Aromatic compounds

• • • •

Organic compound that contains a benzene ring in its molecule is known as an aromatic compounds.

Sometimes called arenes.

Molecular formula: C 6 H 6 Represented as a regular hexagon containing an inscribed circle.

Structure of Benzene

•

Can be represented in two abbreviated ways.

•

The corner of each hexagon represents a carbon and a hydrogen atom.

Kekulé Structure of Benzene

Molecular formula is C 6 H 6 All the hydrogen atoms are equivalent Each carbon atom must have four covalent bonds.

Resonance Structure

•

Resonance theory: the structure of benzene is a resonance hybrid structure of two Kekulé cononical forms.

•

The hybrid structure is often represented by a hexagon containing an inscribed circle.

represents a resonance hybrid between the two

• •

Hexagonal ring – 6 carbon-carbon bonds are equal.

Circle – delocalised electrons of the benzene ring

Naming Aromatic Compounds

• •

A substituted benzene is derived by replacing one or more of benzene’s hydrogen atoms with an atom or group of atoms.

A monosubstituted benzene has the formula C 6 H 5 G where G is the group that replaces a hydrogen atom.

•

All hydrogens in benzene are equivalent.

•

It does not matter which hydrogen is replaced by G.

Monosubstituted Benzenes

• Some monosubstituted benzenes are named by adding the name of the substituent group as a prefix to the word benzene.

• The name is written as one word. nitro group

ethyl group nitrobenzene ethylbenzene

•

Certain monosubstituted benzenes have special names.

•

These are parent names for further substituted compounds.

methyl group hydroxy group toluene phenol

benzoic acid

carboxyl group amino group

aniline

•

Disubstituted Benzenes

•

Three isomers are possible when two substituents replace hydrogen in a benzene molecule.

• The prefixes ortho-, meta- and para- (o-, m- and p-)

are used to name these disubstituted benzenes.

ortho disubstituted benzene substituents on adjacent carbons ortho-dichlorobenzene (1,2-dichlorobenzene) mp –17.2

o C, bp 180.4

o C

meta-dichlorobenzene (1,3-dichlorobenzene) mp –24.82

o C, bp 172 o C meta disubstituted benzene substituents on adjacent carbons

para disubstituted benzene substituents are on opposite sides of the benzene ring para-dichlorobenzene (1,4-dichlorobenzene) mp 53.1, bp 174.4

o C

When one substituent corresponds to a monosubstituted benzene with a special name, the monosubstituted compound becomes the parent name for the disubstituted compound.

phenol 3-nitrophenol

When one substituent corresponds to a monosubstituted benzene with a special name, the monosubstituted compound becomes the parent name for the disubstituted compound.

toluene 3-nitrotoluene

Tri- and Polysubstituted Benzenes

• • • •

When a numbered.

benzene ring has three or more substituents, the carbon atoms in the ring are Numbering starts at one of the substituent groups.

The numbering direction can be clockwise or counterclockwise.

Numbering must be in the direction that gives the substituent groups the lowest numbers.

clockwise numbering 6-chloro 1-chloro 6 5 1 4-chloro 4 2 3 1,4,6-trichlorobenzene

counterclockwise numbering chlorine substituents have lower numbers 3 2-chloro 2 1 1-chloro 4-chloro 4 6 5 1,2,4-trichlorobenzene

• When a compound is named as a derivative of

the special parent compound, the substituent of the parent compound is considered to be C-1 of the ring.

1 6 5 4 toluene 3 2 6 5 1 2 3 4 2,4,6 trinitrotoluene (TNT)

• •

When the hydrocarbon chain attached to the benzene ring is small, the compound is named as benzene derivative.

Example: CH 2 CH 3 ethylbenzene

Benzene’s  electrons participate as a Lewis base in reactions with Lewis acids Lewis acid: electron pair acceptor Lewis base: electron pair donor

Mechanism r.d.s.

slow E H E H :B fast -H (+) E E + H -B

Halogenation of Benzene

Requires a Lewis acid catalyst H Cl 2 FeCl 3 Cl + H -Cl H Br 2 FeBr 3 Br + H -Br Reactivity: F 2 >> Cl 2 > Br 2 >> I 2

Catalyst Br Br + Br Br Fe Br Br + Br Br Fe Br Br Br d + Br Br d Fe Br Br

Mechanism (Cont ’ d) H Br r.d.s.

slow Br H Br H Br H + Br Br Fe Br Br Br + FeBr 3 + H Br

Nitration of Benzene

Electrophile = NO 2 ⊕ (nitronium ion)

Mechanism O O N O H + H O O S O O H O O N O H + O H O O S O O H N O + H O H O N O -H (+) O N O H O N O H O N O H

Sulfonation

H O O S O O H + H O O S O O H H O O H S O O H + O O S O O H O S O O + H O H H + O O S O O H r.d.s

O O S O H O S O O H

repeat next slide

O O S H O

repeat

O S O H O other (

p,o

) resonance structures O O S H O O O S O H + H O H H O O S O H H + O H H O O S O O H O S O O H H O O S O O H

Sulfonation & Desulfonation-useful!

(heat)

Friedel –Crafts Alkylation

Electrophile = R  R = 2 o or 3 o (not vinyl or aryl)

Non-reactive

46

Friedel –Crafts Acylation

O Acyl group: R Electrophile is R –C≡O ⊕ (acylium ion)

RX and Mechanism + O Cl O d + d + Cl Cl Cl Al d Cl Cl Al Cl Cl O R O Cl Cl Al 4 Al Cl Cl + O -H (+) O R H O R H O R H

Acid chlorides (or acyl chlorides) Prep

Ch. 15 - 33

Limitations of Friedel –Crafts Reactions

(not formed) Cl 3 Al carbocations rearrangement

Ch. 15 - 35

Reason 1 o cation (not stable) 3 o cation

Ch. 15 - 36

Questions?

Ch. 15 - 3

Problems: Friedel –Crafts alkylations, acylations, etc. with withdrawing groups & amines (basic) generally give poor yields deactivating gps

Basic amino groups ( –NH 2 , –NHR, & –NR 2 ) form strong electron withdrawing gps with acids Not Friedel-Crafts reactive

Another problem: polyalkylations can occur More common with activated aromatic rings

Electrophilic Aromatic Substitution

Activating and Directing effects of substituents already on the ring

Substituents effect reactivity &

regiochemistry

of substitution

Y

E + possibilities

Y

E

Y Y

ortho o meta m E Y = EDG (

e

lectron-

d onat

ing g roup) or EWG (

e

lectron w ithdrawing g roup) E para p

Ch. 15 - 48

Products of Nitration

CH 3 HNO 3 H 2 SO 4 CN HNO 3 H 2 SO 4 OH HNO 3 H 2 SO 4

63%

CH 3 + NO 2

17%

CN NO 2 +

50%

OH NO 2 + para

3%

NO 2 CH 3 + O 2 N

34%

CH 3 1 hr

81%

CN + O 2 N NO 2

2%

CN 48 hr

0%

NO 2 OH + O 2 N

50%

OH 0.0003 hr

relative to benzene Ring is electron rich; Ring reacts faster than benzene with E + Ring is electron poor; Ring reacts slower than benzene with E +

Ch. 15 - 50

Reactivity towards electrophilic aromatic substitution

Regiochemistry: directing effect General aspects Either

o-

,

p-

directing or

m-

directing Rate-determining-step: p

Y Y Y Y

E + ortho E E E

Ch. 15 - 57

Y

E + para

Y

E

Y Y

E + meta E

Y

E

Y

E

Y

E

Y

E

Ch. 15 - 59

Effect

of

Electron-Donating

(releasing) and

Electron-Withdrawing Groups

If G is

electron-donating

group G then reaction is

faster

than with benzene G G G + E (+) d + E d + H E H E H t.s.

stabilized arenium ion stabilized

Ch. 15 - 67

If G is an electron-withdrawing then reaction is

slower

than with benzene G G + E (+) G d + E d + H t.s.

destabilized G E H arenium ion

de

stabilized E H

Ch. 15 - 68

Inductive

and

Resonance Effects:

Orientation Two types of EDG (1) resonance donation of e (-) s into the benzene ring (2) e (-) -inductive donation (through σ bond)

Ch. 15 - 70

Two types of EDG Positive resonance effect is stronger than positive inductive effect

(if the atom directly attacked to the benzene is in the same row as carbon)

O CH 3

Ch. 15 - 71

EWG negative resonance (mesomeric) or by negative inductive effect O Deactivate the ring by resonance effect Deactivate the ring by negative inductive effect

Ch. 15 - 72

Meta-Directing Groups

EWG EWG E (+) E EWG = –COOR, –COR, –CHO, –CF 3 , –NO 2 , etc.

( EWG ≠ halogen )

Ch. 15 - 73

For example “if” ortho or para CF 3 O N O CF 3 NO 2 CF 3 NO 2 CF 3 NO 2 etc.

CF 3 O N O CF 3 NO 2 CF 3 (highly unstable, negative inductive effect of –CF 3 ) CF 3 etc.

NO 2 NO 2

Ch. 15 - 74

meta

CF 3 CF 3 O N O H NO 2 -H (+) CF 3 CF 3 NO 2 CF 3 NO 2 positive charge never on a carbon adjacent to the

EWG

NO 2

Ch. 15 - 76

Ortho –Para-Directing Groups

EDG E (+) EDG E + EDG E EDG = –NR 2 , –OR, –OH, etc.

Ch. 15 - 77

EDG - para H N O (-) AlCl 4 Cl (+) H N O Cl extra resonance structure, positive resonance effect H N O H N O H N O Cl Cl H N O H Cl -H (+) Cl

Ch. 15 - 78

EDG - ortho H N O Cl (+) (-) AlCl 4 H N O (extra resonance) Cl H N O Cl O H N H Cl H N O Cl -H (+) H N O Cl

Ch. 15 - 79

EDG - (if meta: no extra stabilization) H N O (-) AlCl 4 Cl (+) H N O Cl H N O Cl H N O H Cl -H (+) H N O Cl

Ch. 15 - 80

halogens, two opposing effects X X X X X negative inductive effect positive resonance effect halogens - weak deactivating negative inductive effect > positive resonance

Ch. 15 - 81

But regiochemistry -o,p

Cl O N O Cl H NO 2 Cl NO 2 Cl NO 2 Cl NO 2 Cl -H (+) NO 2 Cl extra resonance Cl NO 2 -H (+) Cl Cl Cl O N O Cl NO 2 NO 2 H NO 2 NO 2

Ch. 15 - 83

Cl Cl Cl Cl O N O NO 2 meta: (no extra stabilization resonance, higher energy rx path) NO 2 -H (+) Cl H NO 2 NO 2

Ch. 15 - 85

Ortho – Para Direction and Reactivity of Alkylbenzenes

Ortho attack Relatively stable contributor

Meta attack

Para attack Relatively stable contributor

Classification of Substituents

Benzene NO 2 SO 3 H CO 2 H CHO

more deactivating

NR 3 + CN CR COR O m-directing deactivators O I Br Cl F o,p-directing deactivators R H Ar OR

more activating

NHCOCH o,p-directing activators 3 NH 2 OH

Product Distribution in Nitration

X ortho (Percent %) meta

(meta-directing Deactivators)

para -N(CH 3 ) 3 -NO 2 -CO 2 H 22 -CN CO 2 CH 2 CH 3 -COCH 3 -CHO 19 2 7 77 17 28 26 72 89 11 91 2 2 81 72 72 9 2 2 2 X ortho meta (Percent %) para

(ortho- and para-directing Deactivators)

-OH -F -Cl 13 35 -Br -I 43 1 45 56 1

(ortho- and para-directing Activators)

-CH 3 50 -NHCOCH 3 19 63 0 1 1 3 50 2 86 64 54 34 79

Summary

Energy Reactants -

NO 2 or -CO 2 H, ortho- and para -NO 2 or -CO 2 H, meta-

-

Cl or -Br, meta-

-

Cl or -Br, ortho- and para-

-

H (unsubstituted) -R or -Ar, meta- -R or -Ar, ortho- and para- Deactivators Activators -NH 2 or -OH, meta- -NH 2 or -OH, ortho- and para-

[Carbocation Intermediate] Reaction Progress

•

Additivity of substituent effects in disubstituted aromatic rings

Rule 1: If the directing effects of two substituents reinforce each other, the predicted product predominates.

CH 3 (o,p) CO 2 H (m) HNO 3 H 2 SO 4 CH 3 NO 2 CO 2 H

Additivity of substituent effects…

• Rule 2: If the directing effects of two substituents oppose each other, the more activating group dominates, but mixtures often result.

NH 2 (o,p; STRONG activator) Br 2 CH 3 (FeBr 3 cat not needed) (o,p; weak activator) NH 2 Br CH 3

Additivity of substituent effects…

• Rule 3: Substitution almost never occurs between two substituents meta to each other.

CH 3 (o,p)

X (too crowded)

SO 3 Cl (o,p) H 2 SO 4 CH 3 CH 3 + HO 3 S SO 3 H Cl but not: CH 3 SO 3 H Cl Cl

Additivity of substituent effects…

• Rule 4: With a bulky o,p- director and/or a bulky electrophile, para substitution predominates.

O OCCH 3 (o,p; BULKY) SO 3 H 2 SO 4 (HSO 3 + is a BULKY electrophile) O OCCH 3 SO 3 H