Derivatives of hydrocarbons I Medical Chemistry Lecture 6 2007 (J.S.) Alcohols, phenols, ethers, thiols, carbonyl compounds, and carboxylic acids Nomenclature Hydrocarbons
May 11, 2015
Derivatives of hydrocarbons I
Medical ChemistryLecture 6 2007 (J.S.)
Alcohols, phenols, ethers, thiols, carbonyl compounds, and carboxylic acids
NomenclatureHydrocarbons
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Nomenclature of organic compounds
Common (trivial) names
Semisystematic (rational) names
Systematic names
Acetic acid - Ethanoic acid
Picric acid - 2,4,6-Trinitrophenol
Stearic acid - Octadecanoic acid
- Acetone Propanone
(Glycerine) Glycerol 1,2,3-Propanetriol
Glutamic acid α-Aminoglutaric acid 2-Aminopentanedioic acid
Tyrosin p-Hydroxyphenylalanine 2-Amino-3-(4-hydroxy-phenyl) propanoic acid
Common (trivial) names are still used; judicious use of them providesa convenient group of parent compounds for ascribing names of their derivatives.
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The six different principles in IUPAC nomenclature
1 Functional (group-functional) names – are the names of hydrocarbons that express their degree of unsaturation by means of suffixes (e.g., pentane, penta-1,3-diene, pent-1-yne, cyclopentane); – also the names of carboxylic acid derivatives (amides, nitriles, anhydrides, halides), ethers, sulfides, simple amines
(e.g., acetonitrile, butyryl chloride, diethyl ether, dimethylamine),
and alternatively the names of alcohols, aldehydes, ketones, and alkyl halides
(e.g., methyl alcohol, acetaldehyde, dimethyl ketone, methyl chloride).
2 Substitutive names are assigned to the majority of organic compounds:
Compounds are viewed as simple parent structures (molecules of hydrocarbons, heterocycles), which are substituted by various functional groups.
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3 Conjunctive names are formed by formal joining the component names without expressing a loss of atoms from any component
(e.g., indole-3-acetic acid, butane-1,4-diamine, 2,2‚-bipyridine).
4 Additive names
To the name of a parent compound a additive prefix or a group name is added
(e.g., tetrahydronaphthalene, homocysteine, styrene oxide).
5 Subtractive names
Subtractive prefixes express taking some atoms or groups away from the parent compound
(e.g., dehydroascorbate, 2-deoxyribose, demethylmorphine, noradrenalin).
6 Replacement names express an exchange of a group of atoms for a different atom or group; these names are nor very frequent
(e.g., 6-azauracil, 3-oxapentan = diethyl ether).
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Functional class
Suffix
(only one is used) Prefix (when other groups
as substituents)
ACIDS carboxylic sulfonic
–oic acid (carboxylic, sulfonic)
carboxy- sulfo-
Acid anhydrides, esters, halides, amides, nitriles
ALDEHYDES
KETONES
–al, –carbaldehyde
–one
oxo-, formyl-
oxo-
ALCOHOLS, PHENOLS –ol hydroxy-
THIOLS –thiol sulfanyl-
AMINES 0 amino-
ETHERS 0 (R)oxy- (e.g. alkyloxy-)
SULFIDES 0 (R)sulfanyl-
NITRO compound 0 nitro-
HALOGEN compound 0 fluoro-, chloro- ….
Substitutive names - selected functional groups
The decreasing order of preference in assigning a substitutive name:
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Assigning a systematic IUPAC name to the compound(Generalities)
1 Assessing the functional class of the compound preliminarily and choosing the kind of name (substitutive, functional,...).
2 If a substitutive name seems to fit, deciding about the parent structure or chain
(in acyclic compounds, the parent chain contains – the majority of principal functions, – as many as possible multiple bonds, – alkyl substituents or groups not having their own suffixes, – the longest sequence of carbon atoms),
3 and assigning the name of hydrocarbon, adding the endings for the multiple bonds, numbering their positions,
4 adding the ending for the characteristic principal group(s),
5 assigning other substituents as prefixes and numerical locants, and listing them in the alphabetical order.
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Example:
CH3
Cl
C CH3
O
CH C
HO CH2 CH
1 The principal characteristic group is carbonyl (of a ketone); there are no cycles in the molecule, a substitutive name will fit.2 The parent "straight" chain has 6 carbons.3 The hydrocarbon is hexane with one double bond in position 3, then hex-3-ene.4 The characteristic group is carbonyl (of a ketone) in position 2 → hex-3-en-2-one.5 The other substituents (in alphabetical order) are 3-chloro, 6-hydroxy, and 5-methyl. The configuration on the double bond is cis- (= Z).
The substitutive name is
3-chloro-6-hydroxy-5-methyl-cis-hex-3-en-2-oneor (Z)-3-chloro-6-hydroxy-5-methyl-hex-3-en-2-one.
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Hydrocarbons are classified as
– acyclic (aliphatic) saturated alkanes (only single bonds), and
unsaturated alkenes and alkynes (with multiple bonds, including also polyenes);
both types may exist as unbranched ("straight" chain)and branched molecules;
– cyclic hydrocarbons are either saturated and unsaturated cycloalkanes or
with the "aromatic" system of conjugated double bonds – arenes.
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AlkanesAll alkanes fit the general molecular formula CnH2n + 2 .
Alkanes with carbon chains that are unbranched forma homologous series (each member of this series differs fromthe next higher and the next lower memberby a methylene group –CH2–..
The first eight unbranched alkanes:
Name Number of carbons Molecular formulaNumber of branchedstructural isomers
MethaneEthanePropaneButanePentaneHexaneHeptaneOctane
12345678
CH4
C2H6
C3H8
C4H10
C5H12
C6H14
C7H16
C8H18
0 0 0 1 2 4 817
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The names for branched alkanes
1 The root name is that of the longest continuous chain of carbon atoms.
2 The groups (alkyls) attached as branches to the main chain are taken as
substituents.
3 The main chain is numbered in such a way that the first substituent encountered along the chain receives the lowest possible number. The names of the substituent groups (with the numerical locants) are placed before the name of the parental structure in the alphabetical order.
4 The names of substituted substituents are enclosed in parenthesis.
Examples:
CH3
CH3–CH2–CH2–CH–CH–CH2–CH2–CH3
CH3–CH2–CH2 CH–CH3
4-propyl-5-(2-propyl)octane3-methylhexane
CH3–CH–CH2–CH2–CH3
CH2–CH3
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The names of substituting groups
Alkyls are derived from alkanes by removing one of the hydrogens:
CH3– CH3-CH2– CH3-CH2-CH2–
methyl ethyl 1-propyl 2-propyl (isopropyl)
CH3 CH3
CH
Alkylenes are divalent groups:
–CH2– –CH2-CH2– CH3-CH2-CH2–
– CH2-CH2-CH2–
methylene ethylene propylene propan-1,3-diyl (ethan-1,2-diyl) (propan-1,2-diyl)
Alkylidenes are also divalent groups but bothhydrogens removed from the same carbon atom:
CH3-CH= CH3-CH
ethylidene ethan-1,1-diyl
Methene (or methenyl)–CH= occurs as a bridgein tetrapyrrols (e.g. haem)and tetrahydrofolate
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Reactions of alkanes
All the bonds in alkanes are single, covalent, and nonpolar; hencealkanes are relatively inert.Alkanes ordinarily do not react with most common acids, bases, oroxidizing and reducing agents.
1 Oxidation and combustionAlkanes are resistant to most common oxidants (at high temperature,the primary carbon atoms give acetic acid).
With excess oxygen, alkanes burn to form CO2 and water → fuels.If insufficient oxygen is available for complete combustion,partial oxidation may occur → carbon monoxide CO, carbon (soot).
2 Substitution reactions Chlorination and other halogenations (at high temperature or insunlight) give alkyl halides (e.g. solvents, alkylating agents,chlorofluoroalkanes).
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Cycloalkanes
are saturated hydrocarbons that have at least one ring of carbon atoms.Cycloalkanes react in the similar way as alkanes.
Cis-trans isomerism occurs when at least two substituents are attachedto the ring structure.
CH2
CH2
CH2
CH2
H2C
H2C
cyclohexaneC6H12
cyclopropaneC3H6
cyclobutaneC4H8
cyclopentaneC5H10
CH3
CH2CH3
1-ethyl-2-methylcyclopentane
X
X
X
X
X
X
trans- (a,a) cis- (e,e) cis- (a,a)
Monocyclic cycloalkanes
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Polycyclic cycloalkanes
bicyclopropane
Isolated rings Spirans(one carbon atom common to two rings)
spiro[4,5]decane
adamantaneC10H16
H
H
H
Hdecalin bicyclo[4,4,0]decane
(decahydronaphthalene) trans-decalin cis-decalin
Two or more carbon atoms common to two or more ringsFused ring systems
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menthane
CH3 CH3
CH3
CH
CH2
CH3
CH3
CH3 CH3
≡
bicyclo[2,2,1]heptane bornane bicyclo[3,2,1]octane
Numerous naturally occurring compounds contain fused ring systems
Carbon skeleton of steroid compounds
Sterane C17H28
(cyclopentanoperhydrophenanthrene)
Terpenes of plants are very oft derivatives of cycloalkanes, e.g.
CH3CH3
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Alkenes and alkynes
Alkenes contain a carbon-carbon double bond (alkadienes two,alkatrienes three, polyenes many double ponds).Alkynes are hydrocarbons with a carbon-carbon triple bond.
Both of these classes of hydrocarbons are unsaturated; alkanescan be obtained from alkenes or alkynes by adding one or two moleculesof hydrogen.
CH3 CH3C CH
H
H
H+ H2
The carbon-carbon double bond consists of one σ bond and one π bond.
C CHH
H H
The rotation round double bonds is restricted.
Double bonds are very polarizable structures:
C C C C C C
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When two or more multiple bonds are present in a molecule, therelative positions of the multiple bonds are important:
–C=C–C–C=C– isolated (nonconjugated) double bonds,
–C=C–C=C– conjugated double bonds,
–C=C=C– cumulated double bonds.
If there are conjugated multiple bonds or multiple bonds conjugated withnonbonding (unshared) electron pairs in the molecule, the π electronsof the multiple bond(s) as well as conjugated unshared electron pairsare spread over such a system in a delocalized molecular π orbital.Such structures are called resonance hybrids.
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Alkenes - the names of substituting groups
Alkenyls are derived from alkenes by removing one of the hydrogens:
CH2=CH– CH3-CH=CH– CH2=CH–CH2–
vinyl 1-propenyl 2-propenyl ( not ethenyl! ) allyl
Alkenylenes are divalent groups:
–CH=CH– CH2=CH
vinylene vinylidene ethen-1,2-diyl ethen-1,1-diyl
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Reactions of alkenes and of other compounds that containa carbon-carbon double bond:
1 Addition is a most common reaction
addition of H2 (hydrogenation) → alkanes
addition of halogens (e.g. Br2) → dibromoalkanes
addition of hydrogen halides (e.g. Cl2) → chloroalkanes
addition of water → alcohols
polymerization
2 Oxidation → alkandiols (glycols) → oxidative cleavage at the site of double bond
(to a carbonyl compound and an acid) → ozonides that also undergo the cleavage
3 Substitution is possible but not for hydrogens attached directly to the unsaturated carbons.
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Aromatic hydrocarbons - arenes
Aromatic benzene ring
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Due to the molecular π orbital (resonance hybrid),benzene ring does not behave as unsaturated compounds:
– additions don't occur readily,
– benzene ring resists to oxidation,only fused rings (naphthalene, anthracene, etc.) can beoxidized easily, as well as side chains on the rings, ifthey are present.
The most common reactions are electrophilic substitutions:
nitration,sulfonation,
halogenation,alkylation, andacylation.
+ X+ X+
X
H+
X
+ H+
-complex -complex
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Benzene ring has an electronegative influence on substituentsattached to the ring.
Polarization of the ring occurs due to directing influence of thesubstituents present on the ring.
IOI H
- -
-
X+
X+X+C
H OI
- -
X+ X+
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CH3
toluene
CH3
CH3
o-xylene
CH CH2
styrene
CH2-CH3
ethylbenzene
Monocyclic arenes
Polycyclic aromatic hydrocarbons
biphenyl difenylmethan
CH2 CH CH
stilbene(1,2-diphenylethene)
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naphthalene anthracene naphthacene
Linear fusion of aromatic rings:
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is one of the most potent carcinogens; the metabolic oxidation to a diol-epoxide andother products seems to be a real culprit incausing cancer.
phenanthrene
pyrene benzo[a]pyrene
Polynuclear aromatic hydrocarbons (PAH)
e.g.
Angular fusion of aromatic rings:
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Names of substituting groups
Aryls
CH2
Phenylalkyls, phenylalkylenes, phenylalkylidenes, etc.
benzyl
CH benzylidene
phenyl
CH34-tolyl(p-tolyl)
1,2-phenylene(o-phenylene)
Arylenes, e.g.
1
2
1-naphtyl(α-naphtyl)
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Alcohols and phenols
Hydroxy derivatives of hydrocarbons
Alcohols R–OH – a hydroxyl is attached to an alkyl group(alcoholic hydroxyl)
Phenols Ar–OH – a hydroxyl is attached directly to an aromatic ring (phenolic hydroxyl);because of the electronegative influence of an aromaticsystem, the properties of phenolic hydroxyls differ from thehydroxyls of alcohols.
Their functional group is the hydroxyl group –OH .
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AlcoholsNomenclature
The ending –ol (-diol, -triol, etc.) is added to the name of thehydrocarbon in the IUPAC substitutive names.
In alternative functional names, the separate word alcohol is placedafter the name of the alkyl group.
HOH
methanol propan-2-ol prop-2-en-1-ol cyclohexanol (methyl alcohol) (isopropyl alcohol) (allyl alcohol) (cyclohexyl alcohol)
CH3–OH CH3-CH-CH3 CH2=CH-CH2–OH
OH
CH2–OH
CH2–OHCH2–OH
CH–OH
CH2–OH
ethan-1,2-diol propan-1,2,3-triol(ethylene glycol) (glycerol)
OH OH
OH
OH
OH
HO
cyclohexan-1,2,3,4,5,6-hexaol(myo-inositol)
OHOH
OHHOHO
OH
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Alcohols are classified as primary, secondary, or tertiary,depending on whether the hydroxyl-bearing carbon is the primary, secondary, or tertiary carbon atom:
R–CH2-OH –CH2-OHprimary alcohol primary alcoholic group
secondary alcohol secondary alcoholic group
tertiary alcohol tertiary alcoholic group
CH-OHR
RCH-OH
C–OHR
R
C-OHR
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General properties of alcohols
Polarity of the hydroxyl group –O H
Nucleophilic atom of oxygen –O–H that enables – alkylation of alcohols to ethers, – acylation of alcohols to esters, – addition of alcohols to carbonyl compounds
results in hemiacetals
Elimination of water (dehydration) to alkenes
Oxidation (dehydrogenation) aldehydes or ketones
1
2
3
4
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O
H
HO
R
HO
R
HO
R
H
O
H
HO
H
H
O
R
H
hydrogen bridges
1 Polarity of alcohols
The lowest three alcohols (C1 - C3) are miscible with water entirely;the hydrophilic character of alcohols decreases with the increasing lengthof their aliphatic chain (and increases with the number of hydroxyl groups.Water-soluble alcohols form clusters connected through hydrogen bonds.
In the presence of water, alcohols are neutral compounds.However, anhydrous alcohols exhibit very weak acidity to alkali metalsand react with them to give unstable alkoxides (alcoholates), e.g.
CH3-OH + Na CH3-O– Na+ + ½H2
sodium methoxide
R-O– Na+ + H2O R–OH + Na+ + OH–
When even traces of water are present, alkoxides are readily hydrolyzedto alcohols and an alkali hydroxide:
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diethyl etherethanol
+ H2OCH3
OCH2
CH2CH3CH3 CH2 OH
CH3 CH2 OH
H2SO4
(140 °C)
Nomenclature: Simple ethers are named by giving the name of eachalkyl or aryl group followed by the word ether. Sometimes it may benecessary to name the –O-R group as an alkoxy group.E.g., CH3CH2–O–CH3 ethyl methyl ether, alternatively methoxyethane.
Ethers are colourless compounds with lower boiling temperatures thanalcohols with an equal number of carbon atoms.Ethers are relatively inert compounds, excellent hydrophobic solvents.
2 /1 Alkylation of alcohols produces ethers
To make symmetric ethers, primary alcohols are heated with H2SO4:
One of the usual methods is the alkylation of sodium alkoxides byan alkyl halide:
R–O– Na+ + R´–Cl R–O–R´ + Na+Cl–
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diethyl peroxide(explosive) diethyl ether hydroperoxide
CH3CH2 CH2CH3
O O2, light
OOH
CH3CH CH2CH3
OCH3CH2 O
O CH2CH3heating
O
O
1,4-dioxan
O
tetrahydropyran
O
oxiran(ethylene oxide)
tetrahydrofuran
O
(oxolan)
CH3CH2O
CH2CH3
diethyl ether
OH
O–CH3
guaiacol guaiaphenesine(analgesic myorelaxant)
O–CH2–CH–CH2
OH OH
O–CH3
OCH3
methyl phenyl ether (anisol)0
O
diphenyl ether
Diethyl ether is used as an solvent. The use ofether as an anaesthetic administered by inhalationis rather limited at present because of its highflammability and some undesirable side effects..
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2 /2 Acylation of alcohols gives rise to esters
R–C
O
OH+ R' OH
H+
+ H2O
esteralcoholcarboxylicacid
–R´R–C
O
O
Esters of inorganic acids
Alcohols can form esters by using acylating agents such as acidanhydrides or acyl halides. In the presence of small amounts of a strong acid, esterificationof alcohols by carboxylic acids is possible:
Alcoholic and phenolic hydroxyls may also take part in formation ofester bonds with different inorganic acids.From biological point of view, the most important inorganic estersare esters of phosphoric, sulfuric, nitric, and nitrous acids.
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H3PO4O
OH
HO–P–OH
Phosphate esters
Phosphorylated sugars (intermediate metabolites)PhospholipidsNucleotides, nucleoside triphosphates, and nucleic acids
(with phosphodiester bonds)Phosphorylated proteins (side chains of Ser, Thr, and Tyr,
phosphorylation as an important regulatory principle)Organophosphate insecticides and nerve gases
CH–OH
CH=O
CH2–O– PO 32–
Examples:
glyceraldehyde 3-phosphate
D-glucose 1-phosphate ATP (adenosine triphosphate
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anionic tenside sodium dodecyl sulfate (SDS, sodium lauryl sulfate)
O
O–S–O
O
Na
O
O
HO–S–OHH2SO4Esters of sulfuric acid (sulfate esters)
alcohol + sulfuric acid(alkyl hydrogen sulfate)
alkyl sulfate dialkyl sulfate
+ ROH – H2O+R OH HO S OH
O
O
S OH
O
O
OR– H2O
S O
O
O
OR R
Sulfate esters of sugarsin glycosaminoglycans
Sulfate esters of phenols indetoxification or in inactivationof phenolic hormones
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R–OH + HO–NO2 R–O–NO2 + H2O
Esters of nitric and nitrous acid (organic nitrates)
glycerol trinitrate ("nitroglycerin",glyceroli trinitras), a vasodilator and
a known explosive
CH2–O–NO2
CH–O–NO2
CH2–O–NO2
isosorbide dinitrate (isosorbidi dinitras)
O
OO2N–O
O–NO2
HNO3O
HO–N(+)
O(–)
C
OCH2
CH2O
CH2O
OCH2
NO2
O2N
O2N
NO2
pentaerythritol tetranitrate
HNO2HO–N=O
alkyl nitrate
CH3
CH3
CH–CH2–CH2–O–N=O
isopentyl nitrite (amyl nitrite)
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Don't confuse
alkyl sulfate (an ester, sulfated alcohol)
O
O
R–O–S–O
O
O
R–S–O
alkanesulfonate(a sulfonated alkane)
with
or
with R–NO2R–O–N=O and R–O–NO2
alkyl nitrite and alkyl nitrate (esters of alcohols)
nitroalkane(a nitrated alkane)
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2 /3 Hemiacetals or hemiketals are products of addition of alcohols to carbonyl compounds
a hemiacetal (1-alkoxyalkan-1-ol)
H
R-OH + R´–CO
R´–C–O-R
H
OH
This addition is of particular importance in chemistry ofmonosaccharides, which form intramolecular hemiacetals –
cyclic forms of monosaccharides.The reaction is also included among the reactions of carbonyl.
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3 Elimination of water from alcohols gives alkenes
Don't confuse dehydration (elimination of water) withdehydrogenation (oxidation by taking off two atoms of hydrogen!
Alcohols can be dehydrated by heating them with a strong acid.E.g., when ethanol is heated at 180 °C (i.e. at higher temperaturethat is required for preparation of diethyl ether):
etheneethanol
+ H2OCH2CH2CH2 CH2
OHH
H+
(180 °C)
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4 Oxidation (dehydrogenation) of alcohols
CH3-CH2–OH + NAD+ + NADH + H+ CH3 C
H
alcohol dehydrogenaseO
R C
O
OH
R C
O
H
R CH2 OH
carboxylic acidaldehydeprimary alcohol
½ O2 – 2H
+ 2H
– 2H
+ 2HCH OH
R
R´
secondary alcohol
R´O
Rketone
C
Tertiary alcohols do not undergo this type of oxidation.
In the reaction catalyzed by alcohol dehydrogenase, NAD+ is the acceptorof hydrogen atoms:
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Alcohols with more than one hydroxyl group are oxidized similarly.
For example, the stepwise oxidation of dihydric alcohol ethylene glycol:
Oxidation of glycerol:
ethylene glycol
CH2-OH
CH2-OH.oxid. .oxid.
glycolaldehyde
CH2-OH
CH=O
CH=O
CH=Oglyoxal
glycolic acid
CH2-OH
COOH
oxid.
oxid.
oxid.
oxid.
glyoxylic acid
CH=O
COOH
oxalic acid
COOH
COOH
.oxid.
glycerol
CH2-OH
CH-OH
CH2-OH oxid.
oxid.
dihydroxyacetone
CH2-OH
C=O
CH2-OH
glyceraldehyde
CH=O
CH2-OH
CH-OH
glyceric acid
CH2-OH
COOH
CH-OH
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Enols represent a particular type of hydroxy derivatives.In spite of their ability to form esters like alcohols and their slightacidity (like phenols), they are tautomeric formsof carbonyl compounds:
the enol form the oxo form (keto form) of a carbonyl compound
OHC C C
OC
H
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PhenolsPhenolic hydroxyl is the hydroxyl group that is attached directly to an aromatic ring (a benzene ring or a pseudo aromatic ring of maximally unsaturated heterocycles).
Alcohols and phenols have many similar properties. However, because of the electronegative influence of an aromatic system, the properties of phenolic hydroxylsdiffer in some features from those of alcoholic hydroxyls:
– Phenols are weak acids mainly because the corresponding phenoxide (phenolate) anions are stabilized by resonance.
– Phenols with a sole hydroxyl cannot be oxidized easily, but o- and p-diphenols are dehydrogenized readily to quinones..– Phenols undergo aromatic ring substitution under very mild conditions.
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Nomenclature of simple phenols:
Monohydric phenols
Diphenols
Triphenols
OH
phenol
OH
CH3
o-cresol
OH
OH
OH
pyrogallol(benzene-1,2,3-triol)
HO
OH
OH
phloroglucinol(benzene-1,3,5-triol)
OH
OH
resorcinol(benzene1,3-diol)
OHOH
pyrocatechol(benzene-1,2-diol)
HO
OH
hydroquinone(benzene-1,4-diol)
HO
OH
OH
hydroxyhydroquinone(benzene-1,2,4-triol)
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Dehydrogenation of o- and p-diphenols
benzene-1,2-diol 1,2-benzoquinone benzene-1,4-diol 1,4-benzoquinone (pyrocatechol) (hydroquinone)
OH
OH
– 2H
O
O
+ 2H
– 2H
+ 2H
OH
OH
O
O
O
O
CH3O CH3
R(isoprenoid chain)
ubiquinone (coenzyme Q)
CH3O
ortho- and para-quinoid systems
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OH
CH3
C(CH3)3(CH3)3C
BHT(t-butylated hydroxytoluene)
antioxidant, food additive
thymol
CH3
CH3
OH
CH3
OH CH3CH3
CH3 CH3
propophol(2,6-diisopropylphenol)
ultra-short intravenous hypnotic
O
HO
isoprenoid chain
α-tocopherol(vitamin E)
CH3
CH3
CH3
CH3
O
R
O
CH3
1,4-naphtoquinone(active part of vitamin K)
(isoprenoid chain)
Examples of phenolic compounds:
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C6H5–SH thiophenol CH3–S–CH2-CH2-CH2–OH 3-methylthiopropan-1-ol
Thiols (thioalcohols and thiophenols)
a thiol R–SH a thiophenol a dialkyl sulfide R–S–R´SH
an alcohol R–OH a phenol an ether R–O–R´OH
are the sulfur analogs of alcohols and phenols:
The –SH group is called the sulfanyl group (formerly also the sulfhydryl or mercapto group).
Nomenclature:
HS–CH2-CH2-CH2–SH propane-1,3-dithiol CH3–S–CH2-CH2-CH3 methyl propyl sulfide
CH3-CH2-CH2–SH propane-1-thiol CH3–S–CH3 dimethyl sulfide
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Properties of thiolsPerharps the most distinctive feature of thiols is their intense and disagreeable stench (e.g., butenethiol responsible for the odour of skunk or fitchew, diallyl disulfide responsible for the odour of fresh garlic).
Some properties of thiols resemble those of alcohols because of the small difference in the electronegativity of sulfur and oxygen; nevertheless, thiols differ from alcohols in being slightly acidic and easily oxidable.
1 Thiols are very weak acids (e.g., pKA of ethanethiol is 10.6) that form thiolates in alkaline solutions. Because of their ability to bind readily some toxic cations, particular thiols serve as antidotes in, e.g., mercury or lead poisoning (the former name for thiols were mercaptans from "mercury captans").
2 Similarly to alcohols, thiols give dialkyl sulfides by alkylation, thioesters by acylation, and hemithioacetals by addition to carbonyl compounds.
3 Thiols are very easily oxidized (dehydrogenized) by mild oxidation agents to disulfides.
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(Formation of disulfide bridges in proteins)
– 2H
+ 2HNH2
2 HS–CH2–CH–COOH
cysteine
HOOC–CH–CH2–S–S–CH2–CH–COOH
NH2NH2
cystine
Oxidation of thiols and sulfides
Mild oxidizing agentsdehydrogenize two molecules of thiols to dialkyl disulfides:
thiol dialkyl disulfide
2 R–SH– 2H
R–S–S–R+ 2H
Example:
Oxidation of thiols and sulfides by strong oxidation agents:
R–SH R–SO2H R–SO3–H+
–II IV VI
alkanethiol alkanesulfinic acid alkanesulfonic acid
dialkyl sulfide dialkyl sulfoxide dialkyl sulfone
R–S–R´ R–SO–R´ R–SO2–R´–II IV VI
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Thiols with their oxidable sulfanyl groups act in living systems asimportant reducing agents (e.g. tripeptide glutathione, G–SH).
On the other hand, lipoic acid (a disulfide) acts as an oxidant;it accepts hydrogen atoms in the course of oxidative decarboxylationof α-ketoacids:
dihydrolipoic acidSHSH
COOH
lipoic acid (an oxidant)
SS
COOH + 2H
- 2H
Examples of other important sulfur containing compounds in living systems:
Coenzyme A is a thiol that transfers acyls in the form of thioesters
Coenzyme A–SH + HOOC–R Coenzyme A–S–CO-R + H2O
Taurine, aminoethanesulfonic acid H2N–CH2-CH2–SO3H forms amides with bile acids secreted from the liver cells.
Methionine, an essential amino acid, is a sulfide in its side chain that servesas a donor of the methyl group: HOOC–CH-CH2-CH2–S–CH3
NH2
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Aldehydes and ketones
Carbonyl compounds
Their functional group is the carbonyl group C=O
Aldehydes have at least one hydrogen atom attached to the carbonyl group.
–CH
O
aldehyde group formaldehyde aliphatic aldehyde aromatic aldehyde
H–CH
OR–C
H
OAr–C
H
Oor –CH=O
In ketones, the carbonyl carbon atom is connected to two othercarbon atoms:
aliphatic ketone alkyl aryl ketone aromatic ketone alicyclic ketone
R–CR´
OR–C
Ar
OAr–C
Ar
OC=O
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Nomenclature
The characteristic ending for aldehydes is –al ; for cyclic aldehydes, the suffix –carbaldehyde is used:
CH=O
ethanal 3-butenal benzenecarbaldehydeacetaldehyde benzaldehyde
–CH
OCH3 –C
H
OCH2=CH–CH2
The ending for ketones is –one ; if there is another preferred groupin the molecule, the presence of carbonyl is expressed by usinga prefix oxo- (or keto- in common names).
=OCH3–C–CH2-CH3
O O
–C–CH3
O
CH3–C–CH2–COOH
2-butanone cyclohexanone methyl phenyl ketone 3-oxopropanoic acidethyl methyl ketone acetophenone (β-ketobutyric acid)
acetoacetic acid
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Some reactions of carbonyl compounds
Polarity of the unsaturated carbonyl group – tautomerization (oxo-forms and enol-forms exist); – additions to a carbonyl group: addition of water → labile hydrates, addition of an alcohol → hemiacetals or hemiketals, addition of ammonia or an amine → unstable adducts
that eliminate water to give aldimines or ketimines.
Oxidation of aldehydes to carboxylic acids.
Aldol "condensation" of two molecules (in slightly alkaline solutions) gives aldols; in acidic solutions, aldehydespolymerize.
1
2
3
C=O
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the keto form of acetone the enol form of acetone (0.0003 %)
C=OCH3
CH3
CH2
CH3
C–OH
R–CH
O+ H2O
aldehyde aldehyde hydrate
HR–C
OHOH
1 /1 Tautomerism of carbonyl compounds
If a carbonyl compound has a hydrogen atom attached to the carbonatom adjacent to the carbonyl group (α-carbon atom), it may exist inan enol form:
Most simple aldehydes and ketones exist mainly in the keto form.
1 /2 Addition of water – hydration of aldehydes and ketones
In water, carbonyl compounds can add reversibly water molecules andexist as their hydrates. The hydrates of most aldehydes and ketones cannot be isolated because they readily lose water to reform the carbonylcompound.
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In acetals, the original hemiacetal hydroxyl is replaced by analkoxy group (–O-R) of an alcohol.
An acetal can be hydrolyzed to its aldehyde or ketone and alcohol components in the presence of an acid; in alkaline solutions, the acetal bond resist hydrolysis.
condensation
addition
R–CH
O+ HO–R´
aldehyde hemiacetal acetal (1-alkoxyalkan-1-ol) (1,1-dialkoxyalkane)
HR–C
OHO–R´ + HO–R´
– H2O HR–C
O–R´O–R´
1 /3 Addition of alcohols gives hemiacetals,
that can react further to form acetals
Ketones react in the same way; the products are sometimes calledhemiketals and ketals.
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Monosaccharides are aldehydes and ketones that have in their molecules appropriately located hydroxyl groups, and thereforethey may form intramolecular cyclic hemiacetals,cyclic forms of monosaccharides (pyranoses or furanoses)..In aqueous solution, both acyclic and cyclic forms of monosaccharidesexist in equilibrium; in most hexoses and pentoses the cyclic hemiacetal form prevails.
the hemiacetalhydroxyl group
a hexose(acyclic aldehyde)
a hexopyranose(cyclic hemiacetal form)
The hemiacetal hydroxyl group of cyclic forms can react with varioushydroxy derivatives to give acetals. Those acetals are called glycosidesand the acetal linkage is called glycosidic bond.
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1 /4 Addition of primary amines or ammonia results in
formation of aldimines (Schiff bases)
R–CH
O+ H2N–R´
aldehyde
HR–C
OHNH–R´ – H2O
labile adduct is stabilized by elimination of water aldimine (Schiff base)
HR–C
NH
addition
Ketones react in the same way, their Schiff bases are ketimines.
Other ammonia derivatives containing an –NH2 group (e.g. hydroxylamine or hydrazine) react with carbonyl similarly to primary amines.
Imines are important intermediates in some biochemical reactions,e.g. in enzyme-catalyzed transamination of amino acids and α-ketoacids, or in undesired non-catalyzed reaction of proteins withmonosaccharides (glycation of proteins).
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2 Oxidation of aldehydes to carboxylic acids
C=OCH3
CH3
CH3-COOH + H-COOHKMnO4
Ketones can be oxidized only by strong oxidants and this oxidation result in splitting the carbon chain:
Oxidation of aldehydes to carboxylic acids with the samenumber of carbon atoms occurs very easily.Therefore, in contrast to ketones, aldehydes arereducing agents.
R–COH
OR–C
H
O oxidation
Both aldehydes and ketones are readily reduced toprimary and secondary alcohols.
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3 Aldol condensation
+OH–
acidic Hon α-carbon
carbanion β-aldol(3-hydroxyaldehyde)
An example of the reversible aldol condensation:In the synthesis of glucose from pyruvate (gluconeogenesis),glyceraldehyde 3-phosphate and dihydroxyacetone phosphateundergo aldol condensation to fructose 1,6-bisphosphate.In glycolysis, fructose 1,6-bisphosphate is split into glyceraldehydephosphate and dihydroxyacetone.The enzyme aldolase catalyzes the reaction in both directions.
Aldehydes and ketones that have a hydrogen atom on theα-carbon can add to the carbonyl group of another aldehyde orketone molecule. This aldol "condensation" forms new C–C bonds.
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Various examples of carbonyl compounds – important in biochemistry
vanillin
OH
CH=O CH=O
OH
salicylaldehyde
O
O
1,4-benzoquinone
CH=O
benzaldehyde
dihydroxyacetone
CH2-OH
C=O
CH2-OH
glyceraldehyde
CH=O
CH2-OH
CH-OH
CH3-CH=O
acetaldehyde
O=CH–CH2–CH=O
malondialdehyde
Monosaccharides are polyhydroxyaldehydes or polyhydroxyketones;the most simple of them are
α-Ketoacids (e.g. pyruvate, oxaloacetate, and 2-oxoglutarate) are intermediatemetabolites of saccharides and amino acids.
CH3–CO–CH3
acetone