Williamson-type ether synthesis

The synthesis of triazole dendrimers starts from 3,5-dichloro-4-(4-methoxyphenyl)-4H-1,2,4-triazole, which can be obtained from methoxy-phenylisocyanate, as shown in Figure 9.4. This substance has an appropriate AB2-symmetry. Therefore, it is well-suited for convergent dendrimer synthesis. The reaction proceeds in the way of a Williamson type ether synthesis. To control the branching, 3,5-bis-(fen-butyl)-phenolis added. ... 

The most common preparative method to prepare the aryl allyl ether is the Williamson s ether synthesis [la,b]. Typically, aryl allyl ethers can be obtained from phenol derivatives and allylic halide under basic conditions (KjCOj) in refluxing acetone. This method is convenient for the preparation of simple allyl aryl ethers. However, some side reactions such as a competitive C-allylation (Sn2 type reaction) often accompany the formation of undesired byproducts. Mitsunobu reaction of phenol derivatives with allylic alcohols instead of allylic halides can be used under mild conditions [13]. In particular, when the allyl halide is unstable, this procedure is effective instead of the Williamson s ether synthesis. This method is also useful for the preparation of chiral allyl aryl ether from chiral allylic alcohol with inversion at the chiral center. Palladium catalyzed O-allylation of phenols is also applicable, but sometimes a lack of site-selectivity with unsymmetrical allylic carbonate [14] may be a problematic issue. 

The methylthiomethyl (MTM) ethers (32), mainly applied in natural product synthesis, represent thioacetals of formaldehyde. These ethers again are formed by Williamson-type reactions however, the... 

Sulfides, or thioethers, are sulfur analogues of ethers, and like ethers they can be either symmetrical (R2S) or unsymmetrical (RSR1, where R and R are different). Sulfides can be prepared from alkyl halides by a Williamson-type synthesis with sodium hydrogen sulfide, sodium thiolate or sodium sulfide from alkyl or aryl halides via the Grignard reagent (11) from alkenes by radical-catalysed addition of thiols or by reduction of sulfoxides (Scheme 9).2b... 

Dendrimers have been used as large compartmented hosts for drug delivery, as carriers for catalytically active sites in flow reactors, and for charge or energy transfer purposes. New types of such dendrimers were prepared starting from functionalized poly-p-phcnylcncs as polymeric cores whose functional groups were further used to anchor dendrons [165]. The polymers were synthesized from dibromide 117 and diboronic acid 118 via a Suzuki crosscoupling the dendrons were attached via a Williamson ether synthesis [165]. 

Not all workers, however, are convinced of the validity of the accepted mechanisms for these types of reactions. Tan et al have studied a phase transfer catalysed Williamson ether synthesis by electrochemical methods including cyclic voltammetry [23], and came to the conclusion that... 

Potassium fluoride coated on alumina has been shown to be an effective and practical base for the usual Williamson-type synthesis of crown ethers from polyethylene glycols and polyethylene glycol ditosylates [equation (23)],giving yields comparable to standard methods. 

The Johnson group also examined a synthesis that relied on the Julia olefin synthesis for construction of the central trisubstituted olefin. In this plan, 1 was to be prepared from an a-haloketone of type 39 via diastereoselective addition of a methyl group to the ketone, followed by a Williamson ether synthesis. Ketone 39 was to be prepared from 40 using an acetoacetic ester synthesis. Compound 40 was to be prepared from 41 using the Julia olefin synthesis. A make-or-break aspect of this plan was the stereochemical course of the Julia synthesis. Of course it was anticipated that the proper stereochemistry would result as will be seen shortly. 

The modified Williamson synthesis with NaOH and chloroacetic acid or monochlorosodium acetate for the preparation of ether carboxylates is very old [3-8] and is suitable for batch production of different types of ethercarboxylates. 

The answer, Meyer thought, lies in the kinetic theory of heat and matter. This physical theory had been given explicit chemical meaning by Williamson s inference from studies of the synthesis of diethyl ether that atoms in chemical compounds must be continually changing places.56 Molecules are not empty boxes in translation or rotation but little Pandora-like boxes filled with active entities. The goal of chemistry must be the understanding of chemical phenomena using theories of motion, not just theories of species or types. 

Illustrate with examples the limitations of Williamson synthesis for the preparation of certain types of ethers. 

The ether linkage ( C—0—C ) is normally prepared by one of the three following procedures. The Williamson synthesis is the most general method, while the diazomethane procedure and the epoxide formation procedure are useful for specific types of... 

Treatments based on condensation reactions (such as in the classical Williamson synthesis) produce the most stable cotton derivatives. On the other hand, treatments based on addition reactions (such as in the Michael reaction) yield cellulose ethers that are somewhat less stable. This lower level of stability is because of the equilibrium nature of the addition reaction. Typical examples of these two types of cellulose etherification are carboxymethyla-tion [9,329,330] and cyanoethylation [9,329,330,332], respectively, both of which proceed in the presence of alkali. 

In the presence of sodium hydroxide, thiols react with alkyl halides to form the sulfides (20) the reaction occurs via the sodium thiolate and is analogous to the well-known Williamson synthesis of ethers and can also be applied to obtain unsymmetrical sulfides (Scheme 18). Symmetrical sulfides may be prepared directly by condensation of sodium sulfide with alkyl halides (Scheme 18). These reactions are of the SN2 type, and consequently the optimum yields of sulfides are realised using primary alkyl halides. 

At the same time Alexander William Williamson (1824-1904) was trying to prepare higher alcohols by substituting the hydrogen in ethanol by an alkyl radical. When he reacted ethanol with potassium ethoxide, he found that instead of another alcohol he obtained diethyl ether. This synthesis meant that ethanol could not be the hydrate of ether as Liebig had proposed, and Williamson suggested the existence of a water type,... 

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