Chloromethylation Friedel-Crafts reaction

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

There are a number of variations of the Friedel-Crafts reactions that are useful in synthesis. The introduction of chloromethyl substituents is brought about by reaction with formaldehyde in concentrated hydrochloric acid and halide salts, especially zinc chloride.62 The reaction proceeds with benzene and activated derivatives. The reactive electrophile is probably the chloromethylium ion. 

Kojic acid was brominated at position 6 with bromine water4 the 2-(chloromethyl) derivative of kojic acid was brominated with N-bromo-succinimide,87 and chlorinated with sulfuryl chloride and aluminum chloride,88 in both cases probably at C6. The C-benzoylation89 and C-acetylation90 of kojic acid, likewise at C6, was accomplished by Woods using a modification of the Friedel-Crafts reaction. The 2-carboxyethyl side chain was introduced at C6 in a reaction with 2-bromopropionic acid.91... 

Examples of chloromethylation and Friedel-Crafts reactions (together with side-chain reactions cf. Section IV,A,5,f) are depicted in Scheme 126. 

The addition of a chloromethyl ether to olefinic linkages takes place under conditions similar to the Friedel-Crafts reaction and leads to y-chloro ethers. Substitution of zinc chloride for mercuric chloride as catalyst has improved the yields. Allyl chloride and chloromethyl ether react to give a high yield of l-methoxy-3,4-dichlorobutane (98%). ... 

Chloromethylation. A Friedel-Crafts reaction between the copolymer and chloromethoxymethane with aluminium chloride as the catalyst introduces chloromethyl groups (—CH2CI) into the ethenylbenzene nuclei. What appears to be a simple step is in fact a critical stage in the synthesis, demanding strict techniques to firstly minimize undesir-... 

The substituted trityl chloride can also be synthesised by Friedel-Craft reaction from trifluoromethyl benzene (50) and chloromethyl ether (51). The product obtained is chlorinated and reacted with benzene in another Friedel-Craft reaction (Biichel and Singer, 1975). 

Other types of hypercrosslinked sorbents, namely commercial Lewatit EP63, laboratory samples obtained by post-crosslinking styrene-DVB copolymer with CCI4 [55], by self-crosslinking macroporous copolymer of vinylbenzyl chloride with 20% DVB via Friedel-Crafts reaction [56], or by bridging preliminary chloromethylated macroporous styrene-DVB copolymer [57, 58], are all superior to XAD-2, XAD-4, and activated carbon Ambersorb XE340 with respect to phenol and nitrophenol removal. Material [20%-VBC(F.C.)] retains 2,4-dichlorophenol much stronger than unsubstituted phenol, and, therefore, the presence of phenol in the solution does not impact the retention of the chlorinated phenol. On the contrary, the sorption of phenol from the binary solution depends heavily on the concentration of 2,4-dichlorophenol. 

Show examples of the Friedel-Craft reactions of polystyrene and chloromethylated polystyrene. 

Certain other reactions of aromatic molecules are closely related to the Friedel-Crafts reaction. The introduction of chloromethyl groups is brought about by formaldehyde in concentrated hydrochloric acid in the presence of halide salts, especially zinc chloride. The reaction is restricted in scope to benzene and derivatives with electron-releasing substituents. Several mechanistic pathways could be operative in the chloromethylation reaction, but the active electrophile is probably protonated chloromethyl alcohol. 

Stannic chloride is a very effective catalyst for this Friedel-Craft reaction [186]. lodomethylation can also be carried out in the same manner with similar results [179]. When the reactions are carried out on cross-linked styrene copolymers with chlorodimethyl ether and stannic chloride catalyst, they are accompanied by strong morphological changes [187]. If these reactions are carried out with low levels of chloromethylating agents or catalysts, they occur more or less homogeneously. Larger levels... 

Suggest a synthesis of ibuprofen (Section 5.11) from benzene, employing chloromethylation as one step. Chloromethylation is a special case of the Friedel—Crafts reaction in which a mixture of HCHO and HCI, in the presence of ZnCl2, introduces a —CH2CI group into an aromatic ring. 

For batchwise synthesis, the base matrix used is almost invariably 1% divinylbenzene cross-linked polystyrene (PS). It is relatively inexpensive to produce, swells in the solvents most commonly used in peptide synthesis, namely DCM, DMF, and NMP, and can be readily functionalized using the Friedel-Crafts reaction with chloromethyl, aminomethyl, and benzhydrylamino groups. 

Traditionally, anion-exchange resins have been made by a two-stage set of reactions (although other synthesis methods are now being used). The first step is a Friedel-Crafts reaction to attach the chloromethyl group to the benzene rings of styrene-divinylbenzene copolymer. Then the anion exchanger is formed by reaction of the chloromethylated resin with an amine. The most common type of... 

In 1898, the first chloromethylation of benzene was performed by Grassi and Maselli. Twenty-five years later, the reaction was extensively redeveloped by Gustave Louis Blanc while he was director at the Intendance militaire aux Invalides. Although his reaction conditions do not differ from the original conditions of Grassi and Maselli, his efforts earned him the honor of having the reaction bear his name. That the reaction seems closely related to the Friedel-Crafts reaction should not be surprising, as Blanc studied under Charles Friedel in Paris. 

Issues of regioselectivity in the Blanc chloromethylation and related Friedel-Crafts reactions have been studied extensively. As is common with a majority of electrophilic aromatic substitution reactions, substitution typically occurs ortho or para to electron-donating substituents, with issues of steric strain playing a role in the relative ratio of ortho and para products. The Blanc reaction is t3q)ically somewhat regioselective, favoring the para-isomer but accompanied by lesser amounts of the ortho product. ... 

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