chapter 2 intro to alkane

Chapter 2:Chapter 2: Alkanes, Alkanes, Thermodynamics, and Thermodynamics, and

KineticsKinetics

2,2,4-Trimethylpentane:2,2,4-Trimethylpentane:An An octaneoctane

CombustionCombustion

How warm,How warm,how fast?how fast?

PetroleuPetroleum!!m!!

All Reactions Are All Reactions Are EquilibriaEquilibria

-23.4 kcal/mol-23.4 kcal/mol

““Barrier” kcal/molBarrier” kcal/mol ExothermicitExothermicityy

CHCH33Cl + NaCl + Na++ --

OHOHCH3OH + Na + Na+ + ClCl--

CHCH4 4 + + OO22

COCO22 + 2H + 2H22OO

What governs these What governs these equilibria?equilibria?

~20~20

highhigh

-213 kcal/mol-213 kcal/molEquilibrium lies very much to the right.Equilibrium lies very much to the right.

oror

1.1. Chemical Thermodynamics:Chemical Thermodynamics:

Energy changes during reaction, extent of Energy changes during reaction, extent of “completion of equilibration,” “to the “completion of equilibration,” “to the left/right,” “driving force.”left/right,” “driving force.”

2. Chemical Kinetics2. Chemical Kinetics: :

How fast is equilibrium established; rates of How fast is equilibrium established; rates of disappearance of starting materials or disappearance of starting materials or appearance of productsappearance of products

Chemical Thermodynamics and Chemical Thermodynamics and KineticsKinetics

The two principles may or may not go in tandemThe two principles may or may not go in tandem

[ ][ ] = concentration in mol = concentration in mol LL-1-1

Equilibria: Two typical casesEquilibria: Two typical cases

[[AA] ] [[reactantsreactants]]

[[BB]] [[productsproducts]]

K K = equilibrium = equilibrium constantconstant

AA BB

KK = =[[CC][][DD]]

[[AA][][BB]]

If If KK large: reaction “complete,” “to the right,” large: reaction “complete,” “to the right,”

“downhill.” “downhill.” How do we quantify?How do we quantify? Gibbs free Gibbs free energy, ∆energy, ∆G°G°

KK

A +BA +B C + C + DD

KK

==KK ==1.1.

2.2.

Gibbs Free Energy, ∆Gibbs Free Energy, ∆G°G°

∆∆G° G° = -= -RRT T lnlnKK = -2.3 = -2.3 RRT T loglogKK

TT in kelvins, K (zero kelvin = -273 °C) in kelvins, K (zero kelvin = -273 °C)

RR = gas constant ~ 2cal deg = gas constant ~ 2cal deg-1-1 mol mol-1-1

Large Large KK : Large : Large negativenegative ∆ ∆G° G° : : downhilldownhill

At 25ºC (298°K): At 25ºC (298°K): ΔΔGºGº = - 1.36 log = - 1.36 logKK

Equilibria and Free Equilibria and Free EnergyEnergy

∆∆G°G° = = ∆∆H°H° - - TT∆∆S°S° calcal-1-1 deg deg-1-1 mol mol-1-1 or or entropy unitsentropy units, ,

Kcal molKcal mol--11

Enthalpy Enthalpy ∆∆H°H° = = heatheat of the reaction; of the reaction; for us, mainly due to changes in bond for us, mainly due to changes in bond strengths: strengths:

∆∆H°H° = (Sum of strength of bonds = (Sum of strength of bonds broken) – (sum of strengths of broken) – (sum of strengths of

bonds made)bonds made)

Enthalpy Enthalpy ∆∆H°H° and and Entropy Entropy ∆∆S°S°

or or e.u.e.u.

CCHH33CCHH22――HH ClCl――ClCl CCHH33CCHH22――ClCl + + HH――ClCl

101101 10310384845858

∆∆H°H° negative: called “ negative: called “exothermicexothermic” ” if positive: called “if positive: called “endothermicendothermic””

∆∆S°S° = change in the = change in the “order” “order” of the of the system. Nature strives for disorder. system. Nature strives for disorder. More disorder = More disorder = positivepositive ∆∆S S °° (makes a negative contribution to (makes a negative contribution to ∆∆G° G° ) )

∆∆H°H° = 159 – 187 = -28 kcalmol = 159 – 187 = -28 kcalmol-1-1

++

Example:Example:

Boltzmann’s Tombstone (1844-Boltzmann’s Tombstone (1844-1906) 1906)

SS = = kk x log x logWW““ChaosChaos””

EntropyEntropyBoltzmann’s constantBoltzmann’s constant

Two balls in two tight boxes:Two balls in two tight boxes:

A.A. Confined to one box: Confined to one box:

1 Way1 Way

B.B. Open access to second box: Open access to second box:

6 Ways: 1-2, 1-3, 1-4, 2-3, 2-4, 3-46 Ways: 1-2, 1-3, 1-4, 2-3, 2-4, 3-4

(Microstates (Microstates or extent of or extent of

freedom)freedom)

Ice cream Ice cream makers:makers:cool withcool withice/NaClice/NaCl;;Dissolution of Dissolution of salt issalt isendothermicendothermic,,but driven bybut driven byentropyentropy

∆∆H°H° = -15.5 kcal mol = -15.5 kcal mol-1-1

If # of molecules If # of molecules unchanged, unchanged, ∆∆S°S° small, small, ∆∆H°H° controls ( we can estimate controls ( we can estimate value from bond strength value from bond strength tables)tables)

∆∆S°S° = -31.3 e.u. = -31.3 e.u.

CCHH2 2 CCHH22 + + HHClCl

CCHH33CCHH22ClCl

2 2 moleculesmolecules

1 1 moleculemolecule

Chemical example:Chemical example:

RatesRatesAll processes have All processes have “activation barriers”“activation barriers”. .

Rate controlled by: Rate controlled by:

1.1. Barrier heightBarrier height (structure of transition (structure of transition state TS)state TS)

2. 2. ConcentrationConcentration (the number of collisions (the number of collisions increase with concentration) increase with concentration)

3. 3. TT (increased T means faster moving (increased T means faster moving molecules; number of collisions molecules; number of collisions increases)increases)

4. “4. “ProbabilityProbability” factor (how likely is a ” factor (how likely is a collision to lead to reaction; depends on collision to lead to reaction; depends on sterics, electronics)sterics, electronics)

Boltzmann DistributionBoltzmann Distribution

The The average kinetic energyaverage kinetic energy of molecules at room of molecules at room temperature is temperature is ~ 0.6 kcal/mol~ 0.6 kcal/mol. .

What supplies the energy to get over the barrier?What supplies the energy to get over the barrier?

Rate measurements Rate measurements : Give : Give Rate LawsRate Laws, tell us , tell us something about TS structure. Most common:something about TS structure. Most common:

If rate = If rate = kk [A] [A]

Unimolecular Unimolecular reaction (TS involves only A) reaction (TS involves only A)

AA BB1.1.

Reaction RateReaction Rate

1st1st order order rate lawrate law

If rate = If rate = kk [A][B] [A][B] 22ndnd order order rate lawrate law

BimolecularBimolecular reaction (TS involves both A and B).reaction (TS involves both A and B).

How do we measure barrier ? How do we measure barrier ? Energy of Energy of activationactivation from Arrhenius equation: from Arrhenius equation:

kk ==

RTRT--EEaa

AeAe

2. A + B C2. A + B C

at high T, k = A, “maximum rate”

Potential Energy Potential Energy DiagramsDiagrams

ReactantReactant

ProductProduct[A][A]

[B][B]

∆∆H H °° (when (when ∆∆S S °° small)small)

∆∆G G °°

EEaa kkrrkkff

Reaction coordinate Reaction coordinate = progress of = progress of reactionreaction

k k forwardforward

k k reversereverse

KK == [A][A]

[B[B]] ==

[TS][TS]

EE

‡

Many reactions have many steps, but Many reactions have many steps, but there is always a there is always a rate determiningrate determining TSTS (bottleneck).(bottleneck).

TSTS

Rate Determining Transition Rate Determining Transition StateState

AABB

CC

Which is right: On heating,Which is right: On heating,a.a. Compound A converts to C directly.Compound A converts to C directly.b.b. It goes first to B and then to C.It goes first to B and then to C.c.c. It stays where it is.It stays where it is.

Problem:Problem:

AcidAcid--BaseBase Equilibria Equilibria

AcidAcid Conjugate BaseConjugate Base

Brønsted and Lowry: Brønsted and Lowry:

Acid = proton donorAcid = proton donor Base = proton Base = proton acceptoracceptor

HHA + HA + H22OO HH33O + O + AA++ --

OO

HH

HHHH ClCl

HH

HH

OOHH ++ ClCl

AcidAcid--BaseBase: Electron : Electron “Pushing” and “Pushing” and ElectrostaticsElectrostatics

++ --

++ ++

++

++11

-1-1AA BB

Charge moves:Charge moves:e-pushing e-pushing arrowsarrows

AcidityAcidityconstantconstant

mol/Lmol/LSolvent 55Solvent 55K K ==[H[H33O] [O] [AA]]

[[HAHA] [H] [H22O]O]

KKa a

==K K x 55 x 55 ==

[H[H33O][O][AA]][[HAHA]]

++

++ --

--

ppKKa a = -log = -log KKaa

HHA + HA + H22OO HH33O + O + AA++ --

AcidityAcidity

AcidityAcidity increases increases with:with:1. Increasing size of A (H A gets weaker; 1. Increasing size of A (H A gets weaker; charge is better stabilized in larger orbital; charge is better stabilized in larger orbital; down the PT)down the PT)

3. Resonance, 3. Resonance, e.g., e.g.,

2. Electronegativity (moving to the right in 2. Electronegativity (moving to the right in PT)PT)

CCHH33OOHH 15.515.5 CCHH33OO--::

:: ::::

::

CCHH33CCOOHH

OO

::::

::::

4.34.3 CCHH33

OO

::::

::::

OOCC ::--

ppKKaa

OOHH

OO

::::

::::

OO SS::--

OO::::

::::HH22SOSO44

-5.0-5.0

HA + H2O H3O+ + A- In water, all acids form hydronium ion,the important factor of difference isthe conjugate base.

EVALUATION OF ACID STRENGTHEVALUATION OF ACID STRENGTH

The difference between a strong acidand a weak acid is in the stability ofthe conjugate base.

HA

A-

A-

strong conj. base(=higher energy)

weak conj. base(=lower energy)

WEAK ACID

STRONG ACID

ENERGY

has

has

ionizationeasier

FACTORS THAT INCREASE ACIDITYFACTORS THAT INCREASE ACIDITY

STABILIZATION OF A CONJUGATE BASE

A-

HA

stabilization

We will study the factors that lead to lower energy (stabilization) inthe conjugate base.

Stabilization of theconjugate basemakes the acidstronger.

STABILIZATION FACTORS

1 Resonance

2 Electronegativity

3 Size of Atoms

4 Hybridization

5 Inductive Effects

6 Charge

7 Solvation

8 Steric Effects*

* usually destabilize

RESONANCERESONANCE

More resonance structures, orbetter resonance structures,for the conjugate base lead toa stronger acid.

RESONANCE EFFECTSRESONANCE EFFECTS

R OH

OH

R C OH

O

R CH3

CH3

R C CH3

O

R C CH2

O

C O

R

CH3O C CH3

O

R C NH2

O

NH2

R NH218

10

5

45

30

25

20

9

28

25

15

pKa Valuesincreasing qualityof resonance

CH3 C O

O

H-H+

CH3 C

O

O

CH3 CO

O

base

_

_

acetate ion

RESONANCE IN THE ACETATE IONRESONANCE IN THE ACETATE ION

acetic acid

equivalent structurescharge on oxygens

PHENOLATE ION RESONANCEPHENOLATE ION RESONANCE

O

-

_

_

_

_

_

O O

OOO

Non-equivalent structurescharge on carbon and oxygen

More structures,but not betterthan acetate.

ELECTRONEGATIVITYELECTRONEGATIVITY

placing the negative charge on amore electronegative element in theconjugate base leads to a stronger acid

When comparing two acids in the same period ...

CH4

NH3

H2O

HF

RCH3

RNH2

ROH

R C

O

CH3

R C NH2

O

R C OH

O

>45

34

16

3.5

45

35

18

20

15

5

EFFECT OF ELECTRONEGATIVITYEFFECT OF ELECTRONEGATIVITYincreasing electronegativity pKa Values

CH

H

H

H N

H

H O F_ _ _ _

conjugatebases :

ELECTRONEGATIVITY VALUESELECTRONEGATIVITY VALUES

H C N O F2.2 2.5 3.0 3.5 4.0

Si P S Cl1.9 2.2 2.5 3.0

Br2.8

I2.5

increase

periodic chart trends

F

( a reminder )

SIZESIZE

placing the negative charge on a larger atom in the conjugate base leads to a stronger acid.

When comparing two acids in the same group ...

EFFECT OF ATOMIC SIZEEFFECT OF ATOMIC SIZE

R C

O

OH

R C SH

O

R C SH

S

HOH

HSH

HSeH

HTeH

HF

HCl

HBr

HI

increasingatom size pKa Values

3.5

-7

-9

-10

16

7

4

3

5

F- Cl- Br- I-

1.36 A 1.81 A 1.95 A 2.16 A

C H 4 5 0

N H 3 3 6

H 2 O 1 6

H F 3 .2

S iH 4 3 5

P H 3 2 7

H 2 S 7

H C l -7

G e H 4 2 5

A s H 3 2 3

H 2 S e 3 .7

H B r -8

H 2 T e 3 .0

H I -9

Electronegativity

Size

Acidity

Acidity

DEPENDENCE OF ACIDITY ON SIZE AND ELECTRONEGATIVITY

PERIOD

GROUP

HYBRIDIZATIONHYBRIDIZATION

More S character in the orbital bearing the negative charge in the conjugate baseleads to a stronger acid.

EFFECT OF HYBRIDIZATIONEFFECT OF HYBRIDIZATION

C C HH

C C HH

H H

C HH

H

H

sp3

sp2

sp

ca. 50

35

25

electrons have lowerenergy in sp hybrid -closer to nucleus

H O H

H

C O HR

R+

+-1.74

-7

pKa values pKa values

:

:

:

C:

C:sp3

sp2

sp

C:

INDUCTIVE EFFECTSINDUCTIVE EFFECTS

Small, but they can add up.

Cl-

C CH3

-

C

ELECTRONWITHDRAWINGGROUPS

ELECTRONDONATINGGROUPS

F, Cl, Br, N, O R, CH3, B, Si

TYPES OF INDUCTIVE EFFECTSTYPES OF INDUCTIVE EFFECTS

electronegative elements take electron densityfrom cabon

alkyl groups and elements less electronegative than carbon donate electron density to carbon

These electron withdrawing and donating groups work throughthe sigma bond system, unlike the similarly named resonance

groups that work through the system.

Cl C C C-

- + - +

O

O

INDUCTIVE EFFECTS INDUCTIVE EFFECTS HALOACIDSHALOACIDS

The effect diminishes with distance - it carries for about 3 bonds.

Cl C

O-Chlorine helps

to stabilize -CO2-

by withdrawingelectrons

O

INDUCTIVE EFFECTS - 1INDUCTIVE EFFECTS - 1

I CH2COOH

Br CH2COOH

Cl CH2COOH

F CH2COOH

CH3 COOH

Cl CH2 COOH

Cl CH COOH

Cl

Cl C COOH

Cl

Cl

3.13

2.87

2.81

2.66

4.75

2.81

1.29

0.65

pKa Valuesincreasingelectronegativity

multiplesubstituents

red=negblue=pos

INDUCTIVE EFFECT IN CHLOROACETIC ACIDSINDUCTIVE EFFECT IN CHLOROACETIC ACIDS

+33 +37 +43elpot values shown

CH3 C

O

OHCH2 C

O

OHCl C C

O

OHCl

Cl

Cl

2.8 0.74.8pKa :

CH3CH2CH2 COOH

COOHCH2CH

Cl

CH3

COOHCH

Cl

CH3CH2

COOHCH2CH2CH2

Cl

COOHH

COOHCH3

COOHCH3CH2

COOHCH3CH2CH2

COOHCCH3

CH3

CH3

INDUCTIVE EFFECTS - 2INDUCTIVE EFFECTS - 2

pKa Values

3.75

4.75

4.87

4.81

5.02

4.8

4.5

4.0

2.9

probably a solvation effect

distance

SOLVATIONSOLVATION

SOLVATION LOWERS ENERGYSOLVATION LOWERS ENERGY

Solvation is a type of weak bonding.Energy is released when an ion is solvated.This lowers the energy of the ion.

Cl- (g) + n H2O Cl- (aq) + HEAT (H)

Cl- (g)

Cl- (aq)

+ n H2O

ENERGY

Cl-H O

H

HO

H

HO

H

HO

H

HO

H

HO

H

solvated ion

H

H

O

+

Polar bonds inwater make it apolar molecule.

+ -

+

--

WATER IS A POLAR SOLVENTWATER IS A POLAR SOLVENT

CATIONS

ANIONS

It can solvate both cations and anions

CO

O-

H

OH

H

OH

H

OHH

O H

H

O H

SIZE AND SOLVATIONSIZE AND SOLVATION

4.75

4.87

4.81

Notice that these are all similar

COOHCH3

COOHCH3CH2

COOHCH3CH2CH2

COOHCCH3

CH3

CH3

5.02

….but this one has a larger pKa

This is probably a solvation effect. Solvation lowers the energy of the ion.

The bulkyt -butyl groupis not as wellsolvated.

StrongerAcid

WeakerAcid

unbranched

steric hindrance

CO

O

-H

OH

H

OH

H

OHO

H

H

H

O H

HALOGEN OXYACIDSHALOGEN OXYACIDS

A highly-charged (+) atom in the center and multiple opportunities for back-bonding resonance make for a strong acid.

HALOGEN OXYACIDSHALOGEN OXYACIDS

HOI

HOBr

HOCl

HClO2

HClO3

HClO4

O Cl O H+1-

Cl O

O

O

O H+3--

-

O Cl O H

O

+2

-

-

10

8.7

7.3

2

-1

-8

pKa

Cl O H0inductive

effect

more oxygen =more resonance(backbonding)

larger chargeon the centralatom (Cl)

H2SO3

H2S

H2SO4

FSO3H

O

OSOH H+1

-

H O S O

O

H

O+2

- -

-

SULFUR OXYACIDSSULFUR OXYACIDS

7 (14)

1.8 (7.2)

-3 (2)

-12

pKa values

F S O H

O

O+2

-

H S H0

An addedinductiveeffect.

EFFECT OF CHARGEEFFECT OF CHARGE

CONJUGATE ACIDS OF BASES

CHARGE versus NO CHARGECHARGE versus NO CHARGE

R NH3+

R O

R

H+

R C O

OH

H+

+H O

H

H

+R C O

R

H

H O H H N H

H

H N H

H

H+

Ar NH2

Ar NH3+

R C N H+

16

-1.74

-3.5

-6

-7

34

9.24

10

-10

25

4

pKa Valuesconjugate acid(extra proton)

neutral molecule

Conjugate acidprotons are always stronger acids than any protons in the original compound.

CONJUGATE ACIDSCONJUGATE ACIDS

The conjugate acid of a weak base will be a strong acid.

weak base = strong conjugate acid

strong base = weak conjugate acid

The conjugate acid of a strong base will be a weak acid.

The strongest bases usually carry a negative charge.

Weaker bases are usually neutral molecules with an unshared pair of electrons.

COMPARATIVE TRENDSCOMPARATIVE TRENDS

Electronegativity

Size

InductiveEffect

Multiple Inductive

Hybridization

Resonance

COMPARATIVE EFFECTS ON pKa VALUES

50 34 16 3

-7

-9

-10

30 25 10

20 15 4.8

2.8 1.3 0.7

35

25

3.1

2.9

2.7

H C C H

H C C H

H H

CH4

CH3

CH3 CH3

O

NH2 OH

NH3 H2O

CH3 NH2

O

CH3 OH

O

HF

HCl

HBr

HI

I CH2 COOH

Br CH2 COOH

Cl CH2 COOH

F CH2 COOH

Cl CHCOOH

Cl

Cl C

Cl

Cl

COOH

The direction of thearrows indicates anincrease in acidity.

sp

sp2

sp3

GENERALIZATIONGENERALIZATION

MAJOR EFFECTS

ElectronegativitySizeHybridizationResonanceHighly-(+)-charged atom

These five cancause big changesin the pKa.

MINOR EFFECT

Inductive Effects

Smaller changes,unless several addtogether.

The effects are purposely not listed in an exact order of importance from top to bottom; it is not really possibleto establish an exact order.

40 20 10 5 0

HCl

HBr

HIR CH3 C C

H

H

H

R

R NH2

H2SO4

HClO4

HNO3

weak acids strong acids

CLASSIFICATION OF WEAK AND STRONG ACIDS CLASSIFICATION OF WEAK AND STRONG ACIDS BY FUNCTIONAL GROUPBY FUNCTIONAL GROUP

pKa

inorganic acidsoxyacids

carboxylic acidsnitrophenols

phenols-diketones

alcoholsketonesamidesalkynes

alkenesamines

alkanes

C C HR

OH

R

O

CH2 R

OR C

O

OH

nitrophenolsdi- and tri-R C CH3

O

R C NH2

OR OH

StrongStrong

WeakWeak

VeryVery weakweak

Relative Acid StrengthsRelative Acid Strengths

Lewis acids: Lewis acids: e-e-deficientdeficientLewis Lewis bases:bases:

BBFF

FF

FF

Lone e-Lone e-pairspairs

6e6e

NN

RR

RR RR

e-pushing e-pushing arrowsarrows

BBFF

FF

FF

RR

RR

OO OO

RR

RR

BFBF33

++ --

R―R―SSR―R―OO―R―R

Lewis Lewis AcidsAcids and and BasesBases

--

Lewis Acid-Base Lewis Acid-Base ElectrostaticsElectrostatics

FF

FF

BBFF

OOCCHH22CCHH33

CCHH22CCHH33

BBFF

FF

FF

OOCCHH22CCHH33

CCHH22CCHH33

++--++

++

EVALUATION OF BASE STRENGTHEVALUATION OF BASE STRENGTH

Since you have learned to evaluate the strengthof an acid by examining its conjugate base youalready know how to evaluate a base!

However, there are some differences in the way

a pKa and a pKb are calculated. In fact, pKa’s are

usually given in the literature for bases (this is actually for their conjugate acids).

EVALUATION OF BASE STRENGTHEVALUATION OF BASE STRENGTH

YOU ALREADY KNOW HOW !

A small value of pKa means B is a weak base.

If BH+ is a strong acid, then B is a weak basethat doesn’t hold (bond to) the proton strongly.

A large value of pKa means B is a strong base.

If BH+ is a weak acid, then B is a strong basethat holds (bonds to) the proton strongly.

WHAT DOES pKWHAT DOES pKaa OF A BASE MEAN ? OF A BASE MEAN ?

Conversely …. small Kb = strong baselarge Kb = weak base

B H:

B H

+

+

SIMPLE AMINESSIMPLE AMINES

ammoniamethylaminedimethylaminetrimethylamine

NH3

NHCH3

CH3

NH2CH3

CH3 N

CH3

CH3

4.75 9.25

3.34 10.66

3.27 10.73

4.19 9.81

pKb pKa

DISSOCIATION CONSTANTS FOR SOME SIMPLE AMINESDISSOCIATION CONSTANTS FOR SOME SIMPLE AMINES

increasing base strength

trimethylamine isout of sequence -probably a stericor a solvation effect

pKa is larger

pKb is smaller

of the conjugate acidelectrondonatinggroup

..

..

..

:

CYCLIC AMINESCYCLIC AMINES

2.73

2.88

3.30

8.75

14.27

decreasingbasicity

pKb

sp3

sp2

pair is not involved in resonance

sp2

pair is involvedin resonance

SOME CYCLIC AMINESSOME CYCLIC AMINES

see next slide

N H

N

N H

N H

NH2

..

..

..

..

:

pyrrolidine

piperidine

aniline

pyridine

pyrrole

N :

....

. . N H

..

. .:

The basic pair(in an sp2 hybrid)is not involvedin resonance

The basic pair is In the resonance system ( in a 2p orbital).PYRIDINEPYRIDINE

PYRROLEPYRROLE

pKb 8.75

pKb 14.27strongbase

weakbase

pKa 5.25

pKa -0.27

ANILINESANILINES

( aminobenzene = aniline )

C

3.30

8.90

9.37

13.0

decreasing base strength

pKb

CYCLOHEXYLAMINE AND SOME ANILINESCYCLOHEXYLAMINE AND SOME ANILINES

10.7

5.10

4.63

1.0

pKa

conjugateacid base

electronwithdrawing

work out theresonance

O

NH2H3

NH2

NH22N

NH2..

..

..

..

p -methylaniline

aniline

p -nitroaniline

cyclohexylamine

SUMMARYSUMMARY

B:R-

B:R-

Electron-donating groupsstrengthen a base.

Electron-withdrawing groupsweaken a base.

SUMMARYSUMMARY

STRONGER BASE

WEAKER BASE

Hydrocarbons Hydrocarbons withoutwithout

Straight chain:Straight chain: CCHH33CCHH22CCHH22CCHH33

AlkanesAlkanes

Branched:Branched: CCCCHH33 CCHH33

CCHH33

HH

CC44HH1010 2-2-MethylpropaneMethylpropane

CC44HH1010 ButaneButane

CCHH33 CCHH33

functional functional groupsgroups

Line Line notation:notation:

1 Å = 101 Å = 10-8-8 cm cm

SameSame molecular formulamolecular formula, , differentdifferent connectivityconnectivity

Cyclic:Cyclic:

Bicyclic:Bicyclic:

Polycyclic . . . . Polycyclic . . . . . . . .

Cyclohexane Cyclohexane CC66HH1212

Bicyclo[2.2.0]octane Bicyclo[2.2.0]octane CC88HH1414

andand are are constitutional isomers.constitutional isomers.

InsertInsert-CH-CH22- - groups into groups into CC--CC bonds. bonds.

Straight chain Straight chain CCHH33((CCHH22))xxCCHH33

General molecular General molecular formulaformulafor acyclic systems.for acyclic systems.

Cyclic alkanes: Cyclic alkanes: CCnnHH22nn

Homologous Homologous series:series:

Barry Sharpless Barry Sharpless (Scripps) (Scripps) NP 2001NP 2001

Date

Mon Sep 12 23:56:24 EDT 2005

Count

26,676,640 organic and inorganic substances

56,744,740 sequences

Angew. Chem. Int. Ed. 2005, 44, 1504 –1508 (edited)

The development of modern medicine largely depends on thecontinuous discovery of new drug molecules for treating

diseases. One striking feature of these drugs is theirrelatively small molecular weight (MW), which averages only

340. Recently, drug discovery has focused on evensmaller building blocks with MW of 160 or less to be used

as lead structures that can be optimized for biological activityby adding substituents. At that size it becomes legitimate to

ask how many such very small molecules would be possible intotal within the boundaries of synthetic organic chemistry? To

address this question we have generated a databasecontaining all possible organic structures with up to 11 main

atoms under constraints defining chemical stability andsynthetic feasibility. The database contains 13.9 million molecules

with an average MW of 153, and opens anunprecedented window on the small-molecule chemical

universe.

Virtual Exploration of the Small-Molecule Chemical Universe below 160 Daltons

Tobias Fink, Heinz Bruggesser, and Jean-Louis Reymond*

The Names of Alkanes are Based The Names of Alkanes are Based on the on the

IUPAC Rules IUPAC Rules

Branched Alkyl GroupsBranched Alkyl Groups

Common names: isopropyl, Common names: isopropyl, terttert-butyl, -butyl, neopentylneopentyl

Problem:Problem:

BrBr

ClCl

II

Longest chain?Longest chain?

33

55

88

66

44

77

2211

BrBr

ClCl

II

Substituents?Substituents?

IodoIodo

1-Chloroethyl1-Chloroethyl

DimethylDimethyl

BromoBromo

33

55

88

66

44

77

2211

BrBr

ClCl

II

Final name?Final name?

IodoIodo

1-Chloroethyl1-Chloroethyl

DimethylDimethyl

BromoBromo

33

55

88

66

44

77

2211

BrBr

ClCl

II

1-Bromo-5-(1-chloroethyl)-7-iodo-2,2-1-Bromo-5-(1-chloroethyl)-7-iodo-2,2-dimethyloctanedimethyloctane

Double Bonds Equivalent Double Bonds Equivalent (DBE) or Degree of (DBE) or Degree of

UnsaturationUnsaturation

Double Bonds Equivalent (DBE) or Double Bonds Equivalent (DBE) or Degree of UnsaturationDegree of Unsaturation

Physical Properties of Alkanes:Physical Properties of Alkanes:Intermolecular Forces Increase With Intermolecular Forces Increase With

SizeSize

Coulomb forces in saltsCoulomb forces in salts Dipole-dipole interactionsDipole-dipole interactionsin polar moleculesin polar molecules

Intermolecular Forces Intermolecular Forces

London forces: Electron correlationLondon forces: Electron correlation(Polarizability: Deformability of e-cloud)(Polarizability: Deformability of e-cloud)

Idealized Idealized (pentane)(pentane) Experimental Experimental (heptane)(heptane)

Intermolecular ForcesIntermolecular Forces

The Rotamers of The Rotamers of EthaneEthane

StaggeredStaggered EclipsedEclipsed StaggereStaggeredd

A. CombustionC8H18 +

Heats (enthalpies) of combustion: DHcomb

More branched isomers have lower DHcomb, are more stable.

1307.5 kcal 1306.3 kcal 1304.6 kcal 1303.0 kcal~ ~ ~ ~

~~~~

CO2 + H2O

Chemical Properties of Chemical Properties of AlkaneAlkane

B. Oxidation and reduction in organic molecules

CH4 + Br2 CH3Br + HBr

C HH

H

H

C HH

OH

HC

O

H HC

O

H OHC

O

O

oxidation

more C-O bonds, fewer C-H bonds

reduction

fewer C-O bonds, more C-H bonds

Chemical Properties of Alkanes

B. Oxidation and reduction in organic molecules

H3C CH3 H2C CH2 HC CH

oxidation

fewer C-H bonds

reduction

more C-H bonds

H2C=CH2 + H2O2 HO–CH2–CH2–OH

H2C=CH2 + H2O CH3–CH2–OH

H2C=CH2 + H2 CH3–CH3


B. Assigning oxidation numbers:1. For each atom in a bond, assign a +1 to the moreelectropositive atom and a -1 to the more electronegativeatom. (If the atoms are the same, each atom gets a 0.)

2. Total each atom.

C O

Cl-1+1

-1+1

H

-1

-1

+1

+1

C O

Cl-1+1

-1+1

H

-1

-1

+1

+1 Oxidation number of carbon is+1 +1 +1 -1 = +2


Determine oxidation numbers for the carbons in each of the following molecules.

H C N

C

H

H

Br

C

O

O H12

C

H

H

OH

Cl


Determine oxidation numbers for the carbons in each of the following molecules.

H C N

C

H

H

Br

C

O

O H12

C

H

H

OH

Cl

C = +2

C1 = +3; C2 = -1

C = 0


Determine whether the following reactions will be oxidation, reduction, or neither.

H2C CH2 + Br2 H2C CH2

Br Br

H2C CH2 + H2O C

H

H

H

C

H

H

OH


Determine whether the following reactions will be oxidation, reduction, or neither.

H2C CH2 + Br2 H2C CH2

Br Br

H2C CH2 + H2O C

H

H

H

C

H

H

OH

Oxidation: Each carbonchanges from a -2 to a -1.

Neither. One carbon changes from a -2 to a -3 (getsreduced), but the other carbon goes from a -2 to a -1 (gets oxidized.) No net change.


Newman ProjectionsNewman Projections

Note: Newman projection occurs along only one bond. Everything else isNote: Newman projection occurs along only one bond. Everything else isa substituent.a substituent.

Rotation with Newman Rotation with Newman ProjectionsProjections

Rotation Around Bonds is Not Rotation Around Bonds is Not “Free”: Barriers to Rotation“Free”: Barriers to Rotation

e-Repulsione-Repulsion

OrbitalOrbitalstabilizationstabilization

Transition stateTransition stateis is eclipsedeclipsed

Most Most stablestablerotamer isrotamer isstaggeredstaggered

Ethane has barrier to rotation of ~3 kcal Ethane has barrier to rotation of ~3 kcal molmol-1-1. Barrier due to steric and electronic . Barrier due to steric and electronic effects.effects.

antibondingantibonding

bondingbonding

Potential Energy Potential Energy DiagramsDiagrams

(TS = transition state)(TS = transition state)

WalbaDStr

Propane: Methyl Increases Propane: Methyl Increases BarrierBarrier

Butane: Isomeric Staggered Butane: Isomeric Staggered and Eclipsed Rotamersand Eclipsed Rotamers

Rotamers and Energy Rotamers and Energy DiagramDiagram

WalbaDylan

H

HHH

HH H

HH

H

HH

lower energy higher energy

G ~ 3 kcal/molK ~ 0.01

torsional strain

DG

0

3

H

HHH

HHH

HHH

HHH

HH

H

HH

Ea ~ 3 kcal/mol

= barrier to free rotation

(but at room temp most molecules have KE > Ea so rotation is essentially “free”)

krot ~ 106 s-1

I. Conformations of AlkanesB. Butane: steric repulsions CH3–CH2–CH2–CH3

CH3

CH3

CH3

H3C

CH3H3C

CH3CH3 CH3CH3

CH3

CH3

Ianti

(180º)

II IIIgauche(60º)

IV VIVgauche(60º)

gauche ~ 0.8 kcal higher energy than anti- van der Waals repulsions= steric strain

eclipsed: 3 kcal torsional strain+ 0.3 kcal each CH3-H eclipse+ ~ 3 kcal each CH3-CH3 eclipse

Chem3D

I. Conformations of AlkanesB. Butane: steric repulsions

I II III IV V VI

0

2

4

6

DG

3.60.8

~6

0.83.6

CH3

CH3

CH3

H3C

CH3H3C

CH3CH3 CH3CH3

CH3

CH3

I II III IV VIV

II. Conformations of CycloalkanesA. Stabilities of cycloalkanes

Ring strain = bond angle strain+ torsional strain (eclipsing)+ steric strain (van der Waals)

The Steroid Sex The Steroid Sex HormonesHormones

TestosteroneTestosterone EstroneEstrone

Regulate growth and function of reproductive organs; Regulate growth and function of reproductive organs; stimulate development of secondary sexual characteristicsstimulate development of secondary sexual characteristics

OOHHCHH33

HH

OO

HH HH

OO

HH

HH HH

CHH33

CHH33

OOHH

CycloalkanesCycloalkanes

Abundant in nature: “rigid Abundant in nature: “rigid scaffolding”. scaffolding”. Names:Names: CycloCycloalkanesalkanes Cyclopropane, , , etc. Cyclopropane, , , etc.

Substituents: Substituents: CycloalkylCycloalkyl. Substituted . Substituted cycloalkanes: single substituent is automatically cycloalkanes: single substituent is automatically at “at “C1C1”.”.

Ethylcyclobutane (no # needed)Ethylcyclobutane (no # needed)

Alkylcycloalkane or Alkylcycloalkane or cycloalkylalkane? cycloalkylalkane?

Larger stem Larger stem controls:controls:

11

22

33

44

55 11--CyclopropylCyclopropyl--pentanepentane

(CH(CH22))nn notnot CCnnHH22nn+2+2

DisubstitutedDisubstituted: :

a.a. Lowest numbering Lowest numbering

b.b. Alphabetical orderAlphabetical order

CCHH33

CCHH22CHCH33

11

22

1-Ethyl-2-methyl-1-Ethyl-2-methyl-

cyclohexanecyclohexane

1122

44

CCHH33

11

3344

ClClBrBr

1,2,41,2,4 not not 1,3,41,3,4

1-Bromo-2-chloro-4-1-Bromo-2-chloro-4-methyl-methyl-

cyclohexanecyclohexane

Cycloalkanes have two sides: “up”, “down”.Cycloalkanes have two sides: “up”, “down”.

With two or more substituents, new type of With two or more substituents, new type of isomerism: isomerism: Same side: cisSame side: cis

Opposite sides: Opposite sides: transtrans

StereoisomersStereoisomers

CHCH33 CHCH33

CisCis-1,2-dimethyl--1,2-dimethyl-cyclopropanecyclopropane

BrBr

FF

TransTrans-1-bromo-3--1-bromo-3-fluorocyclohexanfluorocyclohexanee

StereoisomersStereoisomers

Stereoisomers should be stable at room Stereoisomers should be stable at room temperature. Rotamers interconvert rapidly temperature. Rotamers interconvert rapidly by rotation, whereas by rotation, whereas cis,transcis,trans isomerization isomerization requires bond breaking. requires bond breaking.

Same connectivitySame connectivity (not constitutional isomers), (not constitutional isomers), but but differing arrangement in space.differing arrangement in space.

Note: This definition includes all rotamers (anti, gauche, Note: This definition includes all rotamers (anti, gauche, etc.).etc.).

Definition of stereoisomers:Definition of stereoisomers:

Operational Operational (practical) definition:(practical) definition:

How do we quantify “ring strain”? Need How do we quantify “ring strain”? Need anan““unstrained” reference and a measure of unstrained” reference and a measure of energetic content. We get numbers by energetic content. We get numbers by measuring measuring heats of combustion.heats of combustion.

spsp33-Carbon wants-Carbon wants 109.5°109.5°

60°60° 90°90°120120

°°

108108°°

Ring Ring StrainStrain

~160

~160

~160

IsomersIsomers

An Application: The Relative Heat An Application: The Relative Heat Content of the Two Isomeric ButanesContent of the Two Isomeric Butanes

Most branched alkanes are slightly more stable than their linear isomersMost branched alkanes are slightly more stable than their linear isomers

Are cycloalkanes “normal”? Define Are cycloalkanes “normal”? Define normal from heat of combustion normal from heat of combustion ΔΔH°H°combcomb of CH of CH33(CH(CH22))nnCHCH33

Any Any discrepancydiscrepancy with with ΔΔH°H°exp exp

equals equals ring strain.ring strain.

Every additional (CHEvery additional (CH22) increment ) increment gives an extra gives an extra δΔδΔH°H°combcomb ~ -157.4. ~ -157.4.

We can therefore calculate We can therefore calculate ΔΔH°H°combcomb (expected) (CH(expected) (CH22))nn: : nn x 157.4. x 157.4.

60°60° 90°90°120120

°°

108108°°

1.1.Bond angle, Bond angle, especially in especially in small ringssmall rings

2.2.EclipsingEclipsing

3.3.Transannular, Transannular, especially in especially in medium sized medium sized ringsrings

Ring Ring StrainStrain ::

EclipsedEclipsed

CyclopropaneCyclopropane

Strain Relief Through “Banana” Strain Relief Through “Banana” BondsBonds

Trimethylene diradicalTrimethylene diradical

Weakened:Weakened:65 kcal/mol65 kcal/mol

Hot Recent Research!Hot Recent Research!

J. Am. Chem. Soc.J. Am. Chem. Soc. 20052005, , 127127, 9370-9371, 9370-9371

Cyclobutane: “Puckering” Cyclobutane: “Puckering” Reduces EclipsingReduces Eclipsing

Cyclopentane: Cyclopentane: Envelope ConformationEnvelope Conformation

Almoststaggered

The Unstrained The Unstrained Cyclohexane:Cyclohexane:

A “Chair” ConformationA “Chair” Conformation

Move C1,4

A Newman View of a A Newman View of a Cyclohexane C-C Bond: Cyclohexane C-C Bond:

Staggered!Staggered!

The Cyclohexane Boat is The Cyclohexane Boat is StrainedStrained

+ 6.9 kcal/molMove C1,4

……So it Twists. So it Twists.

But this is only part of its mobility.But this is only part of its mobility.The molecule The molecule “flips”“flips” from one from one chair to another chair form.chair to another chair form.

-1.4kcal mol-1

-1.4kcal mol-1

Cyclohexane Ring FlipCyclohexane Ring FlipHH

HHEEaa = =

10.810.8ΔΔG°G° = = OO eqeq

eqeq

axax

axaxHH

HH

HH HH HH HH

HH HH HH HH

()

()

Transannular Transannular strain strain

Eclipsing strain Eclipsing strain

Chair Chair Boat + 6.9 kcal mol Boat + 6.9 kcal mol-1-1. Boat is a TS.. Boat is a TS.

Complex Movement:Complex Movement: Goes through Goes through boatboat

RingflipRingflip

WalbaWalbaMonkMonk

The Chair-Chair Flip The Chair-Chair Flip ManifoldManifold

RingflipRingflip

100,000 times/sec100,000 times/sec

How to Draw the Chair How to Draw the Chair CyclohexaneCyclohexane

““down”down” ““up”up”This endThis end

Equatorial bonds must be Equatorial bonds must be parallelparallel to the C–C bond(s) to the C–C bond(s) “one “one over”over” [not the attached one(s), [not the attached one(s), but the next one(s)]but the next one(s)]

The Chair-Chair Flip The Chair-Chair Flip CausesCauses

Equatorial-Axial Equatorial-Axial ExchangeExchange

The two structures are the same. However, whatThe two structures are the same. However, whathappens in substituted cyclohexanes?happens in substituted cyclohexanes?

Gº = 0

SubstitutedSubstituted cyclohexanes: cyclohexanes: ΔΔG°≠ G°≠ 00

ΔΔG°G° = = +1.7+1.7

gauchgauchee

HHHH

CCHH33()transannulatransannularr

HH

CCHH33

aaxx

eeqq

Conformational Analysis:Conformational Analysis: Interplay Interplay of energetics of ax-eq substituents. of energetics of ax-eq substituents. Example: MethylcyclohexaneExample: Methylcyclohexane

Axial-Equatorial Axial-Equatorial ConformersConformers

Anti Anti to to ringring

Gauche Gauche to ringto ring

SizeSizevsvs

bondbondlengthlength

Note: These numbers do Note: These numbers do notnot reflect reflect absolute sizeabsolute size, , but size with respect to but size with respect to transannular and gauchetransannular and gauche interactions in interactions in cyclohexanecyclohexane..

The power of conformational analysis: The power of conformational analysis: ΔΔG°G° may be may be additiveadditive. Consider the . Consider the dimethylcyclohexanes:dimethylcyclohexanes:

ΔΔG°G° = = 0 0

ΔΔG°G° = = +3.4!+3.4!

ΔΔG°G° = = 0 0

1,1-1,1-DimethylcyclohexaneDimethylcyclohexane

CisCis-1,4--1,4-dimethylcyclohexanedimethylcyclohexane

CCHH33

CCHH33

CCHH33

CCHH33

CCHH33

CCHH33

HH33CC

CCHH33

CCHH33

HH33CC

diaxiadiaxiall

diequatorialdiequatorialTransTrans-1,4--1,4-dimethylcyclohexanedimethylcyclohexane

CCHH33

CCHH33

But:But:

The largest group often enforces The largest group often enforces one conformation:one conformation:

ΔΔG°G° = 3.4-5 = - = 3.4-5 = -1.6 1.6

axax

eqeq

eqeq

axax

axaxeqeq

+1.+1.77

+1.+1.77

-5-5

Large substituents, such as Large substituents, such as tert-tert-Bu, Bu, are said to “lock” a conformation.are said to “lock” a conformation.

Br COOH

H3C

H3C

Br

COOH

ΔΔG°G° = ? = ?

Problem:Problem:

Br COOH

H3C

H3C

Br

COOHΔΔG°G° = +2.56 = +2.56

+1.70+1.70+1.41+1.41

-0.55-0.55

All-All-cis-cis-hexamethyl-hexamethyl-cyclohexane:cyclohexane:

All-All-trans-trans-hexamethyl-hexamethyl-cyclohexane:cyclohexane:

Medium Rings Suffer Medium Rings Suffer Transannular StrainTransannular Strain

Bicyclo[2.2.1]heptaBicyclo[2.2.1]heptane (norbornane)ne (norbornane)

Bicyclo[4.4.0]decaneBicyclo[4.4.0]decane(decalin), trans and cis(decalin), trans and cis

Bicyclic, Fused, Polycyclic, Polyhedral Bicyclic, Fused, Polycyclic, Polyhedral AlkanesAlkanes

FusionFusion

transtrans ciscis

BridgeBridge

Locked boatLocked boat

HH

HH

HH

HH

Home exercise: Make models and try the ring flip!Home exercise: Make models and try the ring flip!

Strained Hydrocarbons: What is the Strained Hydrocarbons: What is the limit? Exotic polyhedra: The Five limit? Exotic polyhedra: The Five Platonic Platonic or or Cosmic Solids Cosmic Solids (Plato 350 (Plato 350 BC)BC)

TetrahedronTetrahedron(fire)(fire)

CubeCube(earth)(earth)

DodecahedronDodecahedron(“ether”)(“ether”)

Can we make the corresponding hydrocarbon frames (CH)Can we make the corresponding hydrocarbon frames (CH)n n ??

There are two more: icosahedron (water) and octahedron (air)There are two more: icosahedron (water) and octahedron (air)

Maier, Sekiguchi, 2002,Maier, Sekiguchi, 2002,tetrakis(trimethylsilyl)-tetrakis(trimethylsilyl)-tetrahedranetetrahedrane..

m.p. 135°C m.p. 135°C

!! Strain: Strain: 130 kcal 130 kcal molmol-1-1

Strain: Strain: 166 kcal 166 kcal molmol-1-1

Strain: Strain: 60 kcal 60 kcal molmol-1-1

Eaton, 1964,Eaton, 1964,cubanecubane, , CC88HH88

Maier, 1978, Maier, 1978, tetra-tetra-tt-Bu--Bu-tetrahedranetetrahedrane..Substituted Substituted CC44HH44

Paquette, 1982, Paquette, 1982, dodecahedranedodecahedrane, , CC2020HH2020, 12 faces, 12 faces

m.p. 202°C m.p. 202°C

m.p. 126°C m.p. 126°C

m.p. m.p. 430°C !430°C !

Sekiguchi, Angew. 2005, 5821Sekiguchi, Angew. 2005, 5821

Octanitrocubane: a Octanitrocubane: a New Explosive and New Explosive and

Rocket FuelRocket Fuel

Eaton, Eaton, Adv. MatAdv. Mat., ., 2000.2000.

The Allotropes of The Allotropes of Carbon: CCarbon: Cnn

a truncated a truncated icosahedronicosahedron

BenzeneBenzene

Zuo, J. M. et al.Zuo, J. M. et al. ScienceScience 2003, 2003, 300300, 1419, 1419

Atomic Resolution Imaging of a Carbon Nanotube

Carbon Nanotubes: Carbon Nanotubes: Novel Materials for Novel Materials for

the Future the Future


Hcomb

per CH2

Totalring strain

166.6 kcal 31.5 kcal

162.7 26.4

157.3 7.0

156.1 0

157.0 6.3

157.3 9.6

156.2 1.2> C12

small

normal

medium

large

angle strain andtorsional strain

minimal strain

transannularsteric strain


HH

HH

H Hpoor overlap = bond angle strain

(i.e., 109.5º sp3 in 60º triangle)

plus ,

H

H

H

H

H

H

all H’s eclipsed = torsional strain

Chem3D


H

H

H

H

H

H

H

HH

H

H

H

HH

H

H

planar, 90ºbut all eclipsed

“puckered”, 88ºslightly more angle strain,

but less eclipsing strain

Chem3D

planar, 108ºbut all eclipsed

“envelope”relieves eclipsing

II. Conformations of CycloalkanesB. Conformations in cyclohexane

1. chair and boat conformations

H

HH

H

H

H

HH

H

HH

HH

H

H

H

H

H

HH

HH

H

H

“chair” conformation- all staggered- no eclipsing- no steric strain

no ring strain

(99.99% at room temp.)

“boat” conformation- eclipsing ~ 4 kcal- steric strain ~ 3 kcal

ring strain ~ 7 kcal

G ~ 7 kcal

Chem3D

“skewed boat” ~ 1.5 kcalmore stable than boat(0.01% at room temp.)

“flagpole” interaction


2. equatorial and axial positions

H

HH

H

H

H

HH

H

HH

H

H

HH

H

H

H

HH

H

HH

H

axial positions equatorial positions

3. chair-chair interconversion

H

HH

H

H

H

HH

H

HH

H

H

HH

H

H

H

H

H

HH

H

H

Ea ~ 10 kcal


4. drawing cyclohexane chairs

II. Conformations of CycloalkanesC. Substituted cyclohexanes

CH3

CH3

H

H

H

CH3

H

1,3-diaxialrepulsions

equatorial(95%)

no steric strain(anti)

axial(5%)

steric repulsions(gauche)

G ~ 1.8 kcal(or 0.9 kcal per CH3-H repulsion)

Chem3D

Ray

II. Conformations of CycloalkanesC. Substituted cyclohexanes

H

H

More pronounced effect with larger groups:

G ~ 5.5 kcal

(99.99%) (0.01%)

“locked” in equatorial conformation

II. Conformations of CycloalkanesD. Disubstituted cyclohexanes

CH3

CH3

CH3

CH3

transcis-1,4-dimethylcyclohexane

stereoisomers

*configurational conformational (cannot convert from (can be converted from

one to another without to another by rotation breaking bonds) about a bond)

*geometric isomers


CH3

CH3

CH3

CH3

H

HCH3 H

CH3

H

CH3

CH3

G ~ 3.6 kcal

diequatorial no repulsions

diaxial 4 1,3-diaxial repulsions = 4 x 0.9 = 3.6 kcal


CH3

CH3

H3C CH3

CH3

CH3

H

H

H

CH3

CH3

HG = 0 kcal

equatorial-axial 2 x 0.9 = 1.8 kcal

axial-equatorial 2 x 0.9 = 1.8 kcal


CH3

CH3

CH3CH3

H

HH CH3

CH3

H

1 gauche interaction = 0.9 kcal

4 1,3-diaxial repulsions = 4 x 0.9 = 3.6 kcal

G ~ 2.7 kcal


CH3

CH3

CH3H3C

H CH3

CH3G ~ 5.4 kcal

no repulsions 2 1,3-diaxial CH3-H = 1.8 kcal1 1,3-diaxial CH3-CH3 = 3.6 kcal


Larger groups predominate in determining conformation:

CH3

CH3

tBu

CH3

G ~ 3.7 kcal

1.8 kcal5.5 kcal


Draw the most stable chair form of the following compounds.Explain. Click on the arrow to check your answers.

Check Answer

CH3

CH3CH3CH3

CH(CH3)2


Draw the most stable chair form of the following compounds.Explain. Click on the arrow to check your answers.

CH3

CH3CH3

CH3CH3

CH3CH3

CH(CH3)2

All groups can be equatorial. Thischair form is more stable than the other, where all are axial.

Isopropyl is bigger than a methylgroup, so more stable chair is where larger group is equatorial.

CH3

CH(CH3)2

III. Polycyclic Rings

OHdecalin borneol adamantane prismane

bicyclic tricyclic tetracyclic

Bicycloalkanes:bicyclo[x.y.z]alkane (x y z)

numbering starts at a bridgehead, proceeds around the largest bridge first, then around successively smaller bridges

C

C

Cz

Cy

Cx

III. Polycyclic Rings

bicyclo[4.0]decane

bicyclo[2.2.1.]heptane

bicyclo[4.1.0]heptane

bicyclo[3.2.1]octane

IV. Heterocyclic Compounds

O

O

O

O

N

H

N

H

ethylene oxideoxiraneoxacyclopropane

oxetaneoxacyclobutane

tetrahydrofuranoxacyclopentane

tetrahydropyranoxacyclohexane

pyrrolidineazacyclopentane

piperidineazacyclohexane

O O

furan pyran

chapter 2 intro to alkane

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