Amides and anhydrides

G. Ketones from nitriles, thioesters, amides, and anhydrides... 

Procedures for the preparation of several compounds of considerable utility are described. These include 1,1 -carbonyl-diimidazole, which has been used in the preparation of esters, amides, and anhydrides, the hydrochloride and methiodide of l-ethyl-3-(3-dimethylamino)-propylcarbodiimide, which can be used for similar purposes and are especially useful in the preparation of peptides, and (+)- and (— )-< -(2,4,5,7-tetranitro-9-fluorenylideneaminooxy) propionic acid (TAPA), which is used for the resolution of polycyclic aromatic compounds. 

This chapter deals with the kinetics and mechanisms of the hydrolysis of carboxylic acid derivatives of general formula RCOX. These include carboxylic acid halides, amides, and anhydrides with small sections on carboxylic acid cyanides etc. Many recent developments in this field have been made with acid derivatives in which R is not an aliphatic or aromatic group, for example, carbamic acid derivatives, and these are reported where relevant, as are reactions such as ethanolysis, aminolysis, etc. where they throw light on the mechanisms of hydrolysis. 

Trypsin was named more than 100 years ago. It and chymotrypsin were among the first enzymes to be crystallized, have their amino acid sequences determined, and have their three-dimensional structure outlined by x-ray diffraction. Furthermore, both enzymes hydrolyze not only proteins and peptides but a variety of synthetic esters, amides, and anhydrides whose hydrolysis rates can be measured conveniently, precisely and, in some instances, extremely rapidly. As a result, few enzymes have received more attention from those concerned with enzyme kinetics and reaction mechanisms. The techniques developed by the pioneers in these various fields have enabled other serine proteases to be characterized rapidly, and the literature on this group of enzymes has become immense. It might be concluded that knowledge of serine proteases is approaching completeness and that little remains but to fill in minor details. 

Trialkylsilyl alkali metal compounds are readily oxidized by a variety of aromatic compounds, ketones, amides, and anhydrides. Thus electron transfer is likely to be the first step of the majority of RaSi" reactions. 

Values of k2lks = 2kjkii which are smaller than unity indicate that the addition step ( i) is rate-determining. Examples where k characterises the slow step are the alkaline, neutral, and acid hydrolyses of oxygen esters, the acid hydrolysis of amides and anhydrides, and the neutral hydrolysis of anhydrides, acid chlorides, and acetylimidazolium ion. 

From formylation reactions of CH-acidic compounds, which take place if mixtures of carboxylic acid amides and anhydrides are used as formylating agents, it was concluded that the latter compounds form similar adducts to those from amides and acid halides. ... 

Phosphorus trichloride is the starting material used most frequently for the preparation of the esters, amides and anhydrides of phosphoric and phos-phorothioic acids. It can be oxidised to phosphoryl chloride (4) and, heated with sulfur in the presence of a catalyst, to thiophosphoryl chloride (5) (Perot, 1962). 

Oxabis(triphenylphosphonium) fluoTM Dehydration. The salt (1) is an exo fication, amidation, and anhydride forma... 

The reaction between amide and anhydride groups results in PA chain opening and splitting off water molecules (41). The latter can cause hydrolytic splitting of the chains (24). That is why the region of interphase contact becomes enriched with PA chains of a lower molecular weight in comparison with the volume. 

Formation of Esters, Amides, and Anhydrides. Tosyl chloride and JV-methylimidazole in acetonitrile can be used to promote esterifications, thioesterifications, and amide bond formations in excellent yields (eq 46). Various functionalities are tolerated in this reaction and enolizable substrates, including V-Cbz amino acids, can be esterified without racemization. 

The Wittig condensation has a wide range of applicability. The most suitable carbonyl components are generally aliphatic, alicyclic or aromatic aldehydes, but reactive phosphorus ylides also react with ketones, and even esters, amides and anhydrides can be reacted with phosphorus ylides in so-called non-classical Wittig reactions [13]. 

Dicarboxylic acid amides and anhydrides COCl CO Ccoci Qo) " ... 

F. Cramer, Preparation of esters, amides and anhydrides of phosphoric acid, AWC, 72, 236, 1960. 

In addition to carboxylic acid derivatives, anhydrides and acid fluorides are also accessible straightforward via carbonylation reactions depending on the various nucleophiles used. Eor example, water (hydroxycarbonylation) will give carboxylic acid, alcohols (alkoxycarbonylation) will give esters, amines (aminocarb-onylation) will give amides, and anhydrides and acid fluorides can be produced if... 

Carbonyl addition-elimination n. The single most important type of reaction mechanism which has been applied to the preparation of step-growth polymers is the addition-elimination reaction of the carbonyl double bond of carboxylic acids and carboxylic acid derivatives included in this general type of reaction are esterification amidation and anhydride formation from carboxylic acids, esters, amides, anhydrides and acid halides. 

Curing agents are used with epoxy resins, the most commonly used ones are aromatic amines, and two of the most common are 4,4-methylene-dianiline (MDA) and 4,4-sulfonyl-dianiline (DDS). Like the epoxies, these compounds have very low vapour pressures and in principle they should not present any airborne hazard, unless a mixture is sprayed or cured at high temperatures and certainly potential for dermal exposure is high. Several other types of curing agents to consider are aliphatic and cycloaliphatic amines, polyaminoamides, amides, and anhydrides. 

Phosphorylated compounds, e.g., the esters, amides, and anhydrides of phosphoric acid, participate in many secondary reactions. High-energy and low-energy phosphates may be distinguished. The former liberate up to 13,000 cal/mol if the bond between the phosphate residue and the acceptor molecule is hydrolyzed, the latter set free about 3,000 cal/mol (Table 13). 

This chapter will discuss methods for the preparation of esters, acid chlorides, anhydrides, and amides from carboxylic acids, based on acyl substitution reactions. Acyl substitution reactions of carboxylic acid derivatives will include hydrolysis, interconversion of one acid derivative into another, and reactions with strong nucleophiles such as organometallic reagents. In addition, the chemistry of dicarboxylic acid derivatives will be discussed, as well as cyclic esters, amides, and anhydrides. Sulfonic acid derivatives will be introduced as well as sulfate esters and phosphate esters. Finally, nitriles will be shown to be acid derivatives by virtue of their reactivity. 

In connection with a study of mixtures, it is essential to keep in mind continually the possibility of interaction betw een the ingredients and especially the possibility of decomposition during the process of separation for example, easily hydrolyzable esters, amides, and anhydrides may be met in the form of their decomposition products. Cases of doubt call for a study of the original sample. 

A variety of carbonyl compounds, including esters, lactones, amides, and anhydrides, are methylenated upon heating with dimethyltitanocene 30 at 60-80 °C (Scheme 4.23). Generally, at least two equivalents of dimethyltitanocene are required for complete conversion. 

Dicarboxylic acids 1,2-Dicarboxylic acids, and also 1,2-sulfo-carboxylic acids, as well as their derivatives, esters, amides, and anhydrides, when melted with resorcinol in the presence of anhydrous zinc chloride yield the corresponding fluorescein derivatives (see p. 197). 

The mechanism of these reactions is assumed to involve displacement of chloride by the carboxylate anion to give a phospho-rodiamidate (eq 4). Subsequent nucleophilic attack of an alcohol, amine, or a carboxylate anion affords phosphorodiamidic acid and esters, amides, and anhydrides, respectively (eq 5). 

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