Pieter Delbeke

Synthesis of a chiral 2,6-bridged morpholine system: trans-6,7-diol derivatives of 8-oxa-3-azabicyclo[3.2.1]octane

Abstract The title compound 6 , [1R-(6 endo , 7 exo )]-8-oxa-3-azabicyclo[3.2.1]octane-6,7-diol, was derived in nine steps from 1-amino-1-deoxy-D-glucitol 2 . The key step was the acid catalyzed rearrangement of epoxide 3 to the 2,5- cis -disposed hydrofuran compound 5 . Linkage of the 2,5-substituents, to form the bridged secondary amine 23 , proceeded via mesylation of 6-OH and deprotection of 1-NH 2 . Further O -debenzylation and (or) N -substitution afforded the aminodiol 6 and various N -alkylated derivatives. On basis of 1 H NMR analysis the chair form was assigned to the bridged morpholine ring.

Ring transformations of 5-chloro-1,2,3-thiadiazole-4-carbaldehyde with amines, hydrazines and hydroxylamine

5-Chloro-1,2,3-thiadiazole-4-carbaldehyde, prepared in four steps from 1,3-dichloroacetone, reacts with alkyl- and aryl-amines in alcohol solution to give 1,2,3-triazole-4-thiocarboxamides 9a–f. Similarly, hydrazine and N-aminomorpholine furnish the 1,2,3-triazole-4-thiohydrazides 9g and 9h, whereas phenylhydrazine and hydroxylamine yield unrearranged products 8i and 8j. These, however, are transformed into 1,2,3-triazole-4-carboxylic acids 14i and 14j upon storage in dimethyl sulphoxide solution. The mechanism of the rearrangement is discussed.

Reactions of 5-chloro-1,2,3-thiadiazolium salts with activated methylene compounds

The N-3 and N-2 methylated 1,2,3-thiadiazolium tetrafluoroborates 3 and 4 react with aliphatic activated methylene ketones and esters in the presence of a base to give the substitution products 7–11 and 18–24. Under similar conditions activated methylene azoles afford products formulated by NMR analysis as N–S ⋯ O rotamers (25, 26), N–S ⋯ N rotamers (12–15, 27–29), or a mixture of both (16, 17, 30). The X-ray crystal structure analysis of product 21, derived from the thiadiazolium salt 4 and 2,2-dimethyl-1, 3-dioxane-4, 6-dione, reveals a nearly linear N–S ⋯ O sequence (169°) and a short S ⋯ O contact (2.37/2.34 A) for the two independent molecules.

Methylation of 1,2,3-thiadiazole 5-oximes and 5-N-phenylhydrazones

1,2,3-Thiadiazoles unsubstituted at the 4-position and bearing an oxime or phenylhydrazone function at the 5-position have been prepared and treated with Meerweins reagent. In all cases studied, preferential methylation occurs at N-3 yielding the mesoionic compounds 9 and 12. The parent oxime 6a also furnishes the N-2 methylated product 8a in substantial amounts. In contrast, when the methylation of oxime 6a is carried out with diazomethane or with methyl iodide, the nitrone 10a and the oxime ether 11a are formed. The isomeric structures of the reaction products were distinguished by their 13C NMR and mass spectra.