complete organic

118/04/23

First Year Organic Chemistry 2006-07

The Complete Lecture Slides

By Dr Fawaz Aldabbagh

Fawaz.Aldabbagh@nuigalway.ie

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

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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

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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)

+

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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