Dehydroxylation alcohols

Synthetic routes that access appropriately substituted thienobenzazepines are also quite important for medicinal chemistry stracture activity relationship studies, and many involve similar bond connectivity strategies. One notable example employs the use of conunercially available 4-methyl-3-nitrophenol (Scheme 6.3). Methylation of the phenol followed by bromination, hydrolysis, and oxidation of the benzylic alcohol afforded aldehyde 9 in quantitative yield. Treatment of this aldehyde with 5-lithio-2-methylthiophene provided, after dehydroxylation, nitro intermediate A in good overall yield. Reduction of the nitro functionality and treatment with phosgene presented the corresponding isocyanide which upon cychzation using aluminum trichloride in a Friedel-Crafts fashion afforded the... 

The second approach (Equation(3)) has a number of advantages over the first one (Equation(2)). The alkyl complexes are more reactive than the related alkoxides, the latter being for group 4 elements generally associated into dimers or trimers 48 also, reaction (2) liberates an alcohol which may further react with the surface of silica, whereas the alkane ( Equation(3)) is inert. It was demonstrated by various spectroscopic techniques and elemental analysis that with a silica dehydroxylated at 500 °C under vacuum, the stoichiometry of reaction (3) corresponds to n = 1.45,46 Moreover, a better control of the surface reaction was achieved with the procedure represented in Equation(3). 

Fig. 4. Adsorption complex of 2-propanol on a partially dehydroxylated (100) plane of alumina after Sedlacek [72], Small open circles denote H, medium circles with thin hatching O, medium circles with dense hatching C, large open circles Al. For consistency, covalent atomic radii have been used for O in alumina although its structure is partly ionic therefore aluminium atoms appear unusually large. The diagram shows the possibility of a two-point interaction of an alcohol with a surface hydroxyl group and a surface oxygen without any distortion of the molecule.

Dehydroxylation Deoxygenation of the mesylate or tosylate of the alcohol 1, an intermediate in a synthesis of ( + )-hirsutene (2), with Li(C2H5)3BH results... 

In the case of 3,3-dimethyl-1-butanol and 1-methyl-1-hydroxymethylcyclohexane, the reductive dehydroxylation in the presence of thiophene was accompanied by a skeletal isomerization 2,2- and 2,3-dimethylbutane were formed from the former alcohol and a mixture of ethylcyclohexane, methylcycloheptane, and 1,2-dimethylcy-clohexane from the latter alcohol. It has been suggested that the sulfirr compounds accentuate the acid properties of a nickel catalyst through their ability to poison the catalyst. 

Another substrate class for reductive radical cyclisation reactions, which was studied in our laboratories, are 4-(4 -iodoalkyl)quinolones (e.g. 27 Scheme 10). High enantioselectivities could be achieved even at 0 °C (up to 99% ee) or at ambient temperature (up to 96% ee). Furthermore, an unexpected chirality multiplication was observed with low catalyst loadings (Dressel and Bach 2006). 4-(4/-Iodobutyl)quinolone (27) can be synthesised from4-methylquinolonein three steps by alkylation with 3-/< /7-butyldimcthylsilyl(TBDMS)oxy-l-iodopropane, deprotection of the alcohol and iodo-dehydroxylation in an overall yield of 31%. 

As noted in Chapter 1, the specific interactions between polar molecules and silica are virtually eliminated by the removal of all the surface hydroxyls and therefore the effect of partial dehydroxylation is to drastically reduce the adsorption energies of certain molecules. The polar adsorptives studied by Kiselev and his co-workers included alcohols, ketones, ethers and amines (Kiselev, 1965, 1971) with each adsorptive, the reduction in the adsorbent-adsorbate interaction energy was accompanied by a substantial change in the isotherm character. 

Figure 1 illustrates differential distributions of the adsorption energy of n-hexane on partially dehydroxylated silica gel (1) and on carbon-silica adsorbents prepared through the pyrolysis of n-heptyl (2) and benzyl (3) alcohols and their different mixtures (4-6) on the solid surface. The energy distribution function X(E) of n-hexane was measured chromatographically from the pressure dependence of the retention volume [24,25]. 

Tetraneopentylzirconium, ZrNp4, was synthesized according to Lappert et al. [16]. Silica (from Shell, 350 m g-l) was partially dehydroxylated at 450°C (10" torr, 16h). Reactants (from Aldrich) i.e. ketones, alcohols, cyclohexene were used as received. H2O2 (70% wt) was from Atochem. All manipulations were performed under dry Ar,when appropriate. 

Radical dehydroxylation is most effective for secondary alcohols, including those derived from carbohydrates, in which traditional methods such as tosylation (or mesylation) and L1A1H4 reduction often fail. The reaction tolerates many different functional groups, as illustrated in the reduction of the thiocarbonyl compound 8 (4.8). ... 

Pines, in pursuing this reaction, found that running the reaction in the presence of thiophene or methyl sulfide gave only reductive dehydroxylation of a primary alcohol (34). 

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