Synthesis and Reactions of 7‐Oxonorbornane‐2,3‐dicarboximides

Abstract

Ozonizations of several 7-isopropylidenenorbornane-2,3-dicarboximides (2, 10) yield 7,7-dihydroxynorbornane-2,3-dicarboximides (3, 11) and/or 7-oxonorbornane-2,3-dicarboximides (4, 12 In connection with the synthesis of compounds with potential analgesic activity containing the perhydro-4,7-methanoisoindole skeleton (I), structurally related to piperidine analgesics of general structure 11, such as anilidopiperidines According to previous work from our groupk2], these compounds could be obtained from anhydride 1 by standard manipulations of functional groups, with the ozonization of the carbon-carbon double bond as key step.As shown in Scheme 1, reaction of anhydride 1 with ammonia, methylamine, benzylamine, or (2-phenylethy1)amine gave in good yields the corresponding cyclic imides 2 a, 2 b, 2c, and 2d, respectively. Ozonization of imide 2 a in ethyl acetate at -78°C followed by hydrogenation of the ozonide using 10% Pd on charcoal as catalyst afforded an almost insoluble product in very good yield. The analytical data (Tables 1,4, 6 and 7) of this compound were in accordance with the hydrate 3a of the anticipated ketone 4a. Especially significant was the 13C-NMR spectrum in which a signal of a carbonyl carbon atom was absent while an absorption at 6 = 105.2 indicated a carbon atom with two oxygen functionalities. As a proof of the structure, treatment of 3a with phosphorus pentoxide in chloroform gave a solution of the corresponding ketone 4a, from which hydrate 3 a slowly precipitated on standing. Concentration of the above solution led to an oily residue, the elemental analysis of which was in accordance with a mixture of hydrate 3 a and ketone 4a.Similarly, ozonization of imide 2 b followed by catalytic hydrogenation of the ozonide gave in good yield hydrate 3 b. Treatment of 3 b with phosphorus pentoxide in chloroform afforded the corresponding ketone 4 b. However, the best elemental analysis obtained fitted for a mixture of hydrate 3b (85Y0) and ketone 4 b (15%). Hydrate 3b was also obtained, although in lower yield, by methylation of 3a with dimethyl sulfate. The identity of hydrate 3b was confirmed by X-ray diffraction analysis (Figure 2). The distances between atoms of different molecules in the unit cell show the existence of intermolecular hydrogen bonds between the hydroxy hydrogen atoms of one molecule and the carbonyl oxygen atoms of other molecules with significant in-