Carbonyl groups hydration

Carbonyl Group Hydration under Base Conditions or Hydration under Acid Conditions (page 745)... 

We have shown that in aqueous chromic acid, a primary alcohol is oxidized first to an aldehyde and then to a carboxylic acid. In the second step, it is not the aldehyde that is oxidized, but rather the aldehyde hydrate formed by addition of a molecule of water to the aldehyde carbonyl group (hydration). An —OH of the aldehyde hydrate reacts with chromic acid to complete the oxidation of the aldehyde to a carboxylic acid. 

The oxidation may proceed through the hydrated form of the carbonyl group... 

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

C = C triple bonds are hydrated to yield carbonyl groups in the presence of mercury (II) ions (see pp. 52, 57) or by successive treatment with boranes and H2O2. The first procedure gives preferentially the most highly substituted ketone, the latter the complementary compound with high selectivity (T.W. Gibson, 1969). 

Increasing stabilization of carbonyl group decreasing K for hydration... 

A striking example of an electronic effect on carbonyl group stability and its rela tion to the equilibrium constant for hydration is seen m the case of hexafluoroacetone In contrast to the almost negligible hydration of acetone hexafluoroacetone is completely hydrated... 

Steps 1-3 Acid catalyzed nucleophilic addition of 1 mole of ethanol to the carbonyl group The details of these steps are analogous to the three steps of acid catalyzed hydration in Figure 17 7 The product of these three steps is a hemiacetal... 

In the first stage of the hydrolysis mechanism water undergoes nucleophilic addi tion to the carbonyl group to form a tetrahedral intermediate This stage of the process IS analogous to the hydration of aldehydes and ketones discussed m Section 17 6... 

In a synthesis of sativene a carbonyl group was protected as a 2,4-DNP while a double bond was hydrated with BH3/H202/0H . Attempted protection of the carbonyl group as a ketal caused migration of the double bond protection as an oxime or oxime acetate was unsatisfactory since they would be reduced with BH3. 

Mechanism of Base-Catalyzed Hydration The base-catalyzed mechanism (Figure 17.5) is a two-step process in which the first step is rate-detennining. In step 1, the nucleophilic hydroxide ion attacks the carbonyl group, forming a bond to carbon. An alkoxide ion is the product of step 1. This alkoxide ion abstracts a proton from water in step 2, yielding the geminal diol. The second step, like all other proton transfers between oxygen that we have seen, is fast. 

For saturated fatty acids, the process of /3-oxidation involves a recurring cycle of four steps, as shown in Figure 24.10. The overall strategy in the first three steps is to create a carbonyl group on the /3-carbon by oxidizing the C, —C bond to form an olefin, with subsequent hydration and oxidation. In essence, this cycle is directly analogous to the sequence of reactions converting succi-... 

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... 

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). 

The acid-catalvzed 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 aldehyde ot ketone then yields a protonated gem diol, which loses H+ to give the neutral product (Figure 19.5). 

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

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. 

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