22.12Reactions of Amines:A Review and a Preview,Reactions of Amines,Reactions of amines almost always involve thenitrogen lone pair.,as a base:,as a nucleophile:,Reactions of Amines,basicity (Section 22.5) reaction with aldehydes and ketones (Sections17.10, 17.11) reaction with acyl chlorides (Section 20.3),anhydrides (Section 20.5), and esters (Section 20.11),Reactions already discussed,22.13Reactions of Amines with Alkyl Halides,Reaction with Alkyl Halides,Amines act as nucleophiles toward alkyl halides.,X,+,+,Example: excess amine,+,(85-87%),NaHCO3,90C,(4 mol),(1 mol),Example: excess alkyl halide,+,3CH3I,(99%),methanol,heat,+,22.14The Hofmann Elimination,The Hofmann Elimination,a quaternary ammonium hydroxide is the reactantand an alkene is the product is an anti elimination the leaving group is a trialkylamine the regioselectivity is opposite to the Zaitsev rule.,Quaternary Ammonium Hydroxides,Ag2O,H2O, CH3OH,+,HO,are prepared by treating quaternary ammmoniumhalides with moist silver oxide,The Hofmann Elimination,160C,+,HO,on being heated, quaternary ammonium hydroxides undergo elimination,(69%),+,N(CH3)3,+,H2O,Mechanism,H,Regioselectivity,Elimination occurs in the direction that gives the less-substituted double bond. This is called the Hofmann rule.,+,(95%),(5%),Regioselectivity,Steric factors seem to control the regioselectivity.The transition state that leads to 1-butene isless crowded than the one leading to cisor trans-2-butene.,Regioselectivity,largest group is between two H atoms,major product,Regioselectivity,H,H,H,CH3,C,H,C,CH3,H,CH3,largest group is between anH atom and a methyl group,minor product,CH3,22.15Electrophilic Aromatic Substitutionin Arylamines,Nitration of Anililne,NH2 is a very strongly activating group NH2 not only activates the ring toward electrophilic aromatic substitution, it also makes it more easily oxidized attemped nitration of aniline fails because nitric acid oxidizes aniline to a black tar,Nitration of Anililne,Strategy: decrease the reactivity of aniline by converting the NH2 group to an amide,(98%),(acetyl chloride may be used instead of acetic anhydride),Nitration of Anililne,Strategy: nitrate the amide formed in the first step,HNO3,(94%),Nitration of Anililne,Strategy: remove the acyl group from the amide by hydrolysis,KOH,ethanol,heat,(100%),occurs readily without necessity of protecting amino group, but difficult to limit it to monohalogenation,Halogenation of Arylamines,(82%),Monohalogenation of Arylamines,(74%),Decreasing the reactivity of the arylamine by converting the NH2 group to an amide allows halogenation to be limited to monosubstitution,Friedel-Crafts Reactions,The amino group of an arylamine must be protected as an amide when carrying out a Friedel-Crafts reaction.,(57%),NHCCH3,O,CH3,