Toluene benzylic halogenation

Bromo- and chloro-iodinanes (29 and 31) behave as free radical halogenating agents (79JA3060). They give photoinitiated benzylic halogenation of toluene or allylic halogenation of cyclohexene in high yield. Cyclic 10-C1-3 and 10-F-3 species have not yet been reported. 

In the aromatic series it is observed that the introduction of a halogen atom into the side chain of a substance confers lachrymatory properties, while if it replaces a hydrogen atom from the benzene nucleus, a substance results which has no physiopatho-logical properties. Thus, from toluene, benzyl bromide, CgHj—CHjBr, is obtained in the first case. This has energetic lachrymatory properties, while bromotoluene, CgH4Br—CH3, has no toxic action. 

Benzylic halogenation provides a useful way to introduce a leaving group when a leaving group may be needed for subsequent nucleophilic substitution or elimination reactions. For example, if we wished to synthesize benzyl ethyl ether from toluene, benzyl bromide could be prepared from toluene as above, and then benzyl bromide could be allowed to react with sodium ethoxide as follows. 

In the absence of catalysts, toluene when treated with chlorine (or bromine) at the boiling point, preferably with exposure to sunlight or other bright light source, undergoes halogenation in the side chain. The entrance of the first chlorine atom, for example, proceeds at a much faster rate than the entrance of the second chlorine atom so that in practice the major portion of the toluene is converted into benzyl chloride before appreciable chlorination of benzyl chloride occurs ... 

The comparative ease with which a benzylic hydrogen is abstracted leads to high selectivity m free radical halogenations of alkylbenzenes Thus chlorination of toluene... 

Some radicals (e.g., tert-butyl, benzyl, and cyclopropyl), are nucleophilic (they tend to abstract electron-poor hydrogen atoms). The phenyl radical appears to have a very small degree of nucleophilic character. " For longer chains, the field effect continues, and the P position is also deactivated to attack by halogen, though much less so than the a position. We have already mentioned (p. 896) that abstraction of an a hydrogen atom from ring-substituted toluenes can be correlated by the Hammett equation. 

FIG. 1 Molecular structures of the drugs examined in the delivery study the general anesthetics, alkanols (I), halothane (II), enflurane (III), isoflurane (IV), halogenated cyclobutane (V) the local anesthetics, dibucaine hydrochloride (VI), procaine hydrochloride (VII), tetracaine hydrochloride (VIII), lidocaine hydrochloride (IX), benzyl alcohol (X) the endocrine disruptor, bisphenol A (XI), and alkylbenzenes, benzene (XII), toluene (XIII), ethylbenzene (XIV), and propylbenzene (XV). 

Polystyrene-bound allylic or benzylic alcohols react smoothly with hydrogen chloride or hydrogen bromide to yield the corresponding halides. The more stable the intermediate carbocation, the more easily the solvolysis will proceed. Alternatively, thionyl chloride can be used to convert benzyl alcohols into chlorides [7,25,26]. A milder alternative for preparing bromides or iodides, which is also suitable for non-benzylic alcohols, is the treatment of alcohols with phosphines and halogens or the preformed adducts thereof (Table 6.2, Experimental Procedure 6.1 [27-31]). Benzhy-dryl and trityl alcohols bound to cross-linked or non-cross-linked polystyrene are particularly prone to solvolysis, and can be converted into the corresponding chlorides by treatment with acetyl chloride in toluene or similar solvents (Table 6.2 [32-35]). 

Benzyl cyanide is the product of nucleophilic substitution by cyanide ion on benzyl bromide or benzyl chloride. The benzyl halides are prepared by free-radical halogenation of the toluene side chain. 

Non-activated methyl groups are never attacked in these reactions toluene can be functionalized but isolation of the resulting benzyl halides from these PTC mixtures is difficult. Most remarkable is that strained hydrocarbons such as cubane (5) or 2,4-didehydroadamantane (6) can also be halogenated with conservation of the cage [27], in marked contrast with the halogenation reactions of these substrates with halogen radicals [40]. Dihalogenations with either the same or a differ-... 

In the absence of a Lewis acid, halogenation of toluene at its boiling point with bromine or chlorine and under UV irradiation e.g. sunlight) occurs in the side chain. The reaction proceeds by a free-radical mechanism that is initiated by the photolytic dissociation of a chlorine molecule (Scheme 9.10). The benzyl radical is stabilized by resonance (see Chapter 3). 

Halogenation of hydrocarbons. Walling found /-butyl hypochlorite useful for light- or radical-induced chain chlorination of toluene. Thus, in the presence of azobisisobutyronitrile as initiator, the reaction with toluene at 40° affords benzyl chloride (84%), /-butanol (97%), and 1-3% each of chlorololuenes, methyl chloride, and acetone. 

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