Hemetsberger-Knittel reaction

Scheme 5.12 Synthesis of vinyl azides from aldehydes and azidoacetates by Hemetsberger-Knittel reaction ...

Hemetsberger and coworkers published in 1969 the special condensation reaction of benzaldehydes 76 with ethyl azidoacetate (77a) in the presence of sodium ethoxide to get moderate to good yields of the a-azidocinnamic esters 79a (Scheme 5.12). The temperature and the reaction time had to be controlled careMly, because the strongly alkaline reaction conditions induced the danger of decomposition of the base-sensitive azides 77 and other unwanted side reactions. Thus, Knittel reported some years later that usage of methyl azidoacetate (77b) and sodium methoxide offers several advantages in the synthesis of vinyl azides 79b. Nevertheless, the Hemetsberger-Knittel reaction can only be... 

Aza-indoles can be prepared from 2,6-dichloropyridin-3-yl-epoxides by reaction with primary amines " and 5-, 6-, and 7-azaindole-2-esters can be made" via the Hemetsberger-Knittel route. Note that 4-aza-indoles cannot be made this way since cyclisation of the appropriate precursor takes place preferentially onto the ring nitrogen generating a pyrazolo[l,5-fl]-pyridine. 

R =aryl) in aprotic solvents, for example, xylene at 140 °C, is more important and has been applied very frequently to prepare indoles of type 176 via intermediate 172. This method is connected with the names of Hemetsberger and Knittel and can be transferred to the synthesis of azaindoles, fused indoles, and fused pyrrol derivatives. Quite recently, reactions like 171 (R =Ph) —> 176 have been conducted in a rhodium(II)-catalyzed way, which allows to decrease the necessary temperature into a range of 25-60 C. The transformation of 171 into isoquinolines is also possible if one or both ortho positions of the aryl group R are substituted appropriately. ... 

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