Organic Chemistry
A-Levels H2 CHEMISTRY
FORMULAE
Compound
2-methylhex-3-ene
3-methylpentanoic acid
3-nitrophenol
CH2
C3H6O
C6H5NO3
C7H14
C6H12O2
C6H5NO3
CH3CH(CH3)CHCHCH2CH3
CH3CH2CH(CH3)CH2COOH
or
or
Type of formulae
Empirical formula
(Ratio of the number of atoms of each element present in one
molecule)
Molecular Formula
(Actual number of atoms of each element present in one
molecule)
Structural Formula
(Shows how the constituent atoms of a molecule are joined
together)
H3 C
Displayed Formula/ Full Structural Formula
(Shows all bonds and atoms in a molecule)
H
CH3 H
H
CH C
C CH2 CH3
H3C CH2 CH CH2 COOH
H
H
H
H
H
H
C
C
C
C
C
C
H
H
HH C
H
H
OH
O2N
CH3
H
H
H
H
H
H
C
C
C
C
H
H
H C
H
H
H
O
O
C
O
H
H
O
N
O
In writing displayed formula for ring structures,
is the convention for representing benzene, C6H6
is acceptable for cyclohexane, C6H12
Page 2
ISOMERISM
Structural Isomerism
(exhibited by substances with
the same molecular formula but
different structural formula)
Stereoisomerism
(exhibited by substances with the same
attachment of atoms to each other but
different spatial arrangement)
Functional Group Isomerism
(same molecular formula, different
functional groups)
H3C CH2 OH
alcohol
H3C
O
Geometric Isomerism (cis-trans)
(caused by restriction of rotation of
double bond or ring)
CH3
•
ether
Positional Isomerism
(same molecular formula, different
positions of the functional group)
Found in alkenes when the two
groups attached to each of the two
carbons in the double bond are
different.
Br
1-brom opr opane
H 3C
CH
Br
C
Br
H 3C C H 2 C H 2 B r
Chain Isomerism
(same molecular formula, skeletal chain)
H
•
H
B u t a n -1 -o l
C
Br
C
Br
trans-isomer
Double bonds in a ring do not have
geometric isomers as there can only
be the cis configuration.
CH3
H 3 C C H 2 C H 2 C H 2 O H H 3C C H
CH3
H
C
cis-isomer
2-bromopr opane
Br
C
H
CH 3
Optical Isomerism
(present in molecules with no plane of symmetry; molecules
can exist as two non-superimposable mirror images)
Compounds with chiral carbons can exhibit optical isomerism
•
•
•
•
CH2 OH
2 -me th ylpropa n-1- ol
Total number of stereoisomers
n
2
where n = no. of chiral carbons + no. of C=C double bonds
which can exhibit geometric isomerism
•
•
OH
H
CH3
HO
H
C
Br
A compound that exhibits optical isomerism has two
enantiomers.
These enantiomers are non-superimposable mirror
images. Each mirror image is optically active and is able
to rotate plane-polarised light.
A racemic mixture which consists of the two enantiomers
in equal proportions, is optically inactive (does not rotate
plane-polarised light).
Enantiomers have the same physical properties except
for the direction in which they rotate plane polairsed light.
They have the same chemical properties except when
reacting with other chiral compounds.
Nucleophilic addition reactions of carbonyls and
Electrophilic addition reactions of alkenes can form
products that are racemic mixtures.
Page 3
Br2(l) in CCl4
SYNTHETIC ROUTES INVOLVING ALKANES & ALKENES
H
C
H
uv or heat
H
H
C
Cl
H
C
C
H
industrial method:
H2O(g), 300 ºC, 60 atm, conc. H3PO4
ethanolic KOH (or NaOH)
H
H
heat
Br
H
C
H
C
laboratory method:
conc. H2SO4 followed by H2O(l), warm
C
H
C
H2(g) / Ni catalyst
170 ºC
H
150 ºC
OH
Reduction or addition
conc. KMnO4 / H2SO4
heat
H
H
C
conc. KMnO4 / H2SO4
H3C
H3C
C
conc. KMnO4 / H2SO4
Oxidation (oxidative cleavage)
H
industrial method:
H2O(g), 300 ºC, 60 atm, conc. H3PO4
HO
laboratory method:
conc. H2SO4 followed by H2O(l), warm
O
CH3 CH3
H
H3C
H3C
H3C
C
heat
cold, dil. KMnO4 / NaOH(aq)
CO2(g) + H2O(l)
C
heat
C
Br
Br
H
H
C
C
Br
OH
H
H
C
C
H
OH
H
H
C
C
H
H
H
H
C
C
H
H
C
C
H
OH
H
H
OH OH
CH3
CH3 CH3
C
HBr(g)
H3C
H
CH3
C
O
H
Electrophilic addition
ethene
excess conc. H2SO4
H
H
oxidation
H
H3C
H
H
C
Elimination
H
H
H
Electrophilic addition
H
H
C
Br2(aq)
Free radical substitution
H
methane
H
H
limited Cl2(g)
H
H
Electrophilic addition
H
CH3
2-methylbut-2-ene
Electrophilic addition
H
C
C
H
Br
CH3
Ethanedioic acid (HOOC-COOH) can be further oxidised to CO2 and H2O.
Page 4
SYNTHETIC ROUTES INVOLVING BENZENE AND METHYLBENZENE
CH3
CH3
NO2
conc. HNO3 / conc. H2SO4
30 ºC
Electrophilic substitution
Br2(l) / FeBr3
Br
NO2
Electrophilic substitution
CH3
CH3
CH3
CH3Cl / AlCl3
Br2(l) / FeBr3
benzene
Br
or Br2(l) / Fe(s)
Electrophilic substitution
methylbenzene
Electrophilic substitution
conc. HNO3 / conc. H2SO4
Br
NO2
60 ºC
nitrobenzene
Electrophilic substitution
CH2Cl
May have multiple substitution at
higher temperature
Reduction
1. Sn / conc. HCl, heat
Free radical substitution
limited Cl2(g)
uv or heat
2. NaOH(aq)
NH2
Oxidation
COOH
KMnO4 / H2SO4(aq) with heat
benzoic acid
phenylamine
or 1) KMnO4 / NaOH , heat
2) Acidify with H2SO4 (aq)
Page 5
SYNTHETIC ROUTES INVOLVING HALOGENOALKANES
CH3
NaOH(aq)
CH3
H
C
H
H
heat
Br2(l)
C
Nucleophilic substitution
OH
H
uv or heat
Free radical substitution
H
H
H
ethanolic NaOH
heat
CH3
H
H
C
HBr(g)
H
C
H
H
C
C
H
Br
H
CH3
bromoethane
Nucleophilic substitution
concentrated ethanolic NH3
H
C
heat in sealed tube
NH2
H
Substitution
CH3
Elimination of 2-chlorobutane can
produce 3 alkenes – but-1-ene,
cis but-2-ene and trans but-2-ene
elimination
H
Electrophilic addition
C
PBr3
H
C
H
OH
or NaBr with conc. H2SO4
(equivalent to HBr), heat
*If PCl5 is used to obtain the
chloroalkane, no heat is required*
Nucleophilic substitution
ethanolic KCN
H
heat
Reduction
CH3
C
CN
CH3
LiAlH4 in dry ether
Or
H2, Ni (high T,P)
H
H
CH3
H
C
COO Na
H
+ NH3
C
CH2NH2
H
Hydrolysis
Hydrolysis
NaOH(aq)
H2SO4(aq)
heat
heat
CH3
H
C
COOH
H
+ NH4+
Page 6
SYNTHETIC ROUTES INVOLVING PRIMARY ALCOHOLS
Other chlorinating reagents: SOCl2, PCl3, HCl with ZnCl2
CH3
H
C
Cl
CH3
H
PBr3
Electrophilic addition
H
H
C
C
industrial method:
H2O(g), 300 ºC, 60 atm, conc. H3PO4
PCl 5 (s)
r.t.
C
Br
H
CH3
PI3
H
heat
substitution
laboratory method:
conc. H2SO4 followed by H2O(l), warm
H
H
Other brominating reagent: NaBr with conc. H2SO4 (equivalent to HBr),
heat
C
I
H
H
O
K2Cr2O7 / H2SO4
CH3
H
C
H
H
reduction
LiAlH4 in dry ether
O
H3C
or NaBH4
C
H
CH3
heat
X = Cl, Br or I
C
oxidation
NaOH(aq)
X
H3C
heat with immediate distillation
Nucleophilic substitution
C
OH
O
K2Cr2O7 / H2SO4 or KMnO4 / H2SO4
H3C
heat
H
ethanol
OH
oxidation
or H2 / Ni, high T, P
elimination
H
H
excess conc. H2SO4
reduction
OH
Ethanol is the only primary
alcohol that undergoes
iodoform reaction
O
H
O Na
CH3COOH + conc. H2SO4 + heat
or CH3COCl or CH3COBr
CH3
+ CHI3
C
H
C
H
condensation
warm
C
I2(aq) / NaOH(aq)
H3C
LiAlH4 in dry ether
H
C
170 ºC
O
C
redox
H
C
H3C
C
O
Na(s)
oxidation
O
CH2CH3
O Na
H
Page 7
SYNTHETIC ROUTES INVOLVING SECONDARY ALCOHOLS
CH3
PCl 5
H
CH3
C
C
H
H
industrial method:
H2O(g), 300 ºC, 60 atm, conc. H3PO4
H
C
Other chlorinating reagents: SOCl2, PCl3, HCl with ZnCl2
Cl
CH3
laboratory method:
conc. H2SO4 followed by H2O(l), warm
CH3
PBr3
H
C
Other brominating reagent: NaBr with
conc. H2SO4 (equivalent to HBr), heat
Br
CH3
CH3
C
PI3
X
NaOH(aq)
I
C
CH3
CH3
heat
CH3
H
X = Cl, Br or I
LiAlH4 in dry ether
O
or NaBH4
C
OH
O
K2Cr2O7 / H2SO4 or KMnO4 / H2SO4
C
heat
CH3
H 3C
Orange K2Cr2O7 turned green
Purple KMnO4 decolourised
propan-2-ol
CH3
or H2 / Ni, high T, P
C
CH3
Only methyl alcohols,
–CH(OH)CH3, will undergo
iodoform reaction
I2(aq) / NaOH(aq)
H 3C
H
heat
H
or CH3COCl or CH3COBr
Na(s)
H
C
H3C
CH3
C
O
CH3
O Na
H
O
CH3COOH + conc. H2SO4 + heat
O Na
Tertiary alcohols cannot be oxidised.
C
H
+ CHI3
C
C
170 ºC
O
H3C
CH3
excess conc. H2SO4
warm
H
CH3
C
H
Elimination of butan-2-ol
can produce 3 alkenes –
but-1-ene,
cis but-2-ene and
trans but-2-ene
CH3
CH3
Page 8
SYNTHETIC ROUTES INVOLVING PHENOLS
OH
OH
Br2(l) in CCl4
O Na
Redox (Na)
Acid-base (NaOH)
Br
Electrophilic substitution
Na(s) or NaOH(aq)
Br
OH
OH
Phenol cannot react
with carboxylic acid
to form ester.
Phenol is a poor
nucleophile as the
lone pair on oxygen
is delocalized into
the benzene ring.
Electrophilic substitution
acid chloride RCOCl
or acid bromide RCOBr
Br
3Br2(aq)
Condensation
+ 3HBr
room temperature
Br
phenol
O
C
O
Br
R
acid chloride RCOCl
or acid bromide RCOBr
Electrophilic substitution
OH
OH
dil. HNO3(aq)
Condensation
NO2
OH
conc. HNO3
Electrophilic substitution
O2 N
NO2
NO2
Phenols cannot be oxidised.
NO2
Page 9
SYNTHETIC ROUTES INVOLVING ALDEHYDES
O
Oxidation
K2Cr2O7 / H2SO4 or KMnO4 / H2SO4
−
CH3COO + Ag (s)
H3C
C
heat
Note: Benzaldehyde gives negative results
with Fehling’s solution but gives positive
results with Tollen’s reagent on warming.
OH
Silver mirror or
grey ppt
CH3COO− + Cu2O (s)
Red ppt
H
C
LiAlH4 in dry ether
Tollen’s reagent
(also known as ammonical
silver nitrate)
Fehling’s solution
or NaBH4
C
OH
H
Oxidation
heat with immediate distillation
O
Oxidation
I2(aq) / NaOH(aq)
O
K2Cr2O7 / H2SO4
OH
H
or H2 / Ni
Oxidation
CH3
CH3
Reduction
H3C
C
warm
or
H
Condensation
2,4-dinitrophenylhydrazine
Orange ppt
H3 C
C
H
CH2NH2
LiAlH4 in dry ether
C
Nucleophilic
Addition
N
H
C
N
NO2
H
NaOH(aq)
heat
CN
H3C
Hydrolysis
or H2 / Ni, high T, P
NO2
OH
OH
H3C
Ethanal is the only
aldehyde that
undergoes iodoform
reaction
H3C
KCN + H2SO4
Reduction
Yellow ppt
O Na
HCN with trace KCN (or trace NaOH)
OH
CHI3
C
ethanal
H
H
+
C
COO Na
Acid-base
H
H
dil. NaOH(aq)
dil. H2SO4(aq)
OH
dil. H2SO4(aq)
heat
Hydrolysis
H3C
C
COOH
H
Page 10
SYNTHETIC ROUTES INVOLVING KETONES
H
LiAlH4 in dry ether
H3C
or NaBH4
C
OH
CH3
or H2 / Ni
O
I2(aq) / NaOH(aq)
Ketones cannot
undergo oxidation.
C
+ CHI3
C
heat
O Na
O
H
H3C
H3C
Only methyl
ketones, –COCH3,
will undergo
iodoform reaction
OH
K2Cr2O7 / H2SO4 or KMnO4 / H2SO4
H3C
C
heat
H3C
CH3
CH3
NO2
2,4-dinitrophenylhydrazine
propanone
C
N
H3C
HCN with trace KCN (or trace NaOH)
N
NO2
H
or
KCN + H2SO4
OH
H3C
C
OH
OH
CH2NH2
LiAlH4 in dry ether
H3C
C
NaOH(aq)
heat
CN
H3C
COO Na
CH3
or H2 / Ni, high T, P
CH3
C
CH3
dil. NaOH(aq)
OH
dil. H2SO4(aq)
heat
dil. H2SO4(aq)
H3C
C
COOH
CH3
Page 11
SYNTHETIC ROUTES INVOLVING CARBOXYLIC ACIDS
H3C
C
C
H
LiAlH4 in dry ether
Reduction
heat
H
H
C
C
OH
Oxidation
OH
O
K2Cr2O7 / H2SO4 or KMnO4 / H2SO4
PCl 5
heat
H3C
Cl
O
O
K2Cr2O7 / H2SO4 or KMnO4 / H2SO4
C
Oxidation
heat
H3C
C
or Na2CO3(aq)
ethanoic acid
H
O
Na(s) or NaOH(aq)
OH
H
H
H3C
CN
H
+ H2O (if reacts with NaOH)
C
O Na
+ CO2 (if reacts with Na2CO3)
H2SO4(aq), heat
or NaOH(aq), heat followed by
addition of H2SO4(aq)
Carboxylic acids
cannot react with
phenols to form
esters.
O
CH3CH2OH
heat with conc. H2SO4
H3C
C
Condensation
O
O
CH2CH3
H2O(l)
C
Hydrolysis
Cl
Hydrolysis
O
H3C
+ H2 (if reacts with Na)
Hydrolysis
C
H3C
Other chlorinating reagents:
SOCl2, PCl3
C
H
H3C
Acids cannot be reduced by
H2, Ni, nor NaBH4
H
CH3
H
CH3
Oxidation
conc. KMnO4 / H2SO4
CH3
H2SO4(aq), heat
C
O
CH2CH3
O
NH3(aq)
Acid-base
H3C
C
O NH4
or NaOH(aq), heat followed by
addition of H2SO4(aq)
Page 12
H2O(l)
SYNTHETIC ROUTES INVOLVING ACID CHLORIDES
Hydrolysis
O
H3C
C
+ HCl
OH
O
NaOH(aq)
H3C
C
+ HCl
O Na
O
CH3CH2OH
Condensation
H3C
+ HCl
C
O
O
O
H3C
PCl 5
C
H3C
C
O
Cl
OH
CH2CH3
O
ethanoyl chloride
H3C
C
+ Cl –
O
Other chlorinating reagents:
SOCl2, PCl3
O
NH3
Condensation
H3C
C
Primary Amide
+ HCl
NH2
O
CH3NH2
Condensation
H3C
Secondary Amide
C
N
CH3
+ HCl
H
Page 13
SYNTHETIC ROUTES INVOLVING AMINES, AMIDES AND PHENYLAMINES
CH3
CH3Br
Nucleophilic Substitution
H
Nucleophilic Substitution
CH3
Concentrated ethanolic NH3
H
C
X
heat in sealed tube
Acid-base
X = Cl, Br or I
CH3
LiAlH4 in dry ether
CN
H
C
NH2
ethylamine
Acid-base
heat
C
CH3
O
C
NH3 Cl
H
CH3
Condensation
Hydrolysis
Hydrolysis
heat
O
+ NH3
H3C
C
O
C
N
H
H
NH2
NO2
+ NH4+
OH
O Na
H
dil. H2SO4(aq)
ethanamide
C
NH3
CH3COCl
O
H3C
H
LiAlH4 in dry ether
NH2
NaOH(aq)
C
O
CH3
Reduction
C
H
HCl(aq)
H
H3C
H
CH3
H
or H2, Ni high T, P
O
H
CH3
Reduction
N
CH3
CH3CO2H
H
C
Reduction
C
Electrophilic
Substitution
CH3
+ HCl
NH2
Br
Br
3Br2(aq)
1. Sn / conc. HCl, heat
2. NaOH(aq)
dil. H2SO4(aq)
NaOH(aq)
phenylamine
Br
Phenylamine and phenol give the same observation when reacted with aqueous bromine. They can be distinguished by their
respective solubility in acids and bases.
Page 14
MECHANISM:
Free Radical Substitution
CH4(g) + Cl2(g)
Organic compounds involved:
Reagents:
Conditions:
1.
CH3Cl(g) + HCl(g)
uv or heat
Alkanes or organic compounds with alkyl side chain.
Cl2(g) or Br2(l)
uv or heat
Initiation
Homolytic fission of the Cl-Cl bond
Cl
2.
Cl
2Cl
The position and extent of substitution cannot
be controlled.
Propagation
Cl
+
CH4
CH3
3.
uv or heat
CH3
+
Cl2
CH3Cl
+
Cl
CH3Cl
+
Termination
CH3
Cl
CH3
+
Cl
+ CH3
Cl2
HCl
+ Cl
For example, when CH3CH2CH2CH3 is mixed
with chlorine gas, possible products include
CH3CH2CH2CH2Cl, CH3CH2CHClCH3, and
CH3CH2CH2CHCl2 etc.
Hydrogen radical is not formed in the reaction.
CH3CH3
Page 15
MECHANISM:
Electrophilic Substitution
C6H6
conc. HNO3 + conc. H2SO4
C6H5NO2
Other possible substitution
reaction
60 ºC
Organic compounds involved:
Reagents:
Conditions:
Electrophilic substitution of
bromine using bromine liquid with
a Lewis catalyst (e.g. FeBr3 or Fe)
Aromatic compounds
conc. HNO3 + conc. H2SO4
60 ºC
Br2 + FeBr3
!
Br+ FeBr4–
FeBr3 can be generated in-situ:
1.
Generation of electrophile
2H2SO4
2.
3Br2 + 2Fe
NO2
HNO3
H3O
!
2FeBr3
2HSO4
Electron-rich benzene attacks electrophile to form an intermediate.
H
NO2
NO2
slow
(arenium ion)
3.
Stability of the aromatic ring regenerated with the removal of a proton by HSO4–.
HSO4
H
NO2
NO2
fast
+
H2SO4
(regenerated)
Page 16
MECHANISM:
Nucleophilic Substitution
CH3CH2Br + NaOH(aq)
heat under reflux
Organic compounds involved:
Reagents:
Conditions:
CH3CH2OH + NaBr
Halogenoalkanes
NaOH(aq)
heat under reflux
Nucleophilic Substitution Bimolecular SN2
H
d+
H
C
HO
H3C
Br
H
d–
HO
H
H
H
C
CH3
Br
HO
C
+
Br
CH3
transition state
•
•
•
•
•
One-step mechanism
Rate = k [halogenoalkane] [OH–]
Simultaneous bond breaking and bond forming resulting in a transition state where the entering
nucleophile and the leaving halide ion are both partially bonded to the same carbon atom.
Nucleophile approaches electron deficient carbon from the opposite side to the halogen atom.
Product undergoes inversion of configuration (if the carbon bonded to the halogen atom is chiral)
Other nucleophiles to
react with
halogenoalkanes may
include cyanide ion
(CN–) or ammonia
(NH3).
H3N:
NC- :
Page 17
Nucleophilic Substitution Unimolecular SN1
1.
Heterolytic fission of the C–X bond to give a carbocation (an intermediate) and a
halide anion. This is the rate-determining step.
CH3
H3C
d+
C
d–
slow
Br
R1
CH3
H3C
R3
+
C
OH
C
R2
Br
CH3
CH3
OH
2.
The carbocation is very reactive and is readily attacked by the nucleophile (e.g.
OH–).
OH
CH3
H3C
C
fast
OH
CH3
H3C
C
CH3
•
•
Two-steps mechanism
Rate = k [halogenoalkane]
CH3
C
R1
OH
R3
R2
C
R3
R2
R1
If the halogenoalkane is optically
active, a racemic product is
obtained since attack by the
hydroxyl group (OH–) can take
place from both sides of the
carbocation,
yielding
equal
quantities of both the optical
isomer. Thus the product is
optically inactive.
Page 18
MECHANISM:
Electrophilic Addition
C2H4 + Br2(l)
C2H4Br2
Addition of hydrogen halides
(Markovnikov’s Rule)
Organic compounds involved:
Reagents:
Conditions:
Alkenes.
Br2(l) / CCl4
room temperature in the absence of light
H
H
C
H
1.
H
C
Br
CH3
Bromine molecule polarized by approaching alkene molecule which allows the p–electrons to attack
the electrophile to form a bromonium ion intermediate, containing a three-membered ring with the
positive charge on the bromine.
H
H
H
C
H
C
d+
d–
Br
Br
Br
slow
C
H
H
C
H
H
H
H
Br
H
C
H
H
H
CH3
H
C
C
positive charge on
the more substituted carbon
C
H
CH3
positive charge on
the less substituted carbon
Less stable, not formed.
(bromonium ion)
2.
Reaction is completed by the attack of the anion on the bromonium ion, yielding a saturated product.
Br
C
H
fast
C
H
H
C
H
H
H
Br
Br
Br
H
Bromonium ion can be drawn as
Br
+
C
C
H
H
C
H
H
H
H
Br
C
C
H
CH3
H
The addition of a proton to the double
bond of an alkene results in a product
with the hydrogen bonded to the carbon
atom that already has more hydrogen
atoms.
H
Page 19
MECHANISM:
Nucleophilic Addition
CH3CHO
+
trace KCN
HCN
Organic compounds involved:
Reagents:
Conditions:
1.
CH3CH(OH)CN
Carbonyl compounds
HCN with trace KCN
cold
Nucleophile attacks electron-deficient carbonyl carbon to form a tetrahedral intermediate
anion.
H3C
d+
d–
C
O
H3C
s lo w
H
C
H
O
CN
NC
NC
t e t r a h e d ra l i n t e r m e d i a t e
H3C
C
2.
The intermediate will be protonated by attacking an undissociated HCN molecule, regenerating
CN– anion. (KCN acts as a catalyst)
O
H
CN
H 3C
H
C
NC
H3C
O
H
CN
H
fast
C
OH
NC
cyanohydrin
+
CN
If a chiral carbon results
from the addition reaction,
the product mixture will be
optically inactive as the
nucleophile may attack
the planar carbonyl
carbon on equally from
either sides (top and
bottom) that results in a
racemic mixture.
Page 20
COMMON REAGENTS
Reagents
Conditions
Functional Group(s)
Expected Observation
Alkenes
Reddish-brown bromine
decolourised
Remarks
Electrophilic addition reaction.
-
Dibromo-derivative formed.
CH2=CH2 + Br2 ! CH2BrCH2Br
Electrophilic substitution reaction
Monobromo-derivative formed.
OH
OH
OH
Br
+
Br2(l) in CCl4
Phenols
Phenylamines
Br2(l)
+
Reddish-brown bromine
decolourised
Br
2-bromophenol
4-bromophenol
NH2
NH2
NH2
Br
+
+
Br2(l)
Br
2-bromophenylamine
4-bromophenylamine
Free radical substitution reaction.
heat or
uv light
Alkanes
Alkyl chains
Extent and position of substitution cannot be controlled.
Reddish-brown bromine
decolourised
Probability vs stability of radicals: tertiary > secondary >
primary > methyl
CH4 + Br2 ! CH3Br + HBr
Electrophilic substitution reaction.
Monobromo- or monochloro- derivative formed.
Br2 (with FeBr3 or AlBr3)
or Cl2 (with FeCl3 or AlCl3)
-
Benzene
Substituted benzene
Reddish brown bromine
decolourised.
FeBr3
+
Br2
Br
+
HBr
Page 21
Reagents
Conditions
Functional Group(s)
Expected Observation
Remarks
Electrophilic addition reaction.
-
Alkenes
Orange red solution
decolourised.
Bromoalcohol formed as the major product.
CH2=CH2 + H2O + Br2 ! CH2(OH)CH2Br + HBr
Confirmatory test for alkenes
Electrophilic substitution reaction.
Tribromo-derivative formed.
OH
OH
Br
+
Br
3Br2(aq)
+
3HBr(aq)
+
3HBr(aq)
Br2(aq)
-
Phenols
Phenylamines
Br
Orange red solution
decolourised.
White precipitate
formed
2,4,6-tribromophenol
(white ppt)
NH2
NH2
Br
+
Br
3Br2(aq)
Br
2,4,6-tribromophenylamine
(white ppt)
Confirmatory test for phenol and phenylamine. Catalyst not
required as –OH and –NH2 groups are strongly activating.
Page 22
Reagents
Conditions
Functional Group(s)
-
Acid chlorides
Expected Observation
White precipitate
(AgCl)
AgNO3(aq)
Remarks
Hydrolysis of acid halides with precipitation reaction.
No need to add NaOH(aq) first as the halides leave easily on
contact with water.
O
-
Acid bromides
Cream precipitate
(AgBr)
O
+
C
Ag+(aq)
+ H2O
+ AgX(s) + H+
C
X
OH
(X = Cl or Br)
H2O(l)
-
Reagents
Conditions
Acid chlorides
Acid bromides
Functional Group(s)
Hydrolysis of acid halides.
White fumes
RCOX + H2O ! RCOOH + HX
Expected Observation
(X = Cl or Br)
Remarks
Electrophilic Addition reaction.
Markovnikoff’s rule applies
HBr(g) or
HCl(g)
-
Alkenes
-
Stability of carboncation: tertiary > secondary > primary
H
CH3
C
H
HBr(g)
generated
from NaBr
with
conc.H2SO4
C
+
HBr
H
H
H
CH3
C
C
H
Br
H
Substitution reaction.
Alcohols
-
Halogen atom replaces –OH group.
CH3CH2–OH + HBr ! CH3CH2–Br + H2O
Substitution reaction.
HCl(g)
with ZnCl2
catalyst
Alcohols
-
Halogen atom replaces –OH group.
CH3CH2–OH + HCl ! CH3CH2–Cl + H2O
Page 23
Reagents
Conditions
Functional Group(s)
Expected Observation
Remarks
Condensation reaction.
The hydrazone derivative is formed.
O2N
2,4-dinitrophenylhydrazine
(2,4-DNPH)
Aldehydes
Ketones
-
Orange precipitate
formed.
C
R'
O2N
H
R
R
N
O +
H
R, R' = alkyl or H
N
NO2
H
C
R'
N
N
NO2 + H2O
H
2,4-dinitrophenylhydrazine
Confirmatory test for carbonyl group (aldehydes or ketones).
Redox reaction. Cu2+ reduced to Cu+ (Cu2O).
Fehling’s solution
heat
Aldehydes
(except Benzaldehyde)
Reddish-brown
precipitate formed
RCHO + 2Cu2+ + 5OH– ! RCOO– + Cu2O + 3H2O
Confirmatory test for aldehydes except benzaldehyde.
Tollens’ reagent
(Ammonical silver nitrate)
heat
Benzaldehydes
CH3
I2(aq) with NaOH(aq)
heat
Redox reaction. Ag+ reduced to Ag(s)
Aldehydes
C
O
OH
C
CH3
R
Silver mirror formed
Yellow crystals of
tri-iodomethane (CHI3)
formed.
RCHO + 2Ag(NH3)2+ + 3OH– ! RCOO– + 2Ag + 4NH3 + 2H2O
Iodoform reaction is a method of shortening a chain by a
single carbon atom.
RCH(OH)CH3 + 4I2 + 6OH– ! RCOO– + CHI3 + 5I– + 5H2O
RCOCH3 + 3I2 + 4OH– ! RCOO– + CHI3 + 3I– + 3H2O
Nucleophilic addition reaction.
HCN
(with trace of NaOH;
or with trace of KCN)
cold
Aldehydes
Ketones
-
CH3COCH3 + HCN ! (CH3)2C(OH)CN
Carbon chain extended by one. Two functional groups on one
carbon.
Page 24
Reagents
Conditions
Functional Group(s)
Expected Observation
Remarks
Acid hydrolysis.
Dilute acids
(HCl, HNO3, H2SO4)
Nitriles
heat
Amides
CH3CN + H+ + 2H2O ! CH3COOH + NH4+
-
CH3CONH2 + H+ + H2O ! CH3COOH + NH4+
Esters
CH3COOCH3 + H2O ! CH3COOH + CH3OH
Electrophilic addition reaction.
Markovnikoff’s rule applies to the addition process.
-
Alkenes
-
Addition of concentrated sulphuric acid followed by warming
with water
CH2=CH2 + H2O
! CH3CH2OH
Elimination reaction.
–OH group and –H atom on adjacent carbon are removed.
Excess conc. H2SO4 is used.
Concentrated H2SO4
170 °C
Alcohols
-
CH3 CH3
H
C
C
H
OH
H
excess conc. H2SO4
170 oC
H3C
CH3
C
H
C
H
H
(major)
CH2CH3
C
C
H
+ H2O
H
(minor)
May have more than one alkene formed. The more
substituted alkene is the major product.
Condensation reaction.
60 °C
Alcohol + Carboxylic acid
-
Concentrated sulphuric acid is used as a catalyst.
(Dehydrating agent)
CH3CH2COOH + CH3CH2OH ⇌ CH3CH2CO2CH2CH3 + H2O
Page 25
Reagents
Conditions
Functional Group(s)
Expected Observation
Remarks
Electrophilic substitution reaction.
60 °C
C6H6 + HNO3 ! C6H5NO2 + H2O
Benzenes
CH3
CH3
Concentrated HNO3
(with conc. H2SO4)
Yellow oil produced
conc. H2SO4
+ HNO3
30 °C
(methylbenzene)
CH3
NO2
+ H2O
30 oC
Substituted benzenes
NO2
2-nitromethylbenzene
4-nitromethylbenzene
Electrophilic substitution reaction.
Tri-substitution occurs when concentrated nitric acid is used.
OH
OH
O2N
Concentrated HNO3
-
Phenols
+
White precipitate
NO2
3HNO3
+
3H2O
NO2
phenol
2,4,6-trinitrophenol
Note: Mono-substitution occurs when dilute nitric acid is used.
Reagents
Conditions
Functional Group(s)
Expected Observation
Remarks
Complex formation.
3
Neutral FeCl3(aq)
-
Phenol
Violet colouration
Fe3+(aq)
+ 6
OH
Fe O
+
6H+
6
Confirmatory test for compounds with phenol functional group.
Page 26
Reagents
Conditions
Functional Group(s)
Expected Observation
Decolourisation of
purple solution with
effervescence.
H
C
H
Remarks
Oxidative cleavage of terminal alkene.
CO2 and H2O produced
Oxidative cleavage.
R
Carboxylic acid produced.
C
H
CH3CH=CH2 + 5[O] ! CH3COOH + H2O + CO2
(R = alkyl)
Decolourisation of
purple solution.
R
C
R'
Oxidative cleavage. Ketone produced.
(CH3)2C=CH2 + 4[O] ! (CH3)2CO + H2O + CO2
(R = alkyl)
Side chain oxidation. Benzoic acid produced.
CH3
C6H5CH3 + 3[O] ! C6H5COOH + H2O
H
H
Concentrated KMnO4 with
H2SO4(aq)
C
heat
C
R
R
R'
H
Decolourisation of
purple solution with
effervescence.
Side chain oxidation. Benzoic acid, CO2 and H2O produced.
C6H5CH2CH3 + 6[O] ! C6H5COOH + 2H2O + CO2
(R = alkyl)
Oxidation.
Aldehydes
Decolourisation of
purple solution.
Primary alcohols
Secondary alcohols
CH3CH2OH + 2[O] ! CH3COOH + H2O
(CH3)2CHOH + [O] ! (CH3)2CO + H2O
CH3CHO+ [O] ! CH3COOH
Side chain oxidation. Benzoic acid, CO2 and H2O produced.
O
C
R
R
C
C6H5COCH3 + 4[O] ! C6H5COOH + H2O + CO2
OH
R
(R = alkyl)
Methanoic acid
Ethanedioic acid
Decolourisation of
purple solution with
effervescence.
C6H5C(OH)(CH3)2 + 8[O] ! C6H5COOH + 3H2O + 2CO2
Oxidation. These are the only two acids that can be oxidized
by KMnO4. HCOOH + [O] ! CO2 + H2O
(COOH)2 + [O] ! 2CO2+ H2O
Page 27
Reagents
Dilute KMnO4 with
NaOH(aq)
Conditions
Functional Group(s)
cold
Black precipitate of
MnO2 formed.
C
R
OH
C
H
CH2=CH2 + H2O + [O] ! CH2(OH)CH2OH
(CH3)2CHOH + [O] ! (CH3)2CO + H2O
O
C
R
H
(R = alkyl or benzyl)
heat with
immediate
distillation
Mild Oxidation to produce diols.
CH3CH2OH + 2[O] ! CH3COOH + H2O
OH
R'
heat
Remarks
Oxidation.
H
H
K2Cr2O7 (or Na2Cr2O7)
with H2SO4(aq)
Purple KMnO4
decolourised.
Alkenes
R
Expected Observation
H
R
C
H
Orange solution turns
greens
CH3CHO + [O] ! CH3COOH
Note: Oxidation using dichromate(VI) does not affect
carbon-carbon double bonds.
Oxidation to produce aldehydes.
OH
CH3CH2OH + [O] ! CH3CHO + H2O
Page 28
Reagents
Conditions
room temp.
Functional Group(s)
Expected Observation
Phenol
Phenol and carboxylic
acids that are insoluble
dissolves in NaOH(aq).
Carboxylic acids
Remarks
Acid-base reaction.
C6H5OH + NaOH ! C6H5O–Na+ + H2O
CH3COOH + NaOH ! CH3COO–Na+ + H2O
Nucleophilic substitution reaction / Hydrolysis.
R–X + OH– ! R–OH + X–
Halogenoalkanes
-
(X = Cl, Br or I)
To distinguish the different halogenoalkanes, excess
HNO3(aq) is added to the resultant solution (to remove the
excess NaOH) and AgNO3(aq) added to precipitate the silver
halides.
White ppt: AgCl | Cream ppt: AgBr | Yellow ppt: AgI
Alkaline hydrolysis.
Primary amides undergo hydrolysis to give ammonia gas and
a carboxylate salt.
NaOH(aq)
CH3CONH2 + OH– ! CH3COO– + NH3
heat
Amides
Nitriles
Ammonia gas liberated
that turns moist red
litmus paper blue
CH3CN + OH– + H2O ! CH3COO– + NH3
Secondary amides undergo hydrolysis to give amine (may
exist as a basic gas when molecule has small no. of carbon
atoms) and a carboxylate salt.
CH3CONHCH3 + OH– ! CH3COO– + CH3NH2
Confirmatory test for nitriles and amides.
Alkaline hydrolysis.
Esters
-
Esters undergo alkaline hydrolysis to give the corresponding
carboxylate salt and alcohol (or phenoxide salt).
CH3CO2CH3 + OH– ! CH3COO– + CH3OH
CH3CO2C6H5 + 2OH– ! CH3COO– + C6H5O– + H2O
Page 29
Reagents
Conditions
Functional Group(s)
Expected Observation
Remarks
Metal-acid reaction to give salt and hydrogen gas.
Reactants should be pure and not dissolved in water as that
would lead to inaccurate conclusion (H2O reacts with sodium).
Alcohols
Na(s)
-
Phenols
ROH + Na ! RO–Na+ + ½H2
Effervescence
C6H5OH + Na ! C6H5O–Na+ + ½H2
Carboxylic acids
RCOOH + Na ! RCOO–Na+ + ½H2
Reaction with sodium must be treated with caution.
Acid-base reaction to produce CO2(g).
Na2CO3(aq)
or NaHCO3(aq)
2CH3COOH + Na2CO3 ! 2CH3COO–Na+ + H2O + CO2
Carboxylic acids
-
Acid chlorides
Effervescence
Confirmatory test for carboxylic acids.
Acid bromides
CH3COCl + Na2CO3 ! CH3COO–Na+ + NaCl + CO2
Acid chlorides can also give carbon dioxide with carbonates.
Elimination reaction.
Halogen atom and hydrogen atom on adjacent carbon are
removed.
NaOH
(in ethanol)
heat
Halogenoalkane
-
CH3 CH3
H
C
H
C
H3C
H
X
NaOH
(in ethanol)
CH3
C
H
C
H
H
(major)
CH2CH3
C
C
H
+ NaX + H2O
H
(minor)
(X = Cl, Br or I)
May have more than one alkene formed. The more
substituted alkene is the major product.
Page 30
Reagents
Conditions
Functional Group(s)
Expected Observation
-
Carboxylic acids
-
Remarks
Acid-base reaction.
NH3
CH3COOH + NH3 ! CH3COO– NH4+
Substitution reaction.
-
Acid chloride
Acid bromide
White fumes
Primary amide is formed.
CH3COX + NH3 ! CH3CONH2 + HX
(X = Cl or Br)
Nucleophilic substitution reaction. Primary amine is formed
when excess ammonia is used.
CH3Br + NH3 ! CH3NH2 + HBr
Concentrated NH3
heat in sealed
tube
Halogenoalkane
-
When excess halogenoalkane is used, further substitution
may occur that will result in other compounds formed.
CH3Br + CH3NH2 ! (CH3)2NH + HBr
CH3Br + (CH3)2NH ! (CH3)3N + HBr
CH3Br + (CH3)3N ! (CH3)4N+Br–
Substitution reaction.
ROH + PCl5 ! RCl + POCl3 + HCl
PCl5
PCl3
SOCl2
-
Alcohols
Carboxylic acids
RCOOH + PCl5 ! RCOCl + POCl3 + HCl
White fumes
PBr3
RCOOH + SOCl2 ! RCOCl + SO2 + HCl
RCOOH + PBr3 ! RCOCl + POCl3 + HCl
Note: PCl5 also reacts with water to form white fumes, hence
reaction must be conducted in anhydrous environment.
Nucleophilic substitution reaction.
KCN (or NaCN) in ethanol
heat
Halogenoalkanes
-
CH3CH2X + CN– ! CH3CH2CN + X–
(X = Cl, Br or I)
Carbon chain increased by one.
Page 31
Reagents
Conditions
Functional Group(s)
Expected Observation
Remarks
Reduction.
Phenylamine is formed.
Sn with concentrated HCl
heat
Nitrobenzene
-
NO2
NH2
+ 6[H]
1. Sn with conc. HCl
2. NaOH(aq)
+ 2H2O
Reduction.
NaBH4
-
Aldehydes
Ketones
CH3CHO + 2[H] ! CH3CH2OH
-
(CH3)2CO + 2[H] ! (CH3)2CHOH
Reduction. Note: LiAlH4 does not reduce alkenes.
CH3CN + 4[H] ! CH3CH2NH2
Nitriles
LiAlH4
in dry ether
Aldehydes
CH3CHO + 2[H] ! CH3CH2OH
Ketones
(CH3)2CO + 2[H] ! (CH3)2CHOH
Carboxylic acids
Esters
CH3COOH + 4[H] ! CH3CH2OH + H2O
Amides
CH3COOCH3 + 4[H] ! CH3CH2OH + CH3OH
CH3CONH2 + 4[H] ! CH3CH2NH2 + H2O
Reduction.
CH2=CH2 + H2 ! CH3CH3
Alkenes
H2(g) with Ni catalyst
high temp.
Aldehydes
high pressure
Ketones
Nitriles
-
CH3CN + H2 ! CH3CH2NH2
CH3CHO + H2 ! CH3CH2OH
(CH3)2CO + H2 ! (CH3)2CHOH
Note: [H] can be used to replace H2 in equations
Page 32
C
X
C OH
H
Br2(aq)
H
R'
ü
ü
ü
K2Cr2O7 / H2SO4(aq), heat
ü
H
R
C
R'
O
C
OH
O
C
Cl
O
C
OR
ü
ü
PCl5
ü
ü
ü
ü
ü
Fehling’s reagent
ü
ü
ü
ü
ü
«
ü
ü
ü
ü
«
«
ü
«
ü
neutral FeCl3(aq)
ü
ü
AgNO3(aq)
H2O(l)
ü
NaOH(aq), heat then test the gas with wet red litmus paper
NaOH(aq), heat, acidify with HNO3(aq) followed by AgNO3(aq)
ü
1) NaOH(aq), heat, collect distillate
³
2) Test with K2Cr2O7 / H2SO4(aq)
indicates test should not be attempted due to possibility of other undesirable reactions
ü
indicates positive test
primary amides
phenylamines
ü
Na2CO3(aq) or NaHCO3(aq)
I2(aq) with NaOH(aq), heat
O
C
NH2
ü
Tollens’ reagent
Na(s)
NH2
ü
ü
ü
ü
2,4-Dinitrophenylhydrazine
KMnO4 / H2SO4(aq), heat
H
O
esters
C
C
acid chlorides
O
carboxylic acids
O
ketones
OH
R C OH
ü
benzaldehydes
aldehydes
H
secondary alcohols
primary alcohols
CH3
C C
phenols
Common reagents
halogenoalkanes
alkenes
Functional groups
methyl benzenes
SUMMARY OF SIMPLE DISTINGUISHING TESTS
ü
³ positive iodoform test may be used for esters with –CO2CH(CH3)– structure
« indicates that only alcohols with –CH(OH)CH3 group and carbonyl compounds with –COCH3 group can give positive iodoform test
STRUCTURE ELUCIDATION
Page 33
AMINO ACIDS
H
They exist as zwitterions
H2N
H
C
COOH
H3N
R
COO
H2N
H3N
b
g
C
COO
H3N
C
COO
R
H2N
+
Hd
d+
C
H
COO
R
d+
a-amino acid
d-
The twenty essential amino acids that make up all the proteins in
the body are a-amino acids.
The properties of a-amino acids depend on the nature of the
R-group.
O
H
ion-dipole interaction
They can act as buffer solutions
H
H2N
C
H
COO
OHœ
Proteins can be hydrolysed into their constituent
a-amino acids by an appropriate enzyme or by acid (or alkaline)
hydrolysis. This will cause the peptide bonds to break.
H
H+
H3N
R
C
COO
H3N
C
R
COOH
R
at high pH
net charge = œ1
at low pH
net charge = +1
*
H
R1
O
N
C
C
H
O
N
C
C
H
H
*
H+
heat
R1
H2N
R2
breaking of peptide bond
Formation of proteins
n
COOH
R
H
H3N
CH3
C
d+
O
CH2
H
strong electrostatic attraction
d-
COOH
An a-amino acid is one in which the amino group is joined to the
carbon next to the acid group.
H
R
They are readily soluble in water but insoluble in
organic solvents
C
zwitterion
H
H
a
R
a-amino acid
They are crystalline solids with high melting point
H
C
C
H
R2
COOH
H2N
C
H
œH2O
COOH
*
H
R1 O
N
C
H
C
OH–
heat
R2 O
N
C
H
H
peptide bond
C
R1
*
n
H 3N
C
H
R2
CO O H
H 3N
C
H
R2
R1
CO O H
H 2N
C
H
CO O
H 2N
C
CO O
H
Page 34
PROTEINS
PRIMARY STRUCTURE
It is the composition and
sequence of amino acids
in its polypeptide chain.
This covalent structure is
linear, without any
branching.
amino acids
TERTIARY STRUCTURE
The polypeptide with its
primary and secondary
structure can be organized
in space to form a more
complex polypeptide
configuration through the
formation of interactions
between the R-groups of
the amino acids.
SECONDARY STRUCTURE
It is the arrangement of a polypeptide chain in space around a single axis. It is formed and stabilized by the interactions of amino
acids that are fairly close to one another on the polypeptide chain, through hydrogen bonds between the C=O group of one
peptide and the N-H group of another peptide.
a-helix
The hydrogen bonds of the ahelix are parallel to the long axis
of the helix. The coiled
arrangement of the polypeptide
chain forms into a right-handed,
spring-like configuration.
The R groups in the helical
structure point outwards (away
from the axis of the helix). These
R-groups might interact with
other R-groups to stabilize the
overall folding of the polypeptide
chain in globular proteins by
taking part in the tertiary
structure.
Hydrogen bonding: Hydrogen bonds can also
form between amino acid side chains.
Interaction between polar R-groups (e.g those
with H-bonded to O or N)
Disulfide linkages: The –SH side chain of two
cysteine can be oxidised to form a covalent
disulphide (S–S) bond. These disulphide
bonds hold the folded portions of the proteins
together with higher integrity, stabilising the
specific shape of the protein.
b-pleated sheet
They can either be parallel or anti-parallel, with adjacent strands being stabilized
by hydrogen bonds between N–H and C=O group.
Antiparallel b-sheet
O
H
C
N
C
H
O
H
C
H
C
C
R
N
N
C
C
R
O
H
H
R
O
H
R
H
O
H
R
H
N
C
C
O
C
R
C
N
H
H
O
C
C
H
H
hydrogen
bonding
C
H
H
O
O
H
C
O
N
H
H
N
C
H
C
R
H
N
H
H
N
R
C
R
C
C
H
N
C
H
R
N
R
C
H
O
C
O
R
C
H
N
C
C
C
H
R
N
O
N
C
O
H
C
H
C
N
R
Parallel b-sheet
O
C
N
R
Hydrophobic interactions: Proteins often fold
to form inner hydrophobic pockets that are
stabilised by hydrophobic (van der Waals) forces
between uncharged (hydrocarbon) R-groups.
These forces stabilise and maintains the 3-D
configuration of the protein.
Ionic bonds: Electrostatic attraction between
acidic and basic groups. The structure of a
protein can be stabilized by the force of
attraction between amino acid side chains of
opposite charge.
Page 35
H
PROTEINS
QUATERNARY STRUCTURE
Consists of more than one polypeptide chain coming together to form the complete protein maintained by the same forces that are
responsible for tertiary structure.
Haemoglobin
•
•
Protein that carries O2 in red blood cells.
Consists of four polypeptide chains (two a-sub-units and two b–sub-units), each with an associated haem group.
•
•
Each haem group consists of a central Fe2+ ion that can bond to one O2 molecule.
Each haemoglobin is able to carry a maximum of four O2 molecules.
FUNCTIONS OF PROTEINS
•
•
•
•
Enzymes (act as biological catalysts)
Antibodies (produced by immune system in response to foreign antigens)
Transport proteins (carry materials from one place to another in the body)
Regulatory proteins (control cell functions)
•
•
Structural proteins (provide the framework which defines the size and shape of cells)
Movement proteins (for all forms of movement using muscle fibres, through interaction
of actin and myosin proteins)
•
Nutrient proteins (a source of amino acids)
DENATURATION OF PROTEINS
• Highly organized structure of proteins becomes completely
disorganized.
• Quaternary, tertiary and secondary protein structures break down
resulting in the protein unfolding to give a randomly coiled
polypeptide.
•
•
•
Primary structure of the protein remains unaffected.
Leads to the loss of their biological activity.
Often leads to irreversible changes in their physical and chemical
properties (e.g decrease in solubility).
FACTORS LEADING TO PROTEIN DENATURATION
Heat
pH changes
Heavy metal ions
Oxidizing / Reducing agents
Hydrogen bonding
Ionic interactions
Hydrophobic interactions
Disulphide linkages
relatively weak interactions,
easily destroyed by heat
depends on temperature
relatively weak interactions,
easily destroyed by heat
depends on temperature
depends on which functional
group the H-bonding is found
protonation or deprotonation
will occur destroying existing
electrostatic interactions
not affected
not affected
not affected
they interfere with electrostatic
attractions present
not affected
they react with disulphide
bridges to form precipitates
not affected
not affected
not affected
reducing agents break
disulphide bridges
Page 36