Phenyl halides

The lack of a uniform order of relative reactivity of the halogens in reactions of certain nucleophiles with nitro- and polynitro-phenyl halides led Parker and Read to propose a one-stage mechanism for some aromatic nucleophilic substitutions. An alternative explanation within the framework of the two-stage S Ar2 mechanism had been proposed earlier. A range of mechanisms has been considered in the past by Chapman, who properly points out that only in a limited number of examples is the evidence for the two-stage mechanism compelling even though the balance of evidence favors it. 

The radical cyclization test has been applied and although 2-(3-butenyl)phenyl halides give little if any cyclization, substituents that are expected to increase the rate of cyclization to around 109s 1 do give some cyclic product.14... 

Dialkyl esters of 1,3,4-hexatrienephosphonic acid react with alkyl(phenyl)sul-phenyl halides, to form mixture of 2,5-dihydro-l,2-oxaphosphole-2-oxide derivatives and thiophene derivatives (Scheme 69) [147-149]. 

Vinylic halides and phenyl halides are generally unreactive in SnI or SnI reactions. 

The C-X bond of a vinylic or phenyl halide is stronger than that of an alkyl halide and the electrons of the double bond or benzene ring repel the approach of a nucleophile from the back side. 

Low-valent cobalt pyridine complexes, electrogenerated from CoCl2 in DMF containing pyridine and associated with a sacrificial zinc anode, are also able to activate aryl halides to form arylzinc halides.223 This electrocatalytic system has also been applied to the addition of aryl bromides containing an electron-withdrawing group onto activated alkenes224 and to the synthesis of 4-phenylquinoline derivatives from phenyl halides and 4-chloroquinoline.225 Since the use of iron as anode appeared necessary, the role of iron ions in the catalytic system remains to be elucidated. 

It is also possible to make similar arguments for other cases, say photo-decomposition of phenyldiazonium salts 17 ) or phenyl halides. 

The order of reactivity of the C-X bond (generally I > Br > Cl > F) is consistent with its strength. For instance, the experimentally found dissociation energies for phenyl halides (DPh x) are 528, 402, 339, and 272 kj mol-1 at 298 K for X=F, Cl, Br, and I, respectively [2]. Consequently, catalytic defluorination in the literature is comparatively rare. The different reactivity of the C-X bonds renders possible the selective dehalogenation of compounds containing two dissimilar halides, leaving intact the stronger C-X bond. 

Just as in phenyl halides, the halogen can be replaced by hydrogen, by a metal, or be coupled. Two of the four mechanisms of such nucleophilic substitutions are also familiar from benzene chemistry via arynes and by the SRN1 mechanism. However, of the two further mechanisms of nucleophilic replacement, the ANRORC is unique to heterocycles, and SAE reactions occur only with strongly activated benzenoid systems. 

Halogen atoms in pyrones and pyridones e.g. 902) are unreactive toward SAE nucleophilic displacement. 3-Halopyridines are less reactive than the a- and 7-isomers but distinctly more reactive than unactivated phenyl halides. Thus, a bromine atom in the 3-position of pyridine or quinoline can be replaced by methoxy (NaOMe-MeOH, 150°C), amino (NH3-H20-CuS04, 160°C) or cyano (CuCN, 165°C). 5-Halogens in pyrimidines are also relatively unreactive. 

Phosphanions with Phenyl Halides in Liquid Ammonia ... 

What about substituents that are groups other than HO, MeO or MDO (and of course the unsubstituted H) Homologues of MeO such as ethoxy and benzyloxy (EtO, BzO), alkyl groups such as methyl, phenyl, halides, carboxy or substituted carboxy groups, esters of phenols,... 

The reaction of aryl and hetaryl halides with the nitrile-stabilized carbanions (RC -CN) leads to derivatives of the type ArCH(R)CN. Sometimes, however, dimeric products of the type ArCH(R)CH(R)Ar are formed (Moon et al. 1983). As observed, 1-naphthyl, 2-pyridyl, and 2-quinolyl halides give the nitrile-substituted products, while phenyl halides, as a rule, form dimers. The reason consists of the manner of a surplus electron localization in the anion radical that arises upon replacing halogen with the nitrile-containing carban-ion. If the resultant anion radical contains an unpaired electron within LUMO covering mainly the aromatic ring, such an anion radical is stable, with no inclination to split up. It is oxidized by the initial substrate and gives the final product in the neutral form, Scheme 1-7 ... 

Mesylates are used for Ni-catalysed reactions. Arenediazodium salts 2 are very reactive pseudohalides undergoing facile oxidative addition to Pd(0). They are more easily available than aryl iodides or triflates. Also, acyl (aroyl) halides 4 and aroyl anhydrides 5 behave as pseudohalides after decarbonylation under certain conditions. Sulfonyl chlorides 6 react with evolution of SO2. Allylic halides are reactive, but their reactions via 7t-allyl complexes are treated in Chapter 4. Based on the reactions of those pseudohalides, several benzene derivatives such as aniline, phenol, benzoic acid and benzenesulfonic acid can be used for the reaction, in addition to phenyl halides. In Scheme 3.1, reactions of benzene as a parent ring compound are summarized. Needless to say, the reactions can be extended to various aromatic compounds including heteroaromatic compounds whenever their halides and pseudohalides are available. 

Trichlorogermane does not react with phenyl halides and naphthyl halides. This is again indicative of the electrophilic nature of the interaction between trichlorogermane and the aromatic compounds. 

Dichiarante, V., Fagnoni, M. and Albini, A. (2006) Convenient synthesis of electron-donating substituted benzonitriles by photolysis of phenyl halides and esters. Chemical Communications, 3001-3003. 

Nitro-substituted phenyl halides produce radical anions that fragment with a rather low rate (=10 2-102/s) [28]. For this reason the nitro group is not a suitable substituent for most aromatic SrnI reactions. However, exceptions are found with o-iodonitrobenzene [29] whose radical anion has a relatively high rate of fragmentation, and nitroaryldiazo phenyl or tert-butyl sulfides [30]. 

The main feature of carbanions derived from nitriles lies in the dependence on the aromatic substrate involved thus, two different outcomes of the substitution reaction are possible formation of the substitution compound by ET to the substrate from the radical anion intermediate 7, formed by coupling of phenyl radicals and acetonitrile anion, or formation of products from elimination of the cyano group as is the case with phenyl halides [31,32] (Sch. 3). The same reactivity pattern is found with halothiophenes [33]. 

The extensive determination of fragmentation rates of aryl halide radical anions, due to Saveant and coworkers15a by electrochemical methods, indicates that they range from values of 10-2s-1 for nitro-substituted phenyl halides up to 1010 s-1 for />-cyanophenyl halides. These values are in agreement with measurements by pulse radiolysis42. The fragmentation rates for unsubstituted phenyl halides are too high to be measured even by electrochemical techniques. Besides, 1-bromo- and 1-iodoanthraquinone radical anions have been shown to dissociate from their photoexcited state (Section V. D). 

As previously indicated, monoanions of / -dicarbonyl compounds fail to react with phenyl halides however, the 1,3-dianions are suitable nucleophiles and react quite well through the terminal carbanion site185. 

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