Synthesis Williamson

Higher alkyl ethers are prepared by treating the sodium derivative of the phaiol (made by adding the phenol to a solution of sodium ethoxide in ethyl alcohol) with the alkyl iodide or bromide (Williamson synthesis), for example ... 

Williamson synthesis Wohl-Ziegler reaction Wolff rearrangement Wolff Kishner reduction Wurtz reaction Wurtz-Fittig reaction... 

Methyl chloride can be converted iato methyl iodide or bromide by refluxing ia acetone solution ia the presence of sodium iodide or bromide. The reactivity of methyl chloride and other aUphatic chlorides ia substitution reactions can often be iacteased by usiag a small amount of sodium or potassium iodide as ia the formation of methyl aryl ethers. Methyl chloride and potassium phthalimide do not readily react to give /V-methy1phtha1imide unless potassium iodide is added. The reaction to form methylceUulose and the Williamson synthesis to give methyl ethers are cataly2ed by small quantities of sodium or potassium iodide. 

The conversion of chlorohydrins into epoxides by the action of base is an adaptation of the Williamson synthesis of ethers. In the presence of hydroxide ion, a small proportion of the alcohol exists as alkoxide, which displaces the chloride ion from the adjacent carbon atom to produce a cycHc ether (2). 

By use of a modification of the well-known Williamson synthesis it is possible to prepare a number of cellulose ethers. Of these materials ethyl cellulose has found a small limited applieation as a moulding material and somewhat greater use for surfaee eoatings. The now obsolete benzyl cellulose was used prior to World War II as a moulding material whilst methyl eellulose, hyroxyethyl eellulose and sodium earboxymethyl eellulose are useful water-soluble polymers. 

Methoxythiophene and 3-cyanothiophene have been prepared from 3-bromothiophene by means of a cupric oxide-catalyzed Williamson synthesis and by reaction with cuprous cyanide in quinoline, respectively. 

Halothiophenes, which are not activated through the presence of —I—M-substituents, undergo substitution smoothly under more forcing conditions with copper salts in pyridine or quinoline. Hence 3-cyanothiophene and 5-methyl-2-cyanothiophene have been obtained from the corresponding bromo compounds. 2-Bromothiophene reacts readily with aliphatic cuprous mercaptides in quinoline at 200°C to give thioethers in high yields. The use of the copper-catalyzed Williamson synthesis of alkoxythiophenes from iodo- or bromo-thiophenes and alcoholate has been mentioned before. The reaction of 2-bromothiophene with acetanilide in nitrobenzene in... 

For the classical Williamson synthesis an alcohol is initially reacted with sodium or potassium to give an alkoxide, e.g. 1. Alternatively an alkali hydroxide or amide may be used to deprotonate the alcohol. Phenols are more acidic, and can be converted to phenoxides by treatment with an alkali hydroxide or with potassium carbonate in acetone. ... 

A useful variation of the Williamson synthesis involves silver oxide, Ag20, as a mild base rather than NaH. Under these conditions, the free alcohol reacts directly with alkyl halide, so there is no need to preform the metal alkoxide intermediate. Sugars react particularly well glucose, for example, reacts with excess iodomethane in the presence of Ag20 to generate a pentaether in 85% yield. 

Because the Williamson synthesis is an S 2 reaction, it is subject to all the usual constraints, as discussed in Section 11.2. Primary halides and tosylates work best because competitive E2 elimination can occur with more hindered substrates. Unsymmetrical ethers should therefore be synthesized by reaction between the more hindered alkoxide partner and less hindered halide partner rather than vice versa. For example, terf-butyl methyl ether, a substance used in the 1990s as an octane booster in gasoline, is best prepared by reaction of tert-butoxide ion. with iodomethane rather than by reaction of methoxide ion with 2-chloro-2-methylpropane. 

Problem 18,3 How would you prepare the following ethers using a Williamson synthesis ... 

How would you prepare ethyl phenyl ether Use whichever method you think is more appropriate, the Williamson synthesis or the alkoxymercuration reaction. 

Strategy Draw the target ether, identify the two groups attached to oxygen, and recall the limitations of the two methods for preparing ethers. The Williamson synthesis uses an Sn2 reaction and requires that one of the two groups attached to oxygen be either... 

Rank the following halides in order of their reactivity in the Williamson synthesis (a) Bromoethane, 2-bromopropanc, bromobenzene 1 (b) Chloroethane, bromoethane, 1-iodopropene... 

Treatment of a thiol with a base, such as NaH, gives the corresponding thiolate ion (RS-), which undergoes reaction with a primary or secondary alkyl halide to give a sulfide. The reaction occurs by an Sn2 mechanism, analogous to the Williamson synthesis of ethers (Section 18.2). Thiolate anions are among... 

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. 

Conditions employing elevated temperatures with less catalyst, a milder catalyst or without addition of catalyst, can supplant those utilizing aggressive reagents at lower temperatures. A recent example concerns a catalytic, thermal etherification that can be performed near neutrality and that produces minimal waste [41]. This represents a cleaner alternative to the traditional Williamson synthesis, in which the ether is... 

Representative cyclizations. Typically, a given cyclization involves nucleophilic displacement of a halide or tosylate by alkoxide or phenoxide ion (that is, a Williamson synthesis) even though such reactions are frequently quite slow. Schemes [4.1], [4.2] and [4.3] give representative... 

The last profile refers to the formation of diethers [2] by intramolecular Williamson synthesis. The data are in substantial agreement with earlier... 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

Selected examples of the catalysed Williamson synthesis of aliphatic ethers... 

Furthermore, the preparation and reactions of 2-methoxythiophene were studied by Sice (70). This compound was obtained by a copper catalysed Williamson synthesis. It was also found that iodothiophene reacted readily with sodium alkoxides, whereas bromothiophene reacted slowly and chlorothiophene did not react at all. Sodium iodide accelerated the reaction of bromothiophene. The ortho, para orienting alkoxy group on carbon atom 2 increased the directive influence of the sulphur atom to the 5 position but competed with it to induce some attack on the 3 position by electrophilic reagents (nitration, acylation). The acylation of 2-methoxythiophene with stannic chloride at low temperatures furnished a mixture of two isomers. The 5-methoxy-2-acetothienone was obtained in higher yield and was identified by its ultraviolet absorption spectrum. 

Williamson synthesis org chem The synthesis of ethers utilizing an alkyl iodide and sodium alcoholate. wil-yom-san sin-tha-sas )... 

Write the reactions of Williamson synthesis of 2-ethojg -3-methylpentane starting from ethanol and 3-methylpentan-2-ol. 

Ethers may be prepared by (1) dehydration of alcohols and (11) Williamson synthesis. The boiling points of ethers resemble those of alkanes while their solubility Is comparable to those of alcohols having same molecular mass. The C-O bond In ethers can be cleaved by hydrogen halides. In electrophilic substitution, the alkoxy group activates the aromatic ring and directs the Incoming group to ortho and para positions. 

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

G.M. Blackburn, D.L. Jakemean, A.J. Ivory, M.P. Williamson, Synthesis of phosphonate analogues of 1,3-bis-phosphoglyceric acid and their binding to yeast phosphoglycerate kinase, Bioorg. Med. Chem. Lett. 4 (1994) 2573-2578. 

A number of other useful modifications of the intramolecular Williamson synthesis have been developed. Reaction of a,a-dialkyl-/3-tosyloxy aldehydes and ketones with potassium cyanide or with sodium alkoxide gives the corresponding 2-cyano- or 2-alkoxy-oxetanes... 

Problem 14.12 Use any needed starting material to synthesize the following ethers, selecting from among intermolecular dehydration, Williamson synthesis, and alkoxymercuration-demercuration. Justify your choice of method. 

This is better than Williamson synthesis because there is no competing elimination reaction. 

Williamson synthesis of an aryl alkyl ether requires the Ar to be part of the nucleophile ArO and not the halide, since ArX does not readily undergo 5 2 displacements. Note that since ArOH is much more acidic than ROH, it is converted to ArO" by OH instead of by Na as required for ROH. 

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