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

Electrophilic%Aroma.c%Subs.tu.on:$Nitra1on$and$Sulfona1on$

Reading:$Sec1on$16.4$ 9$

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+)?$

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

Electrophilic%Aroma.c%Subs.tu.on:$Alkyla1on$

Reading:$Sec1on$16.4$ 10$

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$alkyla1on?$

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

Electrophilic%Aroma.c%Subs.tu.on:$$Acyla1on$

Reading:$Sec1on$16.4$11$

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$alkyla1on?$

Week$4$ July$15,$2014$$

Electron%Dona.ng%&%Withdrawing%Groups%

Reading:$Sec1on$16.5$12$

Match$the$chemical$ships$with$the$highlighted$protons$in$the$compounds$shown.$Why$are$these$trends$observed?)

RO CH3 R2N CH3 R CH3R

O

CH3

R

O

HH

RNR2

H

OR

H

Week$4$ July$15,$2014$$

Induc.ve%vs.%Resonance%Effects%

Reading:$Sec1on$16.5$13$

Complete$the$following$table,$indica1ng$the$rela1ve$magnitude$of$the$various$effects.$

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

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

Week$4$ July$15,$2014$$

Electrophilic%Aroma.c%Subs.tu.on:$Direc1ng$Effects$(“Regioselec1vity”)$

Reading:$Sec1on$16.5$14$

When$anisole$is$nitrated,$the$ortho$and$para)products$predominate.$$Why?$

When$acetophenone$is$nitrated,$the$meta)product$predominates.$$Why?$

OCH3 OCH3OCH3

NO2

NO2

HNO3H2SO4

+

HNO3H2SO4

O CH3 O CH3

NO2

Week$4$ July$15,$2014$$

Electrophilic%Aroma.c%Subs.tu.on:$Ac1va1ng$Effects$

Reading:$Sec1on$16.5$15$

Explain$the$observed$trend$in$the$rate)of$nitra1on$of$the$following$compounds:$

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

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

OCH3 O CH3

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

Week$4$ July$15,$2014$$

Applica.on%of%Subs.tuent%Effects:$The$Acidity$of$Phenols$

Reading:$Sec1on$18.6$ 16$

Explain$the$observed$trends$in$the$pKa)values)of$the$following$compounds:$

OH OH OH OH

NO2 OCH3

Week$4$ July$15,$2014$$

Applica.on%of%Subs.tuent%Effects:$The$Acidity$of$Phenols,$cont.$

Reading:$Sec1on$18.6$ 17$

Explain$the$observed$trends$in$the$pKa)values)of$the$following$compounds:$

OH

NO2

OH

NO2

Week$4$ July$15,$2014$$

Reac.vity%of%Vinylic%Halides%

Reading:$Sec1on$18.1A18.3$ 18$

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$halide?$

Week$4$ July$15,$2014$$

Reac.vity%of%Aryl%Halides%

Reading:$Sec1on$18.1A18.3$ 19$

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$ca1on?$

Week$4$ July$15,$2014$$

Nucleophilic%Aroma.c%Subs.tu.on:$Addi1onAElimina1on$

Reading:$Sec1on$18.4$ 20$

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$reac1on:$

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

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

Br

O2NF

NO2

Br

O2NSCH3

NO2

NaSCH3

Week$4$ July$15,$2014$$

Nucleophilic%Aroma.c%Subs.tu.on:$Elimina1onAAddi1on$(“The$Benzyne$Mechanism”)$

Reading:$Sec1on$18.5$ 21$

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$formed!$

CH3Br

CH3NH2

CH3

NH2

+NaNH2

Week$4$ July$15,$2014$$

Structure%and%Reac.vity%of%Benzyne%

Reading:$Sec1on$18.5$ 22$

Benzyne$is$a$very$unstable$species.$$How$can$we$think$about$bonding$in$benzynes?$

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

NH

O

BrN O

NaNH2((excess)

Week$4$ July$15,$2014$$

Electrophilic%πXBonds:$Carbonyl$Chemistry$

Reading:$Sec1on$19.1$&$19.4$ 23$

What$func1onal$groups$contain$a$carbonyl$group?$

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

24$

Week$4$ July$15,$2014$$

Oxida.on%Levels%in%Organic%Chemistry%

#%of%bonds%to%%eXXneg%atoms%

Oxida.on%%“level”% Examples%

4$

3$

2$

1$

0$

carbon)dioxide)

carboxylic)acid)

ketone)

alcohol)

alkane)