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.     

5‐Formylsalicylic acid and 5‐(benzimidazolium‐2‐yl)salicylate

Both title compounds are derivatives of salicylic acid. 5‐Formylsalicylic acid (systematic name: 5‐formyl‐2‐hydroxybenzoic acid), C₈H₆O₄, possesses three good hydrogen‐bond donors and/or acceptors coplanar with their attached benzene ring and abides very well by Etter's hydrogen‐bond rules. Intermolecular O—H...O and some weak C—H...O hydrogen bonds link the molecules into a planar sheet. Reaction of this acid and o‐phenylenediamine in refluxing ethanol produced in high yield the new zwitterionic compound 5‐(benzimidazolium‐2‐yl)salicylate [systematic name: 5‐(1H‐benzimidazol‐3‐ium‐2‐yl)‐2‐hydroxybenzoate], C₁₄H₁₀N₂O₃. Each imidazolium N—H group and its adjacent salicyl C—H group chelate one carboxylate O atom via hydrogen bonds, forming seven‐membered rings. As a result of steric hindrance, the planes of the molecules within these pairs of hydrogen‐bonded molecules are inclined to one another by ∼74°. There are also π–π stacking interactions between the parallel planes of the imidazole ring and the benzene ring of the salicyl component of the adjacent molecule on one side and the benzimidazolium component of the molecule on the other side.     

6,6′‐Di­methoxy‐2,2′‐[(1R,2R)‐cyclo­hexane‐1,2‐diyl­bis­(nitrilo­methyl­idyne)]­diphenol: three C—H⃛O hydrogen bonds generate a three‐dimensional framework

Molecules of the title compound, alternatively called (R,R)‐N,N′‐bis(3‐methoxysalicylidene)‐trans‐cyclohexane‐1,2‐diamine, C₂₂H₂₆N₂O₄, contain two intramolecular O—H⃛N hydrogen bonds and adopt a conformation with approximate twofold rotational symmetry. The mol­ecules are linked by three C—H⃛O hydrogen bonds [H⃛O = 2.45–2.55 Å, C⃛O = 3.329 (2)–3.398 (2) Å and C—H⃛O = 142–172°] into a continuous framework.     

N,N‐Di­methyl­anilinium 3‐cyano‐4‐(di­cyano­methyl­ene)‐5‐oxo‐4,5‐di­hydro‐1H‐pyrrol‐2‐olate

In the title compound, C₈H₁₂N⁺·C₈HN₄O₂⁻, the anion and cation lie on a crystallographic mirror plane and form planar ribbons via N—H⋯O [N⋯O = 2.933 (4) Å, H⋯O = 2.01 Å and N—H⋯O = 170°] and N—H⋯N [N⋯N = 3.016 (5) Å, H⋯N = 2.15 Å and N—H⋯N = 169°] hydrogen bonds. The ribbons are further linked via weak C—H⋯O and C—H⋯N hydrogen bonds. In adjacent planes, anions lie opposite cations; π–π interactions (separation a/2 = 3.520 Å) exist between the anions and the cations, and stacks are formed, running along the a axis. The cations are disordered over two interpenetrating sites, with occupancies of 0.833 (5) and 0.167 (5).     

Ethyl 3‐(2′‐deoxyuridin‐5‐yl)‐3‐hydroxy‐2‐iodopropanoate,a ­nucleoside analogue

In the title compound, C₁₄H₁₉IN₂O₈, an almost planar heterocyclic base is oriented anti with respect to the puckered sugar moiety. The sugar pucker is C2′‐endo/C3′‐exo, the N‐glycosidic torsion angle is 166.4 (4)° and the conformation of O5′ is +sc. The mol­ecules are linked by hydrogen bonds of the types N—H?O and O—H?O.     

{4‐[(Carbamimidoylhydrazono)methyl‐κ2N1,N4]‐5‐hydroxymethyl‐2‐methylpyridinium‐3‐olate‐κO}(methanol‐κO)copper(II) dinitrate

The title compound, [Cu(C₉H₁₃N₅O₂)(CH₄O)](NO₃)₂, consists of square‐planar cationic complex units where the Cu^II centre is coordinated by an N,N′,O‐tridentate pyridoxal–aminoguanidine Schiff base adduct and a methanol molecule. The tridentate ligand is a zwitterion exhibiting an almost planar conformation. The dihedral angles between the mean planes of the pyridoxal ring and the six‐ and five‐membered chelate rings are all less than 2.0°. The charge on the complex cation is neutralized by two nitrate counter‐ions. Extensive N—H...O and C—H...O hydrogen bonding connects these ionic species and leads to the formation of layers. The pyridoxal hydroxy groups are the only fragments that deviate significantly from the flat layer structure; these groups are involved in O—H...O hydrogen bonding, connecting the layers into a three‐dimensional crystal structure.     

Hydro­gen bonding in substituted nitro­anilines: isolated nets in 1,3‐­diamino‐4‐nitrobenzene and continuously interwoven nets in 3,5‐­dinitro­aniline

Molecules of 1,3‐diamino‐4‐nitrobenzene, C₆H₇N₃O₂, are linked by N—H?O hydrogen bonds [N?O 2.964 (2) and 3.021 (2) Å; N—H?O 155 and 149°] into (4,4) nets. In 3,5‐di­nitro­aniline, C₆H₅N₃O₄, where Z′ = 2, the mol­ecules are linked by three N—H?O hydrogen bonds [N?O 3.344 (2)–3.433 (2) Å and N—H?O 150–167°] into deeply puckered nets, each of which is interwoven with its two immediate neighbours.     

2‐Amino‐5‐nitro­thia­zole monoethanol solvate: triply‐interwoven hydrogen‐bonded sheets containing centrosymmetric R(8) and R(38) rings

2‐Amino‐5‐nitro­thia­zole crystallizes from solution in ethanol as a monosolvate, C₃H₃N₃O₂S·C₂H₆O, in which the thia­zole component has a strongly polarized molecular–electronic structure. The thia­zole mol­ecules are linked into centrosymmetric dimers by paired N—H⋯N hydrogen bonds [H⋯N = 2.09 Å, N⋯N = 2.960 (6) Å and N—H⋯N = 169°], and these dimers are linked by the ethanol mol­ecules, via a two‐centred N—H⋯O hydrogen bond [H⋯O = 1.98 Å, N⋯O = 2.838 (5) Å and N—H⋯O = 164°] and a planar asymmetric three‐centred O—H⋯(O)₂ hydrogen bond [H⋯O = 2.07 and 2.53 Å, O⋯O = 2.900 (5) and 3.188 (5) Å, O—H⋯O = 169 and 136°, and O⋯H⋯O = 55°], into sheets built from alternating (8) and (38) rings. These sheets are triply interwoven.     

6‐Amino‐3‐methyl‐5‐nitro­so­pyrimi­dine‐2,4(1H,3H)‐dione forms a three‐dimensional hydrogen‐bonded framework structure

Molecules of the title compound, C₅H₆N₄O₃, are linked into a single three‐dimensional framework by a two‐centre N—H⃛O hydrogen bond [H⃛O = 1.92 Å, N⃛O = 2.785 (2) Å and N—H⃛O = 168°], a two‐centre N—H⃛H hydrogen bond [H⃛N = 2.19 Å, N⃛N = 3.017 (2) Å and N—H⃛N = 157°] and the intermolecular component of an effectively planar three‐centre N—H⃛(O)₂ hydrogen bond [H⃛O = 2.03 and 2.31 Å, N⃛O = 2.645 (2) and 2.957 (2) Å, N—H⃛O = 126 and 130°, and O⃛H⃛O = 101°].     

The inner‐salt zwitterion,the dihydrochloride dihydrate and the dimethyl sulfoxide disolvate of 3,6‐bis(pyridin‐2‐yl)pyrazine‐2,5‐dicarboxylic acid

In the inner‐salt zwitterion of 3,6‐bis(pyridin‐2‐yl)pyrazine‐2,5‐dicarboxylic acid, (I), namely 5‐carboxy‐3‐(pyridin‐1‐ium‐2‐yl)‐6‐(pyridin‐2‐yl)pyrazine‐2‐carboxylate, [C₁₆H₁₀N₄O₄, (Ia)], the pyrazine ring has a twist–boat conformation. The opposing pyridine and pyridinium rings are almost perpendicular to one another, with a dihedral angle of 80.24 (18)°, and are inclined to the pyrazine mean plane by 36.83 (17) and 43.74 (17)°, respectively. The carboxy and carboxylate groups are inclined to the mean plane of the pyrazine ring by 43.60 (17) and 45.46 (17)°, respectively. In the crystal structure, the molecules are linked via N—H...O and O—H...O hydrogen bonds, leading to the formation of double‐stranded chains propagating in the [010] direction. On treating (Ia) with aqueous 1 M HCl, the diprotonated dihydrate form 2,2′‐(3,6‐dicarboxypyrazine‐2,5‐diyl)bis(pyridin‐1‐ium) dichloride dihydrate [C₁₆H₁₂N₄O₄²⁺·2Cl⁻·2H₂O, (Ib)] was obtained. The cation lies about an inversion centre. The pyridinium rings and carboxy groups are inclined to the planar pyrazine ring by 55.53 (9) and 19.8 (2)°, respectively. In the crystal structure, the molecules are involved in N—H...Cl, O—H...O_water and O_water—H...Cl hydrogen bonds, leading to the formation of chains propagating in the [010] direction. When (Ia) was recrystallized from dimethyl sulfoxide (DMSO), the DMSO disolvate 3,6‐bis(pyridin‐2‐yl)pyrazine‐2,5‐dicarboxylic acid dimethyl sulfoxide disolvate [C₁₆H₁₀N₄O₄·2C₂H₆OS, (Ic)] of (I) was obtained. Here, the molecule of (I) lies about an inversion centre and the pyridine rings are inclined to the planar pyrazine ring by only 23.59 (12)°. However, the carboxy groups are inclined to the pyrazine ring by 69.0 (3)°. In the crystal structure, the carboxy groups are linked to the DMSO molecules by O—H...O hydrogen bonds. In all three crystal structures, the presence of nonclassical hydrogen bonds gives rise to the formation of three‐dimensional supramolecular architectures.     

4‐(4‐Fluoro‐3‐phenoxy­phen­yl)‐6‐(4‐fluoro­phen­yl)‐2‐oxo‐1,2‐dihydro­pyridine‐3‐carbonitrile and the 6‐(4‐methyl­phen­yl)‐ analogue

The crystal structures of the title compounds, viz. C₂₄H₁₄F₂N₂O₂, (I), and C₂₅H₁₇FN₂O₂, (II), respectively, have been determined in order to unravel the role of an ordered F atom in generating stable supra­molecular assemblies. On changing the substitution from fluorine to a methyl group, C—H⋯F inter­actions are replaced by C—H⋯π inter­actions, revealing the importance of such weak inter­actions when present alongside N—H⋯O and C—H⋯O hydrogen bonds. The dihedral angle between the planes of the 4‐fluoro­phenyl ring and the pyridine ring is 26.8 (1)° in (I), while that between the planes of the 4‐methyl­phenyl and pyridine rings is 29.5 (1)° in (II).     

Three N2‐benzoyl­oxybenz­amidines: sheet structures built from hard and soft hydrogen bonds and aromatic π–π stacking interactions

Molecules of the title compounds N²‐(benzoyl­oxy)­benz­ami­dine, C₁₄H₁₂N₂O₂, (I), N²‐(2‐hydroxy­benzoyl­oxy)­benz­ami­dine, C₁₄H₁₂N₂O₃, (II), and N²‐benzoyloxy‐2‐hydroxybenzamidine, C₁₄H₁₂N₂O₃, (III), all have extended chain conformations, with the aryl groups remote from one another. In (I), the mol­ecules are linked into chains by a single N—H⋯N hydrogen bond [H⋯N = 2.15 Å, N⋯N = 3.029 (2) Å and N—H⋯N = 153°] and these chains are linked into sheets by means of aromatic π–π stacking interactions. There is one intramolecular O—H⋯O hydrogen bond in (II), and a combination of one three‐centre N—H⋯(N,O) hydrogen bond [H⋯N = 2.46 Å, H⋯O = 2.31 Å, N⋯N = 3.190 (2) Å, N⋯O = 3.146 (2) Å, N—H⋯N = 138° and N—H⋯O = 154°] and one two‐centre C—H⋯O hydrogen bond [H⋯O = 2.46 Å, C⋯O = 3.405 (2) Å and C—H⋯O = 173°] links the mol­ecules into sheets. In (III), an intramolecular O—H⋯N hydrogen bond and two N—H⋯O hydrogen bonds [H⋯O = 2.26 and 2.10 Å, N⋯O = 2.975 (2) and 2.954 (2) Å, and N—H⋯O = 138 and 163°] link the molecules into sheets.     

1‐(1H‐Indol‐3‐ylcarbonyl)‐N‐(4‐methoxy­benzyl)formamide

In the title compound, C₁₈H₁₆N₂O₃, the indole ring is planar and the two adjacent carbonyl groups are mutually trans oriented with a torsion angle of 144.8 (3)°. The single C—C bond linking the two carbonyl functionalities is 1.539 (4) Å. Mol­ecules are linked into a two‐dimensional network by inter­molecular N—H⋯O hydrogen bonds.     

N,N′‐Diethyl‐4‐nitrobenzene‐1,3‐diamine, 2,6‐bis(ethylamino)‐3‐nitrobenzonitrile and bis(4‐ethylamino‐3‐nitrophenyl) sulfone

N,N′‐Diethyl‐4‐nitrobenzene‐1,3‐diamine, C₁₀H₁₅N₃O₂, (I), crystallizes with two independent molecules in the asymmetric unit, both of which are nearly planar. The molecules differ in the conformation of the ethylamine group trans to the nitro group. Both molecules contain intramolecular N—H...O hydrogen bonds between the adjacent amine and nitro groups and are linked into one‐dimensional chains by intermolecular N—H...O hydrogen bonds. The chains are organized in layers parallel to (101) with separations of ca 3.4 Å between adjacent sheets. The packing is quite different from what was observed in isomeric 1,3‐bis(ethylamino)‐2‐nitrobenzene. 2,6‐Bis(ethylamino)‐3‐nitrobenzonitrile, C₁₁H₁₄N₄O₂, (II), differs from (I) only in the presence of the nitrile functionality between the two ethylamine groups. Compound (II) crystallizes with one unique molecule in the asymmetric unit. In contrast with (I), one of the ethylamine groups, which is disordered over two sites with occupancies of 0.75 and 0.25, is positioned so that the methyl group is directed out of the plane of the ring by approximately 85°. This ethylamine group forms an intramolecular N—H...O hydrogen bond with the adjacent nitro group. The packing in (II) is very different from that in (I). Molecules of (II) are linked by both intermolecular amine–nitro N—H...O and amine–nitrile N—H...N hydrogen bonds into a two‐dimensional network in the (10) plane. Alternating molecules are approximately orthogonal to one another, indicating that π–π interactions are not a significant factor in the packing. Bis(4‐ethylamino‐3‐nitrophenyl) sulfone, C₁₆H₁₈N₄O₆S, (III), contains the same ortho nitro/ethylamine pairing as in (I), with the position para to the nitro group occupied by the sulfone instead of a second ethylamine group. Each 4‐ethylamino‐3‐nitrobenzene moiety is nearly planar and contains the typical intramolecular N—H...O hydrogen bond. Due to the tetrahedral geometry about the S atom, the molecules of (III) adopt an overall V shape. There are no intermolecular amine–nitro hydrogen bonds. Rather, each amine H atom has a long (H...O ca 2.8 Å) interaction with one of the sulfone O atoms. Molecules of (III) are thus linked by amine–sulfone N—H...O hydrogen bonds into zigzag double chains running along [001]. Taken together, these structures demonstrate that small changes in the functionalization of ethylamine–nitroarenes cause significant differences in the intermolecular interactions and packing.     

1‐Methyl‐4‐nitraminopyridinium nitrate and 4‐nitraminopyridinium methanesulfonate

In the title compounds, C₆H₈N₃O₂⁺·NO₃^? and C₅­H₆­N₃­O₂⁺·­CH₃SO₃^?, respectively, the cations are almost planar; the twist of the nitr­amino group about the C—N and N—N bonds does not exceed 10°. The deviations from coplanarity are accounted for by intermolecular N—H?O interactions. The coplanarity of the NHNO₂ group and the phenyl ring leads to the deformation of the nitr­amino group. The C—N—N angle and one C—C—N angle at the junction of the phenyl ring and the nitr­amino group are increased from 120° by ca 6°, whereas the other junction C—C—N angle is decreased by ca 5°. Within the nitro group, the O—N—O angle is increased by ca 5° and one O—N—N angle is decreased by ca 5°, whereas the other O—N—N angle remains almost unchanged. The cations are connected to the anions by relatively strong N—H?O hydrogen bonds [shortest H?O separations 1.77 (2)–1.81 (3) Å] and much weaker C—H?O hydrogen bonds [H?O separations 2.30 (2)–2.63 (3) Å].     

Hydrogen bonding in 2‐amino‐4,6‐dimethoxypyrimidine, 2‐benzylamino‐4,6‐bis(benzyloxy)pyrimidine and 2‐amino‐4,6‐bis(N‐pyrrolidino)pyrimidine: chains of fused rings and a centrosymmetric dimer

Molecules of 2‐amino‐4,6‐di­methoxy­pyrimidine, C₆H₉N₃O₂, (I), are linked by two N—H?N hydrogen bonds [H?N 2.23 and 2.50 Å, N?N 3.106 (2) and 3.261 (2) Å, and N—H?N 171 and 145°] into a chain of fused rings, where alternate rings are generated by centres of inversion and twofold rotation axes. Adjacent chains are linked by aromatic π–π‐stacking interactions to form a three‐dimensional framework. In 2‐­benzylamino‐4,6‐bis(benzyloxy)pyrimidine, C₂₅H₂₃N₃O₂, (II), the mol­ecules are linked into centrosymmetric R(8) dimers by paired N—H?N hydrogen bonds [H?N 2.13 Å, N?N 2.997 (2) Å and N—H?N 170°]. Molecules of 2‐amino‐4,6‐bis(N‐pyrrolidino)­pyrimidine, C₁₂H₁₉N₅, (III), are linked by two N—H?N hydrogen bonds [H?N 2.34 and 2.38 Å, N?N 3.186 (2) and 3.254 (2) Å, and N—H?N 163 and 170°] into a chain of fused rings similar to that in (I).     

(2S)‐1‐Carbamoylpyrrolidine‐2‐carboxylic acid

In the title compound, also known as N‐carbamoyl‐l ‐proline, C₆H₁₀N₂O₃, the pyrrolidine ring adopts a half‐chair conformation, whereas the carboxyl group and the mean plane of the ureide group form an angle of 80.1 (2)°. Molecules are joined by N—H...O and O—H...O hydrogen bonds into cyclic structures with graph‐set R²₂(8), forming chains in the b‐axis direction that are further connected via N—H...O hydrogen bonds into a three‐dimensional network.     

Methyl 4‐amino‐2,3‐dihydro‐6‐methoxy‐1,3‐dioxo‐1H‐pyrrolo[3,4‐c]pyridine‐7‐carboxylate forms hydrogen‐bonded sheets built from R22(8) and R66(42) rings

In the title compound, C₁₀H₉N₃O₅, which was formed by the reaction of 6‐amino‐2‐methoxy‐4(3H)‐pyrimidinone with di­methyl acetyl­enedi­carboxyl­ate, the mol­ecules are linked by N—H?O hydrogen bonds [N?O 2.8974 (15) and 3.0300 (15) Å, and N—H?O 165 and 174°] into planar sheets built from alternating R₂²(8) and R₆⁶(42) rings.     

π‐Stacked hydrogen‐bonded dimers in 2‐(2‐nitro­phenyl­amino­carbonyl)­benzoic acid,and hydrogen‐bonded sheets in orthorhombic and monoclinic polymorphs of 2‐(4‐nitro­phenyl­amino­carbonyl)­benzoic acid

Molecules of 2‐(2‐nitrophenylaminocarbonyl)benzoic acid, C₁₄H₁₀N₂O₅, are linked into centrosymmetric R(8) dimers by a single O—H⋯O hydrogen bond [H⋯O = 1.78 Å, O⋯O = 2.623 (2) Å and O—H⋯O = 178°] and these dimers are linked into sheets by a single aromatic π–π stacking interaction. The isomeric compound 2‐(4‐nitrophenylaminocarbonyl)benzoic acid crystallizes in two polymorphic forms. In the orthorhombic form (space group P2₁2₁2₁ with Z′ = 1, crystallized from ethanol), the mol­ecules are linked into sheets of R(22) rings by a combination of one N—H⋯O hydrogen bond [H⋯O = 1.96 Å, N⋯O = 2.833 (3) Å and N—H⋯O = 171°] and one O—H⋯O hydrogen bond [H⋯O = 1.78 Å, O⋯O = 2.614 (3) Å and O—H⋯O = 173°]. In the monoclinic form (space group P2₁/n with Z′ = 2, crystallized from acetone), the mol­ecules are linked by a combination of two N—H⋯O hydrogen bonds [H⋯O = 2.09 and 2.16 Å, N⋯O = 2.873 (4) and 2.902 (3) Å, and N—H⋯O = 147 and 141°] and two O—H⋯O hydrogen bonds [H⋯O = 1.84 and 1.83 Å, O⋯O = 2.664 (3) and 2.666 (3) Å, and O—H⋯O = 166 and 174°] into sheets of some complexity. These sheets are linked into a three‐dimensional framework by a single C—H⋯O hydrogen bond [H⋯O = 2.45 Å, C⋯O = 3.355 (4) Å and C—­H⋯O = 160°].