Substitution for halogens

Of the VOCs, the halogenated ones are among the most recalcitrant, and several of them can be harmful at low or very low concentrations. As a consequence, these have been designed as priority pollutants. Unfortunately, substitutes for halogenated compounds cannot always be found in industrial processes. 

The hydroxy groups of pyrrolizidine amino-alcohols are readily replaced by chlorine atoms upon treatment with thionyl chloride (see, e.g., refs. 101 and 103). In this reaction, the allylic hydroxyl group is more reactive and can be selectively replaced by chlorine.79 In some particular cases, methoxyl groups can also be substituted for halogen e.g., l/3-methoxymethyl-8a-pyrrolizidine, when treated with hydro-bromic acid, gives rise to the corresponding bromo derivative.104... 

Scheme 8 summarizes the possibilities. Successful substitution for halogen by carbanions requires reversible addition and that sets upper limits on the reactivity of the anion, although steric effects can also favor equilibration (more-substituted equilibrate faster). As before, fluoride is a better leaving group than chloride. An example is shown in equation (16), producing methyl 2-phenyl-2-(/-butylthio)propionate (24) in 94% yield after 15 h at 25 °C. There is an important solvent effect on the rate of equilibration of the carbanions68 and the conditions chosen for these early experiments are not necessarily die best there may be room to expand the scope of useful anions by careful choice of media (less polar solvents should favor equilibration). 

The halogenopurines react with many other nucleophiles including hydrazines, hydrox-ylamine and alkoxyamines, sulfonic acids and thiocyanates, and compounds with active methylene groups such as diethyl malonate furnish appropriate purine derivatives which offer valuable routes to alkyl and substituted alkyl derivatives. Also aryl groups have been substituted for halogen using aryllithiums (63N224). 

Under basic conditions, all the a-hydrogens are substituted for halogens. 

This type of nucleophilic aromatic substitution for halogen has been studied extensively, and it has been determined that reaction occurs in two steps nucleophilic addition followed by elimination. For the majority of reactions of this type, addition of the nucleophile in Step 1 is the slow, rate-determining step. Elimination of halide ion in Step 2 gives the product. This reaction thus resembles reactions of carboxylic acid derivatives in that it proceeds by an addition-elimination mechanism rather than by direct substitution. 

Reactions via organometallic intermediates achieve position selectivity on the basis of prior substitution, for example through halogen-metal e.xchange... 

The reaction of an alcohol with a hydrogen halide is a substitution A halogen usually chlorine or bromine replaces a hydroxyl group as a substituent on carbon Calling the reaction a substitution tells us the relationship between the organic reactant and its prod uct but does not reveal the mechanism In developing a mechanistic picture for a par ticular reaction we combine some basic principles of chemical reactivity with experi mental observations to deduce the most likely sequence of steps... 

Table 8 1 illustrates an application of each of these to a functional group transfer matron The anionic portion of the salt substitutes for the halogen of an alkyl halide The metal cation portion becomes a lithium sodium or potassium halide... 

The strength of their carbon-halogen bonds causes aryl halides to react very slowly in reactions in which carbon-halogen bond cleavage is rate determining as m nude ophilic substitution for example Later m this chapter we will see examples of such reactions that do take place at reasonable rates but proceed by mechanisms distinctly dif ferent from the classical S l and 8 2 pathways... 

Halogens add to butenediol, giving 2,3-dihalo-l,4-butanediol (90,91). In a reaction typical of aHyhc alcohols, hydrogen haUdes cause substitution of halogen for hydroxyl (103). 

Halogen exchange with KF is not successful ia acetic acid (10). Hydrogen bonding of the acid hydrogen with the fluoride ion was postulated to cause acetate substitution for the haUde however, the products of dissolved KF ia acetic acid are potassium acetate and potassium bifluoride (11). Thus KF acts as a base rather than as a fluorinating agent ia acetic acid. 

The determination of iodine value (IV), AOCS Tg 1-64, is sometimes used to determine the extent of unsaturation. Because the tertiary aUyflc hydrogen ia the compounds is capable of substitution by halogen atoms, this only approximates a value for the degree of unsaturation. 

No simple electrophilic substitution, for example nitrosation, nitration, sulfonation or halogenation of a C—H bond, has so far been recorded in the pteridine series. The strong 7T-electron deficiency of this nitrogen heterocycle opposes such electrophilic attack, which would require a high-energy transition state of low stability. 

The reaction exhibits other characteristics typical of an electrophilic aromatic substitution. Examples of electrophiles that can effect substitution for silicon include protons and the halogens, as well as acyl, nitro, and sulfonyl groups. The feet that these reactions occur very rapidly has made them attractive for situations where substitution must be done under very mild conditions. ... 

Acylhalogenation of haloolefins is most often carried out with aluminum chloride as the catalyst The yields are variable because of side reactions including halogen exehange Halogen exchange is avoided and yields are higher when ferric chloride is substituted for aluminum chloride in the reaction of fluoroethene with acid chlorides [3] (equation 3)... 

When we discussed elimination reactions in Chapter 5, we learned that a Lewis base can react with an alkyl halide to form an alkene. In the present chapter, you will find that the same kinds of reactants can also undergo a different reaction, one in which the Lewis base acts as a nucleophile to substitute for the halogen substituent on carbon. 

The reaction time between 4-iodopyrazoles and 1-alkynes varies from 5 to 25 h and the yield of products is 55-95%. It is noteworthy that the nature of the terminal acetylene has a greater effect on the rate of halogen atom substitution for low-reactive 4-iodopyrazoles. Thus, the reaction time for ethynylarenes is 5-6 h, and for less acidic aliphatic 1-alkynes is 10-25 h (Table XTT). 

The introduction of halogen into organic molecules can be carried out by a variety of addition or substitution reactions. The classical methods for the addition of halogen to double bonds or the substitution of halogen for hydroxyl by hydrohalic acids are too well known to bear repetition here. Discussed below, then, are methods that are of interest because of their stereospecific outcome or because they may be used on sensitive substrates. 

This compound is heated with caustic potash solution, yielding beta-hydroxy-coumarin. From this body, coumarin is obtained by substituting a halogen atom for the OH group, and then reducing the product in alcoholic solution with zinc-dust. 

The negative charge and unshared electron pair on carbon make an acetylide anion strongly nucleophilic. As a result, an acetylide anion can react with an alkyl halide such as bromomethane to substitute for the halogen and yield a new alkyne product. 

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