ORGANIC CHEMISTRY Chapter 16 16.6 Nucleophilic Addition to the Carbon-Oxygen Double Bond Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 16 16.6 Nucleophilic Addition to the Carbon-Oxygen Double Bond
ORGANIC CHEMISTRY Chapter 16 o The most characteristic reaction of aldehydes and ketones is nucleopl chili addition to the carbon-oxygen d d ouble bone C=0+H-Nu° C-OH Nu C=0 Nu Nucleophilic addition to the carbon-oxygen double bond occurs in either of two general ways Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 16 The most characteristic reaction of aldehydes and ketones is nucleophilic addition to the carbon-oxygen double bond. C O + C OH Nu H Nu C O Nu Nucleophilic addition to the carbon-oxygen double bond occurs in either of two general ways
ORGANIC CHEMISTRY Chapter 16 Mechanisms 1. Addition of a Strong Nucleophile to an Aldehyde or Ketone R/88 R C=0 R C-O、H<M,R R LRIC-OH Nu NI NI The important aspect of this step is the ability of the carbonyl oxygen atom to accommodate the electron pair of the carbon-oXygen double bond Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 16 Mechanisms Mechanisms 1. Addition of a Strong Nucleophile to an Aldehyde or Ketone C O R' R δ− δ+ Nu C O R' R Nu H Nu C OH R' R Nu The important aspect of this step is the ability of the carbonyl oxygen atom to accommodate the electron pair of the carbon-oxygen double bond
ORGANIC CHEMISTRY Chapter 16 Mechanisms 2. Acid-Catalyzed Nucleophilic Addition to an Aldehyde or Ketone H+ + e Nu-H C=0 C=OH C-OH Slow -C-OHH* -C-OH NuTH Nu Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 16 Mechanisms Mechanisms 2. Acid-Catalyzed Nucleophilic Addition to an Aldehyde or Ketone C O C OH C OH C OH Nu Nu H Slow H C OH Nu H+ H+
ORGANIC CHEMISTRY Chapter 16 16.6a Reversibility of Nucleophilic Addition to the Carbon-Oxygen Double Bond Many nucleophilic additions to carbon-oxygen double bonds are reversible o The overall results of these reactions depend on the position of an equilibrium R R OH C=0 NaHSO2= H H SO3 Na (CH3) (CH3) Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 16 16.6A Reversibility of Nucleophilic Addition to the Carbon-Oxygen Double Bond Many nucleophilic additions to carbon-oxygen double bonds are reversible, The overall results of these reactions depend on the position of an equilibrium. R C H O (CH3) + NaHSO3 R C H SO3Na OH (CH3)
ORGANIC CHEMISTRY Chapter 16 16.6B Relative Reactivity: Aldehydes versus ketones 9 In general, aldehyde are more reactive in nucleophilic addition than are ketones C R H R R Aldehyde Ketone Carbonyl carbon is Carbonyl carbon is more positive less positive Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 16 16.6B Relative Reactivity: Aldehydes versus Ketones In general, aldehyde are more reactive in nucleophilic addition than are ketones. R C H O δ+ δ− R C R O δ+ δ− Aldehyde Ketone Carbonyl carbon is more positive Carbonyl carbon is less positive
ORGANIC CHEMISTRY Chapter 16 16.6C Subsequent Reactions of Addition products R R-C-OH Nu o Nucleophilic Addition a c=0 may lead to a product that is stable under the reaction conditions that we employ o In other reactions the products formed initially may be unstable and may spontaneously undergo subsequent reactions(elimination reactions) Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 16 16.6C Subsequent Reactions of Addition Products R R C OH Nu Nucleophilic Addition a C=O may lead to a product that is stable under the reaction conditions that we employ. In other reactions the products formed initially may be unstable and may spontaneously undergo subsequent reactions.(elimination reactions)
ORGANIC CHEMISTRY Chapter 16 16. 7 The addition of alcohols Hemiacetals and acetals 半缩醛(酮)和缩醛(酮) Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 16 16.7 The Addition of Alcohols: Hemiacetals and Acetals 半缩醛（酮）和缩醛（酮）
ORGANIC CHEMISTRY Chapter 16 HCi(g) OH OEt Etoh CH3 CH=O + EtOH- CH3CH CH2CH H,o OEt HCl(g) OEt Hemiacetal(半缩醛 Acetal(缩醛) Catalyst: HCl(g), TsOH/C6H6, HCl/EtO o Most open-chain hemiacetals are not sufficiently stable to allow their isolation g Cyclic hemiacetals with five- or Six-membered rings however, are usually much more stable OH HOCHCHCHCH=O Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 16 CH3CH O + EtOH CH3CH OH OEt HCl (g) Hemiacetal (半缩醛) HCl (g) CH3CH OEt OEt + H2O Acetal (缩醛) EtOH Catalyst: HCl (g) , TsOH / C6H6 , HCl / Et2O Most open-chain hemiacetals are not sufficiently stable to allow their isolation. Cyclic hemiacetals with five- or six-membered rings, however, are usually much more stable: HOCH2CH2CH2CH O O OH
ORGANIC CHEMISTRY Chapter 16 M echanism R OH RR C=0. 代,_C=OP、HORR H R ORI (R' may be h H AH+R、(OH2-HOR R OH HORT R OR R' OR R OR R OR"一H R OR H R OR R OR Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 16 Mechanism Mechanism R C R' O R C R' OH R C R' OH OR'' H R C R' OH OR'' R C R' OH2 OR'' R C R' OR'' R C R' OR'' OR'' H R C R' OR'' OR'' H+ HOR'' H+ H+ H2O HOR'' H+ (R' may be H)