Addition of water to aldehydes and ketones

Grignard reagents were discovered by Victor Grignard (1871-1935) at the University of Lyon, who got the Nobel prize for his discovery in 1912. They are made by reacting alkyl or aryl halides with magnesium turnings . 

Nucleophiles don t have to be highly polarized or negatively charged to react with aldehydes and ketones neutral ones will as well. How do we know This NMR spectrum was obtained 

What has happened is that water has added to the carbonyl group to give a compound known as a hydrate or 1,1-diol. 

The hydrated nature of formaldehyde poses a problem for chemistry that requires anhydrous conditions such as the organometalllc additions we have just been talking about. Fortunately, cracking (heating to decomposition) the polymeric paraformaldehyde can provide monomeric formaldehyde In anhydrous solution. 

This reaction, like the addition of cyanide we discussed at the beginning of the chapter, is an equilibrium, and is quite general for aldehydes and ketones. But, as with the cyanohydrins, the position of the equilibrium depends on the structure of the carbonyl compound. Generally, the same steric factors (p. 129) mean that simple aldehydes are hydrated to some extent while simple ketones are not. However, special factors can shift the equilibrium towards the hydrated form even for ketones, particularly if the carbonyl compound is reactive or unstable. 

Grignard reagents are made by reacting alkyl or aryl halides with magnesium turnings . 

Formaldehyde is an extremely reactive aldehyde as it has no substituents to hinder attack—it is so reactive that it is rather prone to polymerization (Chapter 52). And it is quite happy to move from sp2 to sp3 hybridization because there is very little increased steric hindrance between the two hydrogen atoms as the bond angle changes from 120° to 109° (p. 139). This is why our aqueous solution of formaldehyde contains essentially no CH2O—it is completely hydrated. A mechanism for the hydration reaction is shown below. Notice how a proton has to be transferred from one oxygen atom to the other, mediated by water molecules. 

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The Addition of Water to Aldehydes and Ketones. Formation of Hydrates O-Hydro-C-hydroxy-addition... 

The addition of water to aldehydes and ketones occurs rapidly, although it is not thermodynamically favored. What would be the product for the reaction above Hint Think of the selfionization of water and the polarity of the carbonyl group. 

The products from addition of cyanide to aldehydes and ketones are often versatile substrates that lend themselves for further transformations to useful compounds. The early use of the dangerous HCN gas for this cyanohydrin formation could be circumvented by using TMSCN instead, as discovered by Evans etaL [43, 44). Loh et al subsequently reported the first adaptation of the TMSCN addition to aldehydes and ketones in water using Inp3 as the Lewis acid catalyst, with success even for trifluoro ethyl hemiacetal, the commercially available form of trifluoroacetaldehyde [45] (Figure 8.22). However, this procedure is not successful for ketones. 

The acid-catalyzed hydration reaction begins with protonation of the carbonyl oxygen atom, which places a positive charge on oxygen and makes the carbonyl group more electrophilic. Subsequent nucleophilic addition of water to the protonated ketone or aldehyde then yields a protonated gem diol, which loses to give the neutral product (Figure 19.5, p. 766). 

The next section explores the mechanism of nucleophilic addition to aldehydes and ketones There we 11 discuss their hydration a reaction m which water adds to the C=0 group After we use this reaction to develop some general principles we 11 then survey a number of related reactions of synthetic mechanistic or biological interest... 

The first stage of the mechanism is exactly the same as for nucleophilic addition to the carbonyl group of an aldehyde or ketone Many of the same nucleophiles that add to aldehydes and ketones—water (Section 17 6) alcohols (Section 17 8) amines (Sections 17 10-17 11)—add to the carbonyl groups of carboxylic acid derivatives... 

The nucleophilic addition of water to an aldehyde or ketone is slow under neutral conditions but is catalyzed by both base and acid. The base-catalyzed hydration reaction takes place as shown in Figure 19.4. The nucleophile is the... 

Acetal formation is similar to the hydration reaction discussed in Section 19.5. Like water, alcohols are weak nucleophiles that add to aldehydes and ketones only slowly under neutral conditions. Under acidic conditions, however, the reactivity of the carbonyl group is increased by protonation, so addition of an alcohol occurs rapidly. 

Water can add reversibly to o ,/3-unsalurated aldehydes and ketones to yield /3-hydroxy aldehydes and ketones, although the position of the equilibrium generally favors unsaturated reactant rather than saturated adduct. A related addition to an c /S-unsaturated carboxylic acid occurs in numerous biological pathways, such as the citric acid cycle of food metabolism where ds-aconitate is converted into isocitrate by conjugate addition of water to a double bond. 

Addition of water to alkynes preparation of aldehydes and ketones... 

Terminal alkynes are less reactive than internal alkynes towards the acid-catalysed addition of water. Therefore, terminal alkynes require Hg salt (HgS04) catalyst for the addition of water to yield aldehydes and ketones. Addition of water to acetylene gives acetaldehyde, and all other terminal alkynes give ketones. The reaction is regioselective and follows Markovni-kov addition. For example, 1-butyne reacts with water in the presence of H2SO4 and HgS04 to yield 2-butanone. 

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