Unformatted text preview: Chem 215 F07 Notes Dr. Masato Koreeda - Page 1 of 4. Date: October 8, 2007 Chapter 15: Carboxylic Acids and Their Derivatives. III Synthesis of Carboxylic Acids (cont'd) Hydrolysis of nitriles under basic conditions: Under milder basic conditions, an amide is obtained.
Mechanism for the base-catalyzed hydrolysis of nitriles:
H O R C nitrile Alternatively, H O H R O C N H
R O C N H N H O H O H R
H O *H
C N H H O
O H H O H H O R C H O *
N H H H O H R H O O R C N H O C O H H O R C N O H O C R NH2 carboxylate C O O **
H R amide * This is to avoid the generation of highly unfavorable R-NH species. The pKa of R-NH2 is at ~35. **
This N is stabilized by resonance with C=O, thus allowable! The pKa of an amide H is at ~12. IV. Synthesis of Acid Chlorides and Acid Anhydrides (1) Acid Chlorides: highly electrophilic C=O carbons; react with even weak nucleophiles such as
(more common) ROH; need to be prepared under anhydrous conditions. Prepared from carboxylic acids. O O a.With SOCl2: ! + SOCl + SO + HCl
H3C OH O O S OH Cl Cl R O S Cl OH Cl R Cl O
2 H3C Cl (gas) O S OH 2 (gas) mechanism:
O R O S Cl OH R Cl O Cl -SO2 -Cl
R O H Cl Cl -HCl O R Cl b. With PCl3: 3 H3C O OH + PCl3 ! 3 H3C O Cl + H3PO3 (2) Acid Anhydrides
O 2 H3C OH ! high temperatures (800 C) O 2 H3C (H2C)10 OH + H3C O O H3C O CH3 O O O + CH3 bp higher than H2O ! H3C (H2C)10 H3C (H2C)10 H2O removed by heating at ~100 C O O O 2 H3C OH bp 118 C (can be selectively distilled off from the mixture) + O mp 42 C An "acyl transfer reaction" at C=O carbons via intermediate (decanoic anhydride) O H3C R-COOH becomes highly acidic upon O heating at hight emperatures, thus H3C (H2C)10 (mixed anhydride) catalyzes anhydride formation by O protonating the C=Os. Chem 215 F07 Notes Dr. Masato Koreeda - Page 2 of 4. Date: October 8, 2007 V. Esterification (1) Esterification reactions
O H3C OH + H3C-CH2-O-H ethanol H+ ! H3C O O CH2CH3 + H2O acetic acid ethyl acetate The experimental equilibrium constant for the reaction above is: Keq = [ethyl acetate] x [H2O] [acetic acid] x [ethanol] = 3.38 As in any equilibrium processes, the reaction may be driven in one direction by adjusting the concentration of one of the either the reactants or products (Le Chtelier's principle). Equilibrium compositions
CH3COOH + C2H5OH H+ CH3C(=O)OC2H5 + H2O
____________________________________________________________________________________________________________________ i) at start: 1.0 1.0 0 0 at equilibrium 0.35 0.35 0.65 0.65_ ii) at start 1.0 10.0 0 0 at equilibrium 0.03 9.03 0.97 0.97_ iii) at start 1.0 100.0 0 0 at equilibrium 0.007 99.007 0.993 0.993 _____________________________________________________________________________
Taken from " Introduction to Organic Chemistry"; 4th Ed.; Streitweiser, A. et al.; Macmillan Publ.: New York, 1992. (2) The mechanism for the acid-catalyzed esterification [Commonly referred to as the Fischer
esterification: see pp 623-624 of the textbook].
O H3C OH + H3C-CH2-18O-H H+ ! H 3C O
18O CH2CH3 + H2O Suggesting H3C- CH2 ---18OH Also, O H 3C OH
this bond not cleaved not cleaved in this reaction.
this bond not cleaved O HO H CH3 H+ ! H3C + optically active O H CH3 optically active + H2O i) Overall, the Fischer esterification consitutes an acyl transfer from an OH to an OR' group.
O H3C OH H - OR H+ H3C O O R ii) Esterification of a carboxylic acid can't take place in the presence of base. Base deprotonates the carboxylic acid, forming a carboxylate anion, thus preventing a nucleophile (i.e., ROH) from attacking the carbonyl carbon. Chem 215 F07 Notes Dr. Masato Koreeda - Page 3 of 4. Date: October 8, 2007 Chapter 15: Carboxylic Acids and Derivatives. V. Esterification (cont'd) Mechanism for the acid-catalyzed esterification
O H3C OH + H3C-CH2-O-H ethanol H+ ! H3C O O CH2CH3 + H2O acetic acid ethyl acetate resonance stabilized O H3C H O H H3C O H O H alcohol O H3C O H H B C2H5OH H2SO4 (acid catalyst) acid [acetic acid] Use H-B for the Br"nsted acid.
note: H O pKa -9 O S O H O O H3C H pKa -6 O H O H3C H3C O O C2H5 C2H5-OH H H tetrahedral, sp3 intermediate H B ester [ethyl acetate] O H3C C O H O H5C2 H B O H3C C O H O H5C2 ester hydrate B H O C2H5 + H2O O H3C C O H5C2 lone pairassisted H ionization!
H O H H C2H5-O-H pKa - 2.4 ---------------------------------------------------------------------------------------------------------------------------Notes: i) The acid-catalyzed esterification reaction is reversible. The reverse reaction from an ester with an acid and water is the acid-catalyzed hydrolsis of an ester to form the corresponding acid and alcohol. ii) The C=O lone pairs are more "basic" than those of the ether oxygen of an ester (i.e., -OR).
H O H H3C H O H "more basic"
O H3C O H B O H H B O H3C O X H3C O H H The charge stabilized by the two identical resonance contributors. iii) Direct SN2-like substitution not possible at an sp2 center
O C2H5-OH H3C O H H H !+ O C2H5-O H3C no resonance stabilization of the charge O !+ H H Not feasible Chem 215 F07 Notes Dr. Masato Koreeda - Page 4 of 4. Date: October 8, 2007 Chapter 15: Carboxylic Acids and Derivatives. VI. Ester Hydrolysis
As is mentioned on page 3 of this handout, the ester formation from carboxylic acid is reversible. As such, treatment of an ester with water and a catalytic amount of an (strong) acid leads to the formation of the corresponding acid and alcohol. This process is called hydrolysis. 1) Acid-catalyzed Hydrolysis of an Ester: usually requires stronger conditions (i.e., high temp.)
O CH2CH3 H3O+, ! O O H + HO CH2CH3 Mechanism for the hydrolysis of an ester under acidic conditions is virtually identical with that for the esterification from an acid, but to the reverse direction.
H B O CH2CH3 O H CH2CH3
O H H CH2CH3 H O O H CH2CH3 O Use H-B for the Br!nsted acid.
B O O H H H O H HO CH2CH3 B H H B tetrahedral intermediate
H CH2CH3 H O O H good old lone pair-assisted ionization! O O H 2) Base-catalyzed Hydrolysis of an Ester: under much milder conditions (i.e., usually at room temp). Requires acidification of the reaction mixture (pH ~1-2) in order to isolate free carboxylic acid. Namely, a step to protonate the carboxylate species is needed. Overall, the reaction is irreversible.
O CH2CH3 1.NaOH, H2O 2.H3O+ (pH ~1-2) O OH + HO CH2CH3 Mechanism:
O CH2CH3 OH O tetrahedral intermediate
CH2CH3 O O H CH2CH3 or OH O H H O O O H acidification to pH ~1-2 O H O H ...
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