Halogen-substituted alkyl bromides

The effects of halogen atom substituents on the reactivity of alkyl bromides toward 02 have been determined for a series of a-, and Y"kalogen substituted alkyl bromides. Rate constants were determined by stopped-flow techniques and are listed in Table III. Since displacement of chloride by O2 is much slower... 

A slightly different mechanism has been proposed by Cairncross and Sheppard (37) for the reaction of fluoroarylcopper compounds with substituted alkyl halides. Pentafluorophenylcopper can form a complex with bicyclooctyl bromide by coordination with the halogen atom. Such a complex may go directly to coupled product in a four-center process, or, depending on the nature of the group attached and the nature of the alkyl moiety, may form an ion pair which collapses to the coupled... 

We have seen that photolytic halogenation usually leads to a wide variety of products with little or no selectivity. However, the bromination of alkyl bromides gives about 90 per cent substitution on the adjacent carbon. Furthermore, if the adjacent carbon is chiral then it retains its configuration. Suggest a mechanism that may account for these experimental observations. 

The reaction of dibromocarbene with haloalkenes (vinyl halides, alkenes with a halogen more distant from the double bond) leads to the formation of 1,1-dibromocyclopropanes in poor to good yields. However, reactions with allyl halides, particularly substituted allyl bromides, require comment. These alkenes furnish, apart from 1,1-dibromocyclopropanes 1, the alkylation products of tribromomethyl anion 2 and, occasionally, the products of their further transformations (dibromocarbene adducts 3, products of elimination of hydrogen bromide 4 etc.) if they react with bromoform under phase-transfer catalysis conditions (Houben-Weyl, Vol.E19b, pi620). 

Alkylation (R" = alkyl or substituted alkyl) is most satisfactorily accomplished with active halogen compounds such as allyl, benzyl, and propargyl halides, but a-halo ketones, esters, and nitriles can also be used.467,474 Treating l-(l-cyclohexenyl)pyrrolidine with allyl bromide in the presence of /V-ethyl-dicyclohexylamine as base leads to introduction of two allyl groups, i.e., formation of 2,6-diallylcyclohexanone.475 Arylation can be effected by, for example, l-chloro-2,4-dinitrobenzene (R" = 2,4-dinitrophenyl).476 A-Isobutyl-fl-butylamine477 and pyrrolidine478 have been recommended as amine components for C-alkylation by simple alkyl halides such as ethyl and methyl iodides. The following two examples are illustrative ... 

SOLUTION We know that the first reaction has to be a radical halogenation because that is the only reaction that an alkane undergoes. Bromination will lead to a greater yield of the desired 2-halo-substituted compound than will chlorination because the bromine radical is more selective than a chlorine radical. To maximize the yield of substitution product (Section 11.8), the alkyl bromide is treated with acetate ion and the ester is then hydrolyzed to the alcohol, which forms the target compound when it is oxidized. 

In principle, the interaction of a phosphorus(III) ester with an co-haloalkylamine should lead to an (co-aminoalkyl)phosphonic diester or a phosphinic acid analogue (Scheme 11). Such examples in the classical Michaelis-Arbuzov mould have been widely reported, but success in their outcome depends on the relative nucleophilicities of nitrogen and phos-phorus(III) centres towards the displacement of halogen. The interaction of triethyl phosphite and a halogen-substituted tertiary amine, such as 2-chloroethyldiethylamine, does not lead to a phosphonic diester, and in this particular case the product is a piperazinium diquaternary salt. However, successful Michaelis-Arbuzov reactions have been carried out between the bis(bromomethyl)phthalazines 130 (to both the mono- and di-phosphonic acid stages) and the series of [co-(2-cyano-4-pyridine)alkyl]phosphonic diesters 132 (n = 1-4) have been prepared from the 4-pyridinealkyl bromides 131 as precursors to the phosphonoalkylpiperidinecarboxylic acids 133 . ... 

In Chapter IS we introduced nucleophilic substitution at saturated carbon, using as an example some alkyl bromides. Now, radicals do react with alkyl halides—but not at carbon Instead they abstract the halogen, leaving an alkyl radical. 

Another class of esterification reagents are halogenated compounds (alkyl iodides, substituted benzyl, and phena-cyl bromides), which need basic media for their reaction [K2CO3 or DMFA (dimethyl formamide) is normally used for the neutralization of HHal as acid by-product]. For methy-lation of carboxylic acids, some tetra-substituted ammonium hydroxides or halides can be used, e.g., tetramethylammo-nium hydroxide (in aqueous solutions) or trimethylanilinium hydroxide (in methanol solution). The intermediate ammonium carboxylates are thermally unstable and produce methyl alkanoates when the reaction mixtures are heated or when the carboxylates are introduced into the hot injector of the gas chromatograph (flash or on-column methylation) ... 

We have seen several examples of reactions in which two reactants give not a single product but mixtures. Examples include halogenation of alkanes (eq. 2.13), addition to double bonds (eq. 3.31), and electrophilic aromatic substitutions (Sec. 4.11), where more than one isomer may be formed from the same two reactants. Even in nucleophilic substitution, more than one substitution product may form. For example, hydrolysis of a single alkyl bromide gives a mixture of two alcohols in eq. 6.14. But sometimes we find two entirely different reaction types occurring at the same time between the same two reactants, to give two (or more) entirely different types of products. Let us consider one example. 

---