not attack the benzene ring without a catalyst, henzylic positions can often be brominated by simply heating or photolyzing bromine in their presence (Rg. 13.76). 

In addition to the selective oxidation reactions above, a number of other free-radical reactions are summarized herein. Tanko and Blackert (267,268) report the free-radical side-chain bromination of toluene and ethylbenzene in SCCO2 using bromide radicals initiated photochemically from molecular bromine. They report the production of the corresponding benzylic bromides in high yield with selectivities essentially identical to that observed in a conventional chlorinated... 

For each of the following compounds, draw the structure and indicate where radical halogenation is most likely to occur upon heating in the presence of Br2. Then rank the compounds in approximate descending order of reactivity under bromination conditions, (a) Ethylbenzene (b) 1,2-diphenylethane (c) 1,3-diphenylpropane (d) diphenylmethane (e) (l-methylethyl)benzene. 

---