Displacement of the hydroxyl

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)... 

One of the earliest preparations of this ring system starts with displacement of the hydroxyl of benzaldehyde cyanohydrin (125) by urea. Treatment of the product (126) with hydrochloric acid leads to addition of the remaining urea nitrogen to the nitrile. There is thus obtained, after hydrolysis of the imine (127), the hydantoin (128). Alkylation by means of ethyl iodide affords ethotoin (129)... 

During the dehydration stage (between 450°C and 600°C), hydroxyl (OH ) ions in the clay are dislodged from their molecules, combine with each other to form water vapor, and are thus removed from the clay structure and released into the atmosphere. It is during this stage, as a consequence of the displacement of the hydroxyl ions, that the chemical composition and the structure of the clay are irreversibly altered and converted to fired clay. 

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). 

We have no direct evidence for this type of behavior. However, it appears reasonable to expect that hydroxyl oxygens would compete with ether oxygens for coordination. Thus, displacement of the hydroxyl complexes, Equation 6, might be rate controlling. 

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. 

The third approach to obtain diarylmethylpiperazine derivatives uses the highly stereospecific chiral oxazaborolidine-catalyzed reduction, using catecholborane as the reductant of the 4-bromobenzophenone chromium tricarbonyl complex, as described by Corey and Helal [59], followed by the stereospecific displacement of the hydroxyl benzyl group by the /V-substituted-piperazine [44]. As outlined in Scheme 2, Delorme et al. [44] used this approach for the enantioselective synthesis of compound 31, (+)-4-[ (aS)-a-(4-benzyl-l-piperazinyl)benzyl]-lV,lV-diethylben-zamide. Lithiation of the readily available benzene chromium tricarbonyl with n-BuLi in the presence of TMEDA in THF at —78 °C, followed by addition of... 

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. 

Little is known of the mechanism by which ribose is reduced. It has been suggested on the basis of chemical analogy (97) that the process could occur by displacement of the hydroxyl on C-2 of ribose to form the cyclonucleotide (IX). This could be followed bya reductive cleavage of theCj—O bond to form the deoxyribonucleotide. Cyclic nucleoside formation might be assisted by a preliminary phosphorylation of the 2 -hydroxyl group. H H... 

---