Ethylbenzene, benzylic bromination

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. 

The allylic bromination of cyclohexene was successfully done using co(polyethylene-N-bromomaleimide). When polymeric AT-bromosuccin-imide ( -NBS) was used for bromination of cumene, products other than those of benzylic bromination were also formed (Scheme 12-10) (Yaroslavsky et aL, 1970a,b). The change in mechanism has been attributed to the polar environment provided by neighboring succinimide units in (p)-NBS. Polymeric A/-chloromaleimide, synthesized by Yaroslavsky and Katchalski (1972), on reaction with ethylbenzene, also gave products due to aromatic substitution. 

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)-... 

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). 

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... 

The bromination of toluene with bromine in SC-CO2, photochemically initiated through a sapphire window, led to benzyl bromide (74%) and 4-bromotoluene (11%). Ethylbenzene afforded 1-bromo-l-phenylethane in 95 % yield (Scheme 4). [23]... 

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]... 

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). 

Arenes such as ethylbenzene react with NBS to give products in which bromine substitution has occurred at the benzylic position. Explain the result, and propose a mechanism. 

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... 

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