CHEM 346 PROBLEM SET 4 ANSWER KEY 1 Ch 17 39 Amides are less reactive to hydrolysis if the lone pair on nitrogen can fully donate into the carbonyl group The more electrons can delocalize into the substituent therefore the more reactive the amide will be toward hydrolysis O NH O NH O NH NO2 O NH NO2 H N O lone pair can be stabilized thru additional resonance more EWG than just phenyl itself H N O NO2 NO2 no delocalization H N O O N O Ch 17 41 Using an alkyl halide and ammonia can be tricky because of possible polyalkylation R Br H3N R NH3 Br R Br H2N R H2N R R Br Azides and phthalimides are both capable of monoalkylation only so you get a better yield of the desired amine N N N Na N N N Na Sodium azide O O N Na Sodium phthalimide Ch 17 61 amide and ester are sites of potential hydrolysis O NH3 O O OCH3 H N O HCl H2O O NH3 O OH O H2N O OH CH3OH O NH3 HO OH O under acidic conditions H3N O OH CH3OH Ch 17 68 a O H3C Cl KF KCl O H3C F O NH H2O HCl H3N O Cl OH O OH 1 SOCl2 2 2 CH3NH2 O CH3 N H via acid chloride b c d e f h i j Cl Cl g O O O O O O O O HO H2O O O OH OH OH OH H2O excess HCl O OH OH CH3OH excess CH3O O O O O O O O OH O O O NH3 excess O O O OH O O O O O NH2 O O H3CO O via OH O O O O O O O CH3OH excess HCl OCH3 O OCH3 Ch 17 80 a O H H2O NH2 O OH SOCl2 O Cl PBr3 OH Br Mg0 Et2O CO2 MgBr O SOCl2 O H3C H2C 10 OH H3C H2C 10 Cl AlCl3 O H3C H2C 10 H3C H2C 10 H2SO4 H3C H2C 10 NaOH H3C H2C 10 CH3 KMnO4 O OH SOCl2 O Cl NH2 CH3 NBS ROOR H N O O Cl AlCl3 O HCl H2O basic workup Br CN CN H2O SO3H O Cl NH2 Et3N H N O H OH O H2NNH2 OH SO3 O CH3 N H NH2 O OH O b c d e f 2 A B C D E F B C D 3 A Ac2O OH O O NH2 O O Ph O Ph Et3N O Ph N H O Ph OH H3C O OH 1 SOCl2 2 HO H3C O O O O Cl Br O Ph OH O O Ph O O Ph NH2 Et3N Ph N H O O CH3OH H O OCH3 OH O Me N Me H N O O OH 1 SOCl2 2 Me Me N H Et3N 1 HNO3 H2SO4 2 Sn HCl or Pd C H2 3 O Et3N Cl O OH Cl Ph O O O O OH H H3C OH O O 4 O O H2O H O O HO HO O O OH OH O O O O H OH2 O O proton transfer O O O HO OH2 O H HO OH O O O O OH O H HO B OH O HO H O OH H2O H O OH O H O OH B O OH HO OH HO OH HO O HO O OH OH H2O O OH O proton transfer OH OH HO H O OH O