Imidazolides acid anhydride synthesis

The use of imidazolides in organic synthesis has been propagated by Staab and coworkers." " Acid anhydrides can also be prepared with carbonyldiimidazolide. The reaction of a carboxylic acid with this reagent leads to acid anhydride if the transacylation equilibrium (equation 35) can be shifted to the side of the anhydride. This is possible either if the acid is used in twofold excess and forms an insoluble salt with the liberated imidazole or if trifluoro- or trichloro-acetylimidazolide is taken as the reagent. Symmetrical acid anhydrides can be obtained in a number of cases in good yield according to equation (36). 20... 

The imidazolides required for these reactions can be prepared from sulfonyl chlor-ides[1] or sulfonic anhydrides[2] and imidazole, or by treatment of the corresponding sulfonic acid with CDI,[1] ImSOIm,[3] or ImS02Im[3] (see Section 10.1.1). However, for the synthesis of sulfonamides it is more convenient to employ a one-pot reaction starting from the free sulfonic acid, CDI or ImSOIm, and the appropriate amine [1]... 

For reactions carried out in homogeneous solution or under solid-phase conditions the use of Fmoc amino acid chlorides is limited by the competition between their aminolysis and the formation of the less reactive oxazol-5(4//)-ones in the presence of tertiary amines, which are essential components of such reaction systems. To improve the results under these conditions a hindered base, e.g. 2,6-di-/er/-butylpyridine, can be used as a hydrogen chloride acceptor since conversion to oxazol-5(4//)-one is slow with such bases. Although shown to be advantageous in certain cases, Fmoc amino acid chlorides are used in homogeneous solution synthesis only in particular cases. They react efficiently in the presence of pyridine with weak nucleophiles such as imine 2P l (Scheme 2) where other activated species such as an active ester, anhydride, acyl fluoride, and acyl imidazolide fail. 

Several routes to /3-keto-acids, -esters, and -nitriles, based on the acylation of malonate derivatives, have been reported. The dianion of monoethyl malonate is acylated by acid chlorides to give -keto-esters in a one-pot synthesis,and the lithio-derivative of bis(trimethylsilyl) malonate reacts with acid chlorides, giving /3-keto-acids directly.The magnesium derivatives of monomethyl or mono-thioalkyl esters of malonic acid give j8-keto-esters or -thioesters respectively in high yield under virtually neutral conditions with acid imidazolides. Similarly, the trimethylsilyl ester of cyanoacetic acid, after lithiation, reacts with mixed anhydrides to give high yields of j8-keto-nitriles. ... 

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