General regioselective synthesis of 2,2-disubstituted 3-hydroxyimidazolidin-4-ones

Cyclic hydroxamic acids derived from α-amino acids 1. Regioselective synthesis, structure, NO-donor and antimetastatic activities of spirobicyclic hydroxamic acids derived from glycine and DL-alanine

“…9 Unlike 1a and 1e, in which the amide nitro gen atom is slightly pyramidalized 8,9 (ΣωN(3) = 350.8°( 1a) and 350.9° (1e)), the amide nitrogen atom in mole cule 3 has a virtually planar configuration (ΣωN(3) = = 358.8°, Table 2). As a consequence, the exocyclic O(1)-N(3)-C(2) and O(1)-N(3)-C(4) bond angles in molecule 3 are larger (see Table 2) than the corresponding angles in 1a (117.7(2)° and 119.7(2)°, respectively) 8 and 1e (118.1(1)° and 120.0(1)°).…”

“…8,11 This con firms the spirobicyclic structure of the reaction products and rules out the structure of the corresponding azome thines. 9 The 1 H and 13 C NMR spectra of compounds 3 and 4 (in CD 3 OD or DMSO d 6 ) show no signals of azome thine forms, which rules out the ring chain tautomer ism slow on the NMR time scale. 11 The tautomerism be tween the hydroxy amide and hydroxy nitrone forms (O=C-N-OH HO-C=N→O) of acids 3 and 4 fast on the NMR time scale is not observed as well.…”

“…As a consequence, the exocyclic O(1)-N(3)-C(2) and O(1)-N(3)-C(4) bond angles in molecule 3 are larger (see Table 2) than the corresponding angles in 1a (117.7(2)° and 119.7(2)°, respectively) 8 and 1e (118.1(1)° and 120.0(1)°). 9 Table 1. Selected torsion angles in molecule 3…”

“…As a continuation of our research on the structures of 3 hydroxyimidazolidin 4 one derivatives, 8,9 in the present study we investigated the structure of acid 3 and compared it with the previously studied analogs of the glycine series (acid 1a (see Ref. 8) and 1e (see Ref.…”

“…17 Another consequence of the change in the conforma tion of the imidazolidine ring and a decrease in the twist ing of the hydroxamic fragment is that the mutual trans orientation of the polar N(1)-C (2) The piperidine ring of compound 3 in the crystal struc ture adopts a nearly ideal chair conformation (cf., φ 0 -φ 5 , Table 1; ϕ(C(11)-C(8)…C(9)-C(13)) = 0.3(1)°, ϕ(C(12)-C(8)…C(9)-C(14)) = 1.0(1)°) and, accord ing to the general rule, is orthogonal to the imid azolidine ring (ϕ(C(5)-N(1)-C(2)-C(6)) = = 88.2(2)°, ϕ(C(6)-C(2)-N(3)-C(4)) = -96.2(2)°), like the cyclopentane ring in 1e (87.2° and -89.8°, res pectively). 9 According to the known Thorpe-Ingold effect, 22 the fact that the endocyclic C(8)-N(10)-C(9) bond an gle in the six membered ring is larger than the endocyclic C(2)-N(1)-C(5) bond angle in the five membered ring of molecule 3 (see Table 2) corresponds to a decrease in the degree of pyramidalization of the amine nitrogen atom N(10) (ΣωN(10) = 328.3°, see Table 2) compared to the amine nitrogen atom N(1) (ΣωN(1) = 316.3°, see Table 2) exhibiting similar pyramidalization in molecules 1a (317.2°) 8 and 1e (315.0°). 9 The corresponding decrease in the basicity of the N(1) atom compared to the N(10) atom (due to the stronger s character of pseudo e LP N(1) than that of pseudo e LP N(10) , ϕ(C(7)-C( Table 4, Fig.…”