Download 2014MSC(ORGANIC(CHEMISTRY!

2014MSC(ORGANIC(CHEMISTRY!
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Bonding!
o Polar!Covalent!Bonds!
! Polar!covalent!bonds!are!formed!through!the!sharing!of!electrons!between!neutral!atoms!–!
it!is!polar!where!the!electrons!are!attracted!stronger!to!one!atom!over!the!other.!!
! Therefore,!the!electron!distribution!between!the!atoms!is!not!symmetrical,!and!atoms!have!
a!partial!negative!or!positive!charge.!!
! Bond!polarity!is!due!to!differences!in!electronegativity,!which!is!the!atoms!ability!to!attract!
electrons!
! The!halogen!are!the!most!electronegative,!as!electronegativity!increases!from!left!to!right!
and!from!bottom!to!top!on!the!periodic!table.!!
! Each!atom!is!assigned!an!electronegativity!value,!and!generally,!if!two!electronegativity!
values!differ!by!more!than!0.5,!the!bond!will!be!polarised.!!
! The!more!electronegative!atom!is!partially!negative,!and!the!less!is!partially!positive.!!
Nucleophiles!and!Electrophiles!
o Nucleophile!
! An!atom,!group!of!atoms,!ion!or!molecule!that!is:!
• Nucleus!loving!
• Electron!rich!
• Delta!Negative!–!has!a!negative!charge!
• Forms!bonds!by!donating!an!electron!pair!to!an!electrophile!
• For!example,!oxygen!in!H20!is!a!nucleophile.!
o Electrophile!
! An!atom,!group!of!atoms,!ion!or!molecule!that!is:!
• Electron!loving!(electron!poor!of!deficient)!!
• Delta!positive!–!positively!charged!
• Forms!bonds!by!accepting!an!electron!pair!from!a!nucleophile!
• For!example,!the!carbon!in!a!CH2O!molecule!is!an!electrophile!!
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In!a!reaction!mechanism:!
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! Electrons!flow!from!an!electron!rich!source!towards!something!electron!poor!(from!a!
negatively!charged!region!to!a!positively!charged!region).!
! Therefore,!nucleophiles!(electron!rich!matter!–!negatively!charged)!attack!(give!an!electron!
pair!to)!electrophiles!(electron!poor!matter!–!positively!charged)!to!form!a!new!bond!–!
NEVER!THE!OTHER!WAY!AROUND.!!
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Types!of!organic!Reactions!
! Addition:!
• When!two!reactants!add!together!to!form!a!single!product!
! Elimination:!
• When!a!single!reactant!splits!into!two!products!
! Substitution:!!
• When!two!reactants!exchange!parts!to!give!two!new!products!
! Rearrangement!!
• When!a!single!reactant!undergoes!a!reorganisation!of!bonds!and!atoms!to!yield!an!
isomeric!product.!!
o Reaction!Mechanisms!
! A!reaction!mechanism!explains!what!happens!at!each!stage!of!the!reaction!–!
bonds!being!broken!or!formed,!and!in!what!order!this!happens.!!
! It!follows!the!flow!of!electrons,!using!a!curved!arrow!to!show!the!direction!
of!flow!
• This!flow!will!always!be!from!a!nucleophile!to!an!electrophile!!
! It!also!takes!into!account!all!of!the!reactants!used!and!products!formed!in!a!
reaction!
• You!will!need!to!be!able!to!draw!these!mechanisms!!
Polar!Covalent!Reaction!Mechanisms!
! Electrons!move!from!a!nucleophilic!(electron!rich)!source!to!an!electrophilic!
source!(electron!poor)!
! The!nucleophile!can!be!either!negatively!or!neutrally!charged!
! The!electron!can!be!either!positively!charged!or!neutral!
! The!octet!rule!must!be!followed!
Stereochemistry!at!Tetrahedral!Centres!
o Molecular!Handedness!
! The!top!two!molecules!shown!below!are!identical!to!their!mirror!images!
• These!molecular!images!can!superimpose!on!their!mirror!images!
! The!bottom!molecule!is!not!identical!to!its!mirror!image!
• This!molecule!cannot!be!superimposed!on!its!mirror!image!
• This!molecule!is!a!chiral!carbon!–!it!has!4!different!R!groups!attached!
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The!reason!for!handedness!in!molecules:!
! Chirality!Center!!
• The!most!common!cause!of!chirality!in!an!organic!molecule!is!the!presence!of!a!
carbon!atom!bonded!to!four!different!groups.!
Optical!Activity!
o Polarimeter!
! This!device!measures!the!amount/angle!of!rotation!
• A!solution!of!optically!active!organic!molecules!is!placed!in!a!sample!tube!
• Plane"polarised!light!is!passed!through!the!tube!containing!the!sample!
• Rotation!of!the!polarisation!plane!occurs!as!it!passes!through!the!tube!
• Light!goes!through!a!second!polariser!–!the!analyser!!
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The!new!plane!of!polarisation!and!degree!of!rotation!can!be!found!by!
rotating!the!analyser!until!the!light!passes!through!it.!
The!angle!of!rotation,!denoted!alpha,!is!expressed!in!degrees.!
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Rotation!
! Assigning!the!direction!of!rotation:!
• Levorotatory!molecules!
o Optically!active!molecules!that!rotate!plane!polarised!light!to!the!LEFT.!
o Given!the!symbol!(")!
• Dextrorotatory!molecules!
o Optically!active!molecules!that!rotate!plane!polarised!light!to!the!RIGHT.!
o Given!the!symbol!(+)!
! Two!enantiomers!rotate!the!plane"polarised!light!exactly!to!the!same!extent,!but!in!opposite!
directions.!!
o Enantiomers!(optical!isomers)!
! These!have!identical!physical!properties!–!such!as!melting!and!boiling!points.!!
! They!differ!in!the!direction!in!which!their!solutions!rotate!plane"polarised!light!
! They!are!non"superimposable!mirror!images!of!one!another!
! Mirror!images!of!chiral!molecules.!!
Sequence!rules!for!specifying!configuration:!
o Configuration!–!the!three"dimensional!arrangement!of!substituents!at!a!chirality!center!
! Sequence!rules!to!specify!the!configuration!of!a!chirality!center:!
• Look!at!the!four!atoms!directly!attached!to!the!chirality!center,!and!assign!priorities!
in!order!of!DECREASING!ATOMIC!NUMBER!!
o The!atom!with!the!highest!atomic!number!is!ranked!first;!the!atom!with!the!
lowest!atomic!number!(usually!hydrogen)!is!ranked!fourth.!
o Heavier!isotopes!of!the!same!element!rank!higher!than!the!lighter!isotopes.!!
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If!a!decision!cannot!be!reached!by!ranking!the!first!atoms!in!the!substituents,!look!along!the!
chain!to!the!second,!third!or!fourth!atoms!outward!until!a!difference!is!found.!!
• It’s!not!a!matter!of!adding!up!the!atomic!numbers!–!the!molecule!with!the!highest"
ranking!atom!takes!the!higher!priority.!!
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R!Configuration!=!#2!ranked!atom!to!the!left,!#3!ranked!atom!to!the!right!!
• R!Configuration!=!turning!the!steering!wheel!right!
S!Configuration!=!#2!ranked!atom!to!the!right,!#3!ranked!atom!to!the!left!
• L!Configuration!=!turning!the!steering!wheel!left!
#4!ranked!atom!is!always!facing!backward.!!
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Both!of!the!above!molecules!have!the!S!configuration,!yet!one!is!levorotatory!and!one!is!
dextrorotatory!–!there!is!no!connection!between!optical!rotation!and!the!R/S!configuration.!
Diastereomers!!
! Diastereomers!are!molecules!with!more!than!one!chirality!center!
! They!are!stereoisomers!that!are!NOT!mirror!images!–!they!are!definitely!not!super!
imposable.!!
! Diastereomers!have!opposite!configurations!at!one!or!more!of!the!chirality!centers,!but!at!
the!same!configuration!at!others.!!
Epimer!
! If!just!one!of!the!chiral!centers!is!different,!but!all!the!rest!are!the!same,!this!molecule!is!an!
epimer!(a!type!of!diastereomer).!
! They!are!two!diastereomers!that!differ!at!only!one!chirality!center,!yet!have!the!same!at!all!
the!others.!!
• Just!one!of!these!chiral!carbons!having!a!different!configuration!can!produce!entirely!
different!characteristics!of!the!molecule!–!it!will!have!very!different!
properties/shape/effect.!!
Meso!Compounds!
o Meso!compounds!are!those!in!which!carry!identical!compounds!–!symmetrical!to!one!another.!!
! The!molecules!have!a!plane!of!symmetry!between!them!–!they!are!ACHIRAL!!
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Racemic!Mixtures:!
o The!resolution!of!enantiomers!
! Racemic!mixtures!are!denoted!by!either!the!(+")!symbol,!or!the!prefix!d/l!to!indicate!an!
equal!mixture!of!dextrorotatory!and!levorotatory!forms.!!
! They!show!no!optical!rotation!because!the!(+)!rotation!from!one!enantiomer!cancels!out!
exactly!the!same!amount!of!rotation!that!the!(")!molecule!produces.!!
• It’s!a!1:1!ratio!mixture!of!dextrorotatory!and!levorotatory!enantiomers!(same!
compound!–!mirror!images,!non"superimposable)!
Chiral!Centers!
o A!molecule!with!n!chirality!centers!can!have!up!to!2n!stereoisomers.!
! For!example,!an!amino!acid!with!2!chiral!centers!will!have!22!=!4!stereoisomers.!
Enantiomer!vs.!Diastereomer!
o The!two!sets!of!molecules!seen!below!in!their!pairs!are!classified!as!enantiomers,!as!the!chiral!
carbons!are!in!the!same!place,!but!mirror!images!of!one!another.!!
o To!cross!between!the!sets!of!molecules,!they!would!be!classified!as!diastereomers!–!they!have!a!
different!configuration!at!one!of!the!chirality!centers,!but!the!same!configuration!at!the!other.!!
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to!be!swapped!with!something!else,!it!would!then!become!chiral!(4!x!different!
groups!attached.!!
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A!sp "hybridised!atom!is!a!Prochirality!center!if!changing!one!of!its!attached!groups!makes!it!
a!chirality!center.!!
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Distinguishing!between!two!identical!atoms!(or!groups)!on!a!prochirality!center!
! Imagine!raising!the!priority!of!one!atom!over!the!other!without!affecting!its!priority!with!
respect!to!other!attached!groups.!!
• On!the!–CH2OH!carbon!of!ethanol,!imagine!replacing!one!of!the!H!atoms!with!a!2H.!
o The!atom!whose!replacement!leads!to!an!R!chirality!is!said!to!be!pro"R!
o The!atom!whose!replacement!leads!to!an!L!chirality!is!said!to!be!pro"S!
• Be!able!to!recognise!whether!the!hydrogen!is!pro"R!or!pro"S!
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Alcohol!Dehydrogenase!occurs!during!the!reaction!of!ethanol!with!coenzyme!NAD+,!catalysed!by!
yeast.!!
! This!occurs!with!exclusive!removal!of!the!pro"R!hydrogen!from!ethanol!and!with!addition!
only!to!the!Re!face!of!NAD+!
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CHAPTER(6(–(OVERVIEW(OF(ORGANIC(REACTIONS!
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How!organic!reactions!occur:!Mechanisms!
o All!chemical!reactions!involve!bond!breaking!and!bond!making!
o There!are!two!ways!a!covalent!two"electron!bond!can!break:!
! Symmetrically!
• One!electron!remains!with!each!product!fragment!
! Unsymmetrically!
• Both!bonding!electrons!remain!with!one!product!fragment,!leaving!the!other!with!a!
vacant!orbital.!!
Polar!Reactions!
o Certain!bonds!within!molecules,!particularly!those!in!functional!groups,!are!polar.!!
! Oxygen,!nitrogen,!fluorine!and!chlorine!are!more!electronegative!than!carbon!
! Carbon!is!always!positively!polarised!(delta!plus)!when!bonded!to!more!electronegative!
elements!(they!carry!a!partial!negative!charge)!
! Carbon!is!negatively!polarised!(delta!minus)!when!bonded!to!metals!(they!carry!a!partial!
positive!charge)!
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o Product!concentration!is!much!larger!than!the!reactant!concentration!
o Reaction!proceeds!from!left!to!right!(reactants!to!products).!
• If!the!Keq!value!is!around!one:!
o Comparable!amounts!of!both!products!and!reactants!are!present!at!
equilibrium.!
• If!the!Keq!value!is!below!one!<1:!
o Product!concentration!is!much!smaller!than!the!reactant!concentration!
o Reaction!proceeds!from!left!to!right!(products!backwards!to!reactants).!!
! The!Keq!value:!
• Tells!the!position!of!equilibrium!
• Tells!how!much!product!is!theoretically!possible!
• Doesn’t!tell!the!rate!of!the!reaction!
• Doesn’t!tell!how!fast!the!equilibrium!is!established.!!
o For!a!reaction!to!have!a!favourable!equilibrium!constant!and!proceed!from!left!to!right:!
! The!energy!of!the!products!must!be!lower!than!the!energy!of!the!reactants!(the!energy!must!
be!RELEASED)!
o Gibbs!Free"Energy!Change!(ΔG)!
! This!is!the!energy!change!that!occurs!during!a!chemical!reaction!(the!energy!difference!
between!the!reactants!and!products!–!refer!to!the!graph).!!
• ΔG!=!Gproducts!–!Greactants!!
! If!ΔGo!is!negative:!
• The!reaction!is!EXERGONIC!–!ENERGY!LOST!by!system!and!released!to!the!
surroundings!
• It!has!a!favourable!equilibrium!constant!"!Keq!value!is!above!one!>1!
• It!can!occur!spontaneously!
! If!ΔGo!is!positive:!
• The!reaction!is!ENDERGONIC!–!ENERGY!ABSORBED!into!the!system!from!the!
surroundings!
• It!has!an!unfavourable!equilibrium!constant!"!Keq!value!is!below!one!<1!
• Cannot!occur!spontaneously!
Describing!a!Reaction:!
o Bond!dissociation!energies!
! Bond!strength!is!a!measure!of!the!heat!change!that!occurs!on!breaking!a!bond,!formally!
defined!as!bond!dissociation!energy.!!
o Bond!Dissociation!Energy!(D)!
! The!amount!of!energy!required!to!break!a!given!bond!to!produce!two!radical!fragments!
when!the!molecule!is!in!the!gas!phase!at!25!degrees!Celsius.!
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Chemists!use!energy!diagrams!to!graphically!depict!the!energy!changes!that!occur!during!a!chemical!
reaction!
! Vertical!axis:!
• The!total!energy!of!all!
reactants!
! Horizontal!axis:!
• The!‘reaction!coordinate!–!
the!progress!of!the!reaction!
from!beginning!to!end.!!
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The!number!of!rings!and/or!multiple!bonds!present!in!the!molecule!represents!its!degree!of!
unsaturation.!
! Unknown!hydrocarbon!of!formula!C6!H10!with!molecular!weight!of!82!has!two!fewer!pairs!of!
hydrogens!
• The!generic!formula!for!a!straight!chain!hydrocarbon!is!Cn!H2n+2!
• Therefore,!for!a!hydrocarbon!with!6!carbons,!it!can!be!assumed!that!the!straight!
chain!sibling!would!have!14!hydrogens!–!meaning!it!has!4!less.!!
o There!are!two!hydrogens!lost!when!a!double!bond!is!made!
o There!are!two!hydrogens!lost!when!a!cyclic!ring!is!made!
o There!are!four!hydrogens!lost!when!a!triple!bond!is!made!
• However!many!carbons!are!missing,!divide!this!by!2,!and!this!is!the!DEGREE!OF!
UNSATURATION!
• Therefore,!the!degree!of!unsaturation!is!4/2!=!2.!
• The!possible!structures!for!the!unknown!are!shown!below!!
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Calculations!for!compounds!containing!other!elements!in!addition!to!carbon!and!hydrogen:!
! Organohalogen!compounds:!C,H,X!(X=F,!Cl,!Br,!or!I)!
• Add!the!number!of!halogens!and!hydrogens!to!arrive!at!an!equivalent!hydrocarbon!
formula.!
o I.e.!whenever!a!halogen!is!present,!add!1!extra!hydrogen!to!the!equation!
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Organooxygen!compounds!(C,H,O)!
• Oxygen!does!not!affect!the!formula!of!an!equivalent!hydrocarbon!
• Ignore!the!number!of!oxygens!–!they!do!not!affect!the!degree!of!unsaturation!
Organonitrogen!compounds!(C,H,N)!
• Subtract!the!number!of!nitrogens!from!the!number!of!hydrogens!for!equivalent!
hydrocarbon!formula!!
o I.e.!whenever!a!nitrogen!is!present,!take!away!1!nitrogen!from!the!equation.!!
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Cis"Trans!Isomerism!in!Alkenes!
! Carbon"carbon!double!bond!description!
! Valence!Bond!Language!
• The!carbons!in!alkenes!are!sp2!hybridised!
• Three!equivalent!hybrid!orbitals!that!lie!in!a!plane!at!angles!of!120!degrees!to!one!
another!
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Always!indicate!(when!an!alkene!–!double!bond!present)!whether!it!is!E!or!Z!designation!(or!
cis/trans!if!applicable!instead).!!
Electrophilic!Addition!reactions!of!Alkenes!
! Carbon"Carbon!double!bonds!behave!as!nucleophiles!(electron!rich/donating)!in!polar!
reactions!by!donating!a!pair!of!electrons!to!an!electrophile!(electron!poor/accepting).!!
! Successful!not!only!with!water,!but!also!Hbr,!Hcl!and!HI!!
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Mechanism!of!the!acid"catalysed!electrophilic!addition!of!water!to!2"methylpropene!to!give!the!
alcohol!2"methylpropan"2"ol.!
! The!H30!molecule!happily!gives!off!one!of!the!hydrogens!due!to!the!oxygen!being!delta!plus!
(partially!positively!charged).!
! The!hydrogen!is!taken!off!due!to!the!nucleophile!(the!carbons!in!the!double!bond!–!electron!
rich!due!to!the!pie!orbitals!above!and!below!the!double!bond)!attacking!it!with!electrons.!
These!electrons!then!attach!to!the!oxygen,!replacing!the!hydrogen!and!giving!the!water!its!
normal,!neutral!charge.!!
! The!hydrogen!that!was!attacked!will!bond!to!the!carbon!on!the!right,!due!to!Markovnikov’s!
Rule!(the!rich!get!richer).!
! Although,!this!will!cause!the!double!bond!to!disappear!–!the!carbon!on!the!right!now!has!4!
bonds!(the!hydrogen!replaced!one!of!its!double!bonds)!but!the!carbon!on!the!left!now!only!
has!three!bonds!–!meaning!it!becomes!a!carbocation!(positively!charged)!
! Following!this,!the!nucleophile!(water)!with!its!abundance!of!electrons!will!attack!the!
electrophile!(the!carbocation)!and!it!will!bond!to!the!carbon,!producing!its!stable,!fourth!
bond.!Because!the!oxygen!has!donated!a!pair!of!electrons!to!be!able!to!bond!to!the!
carbocation,!it!means!the!oxygen!will!be!positively!charged.!!
! An!external!water!molecule!will!then!come!along!and!remove!one!of!the!hydrogens!attached!
to!the!oxygen!(which!is!now!itself!attached!to!the!carbon),!leaving!behind!a!lone!pair!of!
electrons,!restoring!the!oxygens!neutral!state!and!eliminating!its!positive!charge.!!
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The!acid!originally!used!(H3O)!is!not!consumed!in!the!reaction!–!it!is!reformed!in!the!end!
Proteins!have!an!overall!pI!because!of!the!acidic!or!basic!amino!acids!they!may!contain!
! Lysozyme!has!a!preponderance!of!basic!amino!acids!and!thus!has!a!high!isoelectric!point!of!
11!
! Pepsin!has!a!preponderance!of!acidic!amino!acids!and!thus!a!low!isoelectric!point!of!1!
o The!solubilities!and!properties!of!proteins!with!different!pI’s!are!strongly!affected!by!the!pH!of!the!
medium!
! Solubility!in!water!is!usually!lowest!at!the!isoelectric!point!where!the!protein!has!no!net!
charge,!and!solubility!is!higher!when!above!and!below!the!pI!(i.e.!where!there!is!a!charge!
present).!
Peptides!and!Proteins:!
o Residues:!
! A!residue!is!an!amino!acid!in!a!protein!chain!
! They!are!joined!together!by!amide/peptide!bonds!
o An!amino!group!from!one!residue!forms!an!amide!bond!with!the!carboxyl!group!of!a!second!residue.!!
! Alanylserine!is!the!dipeptide!that!results!when!an!amide!is!formed!between!the!alanine!
carboxyl!and!the!serine!amino!group!
! AMINO!ACIDS!ARE!ALWAYS!WRITTEN!WITH!AMINO!TO!THE!LEFT!&!CARBOXYLIC!ACID!TO!THE!
RIGHT!
o Two!dipeptides!can!result!from!the!reaction!between!alanine!and!serine,!depending!on!which!
carboxyl!group!reacts!with!which!amino!group!
! If!the!alanine!amino!group!reacts!with!the!serine!carboxyl!group,!serylalanine!results.!!
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Proteins:!
! The!proteins!backbone!is!a!continuous!chain!of!atoms!running!the!length!of!a!protein!or!
other!polymer.!!
• This!is!a!repetitive!sequence!of!N"CH"CO"!atoms.!
Polypeptides:!
! Convention!for!writing!peptides:!
• N"terminal!amino!acid!on!the!left!
o These!are!the!peptides!with!the!free!amino!group!
• C"terminal!amino!acid!on!the!right!
o These!are!the!peptides!with!the!free!carboxylic!acid!group!
• The!name!of!the!peptide!is!indicated!using!abbreviations.!!
Amide!Bonds:!
! Amide!nitrogens!are!non"basic!because!their!unshared!electron!pair!is!delocalised!by!the!
interaction!with!the!carbonyl!group.!
! The!overlap!of!the!nitrogen!p!orbital!with!the!p!orbital!of!the!carbonyl!group!imparts!a!
certain!amount!of!double"bond!character!to!the!C"N!bond!and!restricts!rotation!around!it.!!
• AMINE!GROUP!INVOLVED!WITH!AMIDE!BOND!=!NOT!BASIC!
! The!amide!bond!is!planer!(180!degrees)!and!is!often!180!degrees!to!the!C=O!bond.!!