Alkoxide ions halides

Alkoxide ion (RO ) The oxygen atom of a metal alkoxide acts as a nucleophile to replace the halogen of an alkyl halide The product is an ether... 

Recall from Section 8 13 that the major pathway for reaction of alkoxide ions with secondary alkyl halides IS E2 not Sn2... 

Alkanethiolate ions (RS ) are weaker bases than alkoxide ions (RO ) and undergo synthetically useful 8 2 reactions even with secondary alkyl halides... 

The Williamson ether synthesis (Sec tion 16 6) An alkoxide ion displaces a halide or similar leaving group in an Sn2 reaction The alkyl halide cannot be one that is prone to elimination and so this reaction is limited to methyl and primary alkyl halides There is no limitation on the alkoxide ion that can be used... 

The reaction between an alkoxide ion and an aryl halide can be used to prepare alkyl aryl ethers only when the aryl halide is one that reacts rapidly by the addition-elim mation mechanism of nucleophilic aromatic substitution (Section 23 6)... 

Weak acid (Section 1 16) An acid that is weaker than 1130" Weak base (Section 1 16) A base that is weaker than HO Williamson ether synthesis (Section 16 6) Method for the preparation of ethers involving an Sfj2 reaction between an alkoxide ion and a primary alkyl halide... 

The reaction of chlorodifluorotnethane with alkoxide ions generated in low concentration from halide ions and epoxides [28, 29] is an interesting, higher temperature method that gives good to excellent yields of gem-difluorocyclo-propanes from just moderately nucleophilic olefins (equation 9)... 

Substitution of an additional nitrogen atom onto the three-carbon side chain also serves to suppress tranquilizing activity at the expense of antispasmodic activity. Reaction of phenothia zine with epichlorohydrin by means of sodium hydride gives the epoxide 121. It should be noted that, even if initial attack in this reaction is on the epoxide, the alkoxide ion that would result from this nucleophilic addition can readily displace the adjacent chlorine to give the observed product. Opening of the oxirane with dimethylamine proceeds at the terminal position to afford the amino alcohol, 122. The amino alcohol is then converted to the halide (123). A displacement reaction with dimethylamine gives aminopromazine (124). ... 

The E2 reaction (for elimination, bimolecular) occurs when an alkyl halide is treated with a strong base, such as hydroxide ion or alkoxide ion (RO-). It is the most commonly occurring pathway for elimination and can be formulated as shown in Figure 11.17. 

Ethers can often be prepared by SN2 reaction of alkoxide ions, RO-. with alkyl halides. Suppose you wanted to prepare cyclohexyl methyl ether. Which of the two possible routes shown below would you choose Explain. 

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. 

Williamson ether synthesis (Section 18.2) A method for synthesizing ethers by S 2 reaction of an alkyl halide with an alkoxide ion. 

The addition of alcohols to carbon disulfide in the presence of a base produces xanthates. The base is often OH, but in some cases better results can be obtained by using methylsulfinyl carbanion (MeSOCH ) If an alkyl halide RX is present, the xanthate ester ROCSSR can be produced directly. In a similar manner, alkoxide ions add to CO2 to give carbonate ester salts ROCOO. ... 

This is not a new reaction. This is just an Sn2 reaction. We are simply using the alkoxide ion (ethoxide in this case) to function as the attacking nucleophile. But notice the net result of this reaction we have combined an alcohol and an alkyl halide to form an ether. This process has a special name. It is called the Williamson Ether Synthesis. This process relies on an Sn2 reaction as the main step, and therefore, we must be careful to obey the restrictions of Sn2 reactions. It is best to use a primary alkyl halide. Secondary alkyl halides cannot be used because elimination will predominate over substitution (as seen in Sections 10.9), and tertiary alkyl halides certainly cannot be used. 

The oxygen nucleophiles that are of primary interest in synthesis are the hydroxide ion (or water), alkoxide ions, and carboxylate anions, which lead, respectively, to alcohols, ethers, and esters. Since each of these nucleophiles can also act as a base, reaction conditions are selected to favor substitution over elimination. Usually, a given alcohol is more easily obtained than the corresponding halide so the halide-to-alcohol transformation is not used extensively for synthesis. The hydrolysis of benzyl halides to the corresponding alcohols proceeds in good yield. This can be a useful synthetic transformation because benzyl halides are available either by side chain halogenation or by the chloromethylation reaction (Section 11.1.3). 

The alkoxide ion reacts with the substrate in an SN2 reaction, with the resulting formation of the ether. The substrate must bear a good leaving group. Typical substrates are alkyl halides, alkyl sulfonates, and dialkyl sulfates, i.e. 

Numerous reactions in the field of organic chemistry are known to involve the intermediate formation of ions, though only few ionic equilibria are known. Amines, amides, alkoxides or halide ions are known to act as donors and to produce ionic species 24 26 ... 

It is important to be able to look at a molecular structure and deduce the possible reactions it can undergo. Take an alkene, for example. It has a 7t bond that makes it electron-rich and able to attack electrophiles such as water, halogens and hydrogen halides in electrophilic addition reactions. Haloalkanes, on the other hand, contain polar carbon-halogen bonds because the halogen is more electronegative than carbon. This makes them susceptible to attack by nucleophiles, such as hydroxide, cyanide and alkoxide ions, in nucleophilic substitution reactions. 

Ethers containing substituted all rl groups (secondary or tertiary) may also be prepared by this method. The reaction involves Sn2 attack of an alkoxide ion on primary alkyl halide. 

An early report (Briscese and Riveros, 1975) revealed that in the gas phase, alkoxide ions can displace fluoride from fluorobenzene (91). Hydroxide ion fails to react because C6H5F is more acidic than H20 and thus proton transfer becomes the most important channel. Similar reactions with other monohalobenzenes are complicated because these substrates usually generate halide ions directly by dissociative electron attachment. 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetylide ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, halide ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4,-chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4,-sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

Kinetic template effects have been involved in the formation of crown ethers, with respect to the cyclization step involving a nucleophilic displacement of halide or tosylate by alkoxide ions. It has been proposed that cyclization of the linear bifunctional precursor is enhanced by a cyclic conformation in which the alkoxide cation brings the two ends of the molecule into close proximity... 

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