Nucleophilic acyl substitution reactions relative reactivity

MECHANISM OF NUCLEOPHILIC ACYL SUBSTITUTION Acid-Catalyzed Acyl Substitution Reactions Base-Catalyzed Acyl Substitution Reactions Relative Reactivity of Acyl Derivatives... 

Amides, like esters, are abundant in all living organisms—proteins, nucleic acids, and many pharmaceuticals have amide functional groups. The reason for this abundance of amides, of course, is that they are stable to the conditions found in living organisms. Amides are the least reactive of the common acid derivatives and undergo relatively few nucleophilic acyl substitution reactions. 

A carboxyhc acid derivative will undergo a nucleophilic acyl substitution reaction provided that the newly added group in the tetrahedral intermediate is not a much weaker base than the group that was attached to the acyl group in the reactant. The weaker the base attached to the acyl group, the easier it is for both steps of the nucleophilic acyl substitution reaction to take place. The relative reactivities toward nucleo-phihc acyl substitution acyl halides > acid anhydrides > carboxylic acids and esters > amides > carboxylate ions. 

Since we know the relative stabilities of acyl derivatives, we can predict the position of a nucleophilic acyl substitution reaction. The same factors that affect the relative reactivity of acyl derivatives also control their stabilities. The identity of the groups bonded to the tetrahedral carbon atom affects the stabilities of the reactants and products. Thus, destabilizing the reactant and stabilizing the product increase the equihbrium constant. We conclude that the less stable acyl derivative is more reactive and can be converted into a more stable, less reactive acyl derivative. The relative stabihties of acyl derivatives enable us to understand most of the chemical reactions discussed in this chapter. 

Because the addition steps are generally fast and consequently exothermic chain steps, their transition states should occur early on the reaction coordinate and therefore resemble the starting alkene. This was recently confirmed by ab initio calculations for the attack at ethylene by methyl radicals and fluorene atoms. The relative stability of the adduct radicals therefore should have little influence on reacti-vity 2 ). The analysis of reactivity and regioselectivity for radical addition reactions, however, is even more complex, because polar effects seem to have an important influence. It has been known for some time that electronegative radicals X-prefer to react with ordinary alkenes while nucleophilic alkyl or acyl radicals rather attack electron deficient olefins e.g., cyano or carbonyl substituted olefins The best known example for this behavior is copolymerization This view was supported by different MO-calculation procedures and in particular by the successful FMO-treatment of the regioselectivity and relative reactivity of additions of radicals to a series of alkenes An excellent review of most of the more recent experimental data and their interpretation was published recently by Tedder and... 

In the case of the tricarbonylarene metals, enhancement of nucleophilic substitution relative to the free arene is reported 106), In contrast to earlier reports 106) Friedel-Crafts acylation of tricarbonylbenzene chromium occurs under mild conditions 18), Molecular-orbital calculations of the 7r-electron activation energies for these reactions 63) confirm enhanced nucleophilic reactivity and suggest electrophilic activity similar to that of the free arene. The nucleophilic displacement of halide by methoxide ion... 

Ammonium salts with two different alkyl chains were prepared directly via subsequent alkylations of dimethylamine with primary bromides and crystallization. Commercial hexadecyl-methylamine can be conveniently applied in the same way in order to convey functionality to cationic synkinons. A recent example describes subsequent alkylations with a small functional and a long-chain primary bromide (Scheme 2.4). A-acylated / -phenylenediamine was also alkylated at the second nitrogen atom which had two different alkyl chains, with or without extra functionality . After deacylation, this head group can be diazotized or coupled oxidatively with various heterocycles in water (Scheme 2.4). Photoactive and coloured membrane surfaces are thus obtained. Phenylene-diamine, pyridine and in particular A-methyl-4,4-bipyridinium chloride are relatively weak nucleophiles. Substitution of bromides is slow and the more reactive iodides can rarely be obtained commercially, but the selection of nitromethanes as solvent for bromide substitution is of great help as well as the addition of sodium iodide to enforce a Finkelstein reaction or a combination of both. 

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