Anisole reaction with boron tribromide

Heterogeneous reactions lend themselves to continuous flow reactors, which are desirable as they minimise the reacting volume. This reduces operation risks, and allows smaller, more efficient plants to be built. Flow reactors designed for fluorous reactions with both liquid and gaseous substrates have been demonstrated to be effective, at least on a bench scale [49]. Fluorous solvents have also recently found applications as liquid membranes to control the rate of addition of reagents and so control exothermic reactions such as alkene bromination (Fig. 6), and demethylation of anisoles by reaction with boron tribromide [50], This has potential as a clean route as the kinetic control gives improved selectivity. 

Also obtained by demethylation of a mixture of 2-methoxy-4-pentylacetophe-none and 4-methoxy-2-pentylaceto-phenone (I) with boron tribromide in methylene chloride at 0° and separation of isomers by chromatography (21%). The mixture of anisoles (I) was obtained by reaction of acetic anhydride with 3-pentylanisole in the presence of aluminium chloride in refluxing carbon disulfide [3489],... 

Dibutyl ether is the only solvent suitable for this reaction. Dibutyl ether has relatively low volatility and complexes with trimethylaluminum without solvent decomposition. Dibutyl ether complexes with BBr, sulTiciently strongly to slow the rate of reaction ofBBrj with AIMe, to a safe rate. Boron tribromide reacts explosively with trimethylaluminum in diethyl ether or anisole solutions because of the weak complexation between these solvents and BBr,. Tetra-hydrofuran and p-dioxane undergo decom X)sition reactions with trimethylaluminum, and thus are unsuitable as solvents in this synthesis. 

Scheme 8.88. A representation of the acid-catalyzed fragmentation of methyl phenyl ether (anisole) by the reaction with both hydrogen iodide (HI) and boron tribromide (BBrs). In the first case, iodomethane (methyl iodide, CH3I) and phenol are formed. In the second case, bromomethane (methyl bromide, CHsBr) and phenol result. The formation of methyl phenyl ether (anisole) from the reaction between methyl iodide and sodinm phenoxide is also shown.

The synthetic route to dihydroxy[2.n]metacyclophanes 7 is shown in Scheme 1. Anisole derivatives 5 and 6 were treated with excess of boron tribromide in dry CH2CI2 at r.t. for 12 h [19]. Phenol derivatives 7b and c were obtained in 95 and 93% yields, respectively. On the other hand, 5c did not give any desired products under the same conditions. Since the reaction gave a complex product mixture, we chose milder conditions. Thus, 5c was carefully treated with an equimolar amount of BBr3 at 0°C for 2 h and then gave 7a in 78% yield. Unfortunately, 5a, 5b, and... 

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