6‐Propyl‐2‐thiouracil versus 6‐methoxymethyl‐2‐thiouracil: enhancing the hydrogen‐bonded synthon motif by replacement of a methylene group with an O atom

The understanding of intermolecular interactions is a key objective of crystal engineering in order to exploit the derived knowledge for the rational design of new molecular solids with tailored physical and chemical properties. The tools and theories of crystal engineering are indispensable for the rational design of (pharmaceutical) cocrystals. The results of cocrystallization experiments of the antithyroid drug 6‐propyl‐2‐thiouracil (PTU) with 2,4‐diaminopyrimidine (DAPY), and of 6‐methoxymethyl‐2‐thiouracil (MOMTU) with DAPY and 2,4,6‐triaminopyrimidine (TAPY), respectively, are reported. PTU and MOMTU show a high structural similarity and differ only in the replacement of a methylene group (–CH₂–) with an O atom in the side chain, thus introducing an additional hydrogen‐bond acceptor in MOMTU. Both molecules contain an ADA hydrogen‐bonding site (A = acceptor and D = donor), while the coformers DAPY and TAPY both show complementary DAD sites and therefore should be capable of forming a mixed ADA/DAD synthon with each other, i.e. N—H…O, N—H…N and N—H…S hydrogen bonds. The experiments yielded one solvated cocrystal salt of PTU with DAPY, four different solvates of MOMTU, one ionic cocrystal of MOMTU with DAPY and one cocrystal salt of MOMTU with TAPY, namely 2,4‐diaminopyrimidinium 6‐propyl‐2‐thiouracilate–2,4‐diaminopyrimidine–N,N‐dimethylacetamide–water (1/1/1/1) (the systematic name for 6‐propyl‐2‐thiouracilate is 6‐oxo‐4‐propyl‐2‐sulfanylidene‐1,2,3,6‐tetrahydropyrimidin‐1‐ide), C₄H₇N₄⁺·C₇H₉N₂OS⁻·C₄H₆N₄·C₄H₉NO·H₂O, (I), 6‐methoxymethyl‐2‐thiouracil–N,N‐dimethylformamide (1/1), C₆H₈N₂O₂S·C₃H₇NO, (II), 6‐methoxymethyl‐2‐thiouracil–N,N‐dimethylacetamide (1/1), C₆H₈N₂O₂S·C₄H₉NO, (III), 6‐methoxymethyl‐2‐thiouracil–dimethyl sulfoxide (1/1), C₆H₈N₂O₂S·C₂H₆OS, (IV), 6‐methoxymethyl‐2‐thiouracil–1‐methylpyrrolidin‐2‐one (1/1), C₆H₈N₂O₂S·C₅H₉NO, (V), 2,4‐diaminopyrimidinium 6‐methoxymethyl‐2‐thiouracilate (the systematic name for 6‐methoxymethyl‐2‐thiouracilate is 4‐methoxymethyl‐6‐oxo‐2‐sulfanylidene‐1,2,3,6‐tetrahydropyrimidin‐1‐ide), C₄H₇N₄⁺·C₆H₇N₂O₂S⁻, (VI), and 2,4,6‐triaminopyrimidinium 6‐methoxymethyl‐2‐thiouracilate–6‐methoxymethyl‐2‐thiouracil (1/1), C₄H₈N₅⁺·C₆H₇N₂O₂S⁻·C₆H₈N₂O₂S, (VII). Whereas in (I) only an AA/DD hydrogen‐bonding interaction was formed, the structures of (VI) and (VII) both display the desired ADA/DAD synthon. Conformational studies on the side chains of PTU and MOMTU also revealed a significant deviation for cocrystals (VI) and (VII), leading to the desired enhancement of the hydrogen‐bond pattern within the crystal.     

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.     

Cocrystals of 6‐methyl‐2‐thiouracil: presence of the acceptor–donor–acceptor/donor–acceptor–donor synthon

The results of seven cocrystallization experiments of the antithyroid drug 6‐methyl‐2‐thiouracil (MTU), C₅H₆N₂OS, with 2,4‐diaminopyrimidine, 2,4,6‐triaminopyrimidine and 6‐amino‐3H‐isocytosine (viz. 2,6‐diamino‐3H‐pyrimidin‐4‐one) are reported. MTU features an ADA (A = acceptor and D = donor) hydrogen‐bonding site, while the three coformers show complementary DAD hydrogen‐bonding sites and therefore should be capable of forming an ADA/DAD N—H...O/N—H...N/N—H...S synthon with MTU. The experiments yielded one cocrystal and six cocrystal solvates, namely 6‐methyl‐2‐thiouracil–2,4‐diaminopyrimidine–1‐methylpyrrolidin‐2‐one (1/1/2), C₅H₆N₂OS·C₄H₆N₄·2C₅H₉NO, (I), 6‐methyl‐2‐thiouracil–2,4‐diaminopyrimidine (1/1), C₅H₆N₂OS·C₄H₆N₄, (II), 6‐methyl‐2‐thiouracil–2,4‐diaminopyrimidine–N,N‐dimethylacetamide (2/1/2), 2C₅H₆N₂OS·C₄H₆N₄·2C₄H₉NO, (III), 6‐methyl‐2‐thiouracil–2,4‐diaminopyrimidine–N,N‐dimethylformamide (2/1/2), C₅H₆N₂OS·0.5C₄H₆N₄·C₃H₇NO, (IV), 2,4,6‐triaminopyrimidinium 6‐methyl‐2‐thiouracilate–6‐methyl‐2‐thiouracil–N,N‐dimethylformamide (1/1/2), C₄H₈N₅⁺·C₅H₅N₂OS⁻·C₅H₆N₂OS·2C₃H₇NO, (V), 6‐methyl‐2‐thiouracil–6‐amino‐3H‐isocytosine–N,N‐dimethylformamide (1/1/1), C₅H₆N₂OS·C₄H₆N₄O·C₃H₇NO, (VI), and 6‐methyl‐2‐thiouracil–6‐amino‐3H‐isocytosine–dimethyl sulfoxide (1/1/1), C₅H₆N₂OS·C₄H₆N₄O·C₂H₆OS, (VII). Whereas in cocrystal (I) an R₂²(8) interaction similar to the Watson–Crick adenine/uracil base pair is formed and a two‐dimensional hydrogen‐bonding network is observed, the cocrystals (II)–(VII) contain the triply hydrogen‐bonded ADA/DAD N—H...O/N—H...N/N—H...S synthon and show a one‐dimensional hydrogen‐bonding network. Although 2,4‐diaminopyrimidine possesses only one DAD hydrogen‐bonding site, it is, due to orientational disorder, triply connected to two MTU molecules in (III) and (IV).     

3‐Cyano‐6‐hydroxy‐4‐methyl‐2‐pyridone: two new pseudopolymorphs and two cocrystals with products of an in situ nucleophilic aromatic substitution

Four crystal structures of 3‐cyano‐6‐hydroxy‐4‐methyl‐2‐pyridone (CMP), viz. the dimethyl sulfoxide monosolvate, C₇H₆N₂O₂·C₂H₆OS, (1), the N,N‐dimethylacetamide monosolvate, C₇H₆N₂O₂·C₄H₉NO, (2), a cocrystal with 2‐amino‐4‐dimethylamino‐6‐methylpyrimidine (as the salt 2‐amino‐4‐dimethylamino‐6‐methylpyrimidin‐1‐ium 5‐cyano‐4‐methyl‐6‐oxo‐1,6‐dihydropyridin‐2‐olate), C₇H₁₃N₄⁺·C₇H₅N₂O₂⁻, (3), and a cocrystal with N,N‐dimethylacetamide and 4,6‐diamino‐2‐dimethylamino‐1,3,5‐triazine [as the solvated salt 2,6‐diamino‐4‐dimethylamino‐1,3,5‐triazin‐1‐ium 5‐cyano‐4‐methyl‐6‐oxo‐1,6‐dihydropyridin‐2‐olate–N,N‐dimethylacetamide (1/1)], C₅H₁₁N₆⁺·C₇H₅N₂O₂⁻·C₄H₉NO, (4), are reported. Solvates (1) and (2) both contain the hydroxy group in a para position with respect to the cyano group of CMP, acting as a hydrogen‐bond donor and leading to rather similar packing motifs. In cocrystals (3) and (4), hydrolysis of the solvent molecules occurs and an in situ nucleophilic aromatic substitution of a Cl atom with a dimethylamino group has taken place. Within all four structures, an R₂²(8) N—H...O hydrogen‐bonding pattern is observed, connecting the CMP molecules, but the pattern differs depending on which O atom participates in the motif, either the ortho or para O atom with respect to the cyano group. Solvents and coformers are attached to these arrangements via single‐point O—H...O interactions in (1) and (2) or by additional R₄⁴(16) hydrogen‐bonding patterns in (3) and (4). Since the in situ nucleophilic aromatic substitution of the coformers occurs, the possible Watson–Crick C–G base‐pair‐like arrangement is inhibited, yet the cyano group of the CMP molecules participates in hydrogen bonds with their coformers, influencing the crystal packing to form chains.     

2,4‐Disila‐1,3,5‐oxadiazin,Cyclodisilazan‐Carbonsäure‐silylamid und ‐silylester

The lithium salts of the Me₃Si‐ as well as Me₃Si‐ and Me₂SiF‐substituted Cyclotrisilazanes I and II react with tert‐butylacylchloride under ring contraction and formation of the cyclodisilazane‐silylester, Me₃SiN(SiMe₂–N)₂SiMe₂–O–CO–CMe₃ ( 1 ). The lithium salt of the fluorodi‐methylsilyl‐substituted cyclotrisilazan III forms with benzoylchloride primarily in the analogous reaction the carboxy‐silyl‐amide, Me₂SiF(N–SiMe₂)₂SiMe₂–NH–CO–C₆H₅⁺ ( 2 ), which can be converted with III and benzoylchloride into the cyclodisilazane‐silylester, Me₂SiF(NSiMe₂)₂SiMe₂–O–CO–C₆H₅, ( 3 ). A silylester substituted six‐membered disila‐oxadiazine ( 4 ) is the result of the reaction of the lithiated cyclotrisilazane, (Me₂SiNH)₂, (Me₂SiNLi) with tert‐butyl‐acylchloride. The reaction includes anionic ring contraction and can be rationilized by a process analogous to keto‐enol‐tautomerism. Dilithiated octamethyl‐cyclotetrasilazane, (Me₂SiNHMe₂SiNLi)₂, reacts with tert‐butyl‐acylchloride or benzoylchloride in a molar ratio 1:2 to yield symmetrically acylestersubstituted cyclodisilazanes, (RCO–O–SiMe₂–NSiMe₂)₂, R = C₆H₅ ( 5 ), CMe₃ ( 6 ). The reaction mechanisms are discussed and the crystal structures of 2 and 6 are reported.     

Synthesis,crystal structures and anti‐inflammatory activity of four 3,5‐bis(arylidene)‐N‐benzenesulfonyl‐4‐piperidone derivatives

3,5‐Bis(arylidene)‐4‐piperidone (BAP) derivatives display good antitumour and anti‐inflammatory activities because of their double α,β‐unsaturated ketone structural characteristics. If N‐benzenesulfonyl substituents are introduced into BAPs, the configuration of the BAPs would change significantly and their anti‐inflammatory activities should improve. Four N‐benzenesulfonyl BAPs, namely (3E,5E)‐1‐(4‐methylbenzenesulfonyl)‐3,5‐bis[4‐(trifluoromethyl)benzylidene]piperidin‐4‐one dichloromethane monosolvate, C₂₈H₂₁F₆NO₃S·CH₂Cl₂, ( 4 ), (3E,5E)‐1‐(4‐fluorobenzenesulfonyl)‐3,5‐bis[4‐(trifluoromethyl)benzylidene]piperidin‐4‐one, C₂₇H₁₈F₇NO₃S, ( 5 ), (3E,5E)‐1‐(4‐nitrobenzenesulfonyl)‐3,5‐bis[4‐(trifluoromethyl)benzylidene]piperidin‐4‐one, C₂₇H₁₈F₆N₂O₅S, ( 6 ), and (3E,5E)‐1‐(4‐cyanobenzenesulfonyl)‐3,5‐bis[4‐(trifluoromethyl)benzylidene]piperidin‐4‐one dichloromethane monosolvate, C₂₈H₁₈F₆N₂O₃S·CH₂Cl₂, ( 7 ), were prepared by Claisen–Schmidt condensation and N‐sulfonylation. They were characterized by NMR, FT–IR and HRMS (high resolution mass spectrometry). Single‐crystal structure analysis reveals that the two 4‐(trifluoromethyl)phenyl rings on both sides of the piperidone ring in ( 4 )–( 7 ) adopt an E stereochemistry of the olefinic double bonds. Molecules of both ( 4 ) and ( 6 ) are connected by hydrogen bonds into one‐dimensional chains. In ( 5 ) and ( 7 ), pairs of adjacent molecules embrace through intermolecular hydrogen bonds to form a bimolecular combination, which are further extended into a two‐dimensional sheet. The anti‐inflammatory activity data reveal that ( 4 )–( 7 ) significantly inhibit LPS‐induced interleukin (IL‐6) and tumour necrosis factor (TNF‐α) secretion. Most importantly, ( 6 ) and ( 7 ), with strong electron‐withdrawing substituents, display more potential inhibitory effects than ( 4 ) and ( 5 ).     

Cocrystals of 2,6‐dichloroaniline and 2,6‐dichlorophenol plus three new pseudopolymorphs of their coformers

The structures of cocrystals of 2,6‐dichlorophenol with 2,4‐diamino‐6‐methyl‐1,3,5‐triazine, C₆H₄Cl₂O·C₄H₇N₅, (III), and 2,6‐dichloroaniline with 2,6‐diaminopyrimidin‐4(3H)‐one and N,N‐dimethylacetamide, C₆H₅Cl₂N·C₄H₆N₄O·C₄H₉NO, (V), plus three new pseudopolymorphs of their coformers, namely 2,4‐diamino‐6‐methyl‐1,3,5‐triazine–N,N‐dimethylacetamide (1/1), C₄H₇N₅·C₄H₉NO, (I), 2,4‐diamino‐6‐methyl‐1,3,5‐triazine–N‐methylpyrrolidin‐2‐one (1/1), C₄H₇N₅·C₅H₉NO, (II), and 6‐aminoisocytosine–N‐methylpyrrolidin‐2‐one (1/1), C₄H₆N₄O·C₅H₉NO, (IV), are reported. Both 2,6‐dichlorophenol and 2,6‐dichloroaniline are capable of forming definite synthon motifs, which usually lead to either two‐ or three‐dimensional crystal‐packing arrangements. Thus, the two isomorphous pseudopolymorphs of 2,4‐diamino‐6‐methyl‐1,3,5‐triazine, i.e. (I) and (II), form a three‐dimensional network, while the N‐methylpyrrolidin‐2‐one solvate of 6‐aminoisocytosine, i.e. (IV), displays two‐dimensional layers. On the basis of these results, attempts to cocrystallize 2,6‐dichlorophenol with 2,4‐diamino‐6‐methyl‐1,3,5‐triazine, (III), and 2,6‐dichloroaniline with 6‐aminoisocytosine, (V), yielded two‐dimensional networks, whereby in cocrystal (III) the overall structure is a consequence of the interaction between the two compounds. By comparison, cocrystal–solvate (V) is mainly built by 6‐aminoisocytosine forming layers, with 2,6‐dichloroaniline and the solvent molecules arranged between the layers.     

Thermotropic Liquid Crystals Based on Extended 2,5‐Disubstituted‐1,3,4‐Oxadiazoles: Structure–Property Relationships,Variable‐Temperature Powder X‐ray Diffraction,and Small‐Angle X‐ray Scattering Studies

A class of extended 2,5‐disubstituted‐1,3,4‐oxadiazoles R¹‐C₆H₄‐{OC₂N₂}‐C₆H₄‐R² (R¹=R²=C₁₀H₂₁O 1 a , p‐C₁₀H₂₁O‐C₆H₄‐C?C 3 a , p‐CH₃O‐C₆H₄‐C?C 3 b ; R¹=C₁₀H₂₁O, R²=CH₃O 1 b , (CH₃)₂N 1 c ; F 1 d ; R¹=C₁₀H₂₁O‐C₆H₄‐C?C, R²=C₁₀H₂₁O 2 a , CH₃O 2 b , (CH₃)₂N 2 c , F 2 d ) were prepared, and their liquid‐crystalline properties were examined. In CH₂Cl₂ solution, these compounds displayed a room‐temperature emission with λ_max at 340–471 nm and quantum yields of 0.73–0.97. Compounds 1 d , 2 a – 2 d , and 3 a exhibited various thermotropic mesophases (monotropic, enantiotropic nematic/smectic), which were examined by polarized‐light optical microscopy and differential scanning calorimetry. Structure determination by a direct‐space approach using simulated annealing or parallel tempering of the powder X‐ray diffraction data revealed distinctive crystal‐packing arrangements for mesogenic molecules 2 b and 3 a , leading to different nematic mesophase behavior, with 2 b being monotropic and 3 a enantiotropic in the narrow temperature range of 200–210 °C. The structural transitions associated with these crystalline solids and their mesophases were studied by variable‐temperature X‐ray diffractometry. Nondestructive phase transitions (crystal‐to‐crystal, crystal‐to‐mesophase, mesophase‐to‐liquid) were observed in the diffractograms of 1 b, 1 d , 2 b, 2 d , and 3 a measured at 25–200 °C. Powder X‐ray diffraction and small‐angle X‐ray scattering data revealed that the structure of the annealed solid residue 2 b reverted to its original crystal/molecular packing when the isotropic liquid was cooled to room temperature. Structure–property relationships within these mesomorphic solids are discussed in the context of their molecular structures and intermolecular interactions.     

Conformational analysis of some 1R,4S‐2‐arylidene‐p‐menthan‐3‐ones by 1H NMR spectroscopy and molecular simulation

Based on ¹H NMR spectral analysis combined with molecular simulation, conformational states of the cyclohexanone ring were studied for some 1R,4S‐2‐(4‐X‐benzylidene)‐p‐menthan‐3‐ones (X = COOCH₃ or C₆H₅) in CDCl₃ and C₆D₆. The co‐existence of chair conformers with an axial orientation of both alkyl substituents and twist‐boat forms was established for the compounds studied at room temperature (22–23° C). The substituent X does not influence appreciably the ratio of these conformers, but the fraction of twist‐boat forms increases noticeably in benzene solutions as compared with CDCl₃ solutions. Rotameric states of the isopropyl fragment were also characterised for the compounds studied. Distinctions in conformational states for the 1R,4S‐2‐arylidene‐p‐menthan‐3‐ones and (?)‐menthone were revealed and are discussed. Copyright © 2002 John Wiley & Sons, Ltd.     

Hydrogen bonding in polyamino‐polyalcohols: a monohydrated cocrystal of 1,3‐diamino‐5‐azaniumyl‐1,3,5‐trideoxy‐cis‐inositol iodide and 1,3,5‐triamino‐1,3,5‐trideoxy‐cis‐inositol

In the title monohydrated cocrystal, namely 1,3‐diamino‐5‐azaniumyl‐1,3,5‐trideoxy‐cis‐inositol iodide–1,3,5‐triamino‐1,3,5‐trideoxy‐cis‐inositol–water (1/1/1), C₆H₁₆N₃O₃⁺·I⁻·C₆H₁₅N₃O₃·H₂O, the neutral 1,3,5‐triamino‐1,3,5‐trideoxy‐cis‐inositol (taci) molecule and the monoprotonated 1,3‐diamino‐5‐azaniumyl‐1,3,5‐trideoxy‐cis‐inositol cation (Htaci⁺) both adopt a chair conformation, with the three O atoms in axial and the three N atoms in equatorial positions. The cation, but not the neutral taci unit, exhibits intramolecular O—H...O hydrogen bonding. The entire structure is stabilized by a complex three‐dimensional network of intermolecular hydrogen bonds. The neutral taci entities and the Htaci⁺ cations are each aligned into chains along [001]. In these chains, two O—H...N interactions generate a ten‐membered ring as the predominant structural motif. The rings consist of vicinal 2‐amino‐1‐hydroxyethylene units of neighbouring molecules, which are paired via centres of inversion. The chains are interconnected into undulating layers parallel to the ac plane, and the layers are further held together by O—H...N hydrogen bonds and additional interactions with the iodide counter‐anions and solvent water molecules.     

High‐ and low‐temperature phases in isostructural 4‐chloro‐3‐nitroaniline and 4‐iodo‐3‐nitroaniline

The structures of 4‐chloro‐3‐nitroaniline, C₆H₅ClN₂O₂, (I), and 4‐iodo‐3‐nitroaniline, C₆H₅IN₂O₂, (II), are isomorphs and both undergo continuous (second order) phase transitions at 237 and 200 K, respectively. The structures, as well as their phase transitions, have been studied by single‐crystal X‐ray diffraction, Raman spectroscopy and difference scanning calorimetry experiments. Both high‐temperature phases (293 K) show disorder of the nitro substituents, which are inclined towards the benzene‐ring planes at two different orientations. In the low‐temperature phases (120 K), both inclination angles are well maintained, while the disorder is removed. Concomitantly, the b axis doubles with respect to the room‐temperature cell. Each of the low‐temperature phases of (I) and (II) contains two pairs of independent molecules, where the molecules in each pair are related by noncrystallographic inversion centres. The molecules within each pair have the same absolute value of the inclination angle. The Flack parameter of the low‐temperature phases is very close to 0.5, indicating inversion twinning. This can be envisaged as stacking faults in the low‐temperature phases. It seems that competition between the primary amine–nitro N—H...O hydrogen bonds which form three‐centred hydrogen bonds is the reason for the disorder of the nitro groups, as well as for the phase transition in both (I) and (II). The backbones of the structures are formed by N—H...N hydrogen bonding of moderate strength which results in the graph‐set motif C(3). This graph‐set motif forms a zigzag chain parallel to the monoclinic b axis and is maintained in both the high‐ and the low‐temperature structures. The primary amine groups are pyramidal, with similar geometric values in all four determinations. The high‐temperature phase of (II) has been described previously [Garden et al. (2004). Acta Cryst. C 60 , o328–o330].     

Temperature‐controlled ionic liquid‐dispersive liquid‐phase microextraction for preconcentration of chlorotoluron,diethofencarb and chlorbenzuron in water samples

This article describes a new, rapid and sensitive method for the determination of chlorotoluron, diethofencarb and chlorbenzuron from water samples with temperature‐controlled ionic liquid‐dispersive liquid‐phase microextraction. In the preconcentration procedure, ionic liquid 1‐hexyl‐3‐methylimidazolium hexafluorophosphate [C₆MIM] [PF₆] was employed as the extraction solvent. The parameters, such as volume of [C₆MIM] [PF₆], sample pH, extraction time, centrifuging time, temperature and salting‐out effect, were investigated in detail. Under the optimal extraction conditions, it has been found that three analytes had excellent LODs (S/N=3) in the range of 0.04–0.43 μg/L. The RSDs (n=6) were in the range of 1.3–4.7%. The proposed method was evaluated with lake water, tap water and melted snow water samples. The experimental results indicated that the proposed method had excellent prospect and would be widely used in the future.     

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.     

Pseudopolymorphs of 2,6‐diaminopyrimidin‐4‐one and 2‐amino‐6‐methylpyrimidin‐4‐one: one or two tautomers present in the same crystal

The derivatives of pyrimidin‐4‐one can adopt either a 1H‐ or a 3H‐tautomeric form, which affects the hydrogen‐bonding interactions in cocrystals with compounds containing complementary functional groups. In order to study their tautomeric preferences, we crystallized 2,6‐diaminopyrimidin‐4‐one and 2‐amino‐6‐methylpyrimidin‐4‐one. During various crystallization attempts, four structures of 2,6‐diaminopyrimidin‐4‐one were obtained, namely solvent‐free 2,6‐diaminopyrimidin‐4‐one, C₄H₆N₄O, (I), 2,6‐diaminopyrimidin‐4‐one–dimethylformamide–water (3/4/1), C₄H₆N₄O·1.33C₃H₇NO·0.33H₂O, (Ia), 2,6‐diaminopyrimidin‐4‐one dimethylacetamide monosolvate, C₄H₆N₄O·C₄H₉NO, (Ib), and 2,6‐diaminopyrimidin‐4‐one–N‐methylpyrrolidin‐2‐one (3/2), C₄H₆N₄O·1.5C₅H₉NO, (Ic). The 2,6‐diaminopyrimidin‐4‐one molecules exist only as 3H‐tautomers. They form ribbons characterized by R²₂(8) hydrogen‐bonding interactions, which are further connected to form three‐dimensional networks. An intermolecular N—H...N interaction between amine groups is observed only in (I). This might be the reason for the pyramidalization of the amine group. Crystallization experiments on 2‐amino‐6‐methylpyrimidin‐4‐one yielded two isostructural pseudopolymorphs, namely 2‐amino‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐6‐methylpyrimidin‐4(1H)‐one–dimethylacetamide (1/1/1), C₅H₇N₃O·C₅H₇N₃O·C₄H₉NO, (IIa), and 2‐amino‐6‐methylpyrimidin‐4(3H)‐one–2‐amino‐6‐methylpyrimidin‐4(1H)‐one–N‐methylpyrrolidin‐2‐one (1/1/1), C₅H₇N₃O·C₅H₇N₃O·C₅H₉NO, (IIb). In both structures, a 1:1 mixture of 1H‐ and 3H‐tautomers is present, which are linked by three hydrogen bonds similar to a Watson–Crick C–G base pair.     

Supramolecular architectures in the salt trimethoprimium ferrocene‐1‐carboxylate and the cocrystal 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–ferrocene‐1‐carboxylic acid (1/1)

In the salt trimethoprimium ferrocenecarboxylate [systematic name: 2,4‐diamino‐5‐(3,4,5‐trimethoxybenzyl)pyrimidin‐1‐ium ferrocene‐1‐carboxylate], (C₁₄H₁₉N₄O₃)[Fe(C₅H₅)(C₆H₄O₂)], (I), of the antibacterial compound trimethoprim, the carboxylate group interacts with the protonated aminopyrimidine group of trimethoprim via two N—H…O hydrogen bonds, generating a robust R ₂²(8) ring motif (heterosynthon). However, in the cocrystal 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–ferrocene‐1‐carboxylic acid (1/1), [Fe(C₅H₅)(C₆H₅O₂)]·C₆H₈ClN₃, (II), the carboxyl–aminopyrimidine interaction [R ₂²(8) motif] is absent. The carboxyl group interacts with the pyrimidine ring via a single O—H…N hydrogen bond. The pyrimidine rings, however, form base pairs via a pair of N—H…N hydrogen bonds, generating an R ₂²(8) supramolecular homosynthon. In salt (I), the unsubstituted cyclopentadienyl ring is disordered over two positions, with a refined site‐occupation ratio of 0.573 (10):0.427 (10). In this study, the two five‐membered cyclopentadienyl (Cp) rings of ferrocene are in a staggered conformation, as is evident from the C…Cg …Cg …C pseudo‐torsion angles, which are in the range 36.13–37.53° for (I) and 22.58–23.46° for (II). Regarding the Cp ring of the minor component in salt (I), the geometry of the ferrocene ring is in an eclipsed conformation, as is evident from the C…Cg …Cg …C pseudo‐torsion angles, which are in the range 79.26–80.94°. Both crystal structures are further stabilized by weak π–π interactions.     

Three one‐dimensional coordination polymers based on 1,1′‐bis(pyridin‐4‐ylmethyl)‐2,2′‐bi‐1H‐benzimidazole and HgX2 (X = Cl,Br and I)

A new 2,2′‐bi‐1H‐benzimidazole bridging organic ligand, namely 1,1′‐bis(pyridin‐4‐ylmethyl)‐2,2′‐bi‐1H‐benzimidazole, C₂₆H₂₀N₆, L or (I), has been synthesized and used to create three new one‐dimensional coordination polymers, viz.catena‐poly[[dichloridomercury(II)]‐μ‐1,1′‐bis(pyridin‐4‐ylmethyl)‐2,2′‐bi‐1H‐benzimidazole], [HgCl₂(C₂₆H₂₀N₆)]_n, (II), and the bromido, [HgBr₂(C₂₆H₂₀N₆)]_n, (III), and iodido, [HgI₂(C₂₆H₂₀N₆)]_n, (IV), analogues. Free ligand L crystallizes with two symmetry‐independent half‐molecules in the asymmetric unit and each L molecule resides on a crytallographic inversion centre. In structures (II)–(IV), the L ligand is also positioned on a crystallographic inversion centre, whereas the Hg centre resides on a crystallographic twofold axis. Compound (I) adopts an anti conformation in the solid state and forms a two‐dimensional network in the crystallographic bc plane viaπ–π and C—H...π interactions. The three Hg^II coordination complexes, (II)–(IV), have one‐dimensional zigzag chains composed of L and HgX₂ (X = Cl, Br and I), and the Hg^II centres are in a distorted tetrahedral [HgX₂N₂] coordination geometry. Complexes (III) and (IV) are isomorphous, whereas complex (II) displays an interesting conformational difference from the others, i.e. a twist in the flexible bridging ligand.     

BIAN‐Fe(η6‐C6H6): Synthesis,characterization, and l‐lactide polymerization

The α‐diimine‐ligated Fe‐complex, BIAN‐Fe(C₆H₆) , was synthesized and evaluated for the polymerization of l ‐lactide. Characterization of BIAN‐Fe(C₆H₆) reveals that it is redox non‐innocent and suggests that it is an Fe(I) species bearing a radical‐anionic ligand. We will demonstrate that BIAN‐Fe(C₆H₆) is active for the ring‐opening polymerization of l ‐lactide, and that polymer is produced with, or without, the use of an added external initiator. Interestingly, very high molecular weight polymers are produced in the absence of external initiator whereas polymer molecular weights that agree with theoretical calculations are produced in the presence of external initiator. To the best of our knowledge, BIAN‐Fe(C₆H₆) is the first Fe‐based α‐diimine catalyst reported to be active for the polymerization of l ‐lactide. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2824–2830     

Luminescent Amphiphilic 2,6‐Bis(1‐alkylpyrazol‐3‐yl)pyridyl Platinum(II) Complexes: Synthesis,Characterization, Electrochemical,Photophysical, and Langmuir–Blodgett Film Formation Studies

Two series of novel platinum(II) 2,6‐bis(1‐alkylpyrazol‐3‐yl)pyridyl (N5Cn) complexes, [Pt(N5Cn)Cl][X] ( 1 – 9 ) and [Pt(N5Cn)(C?CR)][X] ( 10 – 13 ) (X=trifluoromethanesulfonate (OTf) or PF₆; R=C₆H₅, C₆H₄‐p‐CF₃ and C₆H₄‐p‐N(C₆H₅)₂), with various chain lengths of the alkyl groups on the nitrogen atom of the pyrazolyl units have been successfully synthesized and characterized. Their electrochemical and photophysical properties have been studied. Some of their molecular structures have also been determined by X‐ray crystallography. Two amphiphilic platinum(II) 2,6‐bis(1‐tetradecylpyrazol‐3‐yl)pyridyl (N5C14) complexes, [Pt(N5C14)Cl]PF₆ ( 7 ) and [Pt(N5C14)(C?CC₆H₅)]PF₆ ( 13 ), were found to form stable and reproducible Langmuir–Blodgett (LB) films at the air–water interface. The characterization of such LB films has been investigated by the study of their surface pressure–area (π–A) isotherms, UV/Vis spectroscopy, XRD, X‐ray photoelectron spectroscopy (XPS), FTIR, and polarized IR spectroscopy. The luminescence property of 13 in LB films has also been studied.     

Three Salts Containing the Fullerene Tetra‐Anion C604– – Synthesis,X‐Ray Single‐Crystal Structure Determination and EPR Investigation

A synthesis for four‐fold negatively charged fullerides in solution is presented. Three salts containing discrete C₆₀^4– anions were synthesized by the reduction of C₆₀ in solution using rubidium‐mercury amalgams and rubidium suboxide both in the presence of elemental mercury. The three new salts, [Rb₆DMF₁₄(C₆H₁₃N₂O₂)₂] · C₆₀ ( 1 ), [Rb(diaza‐18‐crown‐6)]₄ · C₆₀ · (en)_4.1 ( 2 ), and [Rb(benzo‐18‐crown‐6)]₄ · C₆₀ ( 3 ), were characterized by single‐crystal X‐ray diffraction. The results clearly indicate a charge of 4– for the fulleride anions. In 1 the fulleride units are ordered, and their distortion from I_h symmetry shows similarities to binary alkali metal fullerides that contain C₆₀^4– anions. In the crystal structures of 2 and 3 the C₆₀^4– anions show a rotational disorder. In all structures the 6:6 bond lengths within the fulleride are strongly enlarged compared to the ones in neutralC₆₀. EPR measurements reveal a singlet state for the C₆₀^4– anion.     

Transition‐Metal Complexes Based on the 1,3,5‐Triethynyl Benzene Linking Unit

The synthesis of a unique series of heteromultinuclear transition metal compounds is reported. Complexes 1‐I‐3‐Br‐5‐(FcC≡C)‐C₆H₃ ( 4 ), 1‐Br‐3‐(bpy‐C≡C)‐5‐(FcC≡C)‐C₆H₃ ( 6 ), 1,3‐(bpy‐C≡C)₂‐5‐(FcC≡C)‐C₆H₃ ( 7 ), 1‐(XC≡C)‐3‐(bpy‐C≡C)‐5‐(FcC≡C)‐C₆H₃ ( 8 , X = SiMe₃; 9 , X = H), 1‐(HC≡C)‐3‐[(CO)₃ClRe(bpy‐C≡C)]‐5‐(FcC≡C)‐C₆H₃ ( 11 ), 1‐[(Ph₃P)AuC≡C]‐3‐[(CO)₃ClRe(bpy‐C≡C)]‐5‐(FcC≡C)‐C₆H₃ ( 13 ), 1‐[(Ph₃P)AuC≡C]‐3‐(bpy‐C≡C)‐5‐(FcC≡C)‐C₆H₃ ( 14 ), [1‐[(Ph₃PAuC≡C]‐3‐[{[Ti](C≡CSiMe₃)₂}Cu(bpy‐C≡C)]‐5‐(FcC≡C)‐C₆H₃]PF₆ ( 16 ), and [1,3‐[(tBu₂bpy)₂Ru(bpy‐C≡C)]₂‐5‐(FcC≡C)‐C₆H₃](PF₆)₄ ( 18 ) (Fc = (η⁵‐C₅H₄)(η⁵‐C₅H₅)Fe, bpy = 2,2′‐bipyridiyl‐5‐yl, [Ti] = (η⁵‐C₅H₄SiMe₃)₂Ti) were prepared by using consecutive synthesis methodologies including metathesis, desilylation, dehydrohalogenation, and carbon–carbon cross‐coupling reactions. In these complexes the corresponding metal atoms are connected by carbon‐rich bridging units comprising 1,3‐diethynyl‐, 1,3,5‐triethynylbenzene and bipyridyl units. They were characterized by elemental analysis, IR and NMR spectroscopy, and partly by ESI‐TOF mass spectrometry., The structures of 4 and 11 in the solid state are reported. Both molecules are characterized by the central benzene core bridging the individual transition metal complex fragments. The corresponding acetylide entities are, as typical, found in a linear arrangement with representative M–C, C–C_C≡C and C≡C bond lengths.