1

AFB QO I 2007/08 1

Química Orgânica I

Ciências Farmacêuticas

Bioquímica

Química

AFB QO I 2007/08 2

Estrutura dos compostos orgânicos

� Estrutura 3D (rev)

� Propriedades (rev)

� Grupos funcionais

� Nomenclatura

� Análise conformacional

� Estereoquímica I

AFB QO I 2007/08 3

Adaptado de:

� Jo Blackburn; 2006, Prentice Hall

� Organic Chemistry, 6th Edition; L. G. Wade, Jr.

AFB QO I 2007/08 4

H2: s-s overlap

=>

AFB QO I 2007/08 5

Cl2: p-p overlap

=>

Constructive overlap along the same

axis forms a sigma bond.

AFB QO I 2007/08 6

HCl: s-p overlap

HCl

=>

2

AFB QO I 2007/08 7

Pi Bonding

� Pi bonds form after sigma bonds.

� Sideways overlap of parallel p orbitals.

=>

AFB QO I 2007/08 8

Multiple Bonds

� A double bond (2 pairs of shared electrons) consists of a sigma bond and a pi bond.

� A triple bond (3 pairs of shared electrons) consists of a sigma bond and two pi bonds.

=>

AFB QO I 2007/08 9

Molecular Shapes

� VSEPR

� Hybridization

AFB QO I 2007/08 10

sp Hybrid Orbitals

� 2 VSEPR pairs

� Linear electron pair geometry

� 180° bond angle

=>

AFB QO I 2007/08 11

sp2 Hybrid Orbitals� 3 VSEPR pairs

� Trigonal planar e- pair geometry

� 120° bond angle

=>

AFB QO I 2007/08 12

sp3 Hybrid Orbitals

� 4 VSEPR pairs

� Tetrahedral e- pair geometry

� 109.5° bond angle

=>

3

AFB QO I 2007/08 13

Molecular Dipole Moments

� Depend on bond polarity and bond angles.

� Vector sum of the bond dipole moments.

=>AFB QO I 2007/08 14

Effect of Lone Pairs

Lone pairs of electrons contribute to the dipole moment.

=>

AFB QO I 2007/08 15

Intermolecular Forces

� Strength of attractions between molecules influence m.p., b.p., and solubility, esp. for solids and liquids.

� Classification depends on structure.� Dipole-dipole interactions

� London dispersions

� Hydrogen bonding

=>

AFB QO I 2007/08 16

Dipole-Dipole Forces

� Between polar molecules.

� Positive end of one molecule aligns with negative end of another molecule.

� Lower energy than repulsions, so net force is attractive.

� Larger dipoles cause higher boiling points and higher heats of vaporization.

=>

AFB QO I 2007/08 17

Dipole-Dipole

=>

AFB QO I 2007/08 18

London Dispersions

� Between nonpolar molecules

� Temporary dipole-dipole interactions

� Larger atoms are more polarizable.

� Branching lowers b.p. because of decreased surface contact between molecules.

=>

4

AFB QO I 2007/08 19

Dispersions

=>

AFB QO I 2007/08 20

Hydrogen Bonding

� Strong dipole-dipole attraction.

� Organic molecule must have N-H or O-H.

� The hydrogen from one molecule is strongly attracted to a lone pair of electrons on the other molecule.

� O-H more polar than N-H, so stronger hydrogen bonding. =>

AFB QO I 2007/08 21

H Bonds

=>AFB QO I 2007/08 22

Boiling Points and Intermolecular Forces

CH3 CH2 OH

ethanol, b.p. = 78°C

CH3 O CH3

dimethyl ether, b.p. = -25°C

trimethylamine, b.p. 3.5°C

N CH3H3C

CH3

propylamine, b.p. 49°C

CH3CH2CH2 N

H

H

ethylmethylamine, b.p. 37°C

N CH3CH3CH2

H

CH3 CH2 OH CH3 CH2 NH2

ethanol, b.p. = 78°C ethyl amine, b.p. = 17 °C

AFB QO I 2007/08 23

Solubility

� Like dissolves like.

� Polar solutes dissolve in polar solvents.

� Nonpolar solutes dissolve in nonpolarsolvents.

� Molecules with similar intermolecular forces will mix freely.

=>AFB QO I 2007/08 24

Ionic Solute with Polar Solvent

Hydration releases energy.

Entropy increases.=>

5

AFB QO I 2007/08 25

Ionic Solute withNonpolar Solvent

=>AFB QO I 2007/08 26

Nonpolar Solute withNonpolar Solvent

=>

AFB QO I 2007/08 27

Nonpolar Solute with Polar Solvent

=>AFB QO I 2007/08 28

Classes of Compounds

� Classification based on functional group.

� Three broad classes� Hydrocarbons

� Compounds containing oxygen

� Compounds containing nitrogen.

=>

AFB QO I 2007/08 29

Hydrocarbons

� Alkane: single bonds, sp3 carbons

� Cycloalkane: carbons form a ring

� Alkene: double bond, sp2 carbons

� Cycloalkene: double bond in ring

� Alkyne: triple bond, sp carbons

� Aromatic: contains a benzene ring

=>

AFB QO I 2007/08 30

Compounds Containing Oxygen

� Alcohol: R-OH

� Ether: R-O-R'

� Aldehyde: RCHO

� Ketone: RCOR'

CH3CH2 C

O

H

CH3 C

O

CH3

=>

6

AFB QO I 2007/08 31

Carboxylic Acids and Their Derivatives

� Carboxylic Acid: RCOOH

� Acid Chloride: RCOCl

� Ester: RCOOR'

� Amide: RCONH2

C

O

OH

C

O

Cl

C

O

O CH3C

O

NH2

=>AFB QO I 2007/08 32

Compounds Containing Nitrogen� Amines: RNH2, RNHR', or R3N

� Amides: RCONH2, RCONHR, RCONR2

� Nitrile: RCN

N

O

CH3

CH3 C N

=>

AFB QO I 2007/08 33

Classification Review

AFB QO I 2007/08 34

Alkane Formulas

� All C-C single bonds

� Saturated with hydrogens

� Ratio: CnH2n+2

� Alkane homologs: CH3(CH2)nCH3

� Same ratio for branched alkanes

=>

C

H

C

H

H

H C H

H

H

C H

H

H

Isobutane, C 4H10

C

H

C

H

H

H C C

H

HH H

H

H

Butane, C4H10

AFB QO I 2007/08 35

Common Names

� Isobutane, “isomer of butane”

� Isopentane, isohexane, etc., methyl branch on next-to-last carbon in chain.

� Neopentane, most highly branched

� Five possible isomers of hexane,18 isomers of octane and 75 for decane!

=>AFB QO I 2007/08 36

Alkane Examples

=>

7

AFB QO I 2007/08 37

IUPAC Names� Find the longest continuous carbon chain.

� Number the carbons, starting closest to the first branch.

� Name the groups attached to the chain, using the carbon number as the locator.

� Alphabetize substituents.

� Use di-, tri-, etc., for multiples of same substituent.

=>

AFB QO I 2007/08 38

Longest Chain

� The number of carbons in the longest chain determines the base name: ethane, hexane. (Listed in Table 3.2, page 82.)

� If there are two possible chains with the same number of carbons, use the chain with the most substituents.

C

CH3

CH2

CH3

CH CH2 CH2 CH3

CH CH2 CH3

H3C

H3C

=>

AFB QO I 2007/08 39

Number the Carbons

� Start at the end closest to the first attached group.

� If two substituents are equidistant, look for the next closest group.

1

2

3 4 5

6 7

CHH3C

CH3

CH

CH2CH3

CH2 CH2 CH

CH3

CH3

=>

AFB QO I 2007/08 40

Name Alkyl Groups

� CH3-, methyl

� CH3CH2-, ethyl

� CH3CH2CH2-, n-propyl

� CH3CH2CH2CH2-, n-butyl

CH3 CH CH2 CH3

sec-butyl

CH3 CH

CH3

CH2

isobutyl

C H3 C H C H3

isopropyl

CH3C

CH3

CH3

tert-butyl

=>

AFB QO I 2007/08 41

Propyl Groups

C

H

H

H

C

H

H

C

H

H

H

n-propyl

C

H

H

H

C

H

C

H

H

H

isopropyl

H

A primary carbon A secondary carbon

=>

AFB QO I 2007/08 42

Butyl Groups

C

H

H

H

C

H

C

H

H

C

H

H

H

C

H

H

H

C

H

C

H

HH

C

H

H

n-butyl sec-butyl

H

H

A primary carbon A secondary carbon

=>

8

AFB QO I 2007/08 43

Isobutyl Groups

CH

H

H

C

C

H H

C

H

H

H H

CH

H

H

C

C

H H

C H

H

H

H

H

H

A primary carbon A tertiary carbon

=>

isobutyl tert-butyl

AFB QO I 2007/08 44

Alphabetize

� Alphabetize substituents by name.

� Ignore di-, tri-, etc. for alphabetizing.

CHH3C

CH3

CH

CH2CH3

CH2 CH2 CH

CH3

CH3

3-ethyl-2,6-dimethylheptane=>

AFB QO I 2007/08 45

Complex Substituents

� If the branch has a branch, number the carbons from the point of attachment.

� Name the branch off the branch using a locator number.

� Parentheses are used around the complex branch name.

12

31-methyl-3-(1,2-dimethylpropyl)cyclohexane =>

AFB QO I 2007/08 46

Physical Properties

� Solubility: hydrophobic

� Density: less than 1 g/mL

� Boiling points increase with increasing carbons (little less for branched chains).

Melting points increase with

increasing carbons (less for odd-

number of carbons).

•

AFB QO I 2007/08 47

Boiling Points of AlkanesBranched alkanes have less surface area contact,so weaker intermolecular forces.

=>

AFB QO I 2007/08 48

Melting Points of Alkanes

Branched alkanes pack more efficiently intoa crystalline structure, so have higher m.p.

=>

9

AFB QO I 2007/08 49

Branched Alkanes

� Lower b.p. with increased branching

� Higher m.p. with increased branching

� Examples:

H

CH3CH

CH3

CH2 CH2 CH3

bp 60°Cmp -154°C

CH3CH

CH3

CHCH3

CH3

bp 58°Cmp -135°C

=>

bp 50°Cmp -98°C

CH3 C

C 3

CH3

CH2 CH3

AFB QO I 2007/08 50

Major Uses of Alkanes

� C1-C2: gases (natural gas)

� C3-C4: liquified petroleum (LPG)

� C5-C8: gasoline

� C9-C16: diesel, kerosene, jet fuel

� C17-up: lubricating oils, heating oil

� Origin: petroleum refining

=>

AFB QO I 2007/08 51

Reactions of Alkanes

� Combustion

CH3CH2CH2CH3 + O2 CO2 + H2Oheat

8 10132

long-chain alkanes catalyst

shorter-chain alkanes

CH4 + Cl2 CH3Cl + CH2Cl2 CHCl3 CCl4+ +

heat or light

=>

• Cracking and hydrocracking (industrial)

• Halogenation

AFB QO I 2007/08 52

Conformers of Alkanes

� Structures resulting from the free rotation of a C-C single bond

� May differ in energy. The lowest-energy conformer is most prevalent.

� Molecules constantly rotate through all the possible conformations.

=>

AFB QO I 2007/08 53

Ethane Conformers

� Staggered conformer has lowest energy.

� Dihedral angle = 60 degrees

H

H

H

H

H H

Newman

projectionsawhorse

=>

modelAFB QO I 2007/08 54

Ethane Conformers (2)

� Eclipsed conformer has highest energy

� Dihedral angle = 0 degrees

=>

10

AFB QO I 2007/08 55

Conformational Analysis

� Torsional strain: resistance to rotation.

� For ethane, only 12.6 kJ/mol

=>AFB QO I 2007/08 56

Propane Conformers

Note slight increase in torsional strain

due to the more bulky methyl group.

=>

AFB QO I 2007/08 57

Butane Conformers C2-C3� Highest energy has methyl groups eclipsed.

� Steric hindrance

� Dihedral angle = 0 degrees

=>totally eclipsed

AFB QO I 2007/08 58

Conformational Analysis

=>

AFB QO I 2007/08 59

Higher Alkanes

� Anti conformation is lowest in energy.

� “Straight chain” actually is zigzag.CH3CH2CH2CH2CH3

C

H CC

CC

H H H H

H H

H H

HH H =>

AFB QO I 2007/08 60

Cycloalkanes� Rings of carbon atoms (-CH2-

groups)

� Formula: CnH2n

� Nonpolar, insoluble in water

� Compact shape

� Melting and boiling points similar to branched alkanes with same number of carbons =>

11

AFB QO I 2007/08 61

Naming Cycloalkanes

CH2CH3

CH2CH3

CH3

AFB QO I 2007/08 62

Cis-Trans Isomerism

� Cis: like groups on same side of ring

� Trans: like groups on opposite sides of ring

=>

AFB QO I 2007/08 63

Cycloalkane Stability

� 5- and 6-membered rings most stable

� Bond angle closest to 109.5°

� Angle (Baeyer) strain

� Measured by heats of combustion per -CH2 -

=>

AFB QO I 2007/08 64

Heats of Combustion/CH2

Alkane + O2 → CO2 + H2O

Long-chain

658.6 kJ 658.6

697.1 686.1664.0 663.6 kJ/mol

=>

662.4

AFB QO I 2007/08 65

Cyclopropane� Large ring strain due to angle compression

� Very reactive, weak bonds

=>AFB QO I 2007/08 66

Cyclopropane (2)

Torsional strain because of eclipsed hydrogens

=>

12

AFB QO I 2007/08 67

Cyclobutane

� Angle strain due to compression

� Torsional strain partially relieved by ring-puckering

=>AFB QO I 2007/08 68

Cyclopentane� If planar, angles would be 108°, but all

hydrogens would be eclipsed.

� Puckered conformer reduces torsionalstrain.

=>

AFB QO I 2007/08 69

Cyclohexane

� Combustion data shows it’s unstrained.

� Angles would be 120°, if planar.

� The chair conformer has 109.5° bond angles and all hydrogens are staggered.

� No angle strain and no torsionalstrain.

=>AFB QO I 2007/08 70

Chair Conformer

=>

AFB QO I 2007/08 71

Boat Conformer

=>

AFB QO I 2007/08 72

Conformational Energy

=>

13

AFB QO I 2007/08 73

Axial and Equatorial Positions

=>

AFB QO I 2007/08 74

Monosubstituted Cyclohexanes

=>

AFB QO I 2007/08 75

1,3-Diaxial Interactions

=>

AFB QO I 2007/08 76

Disubstituted Cyclohexanes

=>

AFB QO I 2007/08 77

Cis-Trans Isomers

Bonds that are cis, alternate axial-equatorial around the ring.

=>

CH3

CH3

One axial, one equatorial

AFB QO I 2007/08 78

Bulky Groups

� Groups like t-butyl cause a large energy difference between the axial and equatorial conformer.

� Most stable conformer puts t-butyl equatorial regardless of other substituents.

=>

14

AFB QO I 2007/08 79

Bicyclic Alkanes� Fused rings share two adjacent carbons.

� Bridged rings share two nonadjacent C’s.

bicyclo[3.1.0]hexane=>

bicyclo[2.2.1]heptane

AFB QO I 2007/08 80

Cis- and Trans-Decalin

� Fused cyclohexane chair conformers

� Bridgehead H’s cis, structure more flexible

� Bridgehead H’s trans, no ring flip possible.

H

H

cis-decalin

H

H

=>

trans-decalin

AFB QO I 2007/08 81

Bicyclo[4.4.0]decane

=>AFB QO I 2007/08 82

STEREOCHEMISTRY I

AFB QO I 2007/08 83

Stereochemistry 1

web.chem.ucla.edu/~harding/ppt/14C_stereo.ppt

AFB QO I 2007/08 84

Stereochemistry: What is It?

Isomers

•Molecules with same chemical formula but different spatial

arrangement of atoms

Constitutional isomers

•Differ in sequence of atom connectivity

Urea

CH4N2O

H2N NH2

O

Ammonium cyanate

CH4N2O

NH

H

H

H

O C N

•Jöns Jakob Berzelius, 1830

15

AFB QO I 2007/08 85

Stereochemistry: What is It?Isomers

•Same sequence of connectivity, but can be interconverted by rotation

around a single bond

rotate around

C2-C3 bond

Butane C4H10

Eclipsed conformation

Conformational isomers

Are other isomers possible? Tetrahedral carbon...

click on movie to play

Butane C4H10

Staggered conformation

AFB QO I 2007/08 86

Historical BackgroundTimeline A: Light

1678: Christiaan Huygens discovers plane-polarized light

many vibrational planes

nonpolarized light

one vibrational plane

plane-polarized light

light beam

Iceland spar crystal

(natural CaCO3)

AFB QO I 2007/08 87

Historical BackgroundTimeline A: Light

1815: Jean Baptiste Biot notes some natural substances rotate plane-polarized light

polarization plane shiftedtube of liquid organic

compound or solution

plane-polarized light

Optically active: the ability to rotate plane-polarized light

Optically inactive: does not rotate plane-polarized light

AFB QO I 2007/08 88

Historical BackgroundTimeline A: Light

Dextrorotatory: rotates plane-polarized light in a clockwise direction (+)

Levorotatory: rotates plane-polarized light in a counterclockwise direction (-)

Optical activity

(-)-Nicotine

N

N

H

CH3

(+)-Methamphetamine

CH3

N

H3C H

H

AFB QO I 2007/08 89

Historical BackgroundTimeline B: Tartaric Acid

Tartaric acid

Racemic acidOH

OH

HO

HO

O

O

1828: Joseph Louis Gay-Lussac shows tartaric acid and racemicacid are isomers

1819: Paul Kester isolates racemic acid from tartar

From Latin racemus: bunch of grapes

1769: Carl Wilhelm Scheele examines tartar (deposited in casks

during wine fermentation); isolates tartaric acid

AFB QO I 2007/08 90

Historical BackgroundTimeline B: Tartaric Acid

1838: Biot notes racemic acid is optically inactive

1832: Jean Baptiste-Biot notes tartaric acid is optically active

1847: Louis Pasteur separates ammonium sodium salt of

racemic acid into (+) and (-) crystals

16

AFB QO I 2007/08 91

Historical BackgroundTimeline B: Tartaric Acid

O Na

O NH4

HO

HO

O

O

Ammonium sodium racemateoptically inactive

(+)-tartaric acidoptically active

identical to Scheele’s tartaric acid

(-)-tartaric acidoptically active

Pasteur’s separation of racemic acid

Quantity: equal

Optical activity: equal but opposite

Conclusion: Racemic acid is a 1:1 mixture of two optically-active substances

separate crystals

AFB QO I 2007/08 92

Historical BackgroundTimeline B: Tartaric Acid

1853: Pasteur investigates mesotartaric acid

Mesotartaric acid

OH

OH

HO

HO

O

O

•Artificial, optically-inactive isomer of tartaric acid

•Cannot be separated into (+) and (-) forms

•Tartaric acid isomers have different biological properties

1854: Pasteur notes a certain plant mold metabolizes (+) but not (-)-tartaric acid

AFB QO I 2007/08 93

Historical BackgroundTimeline C: Tetrahedral Carbon

A molecule having a tetrahedral carbon atom with four unequal

attachments exists as a pair of isomers.

propose:

1874: Joseph Achille Le Bel (age 27) and Jacobus Henricus van’t Hoff (age 22)

AFB QO I 2007/08 94

Historical BackgroundTimeline C: Tetrahedral Carbon

Example: 2-chlorobutane

CH3CH2

C

CH3

Cl H

Stereoisomers: isomers that differ only in the position of atoms in space,

and cannot be interconverted by rotation around a single bond

Constitutional isomers?

Conformational isomers? Cannot be made superposable by bond rotation

Verify with models

Identical? Not superposable Verify with models

Same atom connectivity sequence H C

H

H

C

H

H

C

H

Cl

C

H

H

H

C

CH2CH3CH3

H Cl