The Four Main Types of Organic ReactionsThe Four Main Types of Organic Reactions

+ A B

BA

A+ B + A + BH

A+ B

B+ A Substitution

Elimination

Addition

Rearrangement

Ether NomenclatureEther Nomenclature

Ethers are alkoxyalkanes - the larger portion is thealkane and the smaller portion is the alkoxy

O

O

ethoxycyclohexane1-ethoxypropane

O

2-ethoxypropane

O

diethyl ether

Ethers can also be named by the two groups followed by “ether”

O

methyl ethyl ether

Boiling Points of Ethers and AlcoholsBoiling Points of Ethers and Alcohols

ETHERBOILINGPOINT (°C) 1-ALKANOL

BOILINGPOINT (°C)

CH3OCH3 -23.0 CH3CH2OH 78.5

CH3OCH2CH3 10.8 CH3CH2CH2OH 82.4

CH3CH2OCH2CH3 34.5 CH3(CH2)3OH 117.3

(CH3CH2CH2CH2)2O 142 CH3(CH2)7OH 194.5

Why is the boiling point of dimethyl ether much less than theboiling point of ethanol?

Ethers cannot Hydrogen Bond!

Williamson Ether SynthesisWilliamson Ether Synthesis

Preparation of ethers by SN2 reaction of primary alkyl leavinggroup compounds and alkoxides.

1. Formation of alkoxides

Alcohols with very strong bases (LDA, NaH, or Na)OH 2 Na O Na + H2

2 2

OH NaH O Na + H2

OH LDA O Li + LDAH

LDA = NLi

pKa = 16 pKa = 30

pKa = 40

Williamson Ether SynthesisWilliamson Ether Synthesis

2. Reaction of alkoxide with primary leaving group

Alkoxides are strong bases, anything other than primarywill lead to elimination

Also, hindered bases lead to elimination even with primaryleaving groups

Propose a synthesis of:(any alcohol and alkyl halide)

O

Ether Ether Reactivities Reactivities Under Highly Acidic ConditionsUnder Highly Acidic Conditions

diethyl ether

CH3CH2OH

CH3CH2OH

OCH3CH2

H

H

CH3CH2OH

O

CH3CH2

CH3CH2

H O

CH3CH2

CH3CH2+ H+

- H+

+ H2O

- H+

+ H+

+ H+

OHI

OH

I+

This reaction requires H2SO4 at 130°C

This reaction requires freshly distilled 57% HI

SN2

In General, Ethers are not Reactive CompoundsIn General, Ethers are not Reactive Compounds

OO O

O

tetrahydrofuran

diethyl ether

1,2-dimethoxyethane,glycol dimethyl ether, glyme

These are excellent solvents for many organic reactions- many organics have good solubilities- the ether itself is not reactive

The one class of ethers that are very reactive are the epoxides, why?O

Epoxy polymers are chains of ethers, therefore the polymer is very unreactive

Tremendous Ring-Strain!

Preparation and Reactions of Preparation and Reactions of EpoxidesEpoxides

m-CPBA

O OO

H

O +

O OHCl

Cl

Nu

O O

Nu

H3O+

OH

Nu

+ H2O

This reaction is very powerful because a variety of nucleophiles can be used and thereaction produces specific stereochemistry - stereospecific

SN2 Reaction

Cis-addition

Trans-product

Ring Opening of Ring Opening of Epoxides Epoxides with with Grignard Grignard ReagentsReagents

New Type of Nucleophile - Grignard Reagent

Br

Mg

MgBr

δ

δ

This is a carbon nucleophile

Can be perceived as a Carbanion

MgBr

m-CPBA

O

1. CH3CH2MgBr

2. H3O+

OH

CH2CH3

Carbanions are verystrong bases, the pKa

of cyclohexane is~50! Therefore,carbanions willdeprotonate justabout any acid.

CisCis Addition of Hydrogen to Alkenes - Addition of Hydrogen to Alkenes - HydrogenationHydrogenation

H2

Pt

H

H

Platinum or Palladiumadsorbs hydrogen quitewell

The flat surface of thecatalyst delivers thehydrogens to the sameside of the alkene

Electrophilic Electrophilic Addition to AlkenesAddition to Alkenes

Electrophile - chemical species that is electron deficient

“electron loving”

The hydrogen cation(H+) is one of the best electrophiles - just a proton

+ H Cl

ClH

HCl

This is major product

This product is notFormed

electrophilic addition to alkenes is anexample of a reaction that isregiospecific - given a choice of“regions” in a molecule, the atoms addspecifically and predictably to certainpositions

E,Z Nomenclature of AlkenesE,Z Nomenclature of Alkenes

With disubstituted alkenes, cisor trans are commonly used, butso can E or Z

CH3

CH3

H

Substituents areranked 1 or 2 on eachend of the double bond

1’s same side or 1’s zame zide = “Z”

1

2

1

2

1’s opposite side so “E”

E from entgegen, German, opposite Z from zusammen, German, together

CisCis and Trans and Trans Isomerization Isomerization of Alkenes of Alkenes

For double bonds that are disubtituted (2 other carbons attached) cis andtrans isomerization is possible

trans-3-heptene cis-3-heptene

H

H

H

H

Melting Points of Melting Points of CisCisand Trans Alkenesand Trans Alkenes

The cis-structure ofalkenes inhibits chainsfrom packing closetogether to form a solid.Much coldertemperatures arerequired to “freeze.”

The trans-structure ofalkenes allows chains topack close together toform a solid

In General, trans isomers have highermelting points than cis isomers

Some Oil and Fat Chains - note pages 110Some Oil and Fat Chains - note pages 110-116 of -116 of Pavia Pavia Lab ManualLab Manual

O

OH

O

OH

Stearic Acid - Animal Lard

Oleic Acid - Corn and Olive Oil

HydrogenateH2 /Pt

The hydrogenationchanges the chain shapeand allows for closerpacking and a highermelting point - FryingTemperature instead ofBelow RoomTemperature

PeroxidesPeroxides

Two highly electronegative atoms next toone another makes for a highly unstablemolecule

OO ∆ or hν

OO

Decomposition generates 2alkoxy free-radicals

O

O2Over time, ethers react withoxygen to produce peroxides

We store ethers in tightlysealed containers in therefrigerator to slow reactionwith oxygen

This decomposition reaction can be quiteexothermic, even explosive!

Peroxides are Excellent Initiators for Free-RadicalPeroxides are Excellent Initiators for Free-RadicalReactionsReactions

HBr

peroxides

+

Br BrBr

+

Br BrAnti-Markovnikov Addition

Taking stereochemistry into account, atotal of 4 products are produced

Mechanism of Free-Radical addition of Mechanism of Free-Radical addition of HBr HBr to Alkenesto Alkenes

OO ∆ or hν

OOInitiation Steps

Br

+ H Br

Br

+ Br

Br +HBr +

Br

O+ H Br

OH+ Br

Propagation StepsBr adds to less substituted becausemore stable free radical is formed

Free-Radical Polymerization of Alkenes - PolystyreneFree-Radical Polymerization of Alkenes - Polystyrene

OO ∆ or hν

OO

O

O

O O

Propagation Steps

Initiation Steps

O O

These propagation steps may repeat hundreds or thousands of times to produce astyrene polymer!!!

Styrene monomer

Alkynes - Hydrocarbons with Triple bondsAlkynes - Hydrocarbons with Triple bonds

In General, what ever alkenes do, alkynes do it twice.

The pi bonds of alkynes are two independent pi bonds.

H2

Pt

Instead of one mole of hydrogen foralkenes, alkynes react with two molesof hydrogen

The terminal H on alkynes, if present, is quite acidic pKa = 25.

Bases such as amides are strong enough to deprotonate.

Alkynes as Alkynes as NucleophilesNucleophiles

R HLDA

R + DAH

Li

Alkynyl anion - a great nucleophile

Alkynyl anions react via a SN2 process with primary alkyl halides (leaving group)

R Li

Br

R + LiBr

C C HH Acetylene has two terminal hydrogens so SN2reactions could occur on either or both ends.

In making the alkynyl anion of acetylene, only 1 proton is removed at atime. It is very difficult for any multi-acidic compound to give up multipleprotons at the same time.

pKa ~25

pKa ~36

Almost all of the addition reactions performed on alkenesAlmost all of the addition reactions performed on alkenescan be done with alkynes - Twice!can be done with alkynes - Twice!

In the case of hydration the reaction does not go twice, but a rearrangement occurs

H3O+

OH O

tautomerization

enol

HydroxyHydroxy Functional Group Functional Group

The structure and characteristics resemble those of water

HO

H RO

H

Similar shape andbond polarities δ+

δ+ δ+

δ− δ−

This lead to similar characteristics such as boiling points and solubilities

Hydrophilic - “Water loving”

Hydrophobic - “Water hating”

Because alcohols are polarmolecules like water, they areconsidered hydrophiliccompounds

Boiling Point and Intermolecular InteractionsBoiling Point and Intermolecular Interactions

In the boiling process molecules pass from a liquid state toa gaseous state

Boiling points are greatly affected by molecular weightand intermolecular forces

Molecular Weight - more energy requiredto move a molecule from the liquid state tothe gaseous state as molecular weightincreases

Intermolecular Forces - more energyrequired to break stronger forces holdingmolecules together in liquid state

Characteristics of Characteristics of Alkanes Alkanes andandAlcoholsAlcohols

higher molecular weights have higher boiling points

CH3CH2OH

CH3Cl

Hydrogen BondingHydrogen BondingBonding that occurs between a hydrogen bonded toa O,N,F and another O,N,F

HO

H RO

Hδ+δ+ δ+

δ− δ−

δ+ δ+

δ−

HO

H RO

Hδ+

δ−

The hydrogen bonds arequite strong, on the order of1/2 strength of a covalentbond. They must be brokenin the boiling process

Alcohols typically have higher boiling points than expected for themolecular weight

Alcohol SolubilityAlcohol Solubility

Because alcohols are polar, they are soluble in water. TheOH group of the alcohol is able to form hydrogen bonds withwater.

Rationalizing AciditiesRationalizing Acidities

The acidity of a compound is determined by the stability ofthe resulting Anion

RO-H RO- + H+

The stability determines towhat degree this reactionwill proceed

Reactions with stable anions proceed readily, thus theoriginal compound is considered acidic.

By stabilizing the negative charge on the anion, the moreacidic the original compound becomes

Stabilizing Negative ChargeStabilizing Negative Charge

Stabilizing charge is accomplished by spreading thecharge over several atoms: Inductive, Resonance, andSolvation Effects are important

Methanol more acidic than t-butanol because the anion ofmethanol is better solvated,negative charge spead to solventmolecules

pKa = 15.5CH3OH

pKa = 18(CH3)3COH

Inductive EffectInductive Effect

Inductive effect - transmission of positive or negativecharge through sigma bonds

CH3CH2OH

ClCH2C H2OH

CH3CH2O

ClCH2C H2O

pKa = 15.9

pKa = 14.3

The highly electronegativechlorine atom draws negativecharge toward itself, in themeantime, negative charge isdistributed over the other atoms

Chlorine stablizes theanion, making the chloroalcohol more acidic

Remember: pKa

is a logarithmicfunction, so adifference of 2 is100 times moreacidic

Characteristics of Inductive EffectCharacteristics of Inductive Effect

Greater inductive effects are seen with a greater number ofelectronegative atoms and with closer proximity to theanion

CH3CH2OH pKa = 15.9

ClCH2CH2OH pKa = 14.3

CF3CH2OH pKa = 12.4

CF3CH2CH2OH pKa = 14.6

CF3CH2CH2CH2OH pKa = 15.4

Using Using pKpKaa Values to Predict Acid-Base ReactionsValues to Predict Acid-Base Reactions

NaOH + CH3CH2OH NaOCH2CH3 + HOH

pKa = 15.9 pKa = 15.7

Reactions favor the side with the highest pKa

Sodium hydroxide will not deprotonate most alcohols

base conjugate acidacid conjugate base

Prediction of Acid-Base ReactionPrediction of Acid-Base Reaction

Will potassium ethoxide deprotonate 3,3,3-trifluoroethanol?

KOCH2CH3 + CF3CH2OH HOCH2CH3 + CF3CH2OK

acid conjugate acid

pKa = 12.4 pKa = 15.9

The higher pKa is on the right side of the equation, thereforethe reaction will proceed in this direction: So YES,potassium ethoxide will deprotonate 3,3,3-trifluoroethanol.

Acid-Base reactions favor formation of weaker acids and bases

E1 Elimination of Alcohols with Sulfuric AcidE1 Elimination of Alcohols with Sulfuric Acid

H2SO4 (sulfuric acid) dehydrating acid - the acid can be made tobe nearly 100% pure, no water; also, the acid anions are poornucleophiles (HSO4

- and SO4-2)

OH

H2SO4 + H2O

OH

HBr + H2O + Br-

Br+ H2O

HBr is a strong acid, but the anionis also a good nucleophile that canlead to substitution products