310-36 - Organic Lecture Series CH 310 N LECTURE 36...

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Unformatted text preview: Organic Lecture Series CH 310 N LECTURE 36 Textbook Assignment: Chapter 23 Homework (for credit): POW 12 posted (Due April 25) Today's Topics: Basicity, reactions of amines Notice & Announcements: Exam 3: this week 1 Organic Lecture Series Amines Epinephrine (adrenaline) 2 Organic Lecture Series Reaction with Acids All amines, whether soluble or insoluble in water, react quantitatively with strong acids to form water-soluble salts OH HO NH2 + HCl HO (R)-N orepinep hrine (on ly s ligh tly s olu ble in w ater) H2 O HO HO (R)-N orepinep hrine h yd roch loride (a w ater-s olu ble salt) OH NH3 Cl + - 3 Preparation Organic Lecture Series A summary of synthetic methods: nucleophilic ring opening of epoxides by ammonia and amines (11.9B) addition of nitrogen nucleophiles to aldehydes and ketones to form imines (Section 16.8) reduction of imines to amines (16.8A) reduction of amides by LiAlH4 (18.10B) reduction of nitriles to a 1amine (18.10C) nitration of arenes followed by reduction of the NO2 group to 1amines (22.1B) 4 Preparation Organic Lecture Series Alkylation of ammonia and amines by SN2 CH3 Br + N H3 SN 2 CH3 NH 3 + Br Methylammonium bromide unfortunately, such alkylations give mixtures of products through a series of proton transfer and nucleophilic substitution reactions CH3 Br + NH3 CH3 NH3 + Br + (CH3 ) 2 NH2 Br + - + (CH3 ) 3 NH Br + (CH3 ) 4 N Br 5 + - + - These arise from N-polyalkylation Organic Lecture Series Preparation via Azides Alkylation of azide ion, N3N3 - -: N + N N: - RN 3 R N + N : : Azide ion (a good nucleophile) : + : - N: - An alkyl azide Ph CH2 Cl Benzyl ch loride K N3 Ph CH2 N3 Ben zyl azid e 1 . LiAlH4 2 . H2 O Ph CH2 NH2 Benzylamin e 6 Organic Lecture Series Preparation via Azides alkylation of azide ion ArCO3 H Cyclohexen e 1 . K N3 2 . H2 O + O 1,2-Epoxycyclohexane (chiral) OH N3 trans-2-Azid ocyclohexan ol (racemic) 1 . LiAlH4 2 . H2 O OH NH2 t rans-2-Aminocyclohexan ol (racemic) 7 Organic Lecture Series Reaction with HNO2 Nitrous acid, a weak acid, is most commonly prepared by treating NaNO2 with aqueous H2SO4 or HCl HNO2 + H2 O H3 O + NO2 + - pK a = 3.37 In its reactions with amines, nitrous acid participates in proton-transfer reactions is a source of the nitrosyl cation, NO+, a weak electrophile 8 Organic Lecture Series Reaction with HNO2 NO+ is formed in the following way: H O N O + H+ (1) + H O N O H H O + H + N O + N O (2) The nitrosyl cation Focus upon reactions of HNO2 with 1 aliphatic and aromatic amines 9 Organic Lecture Series RNH2 with HNO2 1aliphatic amines give a mixture of unrearranged and rearranged substitution and elimination products, all of which are produced by way of a diazonium ion and its loss of N2 to give a carbocation. Diazonium ion: an RN2+ or ArN2+ ion 10 Organic Lecture Series 1 RNH2 with HNO2 Formation of a diazonium ion Step 1: reaction of a 1amine with the nitrosyl cation R-NH2 + A 1aliphatic amine + : N O: : H : : : R-N-N=O : An N-nitrosamine keto-enol tautomerism : : : : : R-N=N-O-H A diazotic acid Step 2: protonation followed by loss of water H + R-N=N-O-H A diazotic acid R-N R + N N N H + O-H -H2 O R + + Aliphatic diazonium ions are unstable and lose N2 to give a carbocation which may 1. lose a proton to give an alkene 2. react with a nucleophile to give a substitution product 3. rearrange and then react by 1 and/or 2 Cl NOT useful for org synthesis (25.9%) : : : : A diazoniu m ion 1 RNH2 with HNO2 N N A carbocation 11 Organic Lecture Series (5.2%) OH NH 2 NaNO2 , H Cl + OH 0-5 C o (13.2%) + (25%) (10.6%) 12 Organic Lecture Series 1 ArNH2 with HNO2 The -N2+ group of an arenediazonium salt can be replaced in a regioselective manner by these groups H2 O HBF4 HCl, CuCl Ar-NH2 HNO2 0-5C Ar-N2 + (-N2 ) Ar-OH Ar-F Ar-Cl Ar-Br Ar-CN Ar-I Ar-H 13 Sch ieman n reaction San dmeyer reaction HBr, CuBr KCN, CuCN KI Know these H3 PO2 Organic Lecture Series Medicinal Chemistry Cocaine Topical anesthetic (local) CNS stimulant 14 Organic Lecture Series Medicinal Chemistry 15 Organic Lecture Series Medicinal Chemistry Synthesis of Procaine 16 Organic Lecture Series Medicinal Chemistry Synthesis of Procaine O CH2CH3 + HN CH2CH3 17 Synthesis of Procaine O O2N C O Organic Lecture Series Medicinal Chemistry N(Et)2 H 2 Ni O H2N C O Procaine (novocaine) N(Et)2 18 Organic Lecture Series Medicinal Chemistry 19 ...
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This note was uploaded on 05/16/2011 for the course CH 310 N taught by Professor Blocknack during the Spring '08 term at University of Texas at Austin.

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