Ethoxymethylene cyanoacetate esters

Reiter et al. studied the condensations of 3-methylthio-AT and 3-morpholino-AT, respectively, with ethoxymethylene-cyanoacetate (and -malonitrile) in acetic acid or DMF (or mixtures) and isolated only the corresponding 7-amino-TP (87JHC1149). Analogous reactions of aliphatic (90M173) and alicyclic 3-ketocarbonic esters (87JHC1503 890PP163 91JHC721) always resulted in 7-oxo-TPs as the major products and 5-oxo-TPs as by-products. 

Cyclocondensation of 2-amino-4,5,6,7-tetrahydro-3//-azepine (414) (R = H) with ethoxymethylenemalonate, (ethoxymethylene)cyanoacetate, 2-formyl esters, or 3-oxo esters afforded isomeric mixtures of the 4-oxo- (415,... 

In all cases one of the groups R2 or R3 in Eq. (19) has been an ester, and in most cases the ester group cyclizes on to the pyridine nitrogen atom. However, cyclization of a nitrile can give a quinolizine imine (Eq. 20). In an example where ethyl ethoxymethylene cyanoacetate was used32 the formation of imine was favored at —10° but not at higher temperatures where 4-quinolizone becomes the major product. Examples of the reaction (Eq. 20) have been reported where R1 was a nitrile,32,35 ester,32,35,36 or ketone... 

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