William H. Brown & Christopher S. Foote

Transcription

1 William. Brown & Christopher S. Foote Requests for permission to make copies of any part of the work should be mailed to:permissions Department, arcourt Brace & Company, 6277 Sea arbor Drive, Orlando, Florida

2 Chapter

3 Rexns of Benzene u The most characteristic reaction of aromatic compounds is substitution at a ring carbon alogenation: Fe 3 2 Chlorobenzene Nitration: 2 SO 4 NO 3 2 O Nitrobenzene 20-3

4 Rexns of Benzene Sulfonation: SO 3 2 SO 4 SO 3 Alkylation: Benzenesulfonic acid RX AlX 3 R X An alkylbenzene Acylation: O O RCX AlX 3 CR X An acylbenzene 20-4

5 Electrophilic Aromatic Sub u Electrophilic aromatic substitution: a reaction in which a hydrogen atom of an aromatic ring is replaced by an electrophile E E u We study several common types of electrophiles, how they are generated, and the mechanism by which they replace hydrogen 20-5

6 Chlorination u Chlorination requires requires a Lewis acid catalyst, such as Al 3 or Fe 3 Step 1: formation of a chloronium ion Fe chloronium ion - Fe Fe

7 Chlorination Step 2: attack of the chloronium ion on the ring to give a resonance-stabilized cation intermediate rate-limiting step Resonance-stabilized cation intermediate 20-7

8 Chlorination Step 3: proton transfer to regenerate the aromatic character of the ring - Fe 3 fast Fe 3 Cation Chlorobenzene intermediate u The mechanism for bromination is the same as that for chlorination 20-8

9 EAS: General Mechanism u A general mechanism Step 1: Step 2: E E Electrophile fast ratelimiting step E Resonance-stabilized cation intermediate u General question: what is the electrophile and how is it generated? E 20-9

10 Nitration u The electrophile is, generated as follows O O SO 3 O Nitric acid O O O=N=O Nitronium ion SO

11 Nitration u The particular value of nitration is that the nitro group can be reduced to a 1 amino group O 2 N CO 2 4-Nitrobenzoic acid Ni 3 2 (3 atm) 2 N CO O 4-Aminobenzoic acid 20-11

12 Friedel-Crafts Alkylation u Friedel-Crafts alkylation forms a new C-C bond between a benzene ring and an alkyl group C 3 Al 3 C 3 C Benzene 2-Chloropropane (Isopropyl chloride) C(C 3 ) 2 Cumene (Isopropylbenzene) 20-12

13 Friedel-Crafts Alkylation Step 1: formation of an alkyl cation as an ion pair R Al R R - Al 4 - Al An ion pair containing a carbocation 20-13

14 Friedel-Crafts Alkylation Step 2: attack of the alkyl cation on the aromatic ring R R The positive charge is delocalized onto three atoms of the ring R R 20-14

15 Friedel-Crafts Alkylation Step 3: proton transfer to regenerate the aromatic character of the ring R Al 3 R Al

16 Friedel-Crafts Alkylation u There are two major limitations on Friedel-Crafts alkylations 1. carbocation rearrangements are common C 3 Al 3 C 3 CC 2 Benzene Isobutyl chloride C(C 3 ) 3 tert-butylbenzene 20-16

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

18 Friedel-Crafts Acylation u Friedel-Crafts acylation forms a new C-C bond between a benzene ring and an acyl group O O C 3 C Al 3 CC 3 Benzene Acetyl chloride (an acyl halide) Acetophenone (a ketone) 20-18

19 Friedel-Crafts Acylation u The electrophile is an acylium ion O R-C Al- O R-C - Al O - R-C Al 4 An ion pair containing an acylium ion 20-19

20 Friedel-Crafts Acylation u An acylium ion is a resonance hybrid of two major contributing structures R-C R-C O O complete valence shells The more important contributing structure F-C acylations are free of a major limitation of F-C alkylations; acylium ions do not rearrange 20-20

21 Friedel-Crafts Acylation u A special value of F-C acylations is preparation of unrearranged alkylbenzenes O C 3 Al 3 -C-CC 3 2-Methylpropanoyl chloride O C 3 C 3 N 2 4, KO C-CC 3 C 2 CC 3 diethylene glycol Isobutylbenzene

22 Other Aromatic Alkylations u Carbocations are generated by treatment of an alkene with a protic acid, most commonly 2 SO 4, 3 PO 4, or F/BF 3 C 3 C=C 2 3 PO 4 C(C 3 ) 2 Benzene Propene (Propylene) Cumene

23 Other Aromatic Alkylations by treating an alkene with a Lewis acid Al 3 Benzene Cyclohexene Phenylcyclohexane and by treating an alcohol with 2 SO 4 or 3 PO 4 (C 3 ) 3 CO 3 PO 4 C(C 3 ) 3 2 O Benzene tert-butyl alcohol tert-butylbenzene

24 Di- and Polysubstitution u Existing groups on a benzene ring influence further substitution in both orientation and rate u 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

25 Di- and Polysubstitution u 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

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

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

28 Di- and Polysubstitution Ortho-para Directing Strongly activating N 2 NR NR 2 O Moderately activating Weakly activating Weakly deactivating NCR OR OCR OCAr R F Br I O O O Impotance in Directing

29 Di- and Polysubstitution Meta Directing Moderately deactivating Strongly deactivating O O O O C CR O CN 2 CO COR O SO C N O N 3 CF 3 C 3 Impotance in Directing

30 Di- and Polysubstitution u From the information in Table 20.1, we can make these generalizations 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 20-30

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 20-31

32 Theory of Directing Effects u The rate of EAS is limited by the slowest step in the mechanism u For almost every EAS, the rate-limiting step is attack of E on the aromatic ring to form a resonance-stabilized cation intermediate u The more stable this cation intermediate, the faster the rate-limiting step and the faster the overall reaction 20-32

33 Theory of Directing Effects u For ortho-para directors, ortho-para attack forms a more stable cation than meta attack ortho-para products are formed faster than meta products u For meta directors, meta attack forms a more stable cation than ortho-para attack meta products are formed faster than ortho-para products 20-33

34 Theory of Directing Effects u -OC 3 ; assume meta attack OC 3 slow OC 3 OC 3 OC 3 (a) (b) (c) fast - OC

35 Theory of Directing Effects u -OC 3 : OC 3 assume ortho-para attack OC 3 slow OC 3 OC 3 OC 3 (d) (e) (f) OC 3 (g) fast

36 Theory of Directing Effects u - ; assume meta attack slow fast - (a) (b) (c) 20-36

37 Theory of Directing Effects u - : assume ortho-para attack slow fast - (d) (e) (f) 20-37

38 Activating-Deactivating u Any resonance effect, such as that of -N 2, -O, and -OR, that delocalizes the positive charge on the cation intermediate lowers the activation energy for its formation, and has an activating effect toward further EAS u Any resonance or inductive effect, such as that of -, -CN, -CO, or -SO 3, that decreases electron density on the ring deactivates the ring toward further EAS 20-38

39 Activating-Deactivating u Any inductive effect, such as that of -C 3 or other alkyl group, that releases electron density toward the ring activates the ring toward further EAS u Any inductive effect, such as that of halogen, -NR 3, -C 3, or -CF 3, that decreases electron density on the ring deactivates the ring toward further EAS 20-39

40 alogens u The inductive effect of halogens - and -Br are more electronegative than carbon and have an electron-withdrawing inductive effect aryl halides react more slowly in EAS than benzene u The resonance effect of halogens a halogen ortho or para to the site of EAS can help stabilize the cation intermediate halogens are activating toward EAS 20-40

41 alogens E E E thus, for the halogens, the inductive and resonance effects run counter to each other, but the former is somewhat stronger the net effect is that halogens are deactivating but ortho-para directing 20-41

42 Nucleophilic Aromatic Sub. u Aryl halides do not undergo nucleophilic substitution by either S N 1 or S N 2 pathways u They do undergo nucleophilic substitutions, but by mechanisms quite different from those of nucleophilic aliphatic substitution u Nucleophilic aromatic substitutions are far less common than electrophilic aromatic substitutions 20-42

43 Benzyne Intermediates u When heated under pressure with aqueous NaO, chlorobenzene is converted to sodium phenoxide O - Na Chlorobenzene 2 NaO 2 O pressure, 300 o C Sodium phenoxide Na 2 O neutralization with gives phenol 20-43

44 Benzyne Intermediates u The same reaction with 2-chlorotoluene gives a mixture of ortho- and meta-cresol C 3 1. NaO, heat, pressure 2., 2 O C 3 C 3 O 2-Methylphenol (o-cresol) O 3-Methylphenol (m-cresol) 20-44

45 Benzyne Intermediates u The same type of reaction can be brought about by the use of sodium amide in liquid ammonia C 3 NaN 2 N 3 (l) (-33 o C) C 3 C 3 Na N 2 N 2 4-Methylanilinaniline 3-Methyl- (p-toluidine) (m-toluidine) 20-45

46 Benzyne Intermediates u -elimination of X gives a benzyne intermediate, that then adds the nucleophile to give products C 3 C 3 NaN 2 -elimination A benzyne intermediate 20-46

47 Nu Addition-Elimination u When an aryl halide contains electronwithdrawing - groups ortho and/or para to X, nucleophilic aromatic sub. takes place readily Na 2 CO 3, 2 O 100 o C O - Na Sodium 2,4-dinitrophenoxide 1-Chloro-2,4- dinitrobenzene neutralization with gives the phenol 20-47

48 20 Meisenheimer Complex - O N O Nu - slow, ratelimiting (1) - - O N O Nu A Meisenheimer complex fast (2) - O N O Nu

49 End Chapter