Anhydride leaving group

Two different access routes are used, whether the leaving group is carried on thiazolium derivatives such as anilinovinyl (method A), acetanilidovinyl (method B), formyl methylene, or thioformylmethylene or on the ketomethylene compound (method C). The use of acid anhydride together with pyridine has been patented (method E). 

Alkyl esters of trifluoromethanesulfonic acid, commonly called triflates, have been prepared from the silver salt and an alkyl iodide, or by reaction of the anhydride with an alcohol (18,20,21). Triflates of the 1,1-dihydroperfluoroalkanols, CF2S020CH2R can be prepared by the reaction of perfluoromethanesulfonyl fluoride with the dihydroalcohol in the presence of triethylamine (22,23). Triflates are important intermediates in synthetic chemistry. They are among the best leaving groups known, so they are commonly employed in anionic displacement reactions. 

On dehydration, nitro alcohols yield nitro-olefins. The ester of the nitro alcohol is treated with caustic or is refluxed with a reagent, eg, phthaUc anhydride or phosphoms pentoxide. A mil der method involves the use of methane sulfonyl chloride to transform the hydroxyl into a better leaving group. Yields up to 80% after a reaction time of 15 min at 0°C have been reported (5). In aqueous solution, nitro alcohols decompose at pH 7.0 with the formation of formaldehyde. One mole of formaldehyde is released per mole of monohydric nitro alcohol, and two moles of formaldehyde are released by the nitrodiols. However, 2-hydroxymethyl-2-nitro-l,3-propanediol gives only two moles of formaldehyde instead of the expected three moles. The rate of release of formaldehyde increases with the pH or the temperature or both. 

Closely related to the carboxylic acids and nitriles discussed in the previous chapter are the carboxylic acid derivatives, compounds in which an acyl group is bonded to an electronegative atom or substituent that can net as a leaving group in a substitution reaction. Many kinds of acid derivatives are known, but we ll be concerned primarily with four of the more common ones acid halides, acid anhydrides, esters, and amides. Esters and amides are common in both laboratory and biological chemistry, while acid halides and acid anhydrides are used only in the laboratory. Thioesters and acyl phosphates are encountered primarily in biological chemistry. Note the structural similarity between acid anhydrides and acy) phosphates. 

Notice in both of the previous reactions that only "half" of the anhydride molecule is used the other half acts as the leaving group during the nucleophilic acyl substitution step and produces acetate ion as a by-product. Thus, anhydrides are inefficient to use, and acid chlorides are normally preferred for introducing acyl substituents other than acetyl groups. 

As shown, an asymmetric carboxylic-sulfonic acid anhydride is formed, but the cellulose attack occurs on the C = O group, since a nucleophilic attack on sulfur is slow, and the tosylate moiety is a much better leaving group than the carboxylate group [193]. Similar to other acylation reactions, there is a large preference for tosylation at the 5 position, and cellulose tosylates... 

Note that these mechanisms are the reverse of those involved in the acid-catalyzed hydration of double bonds (15-3), in accord with the principle of microscopic reversibility. With anhydrides (e.g., P2O5, phthalic anhydride) as well as with some other reagents such as HMPA, it is likely that an ester is formed, and the leaving group is the conjugate base of the corresponding acid. In these cases, the mechanism can be El or E2. The mechanism with AI2O3 and other solid catalysts has been studied extensively but is poorly understood. 

Thus acid chlorides and anhydrides react readily with ROH and NH3 to yield esters and amides, respectively, while esters react with NH3 or amines to give amides, but the simple reversal of any of these reactions on an amide, though not impossible, is usually pretty difficult. The relative reactivity will also depend on both the electronic and, more particularly, the steric effect of R. A slightly unusual leaving group is eCX3 (e.g. eCI3) in the haloform (158) reaction (cf. p. 297) ... 

Acid anhydrides, (RC0)20, will also often react with weaker nucleophiles, though more slowly than acid chlorides neither SN1 nor Sn2 types of reaction pathway normally occurs. Anhydrides are essentially intermediate in reactivity—towards a particular nucleophile—between acid chlorides and esters, reflecting the leaving group ability sequence ... 

In summary, reactions of nitronates with acid anhydrides or acyl chlorides give the O-acylated products, and reactions with acyl imidazoles, phenyl esters, acyl nitriles, and enol-lactones gives the C-acylated products, (see Eq. 5.13).25 The C/O selectivity of nitronate acylation by RCOX is qualitatively correlated with strength (pKJ of the acid HX conjugated to the leaving group X .25... 

Nitration of furfuryl alcohol (2-furylmethanol) in acetic anhydride yields the nitro-nitrate 57 which possesses both a reactive methylene group able to undergo aldol reactions, etc., and also a nitrate ion leaving group for nucleophilic substitutions.137 Detailed studies of the nitration disclose various products resulting from the addition of one or even two acetic acid residues to the furan nucleus in competition with the nitrations.138,139... 

A reaction which is related to hydroxy-de-diazoniations is the formation of aryl trifluoromethylsulfonic esters (aryl triflates, ArOSC CFs) which became widely used reagents because of their leaving-group properties. The classical method of synthesis by esterification of phenols with trifluoromethane-sulfonic anhydride or -sulfonyl halide is, however, not applicable for the preparation of aryl triflates bearing a (free)... 

Reactive substrates are those with a good leaving group, such as halide (in acyl halides), hydrosulfide (in thioadds), alkyl thiolate or alkyl mercap-tide (in thioesters), and carboxylate (in anhydrides). 

As one of the most reactive groups of carboxylic acid derivatives, acyl halides are very useful substrates for the preparation of the other classes of derivatives. For example, anhydrides may be synthesized by the reaction of carboxylic acid salts with an acyl halide. In this reaction, the carboxylate anion acts as the nucleophile, eventually displacing the halide leaving group. 

The equilibrium limits the practical applicability of this reaction, and other methods would normally be employed if one were working with uncommon or expensive reagents that could not be used in excess. Esters are actually more conveniently prepared using the more reactive acyl halides or anhydrides, i.e. derivatives with better leaving groups. 

Acyl halides and anhydrides are the most reactive class of carboxylic acid derivatives, and readily react with amines to give amides. It should be noted that in both cases the leaving group is a conjugate base that, upon protonation during the reaction, will become an... 

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