Green chemistry is a rapidly developing new field that provides us with a proactive avenue for the sustainable development of future science and technologies. Green chemistry uses highly efficient and environmentally benign synthetic protocols to deliver lifesaving medicines, accelerating lead optimization processes in drug discovery, with reduced unnecessary environmental impact. From this view point, it is desirable to use water instead of organic solvents as a reaction medium, since water is safe, abundant and an environmentally benign solvent.
A convenient one-pot method for the efficient synthesis of the novel Zwitterion derivatives 4a-pvia a three-component condensation reaction of barbituric acid derivatives 1a,b, dimedone 2, and various aldehydes 3 in the presence of aqueous diethylamine media is described. This new approach is environmentally benign, with clean synthetic procedure, short reaction times and easy work-up procedure which proceeded smoothly to provide excellent yield (88-98%). The synthesized products were characterized by elemental analysis, IR, MS, NMR and CHN analysis. The structure of 4a was further confirmed by single crystal X-ray diffraction. The compound crystallizes in the orthorhombic space group Pbca with α = 14.6669 (5) Å, b = 18.3084 (6) Å, c = 19.0294 (6) Å, α = 90°, β = 90°, = 90°, V = 5109.9 (3) Å3, and Z = 8. The molecules are packed in crystal structure by weak intermolecular C–H⋅ ⋅ ⋅O hydrogen bonding interactions.
An environmentally benign Aldol-Michael protocol for the synthesis of dimedone-barbituric derivatives using aqueous diethylamine medium is achieved.
Tandem Aldol-Michael reactions; MCRs; Barbituric acid; Aqueous media; Green chemistry; Dimedone; Zwitterions
The molecule of the title hydrazine derivative, C15H14N4O6, is essentially planar, the dihedral angle between the substituted benzene rings being 2.25 (9)°. The ethoxy and hydroxy groups are almost coplanar with their bound benzene ring [r.m.s. deviation = 0.0153 (2) Å for the ten non-H atoms]. Intramolecular N—H⋯O and O—H⋯Oethoxy hydrogen bonds generate S(6) and S(5) ring motifs, respectively. In the crystal, molecules are linked by O—H⋯Onitro hydrogen bonds into chains propagating in . Weak aromatic π–π interactions, with centroid–centroid distances of 3.8192 (19) and 4.0491 (19) Å, are also observed.
There are two independent molecules in the asymmetric unit of the title compound, C16H17NO4, with similar conformations but some differences in their bond angles. Each molecule adopts a trans configuration with respect to the methylidene C=N bond and is twisted with a dihedral angle between the two substituted benzene rings of 80.52 (7)° in one molecule and 83.53 (7)° in the other. All methoxy groups are approximately coplanar with the attached benzene rings, with Cmethyl—O—C—C torsion angles ranging from −6.7 (2) to 5.07 (19)°. In the crystal, independent molecules are linked together by O—H⋯N and O—H⋯O hydrogen bonds and a π–π interaction [centroid–centroid distance of 3.6030 (9) Å], forming a dimer. The dimers are further linked by weak C—H⋯O interactions and another π–π interaction [centroid–centroid distance of 3.9452 (9) Å] into layers lying parallel to the ab plane.
In the title compound, C26H37N5OS, the piperazine ring adopts a chair conformation. The triazole ring forms dihedral angles of 67.85 (9) and 59.41 (9)° with the piperazine and benzene rings, respectively, resulting in an approximate V-shaped conformation for the molecule. An intramolecular C—H⋯O hydrogen bond generates an S(6) ring motif. The crystal structure features C—H⋯π interactions, producing a two-dimensional supramolecular architecture.
In the structure of the title salt, C20H20NO+·C6H4FO3S−, the 4-(ethoxyphenyl)ethenyl unit is disordered over two positions with a refined site-occupancy ratio of 0.610 (6):0.390 (6). The cation is nearly planar, the dihedral angle between the quinolinium and benzene rings being 6.7 (4) and 1.7 (7)° for the major and minor components, respectively. The ethoxy group is essentially coplanar with the benzene ring [C—O—C—Cmethy = 177.1 (8) and 177.8 (12)° for the major and minor components, respectively]. In the crystal, cations and anions are linked into chains along the b-axis direction by C—H⋯Osulfonyl weak interactions. These chains are further connected into sheets parallel to (001) by C—H⋯Osulfonyl weak interactions. The chains are also stacked along the a axis through π–π interactions involving the quinolinium and benzene rings [centroid–centroid distances = 3.636 (5) Å for the major component and 3.800 (9) Å for the minor component]. C—H⋯π interactions are also present.
A simple protocol, involving the green synthesis for the construction of novel bis-pyrimidine derivatives, 3a–i and 4a–e are accomplished by the aqueous diethylamine media promoted tandem Aldol-Michael reaction between two molecules of barbituric acid derivatives 1a,b with various aldehydes. This efficient synthetic protocol using an economic and environmentally friendly reaction media with versatility and shorter reaction time provides bis-pyrimidine derivatives with high yields (88%–99%).
tandem Aldol-Michael reactions; MCRs; barbituric acid; aqueous media; green chemistry
The title salt crystallized as the monohydrate C15H16NO2
−·H2O. The cation exists in an E conformation with respect to the ethynyl bond and is essentially planar, with a dihedral angle of 6.52 (14)° between the pyridinium and the benzene rings. The hydroxy and methoxy substituents are coplanar with the benzene ring to which they are attached, with an r.m.s. deviation of 0.0116 (3) Å for the nine non-H atoms [Cmethyl—O—C—C torsion angle = −0.8 (4)°]. In the crystal, the cations and anions are stacked by π–π interactions, with centroid–centroid distances of 3.7818 (19) and 3.9004 (17) Å. The cations, anions and water molecules are linked by O—H⋯O hydrogen bonds and weak C—H⋯O interactions, forming a three-dimensional network.
In the title compound, C26H37N5S, the piperazine ring adopts a chair conformation with the exocyclic N—C bonds in pseudo-equatorial orientations. The piperazine ring (all atoms) subtends dihedral angles of 79.47 (9) and 73.07 (9)° with the triazole and benzene rings, respectively, resulting in an approximate U-shape for the molecule. No significant intermolecular interactions are observed in the crystal.
In the title compound, C20H26N2S, the N-containing six-membered ring adopts a boat conformation and the dihedral angle between the thiocarbamide group and the benzene ring is 49.67 (9)°. An intramolecular C—H⋯S hydrogen bond generates an S(6) ring motif. The N—H group is sterically hindered and there are no significant intermolecular interactions beyond van der Waals contacts.
In the structure of the title nicotinonitrile derivative, C19H15N3O, the pyridine ring makes dihedral angles of 11.50 (7) and 43.36 (8)° with the 4-aminophenyl and phenyl rings, respectively, and the dihedral angle between the phenyl rings is 36.28°. In the crystal, molecules are linked by N—H⋯N hydrogen bonds into wave-like sheets parallel to (10-2). These sheets are stacked by π–π interactions between the 4-aminophenyl rings of adjacent sheets, with centroid–centroid distances of 3.7499 (9) Å. C—H⋯π interactions are also present.
In the title mixed salt, 2C16H15N2
−, one of the cations shows whole molecule disorder over two sets of sites in a 0.711 (7):0.289 (7) ratio. The 4-chorobenzenesulfonate anion is also disordered over two orientations in a 0.503 (6):0.497 (6) ratio. The cations are close to planar, the dihedral angles between the pyridinium and indole rings being 1.48 (3)° in the ordered cation, and 5.62 (3) and 2.45 (3)°, respectively, for the major and minor components of the disordered cation. In the crystal, the cations are stacked in an antiparallel manner approximately along the a-axis direction and linked with the anions via N—H⋯O hydrogen bonds and C—H⋯O interactions, generating a three-dimensional network. Weak C—H⋯π and π–π interactions [with centroid–centroid distances of 3.561 (2)–3.969 (7) Å] are also observed.
The title compound, C15H15NO4S, was obtained by the condensation of 4-aminoacetophenone and 4-methoxybenzenesulfonyl chloride. The dihedral angle between the benzene rings is 86.56 (9)° and the molecule has an approximate V-shaped conformation. The C atom of the methoxy group is roughly coplanar with its attached ring [deviation = 0.177 (3) Å], as is the methyl C atom of the acetyl group with its ring [deviation = 0.065 (2) Å]. An intramolecular C—H⋯O interaction generates an S(6) ring. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds link the molecules into  chains. Weak C—H⋯π interactions are also observed.
In the title hydrated salt, C15H16NO2
+·C6H4BrO3S−·H2O, the cation exists in an E conformation with respect to the ethenyl bond and is almost planar, with a dihedral angle of 2.62 (12)° between the planes of the pyridinium and benzene rings. The methoxy substituent deviates slightly from the plane of its attached benzene ring [Cmethyl—O—C—C torsion angle = −11.6 (6)°]. In the crystal, the cations, anion and water molecules are linked together into chains along  by O—H⋯O hydrogen bonds and weak C—H⋯O interactions. There is a short Br⋯O contact [3.029 (2) Å]. The crystal structure also features C—H⋯π interactions involving the benzene ring of the anion.
In the title complex, [Na(C7H7O4S)]n, the NaI ion is coordinated in a slightly distorted pentagonal-bipyramidal environment by seven O atoms [Na—O = 2.3198 (16)–2.5585 (17) Å]. The 4-methoxybenzenesulfonate anions act as bis-chelating and bridging ligands, forming a two-dimensional polymer parallel to (001), which is further linked into a three-dimensional network by weak C—H⋯O hydrogen bonds.
In the title hydrated molecular salt, C22H25N2
+·C6H4FO3S−·H2O, the cation displays whole molecule disorder over two sets of sites in a 0.780 (5):0.220 (5) ratio. The quinolinium ring system is essentially planar, with r.m.s. deviations of 0.0162 and 0.0381 Å for the major and minor disorder components, respectively. The dihedral angles between the mean plane of the quinolinium ring system and the benzene ring are 5.1 (3) and 7.7 (11)°, respectively, for the major and minor components in the cation. In the crystal, cations, anions and water molecules are linked into chains along  by O—H⋯O hydrogen bonds and are further connected into a three-dimensional network by weak C—H⋯O and C—H⋯F interactions. In addition, π–π interactions with centroid–centroid distances of 3.634 (3), 3.702 (5) and 3.838 (5) Å are observed.
In the title 3-cyanopyridine derivative, C21H19N3O4, the 3-cyano-substituted pyridine ring forms dihedral angles of 2.35 (5) and 41.60 (5)° with the unsubstituted pyridine and 2,4,5-trimethoxy-substituted benzene rings, respectively. The dihedral angle between the unsubstituted pyridine and benzene rings is 39.84 (5)°. The methoxy groups form Cmethyl—O—C—(C,N) torsion angles in the range 0.80 (15)–11.45 (15)°. In the crystal, molecules related by 21 screw axes are linked by weak C—H⋯N hydrogen bonds along . In addition, weak C—H⋯π interactions and π–π stacking interactions between pyridine rings, with a centroid–centroid distance of 3.6448 (6) Å, are observed.
The title xanthone (systematic name: 3,6,11-trihydroxy-1,1-dimethyl-2,3-dihydrochromeno[2,3-f]chromen-7-one monohydrate), known as pruniflorone N, crystallized as a monohydrate, C18H16O6·H2O. The three ring systems of the xanthone skeleton are approximately coplanar, with an r.m.s. deviation of 0.0270 (1) Å from the plane through the 14 non-H atoms. The O atoms of the two hydroxy substituents on the benzene rings also lie close to this plane, with deviations of 0.019 (1) and 0.070 (1) Å. The 2′-hydroxy-4′,4′-dimethylpyran ring is disordered over two positions with a 0.798 (3):0.202 (3) site-occupancy ratio. An intramolecular O—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, the xanthone and water molecules are linked into a three-dimensional network by O—H⋯O hydrogen bonds and weak C—H⋯O interactions. π–π interactions, with centroid–centroid distances of 3.5982 (7), 3.6081 (7) and 3.6456 (7) Å, are also observed.
In the molecule of title pyrazoline derivative, C17H18N4OS, the pyrazole ring adopts an envelope conformation with the flap atom, which bears the methoxyphenyl substituent, displaced by 0.0750 (12) Å from the plane through the other ring atoms. The two substituted benzene rings make a dihedral angle of 70.59 (6)°. The methoxy group is twisted slightly with respect to the attached benzene ring [Cmethyl—O—C—C torsion angle = −8.84 (15)°]. An intramolecular N—H⋯N hydrogen bond occurs. In the crystal, the pyrazoline molecules are linked by N—H⋯O and N—H⋯S hydrogen bonds into zigzag layers parallel to the bc plane and stacked along the a axis by π–π interactions with centroid–centroid distances of 3.4690 (7) and 3.5792 (7) Å. C—H⋯π interactions are also present.
The title compound, C16H16N4O7, is close to being planar, with a dihedral angle of 3.15 (11)° between the benzene rings. The methoxy groups at the ortho- and para-positions of the 2,4,5-trimethoxyphenyl group are almost coplanar with the ring [deviations of the C atoms = 0.017 (2) and −0.025 (2) Å, respectively], whereas the meta-methoxy group deviates slightly [C-atom displacement = 0.162 (2) Å]. Both the ortho- and para-nitro groups are close to being coplanar with their attached ring [dihedral angles = 7.81 (12) and 8.56 (11)°, respectively]. An intramolecular N—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds involving the same H atom as the intramolecular bond generate R
2(12) loops. The dimers are linked by weak C—H⋯O interactions into sheets parallel to the (10-4) plane and the sheets are stacked by π–π interactions, with a centroid–centroid distance of 3.5974 (14) Å.
In the title compound, C18H15N3O5S, the approximately planar quinazoline ring system [maximum deviation = 0.097 (3) Å] forms a dihedral angle of 76.53 (19)° with the phenyl ring. The terminal -C(=O)—O—C group is disordered over two sets of sites with a site-occupancy ratio of 0.811 (17):0.189 (17). In the crystal, molecules are linked via weak C—H⋯O hydrogen bonds into sheets parallel to the ac plane.
The title heteroaryl chalcone derivative, C17H17NO4, is close to planar: the dihedral angle between the pyridine and benzene rings is 3.71 (11)° and the methoxy C atoms deviate from their attached ring by 0.046 (3), −0.044 (2) and 0.127 (3) Å. The disposition of the pyridine N atom and the carbonyl group is anti [N—C—C—O = −177.7 (2)°]. In the crystal, molecules are linked by weak C—H⋯N and C—H⋯O interactions into (100) sheets and an aromatic π–π stacking interaction between the pyridine and benzene ring, with a centroid–centroid separation of 3.7036 (14) Å also occurs.
The molecule of the title heteroaryl chalcone derivative, C13H11NOS, exists in a trans-configuaration and is almost planar with a dihedral angle of 3.73 (8)° between the phenyl and thiophene rings. An intramolecular N—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, two adjacent molecules are linked into a dimer in an anti-parallel face-to-face manner by a pair of C—H⋯O interactions. Neighboring dimers are further linked into chains along the c-axis direction by N—H⋯N hydrogen bonds.
The molecule of the title compound, C15H15NO2, adopts a trans conformation with respect to the methylidene C=N bond and is twisted with a dihedral angle of 26.31 (5)° between the two substituted benzene rings. The ethoxy group is almost coplanar with the bound benzene ring with a C—O—C—C torsion angle of −179.08 (9)°. In the crystal, molecules are linked by O—H⋯N hydrogen bonds and weak C—H⋯O interactions into chains propagating in the  and [01-1] directions. C—H⋯π interactions are also present.
The asymmetric unit of the title compound, C26H18N6O4S, contains two independent molecules (A and B). The dihedral angles between the oxadiazole ring and naphthalene ring system are 42.59 (14) and 6.88 (14) Å in molecules A and B, respectively. The dihedral angles between the pyridine and benzene rings in A and B are 65.53 (13 )and 87.67 (13) Å, respectively. In the crystal, molecules A and B are linked through a pair of N—H⋯N hydrogen bonds involving one -NH2 group H atom and second pair of N—H⋯N hydrogen bonds involving the other -NH2 group H atom, forming an –ABAB– ribbon along  containing R
2(8) and R
2(12) ring motifs. These ribbons are further connected by weak C—H⋯N, C—H⋯O and C—H⋯π interactions, resulting in a three-dimensional network. The crystal studied was a non-merohedral twin with refined components 0.906 (1):0.094 (1).
In the title compound, C13H12O5, the mean plane of the 2H-chromene ring system (r.m.s deviation = 0.026 Å) forms a dihedral angle of 81.71 (6)° with the mean plane of ethyl 2-hydroxyacetate moiety (r.m.s deviation = 0.034 Å). In the crystal, C—H⋯O hydrogen bonds result in the formation of zigzag layers parallel to the bc plane.