1559T_ch17_304-32211/3/0510:48Page306 ⊕ EQA 306.Chapter 17 ALDEHYDES AND KETONES:THE CARBONYL GROUF carbonyl carbon first.followed(usually)by tep).Con 17-6 through 17-9.Addition of Water,Alcohols,and Amines to Aldehydes and Ketones OH 1.R -(H or R)Nue R-C(H or R) Aldehyde or ketone If Nue-一His Product is Aldehyde or ketone hydrate Hemiacta al R'NHz or R2'NH Hemiaminal and leads to relatively stable acetal or thioace S RL OH R'OH (OR'or SR') 2a.R-C-(Hor R)+ (OR'or SR) R'SH Acid R-C-(H or R)+HO (OR or SR IT R'SH: OH 2b.R-C-(H or R)R-C-(H or R)+H NHR' NR Imin H OH .(HorR) 2c.-f (H or R)AodC-C +H20 NR'2 Enamine urposes.acid-catalyzed reaction of an aldehyde or a ketone with any of the nucleophile listed in reaction of the cleonhile carbonyl carbon first, followed (usually) by protonation of oxygen (which may be a separate step). Conversely, addition of weaker nucleophiles, especially neutral NOucH, is helped by prior protonation of the carbonyl oxygen to give the highly electrophilic group. Whichever way the reaction proceeds in any given case, its scope is very broad, and many useful types of addition products are known. These are the subjects of the remaining sections of the chapter. 17-6 through 17-9. Addition of Water, Alcohols, and Amines to Aldehydes and Ketones There are actually two fundamentally different types of reactions in these sections. The first is the reversible addition of a nucleophile to a carbonyl group, which can generally be catalyzed by either base or acid. 1. If NucOH is Product is H2O Aldehyde or ketone hydrate ROH Hemiacetal RSH Hemithioacetal RNH2 or R2NH Hemiaminal The second is really carbocation chemistry. When NucOH is ROH, or RSH, the product in the reaction shown above may have its OH group replaced by a second Nuc. This reaction occurs by the SN1 mechanism and leads to relatively stable acetal or thioacetal products. As the text section shows, these latter two kinds of compounds are resistant to attack by many kinds of basic or nucleophilic reagents, such as RLi, Grignards, and hydrides. Conversion of an aldehyde or ketone CPO to an acetal or thioacetal is a handy way of protecting it when you need to react some other functional group in a molecule with a strong base or nucleophile. When NucOH is a primary amine, RNH2, further reaction of the hemiaminal gives an imine, containing a carbon–nitrogen double bond. Alternatively, when the nucleophile is R2NH, an enamine results. 2a. 2b. 2c. For all practical purposes, acid-catalyzed reaction of an aldehyde or a ketone with any of the nucleophiles listed in reaction 1 will continue straight through to the product of reactions 2a, 2b, and 2c, as the case may be. Conversely, acid-catalyzed hydrolysis of any of the latter products will proceed back all the way to the orig￾inal aldehyde or ketone and the free nucleophile. Acid OH C C C C NR2 NR2 H (H or R) Enamine (H or R)
H2O Acid OH R C C NHR (H or R) R NR Imine (H or R)
H2O Acid OH R C C (OR or SR) ( ( ROH or RSH (H or R) R (OR or SR) (OR or SR) If R
OH: Acetal If R
SH: Thioacetal
(H or R)
H2O O Base or acid R C Aldehyde or ketone (H or R)
Nuc H OH R C Nuc (H or R) C OH
306 • Chapter 17 ALDEHYDES AND KETONES: THE CARBONYL GROUP 1559T_ch17_304-322 11/3/05 10:48 Page 306