1 14/06/22 First Year Organic Chemistry 2006-07 The Complete Lecture Slides By Dr Fawaz Aldabbagh [email protected] Course booklet available from Secretariat
Dec 12, 2015
118/04/23
First Year Organic Chemistry 2006-07
The Complete Lecture Slides
By Dr Fawaz Aldabbagh
Course booklet available from Secretariat
218/04/23
Introduction to Organic Chemistry
What is Organic Chemistry?
It is defined as the study of hydrocarbons (compounds of hydrogen and carbon) and their derivatives
7 million Organic Compounds1.5 million Inorganic Compounds
Animal and plant matter, Foods, Pharmaceuticals, Cosmetics, Fertilizers, Plastics, Petrochemicals, Clothing
418/04/23
Periodic Table
Periodic Table
Periodic Table
Why is it the element of life on earth?
Has Four Bonding Electrons
Unique Strong Covalent Bonds
Strong Single, Double and Triple Bonds
Average Bond Energies (KJ mol-1)
C-C 607 Si-Si 230 C-H 416 Si-H 323
C-N 754 Si-N 470 C-O 336 Si-O 368
O-Si-O = Sand and Rocks
Carbon
H
CH H
H
methane
Carbon has 4 valence electrons
C
H
H
H
H
H C
Ne
Neon
Stable Octet required
Simplest Organic molecule
Covalent Bonding – Atoms Share Electrons
718/04/23
Periodic TablePeriodic Table
C(6) - 1s2, 2s2, 2px1, 2py
1, 2pz0
lowest energy state
Hybridization
C(6) - 1s2, 2s1, 2px1, 2py
1, 2pz1
Excited state
4 sp3
2s 2px2py 2pz
+ + +
4 X sp3
Methane is Tetrahedral
109.50
Sp3 hybridized carbon 4 equivalent C-H bonds (bonds)
All purely single bonds are called bonds
H
CH
HH
1018/04/23
ALKANES
Alkanes CnH2n+2
consist of only carbon and hydrogen bonded by single covalent bonds single
H
CH H
H
H
CH C
H
H
H
H
H
CH C
H
H
C
H
H
H
H
H
CH C
H
H
C
H
H
C
H
H
H
H
CH3
H
CH C
H
H
C
H
H
C
H
H
C
H
H
H
H
methane ethane propane butane
CH3CH3 CH3CH2CH3 CH3CH2CH2CH3
pentane
CH3CH2CH2CH2CH3
Skeletal structure of only carbon atoms
propane
butane
pentane
C1 – C4 n-alkanes are all gasesMethane main component of natural gas
Propane and butane often stored as compressed gases
1218/04/23
Name the following compound
CH3CH2CH2CH2CH CH
CH3CH
CH2CH2
CH
CH3CH3
CH3CH3
longest chain = 9 carbons = nonane1,2-dimethyl propyl substituentmethyl
need to be in alphabetical order
5-(1,2-dimethylpropyl)-2-methylnonane
C C
H H
HHH
H
Ethane
Rotation about single covalent bonds occurs freely. The energy barrier is small. The position of hydrogen atoms relative to one is thus constantly changing
3D – models show that because of the tetrahedral carbon atoms the chains are zig-zagged and not at all straight
1318/04/23
Physical Properties of Alkanes
Non-polar molecules, which are less dense than water. Alkanes are immiscible with water making two layers.
Van-der Waals or dipole-dipole attractive forces, and not H-bonding (as in polar molecules) are the main intermolecular forces
Alkanes show regular increases in bpt and mpt as molecular weight increases down the homolgous series
These weak intermolecular forces operate over small distances, arising because the electron distribution within molecules at any given instance is not uniform. Resulting in tiny electrical attractions between molecules.
These temporary dipoles hold alkanes as liquids or solids, and must be overcome in order to vaporize a liquid or melt a solid (wax)
Isomers – the have the same molecular formula, but a different structuresStructural Isomers – same molecular formula, but atoms are bonded in different orders.
H3C C
CH3
CH3
H
Isobutane
H3C CH
CH3
CH2 CH3
Isopentane
H3C C
CH3
CH3
CH3
Neopentane
Has the same molecular formula as n-pentane, C5H12
Have different PhysicalProperties, Mpt, Bpt,
densities,
C4H10 – has two isomers, n-butane and isobutane (2-methylpropane)
(2,2-dimethylpropane)
(2-methylbutane)
Fractional distillation of crude oil
Petroleum Kerosene (C12-C16)Bpt (200-250 ºC)
Heating oil (C15-C18)Bpt (250-300 ºC)
Natural Gas (C1-C4)
Gasoline (C4-C12)Bpt (40-200 ºC)
Straight-chain alkanes are a pure fuel, because of engine knock.n-Heptane has an octane rating = 02,2,4-trimethylpentane has an octane rating = 100
Catalytic cracking
1618/04/23
CYCLOALKANES and Conformational Analysis
CycloalkanesH2C
CH2
CH2
Cyclopropane
CnH2n
C
C
CH
H
H H
H
H
H2C
H2C CH2
CH2
Cyclobutane
CH2
CH2
CH2H2C
H2C
Cyclopentane
Angle Strain in Cyclopropane and Cyclobutane – weaker “Bent” C-C bonds C-C Bond angles 60 and 88o respectively
Eclipsed hydrogens – Torsional AngleReduced in Cyclobutane by folding or bending
Pentane has C-C bond angles of 108oC-C bonds slightly bent out of planarity in order
to reduce torsional strain
The most stable cycloalkane with 109.5o C-C bond angles
Cycloalkanes have higher bpt/mpt than straight chain alkanes with the same number of carbon atoms
Sir D.H.R. Barton, Nobel Prize 1969
How to draw Cyclohexane ?H
HH
H
H
H
put in axial H’s
put in equitorial H’s
H
HH
H
H
H
HH
H
HH
H
H
H
HHH
H
H
H
CH4O2 CO2
H2O energy+ 2 2+ +
RCH2 CH2R RHC CHR H H+alkene
High Temp.catalyst
Reactions of Alkanes
Combustion
Dehydrogenation
Halogenation – radical substitution reactions
Br2
Br+ + HBr
light or heat
H Cl H Cl+
1 electron 7 electrons in outer shell
Less Energy Demand
Gaseous phase
Monoatomic - Radicals
H Cl H Cl+
0 electrons 8 electrons in outer shell
water
H2O
H3O Cl
Only possible in solution
When bonds break ions are created – driven by the energy of solvation
Each atom gets one electron each – results in the formation of radicalsRadical – neutral species with one unpaired electron
Using Curly Arrows
Sir Robert Robinson, Nobel Prize 1947
Introduced curly arrows in 1922, numerous brilliant syntheses of complex natural products
Halogenation
Substitution Reaction – a reaction in which part of a small reacting molecule replaces an atom or
a group of atoms on the organic molecule
H
CH
H
C
H
H
H + Br2
H
CH
H
C
H
H
Br
Heat or Light or hv
Ethane Bromoethane
HBr+
C
H
H
H + Cl2
Heat or Light or hv
Methane chloromethane
HCl+H C
H
H
ClH
CH2Cl2 and CHCl3may be observed
Mechanisms are widely used by organic chemists to explain reaction pathways to observed reaction products
Initiation
Two highly reactive Chlorine radicals formed
Cl Cl Cl + Clhv or
+Cl
H
C H
H
HH
C HH
H Cl
Hydrogen abstraction to form a methyl radicalPropagation
Cl ClCl+
H
C Cl
H
HH
C HH
Chlorine atom is abstracted to form a chlorine radical
Propagation are the product forming stepsChain Reaction – thousands of radical forming cycles
Cl Cl Cl
CH3H3C CH3CH3
Cl
Cl CH3CH3Cl
Termination
Radicals Couple Product forming Chains are broken
Fluorine is the most reactive halogen – mixtures of fluorine and methane can be explosive. Fluorine radical is very reactive. The reaction is controlled with the addition of an inert gas to dilute the reaction.
Chlorine is next most reactive, followed by bromine. Cl2 and Br2 require heat or light. Iodine does not react with methane easily. Iodine radical is disperse and large - unreactive
As the reaction progresses chloromethane accumulates and its hydrogen atoms can be abstracted.
ClCl ClCl
C
H
H
H
CH
Cl
Cl
Dichloromethane (DCM)
+
2818/04/23
Alkyl Halides or Haloalkanes
CH3 CH
Cl
CH CH3
CH3
Cl
CCl Cl
Cl
CH3 CH
Br
CH2 CH2
Cl
F
CH2CH3
BrCl
Cl
CCl F
Cl
F
CCl F
Cl
F
CF
F
C
F
H
H
Naming them
Tetrachloromethaneor carbon tetrachloride
2-Chloro-3-methylbutane 3-Bromo-1-chlorobutane
1-Ethyl-2-fluorocyclohexane1-Bromobutane 2-Chloropropane or
Isopropyl chloride
Tend to be Heavier than waterMore Toxic than Alkanes
Trichlorofluoromethane (Freon-11)
Dichlorodifluoromethane (Freon-12) 1,1,1, 2-Tetrafluoroethane
Chlorofluorocarbons (CFCs)Refrigerant Gases, Ozone Depletion, More H’s more degradable
X
C X = F, Cl, Br
-
Nu -
Electronegativity is defined as the ability of atoms to attract shared electrons in a covalennt bond ------------ leads to nucleophilic substitution in alkyl halides
X is readily displaced by nucleophiles
ClCCl ClCl
Symmetrical molecules have no dipole moment or have equal distribution of electrons within covalent bondsTherefore, they are unreactive!
3118/04/23
ALKENES
Unsaturated Compounds – contain DB and or TB
ALKENES
CnH2n
End in ene
CH2H2C H3C CH CH2
Ethene Propene
1-Butene1-Pentene
1-Hexene
1,3-Butadiene
3-methyl-1,4-pentadiene
CCH
H
H
H
120oFlat molecule – “Planar”
C(6) - 1s2, 2s2, 2px1, 2py
1, 2pz0
C(6) - 1s2, 2s1, 2px1, 2py
1, 2pz1
Hybridization
3 sp2
Three -bonds
-bondC CH H
HH
-bonds – One C-C, two C-H bonds per carbon atom-bond
s-orbitalp-orbitals
When a single bond ispresent between atoms, thatbond is always bond DB contains one bond andone bond
end to end overlap of orbitals leads to -bond
Spherical Symmetry
bondside ways overlap
Groups or atoms can be rotated about a single bond, but DB is rigid – No rotation about a DB is possible without breaking the bond – This leads to cis-trans Isomerism
-bond
The-bond lies perpendicular to the -bond – overlapping lobes above and below the plane of -bond
cis- trans-
If each of the two carbons has two different groups attached to it
H
R R
H R
R H
H
H
H3C CH3
H CH3
H3C H
H
cis-(Z)-2-butene trans-(E)-2-butene
Z-E system, we take the group with higher priority (here higher molecular weight), and compare it with the group with higher priority on the other carbon
Geometric isomers have different chemical & physical properties
Cl Br
HF
Cl > F Br > H
(Z)-2-Bromo-1-chloro-1-fluoroethene
Cl H
BrF
Cl > F Br > H
(E)-2-Bromo-1-chloro-1-fluoroethene
CH3 H
CH3F
F > CH3 CH3 > H
(Z)-2-fluorobutene
bond lobes represent areas of high electron density
E+
Therefore, the bond is susceptible to attack by electron deficient molecules, called electrophiles, E+
ADDITION REACTIONS
C C + A B CA C B
C C
H XCH C X
X X CX C X
CH C OSO3HH OSO3H
CH C OH
H OH
H+
Alkyl Halides
Alkyl hydrogen Sulfate
Alcohols
Dihaloalkanes
Mechanism
The electrophile is a Lewis acid, its accepted a pair of electrons, the simplest Lewis acid is H+
The nucleophile is a Lewis base, its donated a pair of electrons
X- is the nucleophile, and the carbocation is the electrophile
C C
H X
C C
H
X+Slow
C C
H X
C C
H
X
fast
C C
H OSO2OH
C C
H
C C
H
O
S
O
O O H
OSO3H
Slow
Fast
Markovnikov’s RuleH atom adds to the carbon atom which already has the most H atoms
H2CHC CH3 H2C
HC CH3
H Br Markovnikov addition Product
H Br
Unsymmetrical Alkene
H
C H
H
CH3
C H
H
CH3
C CH3
H
CH3
C CH3
CH3
+ + + +
INCREASING STABILITY OF CARBOCATIONS
This determines the selectivity of addition of HX onto an unsymmetrical alkene
C C
H
H
H
CH3
H Br
C C
H
H
H
CH3
H
Slow
Br
C C
H
H
H
CH3
H Br
C CSlow
CH3
H
H
H
H
2o Carbocation prefered
1o Carbocation
3o > 2o > 1o
Carbocation stability
2-Bromopropaneis the main product
1-Bromopropane – little formed
The Slow Step is the Rate Determining Step
CH3 CHBr CH3
CH3
H2CBrH2C
Bromination of DB – This is an Ionic Mechanism
1. Bromine molecule becomes polarised
3. Formation of Bromonium cation and Bromide anion
2. Bromine bond breaks heterolytically
4. Back-side nucleophilic attack – opening of three membered ring5. Stereospecific Product
Test for DB or TBDecloroization of Br2/CCl4
colourless
Contrast with reaction between Bromine and Alkanes
C C
Br
Br
C C
Br
Br+
Br
C C
Br
C C
Br
Br
C
CH
H
C H
C H
Pt or Pd - catalystsolvent, pressure
C
C
H
H2 X CH H
CH H
Pt - catalystsolvent, pressure
Example Pt ethanol, 1 atm
cyclohexene cyclohexane
Hydrogenation – “Reduction”
H2C CH2KMnO4, -OH, H2O
OH OHH2C CH2 + MnO2
Oxidation of Alkenes
LEO Says GER 1,2-Ethanediol
Reduction = Gain of electronsGain of HydrogenLoss of Oxygen
Oxidation = Loss of electronsLoss of HydrogenGain of Oxygen
An oxidizing agent gets reducedA reducing agent gets oxidized
C C
H
H
H
H H
C C
H
H H
C C
H
H
H
CH3 H
C C
CH3
H H
C C
H
H
H
Cl
C C
F
F
F
F
C C
H H
C C
H
H HH
C C
H
H
ClH
C C
F F
FF
n
Polyethylene
n
Polypropylenepropylene
ethylene
vinyl chloride
n
n
n
n
Poly(vinylchloride), PVC
n
n
n
n
TeflonTetrafluoroethene
Styrene
Polystyrene
Polymers are large molecules containing many identical repeating units (100-1000000)
Polymerisation reaction is a repetition reaction which combines many small molecules of monomer (alkene) to form a polymer
Addition polymer is a polymer in which the monomer simply add together with no other products formed besides polymer
4618/04/23
ALKYNES
AlkynesH C C H H3C C C H
Ethyne(acetylene)
Propyne
180o
Sp3 hybridisation in Saturated Bonds (e.g. alkanes)Sp2 hybridisation in DB (e.g. alkenes)Sp hybridisation in TB (e.g. alkynes)
C(6) - 1s2, 2s2, 2px1, 2py
1, 2pz0
C(6) - 1s2, 2s1, 2px1, 2py
1, 2pz1
Hybridization
2sp 2bondsTwo -bonds (C-H) and (C-C)And Two -bonds between C-C per C atom
Linear Molecule
Therefore, a Triple bond consists of one -bond and two -bondsThe two -bonds are perpendicular to each other and form a cylinder of negative charge about the axis of the bond ---------- No bond rotation about TB
sp-orbitals contain 50% s- and 50% p-characterFar less disperse than sp2, which is less disperse than sp3
The Carbon-Carbon bond is 1.2Ao shorter than C=C, which is 1.3Ao. C-H bond is also shorter than ethene, which is shorter than ethane, because in ethyne it is overlap between an sp orbital and a s-orbital of H to give the -bond.The bonding electrons reside closer to the C-nucleus, and so are held more tightly.
Alkynes are high energy compounds
C CH H + 2.5 O2 2 CO2 + H2O
Welding gas
Combustion
Alkynes are more reactive in halogenation reactions than alkenes (no longer in this course) and --------
5018/04/23
Benzenes & AROMATICS
BenzeneC
CC
C
CC
H
H
H
H
HH
An Aromatic Hydrocarbon is a cyclic compound that does not readily undergo addition reactions Reactivity is different to other unsaturated compounds-Substitution rather than Addition is favoured.
C6H6
Resonance Structure- Rearrange the bonding electrons
Delocalised or Conjugated System – -bonding electrons can move within the molecule
Delocalisation, Resonance-Stabilise molecules, so make them less reactive
High Carbon content – burn with a smoky flame
In aromatic compounds the C atoms are sp2 hybrids, so that each C atom has one remaining p-electron involved in -bonding
C
CC
C
CC
H
H
H
H
HH
Kekul said that he dreamt the structure of benzene – so called Kekul structure of benzene
Three sp2 hybrid orbitals arrange themselves as far apart as possible - which is at 120° to each other in a plane. The remaining p orbital is at right angles to them.
Each carbon atom uses the sp2 hybrids to form sigma bonds with two other carbons and one hydrogen atom.
Each carbon atom uses the sp2 hybrids to form -bonds with two other carbons and one hydrogen atom.
This extensive sideways overlap produces a system of -bonds which are spread out over the whole carbon ring. Because the electrons are no longer held between just two carbon atoms, but are spread over the whole ring, the electrons are said to be delocalised.
= Flat (Planar) MoleculeRegular Hexagon
-Electron Density Rings above and below the plane of the ring – Susceptible to electrophilic attack
Benzene is a colourless odourless liquid that is a suspected carcinogenBenzene and its derivatives are
said to be aromatic - a term coined because of the strong fragrance of some of the derivatives of benzene
Non-aromatic compounds are said to be aliphatic
Michael Faraday first isolated benzene in 1825
=
Flat (Planar) MoleculeRegular Hexagon
Delocalised or Conjugated System – -bonding electrons can move within the molecule
1. Must be cyclic 2. Must be planar 3. Each atom of the ring must have a p orbital and these p orbitals must
be perpendicular to the plane of the ring
4. Must contain 4n+2 electrons (where n = 0, 1, 2, ...) –Hückel Rule
n = 1 , 6electrons
Naphthalene Anthracene Phenanthrene
10 π 14 π
Rules for Aromaticity
Br
OHOOH
N+ OO
NHH
CH31
2
3
4
O
m
p
Vinyl group
Naming Aromatic HydrocarbonsF CH2CH3 CH3 NH2
OH COH
OCl
Cl
Cl
Cl
Cl
Cl
CH3
NO2
NO2
CH3
CH3O2N
Br
Fluorobenzene
EthylbenzeneToluene Aniline
Phenol
Benzoic Acid1,2-Dichlorobenzene1,3-Dichlorobenzene
-meta
-ortho
-para
1,4-Dichlorobenzene 2,4,6-Trinitrotoluene (TNT)
o-Xylene m-Bromostyrene
Electrophilic Aromatic SubstitutionH
H
H
H
H
H
E
H
H
H
H
HE X+ H X
E EH
EH
EH
Electrophilic attack – Slow Rate Determining Step
E
H
sp3
Delocalised Cyclohexadienyl cation
Transition State or Wheland Intermediate
H
E E+ - H+
Fast Step is the loss of a proton
Sir Christopher Ingold's ideas (1930s), terminology and nomenclature for reaction mechanisms (e.g. electrophilic, nucleophilic, inductive, mesomeric, SN1, SN2 etc) were generally accepted and employed everywhere.
HNO3(c), H2SO4(c)NO2
E.g. Nitration of benzene
---rapid re-aromatization
The Nitration of Benzene
O
N
O
NOO
O2NH
NOO
NO2
NOO
+
electrophile
+
_
electrophilic attack
+
slow
+
- H+
fast =
=+
_
+
+
Generating NO2+
Sulfuric acid is a stronger acid than nitric acid
NO2
H
NO2 NO2
Nitrobenzene
S
O
O
OO HH S
O
O
OO
OH NO2 OH
HNO2
__+
H+
+ NO2+ + H2O
2 H+
- [H+]
Professor Charles Friedeland Professor James Crafts
Cl
BrBr2, FeBr3
Cl2, AlCl3
HALOGENATION
BrFeBr4Br Br FeBr3 H +
The Halogen is polarised
Conclusions
Aromatic Compounds are resonance stabilizedThis gives them added stabilityThey undergo Electrophilic Substitution ReactionsUpon substitution, the fast step is the loss of a proton to regenerate aromaticity
H Br H Br H Br+
+
+
Br
+ HBr
FeBr4
FeBr3
Regenerate the catalyst – so only a small amount is required
double-headed arrows
William Perkin
mauve
Write the mechanism for the formation of mauve from the diazonium salt of aniline
Diazonium Coupling Reactions
Azo Dyes
6518/04/23
ALCOHOLS, PHENOL and ETHERS
Alcohols and Ethers
Alcohols and Ethers can be regarded as derivatives of water in which one or two of the H atoms has been replaced by an alkyl group
Electronegativity of oxygen causes an unsymmetrical distribution of charge
Saturated molecules are sp3
hybridized
OH H
104.5o
0.96 AoWater, H2OO
C H
108.5o
0.96 Ao
Methanol, CH3OH
HH
H
1.43 Ao
OC C
111.7o
Methoxymethane, CH3OCH3
HH
H
1.43 Ao
H
HH
109.5o1.10 Ao
OH3C H
- I (net dipole)
Alcohols are found to have much higher bpt than those of alkanes or haloalkanes of comparable size, e.g. Methanol (65 oC), Chloromethane and Methane are gases ; Ethanol (78.5 oC), Chloroethane (12 oC) and Ethane is a gas
Methanol and Ethanol are classed as Polar Molecules (Hydrophilic) – They are Infinitely Soluble in Water
Why? Answer – Hydrogen Bonding
H-bonds weaker than covalent bonds, although these bonds can be continually broken and reformed – a highly ordered structure results – H-Bonding to water can also occur
Water (mw = 18) is a liquid, bpt 100oC – otherwise a gas
R
OH
HO
R
R
OH
H
OH
HO
H
H
OH
As R-group increases in size, so does the solubility in non-polar solvents
As the number –OHs increases so does solubility in waterBpt increase with chain length and number of –OHs
Methanol, CH3OH
- Solvent in varnishes, paint- Racing Car Fuel (easy to put out flames)- Highly Toxic – “Blindness” - Formaldehyde
Ethanol, CH3OH
-Drinking Alcohol
- 50% Ethanol is flammable
C O
H
H
H
C
H
H
H C O
H
H
H
C
H
H
C
H
H
C
H
H
C
H
H
H
Hydrophobic end
Hydrophilic end1-PentanolEthanol
H3C OH
Alcohol Dehydrogenase
O
CH H
O
CH OH
[O]In the Liver
Alcohol Dehydrogenase
O
CH3C H
O
CH3C OH
[O]In the Liver
CH3CH2OH
AcetaldehydeAcetic Acid
Odour on your breath
Symptoms - Hang-over
Preparation of Ethanol
- Fermentation of Sugar – Break down of sugar to CO2 and Ethanol by Yeast Enzymes
- Industrial Process – Hydration of Ethene
CH3CH2OH
H
H
H
H
H3PO4 , 300C
H2O
Ethanol content; Beer, 3-9% ; Wine, 11-13% ; Whisky, 40-45% ; Vanilla Extracts, 35% ; Night Nurse, 25% ; Listerine, 25%
CH3 OH
hydroxy or alcohol group
CH2 OHCH3 CH2 OHCH2CH3
CH3 CH OH
CH3
CH2 CH CH2
CH2 OH
CH3CH3
Naming Alcohols
Methyl alcohol(methanol) Ethyl alcohol
(ethanol)Propyl alcohol (propanol)
Isopropyl alcohol 2-Ethyl-1-butanol
Naming Alcohols
Polyhydroxy alcohols are alcohols that possess more than one hydroxyl group
CH2 CH2
HO OH
1,2-Ethanediol (ethylene glycol)1,2-Propanediol (propylene glycol)
1,2,3-Propanetriol (glycerol)
CH CH2
OH
CH3
HO
CH CH2
OH
CH2
HOHO
Extremely ToxicCalcium Oxalate crystallises in the kidney leading to renal problems
Harmless
C OHC
OO
HOLiver Enzymes Oxalic acid
CH2 CH2
OHHO
CH CH2
OH
CH3 C OHC
OO
H3CLiver Enzymes Pyruvic acidHO
Alcohols are very weak Acids
H
C OHH3C
H
CH3
C OHH3C
H
CH3
C OHH3C
CH3
Primary (1o) AlcoholSecondary (2o) Alcohol
Tertiary (3o) Alcohol
R O H
H
O H R O +
H
O HH
AlcoholAlkoxide
Relative Acidity ; H2O > ROH > C CR H > RH
CH3CH2OH + Na CH3CH2 O Na + H2
Vigorous Reaction
2 2 2
7218/04/23
STEREOCHEMISTRY
Isomers are different compounds that have the same molecular formula
Structural isomers are isomers that differ because their atoms are connected in a different order
Stereoisomers differ only in the arrangement of their atoms in space
Cl H
Cl H
Cl H
H Cl
cis-1,2-Dichloroethene trans-1,2-Dichloroethene
C2H2Cl2
Geometric Isomers
CH3OCH3 ---- dimethyl ether and CH3CH2OH ---- ethanol
Enantiomers are stereoisomers whose molecules are nonsuperimposable mirror images of one another
Objects that are superimposable on their mirror images are said to be achiral
CH3
CH2
CHHO
CH3
CH2
CH
CH3 CH3OH Interchanging any two groups at a
chiral centre (stereocentre) that
bears four different groups converts
one enantiomer into another
Involves a tetrahedral sp3 atom
CH3 C
OH
CH2 CH3
2-Butanol
H
Chiral Centre
One structure can be superimposed on another
If any of the groups attached to the tetrahedral atom are the same, the centre is achiral.
The ultimate way to test for
molecular chirality is to
construct models of the
molecule and its mirror image
and then determine whether
they are superimposable
A molecule will not be chiral if it possess a centre or plane of Symmetry
2-Propanol
CH3
C OHH
CH3
C
CH3HHO
CH3
Screwdriver is achiralSocks are achiralGolf club is chiralGloves are chiral
Properties of EnantiomersEnantiomers have identical melting points and boiling pointsEnantiomers have identical solubilities in solventsEnantiomers have identical spectra and refractive indexEnantiomers interact, and react with achiral molecules in the same mannerEnantiomers interact and react with other
chiral molecules at different ratesEnantiomers rotate plane-polarised light by equal amounts but in opposite directions
Plane-polarised light
Oscillation of electrical field of ordinary lightoccurs in all possible directions
Polarimeter is a devise used to measure the effect of plane-polarised light on an optically active compound
Chiral molecules are optically active
7718/04/23
No Correlation between the direction of rotation of plane polarised light and the absolute configuration of a molecule
Clockwise Rotation (+) – dextrorotatoryAnti-Clockwise Rotation (-) – levorotatory
C
CH2CH3
H2CCH3
HHO
C
CH2CH3
H2CCH3
HCl
(R)-(+)-2-Methyl-1-butanol (R)-(-)-1-Chloro-2-methylbutanol
Same Configuration
An equimolar mixture of two enantiomers is called a Racemic Mixture It is Optically Inactive
7818/04/23
H
O
S-(+)-Carvone
O
R-(-)-Carvone
H
Principle component of Caraway seed oil and responsible for the characteristic odour
Principle component of Spearmint oil and responsible for the characteristic odour
Receptor Sites in the Nose are Chiral
Nobel Prize 2001
For synthesis of optically active compounds – asymmetric synthesis
Professor William KnowlesProfessor Ryoji NoyoriProfessor K. Barry Sharpless
C Br
H3C
HC6H13HO
CHO
CH3
H C6H13
BrCH3
HO
C6H13
H
Transition StateR-(-)-2-BromooctaneS-(+)-2-Octanol
Inversion of Stereochemistry
SN2
SN2 – Substitution, Nucleophilic, Bimolecular
Backside Nucleophilic Attack – Inversion in Configuration
Concerted Mechanism
Optically ActiveEnantiomericaly Pure
C Br
H3C
HC6H13HO
CHO
CH3
H C6H13
BrCH3
HO
C6H13
H
Transition StateR-(-)-2-BromooctaneS-(+)-2-Octanol
Inversion of Stereochemistry
Rate = k2 [R-Br] [Nuc-]
SN1 – Substitution, Nucleophilic, Unimolecular
(CH3)3CCl + 2 H2O (CH3)3COH + 2 H3O+ + Cl -
Professor George OlahNobel Prize 1994
Carbocation is sp2-planar
CH3
CH3C
CH3
Cl
CH2
CH3H3C+ Cl
Slow Step (RDS)
Aided by polar Solvent Stable 3o Carbocation
ions are stabilized via solvation
CH2
CH3H3C
Fast Step
HO
HFront or Backside Attack
CH3
CH3C
CH3
O
tert-Butyl alcohol
H
H
CH3
CH3C
CH3
O H
- H+
CRR
RCR
R
HCR
H
H> >
R groups are electron releasing - delocalise the positive charge
more stable
H3CH2CH2C
C Br
H3CH2CH3C CH2CH2CH3
CHO
CH2CH3CH3
H3CH2CH2C
C OH
H3CH2CH3C
+
- HBr
S-3-Bromo-3-methylhexane
1:1 Mixture of R- and S-3-Methyl-3-hexanol
The Carbocation intermediate is attacked by water from either side by the same rate
Phenols are stronger acids than alcohols
O
CH3
H3CCH3
cyclohexene
phenol
cyclic ether
Tetrahydrocannabinol
OH
OH OH
pKa = 18 pKa = 10
OHO O O
Resonance Stabilised Phenoxide anion
ETHERS, RO-OR CH3CH2 O CH2CH3
CH3CH2 O
H3C O
Ethoxy group
Methoxy group
Diethyl Ether
1-Propoxypropane
Methoxybenzene“anisole”
Methoxycyclohexane
Bpt are similar to alkanes – No H-bonding to one anotherBut are soluble in water- H-bonding to water - PolarFlammable – Ether can cause flash firesLow Reactivity – Make Good Reaction Solvents
OTetrahydrofuran (THF) O
OFuran Pyran
Cyclic Ethers
Non-Flammable Anaesthetics
Cl
CH
F
C
F
F
O C H
F
FEnflurane
F
CF
F
C
H
Cl
O C H
F
FIsoflurane
H3CO O
OCH3
8518/04/23
ALDEHYDES AND KETONES
Aldehydes and Ketones
O 1s2, 2s2 2p2 2p1 2p1
3 sp2 orbitals
CH
RO C
R
RO
Aldehyde Ketone
CH
HO
lone Pairs
bond - two overlapping 2p orbitals
bond
bond- overlapping 1s H-orbital and sp2 C-orbital
C O
H3C
H118o
121o
C C
H
H
H
H118o
121o
C O
H3C
HC O
H3C
H
Resonance Structures
Most Reactive Group –
electrons + polarisation
Useful in Synthesis
Names al – aldehydes, one - ketones
C O
H
HC O
H3C
H
C O
CH3CH2
H
C O
CH3CH2CH2CH2
H
Methanal(formaldehyde)
Ethanal(acetaldehyde)
Propanal Pentanal
O
H
H O
H
H
Benzaldehyde
trans-Cinnamaldehyde
Formalin, 35-40% formadehyde in waterPreservative that reacts with proteins causing them to resist decayCoelacanth, “prehistoric fish”
O
HAcrolein (2-propenal)
S
HThiopropionaldehyde (propanethiol)
- lachrymator from chopped onion- lachrymator and pleasant "odour" from barbacuing meat
Propanone(ACETONE)
Butanone
Acetophenone
Benzophenone
O
H3C CHCH2
CH3
CH3
3-Methyl-2-pentanone
O H
OCH3
OH
Vanillin
CH3
O
Carvone(spearmint flavour)
O O
H3C CH3
Butadione(butter flavour)
O
H3C CH3
O
CH3
O
O
H3C CH2
CH3
Carbonyls readily undergo Nucleophilic Attack
ANHYDROUS Conditions are required for imine formation
O
C
RNH2
O
C
NH
H
R
O
C
NH R
H
O
C
NH R
H
C
NR
- H2O
Imine
Reaction between an amine and a carbonyl compound
Condensation Reaction – Elimination of water
C OCH3
CH3
N N
H
H H
H
C NCH3
CH3
NH
H+
hydrazineacetone hydrazone of acetone
Emil Fischer, Nobel Prize 1902
C OCH3
CH3
N N
H H
H
O2N
O2NC N
CH3
CH3
NH
NO2
NO2
+
2,4-diphenylhydrazine
acetonehydrazone of acetone
DNP test for aldehydes & ketones gives crystalline hydrazones
- H2O
- H2O
Professor Victor Grignard (1912 Nobel Prize)Developed this chemistry with Professor P. A. Barbier
CR O
H
ProtonationH
H2OAlcohol
CR X
H
H
X = I or Br
C
H
H
MgXR RCH2
MgX
Grignard Reagent
Mg
Ether
CR X
H
H
X = I or Br
C
H
H
LiR RCH2
Li
Organolithium Reagent
Li
Ether
C O
R Li
CR O LiADDITION
MgBr
C O
H
H
EtherC
H
H
O MgBr
H3O+
C
H
H
O H
Benzylalcohol
C O MgBr+
Ether
C OH
Triphenylmethanol
Benzyl GroupPhenyl, Ph Group
Ph
2. H3O+
Organometallics add to carbonyls to give alcohols
O
CH H
O
CR H
O
CR R
MgIPh MgIPh MgIPh
O
CH H
H
Ph
O
CR H
H
Ph
O
CR R
H
Ph
+ + +
Primary alcohols Secondary alcohols tertiary alcohols
KetoneAldehydesFormaldehyde
Nucleophilic Addition Reactions
your adding Ph_
Mg Br
OCH2CH3CH3CH2
OCH2CH3CH3CH2
..
..
....
Ethers (Lewis base) stabilize the Grignard Reagent making it more reactive
Organometallic Reactions must always be done under anhydrous conditions
Mg Br
HO
H
H
OH_
+
Grignards are powerful bases and will deprotonate water
9618/04/23
CARBOXYLIC ACIDS and ESTERS
Carboxylic Acids
O
CO H H2O+
O
CO H3O+
pKa = 4 - 5 , water = 16
We can distinguish a water-insoluble carboxylic acid and phenol from an alcohol
O
CO H NaOH+
O
CO
H2ONa
Benzoic acid Sodium Benzoate
Cl
CCl
Cl
C
OH
OH
CCl
Cl
C
OH
OH
CCl
H
C
OH
O H
CH
H
C
OH
O
pKa = 0.7 1.48 2.86 4.76
Highly PolarLow molecular weight acids show Appreciable Solubility in Water
High Bpt – Extensive H-bonds to themselves and water
Carboxylic Acids
NAMES
Methanoic acid Ethanoic acid Propanoic acid
4-Bromo-2-ethylpentanoic acid
O
H OH
O
CH3 OH
O
CH3CH2 OH
O
OH
Br
O
CC OH
HO
O
Ethanedioic acid (oxalic acid)
rhubarbRed ants
O
OH
O
HO ( )n
n = 1 = malonic acidn = 2 = succinic acidn = 3 = glutaric acid
HO2C CO2H CO2H
CO2HTerephthalic acidPhthalic acid
Esterification – condensation reaction, where H2O is lost
Alcohol part appears first in the name
O
CH3 OHCH3CH2 OH+
HCl or H2SO4
H+(catalyst)
O
CH3 O CH2 CH3
Acetic acid(ethanoic acid)
Ethyl acetate
O
Ph OHH3C OH+
H+(catalyst)
O
Ph O CH3
Benzoic acid Methyl benzoate
O
O
O
O
Ethyl propanoate vinyl acetate
O
H OMethyl formate
Ester molecules cannot H-bond to each other, because they do not have an –OHConsequently, B.pt is much lower than that of alcohols and acids of comparable massH-bonding to water is possible-low mw esters are soluble in waterSolubility rapidly decreases with carbon chain length.
O
H O
H
H O
HOR
R
OCR
O H OC R
OH........
........
Two hydrogen bondsOCR
O Rcannot H-bond to another ester molecule
Highest Boiling points and exceedingly water soluble
Hexane = 69 ºCDiethyl ether = 56 ºCEthanol = 78 ºCEthanoic acid = 118 ºCEthyl acetate = 77 ºC
Boiling points
Redox Reactions
Addition of Oxygen or Removal of Hydrogen is OXIDATION
Removal of Oxygen or Addition of Hydrogen is REDUCTION
CH4+ O
CH3OH- 2H
C O
H
H
C O
HO
H+ O - 2H O
C
O
C O
H
R H
CR
H
O
H
Reduction
Oxidation
C O
R
R H
CR
R
O
H
Reduction
Oxidation
Aldehydes Primary Alcohols
Secondary AlcoholsKetones
Examples of Reduction Reactions
O
H2 , PtO HH
Cyclohexanone Cyclohexanol
CH3
H3C
O
H
3-Methylbutanal
H2 , Pd-CCH3
H3C
OH
H
H3-Methylbutanol
Examples of Oxidation Reactions
OHH
OK2Cr2O7, H2SO4, H2OOveroxidation
OH
O
H N H
H
R N H
H
R N H
R
R N R
R
Ammonia Primary (1o) Amine
Secondary (2o) Amine Tertiary (3o) Amine
Organic bases are amines
Amines are derivatives of ammonia
N 1s2, 2s2 2p1 2p1 2p1----------- lone pair occupies an sp3 orbital
10518/04/23
AMINES, AMIDES and ANILINE
Ammonia
3oAmine
Unshared lone pair of electrons in the fourth sp3 hybrid occupies slightly more space than the electrons in the bonds
N
HH
H N
RR
R
..
107O
..
107O
H2NEt HNEt2 NEt3
H2NMe HNMe2 NMe3
where Et = CH2CH3
ethylamine diethylamine triethylamineprimary secondary tertiary
where Me = CH3
methylamine dimethylamine trimethylamineprimary secondary tertiary
Naming amines
NHmethylpropyl amine
H2NNH2
Putrescine(found in decaying meat) NH2
Amphetamine(dangerous stimulant)
N
H Piperidine
N
Triethylamine NH2
Isopropylamine
1,4-butanediamine
Some Common Amines
Both upper amines are 1o
This amine is are 2o This amine is 3o
This amine is 1o
NH2
H Cl
N
H
H
H Cl
Base + Acid = Ammonium Salt
Amines are bases because of the lone pair on the Amines are bases because of the lone pair on the nitrogen atom - nitrogen atom - red litmus paper to bluered litmus paper to blue
O
O HO
OHN(CH2CH3)3
O
OO
O
HN(CH2CH3)3
+ 2 +2
oxalic acid triethylaminetriethylaminium oxalate
= aniline
Aniline is useful in the synthesis of many other aromatic compounds
NO2
NO2NH2
HNO3, H2SO4
Sn, HCl
phenylamine
NH2 N NNaNO2, HCl
benzenediazonium chloride
+Cl-
0 C
Aniline can be converted into useful diazonium salt
N N
N N
Nuc+Cl- Nuc-
-
N N
N N
CN+Cl- CuCN
-+ KCN
N N
N N
I+Cl-NaI
-
Benzene nitrile
N N
N N
Br+Cl-HBr, CuBr
-
iodobenzene
bromobenzene
11318/04/23
NC R
R'
O
NC R
R'
O
Amides
Features of a Peptide Bond;1. Usually inert2. Planar to allow delocalisation3. Restricted Rotation about the amide bond4. Rotation of Groups (R and R’) attached to the
amide bond is relatively free
------------- Not acids or bases
11418/04/23
OC
CH3 NH2
OC
H NH2 NH2
O
OC
NH2 NH2
RCNH2
HCOOH
acetamide benzamide
urea
AMINO ACIDS
formamide
All are high melting point solids, only benzamide not soluble in water