Aminolysis, esters

The heterocyclic scaffolds are prepared from pyroglutamic acid [154, 155]. 1-aminoalkyl boronic acid pinanediol esters are readily available through a diastereoselective homologation with dichloromethyllithium, providing (5)-a-chloroboronic esters. Aminolysis of the chloride yielded... 

Thus, the family of azolides represents a versatile system of reagents with graduated reactivity, as will be shown in the following section by a comparison of kinetic data. Subsequent chapters will then demonstrate that this reactivity gradation is found as well for alcoholysis to esters, aminolysis to amides and peptides, hydrazinolysis, and a great variety of other azolide reactions. The preparative value of azolides is not limited to these acyl-transfer reactions, however. For example, azolides offer new synthetic routes to aldehydes and ketones via carboxylic acid azolides. In all these reactions it is of special value that the transformation of carboxylic acids to their azolides is achieved very easily in most cases the azolides need not even be isolated (Chapter 2). 

For the mechanism of azolide hydrolysis under specific conditions like, for example, in micelles,[24] in the presence of cycloamyloses,[25] or transition metals,[26] see the references noted and the literature cited therein. Thorough investigation of the hydrolysis of azolides is certainly important for studying the reactivity of those compounds in chemical and biochemical systems.[27] On the other hand, from the point of view of synthetic chemistry, interest is centred instead on die potential for chemical transformations e.g., alcoholysis to esters, aminolysis to amides or peptides, acylation of carboxylic acids to anhydrides and of peroxides to peroxycarboxylic acids, as well as certain C-acylations and a variety of other preparative applications. 

Ester aminolysis, in general, occurs under harsh conditions that require high temperatures and extended reaction periods or the use of strong alkali metal catalysts. An efficient solid state synthesis of amides from nonenolizable esters and amines using KO Bu under the action of microwave irradiation [97] has been described. The reaction of esters with octylamine was extensively studied to identify possible micro-wave effects [98] (Eq. (45) and Tab. 3.20). 

Tab. 3.22 Ester aminolysis with different amines under the action of microwave irradiation during...

Ester aminolysis and hydrolysis coi Alkylammonium alkanoates. The amine can react nucleophilically or as a general base Rates of decarboxylation compared in various solvents and in aq. micelles, reversed micelles and vesicles M. I. El Seoud et al., 1982 Sunamoto et a/., 1983a... 

Figure 5. Theozymes for ester aminolysis. (a) Ether theozyme (bold) complexed to the direct displacement transition state for aminolysis. (b) DME theozyme (bold) complexed to the direct displacement transition state for aminolysis.

Zipse, H. Wang, L-H. Houk, K. N. Polyether Catalysis of Ester Aminolysis - A Computational and Experimental Study Liebigs Arm. 1996,1511-1522. 

Before outlining our studies in this area it is useful to have some understanding of what is to know about organic ester aminolysis. 

There have been only two detailed mechanistic studies on metal-activated ester aminolysis where the coordination situation remains certain. The first involves the addition of GlyOEt to [Co(en)2(GlyOi-Pr)](C104)3 in Me2SO (13) and the second the reaction of GlyOEt with... 

LM Siemens, FW Rottnek, LS Trzupek. Selective catalysis of ester aminolysis. An approach to peptide active esters, (phenylthiomethyl esters). J Org Chem 55, 3507,... 

Perreux, L., Loupy, A. and Delmotte, M., Microwave effects in solvent-free ester aminolysis, Tetrahedron, 2003,59,2185. 

The mechanism of catalysis of ester aminolysis by weak amine bases of substituted phenylquinoline-6- and -8-carboxylates were evaluated, and the solvent effects were examined by semiempirical SM2.1/AM1, ab initio SCIPCM [124] and PS-Solv [125]. All these models predicted that a zwitterionic tetrahedral intermediate should be formed in this reaction. The results did not support the proposed earlier proton slide mechanism and allowed to propose a mechanism which was fully consistent with the experimental observations [126]. 

Singleton, D. A. Merrigan, S. R. Resolution of conflicting mechanistic observations in ester aminolysis. A warning on the qualitative prediction of isotope effects for reactive intermediates, 7. Am. Chem. Soc. 2000,122, 11035-11036. 

There are no significant differences between ethyl and methyl esters concerning synthesis or cleavage. Related protocols of the methyl esters (see Section 2.2.1.1.1.1) are, therefore, applied to the ethyl esters. The usefulness of ethyl esters is somewhat limited by the difficulties encountered in their saponification. Hydrolysis with alkali is feasible, but ethyl esters are less sensitive to nucleophilic attack than methyl esters. Aminolysis and hydrazinolysis as well as cleavage of the alkyl-oxygen bond with lithium iodide in pyridineb l proceed several times slower in the case of ethyl esters. Mild enzyme-catalyzed hydrolysis by trypsin and chymotrypsin,t 2° 2 1 or by carboxypeptidase remains an attractive alternative. 

DeTar, D.F. and Delahunty, C. (1983). Ester Aminolysis New Reaction Series for the Quantitative Measurement of Steric Effects. J.Am.Chem.Soc., 105,2734-2739. 

Ester aminolysis Alkylammonium alkanoates. The amine M. I. ElSeoudetal., 1982... 

Figure 18 A possible role for valerolactam in the catalysis of ester aminolysis [17]...

In further control experiments, we found that under these conditions, autocatalysis is not a general feature of ester aminolysis. Parallel experiments with the naphthoyl ester (29) and amine (4) (Figure 22) showed that within experimental error, the amide product (33) did not signihcantly catalyze its own formation (Table 5). Interestingly, complexation of (4) with the diimide methyl ester (11) inhibited the reaction of (4) with (29) just as it did the reaction of (4) with (12). In both cases, the inhibition is presumably due to the ability of the diimide (11) to sequester (4) in an unproductive complex. 

Protease Ester, amide hydrolysis, ester aminolysis, peptide synthesis Many stable proteases No D-proteases... 

In this reaction, an amino acid may be polymerized or a diamine may be polymerized with a diacid. Similar condensation reactions occur with derivatives of the acid moiety. Examples include ester aminolysis (Reaction 2) in which phenyl or higher alkyl esters are preferred, amide aminolysis (Reaction 3), and acidolysis of acyl derivatives of diamines (Reaction 4). 

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