Supramolecular architectures in two 1:1 cocrystals of 5‐fluorouracil with 5‐bromothiophene‐2‐carboxylic acid and thiophene‐2‐carboxylic acid

In solid‐state engineering, cocrystallization is a strategy actively pursued for pharmaceuticals. Two 1:1 cocrystals of 5‐fluorouracil (5FU; systematic name: 5‐fluoro‐1,3‐dihydropyrimidine‐2,4‐dione), namely 5‐fluorouracil–5‐bromothiophene‐2‐carboxylic acid (1/1), C₅H₃BrO₂S·C₄H₃FN₂O₂, (I), and 5‐fluorouracil–thiophene‐2‐carboxylic acid (1/1), C₄H₃FN₂O₂·C₅H₄O₂S, (II), have been synthesized and characterized by single‐crystal X‐ray diffraction studies. In both cocrystals, carboxylic acid molecules are linked through an acid–acid R ₂²(8) homosynthon (O—H…O) to form a carboxylic acid dimer and 5FU molecules are connected through two types of base pairs [homosynthon, R ₂²(8) motif] via a pair of N—H…O hydrogen bonds. The crystal structures are further stabilized by C—H…O interactions in (II) and C—Br…O interactions in (I). In both crystal structures, π–π stacking and C—F…π interactions are also observed.     

Hydrogen bonding and π–π interactions in 1‐benzofuran‐2,3‐dicarboxylic acid and its 1:1 cocrystals with pyridine,phenazine and 1,4‐phenylenediamine

The structure of 1‐benzofuran‐2,3‐dicarboxylic acid (BFDC), C₁₀H₆O₅, (I), exhibits an intramolecular hydrogen bond between one –COOH group and the other, while the second carboxyl function is involved in intermolecular hydrogen bonding to neighbouring species. The latter results in the formation of flat one‐dimensional hydrogen‐bonded chains in the crystal structure, which are π–π stacked along the normal to the plane of the molecular framework, forming a layered structure. 1:1 Cocrystallization of BFDC with pyridine, phenazine and 1,4‐phenylenediamine is associated with H‐atom transfer from BFDC to the base and charge‐assisted hydrogen bonding between the BFDC⁻ monoanion and the corresponding ammonium species, while preserving, in all cases, the intramolecular hydrogen bond between the carboxyl and carboxylate functions. The pyridinium 2‐carboxylato‐1‐benzofuran‐3‐carboxylic acid, C₅H₆N⁺·C₁₀H₅O₅⁻, (II), and phenazinium 3‐carboxylato‐1‐benzofuran‐2‐carboxylic acid, C₁₂H₉N₂⁺·C₁₀H₅O₅⁻, (III), adducts form discrete hydrogen‐bonded ion‐pair entities. In the corresponding crystal structures, the two components are arranged in either segregated or mixed π–π stacks, respectively. On the other hand, the structure of 4‐aminoanilinium 2‐carboxylato‐1‐benzofuran‐3‐carboxylic acid, C₆H₉N₂⁺·C₁₀H₅O₅⁻, (IV), exhibits an intermolecular hydrogen‐bonding network with three‐dimensional connectivity. Moreover, this fourth structure exhibits induction of supramolecular chirality by the extended hydrogen bonding, leading to a helical arrangement of the interacting moieties around 2₁ screw axes. The significance of this study is that it presents the first crystallographic characterization of pure BFDC, and manifestation of its cocrystallization with a variety of weakly basic amine molecules. It confirms the tendency of BFDC to preserve its intramolecular hydrogen bond and to prefer a monoanionic form in supramolecular association with other components. The aromaticity of the flat benzofuran residue plays an important role in directing either homo‐ or heteromolecular π–π stacking in the first three structures, while the occurrence of a chiral architecture directed by multiple hydrogen bonding is the dominant feature in the fourth.     

Design of two series of 1:1 cocrystals involving 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine and carboxylic acids

Two series of a total of ten cocrystals involving 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine with various carboxylic acids have been prepared and characterized by single‐crystal X‐ray diffraction. The pyrimidine unit used for the cocrystals offers two ring N atoms (positions N1 and N3) as proton‐accepting sites. Depending upon the site of protonation, two types of cations are possible [Rajam et al. (2017). Acta Cryst. C 73 , 862–868]. In a parallel arrangement, two series of cocrystals are possible depending upon the hydrogen bonding of the carboxyl group with position N1 or N3. In one series of cocrystals, i.e. 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–3‐bromothiophene‐2‐carboxylic acid (1/1), 1 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–5‐chlorothiophene‐2‐carboxylic acid (1/1), 2 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–2,4‐dichlorobenzoic acid (1/1), 3 , and 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–2‐aminobenzoic acid (1/1), 4 , the carboxyl hydroxy group (–OH) is hydrogen bonded to position N1 (O—H…N1) of the corresponding pyrimidine unit (single point supramolecular synthon). The inversion‐related stacked pyrimidines are doubly bridged by the carboxyl groups via N—H…O and O—H…N hydrogen bonds to form a large cage‐like tetrameric unit with an R₄²(20) graph‐set ring motif. These tetrameric units are further connected via base pairing through a pair of N—H…N hydrogen bonds, generating R₂²(8) motifs (supramolecular homosynthon). In the other series of cocrystals, i.e. 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–5‐methylthiophene‐2‐carboxylic acid (1/1), 5 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–benzoic acid (1/1), 6 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–2‐methylbenzoic acid (1/1), 7 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–3‐methylbenzoic acid (1/1), 8 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–4‐methylbenzoic acid (1/1), 9 , and 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–4‐aminobenzoic acid (1/1), 10 , the carboxyl group interacts with position N3 and the adjacent 4‐amino group of the corresponding pyrimidine ring via O—H…N and N—H…O hydrogen bonds to generate the robust R₂²(8) supramolecular heterosynthon. These heterosynthons are further connected by N—H…N hydrogen‐bond interactions in a linear fashion to form a chain‐like arrangement. In cocrystal 1 , a Br…Br halogen bond is present, in cocrystals 2 and 3 , Cl…Cl halogen bonds are present, and in cocrystals 5 , 6 and 7 , Cl…O halogen bonds are present. In all of the ten cocrystals, π–π stacking interactions are observed.     

Synthesis and structures of 11,11,12,12‐tetracyano‐2,6‐diiodo‐9,10‐anthraquinodimethane and its 2:1 cocrystals with anthracene,pyrene and tetrathiafulvalene

Radical salts and charge‐transfer complexes (CTCs) containing tetracyanoquinodimethane (TCNQ) display electrical conductivity, which has led to the development of many TCNQ derivatives with enhanced electron‐accepting properties that are applicable toward organic electronics. To expand the family of TCNQ derivatives, we report the synthesis and structures of 11,11,12,12‐tetracyano‐2,6‐diiodo‐9,10‐anthraquinodimethane (abbreviated as DITCAQ), C₂₀H₆I₂N₄, and its charge‐transfer complexes with various electron donors, namely DITCAQ–anthracene (2/1), C₂₀H₆I₂N₄·0.5C₁₄H₁₀, (I), DITCAQ–pyrene (2/1), C₂₀H₆I₂N₄·0.5C₁₆H₁₀, (II), and DITCAQ–tetrathiafulvalene (2/1), C₂₀H₆I₂N₄·0.5C₆H₄S₄, (III). The molecular structure of DITCAQ consists of a 2,6‐diiodo‐9,10‐dihydroanthracene moiety with two malononitrile substituents. DITCAQ possesses a saddle shape, since the malononitrile groups bend significantly up out of the plane of the central ring and the two benzene rings bend down out of the same plane. π–π interactions between DITCAQ and the electron‐donor molecules control the degree of charge transfer in cocrystals (I), (II), and (III), which is reflected in both the dihedral angles between the terminal benzene ring and the central ring on the DITCAQ motifs, and their corresponding IR spectra.     

The β‐polymorph of phenazine

In β‐phenazine, C₁₂H₉N₂, the mol­ecules show a sandwich herring‐bone type of packing. The experimental crystal structure shows very good agreement with that predicted earlier from systematic searches of potential packing arrangements for the known unit cell [Hammond, Roberts, Smith & Docherty (1999). J. Phys. Chem. B, 103 , 7762–7770].     

2‐Chloro‐4‐nitrobenzoic acid as a coformer with pharmaceutical cocrystals and molecular salts

A series of five binary complexes, i.e. three cocrystals and two molecular salts, using 2‐chloro‐4‐nitrobenzoic acid as a coformer have been produced with five commonly available compounds, some of pharmaceutical relevance, namely, 2‐chloro‐4‐nitrobenzoic acid–isonicotinamide (1/1), C₇H₄ClNO₄·C₆H₆N₂O, 2‐chloro‐4‐nitrobenzoic acid–3,3‐diethylpyridine‐2,4(1H,3H)‐dione (2/1), 2C₇H₄ClNO₄·C₉H₁₃NO₂, 2‐chloro‐4‐nitrobenzoic acid–pyrrolidin‐2‐one (1/1), C₇H₄ClNO₄·C₄H₇NO, 2‐carboxypiperidinium 2‐chloro‐4‐nitrobenzoate, C₆H₁₂NO₂^?·C₇H₃ClNO₄^?, and (2‐hydroxyethyl)ammonium 2‐chloro‐4‐nitrobenzoate, C₂H₈NO⁺·C₇H₃ClNO₄^?. The coformer falls under the classification of a `generally regarded as safe' compound. All five complexes make use of a number of different heteromeric hydrogen‐bonded interactions. Intermolecular potentials were evaluated using the CSD‐Materials module.     

3,5‐Dimethyl‐4‐[(E)‐(2‐nitrophenyl)diazenyl]‐1‐(2,3,4,5,6‐pentafluorophenyl)‐1H‐pyrazole

The title compound, C₁₇H₁₀F₅N₅O₂, is described and compared with its 4‐nitrophenyl isomer [Bustos, Sánchez, Schott, Alvarez‐Thon & Fuentealba (2007). Acta Cryst. E 63 , o1138–o1139]. The title molecule presents its nitro group split into two rotationally disordered components, which in conjunction with the rotation of the `unclamped' rings constitute the main molecular differences. Packing is directed by a head‐to‐tail type `I' C—F...F—C interaction, generating double‐chain strips running along [100]. These substructures are interlinked by a variety of weak F...F, O...F, F...π and O...π interactions.     

5‐(5‐Nitropyridin‐2‐yldithio)‐1‐phenyl‐1H‐tetrazole

In the title disulfide, C₁₂H₈N₆O₂S₂, all bond lengths and angles are within normal ranges, and the molecules are linked into centrosymmetric R₂²(20) dimers by simple C—H...N interactions. Weak intermolecular C—H...π(arene) and π–π interactions, involving the benzene CH groups and the benzene rings, and the pyridine rings, respectively, further stabilize and reinforce the crystal structure.     

2:1 Complexes of 2‐chloro‐4‐nitro­benzoic acid and 2‐chloro‐5‐nitro­benzoic acid with pyrazine

2‐Chloro‐4‐nitro­benzoic acid and 2‐chloro‐5‐nitro­benzoic acid form O—H?N hydrogen bonds with pyrazine to afford 2:1 complexes of 2C₇H₄ClNO₄·C₄H₄N₂, (I) and (II), respectively, that are located on inversion centers. The 2C₇H₄ClNO₄·­C₄H₄N₂ units in both complexes are connected by weak C—H?O hydrogen bonds; the units build a three‐dimensional hydrogen‐bond network in (I) and a ribbon structure in (II).     

Aryloxy tetrazoles with axial chirality: Synthesis and partial resolution of 5‐(1‐(2‐methoxynaphthalen‐1‐yl)naphthalen‐2‐yloxy)‐1H‐tetrazole

5‐(1‐(2‐Methoxynaphthalen‐1‐yl)naph‐ thalen‐2‐yloxy)‐1H‐tetrazole as the first aryloxy tetrazole with axial chirality was synthesized. Partial resolution was achieved using (S)‐proline and methylbenzylamine as the resolving agents. Best results were obtained using methylbenzylamine with 75–85% ee. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:416–419, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20241     

3,3′,5,5′‐Tetramethyl‐4,4′‐bipyrazole–pentafluorophenol (2/3)

In the title compound, 2C₁₀H₁₄N₄·3C₆HF₅O, one of the pentafluorophenol molecules resides on a mirror plane bisecting the O...F axis. The components aggregate by N—H...N, N—H...O and O—H...N hydrogen bonds involving equal disordering of the H atoms into molecular ensembles based on a 2:1 pyrazole–phenol cyclic pattern [O...N = 2.7768 (16) Å and N...N = 2.859 (2) Å], crosslinked into one‐dimensional columns via hydrogen bonding between the outer pyrazole groups and additional pentafluorophenol molecules. The latter yields a 1:1 pyrazole–phenol catemer with alternating strong O—H...N [2.5975 (16) Å] and weaker N—H...O [2.8719 (17) Å] hydrogen bonds. This is the first reported molecular adduct of a pentafluorinated phenol and a nitrogen base, and suggests the utility of highly acidic phenols and pyrazoles for developing hydrogen‐bonded cocrystals.     

New Energetic Materials: Functionalized 1‐Ethyl‐5‐aminotetrazoles and 1‐Ethyl‐5‐nitriminotetrazoles

A new way to make a bang : Several functionalized 1‐ethyl‐5‐aminotetrazoles, 1‐ethyl‐5‐nitrimino‐tetrazoles, and copper complexes have been synthesized and their chemical and energetic properties have been comprehensively characterized. The compounds belong to all classes of “energetic materials”: explosives, propellants, and pyrotechnics.

     

Two derivatives of 5‐amino­tetrazole: 5‐amino‐1‐phenyl­tetrazole and 5‐amino‐1‐(1‐naphthyl)­tetrazole

In the mol­ecules of 5‐amino‐1‐phenyl­tetrazole, C₇H₇N₅, (I), and 5‐amino‐1‐(1‐naphthyl)­tetrazole, C₁₁H₉N₅, (II), the tetrazole rings and aryl fragments are not coplanar; corresponding dihedral angles are 50.58 (5) and 45.19 (7)° for the two independent mol­ecules of (I), and 64.14 (5)° for (II). Intermolecular N—H⋯N hydrogen bonds between the amino groups and tetrazole N atoms are primarily responsible for formation of two‐dimensional networks extending parallel to the bc plane in both compounds. The presence of the amino group has a distinct effect on the geometry of the tetrazole rings in each case.     

Three cocrystals and a cocrystal salt of pyrimidin‐2‐amine and glutaric acid

Four new cocrystals of pyrimidin‐2‐amine and propane‐1,3‐dicarboxylic (glutaric) acid were crystallized from three different solvents (acetonitrile, methanol and a 50:50 wt% mixture of methanol and chloroform) and their crystal structures determined. Two of the cocrystals, namely pyrimidin‐2‐amine–glutaric acid (1/1), C₄H₅N₃·C₆H₈O₄, (I) and (II), are polymorphs. The glutaric acid molecule in (I) has a linear conformation, whereas it is twisted in (II). The pyrimidin‐2‐amine–glutaric acid (2/1) cocrystal, 2C₄H₅N₃·C₆H₈O₄, (III), contains glutaric acid in its linear form. Cocrystal–salt bis(2‐aminopyrimidinium) glutarate–glutaric acid (1/2), 2C₄H₆N₃⁺·C₆H₆O₄²⁻·2C₆H₈O₄, (IV), was crystallized from the same solvent as cocrystal (II), supporting the idea of a cocrystal–salt continuum when both the neutral and ionic forms are present in appreciable concentrations in solution. The diversity of the packing motifs in (I)–(IV) is mainly caused by the conformational flexibility of glutaric acid, while the hydrogen‐bond patterns show certain similarities in all four structures.     

Synthesis of novel 2‐(2‐methylsulfonyl‐1‐methyl‐1H‐imidazol‐5‐yl)‐5‐(alkylsulfonyl)‐1,3,4‐thiadiazoles

Starting from 5‐hydroxymethyl‐2‐mercapto‐1‐methyl‐1H‐imidazole (1), a series of 2‐(1‐methyl‐2‐methylsulfonyl‐1H‐imidazol‐5‐yl)‐5‐alkylthio and 5‐alkylsulfonyl‐1,3,4‐thiadiazole derivatives ( 9a , 9b , 9c , 9d and 10a , 10b , 10c , 10d ) were prepared as potential antimicrobial agents. The structure of the obtained compounds was confirmed by NMR, IR, Mass spectroscopy, and elemental analysis. J. Heterocyclic Chem., (2010)     

(−)‐(1R,2S,2′R,5R)‐2‐(1‐Hydroxyprop‐2‐yl)‐5‐methylcyclohexanol

Stereoselective hydroboration of (?)‐isopulegol and subsequent fractional crystallization furnishes the title compound, C₁₀H₂₀O₂. The relative configuration of the stereogenic centres has been assigned by means of X‐ray diffraction analysis since the monoterpenediol is employed as a versatile chiral building block in stereospecific natural product synthesis.     

Syntheses of acyclic C‐glycosidic derivatives of 1,2,4‐triazoles by cycloadditions of 1‐aza‐2‐azoniaallene salts to D‐glucononitrile‐2,3,4,5,6‐pentaacetate

Reported are preparations of acyclic derivatives of 1,2,4‐triazole‐5‐glycosidies 9 by cycloadditions of 1‐aza‐2‐azonia‐allene salts 3 to the nitrile group of D‐glucononitrile‐2,3,4,5,6‐pentaacetate 5 affording triazolium salts 8 , which with aqueous sodium hydogencarbonate are hydrolyzed to 9 . Deacetylation of compounds 9 produced the C‐glycosides 10 .     

Sulfur as hydrogen‐bond acceptor in cocrystals of 2‐thio‐modified thymine

Doubly and triply hydrogen‐bonded supramolecular synthons are of particular interest for the rational design of crystal and cocrystal structures in crystal engineering since they show a high robustness due to their high stability and good reliability. The compound 5‐methyl‐2‐thiouracil (2‐thiothymine) contains an ADA hydrogen‐bonding site (A = acceptor and D = donor) if the S atom is considered as an acceptor. We report herein the results of cocrystallization experiments with the coformers 2,4‐diaminopyrimidine, 2,4‐diamino‐6‐phenyl‐1,3,5‐triazine, 6‐amino‐3H‐isocytosine and melamine, which contain complementary DAD hydrogen‐bonding sites and, therefore, should be capable of forming a mixed ADA–DAD N—H…S/N—H…N/N—H…O synthon (denoted synthon 3s_{N·S;N·N;N·O}), consisting of three different hydrogen bonds with 5‐methyl‐2‐thiouracil. The experiments yielded one cocrystal and five solvated cocrystals, namely 5‐methyl‐2‐thiouracil–2,4‐diaminopyrimidine (1/2), C₅H₆N₂OS·2C₄H₆N₄, (I), 5‐methyl‐2‐thiouracil–2,4‐diaminopyrimidine–N,N‐dimethylformamide (2/2/1), 2C₅H₆N₂OS·2C₄H₆N₄·C₃H₇NO, (II), 5‐methyl‐2‐thiouracil–2,4‐diamino‐6‐phenyl‐1,3,5‐triazine–N,N‐dimethylformamide (2/2/1), 2C₅H₆N₂OS·2C₉H₉N₅·C₃H₇NO, (III), 5‐methyl‐2‐thiouracil–6‐amino‐3H‐isocytosine–N,N‐dimethylformamide (2/2/1), (IV), 2C₅H₆N₂OS·2C₄H₆N₄O·C₃H₇NO, (IV), 5‐methyl‐2‐thiouracil–6‐amino‐3H‐isocytosine–N,N‐dimethylacetamide (2/2/1), 2C₅H₆N₂OS·2C₄H₆N₄O·C₄H₉NO, (V), and 5‐methyl‐2‐thiouracil–melamine (3/2), 3C₅H₆N₂OS·2C₃H₆N₆, (VI). Synthon 3s_{N·S;N·N;N·O} was formed in three structures in which two‐dimensional hydrogen‐bonded networks are observed, while doubly hydrogen‐bonded interactions were formed instead in the remaining three cocrystals whereby three‐dimensional networks are preferred. As desired, the S atoms are involved in hydrogen‐bonding interactions in all six structures, thus illustrating the ability of sulfur to act as a hydrogen‐bond acceptor and, therefore, its value for application in crystal engineering.