Electrophilic Aromatic Substitution

Transcription

1 Lecture 12 Electrophilic Aromatic Substitution E E February 22, 2018

2 Electrophilic Aromatic Substitution Electrophilic aromatic substitution: a reaction in which a hydrogen atom on an aromatic ring is replaced by an electrophile We study several common types of electrophiles, how they are generated, and the mechanism by which they replace hydrogen, which is the same for all

3 Electrophilic Aromatic Substitution E E E Please be sure that you can do this and that it makes sense to you!! E E

4 The Energetics E E E

5 Nitration 2 SO 4 NO 3 O O SO 3 O Nitric acid O O O=N=O SO 4 Nitronium ion -

6 Chlorination Chlorination requires requires a Lewis acid catalyst, such as AlCl 3 or FeCl 3 Cl Step 1: formation of a chloronium ion Cl Fe Cl chloronium Cl ion Cl - - Cl Cl Fe Cl Cl FeCl 4 Cl Cl

7 Sulfonation SO 3 2 SO 4 SO 3 Benzenesulfonic acid O O S O O S O O - Sulfonation can be reversed by eating in 2 O

8 The Friedel-Crafts Reaction.. Circa 1877 Charles Friedel James Craft Making C-C bonds is.

9 Friedel-Crafts Alkylation C 3 C 2 Cl C 2 C3 AlCl 3 Stuff!! Cl R Cl Al Cl Cl Cl - R Cl Al Cl R - AlCl 4 Cl An ion pair containing a carbocation

10 A word about the Friedel-Crafts Alkylation 1. Carbocation rearrangements are common C 3 C 3 CC 2 Cl AlCl 3 C(C 3 ) 3 Cl Benzene Isobutyl chloride tert-butylbenzene

11 Role of AlCl 3 Acts as a Lewis acid to promote ionization of the alkyl halide (C 3 ) 3 C Cl AlCl 3 (C 3 ) 3 C Cl AlCl 3 (C 3 ) 3 C Cl AlCl 3

12 Friedel-Crafts Alkylation 2. They are tough to stop! Product is more reactive than the starting material C 3 C 2 Cl AlCl 3 etc.

13 Friedel-Crafts Alkylation alkylation fails on benzene rings bearing one or more strongly electron-withdrawing groups O O O O O C CR CO COR CN 2 SO 3 C N NR 3 CF 3 CCl 3

14 Friedel-Crafts Acylation O RCX AlX 3 O CR X An acylbenzene O R-C Cl Cl Al-Cl Cl O Cl O - - R-C Cl Al Cl R-C AlCl 4 An ion pair Cl containing an acylium ion

15 Friedel-Crafts Acylation An acylium ion is a resonance hybrid of two major contributing structures R C O R C O F-C acylations are free of ONE major limitation of F-C alkylations; acylium ions do not rearrange They still do not work on deactivated Rings They stop after one substitution

16 E d d E Y Y Electrophilic aromatic substitutions include: Nitration Sulfonation alogenation Friedel-Crafts Alkylation Friedel-Crafts Acylation

17 ydrogenolysis O C 3 COCl AlCl 3 2 Pd/C There are two nice tricks hidden here Please be sure to remember this reaction!!!

18 Di- and Polysubstitution Existing groups on a benzene ring influence further substitution in both orientation and rate Orientation: certain substituents direct preferentially to ortho & para positions; others direct preferentially to meta positions substituents are classified as either ortho-para directing.. or meta directing

19 Di- and Polysubstitution Rate: certain substituents cause the rate of a second substitution to be greater than that for benzene itself; others cause the rate to be lower substituents are classified as activating toward further substitution, or deactivating

20 Di- and Polysubstitution -OC 3 is ortho-para directing and activating OC 3 OC 3 OC 3 Br Br 2 C 3 CO 2 Anisole o-bromoanisole (4%) Br p-bromoanisole (96%) Br

21 Di- and Polysubstitution - is meta directing and deactivating! Nitrobenzene NO 3 2 SO 4 m-dinitrobenzene (93%) o-dinitrobenzene p-dinitrobenzene Less than 7% combined

22 Methyl Group C 3 Toluene undergoes nitration 1000 times faster than benzene. A methyl group is an activating substituent.

23 Trifluoromethyl Group CF 3 Trifluoromethylbenzene undergoes nitration 40,000 times more slowly than benzene. The trifluoromethyl group is a deactivating substituent.

24 Relative rates of Nitration O Cl x10-8 Reactivity

25 Real Fast Pretty fast Kinda slow Pretty slow Slow Real Slow

26 Di- and Polysubstitution Some observations Alkyl groups, phenyl groups, and all groups in which the atom bonded to the ring has an unshared pair of electrons are ortho-para directing. All other groups are meta directing. All ortho-para directing groups except the halogens are activating toward further substitution. The halogens are weakly deactivating

27 Effect on Regioselectivity Ortho-para directors direct an incoming electrophile to positions ortho and/or para to themselves. Meta directors direct an incoming electrophile to positions meta to themselves. All meta directors are deactivating All ortho-para directors are activating except halogen

28 Theory of Directing Effects So what s going on here???? The rate of EAS is limited by the slowest step in the mechanism duh For EAS, the rate-limiting step is attack of E on the aromatic ring to form a resonance-stabilized cation intermediate The more stable this cation intermediate, the faster the ratelimiting step and the faster the overall reaction

29 Adding a Second Substiuent Methoxy is is therefore an o-p director

30 Adding a Second Substiuent Nitro is therefore a meta director

31 Di- and Polysubstitution C 3 CO 2 C 3 NO 3 2 SO 4 CO 2 K 2 Cr 2 O 7 2 SO 4 p-nitrobenzoic acid CO 2 K 2 Cr 2 O 7 2 SO 4 NO 3 2 SO 4 m-nitrobenzoic acid

32 ortho Nitration of Toluene C 3

33 ortho Nitration of Toluene C 3 C 3

34 ortho Nitration of Toluene C 3 C 3 C 3 this resonance form is a tertiary carbocation

35 ortho Nitration of Toluene C 3 C 3 C 3 the rate-determining intermediate in the ortho nitration of toluene has tertiary carbocation character

36 meta Nitration of Toluene C 3

37 meta Nitration of Toluene C 3 C 3

38 meta Nitration of Toluene C 3 C 3 C 3 all the resonance forms of the rate-determining intermediate in the meta nitration of toluene have their positive charge on a secondary carbon

39 Nitration of Toluene: Interpretation The rate-determining intermediates for ortho and para nitration each have a resonance form that is a tertiary carbocation. All of the resonance forms for the rate-determining intermediate in meta nitration are secondary carbocations. Tertiary carbocations, being more stable, are formed faster than secondary ones. Therefore, the intermediates for attack at the ortho and para positions are formed faster than the intermediate for attack at the meta position. This explains why the major products are o- and p-nitrotoluene.

40 Nitration of Toluene: Partial Rate Factors The experimentally determined reaction rate can be combined with the ortho/meta/para distribution to give partial rate factors for substitution at the various ring positions. Expressed as a numerical value, a partial rate factor tells you by how much the rate of substitution at a particular position is faster (or slower) than at a single position of benzene.

41 Nitration of Toluene: Partial Rate Factors 1 C All ring positions in toluene are more reactive than any position of benzene. A methyl group activates all of the ring positions but the effect is greatest at the ortho and para positons. Steric hindrance by the methyl group makes each ortho position slightly less reactive than para.

42 Synthesis of m-bromoacetophenone C 3 Br O C 3 Br O Which substituent should be introduced first?