1. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
The functional group of a carboxylic acid is a carboxyl group
the general formula of an aliphatic carboxylic acid is RCOOH
that of an aromatic carboxylic acid is ArCOOH

2. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
IUPAC names: drop the -e from the parent alkane and add the suffix -oic acid
if the compound contains a carbon-carbon double bond, change the infix -an- to -en-

3. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
The carboxyl group takes precedence over most other functional groups

4. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
dicarboxylic acids: add -dioic acid to the name of the parent alkane containing both carboxyl groups
there is no need to use numbers to locate the carboxyl groups; they can only be on the ends of the chain

5. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
if the carboxyl group is bonded to a ring, name the ring compound and add the suffix -carboxylic acid
benzoic acid is the simplest aromatic carboxylic acid
use numbers to show the location of substituents

6. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
when common names are used, the letters etc. are often used to locate substituents
in common nomenclature, keto indicates the presence of a ketone, and CH3CO- is named an aceto group

7. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
Carboxylic acids have significantly higher boiling points than other types of organic compounds of comparable molecular weight
they are polar compounds and form very strong intermolecular hydrogen bonds
Carboxylic acids are more soluble in water than alcohols, ethers, aldehydes, and ketones of comparable molecular weight
they form hydrogen bonds with water molecules through their C=O and OH groups
water solubility decreases as the relative size of the hydrophobic portion of the molecule increases

8. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
Carboxylic acids are weak acids
values of pKa for most aliphatic and aromatic carboxylic acids fall within the range 4 to 5
the greater acidity of carboxylic acids relative to alcohols, both of which contain an OH group, is due to resonance stabilization of the carboxylate anion
electron-withdrawing substituents near the carboxyl group increase acidity through their inductive effect

9. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
the acid-strengthening effect of a halogen substituent falls off rapidly with increasing distance from the carboxyl group

10. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
Carboxylic acids, whether soluble or insoluble in water, react with NaOH, KOH, and other strong bases to give water-soluble salts
They also form water-soluble salts with ammonia and amines

11. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
Higher reactivity of carbonyl!!!

12. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates

13. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
Mechanism:

14. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
Leaving groups:

15. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates

16. Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates
Synthesis of anhydrides

17. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Acid + Alcohol -> Ester
Excess
The functional group of an ester is an acyl group bonded to -OR or -OAr
name the alkyl or aryl group bonded to oxygen followed by the name of the acid
change the suffix -ic acid to -ate

18. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Acid + Alcohol -> Ester
Excess

19. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Acid + Alcohol -> Ester
base-catalysed esterfication -> does not work with acid + alcohol
Pyridine as proton catcher

20. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Acid + Alcohol -> Ester
Transesterfication

21. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Acid + Alcohol -> Ester
Transesterfication

22. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Hydroxyacid -> Lactone
Lactone: a cyclic ester
IUPAC: name the parent carboxylic acid, drop the suffix -ic acid, and add -olactone
the location of the oxygen atom on the carbon chain is commonly indicated by a Greek letter

23. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Hydroxyacid -> Lactone

24. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Hydroxyacid -> Lactone

25. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Hydrolysis of carboxylic acid derivates

26. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Hydrolysis of carboxylic acid derivates

27. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Hydrolysis of carboxylic acid derivates

28. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Hydrolysis of carboxylic acid derivates

29. Nucleophilic substitution on carbonyl groups – Oxygen as nucleophile
Hydrolysis of carboxylic acid derivates Amides (Peptides and Proteins)

30. Nucleophilic substitution on carbonyl groups – Sulfur as nucleophile
Thiols + Carboxylic acid derivates -> Thioacids and Thioesters
Reactivity increased (compared to formation of ester):
Sulfur better nucleotide than oxygen
RS- better leaving group than RO-

31. Nucleophilic substitution on carbonyl groups – Sulfur as nucleophile
Thiols + Carboxylic acid derivates -> Thioacids and Thioesters

32. Nucleophilic substitution on carbonyl groups – Nitrogen as nucleophile
Amines (1º, 2º, 3º) + Carboxylic acid (derivates) -> Amides
-> with Carboxylic acid

33. Nucleophilic substitution on carbonyl groups – Nitrogen as nucleophile
Amines (1º, 2º, 3º) + Carboxylic acid (derivates) -> Amides
-> with Carboxylic acid derivates

34. Nucleophilic substitution on carbonyl groups – Nitrogen as nucleophile
Amines (1º, 2º, 3º) + Carboxylic acid (derivates) -> Amides
-> with esters

35. Nucleophilic substitution on carbonyl groups – Nitrogen as nucleophile
Amines (1º, 2º, 3º) + Carboxylic acid (derivates) -> Amides

36. Nucleophilic substitution on carbonyl groups – Nitrogen as nucleophile
Aminoacids -> Lactams (cyclic amides)
name the parent carboxylic acid, drop the suffix -ic acid and add lactam
the location of the nitrogen atom in the ring is commonly indicated by a Greek letter, α, β, etc.

37. Nucleophilic substitution on carbonyl groups – Nitrogen as nucleophile
Aminoacids -> Lactams (cyclic amides)
Penicillins and Cephalosporins are member of a family of β-lactam antibiotics

38. Nucleophilic substitution on carbonyl groups – Hydride as nucleophile
Reduction of carboxylic acid derivates -> Alkohols
Lithium aluminium hydride (LAH) -> strong hydrid donor
Sodium borohydride (NaBH4) -> weaker hydrid donor
LAH reduces -> acyl halides, anhydrides, esters, and acids -> primary alcohol

39. Nucleophilic substitution on carbonyl groups – Hydride as nucleophile
Reduction of carboxylic acid derivates -> Alkohols
Lithium aluminium hydride (LAH) -> strong hydrid donor -> reduces almost all carboxylic acid derivates
Sodium borohydride (NaBH4) -> weaker hydrid donor -> reduces acyl halides, ketons, aldehydes

40. Nucleophilic substitution on carbonyl groups – Hydride as nucleophile
Reduction of Amides -> Amines -> different mechanism!!!

41. Nucleophilic substitution on carbonyl groups – Hydride as nucleophile
Reduction of Amides -> Amines -> different mechanism!!!

42. Nucleophilic substitution on carbonyl groups – Carbon as nucleophile
Carboxylic acid derivates + Grignard -> Alcohols

43. Nucleophilic substitution on derivates of sulfuric and phosphoric acids

44. Nucleophilic substitution on derivates of sulfuric and phosphoric acids
Sulfuric acid derivates

45. Nucleophilic substitution on derivates of sulfuric and phosphoric acids
Phosphoric acid derivates

46. Nucleophilic substitution on derivates of sulfuric and phosphoric acids
Phosphoric acid derivates

47. Nucleophilic substitution on derivates of sulfuric and phosphoric acids
Phosphoric acid derivates