2,6-di-fert-butylpyridine

Another type of steric effect is the result of an entropy effect. The compound 2,6-di-fert-butylpyridine is a weaker base than either pyridine or 2,6-dimethylpyridine. The reason is that the conjugate acid (8) is less stable than the conjugate acids of nonsterically hindered pyridines. In all cases, the conjugate acids are hydrogen bonded to a water molecule, but in the case of 8 the bulky tert-butyl groups restrict rotations in the water molecule, lowering the entropy. 

Base-sensitive substrates require some special precautions With the very potent alkylating agent methyl triflate, the highly hindered (and expensive) base 2,6-di-fert-butylpyridine can be used as shown in Scheme 4.114 22 205 Alternatively O-methylation using a combination of trimethyloxonium tetrafluoroborate and l,8-bis(dimethylamino)naphthalene in dichloromethane can be used although this is also a very expensive method [Scheme 4 115].206 Evans and co-workers have made a systematic study of the best conditions for 0-methylating hindered multifunctional substrates,207... 

Figure 2.41 IR spectra (a) before and (b) after adsorption of 2,6-di-fert-butylpyridine (DTBP) on beta zeolite. The band of bridging hydroxyl groups at 3610 cm disappears completely, and characteristic signals of the DTBPH ion are formed at 3370,1616, and 1530 cm Reproduced from Ref (478).

Table 2.21 Accessibility of protonic acid sites of different standard zeolites to 2,6-di-fert-butylpyridine (DTBP) (479)...

Hindered nonnucleophilic bases are typically added to sulfoxide glycosylations to buffer the acidic by-products. Classically, the 2,6-di-tert-butylpyridines have been employed for this purpose [86], but the more highly crystalline and easily handled 2,4,6-tri-fert-butylpyrimidine is finding increasing favor in this regard [356]. 

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