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

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

++--++

++

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

Change ending Change ending –ane–ane to to –yl–yl, as in , as in

methmethaneane / meth / methylyl, hex, hexaneane / hex / hexylyl

Short notation: Alkane Short notation: Alkane R-HR-H / alkyl / alkyl R-R-““Lingo”: RCLingo”: RCHH22 ““primaryprimary” ”

Naming Alkyl Naming Alkyl SubstituentsSubstituents

CC

RR

RRRR

““tertiarytertiary””CC

HH

RRRR

““secondarysecondary””

IUPAC RulesIUPAC Rules1.1. Find the Find the longest chainlongest chain and name it (Table and name it (Table

2-5)2-5)CCHH33CCHHCCHH22CCHH33

CCHH33 A (methyl substituted) A (methyl substituted) butanebutane

An An octaneoctane (substituted by (substituted by ethyl, two methyls)ethyl, two methyls)

When there are two When there are two equal longestequal longest chains, choose the one with chains, choose the one with more more substituentssubstituents

4 4 substituentssubstituents

3 substituents3 substituents

2. Name substituents (as alkyl or 2. Name substituents (as alkyl or halohalo))

a.a. For straight chain R: Methyl, ethyl, For straight chain R: Methyl, ethyl, propyl etc.propyl etc.

b.b. For branched chain R: For branched chain R:

αα. Find longest chain (starting from point . Find longest chain (starting from point of attachment) of attachment) ββ. . Name substituents Name substituents

ExamplExample:e:

(Methylpropyl)(Methylpropyl)

Halo: Bromo, fluoro, chloro, iodoHalo: Bromo, fluoro, chloro, iodo

Branched Alkyl GroupsBranched Alkyl Groups

c.c. Multiple same substituents: Multiple same substituents:

For For R = straightR = straight, use prefix di-, tri-, tetra-, , use prefix di-, tri-, tetra-, penta-, etc.: penta-, etc.:

DimethylDimethylhexanhexanee

For For R = branchedR = branched,, use: bis-, tris-, tetrakis-, use: bis-, tris-, tetrakis-, etc., and alkyl name in parentheses: etc., and alkyl name in parentheses:

Bis(methylpropyBis(methylpropyl)l)

dd.. Common names: we will use colloquially Common names: we will use colloquially isopropyl, isopropyl, terttert-butyl, neopentyl-butyl, neopentyl

33. Number stem, starting from the . Number stem, starting from the end closest to a substituent:end closest to a substituent:

Branched substituents: Number from Branched substituents: Number from carbon of carbon of attachmentattachment (C (C11))

11 2233

4477

6655

33

22

11 88 9944

11 22

33Defined as 1Defined as 1

If both ends equidistant to the first substituent, proceed If both ends equidistant to the first substituent, proceed until the first point of difference:until the first point of difference:

7766

55

332211 88 9944

44. . NameName the alkane in the alkane in alphabeticalalphabetical (not (not numericalnumerical) ) order of substituents, order of substituents, location location given by number given by number prefix.prefix.

66 1133

4455

2277

88

5-5-EEthyl-2-thyl-2-mmethyl-ethyl-octaneoctane2-Methylbutane2-Methylbutane

Alphabet:Alphabet: D Di-, i-, ttri-, etc. ri-, etc. not countednot counted for main stem for main stem R. R.

ButBut: : CountedCounted when in branched R when in branched R66 44 11

33

552277

8866 11

3344

552277

88

5-5-EEthyl-2,2-di-thyl-2,2-di-mmethyloctaneethyloctane

5-(1,1-5-(1,1-DDimethylethyl)-3-imethylethyl)-3-eethyloctanethyloctane

Not Not countedcounted

{{

CountedCounted

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

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

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