Nina Lah

1,3-Dipolar Cycloadditions to (5Z)-1-Acyl-5-(cyanomethylidene)- imidazolidine-2,4-diones: Synthesis and Transformations of Spirohydantoin Derivatives

Cycloadditions of various 1,3-dipoles to (5Z)-1-acyl-5-(cyanomethylidene)-3-methylimidazolidine-2,4-diones 8 or 9, prepared in 3 steps from hydantoin (1) (Schemes 1 and 2), were studied. In all cases, reactions proceeded regio- and stereoselectively. The type of product depended on the 1,3-dipole and/or dipolarophile employed as well as on reaction conditions. Thus, with stable dipoles under neutral conditions, spirohydantoin derivatives 12 – 16 were obtained (Scheme 2), while under basic or acidic conditions, pyrazole- or isoxazole-5-carboxamides 18 and 23 – 26 and carboxylate 27 were formed via aromatization of the newly formed dihydroazole ring, followed by the simultaneous cleavage of the hydantoin ring (Schemes 3 – 5).

Copper(II) carboxylates with 4-aminopyridine: neutral mononuclear structures, isomerism of aceto compounds and a novel tetranuclear structure

Reactions of copper(II) carboxylates with 4-aminopyridine (4-apy) were investigated and their products structurally characterized by single crystal X-ray diffraction. Reaction of copper(II) acetate resulted in two isomers of a monomeric complex of composition Cu(ac)2(4-apy)2 with markedly different stabilities: the violet form, 1, unstable in air and the blue, stable form, 2. In both isomers the ligands are arranged around the copper atom in a trans geometry. The 4-apy ligands lie almost in the plane in 1, while they are twisted with respect to each other in 2. Variations were observed also in the coordination of the acetate groups to the copper ion. The energy difference between the two isomers was obtained on the basis of ab initio MO calculations. The result agrees well with the observed relative stabilities in the solid state. Monomeric complexes of the same stoichiometry were obtained also by the reaction of Cu(II) hexanoate and heptanoate with 4-apy. The violet Cu(hex)2(4-apy)2, 3, and Cu(hep)2(4-apy)2, 4, are isostructural and possess trans geometry of the ligands around the copper centre. Reaction of 4-apy with Cu(II) octanoate lead to formation of a novel, unprecedented basic centrosymmetric tetranuclear compound of composition Cu4(oct)6(OH)2(4-apy)2, 5. Complex 5 contains bidentate bridging and monoatomic bridging carboxylate groups, triply bridging hydroxyl groups and 4-aminopyridine as a terminal ligand. In all five compounds 4-apy is coordinated through the endocyclic nitrogen atom only.

Structures of artificial sweeteners--cyclamic acid and sodium cyclamate with other cyclamates.

In the course of a study on artificial sweeteners, new crystal structures of cyclamic acid, sodium cyclamate, potassium cyclamate, ammonium cyclamate, rubidium cyclamate and tetra-n-propylammonium cyclamate have been determined. Cyclamic acid exists in its zwitterionic form in the crystalline state. The zwitterions are connected through hydrogen bonds of the N-H...O type to form two-dimensional sheets. The sodium, potassium, ammonium and rubidium cyclamates are isostructural, with the cyclamate moieties linked through hydrogen bonds into linear chains. Taking into account the connectivity through cations, two-dimensional layers with a hydrophobic surface are constructed. In tetra(n-propyl)ammonium cyclamate the large, non-coordinating cation apparently prevents the formation of chains and thereby facilitates the centrosymmetric head-to-head discrete dimeric arrangement of the cyclamate moieties.

A 1:1 cocrystal of fluconazole with salicylic acid

The interaction of the antifungal pharmaceutical agent fluconazole with salicylic acid in acetonitrile solution yields the 1:1 cocrystal 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol-2-hydroxybenzoic acid (1/1), C(13)H(12)F(2)N(6)O·C(7)H(6)O(3). The asymmetric unit consists of one molecule of fluconazole and one molecule of salicylic acid, both in their neutral forms. Both crystal agents form head-to-tail hydrogen-bonded dimers, which are further connected into hydrogen-bonded extended zigzag tapes propagating along the ac diagonal.

4-Aminopyridinium hydrogen maleate

The title compound, C(5)H(7)N(2)(+)...C(4)H(3)O(4)(-), crystallizes in space group P2(1) with one ion pair in the asymmetric unit. The hydrogen maleate anion possesses nearly planar geometry and displays an extremely short intramolecular O--H...O hydrogen bond, with an O...O distance of 2.4198 (19) A. Classical N-H...O hydrogen bonds, together with short C--H...O contacts, generate an extensive hydrogen-bonding network.

A synthesis of alkyl 4-alkyl-2-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylates

Abstract Reaction of ethyl 4-alkyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylates with sodium hydride in dioxane affords ethyl 4-alkyl-2-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylates. The structure of the products was unambiguously established by X-ray analysis as well as by 1H–13C and 1H–15N NMR correlation spectroscopy.

Crystal Structures of Two Monomeric Copper(II) Carboxylates with 2-Aminopyridine

The crystal structures of two monomeric copper(II) carboxylates with 2-aminopyridine have been determined by X-ray diffraction. The hexanoate complex crystallizes as its acetonitrile solvate [Cu(C6H11O2)2(C5H6N2)2 · CH3CN] in the triclinic space group P-1 with a = 8.1020(6), b = 13.7106(9), c = 13.7673(9) Å, α = 113.79(1), β = 103.86(1), and γ = 94.38(4). The heptanoate compound shows an unsolvated structure [Cu(C7H13O2)2(C5H6N2)2] and also crystallizes in the triclinic space group P-1 with the following cell parameters: a = 8.4487(9), b = 12.238(1), c = 13.504(2) Å, α = 87.034(9), β = 77.489(9), and γ = 71.41(1)°. Both compounds contain the CuO4N2 chromophore, with ligands arranged around the copper center in a cis mode. 2-Aminopyridine is coordinated through the endocyclic nitrogen atom. The ortho position of the amino group, with respect to the pyridine nitrogen atom, allows the formation of both, intra-and intermolecular hydrogen bonds.

Bromidobis[2‐(pyridin‐2‐yl)methanol‐κ2N,O]copper(II) bromide monohydrate

The title compound, [CuBr(C6H7NO)2]Br·H2O, is an ionic mononuclear complex in which the [CuBr(C6H7NO)2](+) cation possesses distorted square-pyramidal geometry. The Cu(II) centre is coordinated by two neutral 2-(pyridin-2-yl)methanol (2-pyMeOH) ligands and a terminal bromide ligand. The 2-pyMeOH ligands are coordinated in a bidentate chelating manner through the pyridine N and hydroxy O atoms, forming a five-membered chelate ring with the Cu(II) centre. The planes of the pyridine rings are twisted by 58.71 (14)° with respect to each other. The charge is balanced by a noncoordinating bromide anion which, together with a solvent water molecule, links the components through hydrogen bonds into infinite chains propagating along the a axis. The mononuclear cations appear to associate in pairs through weak interactions between the metal atom of one cation and the halogen atom of an adjacent cation.

trans-Bis(acetato-O)bis(2-amino-6-methylpyridine-N)copper(II)

In the title compound, [Cu(C 2 H 3 O 2 ) 2 (C 6 H 8 N 2 ) 2 ], the Cu atom is surrounded by two O atoms from the two mono-dentate acetate ligands and by two pyridine N atoms from the two 2-amino-6-methylpyridine ligands in a trans square-planar arrangement. The Cu-O and Cu-N distances are 1.952(2) and 2.046 (2) A, respectively. The complex has an inversion centre. The remaining carboxylate O atoms are located at 2.764 (3) A from the Cu atom, above and below this plane. The coordination around the Cu atom can therefore be described as (4+2). The pyridine ring is twisted 73.2 (1)° with respect to the plane formed by the Cu, the N and the more strongly bonded O atoms.

Fluconazole–malonic acid (1/1)

Co-crystallizaton of the antifungal drug fluconazole [2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol] with malonic acid in acetonitrile solution resulted in the formation of the title 1:1 co-crystal, C13H12F2N6O·C3H4O4. The geometry around the central fluconazole atom is distorted tetrahedral. The dihedral angles between the triazole rings and the fluorinated phenyl ring are 30.64 (7) and 61.91 (5)°. In the crystal, the basic packing motif may be envisioned as a cyclic aggregate formed of two fluconazole molecules linked by two malonic acid molecules through O—H⋯N and O—H⋯O hydrogen bonds. Such aggregates are further connected into (001) layers by further O—H⋯N hydrogen bonds. The structure also features weak non-classical C—H⋯O and C—H⋯N interactions.