Sulphuric acids, reactions with enamines

Compounds of this class are aza-analogues of xanthone. Benzopyrano[2,3-b]pyridine (XXXVI) was synthesised by the cyclisation of 2-phenoxynicotinic acid (XXXV) by means of phosphorus oxychloride [25]. The carbonyl group of (XXXVI) can easily be reduced by sodium amalgam in ethanol. Compound (XXXVI) and its sulphur analogues were screened as possible drugs for treatment of schistosomiasis and for amoebic infection but the initial tests indicated that these compounds have no significant effects on schistosomiasis [25]. Recently, derivatives of (XXXVI) have been prepared from chromonyl-2-isocyanate by its reaction with enamines followed by acid cyclisation [26]. 

The reaction proceeds by way of the imine (109) which is converted into the enamine (110) by proto tropic rearrangement before being cyclised with concentrated sulphuric acid. 

Trimethylquinoline. Add 6g (0.032 mol) of the above enamine, in portions, to 25 ml of concentrated sulphuric acid (d 1.84) contained in a 250-ml conical flask. Swirl the mixture occasionally to ensure thorough mixing. The first portions of the enamine dissolve rather slowly but solution occurs more rapidly with the later portions as the temperature of the mixture increases to 60-70 °C. Heat the reaction mixture on the steam bath for 30 minutes, and then cool the brown solution to room temperature and add it slowly to 250 ml of ice-water in a 1-litre beaker. Add solid sodium carbonate to the solution until it is alkaline. During this addition the quinoline salt tends to separate and the whole mixture may solidify if this happens the mass should be broken up and stirred with a stout glass rod or spatula while the sodium carbonate is added. The quinoline eventually separates as an oil from the alkaline solution. Cool the mixture in an ice-water bath until the quinoline solidifies avoid over-cooling as this will result in the separation of a large... 

The hydroxy-nitrone (8a) gave the isomeric hydroxy-nitrone (9) on treatment with acid. The latter hydroxy-nitrone underwent base-catalysed deuteriation at C-21, presumably via the dihydroxy-enamine tautomer. Treatment of either hydroxy-nitrone with methanolic sulphuric acid gave the unstable methoxy-nitrone (10), which yielded the dimeric compound (11) on attempted crystallization. The reaction of nitrone (8b) with dialkyl phosphite derivatives was reported earlier details of this study have now been published. ... 

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