Mechanisms alkyl halides with alkoxides

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... 

As crowding at the carbon that bears the leaving group decreases the rate of nude ophilic attack by the Lewis base increases A low level of steric hindrance to approach of the nucleophile is one of the special circumstances that permit substitution to pre dominate and primary alkyl halides react with alkoxide bases by an 8 2 mechanism m preference to E2... 

In most cases the alkoxide or phenoxide 1 reacts with the alkyl halide 2 by a bimolecular nucleophilic substitution mechanism ... 

Ethers can be prepared by reaction of an alkoxide or phenoxide ion with a primary alkyl halide. Anisole, for instance, results from reaction of sodium phenoxide with iodomethane. What kind of reaction is occurring Show the mechanism. 

Elimination reactions can also occur when a carbon halogen bond does not completely ionize, but merely becomes polarized. As with the El reactions, E2 mechanisms occur when the attacking group displays its basic characteristics rather than its nucleophilic property. The activated complex for this mechanism contains both the alkyl halide and the alkoxide ion. 

This method cannot be used with tertiary alkyl halides, because the competing elimination reaction predominates. The elimination reaction occurs because the rearward approach that is needed for an S 2 mechanism is impossible due to steric hindrance. An S 1 mechanism is likewise unfavored, because as the 3° carbon attempts to become a carbocation, the hydrogens on the adjacent carbons become acidic. Under these conditions, the alkoxide ion begins to show less nucleophilic character and, correspondingly, more basic character. This basic character leads to an acid-base reaction, which results in the generation of an elimination product (an alkene). 

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. 

Thus, a common way to make ethers is to treat an alkoxide anion with an alkyl halide. If the alkyl halide is a methyl compound, we can be sure that this will be by the Sn2 mechanism. A strong base, here NaH, will be needed to form the alkoxide ion (Chapter 6) and methyl iodide is a suitable electrophile. 

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. 

Rappoport has presented a detailed outline of the mechanisms of the reactions of vinyl halides with nucleophilic reagents. Modena et /. " have provided further evidence in support of a spectrum of transition states for elimination from activated vinyl halides induced by alkoxide bases. Cristol and Whittemore have shown that the stereoselectivity of elimination from vinyl halides is largely determined by the choice of basic reagent alkoxide bases encourage am/-elimination, whereas syn-elimination and alpha-elimination become dominant with lithium alkyls. 

Arsenic and Antimony. Three studies of reaction mechanisms for tetrahedral antimony(v) compounds are reported. These are of the reaction of trimethylantimony sulphide (MegSbS) with alkyl halides, where a four-centre transition state seems possible, the reaction of R4Sb+ cations with alkoxide ions, and the ageing of antimonic acid in aqueous solution. Both thermal and photochemical decomposition of pentaphenylanti-mony have been investigated. Whereas the products of the photochemical reaction are numerous, though all derived from phenyl radicals, the... 

Alcoholates (alkoxides), which were already mentioned in the discussion on the reactions of alcohols with metals, behave as strong bases and are good nucleophiles. In the middle of nineteenth century Alexander William Williamson succeeded in preparing ethers in the reactions of alkoxides with primary alkyl halides. Later it was demonsttated that these reactions follow the Sn2 mechanism. 

The trihalomethane (also called haloform) thus formed doesn t play any further role in the mechanism but the alkoxide ion produced reacts with the phosphonium ion to form a pentavalent, pentacoordinate phosphorus intermediate, which falls apart to the alkyl halide... 

Recall from Table 9.7 that thiols are moderate nucleophiles and thiolates are good nucleophiles. As such, they rank as better nucleophiles in both their neutral and anionic states as compared to alcohols and alkoxides, respectively. The reason thiols and thiolates are better nucleophiles is that the sulfur atom is more polarizable than oxygen, and increased polarizability enhances nucleophilicity. Also, because the values for thiols are generally less than 11, thiolate anions react with secondary alkyl halides primarily through an Sj 2 substitution mechanism rather than an E2 elimination. The reverse is true for the significantly more basic alkoxides. 

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