Six closely related 4,6‐disubstituted 2‐amino‐5‐formylpyrimidines: different ring conformations,polarized electronic structures,and hydrogen‐bonded assembly in zero,one, two and three dimensions

In each of ethyl N‐{2‐amino‐5‐formyl‐6‐[methyl(phenyl)amino]pyrimidin‐4‐yl}glycinate, C₁₆H₁₉N₅O₃, (I), N‐{2‐amino‐5‐formyl‐6‐[methyl(phenyl)amino]pyrimidin‐4‐yl}glycinamide, C₁₄H₁₆N₆O₂, (II), and ethyl 3‐amino‐N‐{2‐amino‐5‐formyl‐6‐[methyl(phenyl)amino]pyrimidin‐4‐yl}propionate, C₁₇H₂₁N₅O₃, (III), the pyrimidine ring is effectively planar, but in each of methyl N‐{2‐amino‐6‐[benzyl(methyl)amino]‐5‐formylpyrimidin‐4‐yl}glycinate, C₁₆H₁₉N₅O₃, (IV), ethyl 3‐amino‐N‐{2‐amino‐6‐[benzyl(methyl)amino]‐5‐formylpyrimidin‐4‐yl}propionate, C₁₈H₂₃N₅O₃, (V), and ethyl 3‐amino‐N‐[2‐amino‐5‐formyl‐6‐(piperidin‐4‐yl)pyrimidin‐4‐yl]propionate, C₁₅H₂₃N₅O₃, (VI), the pyrimidine ring is folded into a boat conformation. The bond lengths in each of (I)–(VI) provide evidence for significant polarization of the electronic structure. The molecules of (I) are linked by paired N—H...N hydrogen bonds to form isolated dimeric aggregates, and those of (III) are linked by a combination of N—H...N and N—H...O hydrogen bonds into a chain of edge‐fused rings. In the structure of (IV), molecules are linked into sheets by means of two hydrogen bonds, both of N—H...O type, in the structure of (V) by three hydrogen bonds, two of N—H...N type and one of C—H...O type, and in the structure of (VI) by four hydrogen bonds, all of N—H...O type. Molecules of (II) are linked into a three‐dimensional framework structure by a combination of three N—H...O hydrogen bonds and one C—H...O hydrogen bond.     

(E)‐4‐[(2‐Carbamoylhydrazinylidene)methyl]‐3‐hydroxy‐5‐hydroxymethyl‐2‐methylpyridin‐1‐ium nitrate

The title compound, C₉H₁₃N₄O₃⁺·NO₃⁻, is the first structurally characterized Schiff base derived from semicarbazide and pyridoxal. Unusually for an unsubstituted semicarbazone, the compound adopts a syn conformation, in which the carbonyl O atom is in a cis disposition relative to the azomethine N atom. This arrangement is supported by a pair of hydrogen bonds between the organic cation and the nitrate anion. The cation is essentially planar, with only a hydroxymethyl O atom deviating significantly from the mean plane of the remaining atoms (r.m.s. deviation of the remaining non‐H atoms = 0.01 Å). The molecules are linked into flat layers by N—H...O and C—H...O hydrogen bonds. O—H...O hydrogen bonds involving the hydroxymethyl group as a donor interconnect the layers into a three‐dimensional structure.     

A toyocamycin analogue with the sugar moiety in a syn conformation

The title compound [systematic name: 4‐amino‐5‐cyano‐1‐(β‐d ‐ribofuranosyl)‐7H‐pyrrolo[2,3‐d]pyrimidine hemihydrate], C₁₂H₁₃N₅O₄·0.5H₂O, is a regioisomer of toyocamycin with the ribofuranosyl residue attached to the pyrimidine moiety of the heterocycle. This analogue exhibits a syn glycosylic bond conformation with a χ torsion angle of 57.51 (17)°. The ribofuranose moiety shows an envelope C2′‐endo (²E) sugar conformation (S‐type), with P = 161.6 (2)° and τ_m = 41.3 (1)°. The conformation at the exocyclic C4′—C5′ bond is +sc (gauche, gauche), with a γ torsion angle of 54.4 (2)°. The crystal packing is stabilized by intermolecular O—H...O, N—H...N and O—H...N hydrogen bonds; water molecules, located on crystallographic twofold axes, participate in interactions. An intramolecular O—H...N hydrogen bond stabilizes the syn conformation of the nucleoside.     

An unusual conformation of gabapentin (Gpn) in Pyr‐Gpn‐NH‐NH‐Pyr stabilized by weak interactions

The crystal structure of N‐[(1‐{2‐oxo‐2‐[2‐(pyrazin‐2‐ylcarbonyl)hydrazin‐1‐yl]ethyl}cyclohexyl)methyl]pyrazine‐2‐carboxamide monohydrate (Pyr‐Gpn‐NN‐NH‐Pyr·H₂O), C₁₉H₂₃N₇O₃·H₂O, reveals an unusual trans–gauche (tg⁻) conformation for the gabapentin (Gpn) residue around the C^γ—C^β (θ₁) and C^β—C^α (θ₂) bonds. The molecular conformation is stabilized by intramolecular N—H...N hydrogen bonds and weak C—H...O interactions. The packing of the molecules in the crystal lattice shows a network of strong N—H...O and O—H...O hydrogen bonds together with weak C—H...O and π–π inteactions.     

7‐Amino‐1‐(2‐deoxy‐β‐erythro‐pentofuranosyl)‐1H‐1,2,3‐triazolo[4,5‐d]pyrimidine: an 8‐azaadenine nucleoside with the nucleobase in a syn conformation

The title compound, C₉H₁₂N₆O₃, shows a syn‐glycosylic bond orientation [χ = 64.17 (16)°]. The 2′‐deoxyfuranosyl moiety exhibits an unusual C1′‐exo–O4′‐endo (₁T⁰; S‐type) sugar pucker, with P = 111.5 (1)° and τ_m = 40.3 (1)°. The conformation at the exocyclic C4′—C5′ bond is +sc (gauche), with γ = 64.4 (1)°. The two‐dimensional hydrogen‐bonded network is built from intermolecular N—H...O and O—H...N hydrogen bonds. An intramolecular bifurcated hydrogen bond, with an amino N—H group as hydrogen‐bond donor and the ring and hydroxymethyl O atoms of the sugar moiety as acceptors, constrains the overall conformation of the nucleoside.     

Conformation of cationic N,N‐di­methyl­glycine in di­methyl­glycinium tri­fluoro­acetate

In the title compound, C₄H₁₀NO₂⁺·C₂F₃O₂^?, the main N—C—COOH skeleton of the protonated amino acid is nearly planar. The C=O/C—N and C=O/O—H bonds are syn and the two methyl groups are gauche to the methyl­ene H atoms. The conformation of the cation in the crystal is compared to that given by ab initio calculations (Hartree–Fock, self‐consistent field molecular‐orbital theory). The tri­fluoro­acetate anion has the typical staggered conformation with usual bond distances and angles. The cation and anion form dimers through a strong O—H?O hydrogen bond which are further interconnected in infinite zigzag chains running parallel to the a axis by N—H?O bonds. Weaker C—H?O interactions involving the methyl groups and the carboxy O atoms of the cation occur between the chains.     

Heterocyclic tautomerism: reassignment of two crystal structures of 2‐amino‐1,3‐thiazolidin‐4‐one derivatives

The structures of 5‐(2‐hydroxyethyl)‐2‐[(pyridin‐2‐yl)amino]‐1,3‐thiazolidin‐4‐one, C₁₀H₁₁N₃O₂S, (I), and ethyl 4‐[(4‐oxo‐1,3‐thiazolidin‐2‐yl)amino]benzoate, C₁₂H₁₂N₂O₃S, (II), which are identical to the entries with refcodes GACXOZ [Váňa et al. (2009). J. Heterocycl. Chem. 46 , 635–639] and HEGLUC [Behbehani & Ibrahim (2012). Molecules, 17 , 6362–6385], respectively, in the Cambridge Structural Database [Allen (2002). Acta Cryst. B 58 , 380–388], have been redetermined at 130 K. This structural study shows that both investigated compounds exist in their crystal structures as the tautomer with the carbonyl–imine group in the five‐membered heterocyclic ring and an exocyclic amine N atom, rather than the previously reported tautomer with a secondary amide group and an exocyclic imine N atom. The physicochemical and spectroscopic data of the two investigated compounds are the same as those of GACXOZ and HEGLUC, respectively. In the thiazolidin‐4‐one system of (I), the S and chiral C atoms, along with the hydroxyethyl group, are disordered. The thiazolidin‐4‐one fragment takes up two alternative locations in the crystal structure, which allows the molecule to adopt R and S configurations. The occupancy factors of the disordered atoms are 0.883 (2) (for the R configuration) and 0.117 (2) (for the S configuration). In (I), the main factor that determines the crystal packing is a system of hydrogen bonds, involving both strong N—H...N and O—H...O and weak C—H...O hydrogen bonds, linking the molecules into a three‐dimensional hydrogen‐bond network. On the other hand, in (II), the molecules are linked via N—H...O hydrogen bonds into chains.     

Redetermination of 6‐amino‐5‐formyl‐1,3‐dimethyluracil monohydrate at 120 K: a polarized molecular structure and two interwoven hydrogen‐bonded frameworks

The title compound [systematic name: 6‐amino‐5‐formyl‐1,3‐dimethylpyrimidine‐2,4(1H,3H)‐dione monohydrate], C₇H₉N₃O₃·H₂O, has been reexamined at 120 K. The improved precision of the intramolecular dimensions provides evidence for a polarized molecular–electronic structure, and the molecular components are linked by one N—H...O and two O—H...O hydrogen bonds into two interwoven three‐dimensional frameworks, which are weakly linked by the longer component of a three‐centre N—H...(O)₂ hydrogen bond.     

Three sterically hindered 6‐amino‐5‐cyano‐2‐methyl‐4‐(1‐naphthyl)‐4H‐pyran‐3‐carboxylate derivatives

In the title compounds, 2‐methoxyethyl 6‐amino‐5‐cyano‐2‐methyl‐4‐(1‐naphthyl)‐4H‐pyran‐3‐carboxylate, C₂₁H₂₀N₂O₄, (II), isopropyl 6‐amino‐5‐cyano‐2‐methyl‐4‐(1‐naphthyl)‐4H‐pyran‐3‐carboxylate, C₂₁H₂₀N₂O₃, (III), and ethyl 6‐amino‐5‐cyano‐2‐methyl‐4‐(1‐naphthyl)‐4H‐pyran‐3‐carboxylate, C₂₀H₁₈N₂O₃, (IV), the heterocyclic pyran ring adopts a flattened boat conformation. In (II) and (III), the carbonyl group and a double bond of the heterocyclic ring are mutually anti, but in (IV) they are mutually syn. The ester O atoms in (II) and (III) and the carbonyl O atom in (IV) participate in intramolecular C—H...O contacts to form six‐membered rings. The dihedral angles between the naphthalene substituent and the closest four atoms of the heterocyclic ring are 73.3 (1), 71.0 (1) and 74.3 (1)° for (II)–(IV), respectively. In all three structures, only one H atom of the NH₂ group takes part in N—H...O [in (II) and (III)] or N—H...N [in (IV)] intermolecular hydrogen bonds, and chains [in (II) and (III)] or dimers [in (IV)] are formed. In (II), weak intermolecular C—H...O and C—H...N hydrogen bonds, and in (III) intermolecular C—H...O hydrogen bonds link the chains into ladders along the a axis.     

2‐Amino‐4‐chloro‐5‐formyl‐6‐[methyl(2‐methylphenyl)amino]pyrimidine and 2‐amino‐4‐chloro‐5‐formyl‐6‐[(2‐methoxyphenyl)methylamino]pyrimidine are isostructural and form hydrogen‐bonded sheets of R22(8) and R66(32) rings

2‐Amino‐4‐chloro‐5‐formyl‐6‐[methyl(2‐methylphenyl)amino]pyrimidine, C₁₃H₁₃ClN₄O, (I), and 2‐amino‐4‐chloro‐5‐formyl‐6‐[(2‐methoxyphenyl)methylamino]pyrimidine, C₁₃H₁₃ClN₄O₂, (II), are isostructural and essentially isomorphous. Although the pyrimidine rings in each compound are planar, the ring‐substituent atoms show significant displacements from this plane, and the bond distances provide evidence for polarization of the electronic structures. In each compound, a combination of N—H...N and N—H...O hydrogen bonds links the molecules into sheets built from centrosymmetric R₂²(8) and R₆⁶(32) rings. The significance of this study lies in its observation of the isostructural nature of (I) and (II), and in the comparison of their crystal and molecular structures with those of analogous compounds.     

Self‐assembly of 2‐pivaloyl‐6‐chloro­pterin

In the title compound, N‐(6‐chloro‐4‐oxo‐3,4‐di­hydro­pteridin‐2‐yl)­‐2,2‐di­methyl­propan­amide, C₁₁H₁₂ClN₅O₂, the rings in the pterin moiety are planar. The amide carbonyl O atom is in syn‐periplanar conformation while the C—N—C—C propanamide linkage is antiperiplanar. The N—H?N and N—H?O intermolecular hydrogen bonds transform the mol­ecules into infinite chains.     

Solid‐state tautomeric structure and invariom refinement of a novel and potent HIV integrase inhibitor

The conformation and tautomeric structure of (Z)‐4‐[5‐(2,6‐difluorobenzyl)‐1‐(2‐fluorobenzyl)‐2‐oxo‐1,2‐dihydropyridin‐3‐yl]‐4‐hydroxy‐2‐oxo‐N‐(2‐oxopyrrolidin‐1‐yl)but‐3‐enamide, C₂₇H₂₂F₃N₃O₅, in the solid state has been resolved by single‐crystal X‐ray crystallography. The electron distribution in the molecule was evaluated by refinements with invarioms, aspherical scattering factors by the method of Dittrich et al. [Acta Cryst. (2005), A 61 , 314–320] that are based on the Hansen–Coppens multipole model [Hansen & Coppens (1978). Acta Cryst. A 34 , 909–921]. The β‐diketo portion of the molecule exists in the enol form. The enol –OH hydrogen forms a strong asymmetric hydrogen bond with the carbonyl O atom on the β‐C atom of the chain. Weak intramolecular hydrogen bonds exist between the weakly acidic α‐CH hydrogen of the keto–enol group and the pyridinone carbonyl O atom, and also between the hydrazine N—H group and the carbonyl group in the β‐position from the hydrazine N—H group. The electrostatic properties of the molecule were derived from the molecular charge density. The molecule is in a lengthened conformation and the rings of the two benzyl groups are nearly orthogonal. Results from a high‐field ¹H and ¹³C NMR correlation spectroscopy study confirm that the same tautomer exists in solution as in the solid state.     

Aripiprazole salts. III. Bis(aripiprazolium) oxalate–oxalic acid (1/1)

The asymmetric unit of the title salt [systematic name: bis(4‐(2,3‐dichlorophenyl)‐1‐{4‐[(2‐oxo‐1,2,3,4‐tetrahydroquinolin‐7‐yl)oxy]butyl}piperazin‐1‐ium) oxalate–oxalic acid (1/1)], 2C₂₃H₂₈Cl₂N₃O₂⁺·C₂O₄²⁻·C₂H₂O₄, consists of one protonated aripiprazole unit (HArip⁺), half an oxalate dianion and half an oxalic acid molecule, the latter two lying on inversion centres. The conformation of the HArip⁺ cation differs from that in other reported salts and resembles more the conformation of neutral Arip units in reported polymorphs and solvates. The intermolecular interaction linking HArip⁺ cations is also similar to those in reported Arip compounds crystallizing in the space group P, with head‐to‐head N—H...O hydrogen bonds generating centrosymmetric dimers, which are further organized into planar ribbons parallel to (01). The oxalate anions and oxalic acid molecules form hydrogen‐bonded chains running along [010], which `pierce' the planar ribbons, interacting with them through a number of stronger N—H...O and weaker C—H...O hydrogen bonds, forming a three‐dimensional network.     

2′‐Deoxyimmunosine: a thiazolo[4,5‐d]pyrimidine nucleoside adopting the syn conformation

The title compound [systematic name: 5‐amino‐3‐(2‐deoxy‐β‐d ‐erythro‐pentofuranosyl)thiazolo[4,5‐d]pyrimidine‐2,7‐(3H,6H)‐dione], C₁₀H₁₂N₄O₅S, exhibits a syn glycosylic bond conformation, with a torsion angle χ of 61.0 (3)°. The furanose moiety adopts the N‐type sugar pucker (³T₄), with P = 33.0 (5)° and τ_m = 15.1 (1)°. The conformation at the exocyclic C4′—C5′ bond is +ap (trans), with the torsion angle γ = 176.71 (14)°. The extended structure is a three‐dimensional hydrogen‐bond network involving O—H...O and N—H...O hydrogen bonds.     

N,N′‐Bis(2‐hydroxybenzylidene)pentane‐1,5‐diamine

In the title potential O,N,N′,O′‐tetradentate Schiff base ligand {systematic name: 2,2′‐[pentane‐1,5‐diylbis(nitrilomethylidyne)]diphenol}, C₁₉H₂₂N₂O₂, the mutual orientation of the three planar fragments determines the conformation of the molecule. The dihedral angles between the planes of the two salicylidene groups and the plane of the central extended pentane chain are 78.4 (2) and 62.0 (3)°, and the angle between the terminal ring planes is 55.4 (1)°. Strong intramolecular O—H...N hydrogen bonds close almost‐planar six‐membered rings, and the O—H bonds are elongated as a result of hydrogen‐bond formation.     

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.     

Nonmerohedrally twinned 6‐amino‐3‐methyluracil‐5‐carbaldehyde: a hydrogen‐bonded ribbon containing four types of ring

In the title compound [systematic name: 6‐amino‐5‐formyl‐3‐methylpyrimidine‐2,4(1H,3H)‐dione], C₆H₇N₃O₃, the intramolecular dimensions provide evidence for some polarization of the electronic structure. There is an intramolecular N—H...O hydrogen bond; this and a combination of three intermolecular N—H...O hydrogen bonds generate an almost planar ribbon containing S(6), R₂²(4), R₂¹(6) and R₄⁴(16) rings. These ribbons are linked into sheets by a dipolar carbonyl–carbonyl interaction. The structure was refined as a nonmerohedral twin, with twin fractions 0.7924 (1) and 0.2076 (10).     

Two 1,4‐dihydropyridine derivatives with potential calcium‐channel antagonist activity

The title compounds, benzyl 4‐(3‐chloro‐2‐fluorophenyl)‐2‐methyl‐5‐oxo‐4,5,6,7‐tetrahydro‐1H‐cyclopenta[b]pyridine‐3‐carboxylate, C₂₃H₁₉ClFNO₃, (I), and 3‐pyridylmethyl 4‐[2‐fluoro‐3‐(trifluoromethyl)phenyl]‐2,6,6‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate, C₂₆H₂₄F₄N₂O₃, (II), belong to a class of 1,4‐dihydropyridines whose members sometimes display calcium modulatory properties. The 1,4‐dihydropyridine ring in each structure has a shallower than usual shallow‐boat conformation and is nearly planar in (I). In each structure, the halogen‐substituted benzene ring is oriented such that the halogen substituents are in a synperiplanar orientation with respect to the 1,4‐dihydropyridine ring plane. The oxocyclopentene ring in (I) is planar, while the oxocyclohexene ring in (II) has a half‐chair conformation, which is less commonly observed than the envelope conformation usually found in related compounds. In (I), the frequently observed intermolecular N—H...O hydrogen bond between the amine group and the carbonyl O atom of the oxocyclopentene ring of a neighbouring molecule links the molecules into extended chains; there are no other significant intermolecular interactions. By contrast, the amine group in (II) forms an N—H...N hydrogen bond with the pyridine ring N atom of a neighbouring molecule. Additional C—H...O interactions complete a two‐dimensional hydrogen‐bonded network. The halogen‐substituted benzene ring has a weak intramolecular π–π interaction with the pyridine ring. A stronger π–π interaction occurs between the 1,4‐dihydropyridine rings of centrosymmetrically related molecules.     

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.