Introduction to Organic Chemistry 2018 moreburton.chem.ox.ac.uk/handout-3_mechanism.pdf ·...

Introduction to Organic Chemistry 59

Introduction to Organic Chemistry

Handout 3 - Mechanism

http://burton.chem.ox.ac.uk/teaching.html

◼ OrganicChemistry J.Clayden,N.Greeves,S.Warren◼ StereochemistryataGlance J.Eames&J.M.Peach◼ Themajorityoforganicchemistrytextbookshavegoodchaptersonthetopicscoveredbytheselectures

◼ ElielStereochemistryofOrganicCompounds(advancedreferencetext)

C O

H

H

Nu

NuO

HH


whenatomisnegativelycharged,thenegativechargeimpliesalonepair(thisisshorthandnotationusedbyorganicchemists)

◼ acidbasereactions

◼ aLewisbaseisanelectronpairdonor(canbechargedorneutral)

◼ aLewisacidisanelectronpairacceptor(canbechargedorneutral)

HC

HH

•

+ electronH

CHH

••

HC

HH

F BF

FH C

H

HH C

H

H H CH

HH


A B A B A B A B••

Lewisacid Lewisbase

◼ conservationofcharge

Bissharinganelectronpairandthereforebecomespositivelycharged

Aisacceptinganelectronpairandthereforebecomesnegativelycharged

HO

H

•• ••

HN

HH

••

HC

HH H

CHH

••


CURLYARROWS – indicatethemovementofapair ofelectrons◼ thearrowstartsattheoriginofthepairofelectrons(lonepairorbondingpair)andtheheadofthearrowindicateswheretheelectronsendup(lonepairorbondingpair)

H

NHH

•• H

H

N H

HH

bond(electronpair)formedbetweenNandHatoms

HO

H

NH

HH H

OH +

H

NH

H

••

1st curlyarrowstartsfromthenegativechargewhichwetreatasalonepair2nd curlyarrowstartsfromtheN–Hbondpair

negativeoxygenhasdonatedelectronssobecomesneutral

positivenitrogenhasacceptedelectronsandbecomesneutral

HO ••H

NH

HH H

OH +

H

NH

H

••

◼ strictlyspeakingthearrowstartsfromanactuallonepairbutitisnormalpracticetodrawitfromthenegativecharge

HO

H

NH

HH H

OH +

H

NH

H

◼ drawingthecurlyarrowtopointattheatomtowhichitisformingabondisalsocommonpractice

thelonepairisgenerallynotdrawnexplicitly


H BH

HH

H

B HH

HF B

F

FF

F

B FF

F


H

B HH

H

planar,B– 6e,sp2

hydride,2e(1s2)

tetrahedralB– 8e,sp3

herethenegative(formal)charge(althoughdrawnonboron)doesnotrepresentalonepair–Bhas8electronsfromthebondingpairs

Me CMe

MeCl

Cl

MeMe

MeMe C

Me

MeCl

Cl

MeMe

Me

Me CMe

MeO

MeMe

MeHOH

••

H HB••

O

MeMe

Me

H

agenericbase

planar,B– 6e,sp2

fluoride,8e tetrahedralB– 8e,sp3

BH+

◼ acommonerror

acurlyarrowcannotbeginfromaproton– Hhasnoelectrons

HX


◼ arrowcomesfromabondpairofelectronsandtransfershydrogenwithitspairofelectronsi.e.ashydrideH(rememberthenegativechargeonBdoesnotrepresentalonepair)

O

Me

Me

NC

NCO

MeMe

◼ additionofaGrignardreagent– CH3–MgBr

◼ furtherexamples– sometypicalreactionsofaldehydesandketones

HNC

OH

MeMe

cyanohydrin

OMe

Me

CN

sp lonepairoverlapswithp-orbitals

NCO

MeMe

◼ orbitals

◼ LiAlH4orNaBH4

O

Me

Me HO

MeMe

H

BH

HH

O

H3C

H3C H3CO

H3CH3CCH3

◼ additionofaneutralnucleophile

O

Me

Me H3NO

MeMe

H3N

••


R

O

N R

O

NR

R

A BR

R

◼ delocalisationa.k.a resonance

H3N

•• H NH4 R3N

•• H R3NH

R=generalalkylgroup

◼ aminesarebasic– thenitrogenlonepairisreadilyprotonated

◼ amides,however,areessentiallyneutral– thelonepairisdelocalisedintothecarbonylgroup

◼ lonepairinA isbondingpairinB

◼ neitherA norB actuallyexist– the realstructureisaweightedaverageofstructuresA andB calledaresonancehybrid

◼ structuresA andB,arereferredtoasresonancestructures

◼ note– thereisnotanequilibriumbetweenA andB

◼ individualLewisstructuresdonotaccommodatetheelectrondistributionincertainfunctionalgroups,anddelocalisation(a.k.a.resonance)isasimplemethodtoaccountfortheactualelectrondistribution

◼ effectonstructure

◼ thecurlyarrowsaboverepresenttheoverlapofthenitrogenlonepairwiththeC-Oπ-orbitals

◼ thebestoverlapoccursiftheN-lonepairisinap-orbital,i.e.Nissp2 hybridised


R

O

N R

O

NR

R

A BR

R

◼ the curlyarrowsaboverepresenttheoverlapofthenitrogenlonepairwiththeC-Oπ-orbitals(theantibondingπ*orbital)

◼ thebestoverlapthereforeisiftheN-atomissp2 hybridised resultingintheN-lonepairbeinginap-orbitalwithexcellentoverlapwiththep-orbitalsoftheC–Oπ-system

◼ iftheN-atomweresp3 hybridised thentheN-lonepairwouldbeinansp3 orbitalwhichwouldresultinpooreroverlapwiththeadjacentC-Oπ-system

◼ generallybetteroverlap(offullandemptyorbitals)=greaterstabilisation

◼ actualstructureiscompositeofA andB – thegeometryofamidesisplanar

C ON

R

RR

N-sp2 hybridisedN-lonepairinp-orbital

C ON

R

RR

N-sp3 hybridisedN-lonepairinsp3-orbital

H

HH

HO

NMeMe

Me

X-raycrystalstructureofdimethylacetamide

restrictedrotationaroundC–Nbond

C–Nbondlength:amines1.47Å,amides1.33Å

R

O

N R

O

NR2R

R

A B


◼ someguidelinesfordrawingdelocalisedstructures(resonancestructures,canonicalforms)

◼ allresonancestructuremustbeproperLewisstructures

◼ thepositionsofthenucleimustbethesameinallstructures

◼ allstructuresmusthavethesamenumberofpaired/unpairedelectrons

◼ allatomsinvolvedindelocalistion shouldbeco-planarornearlyco-planar

◼ theoverallstructureofthemoleculeisaweightedaverageofthevariousresonancestructures–themorestableresonancestructurescontributemoretotheoverallstructureofthemolecule(andgenerallyonlythemoststableresonancestructuresneedtobeconsidered)

◼ chargeseparationisdestabilising

◼ theenergyoftheactualmoleculeislowerthananyoftheresonancestructures

H3C NO

OH3C N

O

O

notaproperLewisstructureN– 10electrons


Me OMe

O HCl+ H2O Me OH

O

MeOH+

◼ someofthearrowsoforganicchemistry

◼ reactionarrowA goestoB

◼ equilibriumarrow- indicatesareversiblereaction

equilibriumarrowstronglyfavouringproducts

equilibriumarrowstronglyfavouringreactants

R NO

OR N

O

O

◼ resonancearrow– indicatesactualstructureofthemoleculeisahybridofthestructuresshown

Ph

Br

EtMe

Ph

EtMe

◼ curlyarrows(doubleheaded)– indicatesmovementofapairofelectrons

◼ curvedsingle-headedarrow– indicatesmovementofsingleelectrons(homolysisofthebondinthisexample)

Br Br Br• + Br•

Me OMe

ONaOH

Me O

O

Na + MeOH


R

O

O R

O

OR R

◼ esters

oxygenatomissp2 hybridised

C OO

R

R

oneoxygenlonepairinp-orbital

oneoxygenlonepairinsp2 hybridorbital

O

OMe

estersaregenerallyplanar

◼ anunusualamide

NO

O– sp2

C– sp2

N– sp3

NO

•• NO

NO

◼ impossibleoverlapoflonepairwithp-orbitals

X◼ theaboveamideismuchmorebasicthananormalamide

◼ delocalisationincommonfunctionalgroups

R

O

OH R

O

OH

◼ carboxylicacidssimilarly ◼ carboxylate

R

O

O R

O

O

◼ azides

R NN

NR N

NN

HN

O N

S

O

OOH

H


OMe OMe OMe OMe OMe

H2C N N H2C N N

◼ ingeneralifaπ-systemhasanadjacentatomwhichcarriesalonepairdelocalisation ofthelonepairintothep-systemispossible

OMe OMe O O

NMe2 NMe2

H OH O

H

NMe2 NMe2

◼ nitrogroups

R NO

OR N

O

O

◼ ketones

R

O

R’ R

O

R’ R

O

R’ R

O

R’

OO

OO

O

OO

O

O

◼ carbonate

C OO

O

O O

enolateanion

enolether enolether

enamine

◼ diazocompounds


H2/Pt catalyst H2/Pt catalyst

H2/Pt catalyst

◼ doublebondresonance

◼ heatsofhydrogenation

ΔHohydrog =-120kJmol-1

ΔHohydrog=3x-120=-360kJmol-1

(hypothetical,1,3,5-cyclohexatriene)ΔHo

hydrog=-210kJmol-1

◼ benzene≈150kJmol-1 morestablethanexpected– (representsstabilityoverhypothetical1,3,5-cyclohextriene)– termedtheempiricalresonanceenergy(valuesvaryenormously)

◼ benzene

benzenebestrepresentedlikethisbutcannotdrawcurlyarrowmechanismsfromthisrepresentation– wewillthereforeusethealternatingdouble/singlebondrepresentationC-C sp3-sp3 1.54 Å

C-C sp3-sp2 1.50 Å

C-C sp3-sp 1.47Å

C-C sp2-sp2 1.46 Å

C-C benzene 1.39 Å

C=C 1.34 Å

C≡C 1.21Å


benzene

◼molecularorbitaldescription

◼ allcarbonatomsaresp2 hybridised

◼ allbondanglesare120°

◼ therearesixp-orbitalswhichoverlaptogivesixmolecularorbitals

Frost-Musulin Diagram– FrostCircle

◼ simplemethodtofindtheenergiesofthemolecularorbitalsforanaromaticcompound

◼ inscribetheregularpolygon,withonevertexpointingdown centredattheenergyofanisolatedp-orbital

◼ eachintersectionofthepolygonwiththecircumferenceofthecirclecorrespondstotheenergyofamolecularorbital

Energy

bondingmolecularorbitals(full)

antibondingmolecularorbital(empty)

◼ thesixelectronaredelocalisedovertheentirering– benzeneisdescribedasaromaticwitharomaticstabilisation


Hbase

◼ cyclopentadienylanion– (4n+2),n=1,6πelectrons

B:

◼ foraromaticityrequire(4n+2)π-electronscyclicallyconjugated

◼ othercommonaromaticsystems negativechargespreadover5carbonatomsEnergy

antibondingmolecularorbital(empty)


Br Br

◼ tropylium cation– (4n+2),n=1,6πelectrons– aromatic antibondingmolecularorbital(empty)


Energy

6electrons,5fromthep-orbitalsonefromthenegativecharge


◼ delocalisationinconjugatedalkenes(non-aromatic)

◼ dienes

◼ overlapofp-orbitalsoncentralcarbonleadstonewextendedmolecularorbital– increasedbonding

O O

◼ a,b-unsaturatedcarbonylcompounds

ab OO

nucleophlies thereforereactatthecarbonylcarbonortheb-position

NO

O NO

O

◼ similary witha,b-unsaturatednitrocompoundsanda,b-unsaturatednitriles

N•N

◼ orwithtriplebondedspecies

OMe

O

• OMe

O OMe • OMe


O NaCN, HCN

5-10 °CNC OH

◼ somemoresimplereactions

O NaCN, HCN

5-10 °CNC OH O NaCN, HCN

80 °C

O

NC

O O O ◼ drawingdelocalisedstructures,showsuswherenucleophilesandelectrophilesmayattacksubstrates

NC

NC O

H CN

O NaCN, HCN

80 °C

O

NC

NC

O

NC

H CN

◼ cyanidewilladdtothecarbonylcarbon,ortheb-positionofana,b-unsaturatedketonesdependingonthereactionconditions


O NaCN, HCN

5-10 °CNC OH

base O+ CN

HNC OO

CN

H

base O+ CN

◼ thesereactionscanbereversible

NC

NC O

H CN

O NaCN, HCN

80 °C

O

NC

NC

O

NC

H CN

B

• •

OCN

B• •

NC O

Introduction to Organic Chemistry 2018 moreburton.chem.ox.ac.uk/handout-3_mechanism.pdf ·...

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