Displacement of the hydroxyl group

Displacement of the hydroxyl group is exemplified by the production of isopropyl haUdes, eg, isopropyl bromide [75-26-3] by refluxing isopropyl alcohol with a halogen acid, eg, hydrobromic acid [10035-10-6] (12). 

Appropriately constructed fluoroallylic alcohols are attacked at the double bond by sodium borohydride with Sfj2 displacement of the hydroxyl group rather than the vmylic fluorine [47] (eqiiauon 36)... 

A mechanism involving nucleophilic displacement of the hydroxyl group on C-2 by the selenium atom at C-5 has been proposed for the formation of the acetal 73. This mechanism does not, however, account for the presence of two products, epimeric at C-2, in the reaction mixture. 

Epoxybutene is also metabolized by human 0-class GST purified from placenta. Products formed were S -(l-hydroxy-3-buten-2-yl)glutathione [.S -( I-hydroxymcthy 1-2-propenylglutathione, using the nomenclature of Figure 1] and 5 -(2-hydroxy-3-buten-1-yl)ghitathione. The latter product is in 1 1 equilibrium with the relatively stable sulfurane tautomer formed by intramolecular displacement of the hydroxyl group by the sulfur atom (Sharer et al., 1991). 

The following sections on the chemical reactions of alcohols has been broken down into five categories (A) Nucleophilic reactions of alcohols, (B) displacement of the hydroxyl group,... 

Direct displacements of the hydroxyl group by azide are uncommon, but carbonium ions derived from alcohols are attacked by the azide ion to give organic azides (43) (Reaction XXVIII). 

Beak used this method in a synthesis of (-)-paroxetine 97 (Paxil or Seroxat), a selective serotonin reuptake inhibitor.9 Lithiation of 92 with n-BuLi-(-)-sparteine and addition of the product 93 to the nitroalkene 94 yields the protected Z-enamine 95, as usual for reactions of lithiated allylamides, in >94% ee. Hydrolysis and reduction of the product, followed by mesylation and cyclisation gave the fnms-substituted piperidine 96. Displacement of the hydroxyl group by sesamol yielded (-)-paroxetine 97. 

Oximes may also be converted by an exchange reaction into methoximes and higher alkyloximes. It was shown [229], in a study involving a number of steroids, that the rate of displacement of the hydroxyl group of an oxime by a methoxyl... 

Treatment of dimethyl ( S)-malate (2) with DAST results in displacement of the hydroxyl group by fluorine [67]. The reaction proceeds stereospecifically with inversion of config-... 

The proposed biosynthesis of piperazate residue of kutznerides, in analogy with monamycin and polyoxypeptin biosynthesis [213, 214], starts from the precursors glutamic acid and glutamine. The N—bond formation is achieved by the initial A-hydroxylation catalyzed by Ktzl, followed by the intramolecular displacement of the hydroxyl group by 5-amine as a nucleophile. The y,5-deidropiperazate is the common intermediate for all four piperazate moieties in kutznerides. Tautomerization of enamine to imine forms the -N unsaturated dehydropiperazate. Reduction of hydrazone leads to piperazate. The biosynthesis of y-chloro-substituted piperazate... 

The Mannich reaction presents a nice mechanistic problem because two routes to product seem possible, and it is the simpler (and incorrect) process that is the easier to find. The difficulty is that we are now experienced in working out aldol condensations and a reasonable person would probably start that way. An acid-catalyzed crossed aldol condensation (p. 982) leads to a P-hydroxy ketone (Fig. 19.118). Displacement of the hydroxyl group (after protonation, of course) would lead to the initial product, the ammonium ion. Treatment with base would surely liberate the free amine. 

Alternatively, 20-deoxy-20-fluorocamptothecin could be prepared from camptothecin or a synthetic intermediate by stereospecific displacement of the hydroxyl group with DAST. °° The cytotoxicity study showed that the (/ )-enantiomer of 20-fluorocamptothecin is essentially inactive, while the (5)-enantiomer is at least 100—1000 times less potent than the natural product. Unfortunately, in this case, the substitution of the hydroxy group by a fluorine atom has a significant detrimental effect on interactions of the drug with the topoisomerase I/DNA complex. 

---