Williamson ether synthesis intramolecular

The intermediate resulting from addition of H is similar to the intermediate in a Williamson ether synthesis. Intramolecular reaction occurs to form the epoxide. 

Next in what amounts to an intramolecular Williamson ether synthesis the alkoxide oxygen attacks the carbon that bears the halide leaving group giving an epoxide As m other nucleophilic substitutions the nucleophile approaches carbon from the side oppo site the bond to the leaving group... 

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). 

Base-promoted cyclization of vicinal halohydrins (Section 16.10) This reaction is an intramolecular version of the Williamson ether synthesis. The alcohol function of a vicinal halohydrin is converted to its conjugate base, which then displaces halide from the adjacent carbon to give an epoxide. 

Another method for the synthesis of epoxides is through the use of halo-hydrins, prepared by electrophilic addition of HO—X to alkenes (Section 7.3). When halohydrins are treated with base, HX is eliminated and an epoxide is produced by an intramolecular Williamson ether synthesis. That is, the nucleophilic alkoxide ion and the electrophilic alkyl halide are in the same molecule. 

This reaction is an intramolecular Williamson ether synthesis. 

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. 

The total synthesis of (+)-asimicin, which belongs to the family of Annonaceous acetogenins, was completed by E. Keinan and co-workers. In order to create one of the tetrahydrofuran rings stereospecifically, an intramolecular Williamson ether synthesis was performed between a secondary alcohol and a secondary mesylate using pyridine as the base. 

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. 

A cyclic ether can be prepared by an intramolecular Williamson ether synthesis (Section 11.9). 

Alkyl halides readily undergo nucleophilic substitution reactions with alkoxides to give ethers (the Williamson ether synthesis). In this case, the reaction would be an Intramolecular... 

An alternative method for the preparation of an epoxide reacts a halohydrin (Chapter 10, Section 10.4.2) with a base such as sodium hydride. The resulting alkoxide undergoes an intramolecular Williamson ether synthesis. Draw the product expected when 2-bromo-l-hexanol reacts with NaH in THF. Based on the two carbons of the epoxide, is this transformation a net oxidation or a reduction ... 

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). 

Be alert for intramolecular, ring-forming versions of the Williamson ether synthesis. Cyclic ethers can be formed by intramolecular Sn2 reactions. There is no mystery in this reaction it is simply the acyclic process applied in an intramolecular way (Fig. 7.108). 

An important use of the intramolecular Williamson ether synthesis is in the making of oxiranes, ethers with the oxygen atom in a three-membered ring, also called epoxides. A 2-halo-1-hydroxy compound (a halohydrin) is treated with base to form the haloalkoxide, which then undergoes an intramolecular backside 8 2 displacement to give the three-membered ring (Fig. 7.109). 

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... 

What effects are at work here Since we are concerned with rates, we need to compare the structures and hence energies of the transition states of the intramolecular Williamson ether synthesis. We shall find that the answer is composed of both enthalpic and entropic contributions (Section 2-1). Recall that enthalpy reflects changes not only in bond strengths during a reaction, but also in strain (Section 4-2). Entropy, on the other hand, is related to changes in the extent of order (or energy dispersal) in the system. What are the differences between the various transition states for ring formation with respect to these quantities ... 

Working with the Concepts Stereochemistry of the Intramolecular Williamson Ether Synthesis... 

Bromoalcohol A transforms rapidly in the presence of sodium hydroxide to give the corresponding oxacyclopropane, whereas its diastereomer B does not. Why [Caution Unlike the previous problem, both substrates are frans-bromoalcohols. Hint Draw the most stable cyclohexane chair conformers of both isomers (Section 4-4) and picture the respective transition states for the intramolecular Williamson ether synthesis.]... 

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