Solvent, phase-transfer benzylation

Table 5.1 Effect of catalyst structure, solvent and aqueous base on the reactivity and selectivity of phase-transfer benzylation of 2. 

If one of the species is anionic and we need to transport it to the organic phase, then a phase-transfer catalyst may be employed. Consider the example of benzyl penicillin where the reaction between phenyl acetic acid and the penicillin carboxylate ion, with penicillin amidase as a catalyst, is relevant, and which at pH 4.5 - 5.0 is shifted in the desired direction. Here a catalyst like tetrabutylammonium halide works, and with chloroform as a solvent 60% yield can be realized in contrast to a yield of only 5 - 10 % in water. 

Adogen has been shown to be an excellent phase-transfer catalyst for the per-carbonate oxidation of alcohols to the corresponding carbonyl compounds [1]. Generally, unsaturated alcohols are oxidized more readily than the saturated alcohols. The reaction is more effective when a catalytic amount of potassium dichromate is also added to the reaction mixture [ 1 ] comparable results have been obtained by the addition of catalytic amounts of pyridinium dichromate [2], The course of the corresponding oxidation of a-substituted benzylic alcohols is controlled by the nature of the a-substituent and the organic solvent. In addition to the expected ketones, cleavage of the a-substituent can occur with the formation of benzaldehyde, benzoic acid and benzoate esters. The cleavage products predominate when acetonitrile is used as the solvent [3]. 

Sodium salts of carboxylic acids, including hindered acids such as mesitoic, rapidly react with primary and secondary bromides and iodides at room temperature in dipolar aprotic solvents, especially HMPA, to give high yields of carboxylic esters.679 The mechanism is Sn2. Another method uses phase transfer catalysis.680 With this method good yields of esters have been obtained from primary, secondary, benzylic, allylic, and phenacyl halides.681 In another procedure, which is applicable to long-chain primary halides, the dry carboxylate salt and the halide, impregnated on alumina as a solid support, are subjected to irradiation by microwaves in a commercial microwave oven.682 In still another method, carboxylic acids... 

Permanganate ion is a strong oxidant and tends to cleave aromatic side chains. However, when used under phase-transfer conditions,109,849 it converts benzylic methine groups into alcohols, and benzylic methylene compounds to ketones. Convenient oxidations can be carried out when KMn04 is applied in Et3N, an organic solvent (CHC13), and traces of water at room temperature.850... 

N-Alkylation is favored by sodium and potassium cations, whereas C-alkylation is promoted by the more strongly coordinating lithium and magnesium cations (90JCS(P1)111). N-Alkylation is also favored by polar solvents and the use of tosylates rather than iodides. Under phase transfer conditions, the preference for A-alkylation in indoles ranges from 1.5 1 for benzyl bromide to 10 1 for benzyl chloride and -alkyl bromides, over 3-alkylation (90H(31)447). 

When benzyl bromide is reacted with acetophenone using a phase-transfer catalyst (but no solvent), the double benzylation product, PhCOCH(CH2Ph)2, is produced almost exclusively.143 The change in substrate acidity does not appear to explain the result. Rather, a n-n interaction in the transition state between mono- and di-benzyl products is proposed. A further investigation144 has more accurately characterized which substrates will display the effect, and has also identified the n-n interaction (or, more properly, a a—n interaction between two 71-systems) as being of the edge-to-face geometry. 

Whereas the results summarized in Scheme 4.32 were achieved under homogeneous reaction conditions, Colonna et al. reported the use of chiral phase-transfer catalysts for asymmetric addition of benzyl mercaptan and thiophenols to cyclohexenone and derivatives [55b], The best result was 85% yield and 36% enantiomeric excess in the addition of thiophenol to cyclohexenone, catalyzed by ca 0.4 mol% N-(o-nitrobenzyl)quininium chloride at 25 °C. In this experiment, CCI4 served as solvent and solid KF as the base. Finally, Aida et al. reported in 1996 that chiral... 

Muzart s group has recently described the use of molybdenum catalysts with the hydrogen peroxide adduct, sodium percarbonate and a phase-transfer agent.198 The molybdenum catalyst used in the study was Mo02(acac)2, and the solvents screened were dichloroethane and acetonitrile. The active species is a Mo peroxo complex and in common with other methods based on Mo and W catalysts, secondary, allylic and benzylic alcohols react quickly, and give higher yields of carbonyl product than primary aliphatic alcohols. 

A three-necked, round-bottomed flask equipped with a thermometer, reflux conductor, N, inlet and an overhead mechanical stirrer was charged sequentially with H O (5 mL), 50% NaOH (2 mL. 39 mmol), and adenine (2 g, 15 mmol). After the adenine had dissolved, a solution of benzylating reagent (16 mmol) and phase-transfer catalyst (5 mol%) in organic solvent (30-40 mL) was added. The system was stirred under reflux and then cooled to rt. The precipitated solids were filtered, washed with lIjO (2x10 mL), and dried in vacuo to give the crude bcnzylated adenine mixtures. For separation see ref 82. 

---