Carbonyl group acid-catalyzed addition

Acid-catalyzed hydration of isolated double bonds is also uncommon in biological pathways. More frequently, biological hydrations require that the double bond be adjacent to a carbonyl group for reaction to proceed. Fumarate, for instance, is hydrated to give malate as one step in the citric acid cycle of food metabolism. Note that the requirement for an adjacent carbonyl group in the addition of water is the same as that we saw in Section 7.1 for the elimination of water. We ll see the reason for the requirement in Section 19.13, but might note for now that the reaction is not an electrophilic addition but instead occurs... 

One method of deciding between Mechanisms I and II is to look at the trend of a in acid-catalyzed additions of various nucleophiles to a carbonyl group.26 It follows from the reacting bond rules that in true general acid catalysis (Mechanism I), the sensitivity of the rate to acidity of the catalyst, and therefore also a, should decrease as the species adding is made more nucleophilic. The reason is that this variation will cause the change in reaction coordinate shown in... 

SE.3.1.2. Desymmetrization of gem-Dwarboxylates An equivalent of asymmetric carbonyl addition can be achieved by the alkylation of gem-dicarboxylates (Scheme 8E.17). The alkylation of gem-dicarboxylates, which are easily prepared by the Lewis acid-catalyzed addition of acid anhydrides to an aldehyde, converts the problem of differentiating the two enantiotopic 7t-faces of a carbonyl group into that of asymmetric substitution of either enantiotopic C-O bond of the gem-dicarboxylate. Although asymmetric induction may be derived from enantio-discrimination in the ionization step or in the alkene coordination step, the fast and reversible nature of alkene coordination suggests that the ionization step is more likely to be the source of enantio-discrimination. 

The first three steps correspond to acid-catalyzed addition of ethanol to the carbonyl group to yield a hemiacetal. 

Section 11.6 discussed the acid-catalyzed addition of water to alkynes. The initial product of this reaction, called an enol, has a hydroxy group attached to one of the carbons of a CC double bond. The enol is unstable and rapidly converts to its tautomer, a carbonyl compound. The carbonyl and enol tautomers of acetone are shown in the following equation ... 

In effect, the base-catalyzed addition to a carbonyl group results from nucleophilic attack of a strong nucleophile followed by protonation. Acid-catalyzed addition begins with protonation, followed by the attack of a weaker nucleophile. Many additions are reversible, with the position of the equilibrium depending on the relative stabilities of the reactants and products. 

The acid-catalyzed hydration is a typical acid-catalyzed addition to the carbonyl group. Protonation, followed by addition of water, gives a protonated product. Deprotonation gives the hydrate. 

Acid-catalyzed addition of the amine to the carbonyl group. 

EXAMPLE Acid-catalyzed formation of methyl benzoate from methanol and benzoic acid. Part 1 Acid-catalyzed addition of methanol to the carbonyl group. 

Although the addition of H2O to an alkyne resembles the acid-catalyzed addition of H2O to an alkene in some ways, an important difference exists. In the presence of strong acid or Hg " catalyst, the elements of H2O add to the triple bond, but the initial addition product, an enol, is unstable and rearranges to a product containing a carbonyl group—that is, a C=0. A carbonyl compound having two alkyl groups bonded to the C=0 carbon is called a ketone. 

The acid-catalyzed addition follows the general mechanism presented in Section 21.7A. For a poorer nucleophile like H2O to attack a carbonyl group, the carbonyl must be protonated by acid first thus, protonation precedes nucleophilic attack. The overall mechanism has three steps, as shown in Mechanism 21.8. 

The first slajge can be viewed as both electrophilic substitution on the ring by the electron-deficient carbon of forrnaldehyde, and nucleophilic addition of the aromatic ring to the carbonyl group ase catalyzes reaction by converting phenol into the more reactive (more nucleophilic) phenoxide ion.jj Acid catalyzes reaction by protonating formaldehyde and increasing the electron deficiency of the carbonyl carbon.)... 

Silylated cyanohydrins have found considerable utility in the regioselective protection of p-qui-nones, as intermediates for the preparation of 3-amino alcohols and as precursors to acyl anion equivalents. Such compounds are typicdly prepared in high yield by either thermal or Lewis acid catalyzed addition of TMS-CN across the carbonyl group. This cyanosilylation has a variety of disadvantages and modified one-pot cyanosilylation procedures have been reported. - The carbonyl group can be regenerated by treatment with acid, silver fluoride or triethylaluminum hydrofluoride followed by base. ... 

Acid-catalyzed addition of aliphatic, aromatic or heteroaromatic cyanohydrins to ethyl vinyl ether, n-butyl vinyl ether or dihydro-4//-pyran provides base stable, protected cyanohydrin derivatives. Phase transfer catalyzed alkylation of aliphatic cyanohydrins with allylic bromides gave a-substituted a-allyl-oxyacetonitrile. Carbonyl compounds react wiA cyanide under phase transfer catalysis to give cyanohydrin anions, which are trapped by an acyl chloride or ethyl chloroformate to give acyl- or alkoxycarbonyl-protected cyanohydrins respectively. The reduction of the carbonyl group of an acyl cyanide by NaBH4 under phase transfer conditions followed by esterification serves as an alternative route to aldehyde-derived cyanohydrin esters. ... 

When an alkyne undergoes the acid-catalyzed addition of water, the product of the reaction is an enol. The enol immediately rearranges to a ketone. A ketone is a compound that has two alkyl groups bonded to a carbonyl (C=0) group. An aldehyde is a compound that has at least one hydrogen bonded to a carbonyl group. The ketone and enol are called keto-enol tautomers they differ in the location of a double bond and a hydrogen. Interconversion of the tautomers is called tautomerization. The keto tautomer predominates at equilibrium. Terminal alkynes add water if mercuric ion is added to the acidic mixture. In hydroboration-oxidation, H is not the electrophile, H is the nucleophile. Consequently, mercuric-ion-catalyzed addition of water to a terminal alkyne produces a ketone, whereas hydroboration-oxidation of a terminal alkyne produces an aldehyde. 

Enamines, the products of the acid-catalyzed addition of secondary amines to aldehydes or ketones, can be viewed as weakly nudeophihc enolate anions. Enamines react with a,p-unsaturated carbonyl systems in a Michael-type reaction, introducing new carbon-carbon bonds adjacent to the carbonyl group. Endocyclic enamines, such as pyrroHnes and tetrahydropyridines, are useful for the synthesis of complex heterocycHc compounds, as found in many alkaloids (Scheme 3.19). 

Steps 1-3 Acid-catalyzed addition of water to the carbonyl group These three steps are the same as those for acid-catalyzed hydration of an aldehyde or ketone (Mechanism 17.2). Steps 1 and 3 are proton transfers between oxygens and are fast. Water acts as a nucleophile in step 2. Step 2 is rate-determining. 

Steps 1-3 Acid-catalyzed nucleophilic addition of methanol to the carbonyl group of D-glucose. (See Mechanisms 17.2 and 17.4 for details of acid-catalyzed addition to aldehydes and ketones.)... 

First ptcrt Acid-catalyzed addition of the amine to the carbonyl group. Step 1 Protonation of the carbonyl. Step 2 Addition of the amine. 

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