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Chapter 20: Carboxylic Acids and Nitriles Nomenclature: O O Carboxylic acid C OH H3C OH CH3COOH IUPAC ending: -oic acid (trivial name) N Nitrile H3C C CH3CO2H ethanoic acid (acetic acid) CH3C N N CH3CN ethanenitrile (acetonitrile) IUPAC ending: nitrile since the acid functional group must be at the end of a chain, it must be numbered 1 – therefore, there is no need to include that number when named as a substituent, it is also number 1 – the highest priority Effect of substituents on acidity of carboxylic acids O R Ka OH Ka = [H+] [RCOO ] [RCOOH} O H+ + R O O R O and pKa = - log Ka pKa methanoic acid HCO2H 3.75 ethanoic acid CH3CO2H 4.75 propanoic acid CH3CH2CO2H 4.87 butanoic acid CH3(CH2)2CO2H 4.82 1 pKa ~16 pKa 4.75 Preparation of acids Oxidation of aromatic side chains cleavage of alkenes, alkynes of alcohols 2 Hydrolysis of nitriles And, lastly, a Grignard-based preparation O C OH N It is important to note that these carbons are at the same oxidation level -- we can see this because each one has three bonds to a heteroatom Remember, cyanide is a good nucleophile, so preparation of nitriles is easy Other preparations of nitriles 20.9 O R More examples: Mg CO2 COOH C N We have not yet discussed amides, but look at these two structures. What is the difference? 86% COOH Br Li O R We can, indeed, fairly easily dehydrate amides: H3O+ dry Et2O Cl NH2 CO2 H3O+ dry Et2O O 97% Reductions – acids Reactions of acids and nitriles What do we expect? O OH C N remember – acids are less reactive than aldehydes or ketones -- NABH4 is less reactive than LAH therefore, only LAH works on acids and derivatives BH3 also works: red sites are positive – therefore susceptible to nucleophilic attack blue site is acidic, therefore pulled off by bases 3 Reductions – nitriles H H R C Al H R H N Li+ N Li+ AlH3 R N AlH3 H H anion reacts with Lewis Acid AlH3, and the resulting anion complexes with Li+ in a tight ion pair; this leaves the C=N bond available for a second addition H H Al H H Li+ AlH3 R R N H H I don’t like this description -- it is better, I believe, shown as on the next slide Li+ AlH3 N H Li+ AlH3 and this species is hydrolyzed on work-up to the 1° amine this mechanism makes the following reaction more understandable: Reaction of a nitrile with an organometallic reagent: And finally, hydrolysis of nitriles: HO HO R HO C N H N O R O R1 R C MgBr R1 N N +MgBr R this species has considerably higher negative charge on the N, resulting in a double bond which is less susceptible to further reaction CN H2SO4 H2O ∆ H2O R1 H N R H2O R H HO H R O O N HO H N H2O NH2 HO R OH + NH 2 HO R now, hydrolysis gives an imine which we know further hydrolyzes to the ketone O R O NH2 O R O + NH 2 this is the same as Fig 20.4 in the text COOH 78% you will note, however, that the amide is an intermediate in this reaction – using milder conditions, it can be the product: CN HCl H2O 40°, 1h CONH2 80% 4