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Chapter 77 These Powerpoint Lecture Slides Were Created and Prepared by Professor William Tam and His Wife, Dr About The Authors Chapter 77 These PowerPoint Lecture Slides were created and prepared by Professor William Tam and his wife, Dr. Phillis Chang. Professor William Tam received his B.Sc. at the University of Hong Kong in Alkenes and Alkynes I: 1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard Properties and Synthesis. University (USA). He joined the Department of Chemistry at the University of Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and Associate Chair in the department. Professor Tam has received several awards Elimination Reactions in research and teaching, and according to Essential Science Indicators , he is currently ranked as the Top 1% most cited Chemists worldwide. He has of Alkyl Halides published four books and over 80 scientific papers in top international journals such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem. Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her Created by M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She lives in Guelph with her husband, William, and their son, Matthew. Professor William Tam & Dr. Phillis Chang Ch. 7 - 1 Ch. 7 - 2 1. Introduction Alkynes ● Hydrocarbons containing C ≡C Alkenes ● Common name: acetylenes ● Hydrocarbons containing C=C H ● Old name: olefins N O I Cl C O C O CH2OH Cl F3C C Cl Vitamin A C H3C Cl H3C HH Efavirenz Haloprogin Cholesterol (antiviral, AIDS therapeutic) (antifungal, antiseptic) HO Ch. 7 - 3 Ch. 7 - 4 2. The ( E) - (Z) System for ● Examples Designating Alkene Diastereomers H (2) vs Cis -Trans System H ● Useful for 1,2-disubstituted alkenes H H ● Examples: trans -3-Hexene cis -3-Hexene H Br Cl Cl (1) Br vs H Br H H (3) Br Br vs Br trans -1-Bromo- cis -1-Bromo- trans -1,3- cis -1,3- 2-chloroethene 2-chloroethene Dibromopropene Dibromopropene Ch. 7 - 5 Ch. 7 - 6 (E) - (Z) System The Cahn-Ingold-Prelog (E) - (Z) ● Difficulties encountered for Convention trisubstituted and tetrasubstituted alkenes ● The system is based on the atomic number of the attached atom CH3 Cl cis or trans? e.g. Br ● The higher the atomic number, the H higher the priority Cl is cis to CH 3 and trans to Br Ch. 7 - 7 Ch. 7 - 8 The Cahn-Ingold-Prelog (E) - (Z) ● Examples Convention CH3 ● (E) configuration – the highest priority Cl 1 groups are on the opposite side of the 2 Br double bond H “E ” stands for “ entgegen ”; it means “opposite ” in German ● (Z) configuration – the highest priority On carbon 2: Priority of Br > C groups are on the same side of the On carbon 1: Priority of Cl > H double bond ⇒ highest priority groups “Z ” stands for “ zusammer ”; it are Br (on carbon 2) means “ together ” in German and Cl (on carbon 1) Ch. 7 - 9 Ch. 7 - 10 ● Examples ● Other examples CH3 Cl Br H (E )-1,2-Dichloroethene (1) Cl [or trans-1,2-Dichloroethene] 1 H 2 Cl ⇒ (E )-2-Bromo-1-chloropropene H C1: Cl > H C2: Cl > H Br Cl 2 CH Cl (Z )-1-Bromo-1,2-dichloroethene 3 (2) 1 Cl H Br C1: Br > Cl ⇒ (Z )-2-Bromo-1-chloropropene C2: Cl > H Ch. 7 - 11 Ch. 7 - 12 ● Other examples 3. Relative Stabilities of Alkenes Br Cis and trans alkenes do not have the 3 1 4 same stability (3) 2 crowding 5 7 8 6 (Z )-3-Bromo-4-tert-butyl-3-octene R R H R CC CC C3: Br > C C4: tBu > nBu H H R H Less stable More stable Ch. 7 - 13 Ch. 7 - 14 33A.A.Heat of Reaction + H2 Pt CC HH CC 7 kJ/mol + + H2 H H ∆H° = -127 kJ/mol 5 kJ/mol + H2 Heat of hydrogenation ∆H° = -120 kJ/mol Enthalpy ● ∆H° ≃ -120 kJ/mol ∆H° = -115 kJ/mol ≈ ≈ ≈ Ch. 7 - 15 Ch. 7 - 16 33B.B.Overall Relative Stabilities of Relative Stabilities of Alkenes Alkenes The greater the number of attached R R R R R H R H R R R H H H > > > > > > alkyl groups (i.e., the more highly R R R H R H H R H H H H H H tetra- tri- di- mono- un- substituted the carbon atoms of the substituted substituted substituted substituted substituted double bond), the greater the alkene’s stability. Ch. 7 - 17 Ch. 7 - 18 Examples of stabilities of alkenes 4. Cycloalkenes Cycloalkenes containing 5 carbon (1) > atoms or fewer exist only in the cis form (2) > cyclopropene cyclobutene cyclopentene Ch. 7 - 19 Ch. 7 - 20 Trans – cyclohexene and trans – Trans – cyclooctene has been isolated cycloheptene have a very short lifetime and is chiral and exists as a pair of and have not been isolated enantiomers cyclohexene Hypothetical trans - cyclohexene (too strained to exist at r.t.) cis - cyclooctene trans - cyclooctenes Ch. 7 - 21 Ch. 7 - 22 5. Synthesis of Alkenes via 6. Dehydrohalogenation of Alkyl Elimination Reactions Halides Dehydrohalogenation of Alkyl Halides The best reaction conditions to use H H H when synthesizing an alkene by H H base CC dehydrohalogenation are those that -HX H X H H H promote an E 2 mechanism Dehydration of Alcohols H H H H + H H E2 H , heat B: CC + B:H + CC CC X H OH -HOH H H X H Ch. 7 - 23 Ch. 7 - 24 66A.A.How to Favor an E2E 2 Mechanism Use a secondary or tertiary alkyl halide Use a high concentration of a strong if possible. (Because steric hinderance and nonpolarizable base, such as an in the substrate will inhibit substitution) alkoxide. (Because a weak and When a synthesis must begin with a polarizable base would not drive the primary alkyl halide, use a bulky base. reaction toward a bimolecular reaction, (Because the steric bulk of the base thereby allowing unimolecular will inhibit substitution) processes (such as S N1 or E1 reactions) to compete. Ch. 7 - 25 Ch. 7 - 26 Sodium ethoxide in ethanol 66B.B.Zaitsev’s Rule (EtONa/EtOH) and potassium tert- Examples of dehydrohalogenations butoxide in tertbutyl alcohol (t-BuOK/t- where only a single elimination product BuOH) are bases typically used to is possible promote E2 reactions EtONa (1) (79%) Br EtOH, 55oC Use elevated temperature because heat generally favors elimination over EtONa (2) (91%) substitution. (Because elimination Br EtOH, 55oC reactions are entropically favored over t -BuOK substitution reactions) (3) ( ) Br ( ) (85%) n t -BuOH, 40oC n Ch. 7 - 27 Ch. 7 - 28 ⊖ H When a small base is used (e.g. EtO Rate = k H3C C CH3 EtO or HO ⊖) the major product will be the Br (2nd order overall) more highly substituted alkene (the ⇒ bimolecular more stable alkene) ̶̶̶ Ha Examples: a b H H NaOEt B a b (1) + H H EtOH 2-methyl-2-butene 70oC Br 69% 31% (eliminate Ha) (eliminate Hb) Br KOEt Br (2) + + b EtOH ̶̶̶ H 51% 18% 31% 2-methyl-1-butene Ch. 7 - 29 69% Ch. 7 - 30 Zaitsev’s Rule Mechanism for an EE22 Reaction ● In elimination reactions, the more Et O highly substituted alkene product Et O H CH3 H CH3 α δ− H3C CH3 predominates C C CH3 C C CH3 C C H C β H C 3 3 δ− H CH3 Stability of alkenes H Br H Br + Me Me Me Me Me H Et OH + Br EtO ⊖ removes CC > CC > CC Partial bonds in a β proton; the transition C=C is fully Me Me Me H H Me C−H breaks; state: C −H and formed and new π bond C−Br bonds the other Me Me Me H forms and Br break, new π products are > CC > CC begins to C−C bond forms EtOH and Br ⊖ depart H H H H Ch. 7 - 31 Ch. 7 - 32 δ− O Et 66C.C.Formation of the Less Substituted H3C H Alkene Using a Bulky Base δ− CH3CH2 C C Et O δ− H Br H H CH3 Hofmann’s Rule C C CH3 H3C δ− ‡ Br ∆G ● Most elimination reactions follow y H 1 g ‡ r G e ∆ 2 Zaitsev’s rule in which the most n E CH 3 e - stable alkenes are the major e CH3 CH CH C CH + EtOH + Br r 3 2 2 F - EtO + CH3CH2 C CH3 products. However, under some Br CH3 circumstances, the major - CH3CH C CH3 + EtOH + Br elimination product is the less substituted, less stable alkene Reaction Coordinate Ch. 7 - 33 Ch. 7 - 34 ● Case 1: using a bulky base ● Case 2: with a bulky group next EtO CH3CH CHCH3 (80%) to the leaving halide + (small) CH3CH2CH CH2 (20%) less crowded β-H CH3CH2CHCH3 Me H Br H Me H Br t BuO CH3CH CHCH3 (30%) EtO + H3C C C C C H H3C C C C CH2 (bulky) CH CH CH CH (70%) 3 2 2 Me H Me H Me H Me EtO ⊖ (small base) (mainly) H H H H tBuO ⊖ more crowded β-H HCCCC H (bulky base) H H Br H Ch. 7 - 35 Ch. 7 - 36 Zaitsev Rule vs. Hofmann Rule ● Examples ● Examples Hb Br a a b H H H (2) + (1) + (eliminate Ha) (eliminate Hb) Br (eliminate Ha) (eliminate Hb) NaOEt, EtOH, 70oC 91% 9% NaOEt, EtOH, 70oC 69% 31% KOtBu, tBuOH, 75oC 7% 93% KOtBu, tBuOH, 75oC 28% 72% Ch. 7 - 37 Ch. 7 - 38 66D.D.The Stereochemistry of E22E Reactions The 5 atoms involved in the transition B B state of an E2 reaction (including the H H LG base) must lie in the same plane CC CC The anti coplanar conformation is the LG preferred transition state geometry Anti coplanar Syn coplanar ● The anti coplanar transition state is transition state transition state (preferred) (only with certain staggered (and therefore of lower rigid molecules) energy), while the syn coplanar transition state is eclipsed Ch.
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