Mechanism Williamson ether synthesis

Williamson, Alexander W., 655 Williamson ether synthesis, 655 carbohydrates and, 988 mechanism of, 655... 

The Williamson ether synthesis proceeds via an S 2 mechanism, in which an alkoxide ion displaces a halogen ion. 

When an alkoxide ion is used as the nucleophile, the reaction is called a Williamson ether synthesis. Because the basicity of an alkoxide ion is comparable to that of hydroxide ion, much of the discussion about the use of hydroxide as a nucleophile also applies here. Thus, alkoxide ions react by the SN2 mechanism and are subject to the usual Sn2 limitations. They give good yields with primary alkyl halides and sulfonate esters but are usually not used with secondary and tertiary substrates because elimination reactions predominate. 

Key Mechanism 11-6 The Williamson Ether Synthesis 500 Problem-Solving Strategy Multistep Synthesis 502 Summary Reactions of Alcohols 505 Essential Terms 508 Study Problems 509... 

We have already seen most of the common methods for synthesizing ethers. We review them at this time, looking more closely at the mechanisms to see which methods are most suitable for preparing various kinds of ethers. The Williamson ether synthesis (Section 11-14) is the most reliable and versatile ether synthesis. This method involves the Sn2 attack of an alkoxide ion on an unhindered primary alkyl halide or tosylate. Secondary alkyl halides and tosylates are occasionally used in the Williamson synthesis, but elimination competes, and the yields are often poor. 

There are two different ways of making 2-ethoxyoctane from octan-2-ol using the Williamson ether synthesis. When pure (— )-octan-2-ol of specific rotation —8.24° is treated with sodium metal and then ethyl iodide, the product is 2-ethoxyoctane with a specific rotation of —15.6°. When pure (— )-octan-2-ol 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 tosylation/ sodium ethoxide procedure, and propose a detailed mechanism to support your prediction. 

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. 

In the case of most alkoxides and primary or secondary alkyl halides, the mechanism of the Williamson ether synthesis proceeds via an Sn2 process. When the alkyl halide Is secondary (R"=H) with a given absolute configuration, the product ether will have a complete Inversion of configuration at that particular stererocenter. E.C. Ashby demonstrated, however, that the reaction between lithium alkoxides and alkyl Iodides proceeds via singleelectron transfer. 

The resulting mechanism is therefore the usual one allowing, e.g., the Williamson ether synthesis through alkylation of alkyl halides with alcohols in the presence of 50% NaOH and Bu4N HS04 as catalyst [27]. 

A MECHANISM FOR THE REACTION ] Intermolecular Dehydration of Alcohols to Form an Ether 517 [ A MECHANISM FOR THE REACTION ] The Williamson Ether Synthesis 518... 

In this book, we will be overwhelmingly concerned with polar or ionic mechanisms. These involve the movement of eleetron pairs, unlike radical reactions which involve unpaired electrons. The components of a polar mechanism can generally be classified as nucleophiles or electrophiles. A nucleophile ( nucleus-lover ) is typically an anion or a neutral molecule that uses an electron pair to attack another atom, ion, or molecule. The species being attacked is called an electrophile ( electron-lover ). The terms nucleophile and electrophile often refer to the classic 8 2 reaction of organic chemistry. In the example below (which happens to be a Williamson ether synthesis), the methoxide anion is the nucleophile, methyl iodide is the electrophile, and iodide is the leaving group. 

Sodium hydride Is a good base, and deprotonates the alcohol alkylation with Mel, via a nucleophilic substitution mechanism, gives the final ether product (Williamson ether synthesis). 

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... 

Disconnection of an ether TM occurs at either C-0 bond, leading to an alkoxide nucleophile and alkyl halide electrophile. This Williamson ether synthesis involves an Sn2 mechanism, so minimization of steric hindrance is the main consideration when determining which disconnection to make in the retrosynthesis. 

The mechanism of solid-liquid phase-transfer catalysis by polymer-supported linear ethers for the Williamson ether synthesis is similar to that for the non-supported process, ... 

The process is achieved via an intramolecular Williamson ether synthesis. An aUcoxide ion is formed, which then functions as a nucleophile in an intramolecular Sn2 -like process (Mechanism 14.4). 

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. 

Show the mechanism of S5mthetic Transformation 23.9 Williamson ether synthesis. 

Williamson s synthesis 1. A method of preparing simple ethers by dehydration of alcohols with concentrated sulfuric acid. The reaction is carried out at 140 C under reflux with an excess of the alcohol 2ROH ROR + H2O The concentrated sulfuric acid both catalyzes the reaction and displaces the equilibrium to the right. Also the ether may be distilled off during the reaction (in which case it is called Wilkinson s continuous process). The product, ether, is termed simple , because the R groups are identical. There are two possible mechanisms for the process, depending on the nature of the alcohol. In the case of primary alcohols, there is a hydrogensulfate formed. For example, with ethanol ... 

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... 

In fact, the reaction of alkoxides with alkyl halides or alkyl sulfates is an important general method for the preparation of ethers, and is known as the Williamson synthesis. Complications can occur because the increase of nucleo-philicity associated with the conversion of an alcohol to an alkoxide ion always is accompanied by an even greater increase in eliminating power by the E2 mechanism. The reaction of an alkyl halide with alkoxide then may be one of elimination rather than substitution, depending on the temperature, the structure of the halide, and the alkoxide (Section 8-8). For example, if we wish to prepare isopropyl methyl ether, better yields would be obtained if we were to... 

With the increasing availability of suitable monomers and the desire for polymers having improved heat resistance combined with higher levels of mechanical properties, displacement (or substitution ) reactions have become of increased interest for polycondensation. A suitable example with monofunctional reactants would be the Williamson synthesis of ethers... 

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