Post on 28-Oct-2014
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