Amides hydrolysis, metal-catalyzed

Amides. Metal ions catalyze the hydrolysis of a variety of amides, including acylamino acids, dipeptides and tripeptides, and amino acid amides. In all these compounds it is possible for a metal ion to complex with one or more ligand groups, either amine or carboxylate ion functions, in addition to the amide group. Thus the structural prerequisites for the metal ion catalysis of amide hydrolysis are the same as those for ester hydrolysis. 

In contrast, tertiary amides are subject to metal catalyzed hydrolysis. 

Hydrolysis of peptides,84 amides,85 phosphate esters,86 sulfonate esters87 and acetals88 can also be metal catalyzed. The hydrolysis of a phosphate ester coordinated to cobalt(III) also occurs at an increased rate (Scheme 19).89 A rather similar reaction occurs in the amine exchange of coordinated dithiocarbamates (equation 21).90 The conversion of imidates to amidines has been mentioned previously and is a similar type of reaction (see Section 7.4.2.2.1). 

The alkaline hydrolysis of the nitrile is accelerated by 7 powers of ten if catalyzed by Ni2+, or by 9 powers of ten if catalyzed by Cu2+. The mechanism of the metal ion catalyzed reaction probably involves external attack of hydroxide ion at the nitrile carbon. It is unlikely that the strong acceleration caused by the metal ion is solely due to the field effect of the positive charge. The metal ion probably interacts (weakly) with the Tf-electrons of the CN multiple bond. The basic hydrolysis of the amide is also catalyzed by transition metal ions, but the acceleration of the reaction rate is much smaller. 

Ottmann with the following results. They found that a trace of heavy metal catalyzes decomposition of the diazo ester and so heated a mixture of the ester with 20 parts of benzene in a glass insert of an autoclave at 136-140° and so obtained 7-carbo-ethoxynorcaradiene (1) in much improved yield. The ester (I) is converted into the amide (2), which on alkaline hydrolysis undergoes rearrangement to a mixture of four cycloheptatrienecarboxylic acids. Characterization of these acids led to assignment of the structures formulated. 

Hydrolysis of carboxylic and phosphoric esters is also a slow process at neutral pH, and is catalyzed by acids and bases by mechanisms similar to those involved in amide and peptide hydrolysis. Metal ions are also good catalysts of both carboxylic and phosphoric ester hydrolysis, typically with rate increases much higher than those observed for hydrolysis of amides or peptides (Table... 

Scheme 19.23 One-pot synthesis of L-alanine based on metal-catalyzed hydrogenation and acylase-catalyzed amide hydrolysis.

Metal-catalyzed racemization of amines generally takes place via reversible dehydrogenation-hydrogenation steps through imine intermediates (Scheme 57.21). During this process, and facilitated by the elevated temperatures required for racemization, the imine intermediate can undergo side reactions (condensation with an amine molecule, hydrolysis, etc.), which could lower the yield of the amide and make it difficult to isolate. 

The amidocarbonylation of aldehydes provides highly efficient access to N-acyl a-amino acid derivatives by the reaction of the ubiquitous and cheap starting materials aldehyde, amide, and carbon monoxide under transition metal-catalysis [1,2]. Wakamatsu serendipitously discovered this reaction when observing the formation of amino acid derivatives as by-products in the cobalt-catalyzed oxo reaction of acrylonitrile [3-5]. The reaction was further elaborated to an efficient cobalt- or palladium-catalyzed one-step synthesis of racemic N-acyl a-amino acids [6-8] (Scheme 1). Besides the range of direct applications, such as pharmaceuticals and detergents, racemic N-acetyl a-amino acids are important intermediates in the synthesis of enantiomeri-cally pure a-amino acids via enzymatic hydrolysis [9]. 

Spontaneous and metal-ion catalyzed base hydrolysis of esters, amides, etc. ... 

Dissolved metals and metal-containing surfaces play an important role in the transformation of organic contaminants in the subsurface environment. Metal ions can catalyze hydrolysis in a way similar to acid catalysis. Organic hydrolyzable compounds susceptible to metal ion catalysis include carboxylic acids, esters, amides, anilides, and phosphate-containing esters. Metal ions and protons... 

This zinc-dependent enzyme [EC 3.4.11.1], also referred to as cytosol aminopeptidase, leucyl aminopeptidase, and peptidase S, catalyzes the hydrolysis of a terminal peptide bond such that there is a release of an N-terminal amino acid, Xaa-Xbb-, in which Xaa is preferably a leucyl residue, but may be other aminoacyl residues including prolyl (although not arginyl or lysyl). Xbb may be prolyl. In addition, amino acid amides and methyl esters are also readily hydrolyzed, but the rates with arylamides are exceedingly slow. The enzyme is activated by heavy metal ions. 

Transition metal catalysts and biocatalysts can be combined in tandem in very effective ways as shown by the following example (Scheme 2.21). An immobilized rhodium complex-catalyzed hydrogenahon of 46 was followed by enzymatic hydrolysis of the amide and ester groups of 47 to afford alanine (S)-9 in high conversion and enanhomeric excess. Removal of the hydrogenation catalyst by filtration prior to addition of enzyme led to improved yields when porcine kidney acylase 1 was used, although the acylase from Aspergillus melleus was unaffected by residual catalyst [23]. 

Metal Ion-Catalyzed Hydrolysis of Esters, Amides, and Thiol Esters... 

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