Succinic,fumaric, adipic and oxalic acid cocrystals of promethazine hydrochloride

Novel cocrystals of promethazine hydrochloride [PTZ‐Cl; systematic name: N,N‐dimethyl‐1‐(10H‐phenothiazin‐10‐yl)propan‐2‐aminium chloride] with succinic acid (PTZ‐Cl‐succinic, C₁₇H₂₁N₂S⁺·Cl^?·0.5C₄H₆O₄), fumaric acid (PTZ‐Cl‐fumaric, C₁₇H₂₁N₂S⁺·Cl^?·0.5C₄H₄O₄) and adipic acid (PTZ‐Cl‐adipic, C₁₇H₂₁N₂S⁺·Cl^?·0.5C₆H₁₀O₄) were prepared by solvent drop grinding and slow evaporation from acetonitrile solution, along with two oxalic acid cocrystals which were prepared in tetrahydrofuran (the oxalic acid hemisolvate, PTZ‐Cl‐oxalic, C₁₇H₂₁N₂S⁺·Cl^?·0.5C₂H₂O₄) and nitromethane (the hydrogen oxalate salt, PTZ‐oxalic, C₁₇H₂₁N₂S⁺·C₂HO₄^?). The crystal structures obtained by crystallization from tetrahydrofuran and acetonitrile include the Cl^? ion in the lattice structures, while the Cl^? ion is missing from the crystal structure obtained by crystallization from nitromethane (PTZ‐oxalic). In order to explain the formation of the two types of supramolecular configurations with oxalic acid, the intermolecular interaction energies were calculated in the presence of the two solvents and the equilibrium configurations were determined using density functional theory (DFT). The cocrystals were studied by X‐ray diffraction, IR spectroscopy and differential scanning calorimetry. Additionally, a stability test under special conditions and water solubility were also investigated. PTZ‐Cl‐succinic, PTZ‐Cl‐fumaric and PTZ‐Cl‐adipic crystallized having similar lattice parameter values, and showed a 2:1 PTZ‐Cl to dicarboxylic acid stoichiometry. PTZ‐Cl‐oxalic crystallized in a 2:1 stoichiometric ratio, while the structure lacking the Cl atom belongs has a 1:1 stoichiometry. All the obtained crystals exhibit hydrogen bonds of the type PTZ…Cl…(dicarboxylic acid)…Cl…PTZ, except for PTZ‐oxalic, which forms bifurcated bonds between the hydrogen oxalate and promethazinium ions, along with an infinite hydrogen‐bonded chain between the hydrogen oxalate anions.     

Crystallographic report: Dimethylammonium phenylphosphonate·2(phenylphosphonic acid)

Individual molecules of NH₂Me₂(HO)O₂PPh·2PhPO(OH)₂ are associated by hydrogen bonding, giving rise to a three‐dimensional supramolecular array. Copyright © 2003 John Wiley & Sons, Ltd.     

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.     

Covalent‐assisted supramolecular synthesis: the effect of hydrogen bonding in cocrystals of 4‐tert‐butylbenzoic acid with isoniazid and its derivatized forms

A series of cocrystals of isoniazid and four of its derivatives have been produced with the cocrystal former 4‐tert‐butylbenzoic acid via a one‐pot covalent and supramolecular synthesis, namely 4‐tert‐butylbenzoic acid–isoniazid, C₆H₇N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(propan‐2‐ylidene)isonicotinohydrazide, C₉H₁₁N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(butan‐2‐ylidene)isonicotinohydrazide, C₁₀H₁₃N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(diphenylmethylidene)isonicotinohydrazide, C₁₉H₁₅N₃O·C₁₁H₁₄O₂, and 4‐tert‐butylbenzoic acid–N′‐(4‐hydroxy‐4‐methylpentan‐2‐ylidene)isonicotinohydrazide, C₁₂H₁₇N₃O₂·C₁₁H₁₄O₂. The co‐former falls under the classification of a `generally regarded as safe' compound. The four derivatizing ketones used are propan‐2‐one, butan‐2‐one, benzophenone and 3‐hydroxy‐3‐methylbutan‐2‐one. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and all of its derivatives. The remaining hydrogen‐bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems.     

Two tautomeric forms of 2‐amino‐5,6‐dimethylpyrimidin‐4‐one

Derivatives of 4‐hydroxypyrimidine are an important class of biomolecules. These compounds can undergo keto–enol tautomerization in solution, though a search of the Cambridge Structural Database shows a strong bias toward the 3H‐keto tautomer in the solid state. Recrystallization of 2‐amino‐5,6‐dimethyl‐4‐hydroxypyrimidine, C₆H₉N₃O, from aqueous solution yielded triclinic crystals of the 1H‐keto tautomer, denoted form (I). Though not apparent in the X‐ray data, the IR spectrum suggests that small amounts of the 4‐hydroxy tautomer are also present in the crystal. Monoclinic crystals of form (II), comprised of a 1:1 ratio of both the 1H‐keto and the 3H‐keto tautomers, were obtained from aqueous solutions containing uric acid. Forms (I) and (II) exhibit one‐dimensional and three‐dimensional hydrogen‐bonding motifs, respectively.     

Two novel ferrocenyl dipeptide‐like compounds generated via the Ugi four‐component reaction

The Ugi four‐component reaction, a powerful method for the synthesis of diverse dipeptide‐like derivatives in combinatorial chemistry, was used to synthesize (S)‐1′‐{N‐[1‐(anthracen‐9‐yl)‐2‐(tert‐butylamino)‐2‐oxoethyl]‐N‐(4‐methoxyphenyl)carbamoyl}ferrocene‐1‐carboxylic acid dichloromethane disolvate, [Fe(C₆H₅O₂)(C₃₃H₃₁N₂O₃)]·2CH₂Cl₂, (I), and (S)‐2‐(anthracen‐9‐yl)‐N‐tert‐butyl‐2‐[N‐(4‐methylphenyl)ferrocenylformamido]acetamide, [Fe(C₅H₅)(C₃₃H₃₁N₂O₂)], (II). They adopt broadly similar molecular conformations, with near‐eclipsed cyclopentadienyl rings and near‐perpendicular amide planes in their dipeptide‐like chains, one of which is almost coplanar with its attached cyclopentadienyl ring but perpendicular to the aromatic ring bound to the N atom. In the supramolecular structure of (I), a two‐dimensional network is constructed based on molecular dimers and a combination of intermolecular O—H...O, N—H...O and C—H...O hydrogen bonds, forming R₂²(11), R₂²(16), R₂²(22) and C(9) motifs. These two‐dimensional networks are connected by C—H...O and C—H...Cl contacts to create a three‐dimensional framework, where one dichloromethane solvent molecule acts as a bridge between two neighbouring networks. In the packing of (II), classical hydrogen bonds are absent and an infinite one‐dimensional chain is generated via a combination of C—H...O hydrogen bonds and C—H...π interactions, producing a C(7) motif. This work describes a simple synthesis and the supramolecuar structures of ferrocenyl dipeptide‐like compounds and is significant in the development of redox‐active receptors.     

Crystal structure of pharmaceutical cocrystals of 2,6‐diaminopyridine with piracetam and theophylline

Pharmaceutical cocrystals are crystalline solids formed by an active pharmaceutical ingredient and a cocrystal former. The cocrystals 2,6‐diaminopyridine (DAP)–piracetam [PIR; systematic name: 2‐(2‐oxopyrrolidin‐1‐yl)acetamide] (1/1), C₅H₇N₃·C₆H₁₀N₂O₂, (I), and 2,6‐diaminopyridine–theophylline (TEO; systematic name: 1,3‐dimethyl‐7H‐purine‐2,6‐dione) (1/1), C₅H₇N₃·C₇H₈N₄O₂, (II), were prepared by the solvent‐assisted grinding method and were characterized by IR spectroscopy and powder X‐ray diffraction. Cocrystal (I) crystallized in the orthorhombic space group Pbca and showed a 1:1 stoichiometry. The DAP and PIR molecules are linked by an N—H…O hydrogen‐bond interaction. Self‐assembly of PIR molecules forms a sheet of C (4) and C (7) chains. Cocrystal (II) crystallized in the monoclinic P 2₁/c space group and also showed a 1:1 stoichiometry. The DAP and TEO molecules are connected by N—H…N and N—H…O hydrogen bonds, forming an R ₂²(9) heterosynthon. A bidimensional supramolecular array is formed by interlinked DAP–TEO tetramers, producing a two‐dimensional sheet.     

Supramolecular interactions in salts/cocrystals involving pyrimidine derivatives of sulfonate/carboxylic acid

The crystal structures of three compounds involving aminopyrimidine derivatives are reported, namely, 5-fluorocytosinium sulfanilate–5-fluorocytosine–4-azaniumylbenzene-1-sulfonate (1/1/1), C₄H₅FN₃O⁺·C₆H₆NO₃S⁻·C₄H₄FN₃O·C₆H₇NO₃S, I , 5-fluorocytosine–indole-3-propionic acid (1/1), C₄H₄FN₃O·C₁₁H₁₁NO₂, II , and 2,4,6-triaminopyrimidinium 3-nitrobenzoate, C₄H₈N₅⁺·C₇H₄NO₄⁻, III , which have been synthesized and characterized by single-crystal X-ray diffraction. In I , there are two 5-fluorocytosine (5FC) molecules (5FC-A and 5FC-B) in the asymmetric unit, with one of the protons disordered between them. 5FC-A and 5FC-B are linked by triple hydrogen bonds, generating two fused rings [two R₂²(8) ring motifs]. The 5FC-A molecules form a self-complementary base pair [R₂²(8) ring motif] via a pair of N—H…O hydrogen bonds and the 5FC-B molecules form a similar complementary base pair [R₂²(8) ring motif]. The combination of these two types of pairing generates a supramolecular ribbon. The 5FC molecules are further hydrogen bonded to the sulfanilate anions and sulfanilic acid molecules via N—H…O hydrogen bonds, generating R₄⁴(22) and R⁶₆(36) ring motifs. In cocrystal II , two types of base pairs (homosynthons) are observed via a pair of N—H…O/N—H…N hydrogen bonds, generating R₂²(8) ring motifs. The first type of base pair is formed by the interaction of an N—H group and the carbonyl O atom of 5FC molecules through a couple of N—H…O hydrogen bonds. Another type of base pair is formed via the amino group and a pyrimidine ring N atom of the 5FC molecules through a pair of N—H…N hydrogen bonds. The base pairs (via N—H…N hydrogen bonds) are further bridged by the carboxyl OH group of indole-3-propionic acid and the O atom of 5FC through O—H…O hydrogen bonds on either side of the R₂²(8) motif. This leads to a DDAA array. In salt III , one of the N atoms of the pyrimidine ring is protonated and interacts with the carboxylate group of the anion through N—H…O hydrogen bonds, leading to the primary ring motif R₂²(8). Furthermore, the 2,4,6-triaminopyrimidinium (TAP) cations form base pairs [R₂²(8) homosynthon] via N—H…N hydrogen bonds. A carboxylate O atom of the 3-nitrobenzoate anion bridges two of the amino groups on either side of the paired TAP cations to form another ring [R₃²(8)]. This leads to the generation of a quadruple DADA array. The crystal structures are further stabilized by π–π stacking ( I and III ), C—H…π ( I and II ), C—F…π ( I ) and C—O…π ( II ) interactions.     

Two Unexpected Temperature-Induced Supermolecular Isomers from Multi-Topic Carboxylic Acid: Hydrogen Bonding Layer or Helix Tube

Under ambient conditions or 160 °C, two supramolecular isomers, namely [(H₄PTTA)(H₂O)₂(DMF)] and [(H₄PTTA)(H₂O)₃]··Guest (1-L and 1-H, H₄PTTA = N-phenyl-N′-phenyl bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxdiimide tetra-carboxylic acid, Guest = DMF and H₂O), were obtained through the reaction of H₄PTTA in a mixture of H₂O and dimethylformamide. The single crystal structures reveal the temperature-dependent supramolecular isomerism derived from the torsion of semi-rigid of H₄PTTA. The 1-L prepared at room temperature is a hydrogen bond based achiral layer, while the hydrothermal synthesized 1-H is isomer resulted in an H-bond-based chiral tubes-packed supramolecular framework.     

Synthesis and structures of two supramolecular complexes constructed via hydrogen bond linking

Two supramolecular complexes,[Ni(rac-L)]3[CrO4]2[ClO4]2-4H2O (1) and [meso-H2L]0.5[VO3]-0.16H2O (2) (L= 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetra-decane),have been prepared in an aqueous solu-tion,and detected by elemental analysis,IR,TG,and single crystal X-ray diffraction analyses. Com-pound 1 shows a one-dimensional hexagonal prism formed by the hydrogen bonding interactions between the secondary amines of rac-L and CrO42-anion/water molecules. Compound 2 displays a three-dimensional structur...     

A competitive molecular recognition study: syntheses and analysis of supramolecular assemblies of 3,5-dihydroxybenzoic acid and its bromo derivative with some N-donor compounds

A molecular recognition study of 3,5-dihydroxybenzoic acid (1) and its bromo derivative 4-bromo-3,5-dihydroxybenzoic acid (2) with the N-donor compounds 1,2-bis(4-pyridyl)ethene (bpyee), 1,2-bis(4-pyridyl)ethane (bpyea), and 4,4'-bipyridine (bpy) is reported. Thus, the syntheses and structural analysis of molecular adducts 1 a-1 c (1 with bpyee, bpyea, and bpy, respectively) and 2 a-2 c (2 with bpyee, bpyea, and bpy, respectively) are discussed. In all these adducts, recognition between the constituents is established through either O--H...N and/or O--H...N/C--H...O pairwise hydrogen bonds. In all the adducts both OH and COOH functional groups available on 1 and 2 interact with the N-donor compounds, except in 2 a, in which only COOH (COO-) is involved in the recognition process. The COOH moieties in 1 a, 1 b, and 2 b form only single O--H...N hydrogen bonds, whereas in 1 c and 2 c, they form pairwise O--H...N/C--H...O hydrogen bonds. In addition, subtle differences in the recognition patterns resulted in the formation of cyclic networks of different dimensions. In fact, only 1 c forms a four-molecule cyclic moiety, as was already documented in the literature for this kind of assemblies. All complexes have been characterized by single-crystal X-ray diffraction. The supramolecular architectures are quite elegant and simple, with stacking of sheets in all adducts, but a rather complex network with a threefold interpenetration pattern was found in 2 c.     

Helical arrangement of a hydrogen‐bonded columnar liquid crystal induced by a centered triphenylene derivative bearing chiral side‐chains

A hydrogen‐bonded helical columnar liquid crystal was synthesized, in which the helical structure is induced by a centered triphenylene derivative bearing chiral side‐chains. The triphenylene derivative, 2,6,10‐tris(carboxymethoxy)‐3,7,11‐tris((S)‐(‐)‐2‐methyl‐1‐butanoxy)triphenylene ( TPC4(S) ), and a dendric amphiphile, 3,5‐bis‐(3,4‐bis‐dodecyloxy‐benzyloxy)‐N‐pyridine‐4‐yl‐benzamide ( DenC12 ), were mixed in a 1:3 ratio to obtain a complex, TPC4(S)‐DenC12 . Analyses by ¹H‐NMR spectroscopy, diffusion ordered spectroscopy (DOSY), CD spectroscopy, infrared (IR) spectroscopy, polarized optical microscopy (POM), differential scanning calorimetry (DSC), and X‐ray diffractometry revealed that TPC4(S)‐DenC12 self‐assembles to form helical columnar stacks in solution and a helical columnar liquid crystal in bulk. The hydrogen bonding between TPC4(S) and DenC12 is essential for the helical columnar organization, and the preference for a one‐handed helical conformation is likely derived from the steric interaction between the chiral side‐chains and the dendric amphiphiles in the packing of the hydrogen‐bonded columnar assemblies. Copyright © 2008 John Wiley & Sons, Ltd.     

Halogen versus Hydrogen Bonding in Binary Cocrystals: Novel Conformation a Coformer with [2+2] Photoreactivity of Criss-Crossed C=C Bonds

A series of cocrystals involving the hydrogen- and halogen-bond donor coformers catechol ( cat ) and 1,2-diiodotetrafluorobenzene ( 1,2-di-I-tFb ), respectively, is reported. Each coformer forms a cocrystal with each of the three symmetric bipyridines trans-1,2-bis(n-pyridyl)ethylene ( n , n′ -bpe , where: n=n′=2, 3, 4). Four novel cocrystals ( cat ) ⋅ ( 3,3′-bpe ), 2( 1,2-di-I-tFb ) ⋅ ( 2,2′-bpe ), 2( 1,2-di-I-tFb ) ⋅ ( 3,3′-bpe ), and ( 1,2-di-I-tFb ) ⋅ ( 4,4′-bpe ) comprise components that assemble by either O−H⋅⋅⋅N hydrogen bonds ( cat ) or N⋅⋅⋅I halogen bonds ( 1,2-di-I-tFb ). In ( cat ) ⋅ ( 3,3′-bpe ), cat acts as a template to support an intermolecular [2+2] photocycloaddition of 3,3′-bpe . The reactivity occurs via a one-dimensional (1D) hydrogen-bonded tape with stacked and criss-crossed olefins that react stereoselectively and quantitatively to form rctt-tetrakis(3-pyridyl)cyclobutane ( 3,3′-tpcb ). The reactivity of the criss-crossed olefins is facilitated by a hitherto not reported cis-gauche conformation adopted by cat . The stereochemistry of 3,3′-tpcb is confirmed in the cocrystal 2( cat ) ⋅ ( 3,3′-tpcb ).     

Supramolecular hydrogen‐bonding patterns in two cocrystals of the N(7)–H tautomeric form of N6‐benzoyladenine: N6‐benzoyladenine–3‐hydroxypyridinium‐2‐carboxylate (1/1) and N6‐benzoyladenine–DL‐tartaric acid (1/1)

Two novel cocrystals of the N(7)—H tautomeric form of N⁶‐benzoyladenine (BA), namely N⁶‐benzoyladenine–3‐hydroxypyridinium‐2‐carboxylate (3HPA) (1/1), C₁₂H₉N₅O·C₆H₅NO₃, (I), and N⁶‐benzoyladenine–DL‐tartaric acid (TA) (1/1), C₁₂H₉N₅O·C₄H₆O₆, (II), are reported. In both cocrystals, the N⁶‐benzoyladenine molecule exists as the N(7)—H tautomer, and this tautomeric form is stabilized by intramolecular N—H...O hydrogen bonding between the benzoyl C=O group and the N(7)—H hydrogen on the Hoogsteen site of the purine ring, forming an S(7) motif. The dihedral angle between the adenine and phenyl planes is 0.94 (8)° in (I) and 9.77 (8)° in (II). In (I), the Watson–Crick face of BA (N6—H and N1; purine numbering) interacts with the carboxylate and phenol groups of 3HPA through N—H...O and O—H...N hydrogen bonds, generating a ring‐motif heterosynthon [graph set R₂²(6)]. However, in (II), the Hoogsteen face of BA (benzoyl O atom and N7; purine numbering) interacts with TA (hydroxy and carbonyl O atoms) through N—H...O and O—H...O hydrogen bonds, generating a different heterosynthon [graph set R₂²(4)]. Both crystal structures are further stabilized by π–π stacking interactions.     

Four related benzazepine derivatives in a reaction pathway leading to a benzazepine carboxylic acid: hydrogen‐bonded assembly in zero,one, two and three dimensions

(2R*,4S*)‐Methyl 2,3,4,5‐tetrahydro‐1,4‐epoxy‐1H‐benz[b]azepine‐2‐carboxylate, C₁₂H₁₃NO₃, (I), and its reduction product (2R*,4S*)‐methyl 4‐hydroxy‐2,3,4,5‐tetrahydro‐1H‐benz[b]azepine‐2‐carboxylate, C₁₂H₁₅NO₃, (II), both crystallize as single enantiomers in the space group P2₁2₁2₁, while the hydrolysis product (2RS,4SR)‐4‐hydroxy‐2,3,4,5‐tetrahydro‐1H‐benz[b]azepine‐2‐carboxylic acid, C₁₁H₁₃NO₃, (III), and the lactone (2RS,5SR)‐8‐(trifluoromethoxy)‐5,6‐dihydro‐1H‐2,5‐methanobenz[e][1,4]oxazocin‐3(2H)‐one, C₁₂H₁₀F₃NO₃, (IV), both crystallize as racemic mixtures in the space group P2₁/c. The molecules of compound (IV) are linked into centrosymmetric R₂²(10) dimers by N—H...O hydrogen bonds, and those of compound (I) are linked into chains by C—H...π(arene) hydrogen bonds. A combination of O—H...O and O—H...N hydrogen bonds links the molecules of compound (III) into sheets containing equal numbers of R₄⁴(14) and R₄⁴(26) rings, and a combination of C—H...π(arene) hydrogen bonds and three‐centre O—H...(N,O) hydrogen bonds links the molecules of compound (II) into a three‐dimensional framework structure. Comparisons are made with some related compounds.     

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.     

Crystal Structure, Hirshfeld Surface Analysis and Quantum Mechanical Study of a Cocrystal Based on 1,3-Di（4-pyridyl）propane and 3-（（4~′-Carboxybenzyl）oxy） Benzoic Acid

A cocrystal based on 1,3-di(4-pyridyl)propane and 3-((4′-carboxybenzyl)oxy)benzoic acid,C13H14N2·C15H12O5,has been synthesized and characterized by single-crystal X-ray diffraction.The compound crystallizes in monoclinic,space group P21 /c with a = 11.639(4),b = 9.808(3),c = 20.854(6),β = 91.242(7)°,V = 2380.0(13)3,C28H26N2O5,Mr = 470.51,Dc = 1.313 g/cm3,μ(MoKα) = 0.091 mm-1,F(000) = 992,Z = 4,the final R = 0.0677 and wR = 0.1477 for 4175 observed reflections(I > 2σ(I)).Intermolecular N H···O hydrogen bonds link two kinds of components into a one-dimensional chain in [10-1] direction and adjacent chains are further arranged into a two-dimensional network by π···π and C H···π interactions.Investigation of intermolecular interactions and crystal packing via Hirshfeld surface analysis reveals that the close contacts are mainly focused on weak interactions.The theoretical investigations with HF/6-31G(d) method were performed,and its stability,frontier molecular orbital composition and Mulliken charge distribution were also discussed.