CUMULATIVE acylation

Ketenes are oxo compounds with cumulated carbonyl and carbon—carbon double bonds of the general stmcture R R2C—C—O, where and R2 may be any combination of hydrogen, alkyl, aryl, acyl, halogen, and many other functional groups. Ketenes with R = sometimes called aldoketenes,... 

A carbocation is strongly stabilized by an X substituent (Figure 7.1a) through a -type interaction which also involves partial delocalization of the nonbonded electron pair of X to the formally electron-deficient center. At the same time, the LUMO is elevated, reducing the reactivity of the electron-deficient center toward attack by nucleophiles. The effects of substitution are cumulative. Thus, the more X -type substituents there are, the more thermodynamically stable is the cation and the less reactive it is as a Lewis acid. As an extreme example, guanidinium ion, which may be written as [C(NH2)3]+, is stable in water. Species of the type [— ( ) ]1 are common intermediates in acyl hydrolysis reactions. Even cations stabilized by fluorine have been reported and recently studied theoretically [127]. 

This reaction takes place because diimides, —N=C=N—, have reactive cumulated double-bond systems like those of ketenes, C=C=0 isocyanates, —N=C=0 and isothiocyanates, —N=C=S and are susceptible to nucleophilic attack at the central carbon. In the first step of the diimide-coupling reaction, the carboxyl function adds to the imide to give an acyl intermediate, 9. This intermediate is an activated carboxyl derivative RCO—X and is much more reactive toward an amino function than is the parent acid. The second step therefore is the aminolysis of 9 to give the coupled product and yV,N -dicyclohexylurea ... 

Five- to seven-membered O-, N-, and S-heterocycles Acyl ylides with a tethered terminal ester function requisite for the construction of five- to seven-membered heterocycles are very conveniently accessible by reaction of the cumulated ylide ketenylidenetriphenylphosphorane 11 with various carboxylic esters bearing OH-, NHR-, and SH-groups in a-, -, or y-position. 

Acyl-, thioacyl- and imidoylcarbodiimides, having a C=X (X = O, S, or NR) adjacent to the cumulative bond are usually not stable at room temperature. However, sterically hindered N-functional carbodiimides with aliphatic t-butyl groups or aromatic 2,6-dimethylphenyl groups are often more stable, and they are generated in situ, for subsequent reactions. For example, N-alkyl substituted imidoylcarbodiimides, RN=C(Ph)N=C=NR are only stable as crystalline compounds for a short period of time. Even in chloroform solution they undergo subsequent reactions as indicated by the disappearance of the carbodiimide infrared band (see Table 5.1). ... 

The results obtained (Table 2) show that the effect of substituents on the reaction rate is comparable to that observed in homogeneous catalysis [2,6,7]. The reaction rate greatly increases in the presence of a strong electron-withdrawing group such as NO2, especially in theorf/io position, due to the destabilization of the N-acyl bond by cumulative resonance and inductive effect. 

When the pattern of primary interaction between toxicant molecules and affected receptors is examined, another primary cumulative effect can be distinguished (in addition to the two mentioned). The third is a mixed type of accumulation in which the radicals of the toxicant are fixed at the receptor site (i.e., reactions involving acylation of new molecules). In this mixed type, particles of material attach to the receptor, but the parent substance is destroyed and therefore incapable of accumulation. This type includes the interaction of organ-ophosphates and carbamates with esterases. The phosphorylation and carbamy-lation of the latter yield an acylated enzyme with a split inhibitor. Only a part of the parent molecule of a substance is the phosphoryl and carbamyl groups remains at the enzyme site. 

An increase in the number of cis double bonds from oleic (9) to linoleic (9, 12) and a-linolenic (9, 12, 15) acid increases the desaturation (Brenner and Peluffo, 1966) and the same happens with 20 3 (9, 12) and 20 3 (9, 12, 15). This increase corresponds to an increase of the curvature of the molecule. Therefore it is possible to explain this effect if we assume that the enzyme also possesses a curve structure where the acyl-CoA will be located. An increase of curvature of the substrate would increase the fitting and bonding by cumulative London - Van der Waals interactions. An addition of 2 carbons in the tail of the acid from 18 2 (9, 12) to... 

We begin with reactions of polar organometallics with aldehydes, ketones, and v/c-dicarbonyl compounds (a-oxoaldehydes, 1,2-diketones, a-oxocarboxamides, and a-oxocarboxylic acids). Next we focus on carboxamides, lithium carboxylates, carboxylic acid esters, and acyl chlorides. Finally we turn to ketenes, (thio)isocyanates, and carbon dioxide, all featuring cumulated double bonds, and last but not least to carbon monoxide. 

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