Catalysts alkyl substituted crowns

Alkyl-substituted crown ethers. Italian chemists have prepared a series of crown ethers (1) substituted with a long alkyl chain and of diaza-croiVn ethers (2) similarly substituted. These proved to be as efficient as any of the most efficient phase-transfer catalysts known to date. 

Synthesis of alkyl-substituted crown ethers efficient phase-transfer catalysts. 

Nucleophilic Substitutions.—Many of the nucleophilic substitutions covered by equation (1) can be catalysed as effectively in liquid-liquid two-phase systems by crown and cryptand compounds as by quaternary ions. Alkyl substitution on the basic crown skeleton of (28), as in (31), was found to increase the efficiency of catalysis for the conversion of alkyl mesylates to halides, presumably by ensuring partitioning of the crown-salt complex between the phases. A similar observation has been made using alkyl-substituted crown (32) and aza-crown compounds (33) as catalysts in two-phase reactions, for example between iodide, cyanide or thiocyanate aniohs and an alkyl bromide. Alkyl substitution in the macrobicyclic cryptands (34) has the same effect on Sn processes, and in all the above cases systems can be devised with catalytic efficiency comparable to or greater than that achieved by quaternary ion PTC. 

Applications to Phase-transfer Methods.—Dehmlow has published a review on advances in phase-transfer catalysis (PTC) which discusses the introduction of crown ethers into this area. The full details are now available of a study of alkyl-substituted azamacrobicyclic polyethers (78a) as PT catalysts. When the alkyl chains are C14—C20, such molecules are very efficient catalysts in both liquid-liquid and solid-liquid phase-transfer modes, which contrasts with the lower catalytic ability of the less organophilic unsubstituted cryptand (78b). Crown ethers immobilized on polymeric supports have been demonstrated to possess increased PTC activity in 5n reactions, up to that of the non-immobilized systems, when the connection to the polymer involves long spacer chains [e.g. (79)]. 

The synthesis of a variety of alkyl substituted (both at carbon and nitrogen) crown and azacrown ethers were reported and found to be efficient catalysts for... 

The advantages of PTC reactions are moderate reaction conditions, practically no formation of by-products, a simple work-up procedure (the organic product is exclusively found in the organic phase), and the use of inexpensive solvents without a need for anhydrous reaction conditions. PTC reactions have been widely adopted, including in industrial processes, for substitution, displacement, condensation, oxidation and reduction, as well as polymerization reactions. The application of chiral ammonium salts such as A-(9-anthracenylmethyl)cinchonium and -cinchonidinium salts as PT catalysts even allows enantioselective alkylation reactions with ee values up to 80-90% see reference [883] for a review. Crown ethers, cryptands, and polyethylene glycol (PEG) dialkyl ethers have also been used as PT catalysts, particularly for solid-liquid PTC reactions cf. Eqs. (5-127) to (5-130) in Section 5.5.4. 

The reaction proceeds almost exclusively by direct substitution (ipso), as shown by reactions of isomeric chlorotolnene complexes (Scheme 38). While polar protic solvents, snch as MeOH, strongly retard reaction,phase transfer catalysis (see Phase Transfer Catalyst) nsing benzene or addition of Crown Ethers to potassium alkoxides in benzene allows reaction at 25 °C. Even with strong electron donors such as alkyl, methoxy, or dialkylamtno in the ortho, meta, or para positions, substitution for chloride by potassium methoxide proceeds smoothly using the crown ether activation in benzene (eqnation 96). ... 

The reaction employed was the substitution of the bromine of 1-bromohexane by nitrile anion. The alkyl bromide composed one phase and a concentrated aqueous solution of either KCN or NaCN made up the other phase. The crown ethers functioned as soluble PTC s while polymer 2 suspended at the interface served as an insoluble catalyst. A reaction temperature of 85° was employed to give reasonable conversion times. The reactions were followed with NMR by monitoring the integrated intensities of the hydrogens adjacent to the halide and nitrile groups. The two triplets associated with these peaks are well separated at 3.236 and 2.156 allowing direct comparison of their relative ratios in the reaction mixtures. While this method has limited accuracy, it does allow rapid initial evaluations. Figure 3 shows the relative rates of conversion of 1-bromohexane to the nitrile with KCN. 

N-Substituted amides can be N-alkylated by alkyl halides using a two-phase system of solid NaOH-KaCOs in refluxing benzene with tetra-n-butylammonium hydrogen sulphate as phase-transfer catalyst." This method works well for the limited range of compounds studied. Potassium t-butoxide in ether containing small amounts of a crown ether has similarly been used to N-alkylate some iV-arylbenzanilides." N-Aryl-jS-keto-amides can be N-alkylated under standard conditions (NaH-DMF-RX) after first blocking the sensitive jS-keto-amide function by formation of a difluoro-oxyborane complex with BFs-EtjO. ... 

The role of crown ethers and their analogues as catalysts, co-catalysts, and substrates in reactions involving ions and ion pairs has been reviewed in Polish. States of solvation or association affect the reactivity of ionic reagents in spectacular ways. A series on mechanoactivated halogen-substitution reactions of alkyl halides has continued in a study of halogen substitution in ethyl bromide on the surface of mechanically... 

Another approach to the synthesis of alkyl azides is the use of a phase-transfer catalyst (see Scheme 3.8). For instance, high yields are obtained when alkyl bromides are treated with NaNs in the presence of aUquat 336 . The use of crown ethers has also been described. An illustrative example is the reported synthesis of glycoside derivatives, which explores the mesylate displacanent with sodium azide in 18-crown-6 to give azide 58. More recently the synthesis of alkyl- and aryl-substituted ( )-2-(azidomethyl)alke-noates from the corresponding aUyUc bromides 59 in aqueous acetone has been reported (Scheme 3.8). 

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