Acid catalysts increase the reactivity of a carbonyl group

Amides react as electrophiles only with powerful nucleophiles such as HO . Acid chiorides, on the other hand, react with even quite weak nucleophiles neutral ROH, for example. They are more reactive because the electron-withdrawing effect of the chlorine atom increases the electrophilicity of the carbonyl carbon atom. 

You may think that a weaker C=0 bond should be more reactive. This is not so because the partial positive charge on carbon is also lessened by delocalization and because the molecule as a whole is stabilized by the delocalization. Bond strength is not always a good guide to reactivity  

For example, in acetic acid the bond strengths are surprising. The strongest bond is the 0-H bond and the weakest is the C-C bond. Yet very few reactions of acetic acid involve breaking the C-C bond, and its characteristic reactivity, as an acid, involves breaking 0-H, the strongest bond of them alii 

The reason is that polarization of bonds and solvation of ions play an enormously important role in determining the reactivity of molecules. In Chapter 37 you will see that radicals are relatively unaffected by solvation and that their reactions follow bond strengths much more closely. 

Carboxylic acids do not undergo substitution reactions under basic conditions 

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Acid catalysts increase the reactivity of a carbonyl group... 

ACID CATALYSTS INCREASE THE REACTIVITY OF A CARBONYL GROUP... 

The Mukaiyama aldol reaction of carbonyl substrates with silyl enol ethers is the most widely accepted of Lewis acid-promoted reactions. Many Lewis acids for the reaction have been developed and used enantioselectively and diastereoselectively. In 1980, catalytic amounts of la were found by Noyori et al. to effect aldol-type condensation between acetals and a variety of silyl enol ethers with high stereoselectivity [2c,20]. Unfortunately, la has poor Lewis acidity for activation of aldehydes in Mukaiyama s original aldol reaction [21]. Hanaoka et al. showed the scope and limitation of 11-cat-alyzed Mukaiyama aldol reaction, by varying the alkyl groups on the silicon atom of silyl enol ethers [22]. Several efforts have been since been made to increase the reactivity and/or the Lewis acidity of silicon. One way to enhance the catalyst activity is to use an additional Lewis acid. 

Nucleophilic addition to carbonyl compounds is the cornerstone of organic synthesis, highlighted by the classical examples of Grignard reactions, aldol condensation, LiA.lH4 reductions, and so on. However, when less reactive nucleophiles are employed, such as allylsilane [1], aUylstannane [1, 2], or CLSiR [3], activation is required. Here, we have a choice of activating either the electrophile or the nucleophile. Activation of the electrophile, that is, the carbonyl reactant, can be attained by coordination of a Lewis acid to the oxygen [4], which increases the electrophilicity of the carbonyl carbon and, consequently, the reactivity of the C=0 group. Alternatively, coordination of a Lewis base to the nucleophile can be assumed to increase its nucleophilicity, which should also allow the addition to occur [5]. Since only the coordinated species will react, the activator can be used in just a catalytic amounL provided that it can be regenerated after completion of the reaction and returned to the next catalytic cycle. Naturally, if the catalyst is chiral, preferential formation of one enantiomer of the product can be expected. 

A MW-assisted protocol for the synthesis of azides, thiocyanates, and sulfones has been developed (Scheme 12) that has proved to be a useful alternative, as the use of environmentally deterimental volatile chlorinated hydrocarbons is avoided.All the reactions with these readily available halides or tosylates have shown significant increase in reactivity, thus reducing the reaction times with substantial improvement in the yields. Various functional groups such as ester, carboxylic acid, carbonyl, and hydroxyl were unaffected under the mild reaction conditions employed. This method involves simple experimental procedures and product isolation which avoids the use of phase-transfer catalysts, and is expected to contribute to the development of greener strategy for the preparation of various azides, thiocyanates, sulfones, and other useful compounds. 

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