1. Chem 1152: Ch. 16
Amines

2. Nitrogen Mostly inert gas (N2) under standard conditions
~78% of atmosphere
Found in:
Ammonia (NH3)
Nitrates (fertilizers)
Nitric acid (HNO3)
Propellants (N2O, nitrous oxide)
Explosives (nitroglycerine)
Cyanides (CN-)
4th most abundant element in human body
Critical to building blocks of life/CNS function
Proteins
DNA
RNA
Neurotransmitters
nitroglycerine
Amino acid

3. Amines Organic derivatives of ammonia
One or more H atoms replaced by aromatic or alkyl group
Primary (1°)
Secondary (2°)
Tertiary (3°) : : : :
ammonia
R-OH
alcohols
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

4. Naming Amines – Common Names
For low MW amines
Alphabetically link names of alkyl or aromatic groups bonded to nitrogen, attach suffix –amine.
methylamine
ethylmethylamine
trimethylamine
methylphenylamine
propylamine

5. Naming Amines – IUPAC Names
Replace –e in alkane with –amine.
Number position of amino group lowest on parent chain.
If substituent on nitrogen, prefixed with N.

6. Naming Amines – IUPAC Names
Replace –e in alkane with –amine.
Number position of amino group lowest on parent chain.
If substituent on nitrogen, prefixed with N.
3-Pentanamine
2-Hexanamine
3-Methyl-1-butanamine
N-Methyl-2-butanamine
N-Methyl-2-hexanamine
N,N-Dimethyl-2-hexanamine
N-Ethyl-N-methyl-2-hexanamine
2,5-hexanediamine
cyclohexanamine

7. Naming Amines – Aromatics
Usually named as substituted anilines
For groups on N of aniline, identify with N to indicate not attached to ring
aniline
2-Methylaniline
3-Ethylaniline
N-Ethylaniline
N-Ethyl-N-methylaniline
N,N-dimethylaniline
diphenylamine
2-Ethyl-N-methylaniline
N-Ethyl-2-methylaniline
3-phenyl-2-heptanamine

8. Priority of Functional Groups in IUPAC Names8 8

9. Physical Properties of Amines
1° and 2° amines form H-bonds among themselves (increases BP)
Bonds weaker for amines than alcohols (EN of oxygen > nitrogen)
BP’s of 1° and 2° amines lower than alcohols of comparable MW
alcohol
amine
Amines with 6 or fewer C’s (1° > 2° > 3°) soluble in water due to H-bonding
Amines stink!
Low MW amines smell like ammonia
Higher MW amines smell like rotten fish
putrescine
cadaverine

10. Chemical Properties of Amines
Basicity: Amines are weak bases
From Brønsted-Lowry
Base accepts proton and becomes a conjugate acid

11. Chemical Reactions of Amines
Amines reversibly react with water, form hydroxide ions
Amines form salts when they react with acids

12. Amine Salts
Naming: Change amine to ammonium and add name of negative ion derived from acid
Ethyldimethylamine (common)
N,N-dimethylethanamine (IUPAC)
ethyldimethylammonium
ethyldimethylammonium bromide
Amine salts are white crystalline solids with high MP’s.
Amine drugs usually given in form of salts to improve their ability to dissolve in body fluids
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

13. Amine Salts Amine salts are pH dependent, like CA’s.
(high pH)
amine salt
(low pH)
Amine salts may have 4 alkyl/benzene groups  quaternary ammonium salts
Acetylcholine is important QA salt involved in transmission of nerve impulses
Some QA salts have antiseptic qualities that kill bacteria and fungi.
e.g. benzalkonium (Zephiran) chloride used by physicians to scrub before surgery and to sterilize instruments
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

14. Cocaine is sold illegally as an amine salt.
is reacted with NaOH to produce the free amine form known as “crack.” 14 14

15. Amides
Amides are combination of CA and ammonia or amine joined by amide linkage.
Amide
Ester
Carboxylic Acid
Carboxylic Acid
Amide linkage
Ammonia or amine
Ester linkage
Alcohol
Not formed by reaction between CA and amine (produces salt)

16. Amines Form Amides
Amides are formed through reaction of primary and secondary amines with acid chlorides and acid anhydrides.
Similar to esterification reactions.
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

17. Amide Reactions
No Rxn

18. Synthesis of Nylon Carpeting Clothing Medical tubing Sutures
Parachutes
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

19. Alkaloids Weakly basic amines derived from plants
Stimulate CNS/Resp. systems
Treatment of malaria
Opiates
CNS Depressants, used as painkillers
Morphine derivative
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

20. Synthesizing Drugs: Pharmacology
Alkaloids can be used as the basis for designing new drugs, such as procaine, lidocaine, and Demerol, that retain some of the characteristics of alkaloids.
modify the structures of cocaine and morphine to produce anesthesia, but without the addictive side effects. 20 20

21. An Amide as an Aspirin Substitute
Acetylsalicylic acid
Aspirin
Pain reliever
Fever reducer
Anti-inflammatory
Acetaminophen
Pain reliever
Fever reducer
Does not irritate intestinal tract
Harmful side effects
Allergic reactions
Gastrointestinal bleeding
Can induce Reye’s syndrome in children
Negatives
Not an anti-inflammatory
Overuse can lead to liver and kidney damage
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

22. Naming Amides
Simple amides named after corresponding carboxylic acids by changing –ic or –oic of acid to –amide.
Common names are used more often than IUPAC names.
Common name
formic acid
formamide
IUPAC name
methanoic acid
methanamide
Common name
acetic acid
acetamide
IUPAC name
ethanoic acid
ethanamide
Common name
benzoic acid
benzamide
IUPAC name
benzoic acid
benzamide

23. Naming Amides
Simple amides named after corresponding carboxylic acids by changing –ic or –oic of acid to –amide.
Common names are used more often than IUPAC names.
Use italicized capital N to identify alkyl groups bonded to nitrogen.
Common
N-methylformamide
N,N-dimethylacetamide
N-ethyl-N-methylbenzamide
IUPAC
N-methylmethanamide
N,N-dimethylethanamide
N-ethyl-N-methylbenzamide

24. N,N-diethylethanamide N-isobutylbutanamide N-ethyl-N-phenylbenzamide
Naming Amides
Simple amides named after corresponding carboxylic acids by changing –ic or –oic of acid to –amide.
Common names are used more often than IUPAC names.
Use italicized capital N to identify alkyl groups bonded to nitrogen.
N,N-diethylethanamide
N-isobutylbutanamide
N-ethyl-N-phenylbenzamide
2,N-dimethylbenzamide

25. Physical Properties of Amides
Unsubstituted amides can form complex networks of intermolecular H-bonds
Increases MP’s of these substances
Increasing the number of substituents on amide reduces H-bonding
Reduces MP’s and BP’s
Amides do form H-bonds with water
Increases solubility
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

26. Amide Hydrolysis Most important rxn is hydrolysis
May involve either acid or base
One of the products will always be a salt
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

27. Amide Hydrolysis
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

28. methylammonium chloride
Amide Hydrolysis
acetamide
Acetic acid
Ammonium chloride
N-methylacetamide
Acetic acid
methylammonium chloride
N-methylacetamide
Sodium acetate
methylamine

29. Ethylammonium chloride
Amide Hydrolysis
N-ethylbenzamide
Ethylammonium chloride
Benzoic acid
N-ethylbenzamide
Ethylamine
Sodium benzoate

30. Amines as Neurotransmitters
Neurotransmitters: Molecules that carry chemical messages between neurons in nervous system
released into synapse (gap between synaptic terminal of one neuron and Dendrite of another) in response to electrical signal
Diffuse across synapse and bind to receptors on dendrites of next neuron
In the CNS, the most important neurotransmitters are amines
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

31. Amine Neurotransmitters: Acetylcholine
Acetylcholine (ACh) was first identified neurotransmitter.
Neurotransmitters communicate between CNS and muscle.
When stimulated, it releases into the synapse where it binds to muscle cell receptors causing the muscles to contract.
Acetylcholine is linked to Alzheimer’s disease
In Alzheimer’s disease, acetylcholine levels may decrease by 90%. 31

32. Catecholamines
Amines derived from the essential AA tyrosine (found in egg whites, turkey, soy)
Include dopamine, norepinephrine, and epinephrine
Closely related in structure, and have similar effects. 32

33. Norepinephrine and Epinephrine
Norepinephrine and epinephrine (adrenaline), produced in adrenal glands, are hormonal neurotransmitters that play a role in sleep, attention and focus, and alertness.
act as drugs related to fight or flight response
directly increasing heart rate
triggers the release of glucose from energy stores
increases blood flow to skeletal muscle
increases the brain's oxygen supply
Excess norepinephrine (NE) results in feelings of elation
Low NE levels may cause depression
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

34. Dopamine
Dopamine is produced in the nerve cells of the midbrain and acts as a natural stimulant to give us energy and feelings of enjoyment.
Cocaine and amphetamine block the reuptake of dopamine resulting in a longer lifetime in synapse. 34

35. Amphetamines
Amphetamines structurally and chemically similar to adrenaline
Raise glucose level in blood
Increase pulse rate
Increase blood pressure
May be legally prescribed to elevate mood or reduce fatigue
Street names:
Bennies, pep pills, Reds, red devils, speed, dexies, uppers
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

36. Serotonin
Serotonin helps us relax, sleep deeply and peacefully, think rationally, and it provides us a feeling of well-being and calmness.
Serotonin is synthesized from the amino acid tryptophan.
Low serotonin levels may be associated with depression, anxiety disorders, etc.
Prozac and Paxil (antidepressant drugs) are selective serotonin reuptake inhibitors (SSRIs). 36

37. Histamine
Synthesized in nerve cells in hypothalamus from AA histidine.
Produced by immune system in response to pathogens and invaders, or injury.
When histamine combines with histamine receptors, it produces allergic reactions. 37

38. AA Neurotransmitter Glutamate
Most abundant neurotransmitter in the nervous system.
Involved in cognitive functions (learning and memory).
Used as a source of energy for certain types of brain tumors.
Too much glutamate in the spinal cord causes degeneration of nerve cells (known as Lou Gehrig’s disease).
Precursor for synthesis of GABA.
GABA produces a calming effect by inhibiting the ability of nerve cells to send electrical signals to nearby nerve cells. 38