Addition of water to a carbonyl

The acidic media additions to carbonyls are often reversible. For example, addition of water to a carbonyl group usually favors the carbonyl. A AH° calculation gives the hydrate as slightly uphill of the carbonyl (two C-0 bonds at 86 kcal/mol (172 kcal/mol) is weaker than one C=0 at 177 kcal/mol). 

FIGURE 16.20 In principle, addition of water to a carbonyl group could occur in two ways. 

FIGURE 16.22 In the addition of water to a carbonyl group, a filled n orbital of water overlaps with the empty Jt orbital of the carbonyl group. This interaction between a filled and an empty orbital is stabilizing. 

In the specific-acid-catalyzed addition of water to a carbonyl group, the nucleophile adds to a fully protonated carbonyl group. In the general-acid-catalyzed addition of water to a carbonyl group, the carbonyl group becomes protonated as the nucleophile adds to it. 

Aldehyde oxidations occur through intermediate l/l-diols, or hydrates, which are formed by a reversible nucleophilic addition of water to the carbonyl group. Even though formed to only a small extent at equilibrium, the hydrate reacts like any typical primary or secondary alcohol and is oxidized to a carbonyl compound (Section 17.7). 

Spontaneous hydrolysis of many activated derivatives of carboxylic or carbonic acids involves nucleophilic addition of water to the carbonyl group, assisted by another water molecule which acts as a general base (Johnson, 1967 Mengerand Venkatasubban, 1976). The tetrahedral intermediate then rapidly goes forward to products (Scheme 3). 

Most of the reactions that we will consider in this chapter involve addition of a proton to a carbon atom or removal of a proton attached to a carbon atom. A frequent metabolic reaction is addition of water to a carbon-carbon double bond that is conjugated with a carbonyl group. This transmits the polarization of the carbonyl group to a position located two carbon atoms further along the chain. 

Scheme 11.8 Protonation as a catalytic process in the nucleophilic addition of water to the carbonyl of an amide.

The effect of proximal groups on the diastereoselectivity in the addition of allylindium to a carbonyl group has been extensively surveyed.153 When a- and /3-hydroxy aldehydes are subjected to the allylation, excellent diastereocontrol is realized, syn- 1,2-Diol and anti- 1,3-diol products are formed, respectively, at accelerated rates (Tables 1 and 2). Protection of the free hydroxy group results in the alternative formation of 1,2-anti products. High stereoselectivities have been observed for indium-promoted allylations of a- and /3-hydroxy aldehydes in aqueous media, implying that a chelate control still operates even in water.72,73,154-158... 

In the second step, it is not possible to differentiate kinetically between (nucleophilic) addition of water to the carbonyl group or a synchronous displacement of a protonated hydroxyl group. 

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. 

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. 

Euxylophorine C (84) exists as red needles (from benzene). The infrared spectrum of this alkaloid exhibits a carbonyl absorption at 1665 cm and unsaturation bands at 1620 and 1555 cmThe uv spectrum shows a maximum at 425 nm (log s 4.51) in chloroform, which shifts to 408 nm in acetonitrile and to 389 nm in absolute ethanol. Reduction with sodium borohydride gives a dihydroderivative. The influence of moisture on a solution of (84) in boiling benzene, or addition of water to a solution of... 

It is not the a-hydroxyketone or aldehyde, however, that undergoes reaction with periodic acid, but the hydrate formed by addition of water to the carbonyl group of the a-hydroxyketone or aldehyde. Write a mechanism for the oxidation of this a-hydroxyaldehyde by HIO. ... 

Second Stage Dissociation of the tetrahedral intermediate Just as steps 1-3 corresponded to addition of water to the carbonyl group, steps 4-6 correspond to elimination of an alcohol, in this case methanol, from the Tl and a restoration of the... 

Boron, with its electron-seeking empty orbital, is the electrophile. When it reacts with a terminal alkyne, it, like other electrophiles, adds preferentially to Ihe less substituted sp carbon (the one bonded to the hydrogen). Since the boron-containing group is subsequently replaced by an OH group, hydroboration-oxidation of a terminal alkyne forms an aldehyde (the carbonyl group is on the terminal carbon), whereas the mercuric-ion-catalyzed addition of water to a terminal alkyne forms a ketone (the carbonyl group is not on the terminal carbon). 

The acid protonates the nitrogen of the cyano group, which makes the carbon of the cyano group more susceptible to the addition of water. (The addition of water to a protonated cyano group is analogous to the addition of water to a protonated carbonyl group.)... 

The addition of water to the carbonyl group in aqueous solutions can lead to the formation of hydrates. The reactions and stability of hydrates depend primarily on the inductive effect of substituents. Hydration of formaldehyde readily yields methylene glycol (methanediol), which polymerises to linear oligomers and also to polymers known as paraformaldehyde. Hydrates of a-dicarbonyl and a-hydroxycarbonyl compounds spontaneously dimerise into various cyclic 1,4-dioxanes (see Figure 4.62). These hydrates are intermediates of other a-dicarbonyl and a-hydroxycarbonyl compounds in the oxidation-reduction reactions and precursors of carboxylic acids. Dialkyl ketones do not form hydrates. 

Table 19.2 lists the values for some representative hydration reactions. These equilibrium constants show the same trends found for the addition of HCN to a carbonyl group. Aldehydes with low molecular weights readily form hydrates. Formaldehyde is over 99% hydrated. Its hydrate is called formalin, a 37% by weight solution of formaldehyde in water that was used in the past to preserve biological specimens. Other aldehydes are substantially less hydrated. Ketones are normally hydrated less than 1%. The hydrates of aldehydes and ketones usually cannot be isolated and exist only in solution. 

The nucleophilic addition product of water to a carbonyl compound is unstable and cannot be isolated. This is true for most products made by nucleophilic addition to a carbonyl by the conjugate base of any strong acid (e.g., H2O, HOR, CH, HS04, etc.)... 

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