Dehydration with rearrangement

B-8. Which of the following alcohols would be most likely to undergo dehydration with rearrangement by a process involving a methyl migration (methyl shift) ... 

Pinacol and other highly substituted 1,2-diols tend to undergo dehydration with rearrangement under acid-catalysis. 

Braude and Evans found the ester (1) remarkably resistant to dehydration by usual methods (heating with KHSO or with iodine, treatment with SOCI. in pyridine or with P2O5 and triethylamine), but effected dehydration, with rearrangement to (3), by heating 1 g. with 20 mg. of naphthalene-/8-suIfonic acid at 1307100 mm. 

Dehydration with rearrangement of extra-framework cations without considerable changes in the geometry of the framework and in the cell volume. Zeolite A, faujasite, natural chabazite, and mordenite provide examples of this thermal behavior. 

Under mild conditions and in a variety of solvents, tertiary steroid alcohols are inert to the fluoroamine. At elevated temperatures, however, they afford exclusively, and in high yield, products resulting from dehydration with or without rearrangement. Thus, 17a-methyltestosterone (10) furnishes in 42% yield the 18-norsteroid (11). 

Normal Fischer esterification of tertiary alcohols is unsatisfactory because the acid catalyst required causes dehydration or rearrangement of the tertiary substrate. Moreover, reactions with acid chlorides or anhydrides are also of limited value for similar reasons. However, treatment of acetic anhydride with calcium carbide (or calcium hydride) followed by addition of the dry tertiary alcohol gives the desired acetate in good yield. 

Dehydration without rearrangement occurs regioselectively with thionyl chloride in pyridine (Eq. 43). The selenium analogues have shown similar behavior (Eq. 44) 87)... 

A similar transformation for hydroxyl derivative 397 requires initial dehydration with mesytyl chloride/pyridine followed by rearrangement to 398 (Scheme 82 (1997TL2271)). 

Grignard gives the tertiary alcohol after hydrolysis. Reaction of the alcohol with hydrochloric acid proceeds with rearrangement and opening of the strained cyclopropane to give a chloride. Sn2 displacement of the chloride with dimethylamine forms amitriptyline. Alternatively, dibenzosuberone can be reacted with dimethylaminopropyl Grignard to form an alcohol, which upon dehydration forms amitriptyline. 

Bomeol is oxidized to camphor with chromic or nitric acid dehydration with dilute acids yields camphene. Bomeol is readily esterified with acids, but on an industrial scale bornyl esters are prepared by other routes. For example, levorotatory bomeol is synthesized industrially from levorotatory pinenes by Wagner Meerwein rearrangement with dilute acid, followed by hydrolysis of the resulting esters [86]. 

Rearrangements have also been observed in such thermolyses.256 Thus, a-(4-chlorophenoxy)propiophenone, dehydrated with PPA, gives exclusively the corresponding 3-phenylbenzofuran (83, R2 = Me, R5 = Cl) in 91% yield thermolysis gives the isomeric 2-phenylbenzo-furan (84, R3 = Me) (4% yield). 

The fact that under the same conditions acetophenone oxime does not form amides, but remains intact, also provides evidence against the classical Beckmann rearrangement. The conditions found can be employed for preparing amides from nitriles and aldoximes, especially when the latter contain fragments unstable to acids. In the absence of DMSO, benzaldoxime is dehydrated with alkali only at the boiling point (200°C). 

D is correct. This reaction is dehydration of an alcohol and proceeds with rearrangement of the carbocation intermediate from secondary to tertiary. (See page 35.)... 

The addition of a-lithiovinyltrimethylsilane 151 83), generated from a-bromovinyl-trimethylsilane84,) with r-BuLi (1.5 equivalents) at —78 °C in ether, to ketones and aldehydes was also investigated. The allylic alcohols 152 thus obtained underwent smooth cyclopropanation when the modified Simmons-Smith procedure utilizing EtZnI85) was applied. The cyclopropylcarbinols 153 were directly dehydrated without rearrangement upon exposure to catalytic amounts of p-TsOH in benzene at 20 °C to give 149 in yields of 52-75%, Eq. (48) 79,8L). 

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