Study of the Factors that Control the Ratio of the Products between 5-Fluorouracil, Uracil, and Tetrahydrobenzoxazepine O,O-Acetals Bearing Electron-Withdrawing Groups on the Nitrogen Atom

(RS)-1-(2-Nitrobenzenesulfonyl)- and (RS)-1-(4-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepines are better substrates than 1-acyl-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine derivatives for the Lewis acid mediated condensation reaction with pyrimidine bases to give O,N-acetals. Acetonitrile, stannic chloride, 50 °C, and a reaction time higher than 48 h are the optimum conditions for such condensation reactions. Under these conditions, 5-fluorouracil preferably links to the aminalic carbon through its N-1‘ ‘ position, while the attachment of the uracil fragment is through N-3‘ ‘ or N-1‘ ‘ of the cyclic or acyclic products, respectively. The causes that influence the course of the reactions are analyzed and discussed. Examination of the 1H NMR spectra revealed the presence of a single form for the secondary amine 11 and of two conformers for the tertiary sulfonamides 7a,b, 9a,b, and 10b and for the amides 7d and 13, with the following distribution: 7a, 59/41; 7b, 53/47; 9a, 52/48; 9b, 59/41; 10b, 56/44; 7d, 50/50; 13, 80/20. On increasing the temperature, the 1H NMR spectrum (DMSO-d 6) of 7b showed coalescence at 110 °C. The torsional barrier determined [ΔG c ⧧ value of 19.0 ± 0.2 kcal·mol-1 (79.1 ± 1.0 kJ·mol-1)] proved to be the highest ever observed for sulfonamide moieties.