Chemistry 102 Week 6

1. Chemistry 102Week 6 • Chapter 16 Amines (nitrogen) • Organic and Biochemistry for the Allied Health Fields • Dr Mark Deming

2. Chapter 16 • AMINES • Aromatic Amines • Alkaloids nitrogens within rings many times doubly bonded or aromatic

3. Amines • Nomenclature: • How to name, Categorize into 1º, 2º, 3º, 4º, aromatic • alkaloids • Physical Properties: • Can potentially H-bond, boiling point, solubility • Chemical Properties: • Act as a base : accept H+ to become ammonium salt • Chapter 19  Can react with carboxylic acids to give amides (not easily, must use tricks) • Biological Relevant Amines

4. Amines classification Amines are derivatives of ammonia, NH3, where one or more hydrogens have been replaced by an organic (R) group. Quaternary (4°)

5. Structure & Classification • Amines are classified as 1°, 2°, or 3° depending on the number of carbon groups bonded to nitrogen. • aliphatic amine: All carbons bonded to nitrogen are derived from alkyl groups. • aromatic amine: One or more of the groups bonded to nitrogen are aryl groups.

6. Structure and Classification (cont) • Quaternary Amines (4°)- When nitrogen has four bonds and all are to carbon. • Four bonded nitrogen has a positive charge • Note if one or more H’s are present we will deal with later

7. Structure & Classification • heterocyclic amine: An amine in which the nitrogen atom is part of a ring. • heterocyclic aliphatic amine: A heterocyclic amine in which the ring is saturated (has no C=C bonds). • heterocyclic aromatic amine: The amine nitrogen is part of an aromatic ring.

8. Nomenclature • IUPAC names • We derive IUPAC names for aliphatic amines just as we did for alcohols. • Drop the final -e of the parent alkane and replace it by -amine. • Use a number to locate the amino group on the parent chain.

9. Naming Primary Amines The –NH2 group is treated as a chain substituent (side group) called the amino group. Examples: Better as 2-propanamine

10. Naming Aromatic Amines Aniline is the simplest aromatic amine. Compounds are named as substituted anilines. An italic “N” is used to indicate that an alkyl group is attached to the nitrogen and not to the ring. Examples:

11. Nomenclature (Aromatic) • IUPAC names (cont’d) • IUPAC nomenclature retains the common name aniline for C6H5NH2, the simplest aromatic amine. • Name simple derivatives of aniline by using numbers to locate substituents or, alternatively, use the prefixes ortho (o), meta (m), and para (p). • Several derivatives of aniline have common names that are still widely used; among them is toluidine:

12. Nomenclature • IUPAC names (cont’d) • Name unsymmetrical secondary and tertiary amines as N-substituted primary amines. • Take the largest group bonded to nitrogen as the parent amine. • Name the smaller group(s) bonded to nitrogen, and show their location on nitrogen by using the prefix N- (indicating that they are bonded to nitrogen).

13. Nomenclature (common names) • Common names • For most aliphatic amines, list the groups bonded to nitrogen as separate side groups in alphabetical order in one word ending in the suffix -amine.

14. Quicky Charged DefinitionsThings you missed in general chemistry • Ions: charged particles • Cations: positive (+) • Single elements charged (like metals) keep same name • If made from multiple atoms, ends in ”-ium” • Anions: negative (-) Ends in –ite, –ate , –ide • Four “-ides” you will see a lot OH– , Cl– , Br – , I– • Some “-ates” carbonate CO32–, bicarbonate HCO3–, organic anions like acetate CH3CH2CO2– (ethanoate) • Ionic compounds: made of charged particles • Equal amounts of positive and negative charges • bound together by the strong “Ionic” IMF • They are solids at room temp

15. Quicky Charged Definitions (cont.)Things you missed in general chemistry • Salts: Ionic compounds that dissolve in water • Compounds made with single charges (1+, 1-), are almost always soluble in water • Compounds that have charges greater than 1 are harder to make soluble Bones are formed from Ca2+ and PO43- , Hmmm… Why don’t bones dissolve? Would bones be considered salts? • Electrolytes: the individual ions dissolved in water • like sodium ion (Na+) , bicarbonate (HCO3-) • ALL electrolytic (salt) solutions are charge balanced (equal number of positive and negative charges). • Separating charges takes energy • (sodium pump in muscle cells) (potassium pump in nerve cells)

16. Nomenclature • Amine salts • When four atoms or groups of atoms are bonded to a nitrogen atom, as for example CH3NH3+, nitrogen bears a positive charge and is associated with an anion as a salt. • Name the compound as a salt of the corresponding amine. • Replace the ending -amine (or aniline or pyridine or the like) by -ammonium (or anilinium or pyridinium or the like) and add the name of the anion.

17. Physical Properties • Like ammonia, low-molecular-weight amines have very sharp, penetrating odors. • Trimethylamine, for example, is the pungent principle in the smell of rotting fish. • Two other particularly pungent amines are 1,4-butanediamine (putrescine) and 1,5-pentanediamine (cadaverine).

18. Biological amines(From Wikipedia, the free encyclopedia) • Cadaverine 1,5-diaminopentane • is a foul-smelling molecule produced by protein hydrolysis during putrefaction of animal tissue. Cadaverine is similar to putrescine.. Cadaverine is the decarboxylation product of the amino acid lysine. • However, this diamine is not purely associated with putrefaction. It is also produced in small quantities by living beings. • (Is that what that scary guy meant when he said that I was “dead meat”?) • Putrescine 1,4-diaminobutane • Putrescine (sometimes spelled putrescin or putrescene) is an organic chemical compound formed by, and having the smell of, rotting flesh. (Icky, go away) • It is related to cadaverine; both are produced by the breakdown of amino acids in living and dead organisms. • Note that putrescine is synthesized by healthy living cells by the action of ornithine decarboxylase. The polyamines, of which putrescine is one of the simplest, appear to be growth factors necessary for cell division. (What!! That’s wicked)

19. Physical Properties- H-bonding • Amines are polar compounds: • Both 1° and 2° amines have N-H bonds, and can form hydrogen bonds with one another. • 3° amines have no N-H bond and cannot form hydrogen bonds with one another.

20. Physical Properties of Amines- IMF and bp The N-H bond is not quite as polar as the O-H bond. Primary and secondary amines can form hydrogen bonds between molecules. The hydrogen bonds are not as strong as those of alcohols, so amine boiling points are somewhat lower than those of alcohols. But ammonium salts are very strongly connected and are solids at room temperature

21. Physical Properties- boiling point • An N-H---N hydrogen bond is weaker than an O-H---O hydrogen bond, because the difference in electronegativity between N and H (3.0 - 2.1 = 0.9) is less than that between O and H (3.5 - 2.1 = 1.4). • We see the effect of hydrogen bonding between molecules of comparable molecular weight by comparing the boiling points of ethane, methanamine, and methanol.

22. Physical Properties- Solubility in H2O • All classes of amines form hydrogen bonds with water and are more soluble in water than are hydrocarbons of comparable molecular weight. • Most low-molecular-weight amines are completely soluble in water. • Higher-molecular-weight amines are only moderately soluble in water or are insoluble. • BUT ammonium salts (full charges) are very soluble in water

23. Solubility in Water Note: all amines or amides can be protonated. O • Salts like RCO–Na+ or RNH3+Cl– • Carboxylic acids • Alcohols • Amines , amides with NH • Aldehydes, ketones, esters, amides No NH • Ethers, tertiary amines • Alkanes H-bonding carbonyl

24. accept onegive two accept onegive one Accept onegive none Physical Properties, cont. Amines can hydrogen bond with water, making smaller amine molecules usually water soluble. 4° amine (quaternary amine) accept zerogive zero But its ionic+, - charge pair

25. + When amines are “protonated” by strong acids they all become charged and are more soluble in water Amines are weak bases (they want to steal an proton, H+ ) p.513

26. Acid and base • An acid will have a loose “H” which comes off as an H+ • Think of water as HOH or H+ + OH- • Any chemical that adds H+ to water is an acid • Any chemical that add OH- to water (or takes an H+ out of water) is a base

27. Basicity of Amines • Like ammonia, amines are weak bases, and aqueous solutions of amines are basic. • The acid-base reaction between an amine and water involves transfer of a proton from water to the amine.

28. Basicity of Amines • The base dissociation constant, Kb, for the reaction of an amine with water has the following form, illustrated for the reaction of methylamine with water to give methylammonium hydroxide. • pKb is defined as the negative logarithm of Kb

29. Basicity of amines • What you need to know • They act like bases • In water only 1 out of a thousand are protonated (moderate to weak base) • At physiologic pH buffered systems (blood and some cell compartments) they will mainly be protonated (ammonium salts)

30. H+ Amine Reactions Amines behave as weak bases in water (similar to ammonia). R-NH2 + H2O  R-NH3+ + OH- Secondary and tertiary amines behave in a similar manner. 3 atoms attached is neutral (and has one lone pair) 4 atoms attached is charged + (and has zero lone pairs)

31. 1 out of 1,000 but enough to make the solution “basic” (pH >7) Examples:

32. Shows that it is quantifiable – don’t need to know Basicity of Amines • Aliphatic amines have about the same base strength, and are slightly stronger bases than NH3. • Aromatic and heterocyclic aromatic amines are considerably weaker bases than aliphatic amines. • Note that while aliphatic amines are weak bases by comparison with inorganic bases such as NaOH, they are strong bases among organic compounds.

33. Basicity of Amines • Assume that the amine, RNH2, has a pKb of 3.50 and that it is dissolved in blood, pH 7.40 (pOH 6.60). • We first write the base dissociation constant for the amine and then solve for the ratio of RNH3+ to RNH2. • substituting values for Kb and OH- gives: Shows that it is quantifiable – don’t need to know

34. Basicity of Amines • Given the basicities of amines, we can determine which form of an amine exists in body fluids, say blood. • In a normal, healthy person, the pH of blood is approximately 7.40, which is slightly basic. • If an aliphatic amine is dissolved in blood, it is present predominantly as its protonated (conjugate acid) form. (Major form by itself or in water)

35. Acids that can react with amines • Weak acids • RCOOH • H2CO3 • HPO32- • HOH • Medium Acids • H2PO3- • HI • Strong Acids • H2SO4 • H3PO4 • HCl • HBr Used to make salts of amines

36. Reactions of Amines • The most important chemical property of amines is their basicity. • Amines, whether soluble or insoluble in water, react quantitatively with strong acids to form water-soluble salts.

37. Amine Reactions, cont. All amines behave as weak bases and form salts when they react with strong acids such as HCl or H2SO4. R-NH2 + HCl  R-NH3+Cl- amine acid amine salt

38. Examples:

39. Reactions of Amines • example: Complete each acid-base reaction and name the salt formed.

40. Reactions of Amines • example: Complete each acid-base reaction and name the salt formed. • solution:

41. Amine Salts Named by changing “amine” to “ammonium” and adding the anion name. More water soluble than parent amine, a useful characteristic for administering amine drugs. Can be converted back to amine form.

42. Amine Neurotransmitters Neurotransmitter – a chemical bridge between nerve cells.

43. Important Amine Neurotransmitters Acetylcholine Dopamine – synthesized from the amino acid tyrosine. Norepinephrine – synthesized from dopamine, may be associated with mental illness. Serotonin – synthesized from the amino acid tryptophan, may be associated with mental illness.

44. Other Biologically Important Amines Epinephrine (adrenaline) – more important as a hormone than a neurotransmitter. Fight-or-flight hormone, released in response to pain, anger, or fear, increases blood glucose level for energy.

45. Other Biologically Important Amines, cont. Amphetamines – nervous system stimulants, similar in structure to epinephrine. Abuse of amphetamines has severe detrimental effects on the body and the mind.

46. Other Biologically Important Amines Alkaloids – a class of nitrogen–containing organic compounds obtained from plants. Examples include: Nicotine – found in tobacco Caffeine – found in coffee and cola drinks Theobromine- the “feel good” chemical found in chocolate Quinine – used to treat malaria Opium – used to make codeine (in cough medicines), morphine (pain killer) and heroin.

47. Some Alkaloids and Serotonin

48. End Chapter 16

49. Biological amines • Cadaverine • Systematic name: pentane-1,5-diamine Chemical formula C5H14N2 • Other names:1,5-diaminopentane; pentamethylenediamine • Cadaverine is a foul-smelling molecule produced by protein hydrolysis during putrefaction of animal tissue. Cadaverine is a toxic diamine with the formula NH2(CH2)5NH2, which is similar to putrescine . Cadaverine is the decarboxylation product of the amino acid lysine. • However, this diamine is not purely associated with putrefaction. It is also produced in small quantities by living beings. It is partially responsible for the distinctive smell of semen. • Putrescine • Systematic name: butane-1,4-diamine Chemical formula C4H12N2 • Other names: 1,4-diaminobutane; tetramethylenediamine • Putrescine (sometimes spelled putrescin or putrescene) is an organic chemical compound NH2(CH2)4NH2 (1,4-diaminobutane or butanediamine) formed by and having the smell of rotting flesh. • It is related to cadaverine; both are produced by the breakdown of amino acids in living and dead organisms. • Note that putrescine is synthesized by healthy living cells by the action of ornithine decarboxylase. The polyamines, of which putrescine is one of the simplest, appear to be growth factors necessary for cell division.