Chloromethylation, of aromatic compounds

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. 

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

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... 

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. 

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. ... 

Bromomethylation is also possible, e.g.y the preparation of benzyl bromide in 86.5% yield from benzene, formaldehyde, and hydrogen bromide in acetic plus sulfuric acid.684,685 So is iodomethylation of aromatic compounds, by reaction of bis(chloromethyl) ether and hydrogen iodide in glacial acetic acid.686... 

The iodination of aromatic compounds using the electrophilic fluorinating agent l-(chloromethyl)-l,4-diazabicyclo[2,2,2]octane tetrafluoroborate and iodine was carried out in a range of [BF4] and [PFe]" ionic liquids and generally gave high yidds [106]. Trihalide-based ionic liquids have been synthesised and the structure of the... 

Sc(OTf)3 was widely used as a Lewis acid catalyst in Friedel-Crafts acylation [38-40], amination [41], chloromethylation [42], and nitration of aromatic compounds [43]. It also exhibited a superior catalytic activity for one-pot three-component phenol-imine Friedel-Crafts reactions to give the corresponding amino acid derivatives. Among various Lewis acids including La(OTf)3, Yb(OTf)3, YbCl3, InCl3, SnCU, and TiCU, Sc(OTf)3gave the best results (Scheme 12.21) [44]. 

Other Alkylations. The chloromethylation of aromatic and heteroaromatic compounds has been reviewed, in Russian/ ... 

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. 

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... 

The photodissociation of aromatic molecules does not always take place at the weakest bond. It has been reported that in a chlorobenzene, substituted with an aliphatic chain which holds a far-away Br atom, dissociation occurs at the aromatic C-Cl bond rather than at the much weaker aliphatic C-Br bond (Figure 4.30). This is not easily understood on the basis of a simple picture of the crossing to a dissociative state, and it is probable that the reaction takes place in the tt-tt Si excited state which is localized on the aromatic system. There are indeed cases in which the dissociation is so fast (< 10-12 s) that it competes efficiently with internal conversion. 1-Chloromethyl-Np provides a clear example of this behaviour, its fluorescence quantum yield being much smaller when excitation populates S2 than when it reaches Figure 4.31 shows a comparison of the fluorescence excitation spectrum and the absorption spectrum of this compound. This is one of the few well-documented examples of an upper excited state reaction of an organic molecule which has a normal pattern of energy levels (e.g. unlike azulene or thioketones). This unusual behaviour is related of course to the extremely fast dissociation, within a single vibration very probably. We must now... 

---