Deprotonation of alcohols

Many different types of bases are used in organic chemistry. Common inorganic bases include the anions of weak bases such as water and ammonia (OH and NH2 ). Similar deprotonation of alcohols leads to the alkoxide bases (RO ). Methoxide (MeO ), ethoxide (EtO ), and ferf-butoxide (Me3C-0 ) are very common and are often used in the alcohol solvents from which they were made (methoxide in methanol, tert-butoxide in ferf-butanol, etc.). The bases used to deprotonate water (p fa = 15.8) or alcohols (pATa 18) are sodium hydride (NaH), potassium hydride (KH), sodium and potassium hydroxide (NaOH, KOH), sodium metal (Na°),... 

So now we can expand our chart of acid and base strengths to include the important classes of alcohols, phenols, and carboxylic acids. They conveniently, and memorably, have piCa values of about 0 for the protonation of alcohols, about 5 for the deprotonation of carboxylic acids, about 10 for the deprotonation of phenols, and about 15 for the deprotonation of alcohols. The equilibria above each piCa shows that at approximately that pH, the two species each form 50% of the mixture. You can see that carboxylic acids are weak acids, alkoxide ions (RO ) are strong bases, and that it will need a strong acid to protonate an alcohol. 

After deprotonation of alcohol (Eq. 5.2) and ion pairing with the quaternary ion (Eq. 5.3), reaction occurs between it and the alkyl halide (Eq. 5.5). For each mole of ether formed, a mole of quaternary ammonium halide is also formed. Exchange of the nucleofuge for a molecule of nucleophile followed by phase transfer completes the catalytic cycle which is shown in equations 5.2—5.6. 

Observations of the extent of reesterification of polysiloxanes [e.g., 26,59] indicate that it proceeds much further under acidic conditions than under basic conditions. This led Keefer [48] to the conclusion that the base-catalyzed mechanism involves inversion of configuration, while the acid-catalyzed mechanism does not. It is likely that the first step of the acid-catalyzed reesterification reaction involves the protonation of a silanol group, whereas under base-catalyzed conditions the first step is the deprotonation of an alcohol to form the nucleophile, OR . Therefore, the tendency for reesterification to be more complete under acidic than basic conditions may also result from the greater ease of protonation of silanol groups under the acidic conditions normally employed in sol-gel processing (pH 1-3) than deprotonation of alcohols under the weakly basic conditions normally employed (pH 8-10). 

We can extend the general principles of electrophilic addition to acid catalyzed hydration In the first step of the mechanism shown m Figure 6 9 proton transfer to 2 methylpropene forms tert butyl cation This is followed m step 2 by reaction of the car bocation with a molecule of water acting as a nucleophile The aUcyloxomum ion formed m this step is simply the conjugate acid of tert butyl alcohol Deprotonation of the alkyl oxonium ion m step 3 yields the alcohol and regenerates the acid catalyst... 

Once formed the tetrahedral intermediate can revert to starting materials by merely reversing the reactions that formed it or it can continue onward to products In the sec ond stage of ester hydrolysis the tetrahedral intermediate dissociates to an alcohol and a carboxylic acid In step 4 of Figure 20 4 protonation of the tetrahedral intermediate at Its alkoxy oxygen gives a new oxonium ion which loses a molecule of alcohol m step 5 Along with the alcohol the protonated form of the carboxylic acid arises by dissocia tion of the tetrahedral intermediate Its deprotonation m step 6 completes the process... 

Deprotonation of enols of P-diketones, not considered unusual at moderate pH because of their acidity, is faciUtated at lower pH by chelate formation. Chelation can lead to the dissociation of a proton from as weak an acid as an aUphatic amino alcohol in aqueous alkaU. Coordination of the O atom of triethanolamine to Fe(III) is an example of this effect and results in the sequestration of iron in 1 to 18% sodium hydroxide solution (Fig. 7). Even more striking is the loss of a proton from the amino group of a gold chelate of ethylenediamine in aqueous solution (17). 

Thus the reactions of cyclic or acyclic enamines with acrylic esters or acrylonitrile can be directed to the exclusive formation of monoalkylated ketones (3,294-301). The corresponding enolate anion alkylations lead preferentially to di- or higher-alkylation products. However, by proper choice of reaction conditions, enamines can also be used for the preferential formation of higher alkylation products, if these are desired. Such reactions are valuable in the a substitution of aldehydes, which undergo self-condensation in base-catalyzed reactions (117,118). Monoalkylation products are favored in nonhydroxylic solvents such as benzene or dioxane, whereas dialkylation products can be obtained in hydroxylic solvents such as methanol. The difference in products can be ascribed to the differing fates of an initially formed zwitterionic intermediate. Collapse to a cyclobutane takes place in a nonprotonic solvent, whereas protonation on the newly introduced substitutent and deprotonation of the imonium salt, in alcohol, leads to a new enamine available for further substitution. 

The use of sodium tribromoacetate as the dibromocarbene precursor has been investigated and found to provide the Ciamician-Dennstedt product in higher yield than the traditional alkoxide/alcohol reaction conditions. Deprotonation of bromoform with sodium ethoxide in ethanol and reaction of the resultant carbene with 6 provides quinoline 9 in 9% yield thermolysis of sodium tribromoacetate in the presence of 6 furnishes 9 in 20% yield (Scheme 8.3.3). 

Step 3 of Figure 29.3 Alcohol Oxidation The /3-hydroxyacyl CoA from step 2 is oxidized to a /3-ketoacyl CoA in a reaction catalyzed by one of a family of L-3-hydroxyacyl-CoA dehydrogenases, which differ in substrate specificity according to the chain length of the acyl group. As in the oxidation of sn-glycerol 3-phosphate to dihydroxyacetone phosphate mentioned at the end of Section 29.2, this alcohol oxidation requires NAD+ as a coenzyme and yields reduced NADH/H+ as by-product. Deprotonation of the hydroxyl group is carried out by a histidine residue at the active site. 

Alkoxide ion (Section 17.2) The anion RO- formed by deprotonation of an alcohol. 

In some cases the yields were poor due to competing deprotonation of the substrate by the organolithium reagent. Deprotonation was the predominant reaction with methyllithium or when (Z)-2-(l-alkenyl)-4,5-dihydrooxazoles were employed. The stereochemical outcome has been rationalized as occurring from a chelated transition state. The starting chiral amino alcohol auxiliary can also be recovered without racemization for reuse. 

Introduction of the phenylthio group onto the 5-carbon atom of alcohols can have valuable synthetic applications. 5-Phenylthio alcohols can be oxidized to the corresponding 5-sulfoxides and sulfones (with their versatile reactivities) or they can be deprotonated by strong base converting the 5-carbon atom to a nucleophilic species. Conversion of 5-phenylthio alcohols to the corresponding 5-carbonyl compounds can be achieved via halogenation followed by subsequent hydrolysis. In this way an inversion of the reactivity of the 5-carbon atom may be accomplished and it can react as an electron acceptor. 

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