Protonation of carbonyl group

Thus far, all examples related to the addition of nucleophiles to carbonyls involve basic (anionic) conditions. However, such conditions are not required. Recalling that a carbonyl oxygen atom possesses a partial negative charge, we recognize that under acidic conditions it can be protonated. The protonation of carbonyl groups, illustrated in Scheme 7.13, was discussed in Chapter 3. Thus, as shown in Scheme 7.14 using acetone, treatment of... 

The a-protons of carbonyl groups are acidic due to both inductive withdrawal of the adjacent carbonyl group, which weakens the carbon-hydrogen bond, and resonance stabilisation of the enolate which is formed. 

Strong acids - PARK can perform well in weak acids but very strong acids can dissolve PARK. Sometimes this is due to protonation of carbonyl groups but in other cases there is actual reaction at the aromatic rings. Often this involves a classic electrophilic attack. Concentrated sulfuric acid dissolves and sulfonates PRRK under mild conditions but forcing conditions are required to sulfonate phenylene groups which are deactivated by carbonyl or sulfone... 

The plausible mechanism for the formation of product involves the protonation of carbonyl group of EAA by Bronsted acid sites of the catalyst (Scheme 18) (08JMCCF222). 

Many compounds contain more than one functional group Prostaglandin Ei a hormone that regulates the relaxation of smooth muscles con tains two different kinds of carbonyl groups Classify each one (aldehyde ketone carboxylic acid ester amide acyl chloride or acid anhydride) Identify the most acidic proton in prostaglandin Ei and use Table 1 7 to estimate its pK ... 

Steric and electronic effects influence the rate of nucleophilic addition to a proton ated carbonyl group m much the same way as they do for the case of a neutral one and protonated aldehydes react faster than protonated ketones... 

The carbonyl oxygen of aldehydes and ketones can form hydrogen bonds with the protons of OH groups. This makes them more soluble in water than alkenes, but less soluble than alcohols. 

The resistance to cleavage is an indication of the superelectrophilic character of dication 150c. Several aromatic compounds have likewise been shown to produce dicationic species upon the protonation of carboxyl and carbonyl functional groups. Other bis-carboxonium dications have been described involving protonation of carbonyl, amide, and other groups.50 These distonic superelectrophiles (152-153) have been shown to be useful in condensation reactions (eqs 52-53). 

The Fischer esterification mechanism (Key Mechanism 20-2) is an acid-catalyzed nucleophilic acyl substitution. The carbonyl group of a carboxylic acid is not sufficiently electrophilic to be attacked by an alcohol. The acid catalyst protonates the carbonyl group and activates it toward nucleophilic attack. Attack by the alcohol, followed by loss of a proton, gives the hydrate of an ester. 

Acid catalysts promote conjugate addition of alcohols to a, p unsaturated carbonyl compounds by protonating the carbonyl group and making the conjugated system more electrophilic. Methanol adds to this ketone exceptionally well, for example, in the presence of an acid catalyst known as Dowex 50 . This is an acidic resin—just about as acidic as sulfuric acid in fact, but completely insoluble, and therefore very easy to remove from the product at the end of the reaction by filtration. 

Since the twin roles of the enophile are to be attacked at one end by a C=C double bond and at the other by a proton, a carbonyl group is actually a very good enophile. These reactions are usually called carbonyl ene reactions. 

You should be abife to write a mechanism for this reaction—ft is much the same es the formation of an acetal, but no acid catalyst is present so you will not need to protonate the carbonyl groups before the amines attack. 

The mechanism of acid-catalyzed hydration of an aldehyde or ketone. Acid protonates the carbonyl group, making it more electrophilic and more reactive. 

Just as addition of a Grignard reagent to an aldehyde or ketone yields an alcohol, so does addition of hydride ion, H (Section 17.4). Although the details of carbonyl-group reductions arc complex, LiAll-14 and N aBH4 act as if they were donors of hydride ion in a nucleophilic addition reaction (Figure 19.7).. Addition of water or aqueous acid after the hydride addition step protonates the tetrahedral alkoxide intermediate and gives the alcohol product. 

In acid, carbonyl compounds are in equilibrium with their protonated counterparts. Protonation is often the first step in nucleophilic addition or substitution of carbonyl groups. For aldehydes and ketones, the protonated carbonyl group is a resonance hybrid of two forms one with positive charge on the carbonyl oxygen and one with positive charge on the carbonyl carbon. 

---