hóa hữu cơ ( organic chemistry )

COURSE OUTLINE • Isomerism • Electronic & steric effects • Common reaction mechanisms • Alkanes • Alkenes • Alkadienes • Alkynes • Aromatic hydrocarbons • Alkyl halides • Alcohols & phenols • Aldehydes & ketones • Carboxylic acids • Amines & diazoniums

[3] Paula Y Bruice, ‘Organic chemistry’, fifth edition,

Pearson Prentice Hall, 2007

[4] Francis A Carey, ‘Organic chemistry’, fifth edition,

McGraw-Hill, 2003

[5] Paula Y Bruice, ‘Study guide and solutions manual - Organic chemistry’, fifth edition, Pearson Prentice

Hall, 2007

[6] Graham T.W Solomons, Craig B Fryhle, ‘Organic

chemistry’, eighth edition, John Wiley & Sons, 2004

COURSE OUTLINE

• Isomerism

• Electronic & steric effects

• Common reaction mechanisms

• Alcohols & phenols

• Aldehydes & ketones

• Carboxylic acids

• Amines & diazoniums

Isomers: Compounds with the same molecular formula

but different structural formulas

Constitutional isomers

Conformational isomers

Optical isomers /Enantiomers &

Diastereoisomers Geometric isomers

Configurational isomers Stereoisomers

Isomers

CONSTITUTIONAL ISOMERSDifferent compounds that have the same molecular

formula – but differ in their connectivity

STEREOISOMERS

Isomers that differ in the way their atoms

are arranged in space

8

Conformations of butane

Conformations of cyclohexane

12

14

GEOMETRIC ISOMERS

There is no rotation around the C=C bond

16

The E,Z system of nomenclature

Cahn-Ingold-Prelog priority rules

Rule 1

Rule 2

Rule 3

Rule 4

Optical isomers are configurational isomers

which are able to rotate plane-polarized light

clockwise or anticlockwise

OPTICAL ISOMERS

plane-polarized light

Optically active

Optically inactive

An asymmetric carbon is a carbon atom that is

bonded to 4 different groups

Asymmetric carbon

Optically active

(chiral)

Isomers with one asymmetric carbon

Nonsuperimposable mirror-image molecules are

called enantiomers

Drawing enantiomersUsing perspective formulas:

• 2 bonds in the paper plane

• 1 bond as a solid wedge

• 1 bond as a hatched wedge

Convention

Drawing enantiomersUsing Fisher Projection formulas:

• Using Cahn-Ingold-Prelog rules

• View the molecule with the lowest priority group pointing away

• If the direction from highest priority group to the next is

clockwise: R

• If the direction is

anticlockwise:S

28

Convention

for Fisher

Projection

formulas

• Using Cahn-Ingold-Prelog rules

• When the lowest priority group is

30

NAMING ENANTIOMERS

RELATIVE CONFIGURATION: D-L SYSTEM

Glyceraldehyde: the standard compound for chemical

correlation of configuration

D-L system is only useful for naming sugars &

aminoacids

Isomers with more than one

asymmetric carbon

34

Meso compounds

Enantiomers vs diastereoisomers

• Enantiomers: Nonsuperimposable mirror images

• Diastereoisomers: not mirror images of each other

• Enantiomers normally have identical physical &

chemical properties

• Enantiomers normally interact differently with

other chiral molecules

• Diastereoisomers can have different physical & chemical properties

• Enantiomers are always chiral

• Diastereoisomers can be chiral or achiral (meso compounds)

Enantiomers vs diastereoisomers

Separating enantiomers

Racemic mixture:

1/1 mixture of 2

enantiomers

CHIRALITY & BIOLOGICAL ACTIVITY

CHIRALITY & BIOLOGICAL ACTIVITY

Chapter 2 : ELECTRONIC & STERIC

The more electronegative the X, the stronger the –I

effect

The more electropositive the Z, the stronger

the +I effect

-I

Through a period in a periodic table

Through a group in a periodic table

CONJUGATION / MESOMERIC

EFFECTS (C / M)

Electron delocalization in a conjugated system:

Alternating single &

multiple bonds

O is more electronegative than CElectrons move through π-bond network towards C=O

The conjugated system is polarized

C=O has negative conjugation / mesomeric effect (-C /

-M) on the conjugated system

+C -C

+C -C

+C -C

-C groups generally contain an electronegative atom (s)

or / and a π -bond (s):

CHO, C(O)R, COOH, COOR, NO 2 , CN, aromatics, alkenes

Cl, Br, OH, OR, SH, SR, NH 2 , NHR, NR 2 , aromatics,

+C

Through a period in a periodic table

Through a group in a periodic table

+C

H O

• C effects can be effective over much

longer distances than I effects –

provided that conjugation is present

• I effects are determined by distance, C

effects are determined by relative

positions

HYPERCONJUGATION EFFECTS (H)

Electron density from Cα-H flows into the vacant p orbital

partially overlap

Hyperconjugation effects (H)

H C

H H

2

CH

3

STERIC EFFECTS

• A steric effect is an effect on relative rates caused

by space-filling properties of those parts of a

molecule attached at / near the reacting site

• Steric hindrance: the spatial arrangement of the

atoms / groups at / near the reacting site hinders / retards a reaction

• Generally, very large & bulky groups can hinder the formation of the required transition state

Steric hindrance

Steric hindrance

ACIDITY & BASICITY

If –C groups are introduced at ortho- & para

position on phenol rings:

+ The anion (-O

-) can be further stabilized by delocalization through the conjugated system as the negative charge can be spread onto the -C

groups

+ The O-H bond is more polarized as electron

density on –OH can be spread onto the -C groups

Acidity of phenols is generally increased

If –I groups are introduced on phenol rings, the

effect will depend on the distance:

+ The closer the –I group is to the negative charge (-O

-), the greater the stabilizing effect is

+ The closer the –I group is to the –OH, the O-H

bond is more polarized

Acidity of phenols is generally increased

Note: there might be ortho-effects

Benzoic acid derivatives

pKa

Position on benzene ring

31

33

STABILITY OF CARBOCATIONS

+H & +I

Allylic & benzylic carbocations

Allylic & benzylic carbocations are generally stable

due to the electron delocalization (+C effects)

Not all allylic & benzylic carbocations have the

same stability

Relative stability of carbocations

STABILITY OF RADICALS

STABILITY OF CARBANIONS

Chapter 3 : COMMON REACTION

MECHANISMS

Elimination Electrophilic substitution

NUCLEOPHILIC SUBSTITUTION

REACTIONS (SN)

• A nucleophile: an electron-rich species that can

form a covalent bond by donating 2 electrons to a positive center

• A nucleophile is any negative / neutral molecule

that has 1 unshared electron pair

• Substitution reaction: chemical reaction in which 1 atom / group replaces another atom / group in the structure of a molecule

• In a nucleophilic substitution reaction, a

nucleophile attacks / bonds with the positive center

BIMOLECULAR NUCLEOPHILIC SUBSTITUTION REACTION (SN2)

Stereochemistry of SN2 reactions

• The nucleophile attacks from the back side / the side

directly opposite the leaving group

• This attacks causes an inversion of configuration

UNIMOLECULAR NUCLEOPHILIC

Note: slow step is rate-determining step

11

Stereochemistry of SN1 reactions

However, few S N 1 reactions occur with complete

racemization

Factors affecting the rates of SN1

& SN2

1 The structure of the substrate

2 The concentration & reactivity of the nucleophile

3 The reaction solvent

4 The nature of the leaving group

Affects of substrate structure

Steric effect in the S

N

2 reaction

Steric hindrance

17

Affects of nucleophile concentration &

strength

N

1

participate in the rate-determining step

Nucleophiles that have the same attacking atom:

nucleophilicity roughly parallels basicity:

ROH, HOH

Affects of solvents on SN2

• In polar aprotic solvent, nuceophilicity parallels basicity

Polar aprotic solvents solvate cation but not anions

Rates of S N 2 reactions are generally increased in

polar aprotic solvent

1 reactions are generally increased in

polar protic solvent

Affects of leaving group

The best leaving groups are those that become the most stable

ions after they depart

The best leaving groups are weak bases

ELIMINATION REACTIONS

In an elimination reaction:

+ Groups / atoms are eliminated from a reactant

+ A double bond is formed between the 2 carbons from

which atoms are eliminated

BIMOLECULAR ELMINATION (E2)

Strong base

Stereochemistry of E2 reactions

• Anti-elimination is highly favored in an E2 reaction

2 groups / atoms are removed from opposite sides of

C-C bond

Regioselectivity of E2 reactions

Zaitsev’s rule for an E2 reaction: more substituted alkene is normally

obtained

In some E2 reactions, the less stable alkene is the

major product due to steric effects

Hofmann’s product

Zaitsev’s product

35

UNIMOLECULAR ELMINATION (E1)

Weak base

Rearrangements in E1 & S

N

1

39

The major product is the

more stable alkene

N

vs E

43

ELETROPHILIC ADDITION

REACTIONS (AE)

• Electrophilic: electron-seeking / loving

• Most electrophiles:

+ Are positively charged

+ Have an atom which carries a partial positive charge

+ Have an atom which does not have an octet of electrons

An electrophilic addition reaction is an addition reaction where carbon-carbon double bonds or triple bonds are attacked by an electrophile

45

•Not a

carbocation, but a cyclic halonium ion

• More

stable than carbocation

Stereochemistry of AE reactions

49

Markovnikov’s rule

Carbocation rearrangement in A

E

More stable

More stable

H H

H H

H3C H

H H

H3C CH3

H H

H3C CH3

CH3H

ELECTROPHILIC SUBSTITUTION

REACTIONS (SE)

In an electrophilic substitution reaction, an

electrophile substitutes for a hydrogen of an

aromatic compound

Although benzene has 3 double bonds, the overall reaction is electrophilic substitution rather than

electrophilic addition

Reaction mechanism

An electrophile

Rate-determining step

Nonaromatic, not stable, not formed

61

Chapter 4 : ALKANES

NOMENCLATURE OF ALKANES

ALKYL SUBSTITUENTS

IUPAC NAMES OF BRANCHED

ALKANES

Determine the parent hydrocarbon – the

longest continuous carbon chain

• Substituents are listed

in alphabetical order

• Carbon chain is

lowest possible number

in the compound

Substituents are the same

NATURAL SOURCES OF ALKANES

Natural gas &

Reduction reactions

Wurtz reactions symmetric alkane

Limitations:

alkanes from alkyl iodides & bromides

separate

+ A side reaction also occurs to produce an alkene

halides are bulky at the halogen-attached carbon

Corey-House synthesis – the reaction of a lithium dialkyl

cuprate with an alkyl halide to form a new alkane

Corey-House synthesis overcomes some of

the limitations of the Wurtz reaction

REACTIVITY OF ALKANES

• Alkanes have only strong σ bonds

• Electronegativity of C & H are approximately

HALOGENATION OF ALKANES

17

PRODUCT DISTRIBUTION

It must be easier to abstract a hydrogen atom from a

secondary carbon than from a primary carbon

Reactivity - relative rate at which a particular hydrogen is

abstracted in chlorination reactions:

At room temperature

Product distribution can be estimated:

Too violent

Too slow

STEREOCHEMISTRY OF RADICAL

SUBSTITUTION REACTIONS

Have no asymetric

carbon

Racemic

mixture

Already have

1 asymetric

carbon

COMBUSTION OF ALKANES

NOMENCLATURE OF ALKENES

• Ethylene is an acceptable synonym for ethene in the IUPAC

system

• Propylene, isobutylene and other common names ending in

The IUPAC name of an alkene is obtained by replacing

the “ane” ending of the corresponding alkane with “ene”

Determine the parent hydrocarbon – the

longest continuous carbon chain containing the C=C

Note: Alkenes can have geometric isomers

isomerization

Eliminations of alkyl halides

Base

Alkyne hydrogenations

Pd/CaCO + Pb(OAc) / quinoline

Carbocation rearrangement

More stable

More stable

Reaction

mechanism:

Racemic mixture

Already has 1 asymmetric carbon

2 asymmetric carbons are created

Additions of halogens

Major addition product –

NOT a dihalide

Stereochemistry

2 asymmetric carbons are created

Trans-2-butene  meso compound

Additions of water – hydration reactions

Alcohols by oxymercuration-reduction

Markovnikov’s rule

No carbocation formation, no rearrangement

Additions of borane: hydroboration-oxidation

Anti-Markovnikov

Additions of hydrogen – hydrogenation

Reaction mechanism:

Syn addition

Stereochemistry

Alkene epoxidations – Anti hydroxylations

Stereochemistry

Reactions of epoxides

Stereochemistry Anti additions

Syn hydroxylations of alkenes

36

Permanganate cleavage of alkenes

Ozonolysis of alkenes

In the presence of an oxidizing agent, the products

will be ketones / carboxylic acids

Polymerizations

Chapter 6: CONJUGATED ALKADIENES

A non-polar molecule

Reactions of isolated dienes are just like

those of alkenes

4

NOMENCLATURE OF

ALKADIENES

6

PREPARATION OF 1,3-ALKADIENE

Dehydrogenations

Eliminations of unsaturated alcohols & alkyl halides

ELECTROPHILIC ADDITION

REACTIONS

Reaction mechanism:

12

DIELS-ALDER REACTIONS

Reactivity of the dienophile is increased if 1 or more

electron-withdrawing groups are present

Partial positive charge

Racemic mixture

In order to participate in a Diels-Alder reaction, the

diene must be in an s-cis conformation

C1 & C4 are too far apart

to react with the

dienophile

Polymerizations

functional group gets the lower number

The same low number for both directions, lower number

for C=C

PREPARATION OF ALKYNES

Sources of acetylene

Alkynes by elimination reactions

REACTIONS OF ALKYNES

Acidic hydrogen

Only for primary alkyl halides

Additions of hydrogen halides (A

E

)

Additions of halogens (A

E

)

Additions of water – hydration reactions

Additions of boran – hydroboration & oxidation

Markovnikov’s rule

Anti-Markovnikov

Ozonolysis of alkynes

Ozonolysis used to be employed in structure determination, but has been superseded by

spectroscopic methods

Polymerizations

Chapter 8: ARENES

Benzene

CRITERIA FOR AROMATICITY

To be classified as aromatic, a compound must

meet both of the following criteria:

• It must have an un-interrupted cyclic π cloud

above & below the plane of the molecule

• The π cloud must contain (4n + 2) π electrons (n

= 0, 1, 2…)

un-interrupted

cyclic π cloud 6 π e = 4 x 1 + 2

cloud

NOMENCLATURE OF MONOSUBSTITUTED BENZENES

Name of substituent + benzene

Names have to be memorized:

1 of the substituents can be incorporated into a name:

Names

incorporating

2 substituents

Alphabetical

order

Lowest possible numbers

PREPARATION OF BENZENE

REACTIONS OF BENZENE

Halogenations of benzene

Reaction mechanism: electrophilic substitution

Catalyst regeneration

Nitration of benzene

Sulfonation of benzene

Reversible reaction

Reaction mechanism: electrophilic substitution

Friedel-Crafts Alkylations of benzene

18

Carbocation

rearrangement

20

Friedel-Crafts Acylations of benzene

Reaction mechanism: electrophilic substitution

Rearrangement

withdrawing

26

E/W

group

E/D

group

E/W

group

ADDITIONAL CONSIDERATIONS

More deactivating than halogen, the ring is too unreactive for

(only) Friedel-Crafts alkylations & acylations

Aniline & N-substituted anilines do NOT undergo Crafts reactions:

Friedel-More deactivating than

halogen

Phenol & anisole do undergo Friedel-Crafts reactions, orienting ortho & para – oxygen does NOT complex with

the Lewis acid

Also can NOT undergo nitration –

primary amines are easily oxidized

SYNTHESIS OF TRISUBSTITUTED BENZENES

More activating substituent controls the regioselectivity

HALOGENATIONS OF ALKYL

SUBSTITUENTS

NOT Lewis acid

Can undergo E1 & E2, S

N

1 & S

N

2 reactions as usual

OXIDATIONS OF ALKYL SUBSTITUENTS

NUCLEOPHILIC AROMATIC SUBSTITUTION REACTIONS

E/W groups must be positioned ortho / para to the halogen