Derivatives of Carboxylic Acids

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Derivatives of Carboxylic Acids

• Nucleophilic
• Acyl Substitution

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Derivatives of Carboxylic Acids Made Directly
from Acids
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Preparation of Acid Chlorides Directly from Acids
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Preparation of Acid Anhydrides Directly from Acids

• Good for acetic and 5- and 6-membered ring
  anhydrides

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Preparation of Esters Directly from Acids
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Preparation of Amides Directly from Acids
(not generally useful, however, due to high
temperature needed)
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Overview of Reactions of Derivatives of Acids
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All have a Common Mechanism!

• 2-step Acyl Substitution
• 1. Addition to CO (to create a tetrahedral C)
• 2. Elimination of the best L to reform the CO

(gem diol-like intermediate unstable w/r to
reformation of the carbonyl group displacement
of the best leaving group)
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Relative Reactivity

• Acid Chlorides gt Acid Anhydrides gt Thioesters
  gt Esters gt Acids gt Amides
• (inversely related to basicity of leaving group)

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Reactions of Acid Chlorides
w/ R2CuLi or 2
w/ LiAlH(t-OBu)3
w/ LiAlH4
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Application Synthesis of Nylon
n
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Reactions of Anhydrides
( low T)
w/ Na2Fe(CO)4
w/ LiAlH4
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Applications Synthesis of Analgesics
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Reactions of Esters
( low T)
w/ DIBAH AlH(i-Bu)2
w/ LiAlH4
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Application Synthesis of Polyethyleneterephthal
ate (PET)
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Review Oxidation at Benzylic Position,
Esterification
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Reactions of Amides (unreactive)
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Reactions of Nitriles

• The nitrile is an anhydride of an amide the CN
  group is a polar group nucleophiles add
  to the CN triple bond as they
  add to a carbonyl group.

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Thiol Esters (thioesters)

• Intermediate in reactivity between anhydrides and
  esters...ideal for biological acylation
  reactions stable to hydrolysis, yet reasonably
  reactive

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Summary of Reactions ofDerivatives of Acids

• Derivative H2O ROH NH3 H
  RMgX
• Acid Chloride acid ester amide (ald)/alc
  (ket)/alc
• Anhydride acid ester amide (ald)/alc
  (ket)/alc
• Ester acid ester amide (ald)/alc (ket)/alc
  
• Amide acid (NR) (NR) amine (NR)
• Nitrile amide ester (NR) amine/
  ketone
• /acid (ald)

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IR Spectroscopy of Carbonyl- Containing Compounds

• RCOOCOR (anhydride) 1820 1760 cm-1
• RCOCl (acid chloride) 1800 cm-1
• RCO2R (ester) 1740 cm-1
• RCHO (aldehyde) 1730 cm-1
• RCOR (ketone) 1715 cm-1
• RCO2H (acid...dimer) 1710 cm-1
• RCONH2 (1o amide) 1690 cm-1
• RCONR2 (3o amide) 1650 cm-1

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Explanation of Carbonyl Stretching Frequency
The polarity of the C-Cl bond increases the
positive charge on the carbon in the dipolar
resonance form. This raises its energy,
resulting in a resonance hybrid with little C-O
(single) bond character. The result is mostly
CO (double) bond character and a high CO bond
stretching frequency.
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Explanation of Carbonyl Stretching Frequency...
Amide resonance results in an additional
resonance form. Two of the resonance forms have
C-O single bond character. The result is a lower
CO bond stretching frequency.
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CO (2) 1822 1756 cm-1
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CO 1792 cm-1
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CO 1739 cm-1
C-O 1189 cm-1
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O-H 3500-2500 cm-1
C-O 1240 cm-1
CO 1716 cm-1
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CO 1690 cm-1
N-H (2) 3363 3192 cm-1
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CO 1669 cm-1
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CN 2248 cm-1