Alkylation hydroxyl groups nucleophilic

Hydroxyl Group. Reactions of the phenohc hydroxyl group iaclude the formation of salts, esters, and ethers. The sodium salt of the hydroxyl group is alkylated readily by an alkyl hahde (WiUiamson ether synthesis). Normally, only alkylation of the hydroxyl is observed. However, phenolate ions are ambident nucleophiles and under certain conditions, ring alkylation can also occur. Proper choice of reaction conditions can produce essentially exclusive substitution. Polar solvents favor formation of the ether nonpolar solvents favor ring substitution. 

The 1,6-anhydride bond is rather stable toward bases, permitting not only highly selective reactions of free hydroxyl groups, such as acylation, sulfonylation, and alkylation by conventional methods, but also by selective nucleophilic attack of the oxirane ring. On the other hand, the 1,6-anhydride bond is cleaved in acid solutions (concurrently with the... 

IR-spectra of pseudostrychnine in the solid phase and in solution indicate that it exists almost entirely in the carbinolamine form CXCVI. Two other forms might be expected to exist in equilibrium with CXCVI in solution the immonium form CXCVII, produced by proton-catalyzed loss of the hydroxyl group, is totally excluded on steric grounds the keto-amine form CXVIII, on the other hand, almost certainly exists in equilibrium with CXCVI in solution, but in concentrations which escape detection by physical methods. Its presence is deduced from some of the chemical reactions of pseudostrychnine. The easy formation of O-alkyl ethers (125) by interaction with methanol or ethanol even at room temperature almost certainly involves nucleophilic attack of the alcohol molecule on the carbonyl carbon in CXCVIII or in the O-protonated form CXCIX (R = H) to yield a hemiacetal as a first step likewise, the formation of 16-cyanostrychnine (XXV CN instead of OH) must involve addition of cyanide ion to CXCVIII, and the reaction with... 

Protection of hydroxyl groups. Alcohols and phenols react with 1 and tri-ethylamine to form tetrahydro-2-furanyl (THF) ethers (85-98% yield). The reaction of acids with 1 results in THF esters. These derivatives are stable to base and nucleophilic reagents they are readily removed by acid-catalyzed hydrolysis or methanolysis. One synthetic application is conversion of the ethers into alkyl bromides by reaction with triphenyphosphine dibromide (1,1247-1248), a reaction that is faster than that with the free alcohols. 

The sulfonyl halides (ArSOjCl) convert the alcohol into a sulfonate (ArSOjOR), which is a better leaving group than the hydroxyl group. This allows a range of nucleophilic substitutions to be carried out, many of which parallel those found with alkyl halides. Alkyl halides such as iodides are formed by the nucleophilic substitution of the sulfonate by an iodide ion. The reaction in this case proceeds with inversion of configuration. Treatment of the sulfonate esters with bases such as sodium methoxide or collidine (2,4,6-trimethylpyridine), or even just heating them, can lead to the elimination of toluene-4-sulfonic acid and the formation of an alkene. 

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