Williamson ether synthesis formation

Williamson ether synthesis Formation of an ether by the 8( 2 reaction of an alkoxide ion with an alkyl halide or tosylate. In neral, the electrophile must be primary, or occasionally secondary. (p. 633)... 

Williamson ether synthesis formation of an ether from the reaction of an alkoxide ion with an alkyl halide. 

Many of the crown ether syntheses with which we are concerned in this book are one form or another of the Williamson ether synthesis. Although the simplest example of such a reaction would involve an co-haloethylene glycol oligomer which undergoes intramolecular cyclization, it is more common for two new bonds to be formed in crown syntheses. An early example of the formation of a crown by a double-Williamson can be found in Dale s synthesis of 18-crown-6. The rather obvious chemical steps are shown in Eq. (2.1). 

Macrocycles have been prepared by formation of macrocyclic imines as well as by using variations of the Williamson ether synthesis ". Typically, a diamine or dialdehyde is treated with its counterpart to yield the Schiff s base. The saturated macrocycle may then be obtained by simple reduction, using sodium borohydride, for example. The cyclization may be metal-ion templated. In the special case of the all-nitrogen macrd-cycle, 15, the condensation of diamine with glyoxal shown in Eq. (4.14), was unsuccess-ful ... 

Unlike the acid-catalyzed ether cleavage reaction discussed in the previous section, which is general to all ethers, the Claisen rearrangement is specific to allyl aryl ethers, Ar—O—CH2CH = CH2. Treatment of a phenoxide ion with 3-bromopropene (allyl bromide) results in a Williamson ether synthesis and formation of an allyl aryl ether. Heating the allyl aryl ether to 200 to 250 °C then effects Claisen rearrangement, leading to an o-allylphenol. The net result is alkylation of the phenol in an ortho position. 

The formation of carbon-oxygen single bonds via the attack of an alkoxide on an alkyl halide, (Williamson ether synthesis) is an extremely important reaction that... 

Hydroxyl Group. Reactions of the phenolic hydroxyl group include the formation of salts, esters, and ethers. The sodium salt of the hydroxyl group is alkylated readily by an alkyl halide (Williamson ether synthesis). Normally, only alkylation of the hydroxyl is observed. However, phenolate ions are ambident nucleophiles and under certain conditions, ring alkylation can also occur. Proper choice of reaction conditions can produce essentially exclusive substitution. Polar solvents favor formation of the ether nonpolar solvents favor ring substitution. 

Alcohol 6 is prepared by a copper-catalyzed reaction of (R)-benzylglycidyl ether with vinylmagnesium bromide. The first step here is a Williamson ether synthesis. The free alcohol 6 reacts with sodium hydride to a sodium alkoxide, which is treated with the sodium salt of bromoacetic acid. The acid is also converted into the sodium salt to avoid the formation of an ester as side product. After the reaction carboxylic acid 20 is released in 93 % yield by acidification with aqueous 10 % HC1 solution. 

Scheme6.16. The formation of alkenes during the Williamson ether synthesis [61,62].

Much of the chemistry of phenols is like that of aliphatic alcohols. For example, phenols can be acylated to give esters, and phenoxide ions can serve as nucleophiles in the Williamson ether synthesis (Section 14-5). Formation of phenoxide ions is particularly easy because phenols are more acidic than water aqueous sodium hydroxide deproto-nates phenols to give phenoxide ions. 

CHAPTER 7 CHAPTER 8 CHAPTER 10 CHAPTER 11 CHAPTER 15 CHAPTER 17 CHAPTER 18 Acid-Catalyzed Dehydration of an Alcohol 313 Electrophilic Addition to Alkenes 330 Grignard Reactions 443 The Williamson Ether Synthesis 500 The Diels-Alder Reaction 684 Electrophilic Aromatic Substitution 757 Nucleophilic Additions to Carbonyl Groups 841 Formation of Imines 851 Formation of Acetals 856... 

The preparation of crown ethers differs principally owing to the presence or absence of nitrogen. The preparation of all-oxygen heteromacrocycles has largely involved the Williamson ether synthesis. The preparation of aza-, diaza-, or triazacrowns has usually required the formation of cyclic amides, followed by reduction. The latter method applies to cryptands as well and has been used for that purpose since 1969. The methods are well known and shown in the lower panel of Figure 4. 

Epoxide Formation (Internal Williamson Ether Synthesis) (3)OC-cyc/o-Alkoxy-de-halogenation... 

The formation of f-butyl methyl ether from methyl iodide and potassium f-butoxide is an example of the Williamson ether synthesis. By analyzing this reaction as it proceeds you can determine the rate of the reaction as well as the order. In this way you also may be able to infer a mechanism for the reaction. 

This formation of an epoxide by treatment of a halohydrin with base is just an intramolecular Williamson ether synthesis. The nucleophilic alkox-ide ion and the electrophilic alkyl halide are in the same molecule. 

Prenyl ethers can be formed using the typical Williamson ether synthesis—that is, by reacting the alcohol with a suitable base and a prenyl halide. Many of the methods used for the formation of allyl and benzyl ethers should be applicable. ... 

If the two halogens are on the same or adjacent carbons, two consecutive E2 dehydrohalogenations can result in the formation of a triple bond. The Williamson ether synthesis involves the reaction of an alkyl halide with an alkoxide ion. If the two functional groups of a bifunctional molecule can react with each other, both intermolecular and intramolecular reactions can occur. The reaction that is more likely to occur depends on the concentration of the bifunctional molecule and the size of the ring that will be formed in the intramolecular reaction. 

There are two different ways of making 2-ethoxyoctane from 2-octanol using the Williamson ether synthesis. When pure (—)-2-octanol of specific rotation —8.24° is treated with sodium metal and then ethyl iodide, the product is 2-ethoxyoc-tane with a specific rotation of —15.6°. When pure (—)-2-octanol is treated with tosyl chloride and pyridine and then with sodium ethoxide, the product is also 2-ethoxyoctane. Predict the rotation of the 2-ethoxyoctane made using the tosy-lation/sodium ethoxide procedure, and propose a detailed mechanism to support your predictioa 14-43 Under base-catalyzed conditions, several molecules of propylene oxide can react to give short polymers. Propose a mechanism for the base-catalyzed formation of the following trimer. 

The Williamson ether synthesis involves treating a haloalkane with a metal alkoxide. Following are two reactions intended to give benzyl tert-butyl ether. One reaction gives the ether in good yield, the other does not. Which reaction gives the ether What is the product of the other reaction, and how do you account for its formation ... 

All characteristic last steps in the synthesis of EDOT, i.e. the ring closure to the dioxane structure, are also sufficient for the formation of the analogous seven-membered rings (1,3-dioxepanes), the 3,4-propylenedioxythiophenes (ProDOTs) Williamson ether synthesis [13], transetherification [30] and Mitsunobu reaction [25]. The analogous basic five-membered ring compound 3,4-methylenedioxythiophene (MDOT, a 1,3-dioxolane derivative) is also accessible by Williamson ether synthesis using bro-mochloromethane [31]. 

This method of thioether formation is the sulfur analog of the Williamson ether synthesis (Section 11.4A). 

Although not proven, the mechanism rationalizes the production of ethers that have been detected in various distillate layers and other residues from the process. Analogous to the Williamson ether synthesis succinate instead of halide, functions as the nucleofuge. Attempts to suppress this depleting side reaction by use of hindered succinate esters have been ineffective. For example, a patent by Hoechst [8C] employing an all isopropyl system claims no ether formation however, a maximum yield of only 84% DMSS is exemplified. 

An efficient method for intramolecular direct arylation was employed on a doubly functionalized caUx[4]arene fixed in the cone conformation (Scheme 3.25). Dihydroxycalixarene 113 was obtained from dibromide 112 in 84% yield using lithiation, calixboronate formation and the final oxidative carbon-boron bond cleavage. The hydroxy groups of 113 were reacted with benzyl bromide (Williamson ether synthesis) and CS2CO3 in acetone to produce corresponding... 

When the same sequence was applied to the corresponding sy -alcohol, 280-sy was obtained in good yield. The sequence shows that the crucial and stereochem-ically decisive part of the synthesis is taking place in the forefront of the process, when the constitution and the configurations are installed. The ether formation itself represents just a simple Williamson ether synthesis. 

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