Structure of Carboxylic Acid Derivatives

1. Structure of Carboxylic Acid Derivatives

2. – •• •• •• O O O •• •• •• •• •• + •• •• RC X RC X RC X + Electron Delocalization and the Carbonyl Group • The main structural feature that distinguishes acyl chlorides, anhydrides, esters, and amides is the interaction of the substituent with the carbonyl group. It can be represented in resonance terms as: –

3. – •• •• •• O O O •• •• •• •• •• + •• •• RC X RC X RC X + Electron Delocalization and the Carbonyl Group • The extent to which the lone pair on X can be delocalized into C=O depends on: • 1) the electronegativity of X • 2) how well the lone pair orbital of X interacts with the p orbital of C=O –

4. Orbital overlaps in carboxylic acid derivatives • p orbital of carbonyl group

5. Orbital overlaps in carboxylic acid derivatives • lone pair orbitalof substituent

6. Orbital overlaps in carboxylic acid derivatives • electron pair of substituent delocalized into carbonyl p orbital

7. •• O •• R C Cl •• •• •• Acyl Chlorides – •• O •• •• • acyl chlorides have the least stabilized carbonylgroup • delocalization of lone pair of Cl into C=O group isnot effective because C—Cl bond is too long R C + Cl •• ••

8. O RCCl least stabilized C=O most stabilized C=O

9. – •• •• •• •• O O O O •• •• •• •• •• + •• C C C C O O R R R R •• •• Acid Anhydrides • lone pair donation from oxygen stabilizes thecarbonyl group of an acid anhydride • the other carbonyl group is stabilized in anmanner by the lone pair

10. O RCCl O O RCOCR' least stabilized C=O most stabilized C=O

11. – •• •• O O •• •• •• + •• C C OR' OR' R R •• •• Esters • lone pair donation from oxygen stabilizes thecarbonyl group of an ester • stabilization greater than comparable stabilizationof an anhydride

12. O RCCl O O RCOCR' O RCOR' least stabilized C=O most stabilized C=O

13. – •• •• O O •• •• •• + •• C C NR'2 NR'2 R R Amides • lone pair donation from nitrogen stabilizes thecarbonyl group of an amide • N is less electronegative than O; therefore, amides are stabilized more than esters and anhydrides

14. – •• •• O O •• •• •• + •• C C NR'2 NR'2 R R Amides • amide resonance imparts significant double-bondcharacter to C—N bond • activation energy for rotation about C—N bondis 75-85 kJ/mol • C—N bond distance is 135 pm in amides versusnormal single-bond distance of 147 pm in amines

15. O RCCl O O RCOCR' O O RCOR' RCNR'2 least stabilized C=O most stabilized C=O

16. – •• •• O O •• •• •• – •• C C O O R R •• •• •• •• Carboxylate ions • very efficient electron delocalization and dispersalof negative charge • maximum stabilization

17. O RCCl O O RCOCR' O O RCOR' RCNR'2 O RCO– least stabilized C=O most stabilized C=O

18. O RCCl O O RCOCR' O RCOR' O RCNR'2 Reactivity is related to structure: Relative rateof hydrolysis Stabilization • The more stabilized the carbonyl group, the less reactive it is. very small 1011 small 107 moderate 1.0 large < 10-2

19. O RCCl O O RCOCR' O O RCOR' RCNR'2 O RCO– most reactive least reactive

20. •• •• O O •• •• C C R R X Y Nucleophilic Acyl Substitution In general: • Reaction is feasible when a less stabilized carbonyl is converted to a more stabilized one (more reactive to less reactive). + HY + HX

21. •• OH •• O O •• •• R C C C Y R X R Y X General Mechanism for Nucleophilic Acyl Substitution involves formation and dissociationof a tetrahedral intermediate HY -HX

22. O RCCl O O RCOCR' O O RCOR' RCNR'2 O RCO– most reactive a carboxylic acid derivative can be converted by nucleophilic acyl substitution to any other type that lies below it in this table least reactive