Chemistry 332 - Winter 1997

Chapter 10 - Carboxyl Compounds

Carboxylic Acids and Derivatives

distinguished from aldehydes and ketones because one substituent is NOT C or H
(usually Cl, O, or N, but it could also be other F, Br, I, S, P, or many other possibilities)



Nomenclature of Carboxylic Acids

• alkanoic acid (-oic acid suffix)
  when the -COOH is part of the parent chain
  assumed #1 position
  
  
• cycloalkanecarboxylic acid
  when the -COOH is not part of the parent name
  assumed attached to the #1 position
  
  
• common names
  formic acid (methanoic acid)
  acetic acid (ethanoic acid)
  notice the prefixes are the same as for aldehydes
  
  
• acyl group names
  needed for naming some derivatives
  formyl (methanoyl)
  acetyl (ethanoyl)

Nomenclature of Carboxyl Derivatives

• acid halides
  alkanoyl halide (-oyl halide suffix)
  or use common acyl name from acid
  
  
• acid anhydrides
  alkanoic anhydride (-oic anhydride suffix)
  
  
• amides
  alkanamide (-amide suffix)
  substituents on N use prefix N- (instead of a number location)
  
  
• nitriles
  alkanenitrile (-nitrile suffix)
  
  
• carboxylate salts
  metal alkanoate (-oate suffix for anion)
  
  
• esters
  alkyl alkanoate (a two-part name)
  alkyl group is attached to the O
  alkanoate analogous to carboxylate salt

Nomenclature Examples

ethyl 4-pentenoate

N,N-dimethyl-3-acetylbenzamide

Structure and Properties of Carboxylic Acids

• very polar functional group with H-bonding
  typically the boiling points are relatively high
  (formic acid, b.p. 100.7°)

Acidity of Carboxylic Acids

• stronger acids than alcohols
  Ka ~ 10^-5 (pKa ~ 5)
  (alcohol pKa values about 15-18)
• electron-withdrawing effects of the carbonyl group tends to further polarize the O-H bond so it is more easily ionized
• the carboxylate anion is stabilized by resonance

• substituent effects
  electron-withdrawing groups (like Cl) increase acidity

Synthesis of Carboxylic Acids

• oxidations
  alkylaromatics to benzoic acids using KMnO4
  primary alcohols to carboxylic acids using CrO3
  aldehydes to carboxylic acids using Tollen's reagent (Ag+)
  
• hydrolysis of nitriles
  alkyl halide to nitrile by S_N2 substitution
  followed by hydrolysis with acid or base catalysis

• addition of CO₂ to a Grignard reagent

Nucleophilic Acyl Substitution

• the major reaction of carboxyl derivatives
• starts like nucleophilic addition, but becomes substitution when the leaving group deoarts

• the tetrahedral intermediate is like that in carbonyl additions
  
• the product is often another carboxyl derivative
  (depnding on what the nucleophile is)
  
• compared to other nucleophilic substitutions:
  S_N2 - simultaneous bonding of nucleophile and loss of leaving group
  S_N1 - first loss of leaving group, then bonding of nucleophile (cation intermediate)
  acyl - first bonding of nucleophile, then loss of leaving group (anion intermediate)

Reactivity in Acyl Nucleophilic Substitution

• better leaving groups increase reactivity
  acid halides > acid anhydrides > esters > amides
  
• the more reactive derivatives can be easily converted to the others
  you can make any of them with the acid chloride - a typical starting point for synthesis
  
• all the derivatives can be hydrolyzed to the carboxylic acid
  (water as the nucleophile - using acid or base catalysis)
  

Examples of Acyl Nucleophilic Substitution

Reactions of Carboxylic Acids

• reduction to primary alcohols by LiAlH4
  
• conversion to acid chlorides with SOCl2
  conversion to other derivatives via the acid chloride

• conversion to esters with alcohol and acid catalysis
  (Fisher esterification method)

• a reversible equilibrium
  favored to the right with excess alcohol
  favored to the left with excess water (hydrolysis)
  
• complete mechanism
  see your text - will also be shown on the computer

Conversion of Acid Halides into Other Carboxyl Derivatives

• acid halides are the most reactive carboxyl derivative
• they can be converted to all the other derivatives

Conversion of Acid Anhydrides into Other Carboxyl Derivatives

• acid anhydrides are the second most reactive carboxyl derivative
• they can be converted to all the other derivatives except acid halides
• but acid chlorides are typically preferred

Synthesis of Esters

• from acid halides plus alcohols
• from acids plus alcohols (Fisher esterification)
• by SN2 reaction of a carboxylate as nucleophile

Hydrolysis of Esters

• water as the nucleophile with either acid or base catalysis
• acid-catalyzed hydrolysis is the exact reverse of Fisher esterification (same mechanism)
• base-catalyzed hydrolysis is often called saponification (soap-making)
  saponification is irreversible because a carboxylate salt is formed

• soaps are the salts of long-chain (fatty) acids (C₈ - C₂₀)
  fats are the esters of fatty acids and glycerol (1,2,3-propanetriol)

Other Reactions of Esters

• reduction by LiAlH4 gives primary alcohols (plus the ester alcohol)
  (H- nucleophile first gives substitution - aldehyde intermediate,
  then another H- nucleophile gives addition - alcohol product)
• Grignard additions give tertiary alcohols (double addition)
  (RMgX nucleophile first gives substitution - ketone intermediate,
  then another RMgX nucleophile gives addition - alcohol product)

Synthesis of Amides

• acid chloride plus ammonia (or amine)

Reactions of Amides

• hydrolysis to carboxylic acid - requires prolonged heating
  proteins are held together by amide bonds
• reduction by LiAlH4 to amines

Synthesis of Nitriles

• S_N2 reaction of primary halides with CN^-
• dehydration of amides

Reactions of Nitriles

• nucleophilc additions similar to carbonyl group (polar triple bond)
• hydrolysis to carboxylic acids
• reduction with LiAlH4 to amines
• addition of Grignards to make ketones

Polymers of Esters and Amides

• step-growth polymers are made by multiple reactions of multifunctional monomers
• a dicarboxylic acid reacts with a diamine to form a polyamide (nylon)

• polyesters are made from dicarboxylic acids and dialcohols
• step-reaction polymerization is a fundamentally different way to make polymers from chain-reaction polymerization
  • chain-reaction: a few reactive sites grow long chains quickly
  • step-reaction: reaction steps slowly grow larger and larger chains
• interfacial polymerization - method of making thin films of polymers
  as in artificial photosynthesis

Thiol Esters

• Nature often uses sulfur groups as excellent nucleophiles (and leaving groups)
• coenzyme A contains a thiol group (coA-S-H)
• acetyl CoA acts like acetyl chloride
  e.g., acetyl CoA + amines gives acetamides
  

Summary - Interconversion of Carboxyl Derivatives

Summary - Hydride Reductions

Summary - Grignard Reactions