Chapter 16 Benzene Derivatives I.Activation and Deactivation of the benzene ring A.Overview 1)Many important compounds are disubstituted aromatic rings 2)In the last chapter, we learned how electrophilic aromatic substitution adds single substituents to benzene 3)In this chapter, we will learn how to control where the 2 nd and 3 rd substituent goes on benzene 4)The first substituent controls where the others go: a)Activator = electron donor, directs to ortho and para sites b)Deactivator = electron acceptor, directs to meta sites

B.Activation and Deactivation 1.Two different effects determine how a substituent effects benzene a.Induction i.e- density transmitted through  -bonds ii.Primarily determined by electronegativity iii.Has an effect only over short distances b.Resonance i.e- density transmitted through multiple resonance structures ii.Involves  -bonds iii.Can be over a fairly long range iv.Strongest in charged systems D = R A = CF 3, NR 2, OR, X,

2.Resonance Donating Groups a)Contains an electron pair adjacent to the ring to delocalize into the ring b)May be counter to the inductive effect of the same group c)Overall effect of this type of substituents is the sum of induction/resonance i.Overall Donating = --NR 2, --OR ii.Overall Accepting = --X 3.Resonance Accepting Groups a)Contains a resonance structure with a cation adjacent to the ring b)Usually reinforces induction

4.Donor/Acceptor Effects on Electrophilic Aromatic Substitution a)Electrophilic aromatic substitution requires a benzene  -bond to attack an electrophile b)If X is electron donating, the rate speeds up = Activated c)If X is electron accepting, the rate slows down = Deactivated d)Nitration rate examples: X = OH, CH 3, H, Cl, COOEt, CF 3, NO 2 Rate = 1000, 25, 1, 0.033, , 2.6 x 10 -5, 6 x II.Inductive Effects on Benzene A.Alkyl groups are activating, ortho/para directors

1)Mechanism:

2)Important Points a.CH 3 is donating by induction b.The ortho and para attacks stabilize the carbocation by having one resonance form where the carbocation is next to CH 3 c.The meta attack gives no stabilized resonance form B.Inductively Withdrawing groups deactivate and direct toward meta positions 1)Mechanism

2)Important Points a)All attacks are destabilized, meta is the least b)Ortho and para have poor resonance structure with (+) next to CF 3 c)Attack is away from ortho and para, not toward meta

III.Resonance Effects on Benzene A.Resonance Donors Activate and ortho, para direct 1)NH 2 and OH substituents strongly activate benzene 2)Reversible Modification of amino and phenol groups can reduce reactivity (later) 3)Mechanism

4)Important Points a)Inductive electron acceptance (N > C electronegativity) b)Lone pair participates in resonance; overall donating c)Ortho and para are activated by extra resonance form d)Polysubstitution is likely because of highly activated ring B.Resonance Acceptors Deactivate and Direct Meta

1)Mechansim 2)Important points: a)Meta attack prevents (+) from being next to COOH group b)Meta attack is still destabilized, so the reaction is slow but specific

3)Halogens are deactivating, but ortho/para directing 4)Mechanism

5)Important points a)Ortho, para attack give a fourth resonance structure b)Meta attack can’t give a fourth resonance structure c)All three are slower reactive than benzene d)Exception to the rule: deactivates, ortho/para directs C.Tables 16-1 and 16-2 summarize substituent effects on benzene substitution