Acylating agents, common

N,N-dicyclohexylcarbodiimide and similar condensing agents, activated esters with A/-hydroxysuccinimide, and N-hydroxybenzotriazole together with other acylating agents commonly used in peptide synthesis. The choice of coupling reaction is invariably dependent on the side chain. The efficiency of the reaction varies considerably between side chains so that optimization of the coupling procedure is often a matter of trial and error. 

These acylating agents are the most commonly used (246). Acid chlorides react with 5-nitro-2-aminothiazoIe (88) despite the deactivating effect of the nitro group (Scheme 61) (247), but more vigorous conditions are required (248). 

Ketone Synthesis. In the Friedel-Crafts ketone synthesis, an acyl group is iatroduced iato the aromatic nucleus by an acylating agent such as an acyl haUde, acid anhydride, ester, or the acid itself. Ketenes, amides, and nittiles also may be used aluminum chloride and boron ttitiuotide are the most common catalysts (see Ketones). 

Esters of the phenohc hydroxyl are obtained easily by the Schotten-Baumaim reaction. The reaction ia many cases iavolves an acid chloride as the acylating agent. However, acylation is achieved more commonly by reaction with an acid anhydride. The single most important commercial reaction of this type is the acetylation of sahcyhc acid with acetic anhydride to produce acetylsahcyhc acid [50-78-2] (aspirin). 

The most common O- and N-acylation procedures use acylating agents that are more reactive than caiboxylic acids or their esters. Carboxylic acid chlorides and anhydrides react rapidly with most unhindered hydroxy and amino groups to give esters and amides, respectively ... 

Enol esters are another useful family of acylating agents. The acetate of the enol form of acetone, isopropenyl acetate, is the most commonly used member of this group of... 

In entirely analogous fashion, the selective esterification of various other common disaccharides by other acylating agents was investigated. One notable example is the selective benzoylation of methyl (3-lactoside with benzoyl chloride, which again produced many interesting results that are recorded in a series of papers with Ram... 

Many such activated acyl derivatives have been developed, and the field has been reviewed [7-9]. The most commonly used irreversible acyl donors are various types of vinyl esters. During the acylation of the enzyme, vinyl alcohols are liberated, which rapidly tautomerize to non-nucleophilic carbonyl compounds (Scheme 4.5). The acyl-enzyme then reacts with the racemic nucleophile (e.g., an alcohol or amine). Many vinyl esters and isopropenyl acetate are commercially available, and others can be made from vinyl and isopropenyl acetate by Lewis acid- or palladium-catalyzed reactions with acids [10-12] or from transition metal-catalyzed additions to acetylenes [13-15]. If ethoxyacetylene is used in such reactions, R1 in the resulting acyl donor will be OEt (Scheme 4.5), and hence the end product from the acyl donor leaving group will be the innocuous ethyl acetate [16]. Other frequently used acylation agents that act as more or less irreversible acyl donors are the easily prepared 2,2,2-trifluoro- and 2,2,2-trichloro-ethyl esters [17-23]. Less frequently used are oxime esters and cyanomethyl ester [7]. S-ethyl thioesters such as the thiooctanoate has also been used, and here the ethanethiol formed is allowed to evaporate to displace the equilibrium [24, 25]. Some anhydrides can also serve as irreversible acyl donors. 

Proton acids can be used as catalysts when the reagent is a carboxylic acid. The mixed carboxylic sulfonic anhydrides RCOOSO2CF3 are extremely reactive acylating agents and can smoothly acylate benzene without a catalyst.265 With active substrates (e.g., aryl ethers, fused-ring systems, thiophenes), Friedel-Crafts acylation can be carried out with very small amounts of catalyst, often just a trace, or even sometimes with no catalyst at all. Ferric chloride, iodine, zinc chloride, and iron are the most common catalysts when the reactions is carried out in this manner.266... 

Amides may be made in a number of ways. Prominent among them is the acylation of amines. The agents commonly used are, in order of reactivity, the acid halides, acid anhydrides, and esters. Such reactions are ... 

The most common acylating agents are the acyl chlorides and acid anhydrides of ethanoic acid and benzoic acid. The amine can be recovered from the amide by acid- or base-catalyzed hydrolysis ... 

Lactams can act as acylating agents to those nucleophiles that effect the cleavage of the (3-lactam Ni C2 bond. Indeed, irreversible acylation of an enzyme amino acid unit belonging to a bacterial cell is the most common type of molecular mechanism for the (3-lactam antibiotics mode of action. Similarly, the process is on grounds of... 

Irreversible inhibitors act by covalently modifying the enzyme, generally at the active site. The active site is then blocked, and the enzyme is permanently rendered inactive. Because functional groups in the active site tend to be electron rich and nucleophilic, irreversible inhibitors tend to be electrophiles. Acylation agents are especially common. 

A global electrophilicity index of common benzylating and acylating agents has been established from MO calculations and it shows a quantitative linear correlation with the experimental substrate selectivity index from a series of benzylation and acylation reactions.21 The values of relative rate coefficients predicted from the index may be accurate to within 10%. The reaction of /-butyl chloride with anisole catalysed by /Moluenesulfonic acid in supercritical difluoromethane has been subject to kinetic analysis.22 The proportions of substitution at the ortho -position and disubstitution increase at lower pressures, attributed to the decrease in the hydrogen-bonding ability of the solvent. 

These derivatives for the analysis of amino acids have been widely investigated and various combinations of acyl and alkyl groups have been tested in order to find the properties most suitable from the viewpoint of chromatography, the reaction yields and the reaction time for the whole group of amino acids. Their preparation is based on the first, i.e., esterification step, when common esterification reactions are applied with minor modifications, and the second step, when amino and other functional groups are acylated with anhydrides, chlorides or other acylating agents. 

Methyl ethers were applied firstly to the GC of cholesterols [390,391]. They are prepared by the method common for the preparation of ethers, e.g., by treatment with dimethyl sulphate or methyl iodide in the presence of potassium rert.-butoxide (cf., p. 64). Their good chromatographic properties, e.g., on SE-30 and PEGS stationary phases, are usually obtained only after further treatment with a silylating or acylating agent. 

As carbamates often tend to decompose during GC analysis, prior to the analysis they have been modified by acetylation [466,467], silylation [468], alkylation [467] and acylation with fluorinated acylating agents [467,469—471]. Other procedures involve hydrolytic decomposition of carbamates and GC analysis of the phenols or amines so produced by procedures common for these substances. 

Perfluoro)acyl anhydrides Common silylation reagents Other derivatizing agents Reaction tubes for GC-derivatization... 

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