Amines, Amides & Esters

BIOB111

CHEMISTRY & BIOCHEMISTRY

Session 10

Session Plan

• Amines

• Nomenclature of Amines

• Biologically Active Amines

• Heterocyclic Amines

• Alkaloids

• Amides

• Nomenclature of Amides

• Peptide Bond

• Esters

Nitrogen-Containing Organic CompoundsStoker 2014, p540

AMINES

• Functional group:

– NH2 (= Amino group)

• General formula:

R – NH2

• IUPAC Name: ALKANAMINE

IUPAC Name Condensed Structural Formula

Methanamine CH3 – NH2

Ethanamine CH3 – CH2 – NH2

1-Propanamine CH3 – CH2 – CH2 – NH2

2-Propanamine

CH3 – CH – CH3

I

NH2

1-Butanamine CH3 – CH2 – CH2 – CH2 – NH2

2-Butanamine

CH3 – CH2 – CH – CH3

I

NH2

Structure & Classification of Amines

• Amines are derivatives of Ammonia (NH3), where 1,2 or 3 H atoms are substituted by Alkyl groups.

• The

Stoker 2014, Figure 17-1 p540

Classification of Amines

• Primary Amine 10

• Amine where the N atom bonds to 1 alkyl group & 2 H atoms

R – : CH3– = Methanamine

. . CH3–CH2– = Ethanamine

• R – N – H

I

H

Classification of Amines

• Secondary Amine 20

• Amine where the N atom bonds to 2 alkyl groups & 1 H atom

. .

• R1 – N – R2

I

HN-Methyl-ethanamine

Classification of Amines

• Tertiary Amine 30

• Amine where the N atom bonds to 3 alkyl groups only

. .

• R1 – N – R2

I

R3N,N-Dimethyl-1-propanamine

Physical Properties of Amines

• Amines are POLAR compounds but their polarity decreases with increasing molecular mass.

• 10 & 20 amines form hydrogen bonds among their molecules.

• 30 amines do not form hydrogen bonds among their molecules.

• Amines with 1–2 C atoms are gases with ammonia-like odor, other amines are mostly liquids & their odors resemble raw fish.

• The foul smell of dead fish & decaying flesh is due to amines released by the bacterial decomposition of proteins – particularly the diamines Putrescine & Cadaverine.

Stoker 2014, Figure 17-4 p546

Amine – Amine Hydrogen Bonding

Hydrogen bonds among amine molecules involve the

H & N atoms of the participating amino groups.

Stoker 2014, Figure 17-6 p546

Amine – Water Hydrogen Bonding

Hydrogen bond between

a tertiary amine & a water molecule.

Amines as Bases

• Amines are weak bases (like Ammonia).

• N atoms generally have an unshared electron pair & can act as H+ acceptors (Brønsted-Lowry base behaviour).

• A basic solution is produced when ammonia or amines are dissolved in water.

Stoker 2014, p547

Methanamine Methanammonium ion

Reactions of Amines with Acids

• NEUTRALIZATION

• All amines (soluble or insoluble in H2O) react with strong acids, forming water-soluble amine salts of those acids.

• The amine always gains a H+ & the acid always loses a H+.

Stoker 2014, p548

Ethanamine Ethanammonium chloride

Reactions of Amines with Acids

• Many amines have biological activity & are used as drugs.

• High molecular mass amines are insoluble in water & body fluids (blood plasma & CSF), however, for drugs to be effective on targeted cells, they have to be soluble in body fluids.

• Drugs are therefore treated with an acid to form water-soluble ammonium salts – many medication labels refer to Hydrochlorides or Hydrogen sulphates, water-soluble salts of Hydrochloric & Sulphuricacids, respectively.

• Amines are susceptible to oxidation & decomposition by O2 & lose their biological activity but water-soluble ammonium salts are far less susceptible to oxidation & have a longer shelf life.

• Amines in fish (strong odour) interact with acids (vinegar or lemon juice), forming odourless salts, making a fish dish more palatable.

https://genevievemorton.wordpress.com

Heterocyclic Amines

• Cyclic organic compounds in which 1 or more C atoms in the ring structure are replaced with N atoms.

Stoker 2014, Figure 17-8 p553

Heterocyclic Amines

• The 2 most widely used CNS stimulants in the world are hetrocyclic amine derivatives – Caffeine & Nicotine.

Stoker 2014, p552-555

Heterocyclic Amines

• Porphyrin ring = a large cyclic structure,

composed of 4 Pyrrole rings, important

for physiology of living organisms.

• Porphyrins form complexes with metal

ions in the middle of the ring.

• Haeme = Iron-Porphyrin complex found

in Haemoglobin in RBCs, responsible for

oxygen transport in the human body.

Stoker 2014, p553

Biochemically Important Amines

• NEUROTRANSMITTERS

• Substances released at the nerve ending that diffuse across the synaptic gap (space between 2 neurons) & bind to a receptor on the other cell, triggering a nerve impulse.

Stoker 2014, Figure 17-10 p556

Neurotransmitters

• Acetylcholine

• Released by many PNS & CNS neurons.

• Excitatory at NMJ but inhibitory elsewhere.

• Inactivated by enzyme Acetylcholinesterase.

Stoker 2014, p556

AcetateAcetylcholine Choline

Acetylcholinesterase+

Neurotransmitters

• Serotonin

• Involved in relaxation, sleep, rational thinking, feeling of wellbeing & calmness, sensory perception, regulation of body temperature & digestive activity.

• Synthesized from the amino acid Tryptophan.

• Serotonin deficiency may be associated with anxiety disorders or depression – treated with SSRIs (selective serotonin reuptake inhibitors) like Prozac.

Stoker 2014, p557

Neurotransmitters

• CATECHOLAMINES

• Include dopamine, noradrenalin & adrenalin.

• Synthesized from the amino acid Tyrosine.CATECHOLAMINES

Include Dopamine, Noradrenalin & Adrenalin.Synthesized from the amino acid Tyrosine.

Timberlake 2014, p.685

Neurotransmitters

• Dopamine

• A natural stimulant, produced in the brain, feelings of enjoyment.

• Dopamine deficiency may cause Parkinson’s disease.

• Cocaine & Amphetamines inhibit the reuptake of Dopamine, resulting in a longer lifetime in synapse.

• Noradrenalin & Adrenalin

• Function as both, neurotransmitters & hormones.

• Play a role in sleep, attention, focus & alertness.

• NA – involved with blood vessel muscle tone maintenance.

• A – is synthesized from NA in the adrenal glands as a hormone during the ”fight-or-flight” response, CNS stimulant.

CNS Stimulants

• Synthetic CNS stimulants, Amphetamine & Methamphetamine, are both derivatives of 2-phenylethylamine.

• Highly addictive & potentially damaging to the CNS in the long term.

• Commonly used for:

• ADHD, as they increase alertness, concentration & overall cognitive performance, while decreasing fatigue.

• Weight control as appetite suppressants.

Stoker 2014, p557

Biochemically Important Amines

• DECONGESTANTS

• Pseudoephedrine & Phenylephrineare synthetic derivatives of 2-phenylethylamine that are used as decongestants

• Pseudoephedrine is the main constituent of the drug Sudafed, which was illegally used to produce metamphetamine.

• Thus Pseudoephedrine has been recently recently replaced by Penylephrine, sold as Sudafed PE.

Stoker 2014, p558

Biochemically Important Amines

• ANTIHISTAMINES

• Drugs that counteract the effect of Histamine.

• Histamine – a potent pro-inflammatory mediator, involved with allergic reactions.

• Histamine is produced from the amino acid Histidine via the enzyme Histidine decarboxylase.

Histidine

decarboxylase

Alkaloids

• Physiologically active N-containing organic compounds produced by plants.

• “Alkaloid” refers to the alkaline nature of these amines.

• Caffeine – coffee & cacao beans, tea leaves

• Quinine – cinchona tree bark, used to treat malaria

• Nicotine – tobbacco plant, addictive stimulant, high doses cause depression, nausea & vomiting

• Atropine – deadly nightshade plant, used as a preoperative muscle relaxant & in ophtalmology (causes mydriasis)

• Morphine – opium poppy plant, strong hallucinogen, depresses the respiratory centre in the CNS & large doses cause respiratory failure.

• Codeine & Heroin are derivatives of Morphine.

• Cocaine – Coca plant Stoker 2014, p561

AMIDES• Functional group:

O

II

– C – NH2

• General formula:

O

II

R – C – NH2

• IUPAC Name: ALKANAMIDE

IUPAC Name Condensed Structural Formula

Methanamide

O

H – C – NH2

Ethanamide

O

II

CH3 – C – NH2

PropanamideCH3 – CH2 – C – NH2

Butanamide

O

II

CH3 – CH2 – CH2 – C – NH2

Amides

• Amides are derivatives of Carboxylic acids, where –OH in the –COOH

group is replaced by –NH2 (amino) group.

Stoker 2014, p563

Classification of Amides

Ethanamide N-Methyl ethanamide N,N-Dimethyl propanamide

Stoker 2014, p563

Cyclic Amides = Lactams

• The ring size in a lactam is indicated by a Greek letter.

• β-Lactams

• 4-membered ring lactams, where the β-C atom of the Carbonyl group is bonded to the N atom.

• Penicilin family of antibiotics are classed as β-lactam antibiotics.

• γ-Lactams

• 5-membered ring lactams.

Stoker 2014, p566

Useful Amides

• UREA

• Simplest one-C atom diamide, produced during the metabolism of proteins, eliminating N atoms from the body.

• MELATONIN

• Hormone of the Pineal gland, that regulates the sleep-wake cycle in humans.

• ACETAMINPHEN / PARACETAMOL

• N-acetyl-p-aminophenol

• Top-selling OTC pain reliever.Stoker 2014, p568

Preparation of Amides

• Reaction of Carboxylic acids with Ammonia or 10 or 20 amine.

Stoker 2014, p571

Dehydration

Synthesis

Polyamides

• Polymers of amides.

• The monomers are joined via Amide bonds.

• The human body naturally produces polyamides, when linking singular amino acids (monomers) via Peptide bonds (type of amide bond) to form proteins.

• Synthetic polyamides:

• Nylon – fabrics, carpets, ropes, parachutes, surgical sutures

• Kevlar – bullet-proof vests

• Nomex – flame-resistant clothing

• Polyurethane – skin substitutes for severe burn victims, foam rubber in furniture & elastic fibres (e.g. Spandex)

Amide bond

ESTERS• Functional group:

O

II

– C – O – or – COO –

• General formula:

O

II

R – C – O – R’ or R – COO – R’

• IUPAC Name: ALKYL ALKANOATE

Ester Functional Group

Preparation of Esters

• ESTERIFICATION

• A reversible chemical reaction.

Carboxylic acid

Methanol

Ester Water

Esterification

Hydrolysis

Ethanoic acid Methyl ethanoate

Alcohol

Stoker 2014, p518

IUPAC Nomenclature of Esters

• Esters have 2 parts to their molecule, corresponding with their name.

• The 1st part of the formula comes form the Carboxylic acid, which appears 2nd in the name.

• The 2nd part of the formula comes form the Alcohol, which corresponds with the 1st part of the name.

OII

R – C – O – R’

Carboxylic acid – alcohol

Alkyl alkanoate

NOTE: The hydroxyl group (–OH) of the carboxylic acid (not the alcohol!) forms the molecule of H2O together with the H atom of the –OH group of the alcohol!

Stoker 2014, p520

Useful Esters

• Medications

• Many esters have medicinal value.

Stoker 2013, p524

Salicylic acid Methanol Methyl salicylate (Wintergreen)Stoker 2014, p523

Stoker 2014, Table 16-4 p520

Physical Properties of Esters

• POLAR compounds – water but solubility decreases with increasing length of the C chain.

• Ester molecules do not form Hydrogen bonds among each other, as there is not H atom bonded to the O atom of the Ester functional group.

• Esters however form Hydrogen bonds with Water molecules.

• Most have pleasant odours.

• NOTE:

• Dietary fats & oils (Triacylglycerols) are Triesters of 1 molecule of Glycerol & 3 molecules of long-chain Carboxylic acids (= fatty acids).

Hydrogen Bonding Hydrogen Bonding between 1 molecule of Ester & 2 molecules of Water.

Stoker 2014, Figure 16-14 p524

Chemical Properties of Esters

• ACID HYDROLYSIS

• The reverse reaction to Esterification.

• Ester reacts with Water, producing Carboxylic acid & Alcohol.

• Acid uses as a catalyst.

Ester Water Carboxylic acid Alcohol

Methyl ethanoate Ethanoic acid MethanolWaterStoker 2014, p525

Chemical Properties of Esters

• BASIC HYDROLYSIS = SAPONIFICATION

• Production of soaps.

• Ester + strong Base (NaOH or KOH) → Carboxylic Salt + Alcohol

Methyl palmitateSodium

hydroxideSodium palmitate Methanol

Nitroglycerin

• The reaction of 1 molecule of Glycerol (Triol)

with 3 molecules of Nitric acid (HNO3), produces

Trinitrate ester known as Nitroglycerin.

• Component of dynamite.

• Used to treat chest pain of Angina pectoris.

• Its metabolism produces NO (nitric oxide),

a potent vasodilator.

Stoker 2013, p535

Readings & Resources• Stoker, HS 2014, General, Organic and Biological Chemistry, 7th edn,

Brooks/Cole, Cengage Learning, Belmont, CA.

• Stoker, HS 2004, General, Organic and Biological Chemistry, 3rd edn, Houghton Mifflin, Boston, MA.

• Timberlake, KC 2014, General, organic, and biological chemistry: structures of life, 4th edn, Pearson, Boston, MA.

• Alberts, B, Johnson, A, Lewis, J, Raff, M, Roberts, K & Walter P 2008, Molecular biology of the cell, 5th edn, Garland Science, New York.

• Berg, JM, Tymoczko, JL & Stryer, L 2012, Biochemistry, 7th edn, W.H. Freeman, New York.

• Dominiczak, MH 2007, Flesh and bones of metabolism, Elsevier Mosby, Edinburgh.

• Tortora, GJ & Derrickson, B 2014, Principles of Anatomy and Physiology, 14th edn, John Wiley & Sons, Hoboken, NJ.

• Tortora, GJ & Grabowski, SR 2003, Principles of Anatomy and Physiology, 10th edn, John Wiley & Sons, New York, NY.