Introduction to Functional Groups and Alcohols

Vinyl halides represent yet another important class of intermediates in the conversion of ketones to alkenes. The most widely applied conditions for the conversion of ketones into vinyl halides are those developed by Barton et a/. ° for the conversion of 3p-acetoxyandrost-5-ene-17-one into 3P-hydroxyandrosta-5,16-diene (Scheme 44). These conditions of vinyl halide formation and subsequent reduction have been useful in a number of steroid systems for the introduction of a A -carbon-carbon double bond and have been shown to be compatible with such functional groups as alcohols, isolated double bonds and acetals. The scope of vinyl iodide formation from hydrazones has been studied by Pross and Stemhell, and recently the original reaction conditions were improved by using sterically hindered guanidine bases rather than triethylamine. Haloalkenes have also been prepared from the corresponding ketones by treatment with iodoform and chromium chloride or with phosphorous penta-halides. ... 

Since a terminal functional group does not appreciably alter the space requirement, urea forms inclusion-compounds with alcohols, aldehydes, carboxylic acids and amines derived from n-C7 and higher hydrocabons. For molecules with cross section too small, the introduction of functional groups of adequate size leads to inclusion. 

Since (A) does not contain any other functional group in addition to the formyl group, one may predict that suitable reaction conditions could be found for all conversions into (A). Many other alternative target molecules can, of course, be formulated. The reduction of (H), for example, may require introduction of a protecting group, e.g. acetal formation. The industrial synthesis of (A) is based upon the oxidation of (E) since 3-methylbutanol (isoamyl alcohol) is a cheap distillation product from alcoholic fermentation ( fusel oils ). The second step of our simple antithetic analysis — systematic disconnection — will now be exemplified with all target molecules of the scheme above. For the sake of brevity we shall omit the syn-thons and indicate only the reagents and reaction conditions. 

A large number of silylating agents exist for the introduction of the trimethylsilyl group onto a variety of alcohols. In general, the sterically least hindered alcohols are the most readily silylated, but are also the most labile to hydrolysis with either acid or base. Trimethylsilylation is used extensively for the derivatization of most functional groups to increase their volatility for gas chromatography and mass spectrometry. 

The application of the HSAB concept to solutions leads to the rule that hard solutes dissolve in hard solvents and soft solutes dissolve in soft solvents (Pearson, 1987). For example, benzene is considered a very soft solvent since it contains only a basic function. Contrary to benzene, water is a very hard solvent, with respect to both its basic and acidic properties, ft is the ideal solvent for hard bases and hard acids. The hardness of water is reduced by the introduction of alkyl substituents in proportion to the size of the alkyl group. In alcohols, therefore, softer solutes become soluble. 

Some strategies used for the preparation of support-bound thiols are listed in Table 8.1. Oxidative thiolation of lithiated polystyrene has been used to prepare polymeric thiophenol (Entry 1, Table 8.1). Polystyrene functionalized with 2-mercaptoethyl groups has been prepared by radical addition of thioacetic acid to cross-linked vinyl-polystyrene followed by hydrolysis of the intermediate thiol ester (Entry 2, Table 8.1). A more controllable introduction of thiol groups, suitable also for the selective transformation of support-bound substrates, is based on nucleophilic substitution with thiourea or potassium thioacetate. The resulting isothiouronium salts and thiol acetates can be saponified, preferably under reductive conditions, to yield thiols (Table 8.1). Thiol acetates have been saponified on insoluble supports with mercaptoethanol [1], propylamine [2], lithium aluminum hydride [3], sodium or lithium borohydride, alcoholates, or hydrochloric acid (Table 8.1). 

Systematic functionalization of the hydroxyl group of lead inhibitor 133 with various alkyl chains allowed for the introduction of hydrophobic groups designed to interact with nonpolar regions of subsites S4 and S5. In every reported case, alkyl ether derivatives were superior inhibitors to the alcohol.121 Analysis of a range of inhibitors led to the conclusion that the length, branching, and... 

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