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The Art of Writing Reasonable Organic Reaction Mechanisms Robert B. Grossman University of Kentucky Professor of Chemistry Synthetic Organic Chemistry.

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Presentation on theme: "The Art of Writing Reasonable Organic Reaction Mechanisms Robert B. Grossman University of Kentucky Professor of Chemistry Synthetic Organic Chemistry."— Presentation transcript:

1 The Art of Writing Reasonable Organic Reaction Mechanisms Robert B. Grossman University of Kentucky Professor of Chemistry Synthetic Organic Chemistry 1987 B.A., Princeton University 1992 Ph. D., Massachusetts Institute of Technology 1992-1994 Post-doctoral Fellow, Cambridge University

2 課程須知 參考書目 Michael B. Smith University of Connecticut A. C. Knipe University of Ulster Organic Reaction MechanismsOrganic Synthesis Robert B. Grossman University of Kentucky

3 一、有機化學反應機制的基本原則 (Basics of Organic Reactions) 二、鹼性條件下的有機化學反應 (Reactions under Basic Conditions) 三、酸性條件下的有機化學反應 (Reactions under Acid Conditions) 四、環化反應 (Pericyclic Reactions) 五、自由基反應 (Free Radical Reactions) * 六、過渡金屬催化有機反應 (Metal-Catalyzed Reactions) 課程須知 授課大綱評量方式 期中考 30% 期中考 30% 期末考 30% 隨堂測驗 20% 期末報告 10% 期末考範圍 : 整學期授課內容 隨堂測驗 : 每節課開始, 共兩題。 期末報告 : 最後一節課分組報告,兩人一組, 每組 5 分鐘,並於課後繳交報告。

4 課程須知 Mechanisms are the means by which organic reactions are discovered, rationalized, optimized, and incorporated into the canon. They represent the framework that allows us to understand organic chemistry. The purpose of this book is to help you learn how to draw reasonable mechanisms for organic reactions. The general approach is to familiarize you with the classes and types of reaction mechanisms that are known and to give you the tools to learn how to draw mechanisms for reactions that you have never seen before. *Common error alerts are scattered throughout the text to warn you about common pitfalls and misconceptions that bedevil students. Pay attention to these alerts, as failure to observe their strictures has caused many, many exam points to be lost over the years.

5 The Basics of Organic Chemistry Chapter One

6 Common Abbreviations for Organic Substructures

7 Formal Charge Formal charges are a useful tool for ensuring that electrons are not gained or lost in the course of a reaction. EX: Calculate the formal charge of Al, N, Br, C *Common error alert: Formal charges are not a reliabe guide to chemical reactivity. CH 3 + NH 4 + which is more stable? 6e - 8e -

8 Resonance Structure For each σ bonding pattern, there are often several ways in which π and nonbonding electrons can be distributed. These different ways are called resonance structures. The true electronic picture of a compound is a weighted average of the different resonance structures. Benzene is neither this nor this. (1+2)/2= 1(1/2) bond Diazomethane is neither this nor this. Which structure is more important? Electronegativity: F> O> N> Cl

9 Types of Resonance Structure: 1. Look for a electron-deficient atom adjacent to a π bond. Resonance Structure 2. Look for a radical adjacent to a π bond. Which structure is more important? 3. Look for a lone pair adjacent to a π bond. 4. In aromatic compounds, π bonds move around to form new resonance structure. 5. The two electrons of a π bond can be divided evenly or unevenly between the two atoms making up that bond. Draw the reasonable resonance structure of following compounds? naphthalene

10 Hyperconjugation: The bonding pair of electrons in the σ orbitals can delocalize into partly P orbital. 3 o cabocation 9 adjacent C-H bonds 2 o cabocation 6 adjacent C-H bonds 1 o cabocation 3 adjacent C-H bonds > > Stability

11 Molecular Shape: Lewis Structure and Molecular Orbitals 1. 劃出分子結構,並使所有原子符合八隅體 (H 例外 ) ,統計其電子數 A 2. 計算所有原子的價電子數總和 B 3. (A- B)/2 為共用電子對,一般形成共用電子對的方法為環、雙鍵或三鍵 Draw the Lewis structure for following molecules and determinate the molecular shape? HI, C 2 2-, CH 3 OH, SiO 2, O 2, CS 2, CN - Lewis Structure eg. COCl 2 A= 26 B= 4+6+(7*2)= 24 (26-24)/2= 1 SP 2 trigonal Linear SP Trigonal SP 2 Tetrahedron SP 3

12 Molecular Orbitals Hybrid Orbitals 1. Atomic Orbital(A.O.) Molecular Orbital(M.O.) Why hydrogen exits as H 2, but helium is monoatomic? Bonding Antionding H2H2 2. sp hybrids produce linear structure: 180 0 degree results from minimizes electron repulsion BeH 2 Be 1S 2 2S 2 2P 0 2 H +.

13 Molecular Shape Hybrid Orbitals 3. sp 2 hybrids create trigonal structure BH 3 4. sp 3 hybridization explain the shape of tetrahedral carbon compounds CH 4 B 1S 2 2S 2 2P 1

14 Structure and Stability of Organic Compounds Determine the hybridization of C, N, O, B and F atoms in each of following compounds? NH 3, H 2 O, BF 3, Bond energy and bond length bond length(pm)bond energy(kJ/mol) C-C 154348 C=C 134614 120839

15 Aromaticity Aromatic 1. Cyclic. 2. P orbitals. 3. Planar. 4. total e - = 4n+2 Stability: cyclic > acyclic > Aromatic compounds furan thiophene pyrrole indole naphthalene azulene phenanthrene Cyclopentadienide tropylium pyrylium Explain why they are nonromatic compounds?

16 Stability: acyclic > cyclic > Nonaromatic If there is no cyclic array of continuously overlapping p orbitals, then the compound is nonaromatic. Antiaromatic 1. Cyclic. 2. P orbitals. 3. Planar. 4. total e - = 4n Structure and Stability of Organic Compounds Nonaromatic

17 Acidity stability 1. Electronegativity HF and H 2 O electronegativity: F > O acidity: HF > H 2 O 2. Size HI, HBr and HCl Size: I - > Br - > Cl - acidity: HI > HBr > HCl 3. Resonance Resonance forms:

18 pK a Values Acidity

19 Indicate which of each pair of compounds is likely to be more acidic and why?

20 Kinetics and Thermodynamics Chemical thermodynamics: determine the reaction will happen or not. ΔH 0 is easier to measure and TΔS 0 is small compared with ΔH 0 for most reaction(T<100 o C). Chemical Kinetics: determine how fast of the reaction. TS ΔG ‡ : activation energy TS: trasition state ΔG‡ΔG‡

21 Kinetic or thermodynamic control endo exo *Common error alert: Don’t confuse TS and Intermediate. Intermediate TS One of the joys of orgaic chemistry is designing condition under which only the kinetic or themodynamic product is obtained. Endo Rule Originate from an attractive interaction between the π system of the diene and dienophile.

22 Basics in Drawing a Mechanism Getting Started in Drawing a Mechanism

23 Classes of Overall Transformation 1. In a addition reaction, two S.M. combine to give a single product. Usually a π bond in one S.M. is replaced by two σ bond. 2. In a elimination reaction, one S.M. is divided into two products. Usually two σ bond in one S.M. are replaced by a new π bond.

24 Classes of Overall Transformation 3. In a substitution reaction, an atom or group that is σ bond to the rest of S.M. is replaced by another σ bond atom or group. 4. In a rearrangement, one S.M. gives one product with a different structure.

25 Classes of Mechanisms Classes of Mechanisms(polar, radical, pericyclic, metal-mediated reaction) 1. Polar Reaction: The chemistry of nuclephiles and electrophiles. Nuclephile a. Nucleophilicity increase as you go down the period table(polarizability). eg. I - > Cl -, Et 2 S > Et 2 O b. Nucleophilicity decrease with increase steric effect. eg. EtO - is good base and nuclephile, but tBuO - is good base bad nuclephile. Poor nuclephile and good base: LDA, LiN(SiMe 3 ) 3, DBU, TEA, EtN(i-Pr) 2, t-BuLi c. Nucleophilicity increase in polar aprotic solvent.

26 Polar Reaction Types of nuclephile a. Lone pair: N, O, S… b. Sigma bond: MH X, RMgBr, RLi, R 2 CuLi c. Pi bond: weak nuclephile and weak electrophile. When π bonds attach a electron-pull heteroatoms, it become much better nuclephile. Nu E+E+

27 Polar Reaction Types of electrophile a. Lewis acid(BF 3, AlCl 3 ), Carbocation b. Sigma bond electrophile: Good leaving group(X) c. Pi bond: When π bonds attach a electron- withdrawing group.

28 Polar Reaction *Common error alert: If a reaction is under acidic conditions, no strong bases can be present! If a reaction is under basic conditions, no strong acids can be present! Basic condition Acidic condition No R 2 O + H present No RO - present Good base and acid can’t exist in one structure. Free H + and R 3 C + should not be drawn under basic conditions

29 Free-Radical Reaction Generation of Free-radical a. Sigma bond homolysis and peroxide compounds b. One-electron reagents: c. The cycloaromatization Oxidative: DDQ, p-Chlornail, CAN, Pb(OAc) 4, Mn(OAc) 3 … Reductive: Na, Li, SmI 2, …

30 Chain Reaction Overall reaction Free-Radical Reaction a. Initiation b. Propagation c. Termination more stable Initiators: Br 2, AIBN, (BzO) 2, (t-Buo) 2, AIBN with light dimerization elimination

31 Pericyclic Reaction a. Electro cyclic reactions(ring opening or ring closing) b. Cycloadditions(two π bonds change to two σ bonds) c. Sigmatropic(σ bond cleavage) d. Ene reaction(six electrons, [4+2]cycloaddition and [1, 5]sigmatropic, allylic H)

32 Define the classes of the following pericyclic reaction? Exercises

33 Transition-Metal-Mediatd Reactions *Common error alert: a. TiCl 4, FeCl 3, AlCl 3, AgOTf, ZnCl 2 are common Lewis acids. b. FeCl 2, TiCl 3, SmI 2, (NH 4 ) 2 Ce(NO) 6 (CAN) are one-electron reducing or oxidizing agents. Transition-Metal-Mediated Reactions Pd, Os, Co, Rh, Ir, Cu…

34 Classify each of the following reactions as polar, free radical, pericyclic or transition-metal- mediated. Exercises a.b. c. d. e. f. h. g.

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