Cyclic hemi-orthoester

Similar experiments were also carried out with dichloroketene diethyl and dimethyl acetals but no intermediate could be detected. This is readily explained since the cyclic ketene acetals undergo acid-catalysed hydration about 30 times more rapidly than the corresponding acyclic ones (Straub, 1970 Chiang et al., 1974 Kresge and Straub, 1983) whereas cyclic hemi-orthoesters undergo acid-catalysed breakdown 50-60 times more slowly than the corresponding acyclic ones do (see p. 70). Therefore the ratio of rate constants favourable for the detection of the cyclic hemiorthoesters becomes unfavourable with the acyclic hemiorthoesters. 

Calculated equilibrium constants and free energies for the formation of cyclic hemi-orthoesters from the corresponding esters at 25° °... 

An additional difficulty occurring with hemisuccinates was discovered by Sandman et al These authors, in studying the stability of chloramphenicol succinate, found an unusual partial acyl transfer reaction of the succinyl group to give a cyclic hemi-orthoester (Figure 38.6). 

FIGURE 38.6 Formation of cyclic hemi-orthoesters from a hemisuccinated ... 

This model was used to explain a number of intriguing experimental observations such as the preference for the acyclic products to the formation of lactones in hydrolysis of cyclic hemi-orthoesters (involved, for example in ozonolysis of acetals ). In this reaction, the equatorial C-O bond needs to be broken for the... 

Figure 5.45 Stereoelectronic control in hydrolysis of cyclic hemi-orthoesters. Only p-type lone pairs antiperipla-...

In a cyclic orthoester such as 55 (Fig. 5) when the two alkoxy groups are different, there is the possibility of forming three different hemi-orthoesters (56, 57, and 58) which can lead to three different esters, the two hydroxy-esters 59 and 60 and the lactone 6K Thus, there is a possibility that some specific hemi-orthoesters will be generated which will lead to the preferential formation of one of the ester products. The mild acid hydrolysis of orthoesters is therefore a potential method to test the principle of stereoelectronic control in the formation and cleavage of hemi-orthoester tetrahedral intermediates. 

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