Aromatic compounds, chloromethylation

Chloromethjlation Reactions. The introduction of the chloromethyl group to both aHphatic and aromatic compounds is carried out by reaction of paraformaldehyde [30525-89-4] and hydrogen chloride. This method is used for synthesizing methyl chloromethyl ether [107-30-2], benzyl chloride [100-44-7], and chloromethyl acetate. 

The introduction of a chloromethyl group on aromatic compounds (e.g. benzene 1) by reaction with formaldehyde 2 and gaseous hydrogen chloride in the presence of a catalyst is called the Blanc reaction ... 

An important side reaction is the formation of diaryl methane derivatives ArCHaAr. Moreover poly substituted products may be obtained as minor products. Aromatic compounds have been treated with formaldehyde and hydrogen bromide or hydrogen iodide instead of hydrogen chloride. The formaldehyde may be replaced by another aldehyde the term Blanc reaction however stands for the chloromethylation only. 

Among the Friedel-Crafts alkylations of aromatic compounds with (chlorinated alkyl)silanes, the alkylation of benzene with (tt>-chloroalkyl)silanes in the presence of aluminum chloride catalyst was generally affected by two factors the spacer length between the Cl and silicon and the electronic nature of substituents on the silicon atom of (w-chloroalkyl)silanes. As the spacer length between the C—Cl and silicon increases from (chloromethyl)silane to (/i-chloroethyl)silane to (/-chloropropyl)silane, the reactivity of the silanes increases. As the number of chloro-groups on the silicon decreases from (chloromethyl)trichlorosilanes to (chloromethyl)methyldichlorosilanes to (chloromethyl)trimethylsilanes, the... 

From chloromethyl or bromomethyl aromatic compounds by heating with hexamethylenetetramine (hexamine) in aqueous alcohol or aqueous ac ic acid. A quaternary ammonium compound is formed, which yields the aldehyde upon treatmait with water in the presence of hexamine for example... 

Many side-chain halogen compounds can be synthesized by reactions that also are applicable to alkyl halides (see Table 14-5), but there are other methods especially useful for the preparation of arylmethyl halides. The most important of these are the chloromethylation of aromatic compounds (to be discussed later in this section) and radical halogenation of alkylbenzenes. 

If the activated aromatic compound reacts with a mixture of formalin, concentrated hydrochloric acid, and ZnCl2, the result is a so-called chloromethylation (Figure 5.29). The stable reaction product is a primary benzyl chloride. This reaction is initiated by an electrophilic substitution by protonated formaldehyde it is terminated by an SN1 reaction in which a chloride ion acts as the nucleophile. 

The reaction of toluene-2,4-diisocyanate with chlorine to l-chloromethyl-2,4-diisocyanatobenzene was carried out in a falling-film microstructured reactor with a transparent window for irradiation [264]. There are two modes of reaction. The desired radical process proceeds with the photoinduced homolytic cleavage of the chlorine molecules, and the chlorine radical reacts with the side chain of the aromatic compound. At very high chlorine concentrations radical recombination becomes dominant and consecutive processes such as dichlorination of the side chain may occur as well. Another undesired pathway is the electrophilic ring substitution to toluene-5-chloro-2,4-diisocyanate, promoted by Lewis acidic catalysts in polar solvents at low temperature. Even small metallic impurities probably from corrosion of the reactor material can enhance the formation of electrophilic by-products. 

If the activated aromatic compound formalin, concentrated hydrochloric acid, and ZnCl2 react with each other, the result is a so-called chloromethylation (Figure 5.24) ... 

The formation of norcaradiene derivatives with naphthalene [reaction (22)] lends some support to this scheme. This mechanism resembles a bimolecular two-step process suggested for the reaction of chloromethyl-aluminum compounds with olefins (199-201). On the other hand, a bimolecular one-step methylene transfer mechanism is generally accepted for the formation of cyclopropane derivatives by the reaction of halo-methylzinc compounds with olefins. This difference between the mechanism proposed for the cyclopropane formation from olefin and that for the ring expansion of aromatic compound may be ascribable to the difference in the stability of intermediates the benzenium ion (XXII) may be more stable than an alkylcarbonium ion (369). 

A survey of the chlotomethylation of aromatic compounds has been made, and a thorough study of the conditions of the reaction for the production of benzyl chloride has been carried out. The reaction is generally applicable to aromatic hydrocarbons. The effect of substituents on the ease of chloromethylation is pronounced alkyl and alkoxyl groups facilitate the introduction of the chloromethyl group, whereas halogen, Carboxyl, and nitro substituents retard or prevent the reaction. Zinc chloride, sulfuric acid, and phosphoric acid have been used as catalysts when needed. A chief by-product is the f is -chloromethyl compound. 

BiscMorome Uition. Electron-poor tetrasubstitutcd aromatic compounds such as nitromesitylene (1) are bischloromethylated when treated with chloromethyl methyl ether and 60% fuming sulfuric acid. ... 

Selective haloalkylation of aromatic compounds has also been achieved by employing alkyl haloalkyl ethers as the haloalkylating agents, as seen from equations (88) and (89). However, the use of chlo-romethyl ethers in chloromethylation (equation 89) is discouraged due to the carcinogenic nature of the ether substrate. As an alternative, chloromethylation reactions can also be carried out using paraformal-dehyde-HCl in the presence of ZnCh or SnCU as catalyst. ... 

Chloromethylation of Aromatic Compounds Reynold C. Fuson and C. H. McKeever... 

---