1,2,4-TRIOXAN-5-ONES, A NEW CLASS OF ENDOPEROXIDES - STRUCTURES OF 3 REPRESENTATIVE DERIVATIVES

(I): 7,8,15-Trioxadispiro[5.2.5.2]hexadecan-16-one, C13H20O4, m.p. 366-367 K, M(r) = 240.3, monoclinic, P2(1)/c, a = 11.160 (2), b = 11.588 (1), c = 11.169 (3) angstrom, beta = 118.72 (2)-degrees, V = 1266.7 (5) angstrom 3, Z = 4, D(x) = 1.26 Mg m-3, lambda(Mo K-alpha) = 0.71069 angstrom, mu = 0.086 mm-1, F(000) = 520, room temperature, R (= wR) = 0.089 for 582 observed reflections [\F(o)\ > 3-sigma-(F(o)) and \F(o)\ > 7.0]. (II): (6RS,3RS)-6-(Adamant-1-yl)-3-cyclohexyl-1,2,4-trioxan-5-one, C19H28O4, m.p. 395 K, M(r) = 320.4, monoclinic, P2(1)/n, a = 12.150 (4), b = 10.693 (2), c = 12.909 (2) angstrom, beta = 90.78 (1)-degrees, V = 1677.0 (7) angstrom 3, Z = 4, D(x) = 1.27 Mg m-3, lambda-(Mo K-alpha) = 0.71069 angstrom, mu = 0.082 mm-1, F(000) = 696, room temperature, R (= wR) = 0.066 for 1804 observed reflections [\F(o)\ > 4-sigma-(F(o)) and \F(o)\ > 8.0]. (III): (6RS,3 SR)-6-(Adamant-1-yl)-3-phenyl-1,2,4-trioxan-5-one, C19H22O4, m.p. 372-375 K, M(r) = 314.4, orthorhombic, P2(1)2(1)2(1), a = 6.5317 (16), b = 11.316 (3), c = 21.216 (3) angstrom, V = 1568.1 (6) angstrom 3, Z = 4, D(x) = 1.33 Mg m-3, lambda-(Mo K-alpha) = 0.71069 angstrom, mu = 0.086 mm-1, F(000) = 672, room temperature, R (= wR) = 0.052 for 1039 observed reflections [\F(o)\ > 4-sigma-(F(o)) and \F(o)\ > 8.0]. 1,2,4-Trioxan-5-ones are potentially fragile entities with respect to concomitant decarboxylation and scission of the endoperoxide bond. However, they are thermally stable at ambient temperatures. Some are suitably crystalline, thereby permitting their structures to be determined. The trioxane rings in (I) and (II) adopt a flattened half-chair conformation and an envelope in (III). In all three compounds the greatest puckering amplitude is associated with the peroxide bond. None displayed significant antimalarial activity.