Cyclic ethers Williamson synthesis

A second synthesis of epoxides and other cyclic ethers involves a variation of the Williamson ether synthesis. If an alkoxide ion and a halogen atom are located in the same molecule, the alkoxide may displace a halide ion and form a ring. Treatment of a halohydrin with base leads to an epoxide through this internal SN2 attack. 

Williamson ether synthesis Claisen rearrangement Cyclic ethers ... 

The conversion of halohydrins into epoxides by the action of base is simply an adaptation of the Williamson synthesis (Sec. 17.5) a cyclic compound is obtained because both alcohol and halide happen to be part of the same molecule. In the presence of hydroxide ion a small proportion of the alcohol exists as alkoxide this alkoxide displaces halide ion from another portion of the same molecule to yield the cyclic ether. 

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

Cyclic ethers are common solvents and, as we will see in Section 7.10, can often be prepared rather easily (Williamson ether synthesis, p. 315). It is possible to make cyclic polyethers, compounds in which there is more than one ether linkage. Figure 6.59 gives some examples of cyclic ethers and cyclic polyethers. 

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). 

Cyclic ethers can be prepared by intramolecular Williamson synthesis... 

Intramolecular Williamson synthesis allows the preparation of cyclic ethers of various sizes, including small rings. 

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. 

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... 

Another research group published numerous studies of syntheses and physical properties of LC-polyethers having linear chains, hyperbranched and cyclic structures or containing discotic mesogens [327-341]. All these different LC-polyethers were prepared via the normal Williamson ether synthesis involving the nucleophilic attack of a phenoxide ion onto a bromoalkane. For instance, numerous linear LC-polyesters were prepared from the mesogenic diphenols outlined in (214) and formulas (215a,b) [327,337]. 

A second method of synthesizing epoxides is an intramolecular variation of the Williamson ether synthesis. First, a halohydrin forms in the reaction of an alkene with an aqueous solution of a halogen. For example, chlorine gives a cyclic chloronium ion, which then reacts with water as the nucleophile to give the chlorohydrin. 

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