Chap 9 Aromatic Compounds Outline of Chap 9 1) Naming of Aromatic Compounds 2) Structure and Properties of Aromatic Compounds - Structure and stability of benzene - Aromaticity and Huckel’s 4n+2 Rule - Aromatic Ions and Heterocycles - Polycyclic Aromatic Compounds 3) Electrophilic Aromatic Substitution Reactions 4) Nucleophilic Aromatic Substitution Reactions 5) Oxidation and Reduction of Aromatic Compounds 6) Synthesis of polysubstituted benzenes Exercises 1. Naming Aromatic Compounds Monosubstituted Benzenes Phenyl (–C6H5) Benzyl (C6H5CH2–) Disubstituted benzenes Benzenes with more than two substituents 2. Structure and Properties of Aromatic Compounds Structure of Benzene • Length of all carbon-carbon bonds are the same. • Planar structure - All C-C-C bond angles are 120° - All six carbon atoms are sp2-hybridized with p orbital perpendicular to the plane of the ring. Stability of Benzene Reactivity of benzene is different from normal alkene. Aromaticity • Benzene is cyclic and conjugated • Benzene is unusually stable. • Benzene is planar and has the shape of a regular hexagon. All bond angles are 120º, all carbon atoms are sp2-hybridized, and all carboncarbon bond lengths are 139 pm. • Benzene undergoes substitution reactions that retain the cyclic conjugation rather than electrophilic addition reactions that would destroy the conjugation • Benzene is a resonance hybrid whose structure is intermediate between two line-bond structures. Hückel 4n + 2 rule Theory devised in 1931 by the German physicist Erich Hückel A molecule is aromatic only if it has a planar, monocyclic system of conjugation and contains a total of 4n + 2 p electrons, where n is an integer (n = 0, 1, 2, 3,…). Only molecules with 2, 6, 10, 14, 18,… p electrons can be aromatic. Aromatic Ions Aromatic Ions Aromatic Heterocycles Aromatic Heterocycles Aromatic Heterocycles Polycyclic Aromatic Compounds # of π electron = 10 3. Electrophilic aromatic substitution reactions Electrophilic aromatic substitution Aromatic Halogenation Aromatic Halogenation Aromatic halogenation can be used in the synthesis of numerous pharmaceutical agents such as the antianxiety agent diazepam (Valium). Aromatic Nitration Aromatic Nitration The nitro substituted aromatic compounds can be reduced to arylamine, ArNH2 Aromatic Sulfonation Hydroxylation of Aromatic Rings Alkylation of Aromatic Rings (Friedel-Crafts Alkylation) Friedel-Crafts alkylation has several limitations 1) Aromatic (aryl) halides and vinylic halides do not react because aryl and vinylic carbocations are too high in energy to form under Friedel-Crafts conditions. Friedel-Crafts alkylation has several limitations 2) It does not occur on aromatic ring having strongly electron-withdrawing substituents. Friedel-Crafts alkylation has several limitations 3) It is often difficult to stop the reaction after a single substitution. Friedel-Crafts alkylation has several limitations 4) A skeletal rearrangement of the alkyl carbocation electrophile sometimes occurs. Friedel-Crafts alkylation has several limitations 4) A skeletal rearrangement of the alkyl carbocation electrophile sometimes occurs. Example) Friedel-Crafts reaction of benzene with 2-chloro-3-methyl-butane in the presence of AlCl3 Acylation of Aromatic Rings (Friedel-Crafts Acylation) An acyl cation is stabilized by interaction of the vacant orbital on carbon with lone-pair electrons on the neighboring oxygen. Because of stabilization, no carbocation rearrangement occurs during acylation. Substituent Effects in Electrophilic Aromatic Substitutions Substituents affect the reactivity of the aromatic • Some substituents activate the ring, making it more reactive than benzene. • Some substituents deactivate the ring, making it less reactive than benzene. Substituent Effects in Electrophilic Aromatic Substitutions Substituents affect the orientation of the reaction. Substituent Effects in Electrophilic Aromatic Substitutions Substituents can be classified into three groups • ortho- and para-directing activators • ortho- and para-directing deactivators • meta-directing deactivators Substituent Effects in Electrophilic Aromatic Substitutions Electron donating & withdrawing of substituents Stabilization of carbocation intermediate in nitration of toluene Stabilization of carbocation intermediate in nitration of chlorobenzene Stabilization of carbocation intermediate in nitration of benzaldehyde Orienting Effects: Ortho and Para Directors - Ortho and para substitutions allow the intermediate to be stabilized by more resonance forms than the meta substitution intermediate Orienting Effects: Meta Directors - Meta substitution allows the lower energy intermediate than ortho and para substitution 4. Nucleophilic aromatic substitution reactions Aryl halides that have electron-withdrawing substituents can undergo a nucleophilic substitution reaction. Mechanism of nucleophilic aromatic substitution reactions Stabilization of anion intermediate Nucleophilic aromatic substitution occurs only if the aromatic ring has an electron-withdrawing substituent in a position ortho or para to the leaving group to stabilize the anion intermediate through resonance Electrophilic aromatic substitution vs. Nucleophilic aromatic substitution Electrophilic substitutions are favored by electron-donating substituents which stabilize the carbocation intermediate Nucleophilic substitutions are favored by electron-withdrawing substituents which stabilize a carbanion intermediate Electron-withdrawing groups that deactivate rings for electrophilic substitution (nitro, carbonyl, cyano, and so on) activate rings for nucleophilic substitution 5. Oxidation and Reduction of Aromatic Compounds Oxidation of butylbenzene into benzoic acid Reduction of Aryl Alkyl Ketone 6. Multistep organic synthesis - Synthesis of polysubstituted benzenes Planning a successful multistep synthesis of a complex molecule requires knowledge of the uses and limitations of numerous organic reactions. The planning an organic synthesis is to work backward, often referred to as the retrosynthetic direction • Keep starting material in mind and work backward to it • Look at the final product and determine possible immediate precursors of that product • Work backward one step at a time Synthesis of 4-bromo-2-nitrotoluene from benzene Synthesis of 4-bromo-2-nitrotoluene from benzene Synthesis of 4-chloro-2-propylbenzenesulfonic acid from benzene Synthesis of 4-chloro-2-propylbenzenesulfonic acid from benzene Exercises Q1. Pyridine은 electrophilic substitution 반응이 일어난다. 맞으면 True, 틀리면 False라고 쓰고, 그 이유를 π orbital 구조를 그리고 설명하시오. [해설] True. Pyridine은 aromatic 하므로, electrophile substitution 반응이 일어난다. Pyridine의 π orbital 구조는 다음과 같이 평면 구조이며, p orbital이 서로 resonance 구조를 이루며 π 전자가 total 6개로써 4n+2 법칙을 만족함. Q2. Cycloocta-1,3,5,7-tetraene은 potassium metal (K)과 반응하여 안정한 구조의 cyclooctatetraenyl dianion (C8H8-2) 이 생성된다. 이러한 반응이 잘 일어나는 이유는? Cyclooctatetraene dianion의 구조를 설명하시오. [해설] Cyclooctatetraene은 다음과 같이 K로 부터 전자 두 개를 accept하여 aromatic 구조의 cyclooctatetraenyl dianion 으로 변환될 수 있어 반응이 매우 잘 일어남. Cyclooctatetraenyl dianion은 평면구조이며 π 전자 개수는 8+2 =10 개로써 Hückel 의 4n + 2 rule을 만족함. Q3. 다음과 같은 구조의 Furan은 aromatic compound이다. 이 물질의 기하학적 구조 및 π orbital 구조를 그리시오. [해설] Furan의 구조는 다음과 같이 평면 구조이며, p orbital이 서로 resonance 구조를 이루며 π 전자가 total 6개로써 Hund의 4n+2 법칙을 만족함. Q4. o-xylene, m-xylene, p-xylene을 각각 Cl2/FeCl3와 반응시켜 얻어지는 생성물들을 모두 쓰시오. [해설] Q5. Benzene의 H를 중수소(D)로 치환시키기 위한 반응식을 쓰시오. 반응메커니즘도 함께 쓰시오. [해설] Benzene(C6H6)을 D2SO4와 오래 반응시키면 benzene의 수소가 모두 D로 치환되어 C6D6가 생성된다. Q6. Benzene을 AlCl3 존재 하에서 1-chloro-2-methylpropane과 반응시키면 tert-butylbenzene이 얻어진다. 이러한 Friedel-Craft alkylation 반응의 메커니즘을 쓰시오. Hydride shift [해설] 1-chloro-2 -methylpropane Q7. 다음과 같은 aromatic ketone을 benzene의 Friedel-Craft acylation 반응으로 제조하는 반응식을 각각 쓰시오. [해설] Acid chloride Q8. 다음 물질들의 구조를 쓰고, electrophilic substitution 반응 속도가 빠른 순으로 부등호로 표시하시오. [해설] > > > > > > > > > Q9. 다음 반응으로 부터 얻어지는 main product를 각각 쓰시오. ? [해설] ? ? Q9. 다음 반응으로 부터 얻어지는 main product를 각각 쓰시오. (계속) (e) (f) ? ? ? [해설] (e) (f) Q10. 제초제의 일종인 oxyfluorfen은 다음과 같은 반응을 이용하여 제조한다. 이 반응의 메커니즘을 쓰시오. [해설] Nuclophilic substitution reaction Q11. 다음 화합물을 산화제인 KMnO4로 처리하여 얻어지는 생성물을 쓰시오. [해설] Q12. Benzene으로 부터 다음 물질을 제조하는 반응식을 각각 쓰시오 (여러 단계가 필요할 수 있음). a) Diphenylmethane [해설] a) b) b) m-Chloronitrobenzene Q12. Benzene으로 부터 다음 물질을 제조하는 반응식을 각각 쓰시오 (계속). c) m-Chloroethylbenzene [해설] c) d) d) p-Chloropropylbenzene Q12. Benzene으로 부터 다음 물질을 제조하는 반응식을 각각 쓰시오 (계속). e) 3-Bromo-2-methylbenzenesulfonic acid [해설] e) Q13. Benzene 또는 toluene으로 부터 다음 물질을 제조하는 반응식을 쓰시오. [해설] Q13. Benzene 또는 toluene으로 부터 다음 물질을 제조하는 반응식을 쓰시오. (계속) [해설] Q14. 다음 반응이 잘 일어날 수 있는가? 맞으면 True, 틀리면 False라 쓰고, 이유를 설명하시오. [해설] a) False. Friedel-Crafts alkylation과 acylation 반응은 electron-withdrawing group을 갖는 aromatic ring과는 반응이 잘 일어나지 못함. Q14. 다음 반응이 잘 일어날 수 있는가? 맞으면 True, 틀리면 False라 쓰고, 이유를 설명하시오. (계속) [해설] b) False. 1) Friedel-Crafts alkylation 반응 시 1차 RX 화합물을 사용하면 carbocation의 재배열이 일어남. 2) Propyl기는 ortho & para director임. 이러한 product를 얻기 위해서는 다음과 같이 반응시켜야 함. Q15. Phenol과 p-nitrophenol 의 pKa 값은 각각 8.89와 7.15 이다. 어떤 것이 더 강산인가? 그 이유를 각 phenoxide anion의 구조를 그려 설명하시오. [해설] p-Nitrophenol이 phenol에 비해 더 강산임. para 위치에 있는 nitro기가 다음과 같이 resonance에 의해 phenoxide anion을 안정화시키기 때문임. Q16. Phenol과 p-methylphenol 중 어느 것이 더 강산인가? 이유를 설명하시오. [해설] Phenol이 p-methylphenol에 비해 더 강산임. para 위치에 있는 methyl기는 electron donating group 이어, phenoxide anion을 더 불안정하게 만들기 때문임.