Amines and Amides

1. Amines and Amides Amines

2. Amines and Amides • Contain a nirogen atom bonded to one, two or three carbon atoms • Amines- a nitrogen atom is directly bonded to a carbon • Amide a nitrogen atom is directly bonded to a carbonyl group carbon • A variety of naturally occurring and synthetic amines and amides • physiologically active and hence biologically important

3. Biological Activity • Amines • Painkillers: heroin, codeine, morphine • Stimulants and decongestants (adrenaline, cocaine, dopamine, amphetamines, nicotine • Neurotransmitters: dopamine • Bioregulators: epinephrine • Vitamins: niacin, Vitamin B6 • Alkaloids: nicotine, morphine, cocaine

4. Amines • Structures of biologically active amines

5. Amides: Biological activity • Pain relievers: acetominophen • Tranquilizers: Phenobarbital, diazepam • Local anesthetics: Novocaine • Caffaeine- both an amine and an amide • Amino acids, polypeptides and synthetic nylon

6. Amines Amines are derivatives of ammonia NH3 • Contain N attached to one or more alkyl or aromatic groups ie • One , two or three of the ammonia hydrogens are replaced by an alkyl or an aryl group CH3 CH3   CH3—NH2 CH3—NH CH3—N—CH3

7. Classification of Amines classified as primary, secondary, or tertiary. • Primary(1°) amine, one carbon group is bonded to the nitrogen atom. (one C-N bond, 2 N-H bonds). • Secondary (2°) amine has two carbon groups(two C-N bonds, 1 N-H bond). • Tertiary (3°) amine has three carbon groups (three C-N bonds, no N-H bond). H CH3 CH3 ||| CH3—N—HCH3—N—H CH3—N—CH3 1° 2° 3° Quaternary (4): four C-N bonds, nitrogen has a + formal charge.

8. Models of Amines • The three-dimensional models show the shapes of amine molecules with one or more alkyl groups bonded to the nitrogen atom. • Can also be classified as • Aliphatic amine-carbon attached to the amine • nitrogen is not part of the aromatic ring • Aromatic:-aromatic carbon is directly bonded • to the nitrogen

9. Nomenclature Common nomenclature system Simple amines – have simple substituent groups • Named as alkylamines: the substituents are named without spaces between then, followed by the suffix –amine • Names of the alkyl or aryl groups bonded to the N atom are listed in alphabetical order then add suffix –amine added • Primary amines are named as derivatives of hydrocarbons by changing the ending of the name from e to amine • CH3—CH2—NH2 ethylamine CH3—NH—CH3dimethylamine CH3 | CH3—N—CH2—CH3 ethyldimethylamine

10. Common Names diethylmethylamine Cyclopentylmethylamine 1-amino-methylcyclopentane Diphenylamine

11. Amine as substituent • On a molecule with a higher priority functional group the amine is named as a substituent. • The NH2 is named as the amino substituent 4-aminobutanoic acid 2-methylaminophenol

12. IUPAC Nomenclature In the IUPAC system, • Amines are named as alkanamines. • Name is based on longest carbon chain. • The ­e in the alkane name of the longest chain is changed to ­amine. • The chain is numbered to locate the amine group and substituents. NH2 | CH3—CH2—NH2 CH3—CH—CH3 Ethanamine 2-Propanamine

13. Secondary and Tertiary Amines In a secondary or tertiary amine, • The longest alkane chain is numbered. • Each alkyl group bonded to the N atom is named as a N-alkyl group (Substituents on nitrogen have N- prefix.) • NHR and the NRR’ substituents are named as N-substitute and N,N-disubstituted amino substituents respectively HN—CH3 | CH3—CH2—CH2—NH—CH3CH3—CH—CH2—CH3 3 2 1 1 2 3 4 N-Methyl-1-propanamine N-Methyl-2-butanamine 3-bromo-1-pentanamine N,N-dimethyl-3-hexanamine =>

14. Learning Check Give the common and IUPAC names, and classify as primary, secondary, or tertiary: A. CH3—CH2—CH2—NH2 CH3 | B. CH3—CH2—N—CH3

15. Learning Check Write a structural formula for A. 2-pentanamine B. N-methyl-1-butanamine

16. aniline N,N-dimethylaniline 4-methylanilineor p-toluidine Aromatic Amines Amino group is bonded to a benzene ring.. The amine of benzene is aniline.

17. Aromatic Amines • Alkyl groups on the N use the prefix N- and the alkyl name. Aniline3-chloroaniline N-methylaniline

18. Learning Check Give a name for each: A. CH3—NH—CH2—CH3 CH3 | B. CH3—CH2—N—CH2—CH2—CH2—CH3 C.

19. Solution A. CH3—NH—CH2—CH3 ethylmethylamine; N-methylethanamine CH3 | B. CH3—CH2—N—CH2—CH2—CH2—CH3 N-ethyl-N-methyl-1-butanamine C. aniline

20. Properties of Amines

21. Properties of Amines • The N-H bond in1° and 2° amines , like the the O-H bond of an alcohol participate in H- bonding • However, the degree of polarisation of the N-H bond is less than that of the O-H bond • This results in weaker H- bonding attractions in amines cfed to alcohols

22. Boiling Points N-H less polar than O-H. Hence have weaker hydrogen bonding. Tertiary amines cannot hydrogen bond.

23. Boiling Points of Amines, cont. The boiling points of 1 and 2 amines are • Higher than corresponding alkanes & ethers • Lower than alcohols of similar mass.

24. Hydrogen Bonding for Amines • N-H bond is polar • Provides hydrogen bonding for the 1°and 2° amines, but not 3°. • The N-H bond in amines is not as polar as the O-H bonds in alcohols.

25. Solubility in Water 1-5 carbon atoms amines are soluble in water the N atom in smaller amines forms hydrogen bonds with the polar O-H bond in water. solubility is comparable to ethers and alcohols

26. 1,5-pentanediamine or cadaverine Solubility and Odor • All amines form hydrogen bonds with water and alcohol. • Branching increases solubility. • Most amines smell like rotting fish.

27. Learning Check Consider the following compounds: 1. CH3—CH2—CH2—NH2 2. CH3—CH2—NH—CH3 3. CH3—CH2—CH2—CH3 A. Which compound has the highest boiling point? B. Which compound(s) is(are) soluble in water?

28. Solution Consider the following compounds: 1. CH3—CH2—CH2—NH2 2. CH3—CH2—NH—CH3 3. CH3—CH2—CH2—CH3 A. Which compound has the highest boiling point? 1. CH3—CH2—CH2—NH2 B. Which compound(s) is(are) soluble in water? 1. CH3—CH2—CH2—NH2 2. CH3—CH2—NH—CH3

29. Amines React as Bases Amines are • Bronsted-Lowry bases • attract a H+ from H2O to the N atom( proton acceptors) • Weak bases in water. NH3 + H2O NH4+ + OH– ammonium hydroxide CH3—NH2 + H2O CH3—NH3+ + OH– methylammonium hydroxide

30. Basicity of Amines • Lone pair of electrons on nitrogen can accept a proton from an acid • Hence aqueous solutions are basic to litmus. • egpKb for Ammonia = 4.74 • Alkyl amines are usually stronger bases than ammonia. • Increasing the number of alkyl groups decreases solvation of ion, so 2 and 3 amines are similar to 1 amines in basicity. =>

31. Neutralization forms Amine Salts An amine salt forms when an amine is neutralized by acid. • Amine salt is named by replacing the amine part of the name with ammonium followed by the name of the negative ion. CH3—NH2 + HCl CH3—NH3+Cl– methylamine methylammonium chloride

32. => Amine Salts

33. Properties of Amine Salts Amine salts are • Solids at room temperature. • Soluble in water and body fluids. • Have no fishy odor • Are used as drugs.

34. Cocaine • Is sold illegally as an amine salt. • Is reacted with NaOH to produce the free amine form known as “crack”.

35. Learning Check Write the equation for ethylamine when it reacts with each of the following: 1. + H2O 2. + HCl

36. Solution Write the equation for ethylamine when it reacts with each of the following: 1. CH3—CH2—NH2 + H2O CH3—CH2—NH3+ OH– 2. CH3—CH2—NH2 + HCl CH3—CH2—NH3+ Cl–

37. Heterocyclic Amines & Alkaloids

38. Heterocyclic Amines A heterocyclic amine • Is a cyclic organic compound.- an amine in which the nitrogen is part of a cyclic structure • Has a five- or six-atom ring. • Contains one or more nitrogen atoms. • Found in a number of compounds of biochemical interest

39. Examples of Heterocyclic Amines Pyrimidine and pyridine are nitrogen analogues of benzene They posses aromatic properties Pyrole and imidazole also posses aromatic properties

40. Learning Check Identify the following heterocyclic amines: 1. 2. 3.

41. Solution Identify the following heterocyclic amines: 1. 2. 3. 1. piperidine 2. pyrrole 3. imidazole

42. Alkaloids Alkaloids are • Physiologically active nitrogen-containing cpds • Produced by plants. • Used as stimulants, anesthetics & antidepressants. • Often habit forming.

43. Caffeine Caffeine • Is a stimulant of the central nervous system. • Is found in coffee beans, tea, chocolate, and soft drinks. • Amine containing an imidazole ring.

44. Nicotine Nicotine • Increases the adrenaline level in the blood. • Causes addiction to tobacco. • Contains a pyrrolidine ring.

45. Alkaloids Related to Morphine Alkaloids • Such as morphine and codeine are produced by the poppy. • Have been used for centuries as painkillers. • Heroin and codeine are modifications of morphine.

46. Morphine and Codeine

47. Pharmacology An area of research • Is to design drugs such as procaine, lidocaine, and demerol that retain some of the characteristics of alkaloids. • Is to modify the structures of cocaine and morphine to produce anesthesia, but without the addictive side effects.

48. Pharmacology

49. Learning Check Identify the heterocyclic amine in serotonin. serotonin

50. Solution Identify the heterocyclic amine in serotonin. pyrrole