Toward electrophilic reagents halogenation

There are a wide variety of methods for introduction of substituents at C3. Since this is the preferred site for electrophilic substitution, direct alkylation and acylation procedures are often effective. Even mild electrophiles such as alkenes with EW substituents can react at the 3-position of the indole ring. Techniques for preparation of 3-lithioindoles, usually by halogen-metal exchange, have been developed and this provides access not only to the lithium reagents but also to other organometallic reagents derived from them. The 3-position is also reactive toward electrophilic mercuration. 

In addition, protic acids also cleave organomercurials to yield the proton-substituted products analogous to those for halogenation above. Finally, mercuric salts also act as electrophilic reagents towards organomercurials. 

The Sn-S, Sn-Se, and Sn Te bonded compounds are less reactive than Sn-O bonded species, e g. towards water. Reactions proceed with a variety of electrophilic reagents (e.g. alkyl halides, halogens, and snlfur(n) halides). 

From the structure of the double bond we might expect that here again it is an electron source, a base, and hence that the halogen acts as an electrophilic reagent, an acid. This idea is supported by the fact that alkenes usually show the same order of reactivity toward halogens as toward the acids already studied electron-releasing substituents activate an alkene, and electron-withdrawing substituents deactivate an alkene. 

Vinylcopper reagents react with a wide variety of electrophilic reagents such as halogens, alkyl halides, allylic halides, acid chlorides, epoxides, a,(3-unsaturated ketones, and a,p-acetylenic esters with complete retention of the double bond stereochemistry. To enhance the reactivity of vinylcopper intermediates toward carbon electrophiles, the coupling is often carried out in the presence of activators such as HMPT, DMPU, and/or P(OEt)3 (triethylphosphite). Some representative examples of stereospecific... 

It is observed that a halogen para to the carbonyl moiety of 2(l//)-pyrazinones is extremely inert towards nucleophilic displacement, whereas an ortho halogen is displaced relatively readily. However, use of butyllithium brings about lithio-dehalogenation in 5-bromo- or 5-iodo-2(l//)-pyrazinones (104), which are prepared from the corresponding 2(l//)-pyrazinones (103) with NBS or NIS, respectively <91H(32)2407>. Electrophilic reagents with these lithio intermediates (105) then afford the 5-substituted 2(l//)-pyrazinones (106 Scheme 24). 

Carbon-carbon double bonds, whether attached directly to or are distant from the phosphorus, can undergo some unusual reactions, particularly when treated with electrophilic reagents such as the halogens or pseudo-halogens, a behaviour attributable to phosphoryl nucleophilic character. Ethenylphosphonic acid and its simple derivatives add chlorine or bromine with the expected overall results, but the normal addition of the latter is rapidly accelerated by UV radiation and inhibited by added iodine, suggestive of a homolytic nature Dialkyl (pent-4-enyl)phosphonates (373 R = RO, X = CH2, n = 2) equally add bromine to give the expected dibromo adducts, but their behaviour towards iodine is more complex (Scheme 49). In reactions in CHCI3 at ambient temperature, not only are the expected 4,5-diiodo adducts 374 formed, but so is an additional species, probably a quasi-... 

Similarly, the cation will be even less reactive than the keto form towards halogens or other electrophilic reagents hence, provided that the reaction between halogen and enol is fast enough, the rate of halogenation will also be equal to the rate of enol formation and independent of the concentration or nature of the halogenating agent, as is usually found. 

The side-chain double bond is more reactive than the aromatic ring toward most electrophilic reagents. Many of the reactions of alkenes that were discussed in Chapter 6 find a parallel in the reactions of alkenylbenzenes. Thus, hydrogenation and halogen addition to a side-chain double bond can be achieved while leaving the ring unchanged. 

The introduction of the halogens onto aromatic rings by electrophilic substitution is an important synthetic procedure. Chlorine and bromine are reactive toward aromatic hydrocarbons, but Lewis acid catalysts are normally needed to achieve desirable rates. Elemental fluorine reacts very exothermically and careful control of conditions is required. Molecular iodine can effect substitution only on very reactive aromatics, but a number of more reactive iodination reagents have been developed. 

The electrophilic substitution reactions commonly used with aromatic compotmds could not be applied to monosubstituted oxadiazoles 25a, 55 b). The hydrogen atoms in position 3 and 5 of these derivatives could not be replaced by a halogen atom or a nitro group and are also inactive towards Friedel-Craft reagents. 

Electrophilic Substitution Iodine labeling can be obtained by using molecular iodine and oxidation reagents, such as peracetic acid, imides and amides, which increase the electrophilic reactivity of the halogen toward aromatic compounds. 

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