Polar addition halogenation

It is important to be able to look at a molecular structure and deduce the possible reactions it can undergo. Take an alkene, for example. It has a 7t bond that makes it electron-rich and able to attack electrophiles such as water, halogens and hydrogen halides in electrophilic addition reactions. Haloalkanes, on the other hand, contain polar carbon-halogen bonds because the halogen is more electronegative than carbon. This makes them susceptible to attack by nucleophiles, such as hydroxide, cyanide and alkoxide ions, in nucleophilic substitution reactions. 

The fact that the Br2 concentration remains at very low levels is important to the success of the allylic halogenation process. The allylic bromination of alkenes must compete with polar addition of bromine via a bromonium ion intermediate. The reactions differ in their dependence on bromine concentration. The allylic substitution is one-half order in bromine, whereas the addition reaction follows a first- or second-order dependence on [Br2] (see Section 5.3). Therefore a low concentration of Br2 favors substitution over addition. 

Although the vast majority of stepwise polar additions to ortho-benzyne involve nucleophilic attack on the aryne, electrophilic attack is also possible provided that the aryne is generated by a method that does not involve strongly basic conditions. Few such additions are synthetically useful, with the exception of the formation of 1,2-dihalobenzenes by reactions of ortho-benzynes with halogens, although alternative mechanisms initiated by nucleophilic attack of halide may be envisaged. Radical reactions of ortHo-benzyne, on the other hand, are extremely rare. 

In photohalogenation reactions, keeping the concentration of X2 low is essential to success. If there is too much halogen, polar addition to give vicinal dihalides competes with formation of the allylic halide, and the desired selectivity is lost. 

Other Reactions of Phospholipids. The unsaturated fatty acid groups in soybean lecithin can be halogenated. Acetic anhydride combined with the amino group of phosphatidylethanolamine forms acetylated compounds. PhosphoHpids form addition compounds with salts of heavy metals. Phosphatidylethanolamine and phosphatidjhnositol have affinities for calcium and magnesium ions that are related to interaction with their polar groups. 

I > Br > Cl > F. In nucleophilic aromatic substitution, the formation of the addition intermediate is usually the rate-determining step so the ease of C—X bond breaking does not affeet the rate. When this is the ease, the order of reactivity is often F > Cl > Br > I. This order is the result of the polar effeet of the halogen. The stronger bond dipoles assoeiated with the more eleetronegative halogens favor the addition step and thus inerease the overall rate of reaetion. 

Typical normal-phase operations involved combinations of alcohols and hexane or heptane. In many cases, the addition of small amounts (< 0.1 %) of acid and/or base is necessary to improve peak efficiency and selectivity. Usually, the concentration of polar solvents such as alcohol determines the retention and selectivity (Fig. 2-18). Since flow rate has no impact on selectivity (see Fig. 2-11), the most productive flow rate was determined to be 2 mL miiT. Ethanol normally gives the best efficiency and resolution with reasonable back-pressures. It has been reported that halogenated solvents have also been used successfully on these stationary phases as well as acetonitrile, dioxane and methyl tert-butyl ether, or combinations of the these. The optimization parameters under three different mobile phase modes on glycopeptide CSPs are summarized in Table 2-7. 

In addition to the polar mechanism already considered (p. 179), halogen addition to alkenes can proceed via radical intermediates. The former is favoured by polar solvents and by the presence of Lewis acid catalysts, the latter by non-polar solvents (or in the gas phase),... 

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