Organic Chemistry with BiologicalApplications,3 Edition JOHN MCMURRY John McMurry Chapter 12 Organohalides:Nucleophilic Organic Chemistry Substitutions and Eliminations wth Biological Applications Nucleophilic substitutions and eliminations are frequently involved in the biochemical pathways of terrestrial organisms and alkyl halide chemistry acts as a relatively simple model of biomolecules. By Junru Wang College of Chemistry and Pharmacy Room C206,Science Building Tel:87092829(O);Email:wangjr07@163.com
By Junru Wang College of Chemistry and Pharmacy Room C206, Science Building Tel: 87092829(O)；Email: wangjr07@163.com Chapter 12 Organohalides: Nucleophilic Substitutions and Eliminations Organic Chemistry with Biological Applications, 3 rd Edition John McMurry Nucleophilic substitutions and eliminations—are frequently involved in the biochemical pathways of terrestrial organisms and alkyl halide chemistry acts as a relatively simple model of biomolecules
Organic Chemistry with BiologicalApplications.3Edition John McMurry Hdomework:P434c:12.42a-912.44:12.51: P434g:12.62:12.67:12.74 Key Notes Nucleophilic Substitution,SN1/SN2,Elimination(E1/E2) Nucleophilicity,Leaving group ethyl bromide (1) isopropyl bromide (2) t-butyl bromide(3°) attack is easy attack is possible attack is impossible HO:CH3 HO:CH3 HO: -Br -Br H H3C H
Organic Chemistry with Biological Applications, 3 rd Edition John McMurry Key Notes Nucleophilic Substitution, SN1/SN2, Elimination（E1/E2） Nucleophilicity, Leaving group Homework： P434c: 12.42a-g; 12.44; 12.51; P434g:12.62; 12.67;12.74;
Main Contents Preparing Alkyl Halides Reactions of Alkyl Halides Organometallic Coupling Reactions Nucleophilic Substitution Reaction √SN2 Reaction SN1 Reaction Biological Substitution Reactions Elimination Reactions:E1 E2
Main Contents ◼Preparing Alkyl Halides ◼Reactions of Alkyl Halides ◼Organometallic Coupling Reactions ◼Nucleophilic Substitution Reaction ✓SN2 Reaction ✓SN1 Reaction ◼Biological Substitution Reactions ◼Elimination Reactions: E1 & E2
Preview:Types of Dihalides Primary,Secondary,Tertiary Alkyl Halides 个 R CH,-X R-CH,一X R-CH-X RC-X methyl halide primary (1)halide secondary (2)halide R CI tertiary (3)halide 2013 Pearson Educat Br a geminal dibromide a vicinal dichloride Geminal dihalide:Two halogen atoms are bonded to the same carbon.偕 Vicinal dihalide:Two halogen atoms are bonded to adjacent carbons..邻
Preview: Types of Dihalides Primary, Secondary, Tertiary Alkyl Halides ◼Geminal dihalide: Two halogen atoms are bonded to the same carbon. ◼Vicinal dihalide: Two halogen atoms are bonded to adjacent carbons. 偕 邻
Alkyl Halides Alkyl halide or haloalkanes -Compounds with a halogen atom bonded to a saturated sp3- hybridized carbon atom Widespread in nature Chloromethane is released in large amounts by ocean kelp,as well as by forest fires and volcanoes Vast array of industrial applications Use as inhaled anesthetics,refrigerants,pesticides,and solvents Br F-C-C-H Cl- C- H-C-Br F CI H Trichloroethylene Halothane Dichlorodifluoromethane Bromomethane (a solvent) (an inhaled anesthetic) (a refrigerant) (a fumigant) Leaing All Rights Reaorved
Alkyl halide or haloalkanes ▪ Compounds with a halogen atom bonded to a saturated sp3 - hybridized carbon atom ▪ Widespread in nature ▪ Chloromethane is released in large amounts by ocean kelp, as well as by forest fires and volcanoes ▪ Vast array of industrial applications ▪ Use as inhaled anesthetics, refrigerants, pesticides, and solvents Alkyl Halides
Uses of Alkyl Halides Solvents-degreasers and dry cleaning fluid Reagents for synthesis of other compounds Anesthetic:Halothane is CFCHCIBr CHCl3 used originally (toxic and carcinogenic)麻醉剂 In 1847,the Edinburgh obstetrician(产科医师) James Young Simpson first used chloroform for general anesthesia during childbirth. Inhalation anesthetics such as Operation of a chloroform inhaler for Halothane,CF3CHBrCl,derive surgical anesthesia around 1850. their biological activity from Valves pass the incoming air through the polar nature of their C-X cotton dampened with chloroform. bonds
Uses of Alkyl Halides ◼Solvents - degreasers and dry cleaning fluid ◼Reagents for synthesis of other compounds ◼Anesthetic: Halothane is CF3CHClBr ⚫CHCl3 used originally (toxic and carcinogenic)麻醉剂 In 1847, the Edinburgh obstetrician（产科医师） James Young Simpson first used chloroform for general anesthesia during childbirth
Uses of Alkyl Halides Freons,chlorofluorocarbons or CFC's Freon 12,CF2Cl2,now replaced with Freon 22, CF,CHCl,not as harmful to ozone layer. Pesticides DDT banned in U.S. extremely toxic to insects but not as toxic to mammals
Uses of Alkyl Halides ◼Freons, chlorofluorocarbons or CFC’s ⚫Freon 12, CF2Cl2 , now replaced with Freon 22, CF2CHCl, not as harmful to ozone layer. ◼Pesticides – DDT banned in U.S. ⚫extremely toxic to insects but not as toxic to mammals
Uses of Alkyl Halides 杀虫剂、杀灭蚊子（疟疾） ■ DDT1939年后广泛使用（残留高） Srilanka ●1934-1935150万(8万died) ●1963：仅15例 ●1968-1969第二季度60万例 1972:环境保护组织（EPA) 废除 ■冷却液和喷气燃料推进剂
Uses of Alkyl Halides ◼杀虫剂、杀灭蚊子（疟疾） DDT 1939年后广泛使用（残留高） Srilanka : ⚫1934-1935 150万（8万 died） ⚫1963:仅15例 ⚫1968-1969第二季度60万例 1972：环境保护组织（EPA）废除 ◼冷却液和喷气燃料推进剂
Halogenated Steroids as Anti-Inflammatory and Anti-Asthmatic Agents OH OH Cortisol Budenoside 0 O-CCH2CH3 SCH,F H:C O-CCH,CH HO CCH-CH HO 氟替卡松 Beclomethasone dipropionate Fluticasone propionate An international study published in early 2004 found that fluticasone was effective in reducing asthma-inducing inflammation in babies from one to three years of age,while having no significant effect on their growth. 哮喘诱发炎症
An international study published in early 2004 found that fluticasone was effective in reducing asthma-inducing inflammation in babies from one to three years of age, while having no significant effect on their growth. 哮喘诱发炎症 氟替卡松
Plant pathologist Frank Westerlund demonstrates the "bromomethane difference"between strawberries grown in a fumigated plot(right)and those not (left).The latter are withered by verticillium wilt,a fungus. The Dilemma of Bromomethane: Highly Useful but Also Highly Toxic
The Dilemma of Bromomethane: Highly Useful but Also Highly Toxic