Halomethylation reactions, aromatic

Aromatic and heteroaromatic aldehydes can alternatively be prepared from the corresponding methyl compound by subjecting the chloromethyl or bromomethyl derivative to the Sommelet reaction. This procedure involves an initial reaction between the halomethyl compound and hexamethylenetetramine (hexamine), and hydrolysing the resulting quaternary hexamine salt (4) with hot aqueous acetic acid. 

Friedel—Crafts reactions with halomethyl aromatic compounds have been used to prepare several types of polymers. The reaction is usually unsatisfactory because of the formation of either low-molecular-weight or crosslinked polymers. Rate studies are complicated by the multifunctional nature of the reactants, and often by limited solubility of the products. The kinetics of the first two steps of the reaction between benzene and p-bis-chloromethylbenzene with SnC catalysts were investigated by Grassie and Meldrum [212]. The activation energy was found to be about 10 kcal mole . ... 

The coupling reaction between p-toluenesulfonamide and the appropriate bis(halomethyl)aromatic compound, followed by removal of the tosyl groups, was developed as a simple and general route to the peraza-cyclophanes (Bot-tino et al., 1988 Takemura et al., 1984). In this reaction, carried out under... 

The a-halomethyl analogs of amino acids have proved to be potent inactivators of their respective decarboxylases, as exemplified by the reaction of a-fluoro-methyl-DOPA (4, Fig. 4) with aromatic-amino-acid decarboxylase (Maycock... 

Chart I shows the structures of the bis(halomethyl) aromatics 18 -- 26 that we have used in our studies. These compounds were commercially available or were prepared by the reaction of N-bromosuccinimide with the corresponding o-xylene derivatives. 

Such is the case also for jV-(halomethyl) carboxamides (R = H or alkyl, R = acyl)721 and iV-(halomethyl) diacylamides (R and R = acyl), which are specific for amidomethylation of / -diketones, a reaction that cannot be effected otherwise) for a review of these reactions see Gross and Hoft679). Amino- and amido-methylation of aromatic carbocyclic and heterocyclic compounds by -halo amines and amides have also been reported.707,722,723... 

In polar solvents, a-halomethyl aromatics give rise to photochemical reactions that can be explained by both radical and ionic mechanisms. Equation 12.77 shows the results for irradiation of 1-chloromethylnaphtha-lene (119) in methanol. The most direct pathway for formation of the methyl ether 120 is heterolytic dissociation of the C-Cl bond to give a chloride ion and a 1-naphthylmethyl carbocation, the latter then undergoing nucleophilic addition by the solvent. Indeed, naphthylphenylmethyl carbocations were detected spectroscopically following laser flash photolysis of (naphthylphenylmethyl)triphenylphosphonium chlorides. On the other hand, products 121, 122, and 123 appear to be formed via the 1-naphthylmethyl radical. Therefore, an alternative source of the carbocation leading to 120 could be electron transfer from the 1-naphthylmethyl radical instead of direct photochemical heterolysis of 119.215-216 jaj-g g p. 

Halomethyl sulfone reagents have been used as a-carbanion stabilizing substituents as well as precursors for alkenes, epoxides, and aziridines syntheses. It is worth mentioning that only aromatic substrates were used, typically phenyl sulfones, and no example has been reported with heterocyclic compounds such as phenyltetrazole. In this regard, we wUl focus on olefination reactions only. 

Recently, Hodgson et al. have employed halomethyl esters to trap the p-oxido phosphonium ylide intermediate generated in Schlosser s modified sequence (Scheme 15) [81, 82]. Aromatic, unsaturated, and aliphatic aldehydes serve as suitable substrates for this reaction, which provides a highly Z-selective access to di- and trisubstituted allylic esters. 

Reactions of formaldehyde with aromatic hydrocarbons are similar in cane respects to those involving olefins and may involve a somewhat similar mechanism. However, reactions apparently proceed further than in the ca of olefins, and the simple addition products of methylene ycol or sahstituted methylene glycol have not been isolated. With aromatic hydrocarbons, formaldehyde and hydrogen halides, the primary reaction products isolated are compounds in which one or two halomethyl groups are substituted for hydrogen on the aromatic nucleus. On further reaction, compounds are obtained in which two or more aromatic nuclei are linked together by methylene gi oups. When sulfuric acid is employed as a reaction catalyst, methylene derivatives of this latter type are apparently the pi incipal products obtained. 

Formation of Diarylmethanes and Hydrocarbon Resins. The foimation of diarylmethanes and compounds in which seA -eral aromatic nuclei are linked by methylene groups represents a further stage of formaldehyde ccaidensation than, that inAmlved in halomethylations. These substances are obtained as by-products of halomethylations and predominate Avhen the reaction is run for an excessive length of time or otherwise subjected to... 

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