Electrophilic Aromatic Substitution

Transcription

1 Electrophilic Aromatic Substitution Chemistry /14/02 Lecture 5

2 Diazonium Salts OH NH 2 NaNO 2 aq. HCl N N Cl H 2 O HCl Cl + H 3 O + Chemistry /16/02

3 Diazonium Salts The -N + 2 group of an arenediazonium salt can be replaced in a regioselective manner by these groups Ar-N 2 + (-N 2 ) H 2 O HBF 4 HCl, CuCl HBr, CuBr KCN, CuCN KI H 3 PO 2 Ar-OH Ar-F Ar-Cl Ar-Br Ar-CN Ar-I Ar-H Schiemann reaction Sandmeyer reaction

4 Vilsmeier Haack Reaction N C Cl H N C Cl H H Chemistry /16/02 R R Only activated substrates!

5 Real Fast Pretty fast Kinda slow Pretty slow Slow Real Slow Chemistry /16/02

6 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 Chemistry /16/02

7 Adding a Second Substiuent Methoxy is is therefore an o-p p director Chemistry /16/02

8 Adding a Second Substiuent Chemistry /16/02 Nitro is therefore a meta director

9 Chemistry /16/02

10 Problem: what reagents and experimental conditions will bring about this conversion? CO 2 H CO 2 H CO 2 H (1) (2) (3) (4) NO 2 NO 2 NH 2 OH

11 Can you fill in the blanks?? Cl NH 2 C N CH 2 NH 2 NH 2 Cl Cl Cl Cl

12 Di- and Polysubstitution Sequence matters! CO 2 H HNO 3 H 2 SO 4 K 2 Cr 2 O 7 H 2 SO 4 NO2 NO 2 p-nitrobenzoic acid CO 2 H CO 2 H K 2 Cr 2 O 7 H 2 SO 4 HNO 3 H 2 SO 4 NO 2 m-nitrobenzoic acid Chemistry /16/02

13 How do you get there from here????? Cl Br Chemistry /16/02

14 One way to skin the cat NO 2 Br 2 FeBr 3 NO 2 Br H 2 Pd/C bb bb NH 2 Br NaNO 2 HCl Br HCl CuCl N + 2 Cl - Cl Br Chemistry /16/02

15 Let s use it!! HNO 3 NO2 CH 2 Cl NO 2 H 2 SO 4 AlCl 3 CH 2 Cl AlCl 3 CH 2 CH 2 HNO 3 H 2 SO 4 CH 2 NO 2 Is this ok???? Add this to your homework assignment Chemistry /16/02

16 Multiple Substituent Effects

17 The Simplest Case all possible EAS sites may be equivalent + O O COC AlCl 3 O C 99%

18 Another Straightforward Case Br 2 Br Fe NO 2 NO % directing effects of substituents reinforce each other; substitution takes place ortho to the methyl group and meta to the nitro group

19 Generalization regioselectivity is controlled by the most activating substituent

20 The Simplest Case all possible EAS sites may be equivalent strongly activating NH Br 2 NH Br acetic acid Cl Cl 87%

21 When activating effects are similar... HNO 3 NO 2 H 2 SO 4 C( ) 3 C( ) 3 88% substitution occurs ortho to the smaller group

22 Steric effects control regioselectivity when electronic effects are similar HNO 3 H 2 SO 4 NO 2 98% position between two substituents is last position to be substituted

23 Chemistry /16/02

24 Chemistry /16/02

25 Chemistry /16/02

26 Chemistry /16/02

27 Chemistry /16/02

28 Chemistry /16/02

29 Substitution in Naphthalene

30 Naphthalene H H H 1 2 H H H H H two sites possible for electrophilic aromatic substitution all other sites at which substitution can occur are equivalent to 1 and 2

31 EAS in Naphthalene O O C CCl AlCl 3 90% is faster at C-1 C 1 than at C-2C

32 EAS in Naphthalene E H E H + + when attack is at C-1C carbocation is stabilized by allylic resonance benzenoid character of other ring is maintained

33 EAS in Naphthalene + E H + E H when attack is at C-2C in order for carbocation to be stabilized by allylic resonance, the benzenoid character of the other ring is sacrificed

34 Substitution in Heterocyclic Aromatic Compounds

35 Generalization There is none. There are so many different kinds of heterocyclic aromatic compounds that no generalization is possible. Some heterocyclic aromatic compounds are very reactive toward electrophilic aromatic substitution, others are very unreactive..

36 Pyridine N Pyridine is very unreactive; ; it resembles nitrobenzene in its reactivity. Presence of electronegative atom (N) in ring causes π electrons to be held more strongly than in benzene.

37 Pyridine SO 3, H 2 SO 4 SO 3 H N HgSO 4, 230 C N 71% Pyridine can be sulfonated at high temperature. EAS takes place at C-3. C

38 Pyrrole,, Furan, and Thiophene N H O Have 1 less ring atom than benzene or pyridine to hold same number of π electrons (6). π electrons are held less strongly. These compounds are relatively reactive toward EAS.. S

39 Example: Furan O + O O COC BF 3 O O C 75-92% undergoes EAS readily C-2 2 is most reactive position

40 Homework: Problem in notes and. Find and write mechanisms for : Hösch Reaction Gatterman Reaction Reimer Tieman Reaction Pschorr Synthesis Chemistry /16/02