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ORGANIC CHEMISTRY

Faculty of Chemical EngineeringHCMC University of Technology

Office: room 211, B2 BuildingPhone: 38647256 ext. 5681

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REFERENCES[1] Nam T. S. Phan, Hoa T. V. Tran ‘Organic chemistry’,

VNU-HCMC Publisher, 2011[2] Nam T. S. Phan, ‘Study guide to organic chemistry’,

VNU-HCMC Publisher, 2011[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

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

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Chapter 1: ISOMERISMIsomers: Compounds with the same molecular formula

but different structural formulas

Constitutional isomers

Conformational isomers

Optical isomers /Enantiomers &DiastereoisomersGeometric isomers

Configurational isomers

Stereoisomers

Isomers

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CONSTITUTIONAL ISOMERSDifferent compounds that have the same molecular

formula – but differ in their connectivity

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STEREOISOMERSIsomers that differ in the way their atoms

are arranged in space

Conformational isomers Configurational isomers

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CONFORMATIONAL ISOMERS

• Different shapes of the same molecule resulting from rotation around a single C-C bond

• Conformational isomers are not different compounds

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Conformations of butane

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Conformations of cyclohexane

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GEOMETRIC ISOMERS

There is no rotation around the C=C bond

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The E,Z system of nomenclature

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Cahn-Ingold-Prelog priority rules

Rule 1

Rule 2

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Rule 3

Rule 4

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A chiral opbject

OPTICAL ISOMERS

Nonsuperimposable mirror image

An achiral object

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Optical isomers are configurational isomerswhich are able to rotate plane-polarized light

clockwise or anticlockwise

OPTICAL ISOMERS

plane-polarized light

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Optically active

Optically inactive

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An asymmetric carbon is a carbon atom that is bonded to 4 different groups

Asymmetric carbon

Optically active (chiral)

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Isomers with one asymmetric carbon

Nonsuperimposable mirror-image molecules are called enantiomers

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Drawing enantiomersUsing perspective formulas:

• 2 bonds in the paper plane• 1 bond as a solid wedge• 1 bond as a hatched wedge

Convention

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Drawing enantiomers

Using Fisher Projection formulas:

Convention

• Carbon chain is drawn along the vertical line

• Vertical lines: bonds going into the page

• Horizontal lines: bonds coming out of the page

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NAMING ENANTIOMERSABSOLUTE CONFIGURATION: R-S SYSTEM

Convention for

perspective 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

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Convention for Fisher Projection formulas

• Using Cahn-Ingold-Prelog rules

• When the lowest priority group is on a vertical bond:+ If the direction from highest priority group to the next is clockwise: R+ If the direction is anticlockwise:S

• When the lowest priority group is on a horizontal bond:+ opposite answers

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NAMING ENANTIOMERSRELATIVE CONFIGURATION: D-L SYSTEM

Glyceraldehyde: the standard compound for chemical correlation of configuration

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D-L system is only useful for naming sugars & aminoacids

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Isomers with more than one asymmetric carbon

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Meso compounds

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Enantiomers vs diastereoisomers

• Enantiomers: Nonsuperimposable mirror images

• Diastereoisomers: not mirror images of each other

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• 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

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Separating enantiomers

Racemic mixture:1/1 mixture of 2 enantiomers

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CHIRALITY & BIOLOGICAL ACTIVITY

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CHIRALITY & BIOLOGICAL ACTIVITY

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Chapter 2: ELECTRONIC & STERIC EFFECTS

Conjugation / Mesomeric

Steric Electronic

Inductive Hyperconjugation

Effects

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INDUCTIVE EFFECTS (I)C-C σ bond in butane: almost completely nonpolar

δ-

δ+δ'+δ''+

δ'''+

C-C σ bond in 1-fluorobutane: polarized

C1 is more positive than C2 as a result of electron-attracting ability of F

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The more electronegative the X, the stronger the –I

effect

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The more electropositive the Z, the stronger the +I effect

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-I

-I

Through a period in a periodic table

Through a group in a periodic

table

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Ka.105

CH3CH2CH2COOH 1.5CH3CH2CH(Cl)COOH 139CH3CH(Cl)CH2COOH 8.9ClCH2CH2CH2COOH 3.0

Strong -I

weak -I

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CONJUGATION / MESOMERIC EFFECTS (C / M)

Electron delocalization in a conjugated system:Alternating

single & multiple bonds

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O is more electronegative than C

Electrons 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

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+C-C

C CH CH CH CHR

+C-C

C O R

CH CH CH CHR O R

+C-C

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OH +C

-C

O H -C

+C

NH2 +C

-C

-C

+C

N

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-C groups generally contain an electronegative atom (s)

or / and a π-bond (s):

CHO, C(O)R, COOH, COOR, NO2, CN, aromatics, alkenes

Cl, Br, OH, OR, SH, SR, NH2, NHR, NR2, aromatics, alkenes

+C groups generally contain a lone pair of electrons

or a π-bond (s):

Aromatics or alkenes can be both +C and-C

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+C

Through a period in a periodic table

Through a group in a periodic

table

+C

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CH CH CH CHH C

H CH CH C

CH CH CH CHCH CCHHO

H

H

O

H

O

INDUCTIVE vs CONJUGATION EFFECTS

Mobility of hydrogen atoms: almost the same

-C

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INDUCTIVE vs CONJUGATION EFFECTS

• C effects are generally stronger than I effects

• 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

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HYPERCONJUGATION EFFECTS (H)

Electron density from Cα-H flows into the vacant p orbital (in carbocation / C=C / C≡C) because orbitals can partially

overlap

Hyperconjugation effects (H)

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H CH

HCH CH CH2 CH3δ+ δ−

HCl

CH3 CH

Cl

CH2 CH2 CH3

•H effect of -CH3 is stronger than H effect of -CH2-

•H effect is generally stronger than I effect

Electron-donating ability of -CH3 is stronger than that of -CH2CH3

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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

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Steric hindrance

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Steric hindrance

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ACIDITY & BASICITY

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Electron-donating groups

Electron-withdrawing

groups

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Electron-donating groups

Electron-withdrawing

groups

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If –C groups are introduced at ortho- & paraposition 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

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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

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OH

NO2

OHNO2

OH

NO2

OH

CH3

OHCH3

OH

CH3

> >

> >

pKa 7.15 7.23 8.4

10.08 10.14 10.28pKa

=

=

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OH

OCH3

OHOCH3

OH

OCH3

OHCl

OH

Cl

OH

Cl

> >

> >

9.65 9.98 10.21

8.48 9.02 9.38

pKa =

pKa =

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Benzoic acid derivativespKa

Position on benzene ringOrtho- Meta- Para-

CH3C6H4COOH 3.91 4.27 4.36NH2C6H4COOH 4.97 4.78 4.92FC6H4COOH 3.27 3.87 4.14ClC6H4COOH 2.92 3.82 3.98BrC6H4COOH 2.85 3.81 3.97IC6H4COOH 2.86 3.85 4.02HOC6H4COOH 2.97 4.06 4.48CH3OC6H4COOH 4.09 4.09 4.47NCC6H4COOH 3.14 3.84 3.55NO2C6H4COOH 2.16 3.47 3.41

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CH3CH2CH CHCOOH CH2 CHCH2CH2COOH CH3CH CHCH2COOH

pKa = 4.83 pKa = 4.68 pKa = 4.48

< <

+C dominates

-I is decreased over long distance

-I dominates

HC C C CCOOH COOHH3C

pKa = 1.84 pKa = 2.60

+C and -I but -I dominates

+C and -I but -I dominates

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X pKa of ammonium cationo- m- p-

CH3 4.39 4.69 5.12CH3O 4.49 4.20 5.29C2H5O 4.47 4.17 5.25C6H5 3.78 4.18 4.27F 3.20 3.59 4.65Cl 2.61 3.34 3.98Br 2.60 3.51 3.91I 2.60 3,61 3,78CH3OCO 2,23 3.64 2.38CF3 --- 3.50 2.60CN --- 2.76 1.74NO2 -0.29 2,50 1,02

Basicity of

XC6H4NH2

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STABILITY OF CARBOCATIONS

+H & +I

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Allylic & benzylic carbocations

+C +C

Allylic & benzylic carbocations are generally stable due to the electron delocalization (+C effects)

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Not all allylic & benzylic carbocations have the same stability

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Relative stability of carbocations

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STABILITY OF RADICALS

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STABILITY OF CARBANIONS

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Chapter 3: INTRODUCTION TO REACTION MECHANISMS

Elimination

Electrophilic substitution

Nucleophilic substitution Nucleophilic addition

Electrophilic addition

Reaction mechanism: the description of the step-by-step process by which reactants

are changed / converted into products

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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

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BIMOLECULAR NUCLEOPHILIC SUBSTITUTION REACTION (SN2)

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UNIMOLECULAR NUCLEOPHILIC SUBSTITUTION REACTION (SN1)

7Note: slow step is rate-determining step

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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

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BIMOLECULAR ELMINATION (E2)

Strong base

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UNIMOLECULAR ELMINATION (E1)

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Weak base

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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 electronsAn electrophilic addition reaction is an addition reaction where carbon-carbon double bonds or

triple bonds are attacked by an electrophile

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•Not a carbocation, but a cyclic halonium ion

• More stable than carbocation

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NUCLEOPHILIC ADDITION REACTIONS (AN)

The carbonyl group is polar because the oxygen, being more electronegative, has greater share of double-bond

electrons

The partial positive carbon can be attacked

by nucleophiles

The addition of nucleophiles to the carbon atom of the carbonyl group in nucleophilic

addition reactions

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Reaction mechanism

A nucleophilePositive center

slow

Rate-determining step

fast

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Examples:

Nucleophiles

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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

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Reaction mechanism

An electrophile

Rate-determining step

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Examples:

An electrophile

Rate-determining step

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Chapter 4: ALKANES

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NOMENCLATURE OF ALKANES

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ALKYL SUBSTITUENTS

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IUPAC NAMES OF BRANCHED ALKANES

Determine the parent hydrocarbon – the longest continuous carbon chain

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• Substituents are listed in alphabetical order

• Carbon chain is numbered with the lowest possible numberin the compound

Substituents are the same

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• Di, tri, tetra, n, sec, and tert are ignored in alphabetizing substituents

• Iso, neo, and cyclo are not ignored

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NATURAL SOURCES OF ALKANES

Natural gas & petroleum

(fossil fuels)

C1-4

C5-11

C9-16

C15-25

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PREPARATION OF ALKANES

Catalytic hydrogenations of alkenes / alkynes

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Reduction reactions

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Wurtz reactions symmetric alkane

Limitations:

+ The Wurtz reaction is limited to the synthesis of symmetric alkanes from alkyl iodides & bromides

+ If two dissimilar alkyl halides are taken as reactants, then the product is a mixture of alkanes that is, often, difficult to separate

+ A side reaction also occurs to produce an alkene

+ The side reaction becomes more significant when the alkyl halides are bulky at the halogen-attached carbon

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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

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REACTIVITY OF ALKANES• Alkanes have only strong σ bonds

• Electronegativity of C & H are approximately the same

• None of the atoms in alkanes have any significant charge

• Neither nucleophiles nor electrophiles are attracted

Alkanes are very unreactive

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HALOGENATION OF ALKANES

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PRODUCT DISTRIBUTION

It must be easier to abstract a hydrogen atom from a secondary carbon than from a primary carbon

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Reactivity - relative rate at which a particular hydrogen is abstracted in chlorination reactions:

At room temperature

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Product distribution can be estimated:

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Br2 is less reactive towards alkane than Cl2, but Br2 is more selective

Bromination at 125 oC

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Too violent

Too slow

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STEREOCHEMISTRY OF RADICAL SUBSTITUTION REACTIONS

Have no asymetric

carbon

Racemic mixture

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Already have 1 asymetric

carbon

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COMBUSTION OF ALKANES

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Chapter 5: ALKENES

An sp2

hybridized carbon

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NOMENCLATURE OF ALKENES

• Ethylene is an acceptable synonym for ethene in the IUPAC system

• Propylene, isobutylene and other common names ending in “ylene” are NOT acceptable IUPAC names

The IUPAC name of an alkene is obtained by replacing the “ane” ending of the corresponding alkane with “ene”

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Determine the parent hydrocarbon – the longest continuous carbon chain containing the C=C

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Note: Alkenes can have geometric isomers

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PREPARATION OF ALKENESDehydrations of alcohols

isomerization

Acid

7isomerization

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Eliminations of alkyl halides

Base

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Alkyne hydrogenationsPd/CaCO3 + Pb(OAc)2 / quinoline

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REACTIONS OF ALKENESAdditions of hydrogen halides (AE)

More stable

Markovnikov’s rule

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Carbocation rearrangement

More stable

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Stereochemistry

Racemic mixture

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Already has 1 asymmetric carbon

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2 asymmetric carbons are created

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Additions of hydrogen bromide (AR)

Radical addition (AR) – only for HBr

Electrophilic addition (AE)

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Reaction mechanism:

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Additions of halogens

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Major addition product –NOT a dihalide

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Stereochemistry

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Stereochemistry

2 asymmetric carbons are created

Trans-2-butene meso compound

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Additions of water – hydration reactionsWater is too weakly acidic to allow the hydrogen to act

as an electrophile

H2SO4, H3PO4…

Markovnikov’s rule

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Reaction mechanism:

Carbocation rearrangement

might occur

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Alcohols by oxymercuration-reduction

Markovnikov’s rule

No carbocation formation, no rearrangement

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Additions of borane: hydroboration-oxidation

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Regioselectivity:

Anti-Markovnikov

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Additions of hydrogen – hydrogenation

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Reaction mechanism:

Syn addition

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Stereochemistry

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Alkene epoxidations – Anti hydroxylations

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Stereochemistry

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Reactions of epoxides

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Stereochemistry Anti additions

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Syn hydroxylations of alkenes

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Reaction mechanism: Syn additions

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Permanganate cleavage of alkenes

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Ozonolysis of alkenes

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In the presence of an oxidizing agent, the products will be ketones / carboxylic acids

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Polymerizations