Week$4$ July$14,$2014$$

Electrophilic%Aroma.c%Subs.tu.on:$
Nitra1on$and$Sulfona1on$
How$can$we$replace$a$hydrogen$(H+)$with$a$nitro$group$(NO2+)?$

How$can$we$replace$a$hydrogen$(H+)$with$a$sulfonic$acid$group$(SO3H+)?$

9$
Reading:$Sec1on$16.4$
Week$4$ July$14,$2014$$
Electrophilic%Aroma.c%Subs.tu.on:$
Alkyla1on$
How$can$we$replace$a$hydrogen$(H+)$with$an$alkyl$group$(R+,$a$carboca1on)?$
This$reac1on$is$known$as$Friedel:Cra<s)Alkyla2on.$

What$are$the$significant$problems$with$FriedelACraps$alkyla1on?$

10$
Reading:$Sec1on$16.4$
Week$4$ July$14,$2014$$
Electrophilic%Aroma.c%Subs.tu.on:$$
Acyla1on$
How$can$we$replace$a$hydrogen$(H+)$with$an$acyl$group$(a$ketone)?$
This$reac1on$is$known$as$Friedel:Cra<s)Acyla2on.$

How$can$use$acyla2on$to$avoid$some$of$the$problems$of$alkyla1on?$

11$
Reading:$Sec1on$16.4$
Week$4$ July$15,$2014$$
Electron%Dona.ng%&%Withdrawing%Groups%
Match$the$chemical$ships$with$the$highlighted$protons$in$the$compounds$shown.$
Why$are$these$trends$observed?)

O
RO CH3 R2N CH3 R CH3
R CH3

H
H H H
R
OR NR2 R
O

12$
Reading:$Sec1on$16.5$
Week$4$ July$15,$2014$$
Induc.ve%vs.%Resonance%Effects%
Complete$the$following$table,$indica1ng$the$rela1ve$magnitude$of$the$various$effects.$

Func.onal%Group % %Induc.ve%Effect % %Resonance%Effect%

−NMe2$
$
$
$
−OH$
$
$
$
−CH3$
$
$
$
−Cl$
$
$
$
−C(=O)OEt$
$
$
$
−CN$
$
$
$
−N+Me3$
$
$
$
−NO2$
$
$

13$
Reading:$Sec1on$16.5$
Week$4$ July$15,$2014$$
Electrophilic%Aroma.c%Subs.tu.on:$
Direc1ng$Effects$(“Regioselec1vity”)$
When$anisole$is$nitrated,$the$ortho$and$para)products$predominate.$$Why?$
OCH3
OCH3 OCH3
HNO3 NO2 +
H2SO 4
NO2

When$acetophenone$is$nitrated,$the$meta)product$predominates.$$Why?$
O CH3 O CH3
HNO3
H2SO 4
NO2

14$
Reading:$Sec1on$16.5$
Week$4$ July$15,$2014$$
Electrophilic%Aroma.c%Subs.tu.on:$
Ac1va1ng$Effects$
Explain$the$observed$trend$in$the$rate)of$nitra1on$of$the$following$compounds:$
OCH3 O CH3

Rela1ve$rate$of$
reac1on$with$$
HNO3/H2SO4:$ fast))))))))))))))))))))))))))))normal))))))))))))))))))))))))))slow)

In$general,$ortho/paraAdirec1ng$groups$are$ac2va2ng,$while$metaAdirec1ng$groups$
are$deac2va2ng.$$Why?$

However,$halogen)subs1tuents$are$deac2va2ng,$but$are$o/pAdirectors.$$Why?$

15$
Reading:$Sec1on$16.5$
Week$4$ July$15,$2014$$
Applica.on%of%Subs.tuent%Effects:$
The$Acidity$of$Phenols$
Explain$the$observed$trends$in$the$pKa)values)of$the$following$compounds:$

OH OH OH OH

NO2 OCH3

16$
Reading:$Sec1on$18.6$
Week$4$ July$15,$2014$$
Applica.on%of%Subs.tuent%Effects:$
The$Acidity$of$Phenols,$cont.$
Explain$the$observed$trends$in$the$pKa)values)of$the$following$compounds:$

OH OH

NO2
NO2

17$
Reading:$Sec1on$18.6$
Week$4$ July$15,$2014$$
Reac.vity%of%Vinylic%Halides%
Draw$an$example$of$a$vinylic$halide.$

Why$does$that$halide$not$usually$exhibit$SN2$reac1vity?$

Why$does$that$halide$not$usually$exhibit$SN1$or$E1$reac1vity?$

What$product$would$be$formed$from$an$E2$reac1on$of$that$halide?$

18$
Reading:$Sec1on$18.1A18.3$
Week$4$ July$15,$2014$$
Reac.vity%of%Aryl%Halides%
Draw$an$example$of$an$aryl$halide;$how$is$it$different$from$a$benzylic$halide?$

Why$are$SN2$reac1ons$of$aryl$halides$impossible?$

Why$are$SN1$reac1ons$of$aryl$halides$(very$nearly)$impossible?$

Are$there$any)leaving$groups$that$can$provide$SN1$reac1vity$by$forming$an$aryl$ca1on?$

19$
Reading:$Sec1on$18.1A18.3$
Week$4$ July$15,$2014$$
Nucleophilic%Aroma.c%Subs.tu.on:$
Addi1onAElimina1on$
When$an$aryl)halide$has$nitro)groups)in$o/p$posi1ons,$then$nucleophilic$subs1tu1on$
can$take$place$IF$you$have$a$good$nucleophile.$$This$reac1on$is$referred$to$as$$
“Nucleophilic)aroma2c)subs2tu2on)(SNAr)$by)the)addi2on:elimina2on)mechanism.”$

Consider$the$following$reac1on:$
Br Br

NaSCH3

O2N NO2 O2N NO2

F SCH3

Provide$a$complete$curvedAarrow$mechanism$for$this$transforma1on.$

Why$does$subs1tu1on$replace$the$fluoride,$but$not$the$bromide?$

20$
Reading:$Sec1on$18.4$
Week$4$ July$15,$2014$$
Nucleophilic%Aroma.c%Subs.tu.on:$
Elimina1onAAddi1on$(“The$Benzyne$Mechanism”)$
When$an$aryl)halide$does$not$have$EWGs$in$o/p$posi1ons,$and$it$is$treated$with$a$very$
strong$base,$then$nucleophilic$subs1tu1on$can$take$place$via$an$intermediate$known$as$
a$benzyne.$$Subs1tu1on$by$this$mechanism$is$referred$to$as$
“Nucleophilic)aroma2c)subs2tu2on)(SNAr)$by)the)elimina2on:addi2on)mechanism.”$

Provide$a$curvedAarrow$mechanism$for$the$following$reac1on;$this$mechanism$must$$
account$for$why$a$mixture)of$products$is$formed!$

CH3 CH3 CH3

Br NaNH2 NH2 +

NH2

21$
Reading:$Sec1on$18.5$
Week$4$ July$15,$2014$$
Structure%and%Reac.vity%of%Benzyne%
Benzyne$is$a$very$unstable$species.$$How$can$we$think$about$bonding$in$benzynes?$

Provide$a$complete$curvedAarrow$mechanism$for$the$following$transforma1on:$

O
NaNH2 ((excess)
N N O
H
Br

22$
Reading:$Sec1on$18.5$
Week$4$ July$15,$2014$$
Electrophilic%πXBonds:$Carbonyl$Chemistry$
What$func1onal$groups$contain$a$carbonyl$group?$

What$dis1nguishes$some$carbonylAcontaining$compounds$from$others?$

23$
Reading:$Sec1on$19.1$&$19.4$
Week$4$ July$15,$2014$$
Oxida.on%Levels%in%Organic%Chemistry%
#%of%bonds%to%% Oxida.on%%
eXXneg%atoms% “level”% Examples%

4$ carbon)dioxide)

3$ carboxylic)acid)

2$ ketone)

1$ alcohol)

0$ alkane)

24$
Week$4$ July$15,$2014$$
Molecular%Orbitals%of%Aldehydes%&%Ketones%
Draw$molecular$orbital$diagrams$for$the$following$molecules$and$iden1fy$the$
HOMO$and$LUMO$of$each.$$In$what$ways$are$they$similar;$in$what$ways$are$they$
different?$$
H H O
O
H H H H

25$
Reading:$Sec1on$19.1$&$19.4$
Week$4$ July$15,$2014$$
Irreversible%Addi.on%to%Aldehydes%&%Ketones:$
Organometallic$Reagents$
Provide$a$curvedAarrow$mechanism$and$predict$the$product$of$the$following$reac1ons:$
MgBr
O H⁺ (w/up
+

MgBr O H⁺ (w/up
+
H H

O
Li + H⁺ 'w/up

26$
Reading:$Sec1on$19.9$
Week$4$ July$15,$2014$$
Irreversible%Addi.on%to%Aldehydes%&%Ketones:$
Hydride$Reducing$Reagents$
Provide$a$curvedAarrow$mechanism$and$predict$the$product$of$the$following$reac1ons:$
O
LiAlH 4 H⁺ ,w/up
Et2O

O NaBH 4
H CH3OH

Why$is$acid$workAup$required$for$reduc1on$with$LiAlH4,$$
but$not$for$reduc1on$with$NaBH4?$

27$
Reading:$Sec1on$19.8$
Week$4$ July$15,$2014$$
Puang%it%Together:%Synthesis%
Star1ng$from$benzene,$provide$a$synthesis$of$the$following$compound:)

OH

NO2

28$