2. Chem 150 Unit 7 - Organic Molecules II Carboxylic Acids, Phenols & Amines In this unit and the next we look at the chemical and physical properties of a variety of organic families, all of which play important roles in biochemistry. These include the carboxylic acids, phenols, amines and amides. We also look at a new type of stereoisomer that figures predominantly in biological chemistry; the optical isomer.

3. 2 Introduction T he organic groups covered in this Unit all have important biological roles Carboxylic acids Carboxylic acids Fatty acids Fatty acids Amino acids and proteins Amino acids and proteins Phenols Phenols Colors and flavorings Colors and flavorings Amino acids and proteins Amino acids and proteins Signal molecules Signal molecules Amines Amines Amino acids and proteins Amino acids and proteins Signal molecules Signal molecules Drugs Drugs Amides Amides Amino acids and proteins Amino acids and proteins

5. 4 Carboxylic Acids Naming carboxylic acids The IUPAC ending is -oic acid. The IUPAC ending is -oic acid.

6. 5 Question Give the IUPAC names for the following carboxylic acids: A) A) B) B)

7. 6 Carboxylic Acids Carboxylic acid have high melting points Carboxylic acid have high melting points Small carboxylic acids are quite soluble in water Small carboxylic acids are quite soluble in water

8. 7 Carboxylic Acids Small (volatile) carboxylic acids have noticeable odors. Ethanoic acid (acetic acid) vinegar Ethanoic acid (acetic acid) vinegar Butanoic acid (butyric acid) vomit, dirty socks Butanoic acid (butyric acid) vomit, dirty socks Hexanoic acid (caproic acid) goats, ripe cheese Hexanoic acid (caproic acid) goats, ripe cheese

9. 8 Phenols Simplest phenol is phenol. A hydroxyl group attached to a benzene ring. A hydroxyl group attached to a benzene ring.

10. 9 Phenols All phenols contain hydroxyl groups attached to aromatic rings.

11. 10 Phenols All phenols contain hydroxyl groups attached to aromatic rings.

12. 11 UCSF Study Suggests Capsaicin Significantly Reduces Debilitating Nerve Pain. Mice without it don’t experience pain from heat (Science,2000).(Science,2000). neurogenic inflammation capsaicin Ca ++ capsaicin receptor capsaicin activated channel Substance P Sensory nerve terminal Time

13. 12 These have 2 hydroxyl groups attached to a benzene ring

14. 13 Carboxylic Acids & Phenols as Weak Acids Both carboxylic acids and phenols are weak acids pK a ≈ 5 pK a ≈ 10

15. 14 Questions (Clickers) Which is the stronger acid? A)Acetic acid B)Phenol pK a ≈ 5 pK a ≈ 10

16. 15 Carboxylic Acids & Phenols as Weak Acids The acidity of hydroxyl groups depend on what they are connected to:

17. 16 Question (Clickers) At pH 7, which will be the predominant species? A)Carboxylic acid B)Carboxylate ion pK a ≈ 5 carboxylic acid carboxylate ion

18. 17 Question (Clickers) At pH 7, which will be the predominant species? A)Phenol B)Phenoxide ion phenolphenol phenoxide ion pK a ≈ 10

19. 18 Carboxylic Acids & Phenols as Weak Acids At pH 7, the carboxylate ion of carboxylic acids predominate At pH 7, the carboxylate ion of carboxylic acids predominate At pH 7, the phenol of phenol predominate At pH 7, the phenol of phenol predominate pK a ≈ 5 pK a ≈ 10 pH = 7

20. 19 Carboxylic Acids & Phenols as Weak Acids Strong bases can be used to convert carboxylic acids and phenols to their corresponding carboxylate and phenoxide ions

21. 20 Carboxylic Acids & Phenols as Weak Acids Fatty acids are carboxylate ions at pH 7 Fatty acids with less that 12 carbons are soluble in water Fatty acids with less that 12 carbons are soluble in water Fatty acids with greater than 12 carbons are amphipathic, and form micelles when mixed with water. Fatty acids with greater than 12 carbons are amphipathic, and form micelles when mixed with water.

22. 21 Carboxylic Acids & Phenols as Weak Acids IUPAC names for carboxylate ions: Remove the “-ic acid” from the corresponding conjugate acids name and replace it with “-ate ion”. Remove the “-ic acid” from the corresponding conjugate acids name and replace it with “-ate ion”.

23. 22 Carboxylic Acids & Phenols as Weak Acids Examples:

24. 23 Carboxylic Acids & Phenols, Other Reactions We have already seen how carboxylic acids and carboxylate ions can be made from from the hydrolysis of esters. Base-catalyzed hydrolysis of esters: Base-catalyzed hydrolysis of esters: Acid-catalyzed hydrolysis of esters: Acid-catalyzed hydrolysis of esters:

25. 24 Carboxylic Acids & Phenols, Other Reactions The acid-catalyzed hydrolysis of esters is reversible and can be used to make esters from carboxylic acids and alcohols: Synthesis of esters from carboxylic acids and alcohols: Synthesis of esters from carboxylic acids and alcohols:

26. 25 Carboxylic Acids & Phenols, Other Reactions A biologically important reaction involving carboxylic acids is the decarboxylation of α-keto and β-keto acids:

27. 26 Carboxylic Acids & Phenols, Other Reactions The decarboxylation of β-keto acids produces ketones The decarboxylation of α-keto acids produces aldehydes

28. 27 Carboxylic Acids & Phenols, Other Reactions The oxidation of hydroquinones is also an important biological reaction. A chemical oxidation of hydroquinones can be carried out the oxidizing agent K 2 Cr 2 O 7 (potassium dichromate) A chemical oxidation of hydroquinones can be carried out the oxidizing agent K 2 Cr 2 O 7 (potassium dichromate)

29. 28 Carboxylic Acids & Phenols, Other Reactions Example: Coenzyme Q and the Electron Transport Chain Coenzyme Q and the Electron Transport Chain

30. 29 Carboxylic Acids & Phenols, Other Reactions Example: Coenzyme Q and the Electron Transport Chain Coenzyme Q and the Electron Transport Chain

31. 30 Amines Amines are a nitrogen with one or more carbons attached: Amines are classified based on the number of carbons that are attached to the nitrogen. Amines are classified based on the number of carbons that are attached to the nitrogen. Primary amine (1°): 1 carbons Primary amine (1°): 1 carbons Secondary amine (2°): 2 carbons Secondary amine (2°): 2 carbons Tertiary amine (3°): 3 carbons Tertiary amine (3°): 3 carbons

32. 31 Amines It is possible for a fourth carbon to attach to the nitrogen The nitrogen will take on a positive charge to become an ion. The nitrogen will take on a positive charge to become an ion. Quaternary (4°) ammonium ions: 4 carbon atoms Quaternary (4°) ammonium ions: 4 carbon atoms

33. 32 Amines

34. 33 Amines The IUPAC names for 1°, 2°, and 3° amines. Create the parent name by picking the longest chain of carbons that is attached to the nitrogen. Create the parent name by picking the longest chain of carbons that is attached to the nitrogen. Replace the “-e” in the parent with the ending “-amine”. Replace the “-e” in the parent with the ending “-amine”. Number the longest chain from the end that gets you to the the carbon to which the nitrogen is attached in the fewest number of carbons. Number the longest chain from the end that gets you to the the carbon to which the nitrogen is attached in the fewest number of carbons. Use a numbered prefix to indicate which the carbon in the longest chain the nitrogen is bonded to. Use a numbered prefix to indicate which the carbon in the longest chain the nitrogen is bonded to. If other substituents are attached to the nitrogen, list them and use the prefix “N-” to indicate that they are attached to the nitrogen. If other substituents are attached to the nitrogen, list them and use the prefix “N-” to indicate that they are attached to the nitrogen.

35. 34 Questions Give the IUPAC names for the following amines: A) A)

36. 35 Questions Give the IUPAC names for the following amines: A) A) 2-butanamine2-butanamine 2-butanamine2-butanamine N-ethyl-N-ethyl- N-propylN-propyl N-ethyl-N-propyl-2-butanamineN-ethyl-N-propyl-2-butanamine

37. 36 Amines For heterocyclic amines the nitrogen is part of a ring. The ring can be either aromatic or not. The ring can be either aromatic or not. The nucleic acid nucleotide bases are good examples of hetoercyclic amines The nucleic acid nucleotide bases are good examples of hetoercyclic amines

38. 37 Amines Hydrogen Bonding 1° and 2° amines can serve as both a hydrogen bond donor and acceptor. 1° and 2° amines can serve as both a hydrogen bond donor and acceptor. 3° amines can server as a hydrogen bond acceptors, but not donors. 3° amines can server as a hydrogen bond acceptors, but not donors.

39. 38 Amines Hydrogen Bonding 4° ammonium ion cannot form hydrogen bonds, but because they are charged, form ionic bonds: 4° ammonium ion cannot form hydrogen bonds, but because they are charged, form ionic bonds:

40. 39 The ability to hydrogen bond give amines moderately high boiling points and high solubilities in water. Amines

41. 40 Another notable property of amines is their odor. Like carboxylic acids, they can also produce foul odor. Like carboxylic acids, they can also produce foul odor. The produce a “fishy” smell. The produce a “fishy” smell. Examples of amines, whose names imply their odoriferous properties, include Examples of amines, whose names imply their odoriferous properties, include Amines

42. 41 Amines as Weak Bases In Unit 6, while discussing the definitions of acids and bases, we saw that ammonia, NH 3, is operationally a base That is, when added to water ammonia causes the pH to rise above pH 7. That is, when added to water ammonia causes the pH to rise above pH 7. Ammonia was the example we used to demonstrate the need for the Brønsted-Lowry definition of acids and bases. Ammonia was the example we used to demonstrate the need for the Brønsted-Lowry definition of acids and bases. See the Unit 6 Elaboration - Definitions of Acids and Bases - Part III: Brønsted-Lowry Definition Definitions of Acids and Bases - Part III: Brønsted-Lowry Definitio Definitions of Acids and Bases - Part III: Brønsted-Lowry Definitio See the Unit 6 Elaboration - Definitions of Acids and Bases - Part III: Brønsted-Lowry Definition Definitions of Acids and Bases - Part III: Brønsted-Lowry Definitio Definitions of Acids and Bases - Part III: Brønsted-Lowry Definitio

43. 42 Amines as Weak Bases Like ammonia, 1°, 2° and 3°, act as Brønsted-Lowry bases.

44. 43 Amines as Weak Bases The conjugate acids are called ammonium ions When placed in water, these ammonium ions will behave like acids. When placed in water, these ammonium ions will behave like acids.

45. 44 Amines as Weak Bases Because it is charged, the conjugate acid is even more soluble that the amine. Many drugs are amines and are sold the ammonium salts, which are more readily absorbed, due to their increased solubility. Many drugs are amines and are sold the ammonium salts, which are more readily absorbed, due to their increased solubility. Ephedrine is used as a decongestant. Ephedrine is used as a decongestant.

46. 45 Amines as Weak Bases EphedrineEphedrine is an example of an alkaloid. Ephedrine Alkaloids are alkaline molecules that are derived from plants. Alkaloids are alkaline molecules that are derived from plants. “alkaline” and another name for basic. “alkaline” and another name for basic. Ephedrine is isolated from the Chinese ma huang plant(Ephedra sinica)hyperlink Ephedrine is isolated from the Chinese ma huang plant(Ephedra sinica)hyperlink

47. 46 Amides When a carboxylic acid reacts with an amine it also produces and ammonium salt When a carboxylic acid reacts with an amine it also produces and ammonium salt If the ammonium salt is then heated, an amide is produced. If the ammonium salt is then heated, an amide is produced.

48. 47 Amides Amides are important in biochemistry. For example, amino acids are connected together to form proteins using amide groups. For example, amino acids are connected together to form proteins using amide groups. amino acid

49. 48 Amides Amides can be hydrolyzed back to carboxylic acids and amines by heating them in the presence of an acid

50. 49 Stereoisomers So far we have encountered two different types of isomers. Constitutional Isomers Constitutional Isomers Stereoisomers Stereoisomers cis/trans isomers with alkenes and cycloalkanes, that arise from restricted rotation about bonds. cis/trans isomers with alkenes and cycloalkanes, that arise from restricted rotation about bonds. There is one more type of stereoisomer, which is important in biochemistry. optical isomers optical isomers

51. 50 Stereoisomers Optical isomers arise when a carbon atom has four different things attached to it. These carbons are called chiral carbons. These carbons are called chiral carbons. The a molecule containing a chiral carbon is non superimposable on its mirror image. The a molecule containing a chiral carbon is non superimposable on its mirror image. The molecule and its mirror image are referred to as enantiomers The molecule and its mirror image are referred to as enantiomers

52. 51 Stereoisomers

53. 52 Stereoisomers

54. 53 Stereoisomers

55. 54 Stereoisomers

56. 55 Stereoisomers

57. 56 Stereoisomers When developing drugs that are chiral, it is important to look at the effects of both the enantiomers. R -thalidomide S -thalidomide is effective in treating morning sickness in pregnant women is effective in treating morning sickness in pregnant women is a teratogen, causing birth defects teratogen is a teratogen, causing birth defects teratogen R and S are another way of distinguishing enantiomers; R is the rectus (right) isomer, while S is the sinister (evil) isomer!

58. 57 Stereoisomers When chiral molecules contain more than one chiral carbon, it is possible for two molecules to be stereoisomers without being mirror images. Such molecules are referred to as diastereomers. Such molecules are referred to as diastereomers.

59. 58 Stereoisomers Each chiral carbon that a chiral molecule contains doubles the number of stereoisomers for that molecule. Ephedrine has two chiral carbons, it therefore has 2 x 2 = 4 stereoisomers. Ephedrine has two chiral carbons, it therefore has 2 x 2 = 4 stereoisomers. pseudoephedrine is one of 4 stereoisomers. pseudoephedrine is one of 4 stereoisomers.

60. 59 Question (Clicker) How many stereoisomers does the sugar glucose have? A)2 B)4 C)8 D)16 E)32

61. The End