2‐Acetamido‐N‐benz­yl‐2‐(methoxy­amino)acetamides: functionalized amino acid anticonvulsants

In the crystal structure of 2‐acetamido‐N‐benz­yl‐2‐(methoxy­amino)acetamide (3L), C₁₂H₁₇N₃O₃, the 2‐acetyl­amino­acetamide moiety has a linearly extended conformation, with an inter­planar angle between the two amide groups of 157.3 (1)°. In 2‐acetamido‐N‐benz­yl‐2‐[meth­oxy(meth­yl)­amino]­acetamide (3N), C₁₃H₁₉N₃O₃, the planes of the two amide groups inter­sect at an angle of 126.4 (4)°, resulting in a chain that is slightly more bent. The replacement of the methoxy­amino H atom of 3L with a methyl group to form 3N and concomitant loss of hydrogen bonding results in some positional/thermal disorder in the meth­oxy­(methyl)­amino group. In both structures, in addition to classical N—H⋯O hydrogen bonds, there are also weak non‐standard C—H⋯O hydrogen bonds. The hydrogen bonds and packing inter­actions result in planar hydro­philic and hydro­phobic areas perpendicular to the c axis in 3L and parallel to the ab plane in the N‐meth­yl derivative. Stereochemical comparisons with phenytoin have identified two O atoms and a phenyl group as mol­ecular features likely to be responsible for the anticon­vulsant activities of these compounds.     

N‐(3H‐Thia­zol‐2‐yl­idene)­nitr­amine and N‐methyl‐N‐(thia­zol‐2‐yl)­nitr­amine

The geometries of the thia­zole ring and the nitr­amino groups in N‐(3H‐thia­zol‐2‐yl­idene)­nitr­amine, C₃H₃N₃O₂S, (I), and N‐­methyl‐N‐(thia­zol‐2‐yl)­nitr­amine, C₄H₅N₃O₂S, (II), are very similar. The nitr­amine group in (II) is planar and twisted along the C—N bond with respect to the thia­zole ring. In both structures, the asymmetric unit includes two practically equal mol­ecules. In (I), the mol­ecules are arranged in layers connected to each other by N—H⋯N and much weaker C—H⋯O hydrogen bonds. In the crystal structure of (II), the mol­ecules are arranged in layers bound to each other by both weak C—H⋯O hydrogen bonds and S⋯O dipolar interactions.     

cis‐Dioxocyclam

Molecules of 1,4,8,11‐tetra­aza­cyclo­tetra­decane‐5,7‐dione, or cis‐dioxocyclam, C₁₀H₂₀N₄O₂, lie across mirror planes in space group Cmca; the crystal structure reveals interleaved columns of cis‐dioxocyclam mol­ecules along the 2₁ screw axis parallel to the crystallographic b axis. The columns are interconnected in a chain‐like arrangement by an amido hydrogen‐bonding network (N?O = 2.816 Å) and an amino hydrogen‐bonding network (N?N = 3.193 Å). The intracolumn spacing is 9.02 Å.     

O‐Benzyl‐N‐tert‐butoxy­carbonyl‐N‐methyl‐l‐tyrosine

The crystal structure of the title compound, alternatively called 3‐[4‐(benzyl­oxy)­phenyl]‐2‐(N‐tert‐butoxy­car­bonyl‐N‐methyl­amino)­propi­onic acid, C₂₂H₂₇NO₅, has been studied in order to ex­amine the role of N‐methyl­ation as a determinant of peptide conformation. The conformation of the tert‐butoxy­carbonyl group is trans–trans. The side chain has a folded conformation and the two phenyl rings are effectively perpendicular to one another. The carboxyl­ate hydroxyl group and the urethane carbonyl group form a strong intermolecular O—H?O hydrogen bond.     

N,N′‐Bis(2‐methoxy­benzyl­idene) adducts of ethane‐1,2‐di­amine,propane‐1,3‐di­amine and butane‐1,4‐di­amine

We have isolated and crystallographically characterized the three homologous compounds N,N′‐bis(2‐methoxy­benzyl­idene)­ethane‐1,2‐di­amine (MeSalen), C₁₈H₂₀N₂O₂, N,N′‐bis(2‐methoxy­benzyl­idene)­propane‐1,3‐di­amine (MeSalpr), C₁₉H₂₂N₂O₂, and N,N′‐bis(2‐methoxy­benzyl­idene)­butane‐1,4‐di­amine (MeSalbu), C₂₀H₂₄N₂O₂. In contrast with MeSalpr, the mol­ecules of MeSalen and MeSalbu, which have an even number of methyl­ene units, have crystallographic symmetry. Comparing these methoxy‐substituted species with their hydroxy equivalents shows that the aryl rings rotate upon removal of the O—H⋯N hydrogen bonds. The packing of MeSalen and MeSalpr is controlled by C—H⋯π interactions, whereas that of MeSalbu has only van der Waals contacts.     

N‐(4‐Methyl­phenyl)‐N‐(5‐nitro­furfuryl)‐N‐prop‐2‐ynyl­amine

The title compound, C₁₅H₁₄N₂O₃, is the first example of a structurally determined tertiary amine with both N‐5‐nitro­furfuryl and N‐prop‐2‐ynyl moieties. The mol­ecule is not planar, i.e. the furan ring is inclined at an angle of 84.35 (4)° to the phenyl ring. The crystal structure is dominated by van der Waals forces. The terminal alkynyl group as the strongest C—H hydrogen‐bond donor is not involved in hydrogen‐bond formation.     

Bis­(saccharinato‐κN)zinc(II) com­plexes with N,N′‐bidentate 2‐amino­methyl­pyridine and 2‐amino­ethylpyridine

The structures of trans‐bis[2‐(amino­methyl)­pyridine‐κ²N,N′]­bis­(saccharinato‐κN)­zinc(II), [Zn(C₇H₄NO₃S)₂(C₆H₈N₂)₂], (I), and [2‐(amino­ethyl)­pyridine‐κ²N,N′]bis­(saccharinato‐κN)­zinc(II), [Zn(C₇H₄NO₃S)₂(C₇H₁₀N₂)], (II), exhibit octa‐ and tetrahedrally coordinated Zn^II atoms, respectively. The di­amine ligands behave as N,N′‐bidentate ligands, while saccharinate (sac) is coordinated through the N atom. In (I), the complex lies about an inversion centre with the Zn atom disordered and displaced by 0.256 (2) Å from a centre of symmetry towards a sac N atom. The crystal structure of (I) is stabilized by N—H⋯O hydrogen bonds and the crystal packing of (II) is determined by hydrogen bonding as well as weak π–π stacking interactions between the sac ligands.     

4‐Methyl‐2‐[N‐(3,4‐methyl­ene­dioxy­benzyl­idene)hydrazino]­thia­zole and its reduction product, 4‐methyl‐2‐[N‐(3,4‐methyl­ene­dioxybenzyl­idene)hydrazono]‐4,5‐di­hydro­thia­zole

The crystal structures of 4‐methyl‐2‐[N‐(3,4‐methyl­ene­dioxybenzyl­idene)hydrazino]­thia­zole, C₁₂H₁₁N₃O₂S, and its reduction product 4‐methyl‐2‐[N‐(3,4‐methyl­ene­dioxybenzyl­idene)hydrazono]‐4,5‐di­hydro­thia­zole, C₁₂H₁₃N₃O₂S, have been determined and compared. In the reduction product, the tautomer observed bears an H atom on the exocyclic N atom. Both compounds form hydrogen‐bonded dimers over centers of inversion.     

From α‐carbamoyl‐α‐cyano­oxiranes to 3‐halogenopyruv­amides

The crystal structures of the first stable α‐diol from the α‐halogenopyruv­amide series, 3‐chloro‐2,2‐di­hydroxy‐3‐phenyl­propan­amide, C₉H₁₀­ClNO₃, and three products [3‐(4‐chloro­phenyl)‐2‐cyano‐2,3‐epoxy­propan­amide, C₁₀H₇­ClN₂O₂, 3‐bromo‐2‐cyano‐2‐hydroxy‐3‐p‐tolyl­propan­amide, C₁₁H₁₁Br­N₂O₂, 3‐bromo‐2‐oxo‐3‐p‐tolyl­propan­amide, C₁₀H₁₀­BrNO₂] obtained during the systematic synthesis of α‐halogenopyruv­amides are reported. The crystal structures are dominated by hydrogen bonds involving an amide group. The stability of the geminal diol could be ascribed to hydrogen bonds which involve both hydroxyl groups.     

The tetrapeptide Z‐Leu‐Aib‐Pro‐Val‐OBg monohydrate

The intramolecular hydrogen‐bonding pattern of Z‐Leu‐Aib‐Pro‐Val‐OBg monohydrate [(N‐benzhydryl­amino)­carbonyl­methyl N‐benzyl­oxy­carbonyl‐α‐amino­isobutyryl­prolyl­valinate monohydrate], C₄₃H₅₅N₅O₈·H₂O, is unusual for a tetrapeptide because, in addition to a 14 hydrogen bond, a second hydrogen bond of the type 15 is formed. This folding reflects the intramolecular hydrogen‐bonding pattern that this amino acid sequence adopts in the naturally occurring peptaibol alamethicin.     

[N,N′‐Bis(3‐aminopropyl)ethylenediamine‐κ4N,N′,N′′,N′′′](trithiocyanurato‐κ2N,S)zinc(II) ethanol solvate

In the crystal structure of the title compound, [N,N′‐bis(3‐­amino­propyl)­ethyl­enedi­amine‐κ⁴N,N′,N′′,N′′′][1,3,5‐triazine‐2,4,6(1H,3H,5H)‐tri­thionato(2−)‐κ²N,S]­zinc(II) ethanol sol­vate, [Zn(C₈H₂₂N₄)₂(C₃HN₃S₃)]·C₂H₆O, the Zn^II atom is octa­hedrally coordinated by four N atoms [Zn—N = 2.104 (2)–2.203 (2) Å] of a tetradentate N‐donor N,N′‐bis(3‐­amino­propyl)­ethyl­enedi­amine (bapen) ligand and by two S and N atoms [Zn—S = 2.5700 (7) Å and Zn—N = 2.313 (2) Å] of a tri­thio­cyanurate(2−) (ttcH²⁻) dianion bonded as a bidentate ligand in a cis configuration. The crystal structure of the compound is stabilized by a network of hydrogen bonds.     

Two enamines derived from 1‐n‐alkyl‐3‐methylpyrazol‐5‐ones

The first two crystal structures of en­amines derived from 1‐n‐alkyl‐3‐methyl‐5‐pyrazolones, namely 1‐(n‐hexyl)‐3‐methyl‐4‐[1‐(phenyl­amino)­propyl­idene]‐2‐pyrazolin‐5‐one, C₁₉H₂₇N₃O, (I), and N,N′‐bis{1‐[1‐(n‐hexyl)‐3‐methyl‐5‐oxo‐2‐pyrazolin‐4‐yl­idene]­ethyl}hexane‐1,6‐di­amine, C₃₀H₅₂N₆O₂, (II), are reported. The mol­ecule of (II) lies about an inversion centre. Both (I) and (II) are stabilized by intramolecular N—H⋯O hydrogen bonding. This confirms previous results based on spectroscopic evidence alone.     

2,3‐Dihydro‐3‐methyl‐2‐nitrimino‐1,3‐thiazole

The title compound {alternatively, 3‐methyl‐2‐[oxido(oxo)hydrazono]‐2,3‐dihydro‐1,3‐thiazole}, C₄H₅N₃O₂S, was obtained by methyl­ation of N‐(2‐thia­zolyl)­nitr­amine. The molecule lies on a mirror plane and the thia­zole ring is planar, regular in shape and aromatic. The S atom participates in the aromatic sextet via an electron pair on the 3p_z orbital. In the crystal, the mol­ecules are arranged in parallel layers, bound to each other by weak C—H?O and C—H?N hydrogen bonds and by S?O dipolar interactions, with an interlayer separation of 3.23 Å.     

1H‐Imidazol‐1‐yl 1,2,3,4‐tetra­hydro­isoquinolin‐2‐yl ketone

In the crystal structure of the title compound, C₁₃H₁₃N₃O, the C—N_imidazole bond length of 1.431 (3) Å is shorter than that observed [1.466 (6) Å] in the corresponding carbamoyl­imidazolium salt 3‐methyl‐1‐(1,2,3,4‐tetra­hydro­isoquinolin‐2‐yl­carbonyl)­imidazolium iodide. A comparision of these compounds is used to highlight the structural differences that occur as a result of the imidazolium effect. Weak C—H⋯O hydrogen bonds link mol­ecules into extended tapes in the a direction.     

Mono­alkyl­ated 4′‐aryl‐substituted terpyridines

1‐Methyl‐2‐[4‐phenyl‐6‐(pyridinium‐2‐yl)­pyridin‐2‐yl]­pyridinium diperchlorate, C₂₂H₁₉N₃²⁺·2ClO₄⁻, (I), and 2‐[4‐(methoxy­phenyl)‐2,2′‐bipyridin‐6‐yl]‐1‐methyl­pyridinium iodide, C₂₃H₂₀N₃O⁺·I⁻, (II), both crystallize in the monoclinic space group P2₁/c. In contrast with the monocharged mol­ecule of (II), the doubly charged mol­ecule of (I) contains an additional protonated pyridine ring. One of the two perchlorate counter‐anions of (I) interacts with the cation of (I) via an N—H⋯O hydrogen bond. In (II), two mol­ecules related by a centre of symmetry are connected by weak π–π interactions, forming dimers in the crystal structure.     

Two 2,2‐dihalo‐N‐(1‐phenyl­ethyl)­cyclo­propane‐1‐carbox­amides

The crystal structures of (1R,1′S)‐2′,2′‐di­chloro‐N‐(1‐phenyl­ethyl)­cyclo­propane‐1′‐carbox­amide, C₁₂H₁₃Cl₂NO, (I), and (1R,1′R)‐2′,2′‐di­fluoro‐N‐(1‐phenyl­ethyl)­cyclo­propane‐1′‐car­box­amide, C₁₂H₁₃F₂NO, (II), have been determined. Both crystals contain two independent mol­ecules with different conformations of the phenyl­ethyl groups. In the crystals of both compounds, the mol­ecules are linked together by N—H⃛O hydrogen bonds, thus forming chains in the a direction.     

N‐Meth­yl‐N‐(2‐nitro­phen­yl)nitramine and N‐meth­yl‐N‐(3‐nitro­phen­yl)­nitramine

The structures of the two title isomeric compounds (systematic names: N‐meth­yl‐N,2‐dinitro­aniline and N‐meth­yl‐N,3‐di­nitro­aniline, both C₇H₇N₃O₄) are slightly different because they exhibit different steric hindrances and hydrogen‐bonding environments. The aromatic rings are planar. The –N(Me)NO₂ and –NO₂ groups are not coplanar with the rings. Comparison of the geometric parameters of the ortho, meta and para isomers together with those of N‐meth­yl‐N‐phenyl­nitramine suggests that the position of the nitro group has a strong influence on the aromatic ring distortion. The crystal packing is stabilized by weak C—H⋯O hydrogen bonds to the nitramine group.     

trans‐Dioxocyclam (1,4,8,11‐tetraazacyclotetradecane‐2,9‐dione) dihydrate and its NiII complex

The crystal structures are reported of trans‐dioxocyclam dihydrate, C₁₀H₂₀N₄O₂·2H₂O, a structural isomer of the well known cis‐dioxocyclam, and of its novel Ni complex, (1,4,8,11‐tetra­aza­cyclo­tetra­decane‐2,9‐dionato‐κ⁴N)­nickel(II) dihydrate, [Ni(C₁₀H₁₈N₄O₂)]·2H₂O, the first example of a trans­ition metal complex of this ligand. Both mol­ecules lie on crystallographic centres of inversion. The free ligand has two of its N atoms turned outwards from the ring and hydrogen bonded to water mol­ecules. A major conformational change takes place in the complex in which the ligand binds in a trans tetradentate fashion, as suggested by the electronic spectrum. The nickel(II) ion is low spin, although the electronic spectrum of the complex in water indicates an equilibrium mixture of low‐spin and high‐spin species. The irreversible electrochemical oxidation of [NiL¹] (L¹ is deprotonated trans‐dioxocyclam, C₁₀H₁₈N₄O₂) in water occurs at a potential of 0.964 V [versus SHE (standard hydrogen electrode)], which is very similar to that for the Ni–cis‐dioxocyclam complex.     

Unusual molecular conformation in dissymmetric propyl­ene‐linker compounds containing pyrazolo­[3,4‐d]­pyrimidine and phthalimide moieties

The crystal structure of 4,6‐bis(methylsulfanyl)‐1‐phthalimidopropyl‐1H‐pyrazolo[3,4‐d]pyrimidine, C₁₈H₁₇N₅O₂S₂, (VI), reveals an unusual folded conformation due to an apparent intramolecular C—H⃛π interaction between the 6‐methyl­­sul­fanyl and phenyl groups. However, the closely related compound 6‐methyl­sulfanyl‐1‐phthalimido­propyl‐4‐(pyrroli­din‐1‐yl)‐1H‐pyrazolo­[3,4‐d]­pyrimidine, C₂₁H₂₂N₆O₂S, (VII), exhibits a fully extended structure, devoid of any intramol­ecular C—H⃛π or π–π interactions. The crystal packing of both mol­ecules involves intermolecular stacking interactions due to aromatic π–π interactions. In addition, (VI) exhibits intermolecular C—H⃛O hydrogen bonding and (VII) exhibits dimerization of the mol­ecules through intermolecular C—H⃛N hydrogen bonding.     

A complex containing both five‐ and six‐coordinate [bis(5‐bromosalicyli­dene)benzene‐1,2‐diimine]chloro­iron(III)

The title compound, aqua­chloro{4,4′‐di­bromo‐2,2′‐[o‐phenylenebis­(nitrilo­methyl­idyne)]­diphenolato‐O,N,N′,O′}iron(III)–chloro{4,4′‐di­bromo‐2,2′‐[o‐phenyl­enebis­(nitrilomethyli‐dyne)]diphenolato‐O,N,N′,O′}iron(III)–di­methyl­form­amide (1/1/1), [FeCl(C₂₀H₁₂Br₂N₂O₂)][FeCl(C₂₀H₁₂Br₂N₂O₂)(H₂O)]·C₃H₇NO, contains one independent five‐coordinate [FeCl(C₂₀H₁₂Br₂N₂O₂)] monomer, one six‐coordinate [FeCl(C₂₀H₁₂Br₂N₂O₂)(H₂O)] monomer and a non‐coordinating di­methyl­form­amide solvent mol­ecule in the asymmetric unit. In the five‐coordinate monomer, the Fe atom shows distorted square‐pyramidal geometry, with the N and O atoms of the ligand at the base and the Cl atom at the apex of the pyramid. In the six‐coordinate monomer, the Fe atom is in a distorted octahedral geometry and coordinated by the donor atoms of the tetrafunctional ligand in the horizontal plane, and the coordination sphere is completed by the O atom of the water mol­ecule and the Cl atom at the axial positions. The title compound contains intermolecular O—H?O hydrogen bonds. Apart from these hydrogen bonds, there are also intermolecular C—H?Cl and C—H?O contacts.