ORGANIC CHEMISTRY

For General Medicine

Ďuračková Zdeňka

Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry

Medical Faculty of Comenius University

1
 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 2px12py1 C=O

Carbon in basic state

2
 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 2px12py1 2pz C=O

Carbon in basic state

6C 1s2 2s1 2px1 2py1 2pz1 O =C = O

Carbon in excited state
C
3
Electron configuration of carbon

1s 2s 2px 2py 2pz

➢ basic state    
    
➢ excited state

➢ 4 unpaired electrons – four covalent bonds

C
4
 Basic principles of the structure of organic
compounds
- carbon forms four covalent bonds C

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

– equalization of all 4 bonds)
- between carbons can be simple, double, or triple bond
(σ and π bond)
–C–C– –C=C– –C=C–

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

cyclic forms
- between carbon atoms, atoms of oxygen, nitrogen or
5
sulfur can be bound
 Types of hydrocarbon structures
Alkenes
Non-saturated
Alkynes
Acyclic
(non-cyclic) Saturated

HYDROCARBONS Alicyclic
Cycloalkanes

Cyclic Cycloalkenes
Aromatic

Heterocyclic compounds (O, S, N,)

6
 STRUCTURE of ORGANIC COMPOUNDS

Organic compounds – according to hydrocarbone chain arrangement

1. Acyclic (non-cyclic) 2. Cyclic

➢ Unbranched (straight chain) ➢ alicyclic (cyclic)

CH3-CH2-CH3
➢ Branched chain
➢ aromatic (arenes)
CH3-CH-CH3

CH3 ➢ heterocyclic
N 7
 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)
8
 Relation between structure and biological properties
• Isomerism
- identical sum (molecular) formula
- different arrangement of atoms and atom groups (different structure)
1. Constitutional isomerism
- different constitution placement of atoms or kind of bonds

➢ carbon skeleton n-butane CH3 isobutane

CH3 – CH2 – CH2 – CH3 CH3 – CH –CH3 C4H10

➢ placement 1-propanol OH 2-propanol

C 3H 8O
CH3 – CH2 – CH2 – OH CH3 – CH – CH3

➢ placement of double bounds 1-butene 2-butene

1CH = CH – CH2 – CH3 CH3 –2CH = CH – CH3 C 4H 8

2

➢ Tautomerism (oxo-enol, or lactam-lactim tautomerism)

CH2 = CH – OH CH3 – C = O
C 2H 4O 9
vinylalcohol
H acetaldehyde
Tautomerism - positional isomerism –
reverse position of H and the double bond
CH2 = CH – OH → CH3 – C = O

H

vinylalcohol ethanal
(acetaldehyde)

O OH
guanine

HN N N N

H 2N N N H 2N N N
H H
Lactam – form Lactim – form
 Amino - / Imino-tautomerison

In DNA – They cause mutagenic mispairings during DNA replication

In RNA -Tautomeric nucleoside analogs have therapeutic applications as antiviral
11
drugs because of their ability to induce lethal mutagenesis
Amino - / Imino-tautomerison

Change pairing from A-T to G-C

Use in antivirals 12
Configuration isomerism (stereoisomerism)
➢ different arrangement of atoms in space, the same connectivity (order of atoms and
double bonds are identical)
➢ geometrical isomerism, cis – trans (maleic and fumaric acids)
conditioned by the presence of double bond
Maleic acid (cis) Fumaric acid (trans)
H – C – COOH HOOC – C – H
|
H – C – COOH H – C – COOH
➢ optical - conditioned by chiral carbon C* (asymmetric carbon)
- optical isomers - enantiomers
- rotation of the plane of polarized light to the same degree but to opposite
direction (+ / - )
H–C=O H–C=O
configuration D- a L- |
H – C* – OH HO – C* – H
|
CH2OH CH2OH
D(+)- glyceraldehyde L(-) - glyceraldehyde
13
What does it mean + or - ?????
An optically active substance (optically active carbon is
present – C*) in solution is able to rotate the plane of
polarised monochromatic light (light of only a single
frequency) passing through a solution to the right or to
the left

Not linear
polarised light
Linear polarised light

15
Conformation of molecules

➢ Arrangement in space

➢ Rotation of atom groups around axis passing two carbon atoms linked by simple

bond

Example: two conformations of cyclohexane:

Chair Boat 16
 REAGENTS in ORGANIC CHEMISTRY

➢ low-molecular weight compounds (molecules, ions, radicals) react with

substrate

Nucleophilic – donor of electrons to substare for new bond formation is

reagent: OH- , X- (halogenid), H2O, NH3

Nu + -C+ Cl

Electrophilic – acceptor of electrons from substrate for new bond

formation is reagent : +SO3H, +NO2 , Cl+, H+

E+ + CH2=CH- ...
INDUCTIVE EFFECT, I ( for - bond) – related to saturated hydrocarbons

➢ effect of polar bond on polarisation of neighbouring bonds

➢ direction of polarisation is identical with polarity of original bond

➢ effect is dependent on distance

Negative inductive effect – I

-atom, resp. group of atoms linked to carbon, which attracts electrons :
–F, –Cl , –Br , –I, =O, –OR, –SR, –NH2 , –NO2

Positive inductive effect + I

-atom, resp. group of atoms, which push electrons back:
–CH3 (alkyls)

18
 MESOMERIC EFFECT, M Characteristic for  electrons

➢ transformation of polar group effects the conjugation system of double bonds

Negative mesomeric effect -M

➢ groups attracting electrons

➢ dilution of electron density on neighbouring double bonds

➢ groups: -NO2 , -COH, =C=O, -COOH, -C=N

+M -M
+M -M
NO2 R – CH = CH – C = O

10  H
6 electrons 19
electrons
Possitive mesomeric effect, +M

➢ groups that repel (press out) electrons

➢ thickening of electrons on adjacent carbons with double bonds

➢ groups: -NH2 , -OH , -OR, -SH, -SR, -X (halogens)

-M +M
O–H

4
6 electrons 20
electrons
 Reactivity of hydrocarbons
• Saturated hydrocarbons (alkanes)
- substitution (radical reaction, catalyst, UV)
- elimination (dehydrogenation) (catalyst) (Pt, enzyme)

• Non-saturated hydrocarbons (alkenes, alkynes)

- addition: hydrogene (hydrogenation) alkanes
halogene (halogenation) dihalogenalkanes
halogene derivatives monohalogenalkanes
water hydroxy derivatives
(alcohols)
- oxidation – cleavage of bond

• aromatic hydrocarbons X
- substitution: halogenation - Cl
X
(electrophilic sulphonation - SO3H
substitution) nitration - NO2
acylation - CO-R 21
alkylation - CH2-CH3
 REACTIONS of ORGANIC COMPOUNDS
1. Addition
2H
CH2 = CH2 --------> CH3 – CH3

2. Substitution (displacement of atom/atom group)

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

- H 2O
3. Elimination CH3 – CH – CH – CH2 ---------> CH3 – CH = CH – CH3
| |
OH H

2 – butanol 2 – butene 22
Prefix de - .....
Elimination of something - double bond is formed

Dehydration - H 2O
CH3 – CH – CH – CH2 ---------> CH3 – CH = CH – CH3
| |
OH H
2 – butanol 2 – butene

- 2H
Dehydrogenation CH3 – CH – CH – CH2 ---------> CH3 – CH = CH – CH3
| |
H H
butan 2 – butene
- NH3
CH3 – CH – CH – CH2 ---------> CH3 – CH = CH – CH3
Deamination | |
NH2 H
23
2 – aminobutan 2 – butene
 HYDROCARBONS
Acyclic (aliphatic) hydrocarbons
Alkanes:
➢ Saturated hydrocarbons, simple () bonds, binding angle 109°

➢ homologic chain, -CH2- homologic increase, molecular formula

CnH2n+2

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

H2O

➢ Small reactivity, characteristic reaction - substitution (temperature,

UV radiation)
24
- example: methane, ethane, propane, butane, pentane,
Alkenes
➢ non-saturated hydrocarbons, double bond (), binding angle 120°

➢ homological chain, sum formula CnH2n

➢ high reactivity, characteristic reaction – addition

(Markovnik rule)

CH2 = CH2 + HOH CH2 – CH2

 
OH H
ethene (ethylene) ethanol

catalyst
CH2 = CH2 + 2H CH3 – CH3
ethene ethane 25
Dienes (2 double bonds)

➢ cumulated, 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)

26
Alkynes
➢ non-saturated hydrocarbons, triple bond (), binding angle 180°

➢ homological chain, sum formula CnH2n-2

➢ high reactivity, characteristic reaction – addition

CH  CH + HCl → CH2 = CH – Cl
Ethyne (acethylene) chloroethene (vinylchloride)

CH  CH + HOH →  CH2 = CH – OH → CH3 – C = O


H
Ethyne (acetylene) vinylalcohol ethanal
(acetaldehyde)

Tautomerism :
enol- oxo- 27
Markovnik´s rule
Addition of
non-symetric non-symetric
hydrocarbon molecule

CH2 = CH – CH3 + H - OH CH2 – CH – CH3

 
H OH

1-propene 2-propanol

28
Cyclic hydrocarbons

ALICYCLIC

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

cyclopentanoperhydrophenantrene

Stereochemistry cyclohexane

➢ chair and boat form (bound angle 109°)

Chair - more stable Boat

29
AROMATIC hydrocarbons (ARENS)

➢ basic hydrocarbon – benzene (benzol)

➢ aromatic character –
- plane structure (120°bound angle) 1858, F. A. Kekule
(Heidelberg)
π – electrons are delocalized arround whole circle

= =

30
 Polycyclic arens

NAPHTHALEN E ANTHRACENE

PHENANTHRENE BENZPYRENE

➢ Toxicity of arens (benzene, benzpyrene)

➢ Stability towards oxidation
➢ Characteristic substitution reaction
31
(nitration, halogenation, sulphonation)
 HETEROCYCLIC COMPOUNDS
➢ five- or six-membered rings with one or more heteroatoms

➢ condensed heterocyclic compounds with two or more heteroatoms

O NH S

furane pyrrole thiophene

N N

NH S

imidazole thiazole 32
 N

N N O

pyridine pyrimidine pyran

(2H-pyran)

N N

N NH N
H

purine indole
pyrimidine + imidazole benzpyrole

33
Biologically important derivatives of heterocyclic compounds
O

Furan Tiophene

S CH3

Methyltiophene
- in grill meat
Ribose Deoxyribose 34
Biologically important derivatives of heterocyclic compounds - 2

N NH
pyrol
thiazol

P P
Thiamin – vitamin B1

• Component of carboxylases – oxidative decarboxylation

alpha-oxoacids
• Metabolism of saccharides in brain Porphin – porphyrin - haeme
35
Biologically important derivatives of heterocyclic compounds - 3

N
Biotin
NH

imidasol

Histidin Purin 36
Biologically important derivatives of heterocyclic compounds - 4

O
O

Pyran

saturated

Glucose Vitamin E 37
chroman ring
Biologically important derivatives of heterocyclic compounds - 5

N
pyridin

Amid of nicotinic acid NAD+

Niacin
Vitamin PP 38
Biologically important derivatives of heterocyclic compounds - 6

N
Purin
pyrimidin

Pyrimidin nitrogene bases

39
Biologically important derivatives of heterocyclic compounds - 7

Uric acid

40
caffeine theophilline
Biologically important derivatives of heterocyclic compounds - 8

N
H
Tryptophan
Indol
benzene + pyrol

Lysergic acid 41
 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 Prefix Affix

group
Halogen hydrocarbons ⎯F Fluoro-
⎯ Cl Chloro-
⎯ Br Bromo-
⎯I Iodo-
Nitroderivatives ⎯ NO2 Nitro-
Nitrosoderivatives ⎯ NO Nitróso-
Aldehydes ⎯ HC=O Oxo- -e
Ketones ⎯ C=O Oxo- -on

Carboxylic acid ⎯ COOH Carboxy- -ic acid
42
Alcohols ⎯ OH Hydroxy- -ol

Thiols ⎯ SH Merkapto- -tiol

Thio-
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 ⎯ CN Cyano- - nitril

43
 HALOGEN DERIVATIVES
nucleophilic substitution

‫׀‬
Cδ+ X δ- + OH- ↔ H-C-OH + X-

High TOXICITY

Tyroxine – Tetraiodothyronine T4
– Triiodothyronine T3
45
 HALOGENE DERIVATIVES of HYDROCARBONS

- insoluble in water, soluble in alcohols and ethers

- polar covalent bond between –C halogene

• characteristic reaction
- substitution (heterolytical cleavage of bonds), as alkylation reagents

• practical use
➢ solvents for non-polar compounds (CCl4)
➢ monomers for preparation of macromolecular compounds (PVC, artificial rubber,
tephlon),
➢ in refrigerator industry (freons – dichloro-difluoromethane)
➢ iodoform CHI3 – disinfection effects
➢ insecticides
➢ dioxins
➢ narcotics (halotan, CF3-CHBrCl) 46
Toxicity of halogene derivatives
• toxicity

➢ influence on central nervous system (CNS)

➢ tetrachlorodibenzodioxin – carcinogenic, teratogenic, mutagenic effects
(c  1mg.l-1) (dioxins)
➢ cancerogens or suspected carcinogens (CHCl3 , CCl 4)

DDT – insecticide DichloroDiphenylTrichlorethane

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

47
 Key facts related to dioxins

➢ Dioxins are a group of chemically-related compounds that are persistent

environmental pollutants.
➢ Dioxins are found throughout the world in the environment and they accumulate in
the food chain, mainly in the fatty tissue of animals, mainly meat and dairy
products, fish and shellfish.
➢ Dioxins are highly toxic and can cause reproductive and developmental
problems, damage the immune system, interfere with hormones and also cause
cancer.
➢ Due to the omnipresence of dioxins, all people have background exposure, which
is not affecting human health. However, due to the highly toxic potential of
this class of compounds, efforts need to be undertaken to reduce current
background exposure.
➢ Prevention or reduction of human exposure is best done via source-directed
measures, i.e. strict control of industrial processes to reduce formation of dioxins
as much as possible.
48
 Sources of dioxin contamination

➢ products of industrial processes or also result from

natural processes (volcanic eruptions and forest fires)
➢ products of a wide range of manufacturing processes
(smelting, chlorine bleaching of paper pulp, the
manufacturing of some herbicides and pesticides)
➢ uncontrolled waste incinerators (solid waste and hospital
waste) are often the worst culprits, due to incomplete
burning

49
 HYDROXYDERIVATIVES of HYDROCARBONS
(alcohols a phenols)
1. ALCOHOLS
Polarity of bond R O H - reactivity of hydroxyderivatives

Dividing:
1. according to the place of -OH group bound in the chain

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

- secondary (2-butanol)
CH3 – CH2 – CH – CH3

OH
CH3
- tertiary (tert. butanol) 
CH3 – C – CH3
 50
OH
2. According to a number of –OH groups

- monohydroxyderivatives (monohydric)

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

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

- polyhydroxyderivatives (polyols) (saccharides)

CH2OH
CH2 – OH CH2 – OH O OH
  OH
CH2 – OH CH – OH OH
 OH
CH2 – OH
ethyleneglycol glycerol glucose 51
Acidic character of alcohols
CH3- CH2-O-H + NaOH CH3- CH2-O- + Na+ + H2O
Sodium alcoholate

Alkaline character of alcohols and ethers

H +
CH3- CH2-O-H + H+Cl- CH3- CH2- O-H Cl-
Alcoxonic salt
H +

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

52
Alcoxonic salt
HYDROXYDERIVATIVES H -O- H

Oxidation of alcohols R - alcohol R – OH

Ar – phenol Ar – OH

Ether R–O–R

ox ox
R-CH2-OH -2H
R-CH=O R-COOH
H2O

R R
ox ox
CH-OH -2H
C=O
R R
bond cleavage
between carbon atoms
53
3. Tertiary alcohols:

➢ stable against moderate oxidative reagents

➢ cleavage of - C – C - bond with strong oxidative reagent (K2Cr2O7)

CH3 CH3
 oxidation 
CH3 –C – OH CH3 –C = O + HCOOH

CH3 acetone formic acid

54
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

55
Hydrogene bond formation

δ- δ+
R–O H Higher boiling
point
δ+ δ-
H O–R cca 80°C

R–O–R H3C – O – CH3

cca 40°C

R–O–R
56
 Esterification with organic acids

R – OH + HOOC – R R – O – CO – R + H2O

ester

57
 Reaction with inorganic acids
Esterification of alcohols with sulphuric acid

R – O –H + HO – SO2 – OH - H2O

Alcohol H2SO4

58
 Esterification of alcohols with suphuric acid

R – O –H + HO – SO2 – OH - H2O R – O – SO2 – OH

Alkylsulphate, ester of sulphuric acid

- heteropolysaccharides
chondroitinsulphate
dermatansulphate
- glycolipids
sulphatides
59
Esterification with nitric acid
HNO3

CH2 – OH + H – O – NO2 CH2 – O – NO2

 
CH – OH + H – O – NO2 → CH – O – NO2 + 3 H 2O
 
CH2 – OH + H – O – NO2 CH2 – O – NO2

glyceroltrinitrate
(drug for heart diseases)

Alfred Nobel (1833-1896) explosive compound

dynamit discovering (1867)
– Nobel foundation - 9 millions for Nobel prices

60
Reactions with inorganic phosphoric acid

OH OH
- H2O
R – OH + HO – P = O R–O–P=O
OH OH
monoester

61
Reaction with inorganic acids

OH OH
- H2O
R – OH + HO – P = O R–O–P=O
OH OH
monoester

OH + HO – R
- H2O
R–O–P=O
OH

62
Reaction with inorganic acids

OH OH
- H2O
R – OH + HO – P = O R–O–P=O
OH OH
monoester

OH + HO – R O–R
R–O–P=O - H2O R–O–P=O
OH OH

diester
63
Esterification of glycerol with phosphoric acid

H3PO4

CH2 – OH 1CH
2– OH
 
CH – OH OH CH – OH OH + H 2O
   
CH2 – OH + H–O–P=O 3CH – O – P = O
2
 
OH OH

glycerol-3-phosphoric acid
( unit of complex lipids)

64
- in the form of ions at different pH values of body fluids:

O 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

65
➢ esters of phosphoric acid, diphosphoric and triphosphoric acids in living systems

O O O O O O

HO –P– OH HO –P– O – P– OH HO – P– O –P– O – P – OH

     
OH OH OH OH OH OH

phosphoric diphosphoric triphosphoric

acid acid acid

O O O O O O
=

=
=

=
R-O–P– OH R-O –P– O – P– OH R-O – P– O – P– O – P – OH
     
OH OH OH OH OH OH

alkyl phosphate alkyl diphosphate alkyl triphosphate

66
 phosphoanhydric arrangement

O O
 
R – O - P – O ~ P – OH

protone-donor
OH OH groups

phosphoester bond

67
ATP + H2O ADP + Pi G0  - 32 kJ.mol-1 68
PHENOLS

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

- higher acidity of phenols in comparison to alcohols

- chemical reactions

OH
COOH
OH

OH
OH

Phenol Hydroquinone Salicylic acid 69

- Acidic character of phenols
(higher than of alcohols)

OH + NaOH O - + Na+ + H2O

Sodium phenolate

- Toxicity of alcohols and phenols

70
 Oxidation of dihydroxyarenes – diphenols

- formation of quinones, cyclic conjugated diketones

OH O
Cyclic,
-2H
nonsaturated
di-ketone
+2H
OH O

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)

71
 - 2H

+ 2H

1,2-hydroquinone 1,2-benzoquinone
(pyrocatechol)

oxidátion

Pyrogalol
resorcinol use in photograph,
hair coloring
- CO2

Gallic acid
bound to saccharide Tannins, antioxidant
unit 72
 Coenzyme Q

Reduction Oxidation
+ 2H - 2H

Involved in respiratory chain in mitochondria 73

 Vitamin K
phylochinone
O
CH3

CH2CH C (CH2CH2CH2CH)3 CH3

O CH3 CH3

Important for blood coagulation (prothrombin formation).

It is important for photosynthesis in plants.
Deficiency – malfunction of blood coagulation – risk of bleeding
Source – vegetable leafs
74
OXO-compounds (aldehydes and ketones)
(polarisation of bond to oxygen)

Oδ- R
R – Cδ+ Cδ+ = Oδ-
H R

Aldehydes Ketones

75
 OXO-compounds

+ −
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 Ketones C=O
H R

- polarisation of group – reactivity of aldehydes and ketones

76
Chemical reactions of oxo-compounds

Oxidation and reduction

O
oxidation 
O R – C –OH
 - 2H
carboxylic acid
R–C–H
reduction
aldehyde R – CH2 –OH
+2H (Ni) primary alcohol
or donor H atom

77
 Oxidation relatively stable against oxidation
O - 2H
 OH
R–C–R 
Reduction
R – CH – R
secondary alcohol
Ketone
catalyst Ni
or donor of H atoms

78
oxidation and reduction in living systems

(coenzymes of dehydrogenases as acceptors and donors of H atoms)

- NAD+ - acceptor of H− (hydride ion) during the oxidation of alcohol

- NADH – reduced form of coenzyme – donor of H− (hydride ions)

CH3 CH – OH + NAD+ CH3 C = O + NADH + H+

 
H H
ethylalcohol acetaldehyde

79
Redox properties
O O
-2H H2O
R – CH2 – OH R–C -2H R–C
+ 2H
H OH
Aldehyde
Reducing properties

R -2H R Ox
CH – OH C=O
+2H
R R
Ketone
80
 Addition and condensation reactions
- formation of hemiacetals and acetals
hemiacetal
hydroxyl

OH O – CH3
O

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

O – CH3 O – CH3

Aldehyde Alcohol Hemiacetal Acetal

- hemiacetals are unstable

- hemiacetal in cyclic form (cyclic monosaccharides - relatively stable
intermediates at the formation of acetals - glycosides)
81
 Addition and condensation reactions
- formation of hemiacetals and acetals
hemiacetal
hydroxyl

OH O – CH3
O

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

O – CH3 O – CH3

Aldehyde Alcohol Hemiacetal Acetal

- hemiacetals are unstable

- hemiacetal in cyclic form (cyclic monosaccharides - relatively stable
intermediates at the formation of acetals - glycosides)
82
Aldol condensation (aldehydes with -hydrogene)

O OH
  OH −   1
CH3 – C – H + CH3 – CH2– C – H CH3 – CH – CH – C – H
 3
O CH3 O

3- hydroxyaldehyde = aldol
O OH
 OH − 
CH3 – C – H + CH3 – C – CH3 CH3 – CH – CH2 – C – CH3

O O
4-hydroxy-2-pentanone
83
Aldol condensation (aldehydes with -hydrogene)

O OH
  OH −   1
CH3 – C – H + CH3 – CH2– C – H CH3 – CH – CH – C – H
 3
O CH3 O

3- hydroxyaldehyde = aldol
O OH
 OH − 
CH3 – C – H + CH3 – C – CH3 CH3 – CH – CH2 – C – CH3

O O
4-hydroxy-2-pentanone
84
 Aldol condensation in metabolism

H Oδ¯
Cδ+ H2C O P
H2C O P

H C OH C O
C O
aldolase
H2C O P (CHOH)3
HO CH2
H2C O P
dihydroxyaceton- glyceraldehyd-
-phosfate -phosfate fructose -1,6-bifosphate

P = PO3H2

85
Condensation with primary amines -
Formation of imines (Schiff bases)

- H 2O
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 intermediates of biochemical reactions
- binding of carbonyl compounds to free amino groups of proteins
86
 Biological importance of Schiff bases formation

+ H 2N opsin

- H 2O

retinal (vitamin A)

CH=N opsin

rhodopsin

Rhodopsin – red color pigment in the retina of the eye sensitive to light 87
 H O + H2N proteín
protein
C
OH
OH HO - H2O
OH
OH
Nonezymatic CH2 OH
CH N proteín
OH
protein

glycation of D- glukóza
D-glucose
OHHO
OH
proteins OH
CH2 OH
aldimine
aldimín
CH2 NH proteín
protein
(Schiffova zásada)
O Schiff base
OH HO
OH
OH
CH2 OH
ketoamín
Ketoamine
(fruktózamín) 88
(fructosamine)
 CARBOXYLIC ACIDS
- Shift of - electrons in group C=O
120°
O
- Polarisation of – O H bond C 120°
120°
OH
O H O
R–C + H+
R–C=O O

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

- According to the number of – COOH groups:

mono-, di- and tricarboxylic acids
- Saturated and unsaturated 89
 Examples of saturated mono- and dicarboxylic acids
Monocarboxylic acids Dicarboxylic acids

Name Name

formula formula
substitutio common substitutional common
nal

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

90
CH3(CH2)4 COOH Hexanoic Caproic HOOC–(CH2)4COOH Hexanedioic Adipic
 Important dicarboxylic and hydroxy-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 Maleic (cis-form)

Maleate

Lactic CH3–CH–COOH Lactate


OH

91
Important dicarboxylic, hydroxy- and oxo- acids II
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

Tartaric HOOC–CH–CH–COOH Tartarate

 
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 92

 Chemical reactions
1. Neutralisation - salt formation

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

Acetic acid sodium acetate

Sodium and potassium salts – well soluble in water

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

Oxalic acid calcium oxalate - insoluble (urine stones)

- 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 94
2. Decarboxylation
- CO2
CH3 – CH2 – COOH CH3 - CH3
propanoic acid ethane

O=C–COOH
CH – COOH
CH2– COOH HOOC–CH=CH–COOH
Oxalsuccinic acid
Fumaric acid
– CO2 dehydrogenation
– CO2
HOOC–CH2–CH2–CO–COOH HOOC–CH2–CH2–COOH
(O)
Oxoglutaric acid Succinic acid

95
 DERIVATIVES of CARBOXYLIC ACIDS

1. Functional derivatives
- substitution of – H or - OH group of carboxyl with another atom
or atom group
- esters, thioesters, halogenides, amides, anhydrides

2. Substitution derivatives
- substitution of hydrogen atom/s in side chain of carboxylic acids
with another atom or atom group
- hydroxyacids, oxoacids, amino acids, halogene acids

96
 DERIVATIVES of CARBOXYLIC ACIDS

Functional derivatives
O
+
R–C–O–H

- M (salt)
–––––––––––––––––
– X (halogenides)
Acyl- – NH2 (amides)
– O – R (esters)
– O – CO – R (anhydrides)
≡ N (nitrils)

97
3. Nucleophilic substitution reactions

- formation of functional derivatives (esters, amides,

anhydrides, halogenides)
- substitution of –OH group in carboxyl by nucleophile
(esterification)

(+) H+
(-)
H – COOH + HO – CH3 H – CO – O –CH3 + H2O
Formic acid Methyl formiate
Methylester of formic acid
Charles Frederic
Gerhardt (1853) Synthesis of aspirin

1899 The First Bottle

of Aspirin

esterification
COOH COOH
- H2O
+ CH3COOH
OH O CO CH3
2-Hydroxybenzoic acid Acetic acid Acetylsalicylic acid
(salicylic acid)
aspirin
100
-Transport of acyl in biochemical reactions

coenzyme A, (CoA  SH)

- activation of carboxylic acid in metabolic pathways:

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

Acyl- thioester

- thioesters – active form of carboxylic 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)

101
2. Hydrolysis of esters

R – CO – O – R1 + HOH → R – COOH + R1 – OH

Ester Acid Alcohol

Alkaline hydrolysis of esters, so called saponification:

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

R – rest of fatty acid Salt of fatty acid

Soap – sodium or potassium salt of fatty acids

103
 Amides of carboxylic acid

O O

R–C–O–H + NH3 R – C – NH2 + H2O

Amide of carboxylic acid

Amide of nicotic acid

NAD+
Niacine
Vitamin PP 105
- Substitution derivatives

γ(4) β(3) α(2) 1 O

R – CH2 – CH2 – CH – C
OH
H

- X (halogene of carboxylic acid)

! - OH (hydroxy acids)
- NH2 (amino acids)
= O (aldehyde- and oxo-acids)

106
 - Hydroxy acids

α –hydroxy acids eliminate water to lactides at higher temperature

 - 2 H2O
CH3 – CH – COOH HO CH3 – CH CO O
+
OH HOOC CH – CH3 O CO CH –CH3

lactide

Cyclic diester

107
 ß- a - Hydroxy acids
 –hydroxy acids eliminate water (dehydrated) to unsaturated acids at
higher temperature:
 -H2O
CH3 − 3CH – CH2 – 1COOH CH3 − CH = CH − COOH
 Temp.
OH
3–Hydroxybutanoic acid 2- Butenoic acid

γ –hydroxy acids dehydrated to lactons at higher temperature:

γ β α O -H2O
R – CH – CH2 – CH2 – C R–CH–CH2–CH2–C=O
OH OH O

γ– hydroxy acid γ – lactone

109
 Oxidation of hydroxy acids

+2H
CH3 – CH – COOH CH3 – C – COOH
-2H O
OH

Lactic acid Pyruvic acid

β α +2H
CH3 – CH – CH2 –COOH CH3 – CO –CH2 –COOH
OH -2H

β – hydroxybutyric acid Acetoacetic acid

112
 Reaction of ß-oxoacids
important in the metabolism of fat

NADH + H+
hydrogenation CH3−CH−CH2−COOH

OH
− CO2 ketone -Hydroxybutyric acid
CH3−C−CH2−COOH forming
║ cleavage CH3−CO−CH3
O Acetone
Acetoacetic acid (OH- ) acid
forming cleavage 2 CH3−COOH
Acetic acid

113
 Ketone bodies in the organism
In trace amount in blood, urine
At higher concentration in urine – ketonuria (ketoacidosis) (starvation, diabetes)

CH3 – CO – CH2 – COOH acetoacetic acid

CH3 – CH – CH2 COOH β – hydroxybutyric acid

OH

CH3 – CO –CH3 acetone

114
 Transamination

transaminases

Glutamic acid Phenylpyruvic acid 2-oxo-glutaric acid Phenylalanine

115
 Citrate cycle

C2

C4
C6

C4

C5 116
Krebs Hans Adolf (1900 - 1981)

Nobel price for physiology and

medicine, 1953
Discovery of citric acid cycle
He was born in Hildesheimu (Germany) in the family of Judaic
physician. After studying medicine he studied also chemistry
in Berlin for one year.
His most important discovery was Citric cycle (Krebs cycle).

117
118
Citrate formation from Oxaloacetate and
Acetyl-CoA

- CoA-SH

119
Citrate/Isocitrate isomerisation

120
Oxalosuccinate and α-oxoglutarate formation

CO2

CO2

121
Succinyl-CoA formation

CO2

122
Succinate formation

HOH
Fumarate formation

124
Malate formation through water addition

H2O
Fumarate

125
Malate dehydrogenation

126
Derivatives of H2CO3 NaHCO3 Na2CO3 inorganic salts

O
H C OH Formic acid

oxidation
O
HOOC – OH = HO C OH Carbonic acid

Hydroxyformic acid
O
Phosgene
Cl C Cl
O
Urea
H2N C NH2
diamide of carbonic acid

NH S
H2N C NH2 H2N C NH2
Iminourea - guanidine Thiourea
 Macroergic compounds

NH2
O=C
P
O~
Carbamoyl phosphate

O
O
CH2 O P O–
–O P O–
~
HC OH O–
~

O O
O
H2C C C
O C O P O–
O– ~
O–
phosphoenolpyruvate 1,3–bisphosphoglycerate 130
Free energy releases through hydrolyses of
phosphates of some macroergic compounds

Compound ∆G0´ kJ.mol-1)

Phosphoenolpyruvate -61,86
Carbamoyl phosphate -51,41
Acetyl phosphate -43,05
Creatine phosphate -43,05
ATP (na ADP) -30,51
Glucose-1-phosphate -30,51
Glucose-6-phosphate -13,79
Glucose-3-phosphate -9,19

131
Organic compounds of nitrogen

Amines - primary R-NH2

- secondary R-NH-R
- tertiary R-N-R
Basic properties
Formation of amonium salts

R – NH2 + H+ R – NH3+
132
 AMINODERIVATIVES OF HYDROCARBONS
AMINOFENOS - Catecholamines

OH
OH
HO CH – CH2 – NH2 HO CH – CH2 – NH – CH3
HO HO
noradrenaline adrenaline

BIOGENIG AMINES
- decarboxylation of aminoacids

CH2 – CH - COOH

OH NH2 CH2 – CH2

- CO2
OH NH2 ethanolamine
serine

133
Biological important amines formation

N – CH2 – CH – COOH N – CH2 –CH2 –NH2

NH2 – CO2
N N
histidine H histamine
H

134
CH2 – CH2 – CH2 – CH2 – CH – COOH
‫׀‬ ‫׀‬
NH2 NH2 Lysine

CO2

CH2 – CH2 – CH2 – CH2 – CH2

‫׀‬ ‫׀‬
NH2 NH2 Cadaverine
NH3
Putrid process
In dunghill
Pyrolidine
N 135
Reaction of amines with nitric acid/nitrates

Primary amine

R – CH2 – NH2 + HNO2 R – CH2 – OH + N2 + H2O

Secondary amine

R R
NH + HO N O N N O + H 2O
R R
sekundárny
Secondary
amine kyselina
Nitrous
acid nitrózamín
nitrosoamine
Nitrosamine

amín dusitá
Carcinogen !! 137
 ALCALOIDs
 natural compounds with nitrogene – basic
properties
 occurence: products of aminoacid metabolism in
plants
 nitrogen - as heterocycle
 in water insoluble
 botter taste

 strong effect on organisms,

high doses are toxic
138
➢Alcaloids derived from pyridine
nicotine – isolated from tabacco leaf
- lethal dose for man - 50 mg
➢Alcaloids derived from thropane
atropine - has very specific effect on the body – is used in treating colitis,
renal and biliary colic, peptic ulcer and irritable bowel syndrome
cocaine - local analgetic
➢Alcaloids derived from chinoline and isochinoline
morphine - a potent opiate analgesic medication
codeine – make softer caugh
heroine (diacetylmorphine) - a semi-synthetic opioid drug synthesized from
morphine, a derivative of the opium poppy - is used as an analgesic.
Frequent and regular administration is associated with
tolerance and physical dependence, which may develop into addiction
➢Alcaloids derived from indole (produced by the ergot fungus and some plants)
lysergid (LSD) – hallucinogens
➢Alcaloids derived from purine Analeptics stimulate CNS, but did
copheine not influence significantly psychic
theobromine functions
theophyline 139
 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)
N

S S

thiophene thiazol
140
Tiols and sulfides

Aminoacid methionine

141
 Redox reaction of thiols

oxid

R – SH + HS – R R–S–S–R + 2H
red
disulfid

142
Disulfides formation

+ 2H - 2H

143
Redox reactions of thiols – structure of proteins is
changed

Oxidation – 2H S
S
Reduction + 2H

144
 Oxidation of glutathione
OOC-CH-CH2-CH2-CO-NH-CH-CO-NH-CH2-COO-
NH3+ CH2
SH dehydrogenation

SH - 2H
NH3+ CH2
OOC-CH-CH2-CH2-CO-NH-CH-CO-NH-CH2-COO

2 GSH GSSG + 2H
145
Thank you for your

attention........

147