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ORGANIC CHEMISTRY

For Dentistry students

Ďuračková Zdeňka

2018

Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry

Medical School UK

Structure of organic compounds(relation between structure and properties and functions of biologically important

organic compounds)

Organic chemistry – chemistry of hydrocarbons and their derivatives

6C 1s2 2s2 2px12py

1 C = O

Carbon in basic state

6C 1s2 2s1 2px1 2py

1 2pz1 O = C = O

Carbon in excited stateC

Basic principle of the structure of organic

compounds- carbon forms four covalent bonds C

- all 4 bonds are equivalant (hybridization s-, and p-orbitals

on valence layer of carbon atom)

- between carbons can be simple, double, or triple bond

(σ and π bound)

– C – C – – C = C – – C = C –

- atoms of carbon form chains – simple straight, branched and

cyclic forms

- between of carbon atoms, atoms of oxygen, nitrogen or

sulphur can be bound

Types of hydrocarbon structures

HYDROCARBONS

Heterocyclic compounds (O, S, N,)

Acyclic

(non-cyclic)

Cyclic

Saturated

Non-saturated

Alkenes

Alkynes

Alicyclic

Aromatic

Cycloalkanes

Cycloalkenes

STRUCTURE of ORGANIC COMPOUNDS

1. Acyclic (non-cyclic)

unbranched (straight chain)

CH3-CH2-CH3

Branched chain

CH3-CH-CH3

CH3

2. Cyclic

alicyclic (cyclic)

aromatic (arenes)

heterocyclic

Organic compounds – according hydrocarbone chain arrangement

N

Isomerism of organic compounds

(two or more compounds with identical molecular formula,

but different structure)

Types of isomerism

• Constitutional (n-propanol, 2-propanol)

• Configuration (stereoisomerism)

- geometrical (cis-, trans-) (fumaric, maleinic acids)

- optical (chirality, D/L - isomers) (D-AA, L-AA)

• Conformation of molecules (chair, boat)

REACTIONS of ORGANIC COMPOUNDS

1. Addition

2. Substitution (displacement of atom/atom group)

3. Elimination

2H

CH2 = CH2 --------> CH3 – CH3

CH3 – CH2 – Cl + OH- --------> CH3 – CH2 – OH + Cl-

- H2O

CH3 – CH – CH – CH2 ---------> CH3 – CH = CH – CH3

| |

OH H

2 – butanol 2 – butene 8

Acyclic (aliphatic) hydrocarbons

Alkanes:

Saturated hydrocarbons, simple () bonds, binding angle 109°

homologic chain, -CH2- homologic increase, sum formula CnH2n+2

Non-polar compounds, soluble in non-polar solvents, non-soluble

in H2O

Small reactivity, characteristic reaction - substitution (temperature,

UV radiation)

- example: methane, ethane, propane, butane, pentane,

hexane…, isobutane

HYDROCARBONS

Alkenes

non-saturated hydrocarbons, double bond (), binding angle 120°

homological chain, sum formula CnH2n

high reactivity, characteristic reaction – addition

(Markovnik rul)

CH2 = CH2 + HOH CH2 – CH2

OH H

ethene (ethylene) ethanol

catalyst

CH2 = CH2 + H2 CH3 – CH3

ethene ethane

Dienes (2 double bonds)

cummulated, conjugated or isolated double bonds

high reactivity, important reaction – addition polymerisation

n CH2 = C – CH = CH2 ----- --CH2 - C = CH – CH2-n-

CH3 CH3

2-metyl-1,3-butadiene natural rubber

isoprene polymer of isoprene

- Isoprenoids (for example: terpenes, steroids)

Alkynes

non-saturated hydrocarbons, triple bond (), binding angle 180°

homological chain, sum formula CnH2n-2

high reactivity, characteristic reaction – adition

CH CH + HCl CH2 = CH – Cl

Ethyne (acethylene) chloroethene (vinylchloride)

CH CH + HOH CH2 = CH – OH CH3 – C = OH

Ethyne (acetylene) vinylalcohol ethanal (acetaldehyde)

Tautomerism :enol- oxo-

Cyclic hydrocarbons

ALICYCLIC

For ex.: cyclopentane, cyclohexane, cyclohexene, cyclohexadiene,

cyclopentanoperhydrophenantrene

Stereochemistry cyclohexane

chair and boat form (bound angle 109°)

Chair Boat

AROMATIC hydrocarbons (ARENS)

basic hydrocarbon – benzene (benzol)

aromatic character – plane structure (120°bound angle)

π – electrons are delocalized arround whole circle

polycyclic arens

NAPHTHALEN E

ANTHRACENE

five- or six-membered rings with one or more heteroatoms

condensed heterocyclic compounds with two or more heteroatoms

HETEROCYCLIC COMPOUNDS

O NH S

N

NH

N

S

furane pyrrole thiophene

imidazole thiazole

N

N

N

pyridine pyrimidine pyran

(2H-pyran)

N

N NH

N

O

purine indole

pyrimidine + imidazole benzpyrole

NH

DERIVATIVES of HYDROCARBONS

replacing hydrogen atom/atoms in hydrocarbons with another atom

or a group of atoms, so called functional group

CHARACTERISTIC GROUPS and their marking

Compound Characteristic

group

Prefix Affix

Halogenhydrocarbons F

Cl

Br

I

Fluoro-

Chloro-

Bromo-

Iodo-

Nitroderivatives NO2 Nitro-

Nitrosoderivatives NO Nitróso-

Aldehydes HC=O Oxo- - e

Ketons C=O

Oxo- -on

Carboxylic acid COOH Carboxy- -ic acid

Alcohols OH Hydroxy- -ol

Thiols SH Merkapto-

Thio-

-tiol

Ethers O-R R-oxy

Sulphides S-R R-thio

Disulphides S-S

Sulphonic acids SO3 H Sulpho- Sulphonic acid

Amines NH2 Amino- - amine

Imines =NH Imino- - imine

Oxims =N-OH Hydroxylimino- - oxime

Nitrils CN Cyano- - nitril

HALOGENDERIVATIVES

Tyroxine – Tetraiodothyronine T4

– Triiodothyronine T3

nucleophilic substitution

׀

C X δ- + OH-

↔ H-C-OH + X-

19

δ+

High TOXICITY

HALOGENEDERIVATIVES of HYDROCARBONS

- insoluble in water, soluble in alcohols and ethers

- polar covalent bond between – C halogene

• characteristic reaction

- substitution (heterolytical termination of bound), as alkylation reagents

• practical use

solvents for non-polar compounds (CCl4)

monomers for preparation of macromolekular compounds (PVC, artificial rubber,

tephlon),

in refrigerator industry (freons – dichloro-difluoromethane)

iodoform CHI3 – disinfection effects

insecticides

dioxins

narcotiks (halotan, CF3-CHBrCl)

• toxicity

influence on central nerves system (CNS)

tetrachlorodibenzodioxin – carcinogenic, teratogenic, mutagenic effects

(c 1mg.l-1) (dioxins)

cancerogens or suspect carcinogens (CHCl3 , CCl 4)

Toxicity of halogenederivatives

DDT – insecticide DichloroDiphenylTrichlorethane

(1948 Paul Hermann Müller won Nobel Price for DDT discovering)

Dioxin

1. ALCOHOLS

Polarity of bond R O H - reactivity of hydroxyderivatives

Association of molecules of alcohols with hydrogene bounds =

increasing of boiling and melting point)

Dividing:

1. according place of -OH group bounding in the chain

- primary ( 1- butanol) CH3 – CH2 – CH2 – CH2 – OH

CH3 – CH2 – CH – CH3

OH

CH3

CH3 – C – CH3

OH

- secondary (2-butanol)

- tertiary (tert. butanol)

HYDROXYDERIVATIVES of HYDROCARBONS

2. According to a number of –OH groups

- monohydroxyderivatives (monohydric)

- dihydroxyderivatives (diols) (dihydric), ethanediol (ethyleneglycol)

- trihydroxyderivatives (triols) (trihydric), propanetriol (glycerol)

- polyhydroxyderivatives (polyols) (saccharides)

CH2 – OH

CH2 – OH

CH2 – OH

CH – OH

CH2 – OH

O

CH2OH

OH

OH

OH

OH

ethyleneglycol glycerol glucose

R-CH2-OH R-CH=O R-COOH

R R

CH-OH C=O

R R

R - alcohol R – OH

Ar – phenol Ar – OH

H H- O -

Ether R – O – R

HYDROXYDERIVATIVES

(alcohols a phenols)

ox

-2H

ox

-2H

ox

H2O

bond cleavage

between carbon atoms

ox

Oxidation of alcohols

Oxidation of diols

CH2 – OH COOH COOH COOH

CH2 – OH CH2 – OH HC=O COOH

Ethylene glycol

Ethane diole glycolic acid glyoxalic acid oxalic acid

Oxidation of triols

CH2 – OH CH2 – OH HC = O COOH

ox. ox ox

C = O CH – OH CH – OH CH – OH

CH2 – OH CH2 – OH CH2 – OH CH2 – OH

dihydroxyacetone glycerol glyceraldehyde glyceric acid

26

- Acidic character of phenols and alcohols

- Toxicity of alcoholate and phenols

O - + Na+ + H2OOH + NaOH Sodium phenolate

CH3- CH2-O-H + NaOH CH3- CH2-O- + Na+ + H2O

Sodium alcoholate

Alkaline character of alcohols and ethers

CH3- CH2-O-H + H+ Cl- CH3- CH2- O-H Cl-

H +

Alcoxonic salt

Alcoxonic salt

H

CH3 – O – CH3 + H+ Cl- CH3 – O – CH3 Cl-

+

Hydrogene bond formation

R – O Hδ- δ+

δ-δ+

H O – R

Higher boiling

point

cca 80°C

Esterifikacion with organic acids

R – OH + HOOC – R

ester

+ H2OR – O – CO – R

Reactions with inorganic phosphoric acid

OH OH

R – OH + HO – P = O R – O – P = O

OH OH

- H2O

monoester

Reaction with inorganic acids

OH OH

R – OH + HO – P = O R – O – P = O

OH OH

OH + HO – R

R – O – P = O

OH

- H2O

monoester

- H2O

Reaction with inorganic acids

OH OH

R – OH + HO – P = O R – O – P = O

OH OH

OH + HO – R O – R

R – O – P = O R – O – P = O

OH OH

- H2O

diester

monoester

- H2O

Esterification of glycerol with phosphoric acid

H3PO4

CH2 – OH CH2 – OH

CH – OH OH CH – OH OH + H2O

CH2 – OH + H – O – P = O CH2 – O – P = O

OH OH

1-glycerolphosphoric acid (phosphatidic acid)

( unit of complex lipids)

- in the form of ions at different pH values of body fluids:

O O

- H+ - H+

R-O – P – OH R-O – P – O- R-O – P – O-

+ H+ + H+

OH OH O-

pH << 7 pH 7 pH 7

= = =

o

phosphoanhydric arrangement

O O

R – O - P – O ~ P – OH

protone-donoric

OH OH groups

phosphoester bound

ATP + H2O ADP + Pi G0 - 32 kJ.mol-1

PHENOLS

- one or more - OH groups are linked directly to aromatic ring

- higher acidity of phenols in comparison to alcohols

- chemical reactions

COOH

OH

Salicylic acid

OH

OH

Hydroquinone

OH

Phenol

Oxidation of dihydroxyarenes – diphenols

- formation of quinones, cyclical conjugated diketons

OH

OH

O

O

-2H

+2H

p-dihydroxybenzene p-benzoquinone

( hydroquinone) (1,4-benzoquinone)

- antioxidant function of phenols is related to reversible oxidation of

diphenols to quinones (CoQ – ubiquinone in mitochondria)

-Desinfective properties of phenols (carbolic acid)

Cyclic,

nonsaturated

di-keton

OXO-compounds (aldehydes and ketons)(polarisation of bound to oxygen)

R – Cδ+ Cδ+ = Oδ-

Oδ-

H

R

R

Aldehydes Ketons

+

Carbonyl group (oxo-group) - C = O

- all three atoms linked to carbonyl carbon form angle 120°

- they lie in one plane

R R

Aldehydes C = O Ketons C = O

H R

- polarisation of group – reactivity of aldehydes and ketons

OXO-compounds

Chemical reactions of oxo-compounds

Oxidation and reduction

aldehyde

reductionR – CH2 –OH

primary alcohol

O

R – C – H

oxidationO

R – C –OH

carboxylic acid

+2H (Ni)

or donor H atom

- 2H

O

R – C – R

Ketone

Reduction

catalyst Ni

or donor H atoms

relatively stable against oxidation

OH

R – CH – R

secondary alcohol

Oxidation

- 2H

Addition and condensation reactions

- formation of hemiacetals and acetals

Aldehyde Alcohol Hemiacetal Acetal

- hemiacetal in cyclic form (cyclic monosaccharides - relatively stable

intermediates at the formation of acetals - glycosides)

R – C – H + CH3 – OH R– C – H + CH3OH R – C –H + H2O

O – CH3 O – CH3

O – CH3

hemiacetal

hydroxyl

OHO

- hemiacetals are unstable

O OH

OH

CH3 – C – H + CH3 – CH2– C – H CH3 – CH – CH – C – H

O OCH3

Aldol condensation (aldehydes with - hydrogene)

3- hydroxyaldehyde = aldol

O OH

OH

CH3 – C – H + CH3 – C – CH3 CH3 – CH – CH2 – C – CH3

4-hydroxy-2-pentanone

O O

1

3

Condensation with primary amines -

Formation of imines (Schiff bases)

R – CH = O + H2N – CH3 R – CH = N – CH3

• aldimine

R – C = O + H2N – CH3 R – C = N – CH3

| |

R ketone R ketimine

Schiff bases

- important intermediators of biochemical reactions

- binding of carbonyl compounds to free aminogroups of proteins

CARBOXYLIC ACIDS

C

O

OH

120°

120°

120°

- Shift of - elektrons in group C = O

- Polarisation of – O H bound

O H

R – C = OR – C

O

O

+ H+

- Mostly weak acids, K(ionis.const.) = neer to 10-5

- According to number of – COOH groups:

mono-, di- and tricarboxylic acids

- Saturated and unsaturated

Monocarboxylic acids Dicarboxylic acids

formula

Name

formula

Name

substitutio

nal

common substitutional common

HCOOH Metanoic Formic

CH3 COOH Ethanoic Acetic HOOC–COOH Ethanedionic Oxalic

CH3 CH2 COOH Propanoic Propionic HOOC– CH2 –COOH Propanedioic Malonic

CH3(CH2)2 COOH Butanoic Butyric HOOC–(CH2)2 COOH Butanedioic Succinic

CH3(CH2)3 COOH Pentanoic Valeric HOOC–(CH2)3COOH Pentanedioic Glutaric

CH3(CH2)4 COOH Hexanoic Caproic HOOC–(CH2)4COOH Hexanedioic Adipic

Examples of saturated mono- and dicarboxylic acids

Acid name formula R-COOH salt name R-COO

Oxalic HOOC–COOH Oxalate

Malonic HOOC–CH2–COOH Malonate

Succinic HOOC– (CH2)2–COOH Succinate

Glutaric HOOC– (CH2)3–COOH Glutarate

Fumaric (trans- form) HOOC–CH=CH-COOH Fumarate Maleinic (cis-

form) Maleinate

Lactic CH3–CH–COOH Lactate

OH

Important dicarboxylic and hydroxy-acids

Important dicarboxylic, hydroxy- and oxo- acids II

Tartaric HOOC–CH–CH–COOH Tartarate

Acid name formula R-COOH salt name R-COO

3-Hydroxybutyric CH3–CH–CH2–COOH 3-Hydroxybutyrate

OH

Malic HOOC–CH–CH2–COOH Malate

OH

OH OH

Citric CH2–COOH Citrate

HO–C–COOH

CH2–COOH

Pyruvic CH3–CO–COOH Pyruvate

Acetoacetate CH3–CO-CH2-COOH Acetoacetate

Oxalacetic HOOC-CO–CH2-COOH Oxalacetate

2-Oxoglutaric HOOC–(CH2)2–CO–COOH 2-Oxoglutarate

(α-ketoglutaric) (α-ketoglutarate)

Oxalosuccinic HOOC–CO–CH(COOH)CH2(COOH) Oxalosuccinate

DERIVATIVES of CARBOXYLIC ACIDS

1. Functional derivatives

- substitution of – H or - OH group of carboxyl by another atom

or atom group

- esters, thioesters, halogenides, amides, anhydrides

2. Substitutional derivatives

- substitution of hydrogen atom/s in side chain of carboxylic acid

by another atom or atom group

- hydroxyacids, oxoacids, aminoacids, halogeneacids

DERIVATIVES of CARBOXYLIC ACIDS

O

R – C – O – H

- M (salt) –––––––––––––––––

– X (halogenides)

– NH2 (amides)

– O – R (esters)

– O – CO – R (anhydrides)

≡ N (nitrils)

Function derivatives

Acyl-

Chemical reactions

1. Neutralisation - salt formation

CH3 – COOH + NaOH CH3 – COO- Na+ + H2O

Acetic acid sodium acetate

Sodium and potassium salts – good soluble in water

(COOH)2 + Ca(OH)2 (COO)2 Ca + H2O

Oxalic acid calcium oxalate - insoluble (urine stons)

- organic acids at pH near to 7,4 form in cells salts

- dissociated in the form of anions R – COO-

- soaps – sodium and potassium salts of fatty acids

- palmitic acid CH3–(CH2)14 - COONa

- stearic acid CH3–(CH2)16 - COOK

Esterifikation)

H+

H – COOH + HO – CH3 H – CO – O –CH3 + H2O

Formic acid Methyl formiate

Methylester of formic acid

Hydrolyses of esters

R – CO – O – R1 + H2O R – COOH + R1 – OH

R – rest of fatty acid Salt of fatty acid

Alcaline hydrolyse of esters, so called as saponification:

R – CO – OR1 + NaOH R – COO Na+ + R1 – OH

Ester Acid Alcohol

Soap – sodium or potassium salt of fatty acids

-Transport of acyl in biochemical reactions

coenzyme A, (CoA SH)

- activation of carboxylic acid in v metabolic pathways:

R – COOH + HS – CoA R – CO ~ SCoA + H2O

thioester

- thioesters – activ form of carbocylic acids (acyls) in cells

CH3– CO ~ S-CoA acetyl – CoA

CH3 – CO ~ CoA the key intermediate of metabolism

of lipids, saccharides and proteins

- substrate for Krebs cycle (citric acid cycle) 56

Acyl-

Amides of carboxylic acid

O

R – C – O – H

O

R – C – NH2+ NH3 + H2O

Amide of carboxylic acid

Amid of nicotic acid

Niacine

Vitamin PP

- Substitutional derivatives

γ(4) β(3) α(2) 1 O

R – CH2 – CH2 – CH – C

OH

- X (halogene of carboxylic acid)

- OH (hydroxyacids)

- NH2 (aminoacids)

= O (aldehyde- and oxo-acids)

H

!

Hydroxyacids

CH3 – CH CO O

O CO CH –CH3

lactid

CH3 – CH – COOH HO

OH HOOC+

CH – CH3

- 2 H2O

α –hydroxyacids eliminate water to lactids at higher temperature

Hydroxyacids

–hydroxyacids eliminate water (dehydrated) to unsaturated acids at

higher temperaturae:

-H2O

CH3 3CH – CH2 – 1COOH CH3 CH = CH COOH

T

OH

3–Hydroxybutanoic acid 2- Butenoic acid

λ –hydroxyacids dehydrated to lactons at higher temperaturae:

R – CH – CH2 – CH2 – C

O H OH

γ β α

R–CH–CH2–CH2–C=O

O

γ – hydroxyacid γ – lacton

-H2OO

Synthesis of ascorbic acid

O = C

HO – CH

HO – CH

HO – CH2

HC

O

HO – CH

L-gulono-

lacton

L-gulonoic

acid

D – glukuronic

acid

COOH

HO – CH

HO – CH

HO – CH2

HC – OH

HO – CH

+ 2H

L-gulonolacton dehydrogenase

O

=O

OH OH

CH2 – OH

HO – CH

Kys. L-ascorbic

acid (vitamín C)

- 2H

Synthesis of aspirin

COOH

OH

+ CH3COOH- H2O

COOH

O CO CH3

2-Hydroxybenzoic acid (salicylic acid)

Acetic acid Acetylsalicylic acid

aspirin

esterification

CH3 – CH – COOH

OH

+2H

-2H

CH3 – C – COOH

O

Lactic acid Pyruvic acid

CH3 – CH – CH2 –COOH

+2H

-2H

CH3 – CO –CH2 –COOH

OH

αβ

β – hydroxybutiric acid Acetacetic acid

Oxidation of hydroxyacids

Dekarboxylation

- CO2CH3 – CH2 – COOH CH3 - CH3

propanoic acid etane

HOOC–CH2–CH2–CO–COOH (O)

– CO2

HOOC–CH2–CH2–COOH

Succinic acidOxoglutaric acid

– CO2

O=C–COOH

CH – COOH

CH2– COOH

Oxaljantaric acid

dehydrogenation

HOOC–CH=CH–COOH

Fumaric acid

Reaction of ß-oxoacidsimportant in the metabolism of fatt

CH3CCH2COOH

║

O

Acetoacetic acid

NADH + H+

hydrogenation

CO2 ketone

forming

cleavage

(OH- ) acid

forming cleavage

CH3CHCH2COOH

OH

-Hydroxybutyric acid

CH3COCH3

Acetone

2 CH3COOH

Acetic acid

CH3 – CH – CH2 COOH

OH

β – hydroxybutyric acid

CH3 – CO – CH2 – COOH acetoacetic acid

CH3 – CO –CH3 aceton

Ketone bodies in the organism

In trace amount in blood, urine

At higher concentration in urine – ketonuria (ketoacidosis) (starvation, diabetes)

Transamination

transaminases

Glutamic acid Phenylpyruvic acid 2-oxo-glutaric acid Phenylalanine

67

Citrate cycle

C4C6

C2

C5

C4

Nobel price for physiology and

medicine, 1953

Discovery of citric acid cycleHe was born in Hildesheimu (Germany) in the family of Judaic

physician. After studying of medicine he studied in Berlín also

chemistry one year.

His most important discovery was Citric cycle (Krebsov)

cyklus.

Krebs Hans Adolf (1900 - 1981)

Citrate formation from Oxylacetate and

Acetyl-CoA

- CoA-SH

H

Citrate/Isocitrate isomerisation

Oxalosuccinate and α-oxoglutarate formation

CO2

Succinyl-CoA formation

CO2

Fumarate formation

Malate formation through water addition

H2O

Malate dehydrogenation

H2O

O=C-COOH H2C-COOH

CH2-COOH + CH3-CO-S-CoA HO-C-COOH + CoA-SH

H2C-COOH

Oxalacetic acid Acetyl-CoA Citric acid

Synthesis of citric acid

Organic compounds of nitrogene

Amines - primare R-NH2

- secondary R-NH-R

- tertiare R-N-R

R – NH2 + H+ R – NH3+

Basic properties

Formation of amonium salts

Biological important amines formation

– CH2 – CH – COOH

NH2 – CO2

– CH2 –CH2 –NH2

HistamineHistidineN

H

N

N

H

N

HO CH2 CH

NH2

COOH HO CH2 CH2 NH2HO CH2 CH2 N

CH3

CH3

CH3

++ 3 CH3

cholínCO2

Serine EtanolamineCholine

ORGANIC COMPOUNDS OF SUPHUR

• Thiols R-SH (disulphides, thioesters)

• Sulphides R-S-R (sulphoxides, sulphons)

• Sulphonic acids, sulphonamides R – SO3H

• Heterocyclic compounds with suphur

(thiophene, thiazol)

S

N

S

thiophene thiazol

Redox reaction of thiols

R – SH + HS – R R – S – S – R + 2H

oxid

red

disulfid

Redox reactions of thiols – structure of proteins is

changed

Oxidation – 2H

Reduction + 2H

S

S

OOC-CH-CH2-CH2-CO-NH-CH-CO-NH-CH2-COO-

NH3+ CH2

SH

SH

NH3+ CH2

OOC-CH-CH2-CH2-CO-NH-CH-CO-NH-CH2-COO

dehydrogenation

- 2H

2 GSH GSSG + 2H

Oxidation of glutathione

Derivatives of sulfanilic acid

sulfonamides

Folic acid

Sulfanilic acid sulfonamid

Sulfanic acid

85

Thank you

for your attention.....