2. Aromatic Carboxylic Acid 1 Dr Md Ashraful Alam

3. 2 A carboxylic acid Contains a carboxyl group, which is a carbonyl group (C=O) attached to a hydroxyl group (—OH). Has the carboxyl group on carbon 1. carbonyl group O  CH 3 — C—OHhydroxyl group or CH 3 COOH carboxyl group Carboxylic Acids

4. 3 The IUPAC names of carboxylic acids Replace the -e in the alkane name with -oic acid. CH 4 methane HCOOH methanoic acid CH 3 —CH 3 ethane CH 3 —COOH ethanoic acid Number substituents from the carboxyl carbon 1. CH 3 O | ║ CH 3 —CH—CH 2 —C—OH 4 3 2 1 3-methylbutanoic acid IUPAC Names

5. 4 The common names of simple carboxylic acids Are formic acid (1C), acetic acid (2C), propionic acid (3C), and butyric acid (4C). HCOOH formic acid CH 3 —COOHacetic acid Locate substituents using , , γ for the carbon atoms adjacent to the carboxyl carbon. CH 3 γ  |  CH 3 —CH—CH 2 —COOH 3-methylbutanoic acid (  -methylbutryic acid) Common Names

6. 5 Alpha Hydroxy Acids Alpha hydroxy acids (AHAs) Occur naturally in fruit, milk, and sugarcane. Are used in skin care products.

7. 6 Names and Sources of Some Carboxylic Acids TABLE 16.1

8. 7 Common Carboxylic Acids Methanoic acid (formic acid) O ║ H─C─OH ethanoic acid (acetic acid) O ║ CH 3 ─C─OH

9. Aromatic Carboxylic Acid Benzoic Acid Phthalic Acid Salicylic Acid 8

10. 9 Acidity of Carboxylic Acids Carboxylic acids Are weak acids. Ionize in water to produce carboxylate ions and hydronium ions. O O ║ ║ CH 3 − C − OH + H 2 O CH 3 − C − O – + H 3 O +

11. 10 Neutralization of Carboxylic Acids Carboxylic acid salts Are a product of the neutralization of a carboxylic acid with a strong base. CH 3 —COOH + NaOH CH 3 —COO – Na + + H 2 O acetic acid sodium acetate (carboxylic acid salt) Are used as preservatives and flavor enhancers.

12. 11 Naming Acid Derivatives X Acid Halides, RCOX – Derived from the carboxylic acid name by replacing the -ic acid ending with -yl or the – -carboxylic acid ending with –carbonyl and – specifying the halide Benzoic Acid  Benzoyl bromide

13. 12 Naming Acid Anhydrides, RCO 2 COR' If symmetrical replace “acid” with “anhydride” based on the related carboxylic acid Unsymmetrical anhydrides - cite the two acids alphabetically Acetic anhydrideBenzoic anhydrideSuccinic anhydride

14. The essential idea is this: if a substituent removes electrons from the negative oxygen of a carboxylate ion, it will stabilize the ion. This effect shifts the equilibrium to the right and increases acidity. If a substituent pours electrons toward the negative oxygen of a carboxylate ion, it will destabilize the ion. This effect will shift the equilibrium to the left and decrease acidity. 13 Substituent Effects on Acidity

15. Electron-withdrawing Effects: – strengthen acids – weaken bases Electron-releasing Effects: – weaken acids – strengthen bases 14 Substituent Effects on Acidity

16. Consider a para- substituted benzoic acid. We can draw resonance forms: 15 Substituent Effects on Acidity

17. For the carboxylate ion, the corresponding resonance forms would be: 16 Substituent Effects on Acidity

18. The positive charge in the ring attracts the electrons on the carboxylate group. The resonance effect of the substituent thus acts to stabilize the anion and shift the equilibrium to the right. In the unsubstituted benzoic acid, we are assuming that the substituent (H) makes no difference in the electron distribution in the ring. Thus, we would expect the -A=B substituted benzoic acid to be a stronger acid than benzoic acid itself. 17 Substituent Effects on Acidity

19. The nitro group stabilizes the carboxylate anion and shifts the equilibrium to the right. NOTE: The nitro group also has an electron-withdrawing inductive effect 18 Substituent Effects on Acidity

20. The resonance effect of a substituent of the -A=B type reduces the electron density in the benzene ring. The resonance forms shown here represent this reduction of electron density by showing positive charge in the ring. As a result, these substituents exert an electron-withdrawing resonance effect (sometimes represented as a -R effect). 19 Substituent Effects on Acidity -R substituents strengthen acids and weaken bases

21. 20 Substituent Effects on Acidity Electron-donating resonance effect

22. The negative charge in the ring repels the electrons on the carboxylate group. The resonance effect of the substituent thus acts to destabilize the anion and shift the equilibrium to the left. Remember that we are comparing the substituted benzoic acid with unsubstituted benzoic acid. In the unsubstituted benzoic acid, we are assuming that the substituent (H) makes no difference in the electron distribution in the ring. Thus, we would expect the -Y substituted benzoic acid to be a weaker acid than benzoic acid itself. 21 Substituent Effects on Acidity

23. The resonance effect of a substituent of the -Y type increases the electron density in the benzene ring. The resonance forms shown here represent this increase of electron density by showing negative charge in the ring. As a result, these substituents exert an electron-releasing/ electron-donating resonance effect (sometimes represented as a +R effect). The following table shows several substituent groups that exert an electron-releasing resonance (+R) effect. +R substituents weaken acids and strengthen bases 22 Substituent Effects on Acidity

24. Substituents with Electron-Releasing Resonance Effects 23

25. Electronegative substituents attract electrons. When electronegative elements are present in a molecule that can act as an acid, they enhance the acidity of the bond because they lower the electron density in that bond and because they stabilize the conjugate base. Substituents of this type are said to have an electron- withdrawing inductive effect. This type of effect is often known as a -I effect. +I substituents weaken acids and strengthen bases 24 Substituent Effects on Acidity -I substituents strengthen acids and weaken bases

26. -Cl has two competing effects: +R and -I In the case of the chloro group, the -I effect is larger than the +R effect, so we see the -I effect. As the chloro group moves farther away from the carboxyl group, the acid becomes weaker. In the case of the nitro substituent, both the inductive and resonance effects are electron-withdrawing (acid strengthening). But the nitro group is more effective from the para position than from the meta position. This is because the resonance effect is contributing in the para position. 25 Substituent Effects on Acidity

27. Benzoic Acid: pK a = 4.19 26 Substituent Effects on Acidity

28. In the next example, we see the larger +R effects of the methoxy and hydroxy groups predominating over the smaller -I effects. We can see that the substituted benzoic acids are significantly weaker when the -OH or -OCH 3 groups are in the para positions than when they are in the meta positions (where the +R effect is not significant). ortho-Hydroxybenzoic acid (salicylic acid) is much stronger than we would predict. 27 Substituent Effects on Acidity

29. Benzoic Acid: pK a = 4.19 2.97 28 Substituent Effects on Acidity

30. 29 Substituent Effects on Acidity pK a = 4.46pK a = 4.19pK a = 3.47pK a = 3.41pK a = 2.16 =>

31. Reactions

32. 31 Reduction to 1  Alcohols Use strong reducing agent, LiAlH 4. Borane, BH 3 in THF, reduces carboxylic acid to alcohol, but does not reduce ketone.

33. 32 Alkylation to Form Ketones React 2 equivalents of an organolithium reagent with a carboxylic acid.

34. 33 Fischer Esterification Heating a carboxylic acid in an alcohol solvent containing a small amount of strong acid produces an ester from the alcohol and acid

35. 34 Mechanism of the Fischer Esterification acid-catalyzed, nucleophilic acyl substitution of a carboxylic acid

36. When 18 O-labeled methanol reacts with benzoic acid, the methyl benzoate produced is 18 O-labeled but the water produced is unlabeled Mechanism of the Fischer Esterification 35

37. Aspirin, Arachidonic Acid, and Prostaglandins Aspirin (acetylsalicylic acid) is a synthetic carboxylic acid, similar in structure to salicin, a naturally occurring compound isolated from willow bark, and salicylic acid, found in meadowsweet. Salts of carboxylic acids are commonly used as preservatives. Sodium benzoate is a preservative used in soft drinks and baked goods.

38. Preparation of Carboxylic Acids Oxidation of alkyl benzenes An acid can be deprotonated by a base having a conjugate acid with a higher pK a. Because the pK a values of many carboxylic acids are ~5, bases that have conjugate acids with pK a values higher than 5 are strong enough to deprotonate them.