8Chapter 12b

8Chapter 12b - Chapter 12 (Part b) Aryl Halides Dr. Wolf's...

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Unformatted text preview: Chapter 12 (Part b) Aryl Halides Dr. Wolf's CHM 201 & 202 12-1 Aryl Halides Aryl halides are halides in which the halogen is Aryl attached directly to an aromatic ring. attached Carbon-halogen bonds in aryl halides are Carbon-halogen shorter and stronger than carbon-halogen bonds in alkyl halides. in Dr. Wolf's CHM 201 & 202 12-2 Table 23.1: C—H and C—Cl Bond Table Dissociation Energies of Selected Compounds Dissociation Bond Energy: kJ/mol (kcal/mol) X=H X = Cl sp3 410 (98) 339 (81) CHX sp2 452 (108) 368 (88) X sp2 469 (112) 406 (97) CH3CH2X H2C Dr. Wolf's CHM 201 & 202 12-3 Aryl Halides Aryl halides are halides in which the halogen is Aryl attached directly to an aromatic ring. attached Carbon-halogen bonds in aryl halides are Carbon-halogen shorter and stronger than carbon-halogen bonds in alkyl halides. in Because the carbon-halogen bond is stronger, Because aryl halides react more slowly than alkyl halides when carbon-halogen bond breaking is rate determining. determining. Dr. Wolf's CHM 201 & 202 12-4 Physical Properties of Aryl Halides resemble alkyl halides all are essentially insoluble in water less polar than alkyl halides Cll C µ 2.2 D 2.2 Dr. Wolf's CHM 201 & 202 Cll C µ 1.7 D 1.7 12-5 Reactions of Aryl Halides Electrophilic Aromatic Substitution (Chapter 12a) Formation of aryl Grignard reagents (Chapter 14) We have not yet seen any nucleophilic substitution We reactions of aryl halides. Nucleophilic substitution on chlorobenzene occurs so slowly that forcing conditions are required. conditions Dr. Wolf's CHM 201 & 202 12-6 Example Cll C 1. NaOH, H2O 370°C OH OH 2. H+ (97%) Dr. Wolf's CHM 201 & 202 12-7 Reasons for Low Reactivity Cll C + + Cl – SN1 not reasonable because: 1) C—Cl bond is strong; therefore, ionization C—Cl to a carbocation is a high-energy process to 2) aryl cations are less stable than alkyl 2) cations cations Dr. Wolf's CHM 201 & 202 12-8 Reasons for Low Reactivity SN2 not reasonable because ring blocks attack not of nucleophile from side opposite bond to leaving group leaving Dr. Wolf's CHM 201 & 202 12-9 12.20 Nucleophilic Substitution in Nitro-Substituted Aryl Halides Dr. Wolf's CHM 201 & 202 12-10 But... nitro-substituted aryl halides do undergo nitro-substituted do nucleophilic aromatic substitution readily Cll C OCH3 + NaOCH3 NO2 CH3OH + NaCl 85°C NO2 (92%) Dr. Wolf's CHM 201 & 202 12-11 Effect of nitro group is cumulative Effect especially when nitro group is ortho and/or para to leaving group Cll C Cll C Cll C Cll C NO2 NO2 O2N NO2 1.0 7 x 1010 Dr. Wolf's CHM 201 & 202 NO2 2.4 x 1015 NO2 too fast to measure 12-12 Kinetics follows second-order rate law: rate = k[aryl halide][nucleophile] rate inference: both the aryl halide and the nucleophile are both involved in rate-determining step involved Dr. Wolf's CHM 201 & 202 12-13 Effect of leaving group unusual order: F > Cl > Br > I X X F Relative Rate* 312 Cl Br NO2 1.0 0.8 I 0.4 NaOCH3, CH3OH, 50°C Dr. Wolf's CHM 201 & 202 12-14 General Conclusions About Mechanism bimolecular rate-determining step in which nucleophile attacks aryl halide rate-determining step precedes carbon-halogen bond cleavage rate-determining transition state is stabilized by electron-withdrawing groups (such as NO2) Dr. Wolf's CHM 201 & 202 12-15 12.21 The Addition-Elimination Mechanism of of Nucleophilic Aromatic Substitution Nucleophilic Dr. Wolf's CHM 201 & 202 12-16 Addition-Elimination Mechanism Two step mechanism: Step 1) nucleophile attacks aryl halide and bonds to the carbon that bears the halogen bonds (slow: aromaticity of ring lost in this step) Step 2) intermediate formed in first step loses halide (fast: aromaticity of ring restored in this step) Dr. Wolf's CHM 201 & 202 12-17 Reaction F OCH3 + NaOCH3 NO2 CH3OH + NaF 85°C NO2 (93%) Dr. Wolf's CHM 201 & 202 12-18 Mechanism Step 1 H •• F• • •• H – H H •• • OCH3 •• • bimolecular bimolecular consistent with secondorder kinetics; first order order in aryl halide, first order in nucleophile in NO2 Dr. Wolf's CHM 201 & 202 12-19 Mechanism Step 1 H •• F• • •• H – H H NO2 Dr. Wolf's CHM 201 & 202 •• • OCH3 • •• slow H •• F• • •• – •• • • OCH3 ••H H H NO2 NO 12-20 Mechanism Mechanism iintermediate is ntermediate negatively charged negatively formed faster when formed ring bears electronring withdrawing groups withdrawing such as NO2 such •• F• • H – •• •• • • OCH3 ••H H H NO2 Dr. Wolf's CHM 201 & 202 12-21 Stabilization of Rate-Determining Intermediate by Nitro Group •• •• F• • • OCH3 ••• H H – •• H H O • •• • N + Dr. Wolf's CHM 201 & 202 •• O • •• – • 12-22 Stabilization of Rate-Determining Intermediate by Nitro Group •• •• F• • • OCH3 ••• H H – •• H H O • •• • N + Dr. Wolf's CHM 201 & 202 •• O • •• – • H •• •• F• • • OCH3 ••• H H •• O – ••• • H N + •• O • •• – • 12-23 Mechanism Mechanism Step 2 •• F• • H – •• •• • • OCH3 ••H H H NO2 Dr. Wolf's CHM 201 & 202 12-24 Mechanism Step 2 – •• F• • •• •• H •• • OCH3 • H H H NO2 Dr. Wolf's CHM 201 & 202 fast •• F• • H – •• •• • • OCH3 ••H H H NO2 NO 12-25 Leaving Group Effects F > Cl > Br > I is unusual, but consistent with mechanism carbon-halogen bond breaking does not occur until after the rate-determining step electronegative F stabilizes negatively electronegative charged intermediate charged Dr. Wolf's CHM 201 & 202 12-26 12.22 Related Nucleophilic Aromatic Substitution Reactions Dr. Wolf's CHM 201 & 202 12-27 Example: Hexafluorobenzene F OCH3 F F F F F NaOCH3 CH3OH 65°C F F F F F (72%) Six fluorine substituents stabilize negatively Six charged intermediate formed in rate-determining step and increase rate of nucleophilic aromatic substitution. substitution. Dr. Wolf's CHM 201 & 202 12-28 Example: 2-Chloropyridine NaOCH3 N Cll C CH3OH 50°C N OCH3 2-Chloropyridine reacts 230,000,000 times 2-Chloropyridine faster than chlorobenzene under these conditions. conditions. Dr. Wolf's CHM 201 & 202 12-29 Example: 2-Chloropyridine – N •• •• • OCH3 •• • Cll C Nitrogen is more electronegative than carbon, Nitrogen stabilizes the anionic intermediate, and increases the rate at which it is formed. increases Dr. Wolf's CHM 201 & 202 12-30 Example: 2-Chloropyridine Example: – N •• Cll C •• • OCH3 •• • •• OCH3 •• •• –N •• Cll C Nitrogen is more electronegative than carbon, Nitrogen stabilizes the anionic intermediate, and increases the rate at which it is formed. increases Dr. Wolf's CHM 201 & 202 12-31 Descriptive Passage (End of Chapter, p534) The Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution: Benzyne Dr. Wolf's CHM 201 & 202 12-32 Aryl Halides Undergo Substitution When Treated With Very Strong Bases Cll C KNH2, NH3 NH2 NH –33°C (52%) Dr. Wolf's CHM 201 & 202 12-33 Regiochemistry new substituent becomes attached to either the carbon that bore the leaving group or the carbon adjacent to it CH3 CH CH3 CH Br NaNH2, NH3 –33°C Dr. Wolf's CHM 201 & 202 CH3 CH NH2 + NH2 12-34 Regiochemistry new substituent becomes attached to either the carbon that bore the leaving group or the carbon adjacent to it CH3 CH3 CH CH CH3 CH NaNH2, NH3 –33°C Br Dr. Wolf's CHM 201 & 202 + NH2 NH2 12-35 Regiochemistry CH3 CH Cl NaNH2, NH3 CH3 CH –33°C CH3 CH CH3 CH NH2 + + NH2 Dr. Wolf's CHM 201 & 202 NH2 12-36 14 Same result using 14C label Same * Cll C KNH2, NH3 –33°C NH2 NH * Dr. Wolf's CHM 201 & 202 (52%) + * (48%) NH2 NH 12-37 Mechanism Step 1 H •• H Cl •• H H • • – •NH2 •• • H Dr. Wolf's CHM 201 & 202 12-38 Mechanism Step 1 H H •• H Cl •• H H H • • Cl • • • •• • H – •NH2 •• • – •• H H NH2 H •• compound formed in this step is called benzyne compound benzyne Dr. Wolf's CHM 201 & 202 12-39 Benzyne H H H H Benzyne has a strained triple bond. It cannot be isolated in this reaction, but is It formed as a reactive intermediate. formed Dr. Wolf's CHM 201 & 202 12-40 Mechanism Step 2 H H – •NH2 •• • H H Dr. Wolf's CHM 201 & 202 12-41 Mechanism Step 2 H H H – •NH2 •• • H H – H •• NH2 H •• H Angle strain is relieved. The two sp-hybridized Angle sp-hybridized ring carbons in benzyne become sp2 hybridized sp in the resulting anion. in Dr. Wolf's CHM 201 & 202 12-42 Mechanism Step 3 H – H NH2 H •• •• NH2 H •• H Dr. Wolf's CHM 201 & 202 12-43 Mechanism Step 3 – •NH2 H H H H NH2 •• H Dr. Wolf's CHM 201 & 202 • H •• – H NH2 H •• •• NH2 H •• H 12-44 Hydrolysis of Chlorobenzene C llabeling abeling indicates that the highthe temperature temperature reaction of chlorobenzene with NaOH goes via benzyne. benzyne. * 14 Dr. Wolf's CHM 201 & 202 Cll C NaOH, H2O 395°C OH * (43%) + * (54%) OH 12-45 Diels-Alder Reactions of Benzyne Dr. Wolf's CHM 201 & 202 12-46 Other Routes to Benzyne Benzyne can be prepared as a reactive Benzyne intermediate by methods other than treatment of chlorobenzene with strong bases. chlorobenzene Another method involves loss of fluoride ion Another from the Grignard reagent of 1-bromo-2from fluorobenzene. Dr. Wolf's CHM 201 & 202 12-47 Other Routes to Benzyne Br Mg, THF Mg, •• F •• • • heat MgBr •• F •• + Dr. Wolf's CHM 201 & 202 • • FMgBr 12-48 Benzyne as a Dienophile Benzyne is a fairly reactive dienophile, and Benzyne gives Diels-Alder adducts when generated in the presence of conjugated dienes. presence Dr. Wolf's CHM 201 & 202 12-49 Benzyne as a Dienophile Br + F Mg, THF Mg, heat (46%) (46%) Dr. Wolf's CHM 201 & 202 12-50 End of Chapter 12 (part b) Dr. Wolf's CHM 201 & 202 12-51 ...
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This document was uploaded on 01/03/2012.

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