19_BRCLoudon_pgs5-0.qxd 12/9/08 11:41 AM Page 907 19.7 REVERSIBLE ADDITION REACTIONS OF ALDEHYDES AND KETONES 907 REVERSIBLE ADDITION REACTIONS 19.7 OF ALDEHYDES AND KETONES One of the most typical reactions of aldehydes and ketones is addition to the carbon– oxygen double bond. To begin with, let’s focus on two simple addition reactions: addition of hydrogen cyanide (HCN) and hydration (addition of water). Addition of HCN: O OH S pH 9–10 H3CCCH3 H CN' H3CC" CH3 (19.15) LLacetone + L LL "C ' N acetone cyanohydrin (77–78% yield) The product of HCN addition to an aldehyde or ketone is called a cyanohydrin. Cyanohydrins constitute a special class of nitriles (organic cyanides). (The chemistry of nitriles is discussed in Chapter 21.) The preparation of cyanohydrins is another method of forming carbon–carbon bonds. Addition of water (hydration): O OH S H3CCH H OH H3CH"C (19.16) acetaldehydeLL + L LL "OH acetaldehyde hydrate The product of water addition to an aldehyde or ketone is called a hydrate, or gem-diol. (The prefix gem stands for geminal, from the Latin word for twin, and is used in chemistry when two identical groups are present on the same carbon.) In all carbonyl-addition reactions, the more electropositive species (for example, the hydro- gen of H CN or H OH) adds to the carbonyl oxygen, and the more electronegative species (for example,L the LCN or the OH) adds to the carbonyl carbon. L L A. Mechanisms of Carbonyl-Addition Reactions Carbonyl-addition reactions occur by two general types of mechanisms. The first mechanism, called nucleophilic carbonyl addition, involves the reaction of a nucleophile at the carbonyl carbon. In cyanohydrin formation (Eq. 19.15), the nucleophile is cyanide ion, which is formed by the ionization of HCN: (19.17a) H CN _OH _ CN H2O pKLa 9.4 + 3 + = cyanide ion Cyanide ion donates electrons to the carbonyl carbon of the aldehyde or ketone, and the car- bonyl oxygen accepts the displaced electron pair and assumes a negative charge. We can think of this process in the same way that we think of nucleophilic reactions at saturated carbon atoms (Sec. 3.4B). The electrophile is the carbonyl carbon, and the “leaving group” is one of the two carbon–oxygen bonds of the carbonyl group. Because the other carbon–oxygen bond remains intact, the “leaving group” doesn’t actually leave. 19_BRCLoudon_pgs5-0.qxd 12/9/08 11:41 AM Page 908 908 CHAPTER 19 • THE CHEMISTRY OF ALDEHYDES AND KETONES. CARBONYL-ADDITION REACTIONS one carbon–oxygen bond O serves as the “leaving group” O _ electrophile 3 3 3 2 3 C CN nucleophile H3C "C CH3 (19.17b) H C CH _ 3 % % 3 3 LL "CN To complete the nucleophilic addition, the negatively charged oxygen—an alkoxide ion, and a relatively strong base—is protonated by either water or HCN. O _ H CN OH 332 L 3 2 H3C"C CH3 H3C "C CH3 _ CN (19.17c) LL LL + 3 "CN "CN The nucleophilic carbonyl-addition mechanism finds no analogy in additions to ordinary carbon–carbon double bonds. Yet, nucleophilic carbonyl addition occurs even though the car- 1 1 STUDY GUIDE LINK 19.1 bon–oxygen p bond is 62 kJ mol_ (15 kcal mol_ ) stronger than the carbon–carbon p bond Why Nucleophiles of an alkene. The stronger bond is more reactive because the unshared electron pair (and neg- React at the Carbonyl Carbon ative charge) formed in the carbonyl-addition mechanism is transferred to a very electronega- tive atom, oxygen. The same reaction of an alkene would place an unshared pair and negative charge on a carbon, a much less electronegative atom. additional unshared pair and unshared pair and negative charge on oxygen negative charge on carbon % % O O _ C "C _ 3S3 332 S L 3 C "C C "C % % LL % % L L "CN "CN _ CN _ CN 3 observed 3 not observed with ordinary alkenes The reaction of a nucleophile with the carbonyl group, then, is driven by the ability of oxygen to accept the unshared electron pair. For this reason, a nucleophile cannot add to the carbonyl oxygen. Nucleophiles always react with carbonyl groups at the carbonyl carbon. The geometry of nucleophilic addition and the reason for it are shown in Fig. 19.8. The car- bonyl group and the two atoms bound to the carbonyl carbon define a reference plane. The nu- cleophile approaches the carbonyl carbon from above or below this plane, as shown in Fig. 19.8a. As a result of this reaction, the carbonyl carbon changes hybridization from sp2 to sp3, the oxygen accepts an electron pair, and the geometry at the carbonyl carbon changes from trig- onal planar to tetrahedral. In other words, the angle between the bonds to the carbonyl carbon, initially about 120 , compresses to about 109 , the tetrahedral angle. As a result of the reaction, then, the groups bound° to the carbonyl carbon° become closer together. The reason for the addition geometry is similar to the reason for backside substitution in the SN2 reactions of alkyl halides (Sec. 9.4C, Fig. 9.3). The curved-arrow notation might convey the impression that the nucleophile reacts at the p bond. However, the bonding p molecular orbital of the carbonyl group (Fig. 19.1) is fully occupied with two electrons and cannot ac- commodate any more electrons. The electron pair of the nucleophile interacts instead with the unoccupied MO of lowest energy (LUMO), which, in the case of the carbonyl group, is the an- tibonding p* molecular orbital. This MO is shown in Fig. 19.8b. This MO has lobes above and 19_BRCLoudon_pgs5-0.qxd 12/9/08 11:41 AM Page 909 19.7 REVERSIBLE ADDITION REACTIONS OF ALDEHYDES AND KETONES 909 sp2-hybridized sp3-hybridized carbon carbon ≈109Њ .. 1 R .. O.. ≈120Њ R´ 1 Nuc _ Nuc 3 (a) antibonding (p*) MO .. bonding overlap Nuc (b) Figure 19.8 (a) The geometry of nucleophilic reaction with the carbonyl carbon of formaldehyde, with the nu- cleophile represented by Nuc _. The reference plane (gray) is the plane defined by the carbonyl group and the atoms attached to the carbonyl3 carbon.The nucleophile approaches this carbon from above or below this plane. As a result, the carbonyl carbon changes hybridization from sp2 to sp3,the bond angles at the carbonyl carbon compress from 120 to 109 ,and the groups attached to the carbonyl carbon move as shown by the green arrows. (b) The interaction °of a nucleophile° with the p* antibonding MO of formaldehyde.The lobes of this MO are con- centrated above and below the plane of the molecule.The interaction of the nucleophile with this MO defines the direction of nucleophilic approach to the carbonyl carbon. below the reference plane. The nucleophile, then, must begin its bonding interaction with the carbonyl carbon from the direction along which the LUMO is concentrated, as shown in Fig. 19.8a. When the antibonding p* MO is filled, even with electrons from another molecule, the CAO p bond is weakened. (Remember that when an antibonding molecular orbital is popu- lated, the energetic advantage of bonding disappears.) This is the reason that the p bond breaks. The energetic “trade-off” for loss of this bonding is formation of the new bond to the nucleophile. The second mechanism for carbonyl addition occurs under acidic conditions and is closely analogous to the mechanism for the addition of acids to alkenes (Secs. 4.7 and 4.9B). Acid- catalyzed hydration of aldehydes and ketones (Eq. 19.16) is an example of this mechanism. The first step in hydration is protonation of the carbonyl oxygen (Sec. 19.6). |1 | O H OH2 O H 1 S S 3 3 L 3 L 1 C C OH2 (19.18a) H3CH% % H3CH% % + 19_BRCLoudon_pgs5-0.qxd 12/9/08 11:41 AM Page 910 910 CHAPTER 19 • THE CHEMISTRY OF ALDEHYDES AND KETONES. CARBONYL-ADDITION REACTIONS A positively charged oxygen attracts electrons even more strongly than the oxygen of an un- protonated carbonyl group. In other words, the protonated carbonyl compound is a much stronger Lewis acid (electron acceptor) than an unprotonated carbonyl compound. As a result, even the relatively weak base H2O can react at the carbonyl carbon. Loss of a proton to solvent completes the reaction. | 1 O H 1 O H OH S L 3 L 1 3 2 H2O 3 2 C OH2 H3C "C HH3 3CH"C H3O| (19.18b) H C H LL LL + 3 3 % % "O| H "OH 3 L 3 "H 2 Hydration of aldehydes and ketones also occurs in neutral and basic solution (Prob- lem 19.15). The direction of approach of the nucleophile to the protonated carbonyl group is the same as it is for approach to the unprotonated carbonyl group (Fig. 19.8)—from above or below the reference plane. This is explained by the shape of the LUMO of the protonated carbonyl group, which is very similar to the shape of the LUMO of the carbonyl group itself. PROBLEMS 19.15 (a) Write a curved-arrow mechanism for the hydroxide-catalyzed hydration of acetalde- hyde. (b) Write a curved-arrow mechanism for the decomposition of acetone cyanohydrin (Eq. 19.15) in aqueous hydroxide. Explain why the ketone–cyanohydrin equilibrium favors the ketone at high pH. 19.16 Write a curved-arrow mechanism for (a) the acid-catalyzed addition of methanol to benzaldehyde. (b) the methoxide-catalyzed addition of methanol to benzaldehyde. B. Equilibria in Carbonyl-Addition Reactions Hydration and cyanohydrin formation are both reversible reactions.