Verner Schomaker

Syntheses of iron(III) aroyl hydrazones containing pyridoxal and salicylaldehyde. The crystal and molecular structure of two iron(III)-pyridoxal isonicotinoyl hydrazone complexes

Abstract Iron(III) complexes of three aroyl hydrazones, pyridoxal isonicotinoyl hydrazone (H 2 pih), pyridoxal benzoyl hydrazone (H 2 pbh), and salicylaldehyde benzoyl hydrazone (H 2 sbh), were synthesized and characterized. In aqueous medium at pH 7, [Fe(pih)(Hpih)]·3H 2 O is formed. In acidic methanol, a 1:1 ligand-to-metal complex is formed, [FeCl 2 (H 2 pih)]Cl ( 1 ), whereas in aqueous medium at low pH cis -[FeCl 2 (H 2 pih)(H 2 O)]Cl·H 2 O ( 2 ) is formed. Compounds 1 and 2 are high-spin d 5 with μ eff = 5.88 μ B and 5.93 μ B (298 K). The crystal structures of 1 and 2 show that H 2 pih acts as a tridentate neutral ligand in which the phenolic and hydrazidic protons have shifted to the pyridine nitrogen atoms. The co- ordination polyhedron of 1 is ‘square’ pyramidal, whereas that of 2 is pseudo-octahedral. Compound 1 is triclinic, space group P l , with a = 12.704(2) A, b = 8.655(2) A, c = 8.820(2) A, α = 105.42(1)°, β = 89.87(1)°, γ = 107.60(1)°, V = 888 A 3 , and Z = 2; 2 is monoclinic, space group P 2 1 / c , with a = 15.358(4) A, b = 7.304(3) A, c = 17.442(4) A, β = 101.00(2)°, V = 1921 A 3 , and Z = 4.

Structural studies of Fe(III) and Cu(II) complexes of salycylaldehyde benzoyl hydrazone, a synthetic chelating agent exhibiting diverse biological properties

Salicylaldehyde benzoyl hydrazone (SBH) is a Schiff base that can function as a tridentate chelating agent [l-3]. Some thirty years ago, it was shown that this compound has modest bacteriostatic properties when tested in vitro against microorganisms such as Mycobacten’um tuberculosis, Mycobacterium smegmatis, Candida albicans and Aspergillus niger, although these effects were not sufficiently marked to encourage further study at that time [4, 51. Recently, however, interest in the biological properties of SBH has been renewed with the recognrtion that aroylhydrazones of this type are able to induce iron excretion in mammals and thus are potentially of use in the treatment of iron overload on man [6, 71. SBH itself can mobilize iron from iron-loaded reticulocytes in vitro [8] and produces high levels of iron excretion when administered to rats [9] . preliminary studies have also shown that SBH is an unusually potent inhibitor of DNA synthesis in a variety of cultured human and rodent cells and that the complex [CuCl(SBH)]*H,O produces significant inhibition of tumor growth when given to mice bearing a transplanted fibrosarcoma [lo-121. The common mechanism underlying these various biological effects of SBH appears to be an ability to penetrate cell membranes and disrupt the intracellular metabolism of essential metal ions. The exact nature of such disruptions, and the extent to which they may be exploited for therapeutic purposes, require much additional study, including detailed elucidation of the chemical properties of complexes formed between SBH and physiologically-important transition metals. This paper reports single crystal X-ray diffraction studies of two such complexes, [FeCla(SBH)(CHsOH)] and [CuCl(SBH)]~H,O. TABLE I. Selected Bond Distances, in A.

Structures of four trans-2-hydroxy- and methoxy-2-methyl-3,4-dihydro-4-alkyl-2H,5H-pyrano[3,2-c][1]benzopyran-5-ones

Derivatives of 2-methyl-3,4-dihydro-2H,5Hpyrano[ 3,2-c)[ l)benzopyran-5-one. ( l) Racemic trans2-methoxy-4-(2-propyl), Mr= 288·3, monoclinic, P2ifc, a= 13· 737 (3), b = 13·228 (6), c = l7·229(4)A, P=l02·93(2) 0 , V=3051·4A3, Z=8 (two molecules/asymmetric unit), Dx = 1 ·255 g cm3, )..(Mo Ka) = O· 71073 A, μ = 0·908 cm· , F(OOO) = 1232, T = 298 K, final R = 0·050 for 3988 unique intensities. Dihydropyran rings in C 17H 200 4 are halfchairs, one being distorted toward the d,e-diplanar form. (2) Resolved trans-2-methoxy-4-cyclohexyl, Mr = 328-4, orthorhombic, ni2121, a = 10·468 (5), b = 11·245 (5). C = 14·465 (4)A, V= 1702·7 A3, Z=4, Dx= 1·281 g cm3, A.(MoKa) = 0·71073 A, μ = 0·823 cm, F(OOO) = 704, T = 298 K, final R = 0·051 for 2481 unique intensities. Compound, C 20H240 4 , spontaneously resolves on crystallization from methanol:acetone; data specimen determined to be 2R,4R by circular dichroism spectrum and comparison with structures of known configuration. Dihydropyran ring has a d,e-diplanar conformation. (3) Racemic trans2-hydroxy-4-(2-propyl). Compound crystallizes as the hemihydrate C 16H 180 4.!H10; Mr= 283-3, triclinic, PI, a = 9·015 (4), b = 10·216 (4), c = 16·208 (5) A, «= 103·08 (3), P= 95·42 (3), Y= 95·28 (3) , V = 1437 ·6 A 3, Z = 4 (two molecules/asymmetric unit), Dx = 1·309 g cm-, A.(Mo Ka)= O· 71073 A, μ = 0· 890 cm, F(OOO) = 604, T = 298 K, final R = 0· 040 for 4656 unique reflections. One dihydropyran ring is a half-chair, the other has an e/-diplanar conformation. Intermolecular hydrogen bonding occurs between the water and the hydroxyls and lactone carbonyls of each coumarin with Q ... Q distances between 2·82 and 2-90 A. (4) Racemic trans-2-hydroxyl-4-(2-propyl) derivative also cocrystallizes with 4-hydroxy-2H-benzopyran-2-one (1:1), M,=436·4, triclinic, PI, a = 8·669 (2), b = 10·506 (4), c = 12.559 (2) A, a = 0108-2701/87 /0305 3 3-04

A structure containing diastereomers, (2S,4R)-trans- and (2R,4R)-cis-2-hydroxy-2,4-dimethyl-3,4-dihydro-2H,5H-pyrano[3,2-c][1]benzopyran-5-one, C14H14O4

0 1.50 102·98 (2), f3= 107·56 (2), /= 93 ·63 (2) , V= 1052·0A3, Z=2, Dx=l·378gcm-3, ..l.(Mo Ka)= 0·71073 A,μ= 0·941 cm1, F(OOO) = 460, T= 298 K, final R = 0·041 for 3322 unique reflections. Cocrystalline C 16H180 4.C9H60 3 shows chains of H bonds linking the hydroxyls of the coumarins alternately with the lactone carbonyls, O· · ·O distances 2·68 and 2·75 A. The dihydropyran ring has a half-chair conformation. Introduction. Analogs of the clinically useful oral anticoagulant drug warfarin, with alkyl substituents in place of the side-chain phenyl group, can be prepared by Michael-type addition of a,,li-unsaturated methyl ketones with 4-hydroxycoumarin. Products invariably crystallize as one of the cyclic diastereomeric hemiketals but in solution the open-chain keto form generally predominates. Methyl ketals can be made by treatment of the hemiketal/keto mixture with acidic methanol. Structures of 4-alkyl-2-hydroxyand methoxy-2-methyl-3,4-

Organometallic sulfur complexes. 1. Syntheses, structures, and characterizations of organoiron sulfane complexes (.mu.-Sx)[(.eta.5-C5H5)Fe(CO)2]2 (x = 1-4)

Mr= 246·3, monoclinic, P21, a= 7·804 (3), b=18·248(8), c=8·752(5)A, P=99·59°, V= 1233 A, Z = 4 (2 molecules/asymmetric unit), Dx =1·33gcm-3, l(MoKa)=0·71067A, μ= O· 91 cm-1, F(OOO) = 520, T = 293 K. Final R = 0-066 for 1123 observed independent intensities. The structure consists of diastereomers approximately inversionrelated through a pseudocenter of symmetry at x = 0-241(4),z=0·281 (3) except the 4-methyl groups. The dihydropyran rings are half chairs distorted towards the eJ-diplanar conformation. Like molecules are hydrogen-bonded between hydroxyl and carbonyl groups along a, O···O distances being 2·781 (7) (trans) and 2· 780 (7) A (els). Introduction. Michael-type addition of certain a,/Junsaturated ketones with 4-hydroxycoumarin leads to •Current address: Department of Chemistry, Mississippi College, Clinton, MS 39058, USA. 3-substituted 4-hydroxycoumarins. In solution these products exist in a dynamic equilibrium between diastereomeric hemiketals and the open (keto) form of the molecule. The compound so obtained using 3penten-2-one (R = CH3) consists of about equal parts of each isomer in chloroform solution (Valente, Santarsiero & Schomaker, 1979), and its crystalline . racemate consists of cis diastereomeric forms. As part of a structural study of this Michael addition product, we resolved the optical isomers and undertook a crystallographic investigation. In crystallizing the compound under different conditions, we hoped to observe another of the isomeric forms apparently present in solution.