Tert-butoxide ion

As a practical matter elimination can always be made to occur quantitatively Strong bases especially bulky ones such as tert butoxide ion react even with primary alkyl halides by an E2 process at elevated temperatures The more difficult task is to find condifions fhaf promofe subsfifufion In general fhe besf approach is fo choose condi lions lhal favor fhe 8 2 mechanism—an unhindered subslrale a good nucleophile lhal IS nol slrongly basic and fhe lowesl praclical lemperalure consislenl wilh reasonable reaclion rales... 

Because the Williamson synthesis is an S 2 reaction, it is subject to all the usual constraints, as discussed in Section 11.2. Primary halides and tosylates work best because competitive E2 elimination can occur with more hindered substrates. Unsymmetrical ethers should therefore be synthesized by reaction between the more hindered alkoxide partner and less hindered halide partner rather than vice versa. For example, terf-butyl methyl ether, a substance used in the 1990s as an octane booster in gasoline, is best prepared by reaction of tert-butoxide ion. with iodomethane rather than by reaction of methoxide ion with 2-chloro-2-methylpropane. 

Polymeric forms have also been reported. One example, which also includes germanium heteroatoms terminating the chain, is the oligomer (RO)Ge(RO)2Co(RO)2Co(RO)2Ge(OR), (97) where each Co center is surrounded by four bridging tert-butoxide ions.416 These form via a photochemically induced labile solvent complex, or else through thermally induced substitution... 

In this regard Gedye et al. studied reactions of alkyl halides with bases in which the amounts of elimination and substitution were compared and a Diels-Alder reaction in which the ratio of endo to exo adducts was investigated [71]. In the first set of experiments, the ratios of elimination to substitution products for the reactions of 1-and 2-bromooctane with methoxide ion in methanol and with tert-butoxide ion in tert-butyl alcohol, obtained under MW heating in a sealed Teflon container, were compared with those found using normal reflux conditions (Scheme 4.25). 

Scheme 6.58 Generation of 3<52-chromene (258) and its interception by the tert-butoxide ion and various activated alkenes.

The formation of the acetal 271 is evidence for a polar nature of 258 in terms of the zwitterions 258-Zi, whose pyrylium-ion character explains the attack of the tert-butoxide ion to give the vinyl anion 265 (Scheme 6.58). In contrast to 260/260-Zi, 258 does prefer cycloadditions if it is generated in the presence of an activated... 

This is manifest in the reactivity of 180/180-Z1 which was generated from 3-bromo-41-f-pyran (283) by /3-elimination of hydrogen bromide with KOtBu (Scheme 6.61). Whether or not this reaction was conducted in the presence of styrene or furan, the only product identified was tert-butyl 4H-pyran-4-yl ether (284). This is in line with the relationship of the intermediate to a pyrylium ion. Thus, the addition of the tert-butoxide ion to 180/180-Zj has to be expected at the 4-position with formation of the vinyl anion 285, which is then protonated to give 284. Likewise, the attack of the nucleophile is predicted at C2and C6 leading to the vinyl anions 286, which... 

Scheme 6.61 Generation of 3<52-pyran (180) and trapping by the tert-butoxide ion.

Attempts to liberate l-methyl-l-aza-2,3-cyclohexadiene (329) from 3-bromo-l-methyl-l,2,5,6-tetrahydropyridine (326) by KOtBu in the presence of [18]crown-6 and furan or styrene did not lead to products that could have been ascribed to the intermediacy of 329 (Scheme 6.70) [156], Even if there is no doubt as to the allene nature of 329 on the basis of the calculations on the isopyridine 179 and 3d2-lH-quinoline (257), it is conceivable that the zwitterion 329-Za is only a few kcal mol-1 less stable than 329. This relationship could foster the reactivity of 329 towards the tert-butoxide ion to an extent that cycloadditions to activated alkenes would be too slow to compete. On the other hand, the ultimate product of the trapping of 329 by KOtBu could have been an N,0-acetal or a vinylogous N,0-acetal, which might not have survived the workup (see, for example, the sensitivity of the N,0-acetal 262 [14], Scheme 6.57). 

Formation of the Hofmann Product Bulky bases can also accomplish dehydrohalo-genations that do not follow the Zaitsev rule. Steric hindrance often prevents a bulky base from abstracting the proton that leads to the most highly substituted alkene. In these cases, it abstracts a less hindered proton, often the one that leads to formation of the least highly substituted product, called the Hofmann product. The following reaction gives mostly the Zaitsev product with the relatively unhindered ethoxide ion, but mostly the Hofmann product with the bulky tert-butoxide ion. 

In some elimination reactions, the less stable alkene is the major product. For example, if the base in an E2 reaction is sterically bulky and the approach to the alkyl halide is sterically hindered, the base will preferentially remove the most accessible hydrogen. In the following reaction, it is easier for the bulky tert-butoxide ion to remove one of the more exposed terminal hydrogens, which leads to formation of the less substituted alkene. Because the less substituted alkene is more easily formed, it is the major product of the reaction. 

This is the procedure first reported in 1961. It involves generation of phenylchlorocarbene, or more likely a related carbenoid, which adds to the acetylene to form triphenylcyclopropenium chloride. This chloride reacts with tert-butoxide ion to form the covalent tert-butyl ether, which can be isolated. With water, this ether hydrolyzes to bis(triphenylcyclopropenyl) ether, but either of these compounds is converted to the ionic bromide salt with HBr. 

Size of the Base/Nucleophile Increasing the reaction temperature is one way of favorably influencing an elimination reaction of an alkyl halide. Another way is to use a strong sterically hindered base such as the tert-butoxide ion. The bulky methyl groups of the... 

In Section 10.1, we saw that the difference in the sizes of the methoxide ion and the tert-butoxide ion causes marked differences in the rates of Sj 2 reactions. We noted that steric factors are much less important in determining the ease of abstraction of a proton. However, such effects do exist, and they are in the direction that we would expect. That is, more highly hindered bases tend to abstract the least sterically hindered protons. This fact is established for the reaction of 2-bromo-2,3-dimethylbutane with various alkoxide ions. The major product with methoxide ion is the more highly substituted alkene—the Zaitsev product. However, with rerr-butoxide, the major product is the least substituted alkene. 

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