columbia大学有机化学课件20_18_20 html

1、20.18Preparation of NitrilesNitriles are prepared by:nucleophilic substitution by cyanide on alkyl halides (Sections 8.1 and 8.13)cyanohydrin formation (Section 17.7) dehydration of amidesPreparation of NitrilesKCNCH3(CH2)8CH2ClCH3(CH2)8CH2CNethanol- water(95%)SN2ExampleOOHKCNH+CH3CH2CCH2CH3CH3CH2CC

2、H2CH3CN(75%)ExampleBy dehydration of amidesuses the reagent P4O10 (often written as P2O5) OP4O10200C(CH3)2CHCNH2(CH3)2CHCN(69-86%)Preparation of Nitriles20.19Hydrolysis of NitrilesHydrolysis of nitriles resembles the hydrolysisof amides.The reaction is irreversible.Ammonia is produced and is protona

3、ted toammonium ion in acid solution.ORCOH+ NH4+2H2OHRCNHydrolysis of NitrilesIn basic solution the carboxylic acid productis deprotonated to give a carboxylate ion.O+H OHORCORCNNH32Hydrolysis of NitrilesOCH2CNCH2COHH2OH2SO4heatNO2NO2(92-95%)Example:Acid HydrolysisO1. KOH, H2O, heat2. H+CH3(CH2)9CNCH

4、3(CH2)9COH(80%)Example:Basic HydrolysisOOH2OH2ORCNRCNH2RCOHHydrolysis of nitriles proceeds via the corresponding amide.We already know the mechanism of amide hydrolysis.Therefore, all we need to do is to see how amides are formed from nitriles under the conditions of hydrolysis.Mechanism of Hydrolys

5、is of NitrilesOHOH2ORCNRCNHRCNH2The mechanism of amide formation is analogous to that of conversion of alkynes to ketones.It begins with the addition of water across the carbon-nitrogen triple bond.The product of this addition is the nitrogenanalog of an enol.It is transformed to an amideunder the r

6、eaction conditions.Mechanism of Hydrolysis of NitrilesH O RCNStep 1HH O ORRC N CNStep 1H ORCH N HO Step 2H ORCH N HO HORCH N OHStep 2H O HORC NHStep 3H O HH O O RC NH NHHORCStep 3O RC NHO H HStep 4O O RCRC N NHH O HO HHHStep 420.20Addition of Grignard Reagents to NitrilesNMgXNHRMgXdiethyl etherH2ORC

7、NRCRRCRGrignard reagents add to carbon-nitrogen triple bonds in the same way that they add to carbon- oxygen double bonds.The product of the reaction is an imine.Addition of Grignard Reagents to NitrilesNMgXNHRMgXdiethyl etherH2ORCNRCRRCRH3O+Imines are readily hydrolyzed to ketones. Therefore, the reaction of Grignard reagents with nitriles can be used as a synthesis of