Chemistry 332 - Spring 1996
Elements of Organic Chemistry II

Professor Carl C. Wamser

Chapter 11 - Condensation Reactions

• alpha position is the carbon that is attached to the functional group

• tautomers - constitutional isomers that are easily interconverted
  enol structure vs. carbonyl (keto) structure differs by location of one H (and double bond)
  
  
  
• most carbonyl and carboxyl compounds are in equilibrium with just small amounts of enol
  enol form is favored only in special cases if the C=C double bond or the O-H group is specially stabilized
  
  cyclohexanone (1 enol per million ketone molecules)
  
  
  24% 2,4-pentanedione : 76% 4-hydroxy-3-penten-2-one
  (see problem 11.21 - the extra stabilization of the enol is H-bonding)
  
  
• knowing the right keto-enol forms for the nucleic acid bases allowed Watson and Crick to develop the double-helix concept for DNA
  
  guanine (keto form - as in DNA) // guanine (enol form - aromatic but less stable)

• enols behave like C=C double bonds - react with electrophiles
  the net reaction is alpha-substitution

• carbonyl compounds have pKa values about 20
  see Table 11.1 to compare other families
  
  
• strong bases can deprotonate carbonyl compounds

• two carbonyl groups increases the acidity further
  pKa of 1,3-diketones is about 9

• enolates are good nucleophiles
• enolates are ambident (two-toothed) nucleophiles
  usually they react at the C rather than the O anion site
  

• use of enolate nucleophile in an S_N2 substitution
  product is an alpha-substituted carbonyl (or carboxyl) compound

• reaction of an enolate as nucleophile with a carbonyl group,
  usually from the same compound

• the reaction is a reversible equilibrium
  favored towards product (aldol) only for simple aldehydes
  greater substitution favors starting compounds at equilibrium

• the aldol reaction is often combined with dehydration of the initial aldol product, forming a conjugated double bond (an enone)

• condensation with a carboxyl derivative gives substitution instead of addition
• the Claisen condensation gives beta-ketoesters

• alpha-anions (nucleophiles) can be made next to any good electron-withdrawing group
  
  
• these anions can react with carbonyl compounds to give addition
  or with carboxyl compounds to give substitution
  
  
• acetyl coA often acts as a biological nucleophile at its alpha-position
  formation of acetoacetyl coA is the first step in building up fatty acids

• write both keto and enol forms of carbonyl and carboxyl compounds
• identify acidic hydrogens at alpha-positions
• know the relative acidity order of the major functional groups
  (carboxylic acids, alcohols, carbonyl compounds, hydrocarbons)
• draw resonance forms for enolate anions
• write mechanisms for acid or base-catalyzed enolization
• write mechanisms for alpha-substitution reactions
• write mechanisms for aldol condensations
• synthesize aldols or enones using the aldol condensation
• recognize related carbonyl condensation reactions
• write mechanisms for the Claisen condensation
• synthesize beta-ketoesters using the Claisen condensation
• recognize related carboxyl condensation reactions
• (we skipped the malonic ester synthesis)