Hydrolysis in base

Hydrolysis (Sections 20 10 and 20 11) Ester hydrolysis may be catalyzed either by acids or by bases Acid catalyzed hydrolysis is an equilibrium controlled process the reverse of the Fischer esterification Hydrolysis in base IS irreversible and is the method usual ly chosen for preparative purposes... 

Ester hydrolysis in base is called saponification, which means soap making Over 2000 years ago the Phoenicians made soap by heating animal fat with wood ashes Animal fat is rich m glycerol triesters and wood ashes are a source of potassium car bonate Basic hydrolysis of the fats produced a mixture of long chain carboxylic acids as their potassium salts... 

Convincing evidence that ester hydrolysis in base proceeds by the second of these two paths namely nucleophilic acyl substitution has been obtained from several sources In one experiment ethyl propanoate labeled with 0 m the ethoxy group was hydrolyzed On isolating the products all the 0 was found m the ethyl alcohol there was no 0 enrichment m the sodium propanoate... 

In an extension of the work desciibed in the preceding section. Bender showed that basic ester hydrolysis was not conceited and, like acid hydrolysis, took place by way of a tetrahedral intennediate. The nature of the experiment was the sane, and the results were similai to those observed in the acid-catalyzed reaction. Ethyl benzoate emiched in 0 at the caibonyl oxygen was subjected to hydrolysis in base, and samples were isolated before saponification was complete. The recovered ethyl benzoate was found to have lost a portion of its isotopic label, consistent with the fonnation of a tetrahedral intennediate ... 

Carboxyl groups of ffluino acids and peptides are normally protected as esters. Methyl and ethyl esters ar e prepared by Fischer esterification. Deprotection of methyl and ethyl esters is accomplished by hydrolysis in base. Benzyl esters are a popular- choice because they can also be rer-noved by hydrogenolysis. Thus a synthetic peptide, protected at both... 

For amide hydrolysis in base, the initial adduct would revert to starting materials (without remarkable stabilization, an amide ion is a hopeless leaving group, so that path b does not compete with path a), bnt a not very difflcnlt proton transfer gives an intermediate in which the amine is the better leaving gronp and path b can compete with path a. ... 

Tryptophan is commonly determined by one of two general categories of sample hydrolysis (a) chemical hydrolysis in base (NaOH, LiOH, etc.) or (b) enzymatic hydrolysis. Attempts to adapt the standard acid hydrolysis to accommodate the problematic amino acids will be addressed in later subsections of this chapter. 

Because ester hydrolysis in base proceeds by acyl-oxygen cleavage, the 180 label becomes incorporated into acetate ion (0 = 180). 

Basolo555 noted that reactions of Rh111 amine complexes were not dramatically accelerated by hydroxide ion, but did show that substitutions in base do follow the standard kobs = k, + k2[OH" ] format, with k, representing the first-order aquation observed in acidic solution, and k2 representing the second-order base-catalyzed path. Poe has studied the kinetics of the base hydrolysis of a variety of frans-[Rh(en)2XY]"+ complexes (Table 41). Studies on the base hydrolyses of trans-[Rh(en)2(OH)X]+ (X = Cl, Br, I) showed that the coordinated hydroxide has an intrinsic kinetic tram effect comparable to that of Cl" but that its position in a thermodynamic trans effect series is much higher.635 For oms-[Rh(en)2X2]+ (X = Cl, Br), virtually complete tram -+ cis isomerization occurs upon hydrolysis in base, and ca. 50% isomerization is observed when X = I.653 No such... 

The mechanism of amide hydrolysis in base has the usual two steps of the general mechanism for nucleophilic acyl substitution—addition of the nucleophUe followed by loss of a leaving group— plus an additional proton transfer. The initially formed carboxylic acid reacts further under basic conditions to form the resonance-stabilized carboxylate anion, and this drives the reaction to completion. Mechanism 22.10 is written for a 1° amide. 

A. J. Bennet, Q.-P. Wang, H. Slebocka-Tilk, V. Somayaji, R. S. Brown, and B. D. Santarsiero, /. Am. Chem. Soc., 112, 6383 (1990). Relationship Between Amidic Distortion and Ease of Hydrolysis in Base. If Amidic Resonance Does Not Exist, Then What Accounts for the Accelerated Hydrolysis of Distorted Amides ... 

Unterhalt and Hanemacker have recently reported the synthesis of sweet-tasting N-(phenyl)-iV -carboxymethyl sulphamides (401)377. The compounds were prepared by the reaction (equation 131) of amino carboxylic acids with sulphuryl chloride and subsequent condensation with 4-substituted anilines followed by hydrolysis in base. 

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