Structural consequences of weak interactions in dispirooxindole derivatives

Spiro scaffolds are being increasingly utilized in drug discovery due to their inherent three‐dimensionality and structural variations, resulting in new synthetic routes to introduce spiro building blocks into more pharmaceutically active molecules. Multicomponent cascade reactions, involving the in situ generation of carbonyl ylides from α‐diazocarbonyl compounds and aldehydes, and 1,3‐dipolar cycloadditon with 3‐arylideneoxindoles gave a novel class of dispirooxindole derivatives, namely 1,1′′‐dibenzyl‐5′‐(4‐chlorophenyl)‐4′‐phenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione, C₄₄H₃₃ClN₂O₃, (I), 1′′‐acetyl‐1‐benzyl‐5′‐(4‐chlorophenyl)‐4′‐phenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione, C₃₉H₂₉ClN₂O₄, (II), 1′′‐acetyl‐1‐benzyl‐4′,5′‐diphenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione, C₃₉H₃₀N₂O₄, (III), and 1′′‐acetyl‐1‐benzyl‐4′,5′‐diphenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione acetonitrile hemisolvate, C₃₉H₃₀N₂O₄·0.5C₂H₃N, (IV). All four compounds exist as racemic mixtures of the SSSR and RRRS stereoisomers. In these structures, the two H atoms of the dihydrofuran ring and the two substituted oxindole rings are in a trans orientation, facilitating intramolecular C—H...O and π–π interactions. These weak interactions play a prominent role in the structural stability and aid the highly regio‐ and diastereoselective synthesis. In each of the four structures, the molecular assembly in the crystal is also governed by weak noncovalent interactions. Compound (IV) is the solvated analogue of (III) and the two compounds show similar structural features.     

A structural study of 4‐aminoantipyrine and six of its Schiff base derivatives

Six derivatives of 4‐amino‐1,5‐dimethyl‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐3‐one (4‐aminoantipyrine), C₁₁H₁₃N₃O, (I), have been synthesized and structurally characterized to investigate the changes in the observed hydrogen‐bonding motifs compared to the original 4‐aminoantipyrine. The derivatives were synthesized from the reactions of 4‐aminoantipyrine with various aldehyde‐, ketone‐ and ester‐containing molecules, producing (Z)‐methyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₆H₁₉N₃O₃, (II), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₇H₂₁N₃O₃, (III), ethyl 2‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]cyclohex‐1‐enecarboxylate, C₂₀H₂₅N₃O₃, (IV), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]‐3‐phenylacrylate, C₂₂H₂₃N₃O₃, (V), 2‐cyano‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, C₁₄H₁₄N₄O₂, (VI), and (E)‐methyl 4‐{[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]methyl}benzoate, C₂₀H₁₉N₃O₃, (VII). The asymmetric units of all these compounds have one molecule on a general position. The hydrogen bonding in (I) forms chains of molecules via intermolecular N—H...O hydrogen bonds around a crystallographic sixfold screw axis. In contrast, the formation of enamines for all derived compounds except (VII) favours the formation of a six‐membered intramolecular N—H...O hydrogen‐bonded ring in (II)–(V) and an intermolecular N—H...O hydrogen bond in (VI), whereas there is an intramolecular C—H...O hydrogen bond in the structure of imine (VII). All the reported compounds, except for (II), feature π–π interactions, while C—H...π interactions are observed in (II), C—H...O interactions are observed in (I), (III), (V) and (VI), and a C—O...π interaction is observed in (II).     

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.     

Synthesis and Structures of New Oxidation/ Cycloaddition Products of λ3‐Cyclodiphosphazanes

Reaction of the cyclodiphosphazane [(OC₄H₈N)P(μ‐N‐t‐Bu)₂P(HN‐t‐Bu)] ( 1 ) with an equimolar quantity of diisopropyl azodicarboxylate afforded the phosphinimine product [(OC₄H₈N)P(μ‐N‐t‐Bu)₂P=N‐t‐Bu)(N(CO₂ ‐i‐Pr)NHCO₂‐i‐Pr] ( 6 ) having a P^III‐N‐P^V skeleton. Similar products [(t‐BuNH)P(μ‐N‐t‐Bu)₂P=N‐t‐Bu)(N(CO₂Et)NHCO₂Et] ( 7 ) and [(CO₂‐i‐Pr)HNN(CO₂‐i‐Pr)](t‐BuN=P(μ‐N‐t‐Bu)₂POCH₂CMe₂CH₂O[P(μ‐N‐t‐Bu)₂P=N‐t‐Bu)(N(CO₂‐i‐Pr)NH(CO₂‐i‐Pr)] ( 8 ) were spectroscopically characterized in the reaction of [(t‐BuNH)P‐N‐t‐Bu]₂ ( 2 ) and [(t‐BuNH)P(μ‐N‐t‐Bu)₂POCH₂CMe₂CH₂OP(μ‐N‐t‐Bu)₂P(NH‐t‐Bu)] ( 3 ) with diethyl‐ and diisopropyl azodicarboxylate, respectively. By contrast, the reaction of [(μ‐t‐BuN)P]₂[O‐6‐t‐Bu‐4‐Me‐C₆H₂]₂CH₂ ( 4 ) and [(C₅H₁₀N)P‐μ‐N‐t‐Bu]₂ ( 5 ) with diisopropyl azodicarboxylate afforded the mono‐ and bis‐oxidized compounds [(O)P(μ‐N‐t‐Bu)₂P][O‐6‐t‐Bu‐4‐Me‐C₆H₂]₂CH₂ ( 9 ) and [(C₅H₁₀N)(O)P‐μ‐N‐t‐Bu]₂ ( 10 ), respectively. Oxidative addition of o‐chloranil to 7 and its DIAD analogue [(t‐BuNH)P(μ‐N‐t‐Bu)₂P=N‐t‐Bu)(N(CO₂‐i‐Pr)NHCO₂‐i‐Pr] ( 11 ) afforded [(C₆Cl₄‐1, 2‐O₂)(t‐BuNH)P(μ‐N‐t‐Bu)₂P=N‐t‐Bu)(N(CO₂R)NHCO₂R] [R = Et ( 12 ) and i‐Pr ( 13 )] containing tetra‐ and pentacoordinate P^V atoms in the cyclodiphosphazane ring. The structures of 6 , 9 , 12 and 13 have been confirmed by X‐ray structure determination. For comparison, the X‐ray structure of the double cycloaddition product [(C₆Cl₄‐1, 2‐O₂)(t‐BuNH)PN‐t‐Bu]₂ ( 14 ), obtained from the reaction of 2 with two mole equivalents of o‐chloranil is also reported.     

The influence of sulfur substituents on the molecular geometry and packing of thio derivatives of N‐methylphenobarbital

The room‐temperature crystal structures of four new thio derivatives of N‐methylphenobarbital [systematic name: 5‐ethyl‐1‐methyl‐5‐phenylpyrimidine‐2,4,6(1H,3H,5H)‐trione], C₁₃H₁₄N₂O₃, are compared with the structure of the parent compound. The sulfur substituents in N‐methyl‐2‐thiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐2‐thioxo‐1,2‐dihydropyrimidine‐4,6(3H,5H)‐dione], C₁₃H₁₄N₂O₂S, N‐methyl‐4‐thiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐4‐thioxo‐3,4‐dihydropyrimidine‐2,6(1H,5H)‐dione], C₁₃H₁₄N₂O₂S, and N‐methyl‐2,4,6‐trithiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenylpyrimidine‐2,4,6(1H,3H,5H)‐trithione], C₁₃H₁₄N₂S₃, preserve the heterocyclic ring puckering observed for N‐methylphenobarbital (a half‐chair conformation), whereas in N‐methyl‐2,4‐dithiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidine‐6(5H)‐one], C₁₃H₁₄N₂OS₂, significant flattening of the ring was detected. The number and positions of the sulfur substituents influence the packing and hydrogen‐bonding patterns of the derivatives. In the cases of the 2‐thio, 4‐thio and 2,4,6‐trithio derivatives, there is a preference for the formation of a ring motif of the R₂²(8) type, which is also a characteristic of N‐methylphenobarbital, whereas a C(6) chain forms in the 2,4‐dithio derivative. The preferences for hydrogen‐bond formation, which follow the sequence of acceptor position 4 > 2 > 6, confirm the differences in the nucleophilic properties of the C atoms of the heterocyclic ring and are consistent with the course of N‐methylphenobarbital thionation reactions.     

Comparison of the structure of (E)‐2‐(2‐benzylidenehydrazinylidene)quinoxaline with those of its chloro‐ and bromobenzylidene analogues

(E)‐2‐(2‐Benzylidenehydrazinylidene)quinoxaline, C₁₅H₁₂N₄, crystallized with two molecules in the asymmetric unit. The structures of six halogen derivatives of this compound were also investigated: (E)‐2‐[2‐(2‐chlorobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁ClN₄; (E)‐2‐[2‐(3‐chlorobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁ClN₄; (E)‐2‐[2‐(4‐chlorobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁ClN₄; (E)‐2‐[2‐(2‐bromobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁BrN₄; (E)‐2‐[2‐(3‐bromobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁BrN₄; (E)‐2‐[2‐(4‐bromobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁BrN₄. The 3‐Cl and 3‐Br compounds are isomorphous, as are the 4‐Cl and 4‐Br compounds. In all of these compounds, it was found that the supramolecular structures are governed by similar predominant patterns, viz. strong intermolecular N—H...N(pyrazine) hydrogen bonds supplemented by weak C—H...N(pyrazine) hydrogen‐bond interactions in the 2‐ and 3‐halo compounds and by C—H...Cl/Br interactions in the 4‐halo compounds. In all compounds, there are π–π stacking interactions.     

Design and Synthesis of Two Aromatic Amines with Dendritic Structure

The design and synthesis of two aromatic amines with dendritic structures, i.e. 3,4,5‐tribenzyloxyaniline (3,4,5‐G₁‐NH₂) and 2,5‐dibenzyloxyaniline (2,5‐G₁‐NH₂), were conducted. A coupling reaction of three or two equivalents of benzyl bromide to one equivalent of methyl hydroxybenzoate generated methyl 3,4,5‐tribenzyloxybenzoate (3,4,5‐G₁‐COOCH₃), methyl 2,5‐dibenzyloxybenzoate (2,5‐G₁‐COOCH₃) and 2,6‐dibenzyloxybenzoate (2,6‐G₁‐COOCH₃) in high yields. All G₁‐COOCH₃ derivatives were studied by X‐ray analysis. The results show that these dendrons have sufficient volume to be used as the fine ligands for certain catalysts. The amide intermediates (benzamide, G₁‐CONH₂) were obtained by reaction between ammonia and G₁‐COOCH₃. Interestingly, 2,6‐dibenzyloxybenzamide (2,6‐G₁‐CONH₂) can not be prepared in the same condition, which may be due to the overlarge steric block. Sodium hypochlorite was an effective oxidant to generate methyl carbamates G₁‐ NHCO₂CH₃.     

Regiospecific one‐pot synthesis of new trifluoromethyl substituted heteroaryl pyrazolyl ketones

A convenient and general method for the regiospecific synthesis of three novel series of 1‐(2‐thenoyl)‐, 1‐(2‐furoyl)‐ and 1‐(isonicotinoyl)‐3‐alkyl(aryl)‐5‐hydroxy‐5‐trifluoromethyl‐4,5‐dihydro‐1H‐pyrazoles, in good yields (53 – 91 %), from the cyclocondensation reactions of 1,1,1‐trifluoro‐4‐alkoxy‐4‐alkyl(aryl)‐but‐3‐en‐2‐ones, where alkyl = H and Me; aryl = ‐C₆H₅, 4‐CH₃C₆H₄, 4‐CH₃OC₆H₄, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐BrC₆H₄, 4‐NO₂CgH₄ with 2‐thiophenecarboxylic hydrazide, furoic hydrazide and isonicotinic acid hydrazide, respectively, is reported. Subsequently dehydration reaction of phenyl substituted 2‐pyrazolines with P₂O₅ furnished the corresponding 1H‐pyrazoles as mixture of regioisomers and in low yields (35 – 36 %).     

Synthesis of Fe3O4 Microspheres-Supported Catalysts for Suzuki Coupling Reaction

Two new Fe₃O₄ microspheres‐supported semi‐homogeneous catalysts, namely Fe₃O₄‐G4‐polyaminoamido (PAMAM) dendrimers‐Pd(0) and Fe₃O₄‐polyethylene glycols (PEGs)‐Pd(0) were synthesized and characterized by X‐ray powder diffraction, infrared spectrum, scanning electron microscopy, transmission electron microscopy, X‐ray photoelectron spectroscopy and thermal gravimetric analysis, which can catalyze Suzuki coupling reactions. The performance of catalysts was tested for the reactions of aryl halides with phenyl boronic acid and compared with a heterogeneous catalyst Fe₃O₄‐(3‐aminopropyl)triethoxysilane (APTS)‐Pd(0), in which Fe₃O₄‐G4‐PAMAM dendrimers‐Pd(0) shows the best activity among the three catalysts. The order of the catalytic activities is Fe₃O₄‐G4‐PAMAM dendrimers‐Pd(0)>Fe₃O₄‐PEGs‐Pd(0)>Fe₃O₄‐APTS‐Pd(0). The catalysts can be quickly and completely recovered by simply applying a magnet of 105 mT and the efficiencies remain unaltered even after four recycles.     

Crystal structures of deprotonated nucleobases from an expanded DNA alphabet

Reported here is the crystal structure of a heterocycle that implements a donor–donor–acceptor hydrogen‐bonding pattern, as found in the Z component [6‐amino‐5‐nitropyridin‐2(1H)‐one] of an artificially expanded genetic information system (AEGIS). AEGIS is a new form of DNA from synthetic biology that has six replicable nucleotides, rather than the four found in natural DNA. Remarkably, Z crystallizes from water as a 1:1 complex of its neutral and deprotonated forms, and forms a `skinny' pyrimidine–pyrimidine pair in this structure. The pair resembles the known intercalated cytosine pair. The formation of the same pair in two different salts, namely poly[[aqua(μ₆‐2‐amino‐6‐oxo‐3‐nitro‐1,6‐dihydropyridin‐1‐ido)sodium]–6‐amino‐5‐nitropyridin‐2(1H)‐one–water (1/1/1)], denoted Z‐Sod, {[Na(C₅H₄N₃O₃)(H₂O)]·C₅H₅N₃O₃·H₂O}_n, and ammonium 2‐amino‐6‐oxo‐3‐nitro‐1,6‐dihydropyridin‐1‐ide–6‐amino‐5‐nitropyridin‐2(1H)‐one–water (1/1/1), denoted Z‐Am, NH₄⁺·C₅H₄N₃O₃⁻·C₅H₅N₃O₃·H₂O, under two different crystallization conditions suggests that the pair is especially stable. Implications of this structure for the use of this heterocycle in artificial DNA are discussed.     

The structures of 1,4‐diaryl‐5‐trifluoromethyl‐1H‐1,2,3‐triazoles related to J147, a drug for treating Alzheimer's disease

J147 [N‐(2,4‐dimethylphenyl)‐2,2,2‐trifluoro‐N′‐(3‐methoxybenzylidene)acetohydrazide] has recently been reported as a promising new drug for the treatment of Alzheimer's disease. The X‐ray structures of seven new 1,4‐diaryl‐5‐trifluoromethyl‐1H‐1,2,3‐triazoles, namely 1‐(3,4‐dimethylphenyl)‐4‐phenyl‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₇H₁₄F₃N₃, 1 ), 1‐(3,4‐dimethylphenyl)‐4‐(3‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₆F₃N₃O, 2 ), 1‐(3,4‐dimethylphenyl)‐4‐(4‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₆F₃N₃O, 3 ), 1‐(2,4‐dimethylphenyl)‐4‐(4‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₆F₃N₃O, 4 ), 1‐[2,4‐bis(trifluoromethyl)phenyl]‐4‐(3‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₀F₉N₃O, 5 ), 1‐(3,4‐dimethoxyphenyl)‐4‐(3,4‐dimethoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₉H₁₈F₃N₃O₄, 6 ) and 3‐[4‐(3,4‐dimethoxyphenyl)‐5‐(trifluoromethyl)‐1H‐1,2,3‐triazol‐1‐yl]phenol (C₁₇H₁₄F₃N₃O₃, 7 ), have been determined and compared to that of J147 . B3LYP/6‐311++G(d,p) calculations have been performed to determine the potential surface and molecular electrostatic potential (MEP) of J147 , and to examine the correlation between hydrazone J147 and the 1,2,3‐triazoles, both bearing a CF₃ substituent. Using MEPs, it was found that the minimum‐energy conformation of 4 , which is nearly identical to its X‐ray structure, is closely related to one of the J147 seven minima.     

Investigation of the effect of the N‐oxidation process on the interaction of selected pyridine compounds with biomacromolecules: structural,spectral, theoretical and docking studies

Two new N‐oxide compounds, namely glycinium 2‐carboxy‐1‐(λ¹‐oxidaneyl)‐1λ⁴‐pyridine‐6‐carboxylate–glycine–water (1/1/1), C₂H₆NO₂⁺·C₇H₄NO₅^?·C₂H₅NO₂·H₂O or [(2,6‐HpydcO)(HGLY)(GLY)(H₂O)], 1 , and methyl 6‐carboxy‐1‐(λ¹‐oxidaneyl)‐1λ⁴‐pyridine‐2‐carboxylate, C₈H₇NO₅ or 2,6‐HMepydcO, 2 , were prepared and identified by elemental analysis, FT–IR, Raman spectroscopy and single‐crystal X‐ray diffraction. The X‐ray analysis of 1 revealed an ionic compound containing a 2,6‐HpydcO^? anion, a glycinium cation, a neutral glycine molecule and a water molecule. Compound 2 is a neutral compound with two independent units in its crystal structure. In addition to the hydrogen bonds, the crystal network is stabilized by π–π stacking interactions of the types pyridine–carboxylate and carboxylate–carboxylate. The thermodynamic stability and charge‐distribution patterns for isolated molecules of 2,6‐H₂pydcO and 2,6‐HMepydcO, and their two similar derivatives, pyridine‐2,6‐dicarboxylic acid (2,6‐H₂pydc) and dimethyl 1‐(λ¹‐oxidaneyl)‐1λ⁴‐pyridine‐2,6‐dicarboxylate (2,6‐Me₂pydcO), were studied by density functional theory (DFT) and natural bond orbital (NBO) analysis, respectively. The ability of these compounds and their analogues to interact with nine selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS and Top II) was investigated using docking calculations.     

Multicomponent crystals of erlotinib

Erlotinib [systematic name: N‐(3‐ethynylphenyl)‐6,7‐bis(2‐methoxyethoxy)quinazolin‐4‐amine], a small‐molecule epidermal growth factor receptor inhibitor, useful for the treatment of non‐small‐cell lung cancer, has been crystallized as erlotinib monohydrate, C₂₂H₂₃N₃O₄·H₂O, (I), the erlotinib hemioxalate salt [systematic name: 4‐amino‐N‐(3‐ethynylphenyl)‐6,7‐bis(2‐methoxyethoxy)quinazolin‐1‐ium hemioxalate], C₂₂H₂₄N₃O₄⁺·0.5C₂O₄²⁻, (II), and the cocrystal erlotinib fumaric acid hemisolvate dihydrate, C₂₂H₂₃N₃O₄·0.5C₄H₄O₄·2H₂O, (III). In (II) and (III), the oxalate anion and the fumaric acid molecule are located across inversion centres. The water molecules in (I) and (III) play an active role in hydrogen‐bonding interactions which lead to the formation of tetrameric and hexameric hydrogen‐bonded networks, while in (II) the cations and anions form a tetrameric hydrogen‐bonded network in the crystal packing. The title multicomponent crystals of erlotinib have been elucidated to study the assembly of molecules through intermolecular interactions, such as hydrogen bonds and aromatic π–π stacking.     

Thermal isomerization of ruthenium hydride compounds containing asymmetric bidentate pyrrole‐imine ligands

A series of ruthenium hydride compounds containing substituted bidentate pyrrole‐imine ligands were synthesized and characterized. Reacting RuHCl(CO)(PPh₃)₃ with one equivalent of [C₄H₃NH(2‐CH=NR)] in ethanol in the presence of KOH gave compounds {RuH(CO)(PPh₃)₂[C₄H₃N(2‐CH=NR)]} where trans‐Py‐Ru‐H 1, R = CH₂CH₂C₆H₉; cis‐Py‐Ru‐H 2, R = Ph‐2‐Me; and cis‐Py‐Ru‐H 3, R = C₆H₁₁. Heating trans‐Py‐Ru‐H 1 in toluene at 70°C for 12 hr resulted a thermal conversion of the trans‐Py‐Ru‐H 1 into its cis form, {RuH(CO)(PPh₃)₂[C₄H₃N(2‐CH=NCH₂CH₂C₆H₉)]} (cis‐Py‐Ru‐H 1) in very high yield. The ¹H NMR spectra of trans‐Py‐Ru‐H 1, cis‐Py‐Ru‐H 2, cis‐Py‐Ru‐H 3, and cis‐Py‐Ru‐H 1 all show a typical triplet at ca. δ–11 for the hydride. The trans and cis form indicate the relative positions of pyrrole ring and hydride. The geometries of trans‐Py‐Ru‐H 1, cis‐Py‐Ru‐H 1, and cis‐Py‐Ru‐H 3 are relatively similar showing typical octahedral geometries with two PPh₃ fragments arranged in trans positions.     

The Versatile Coordination Modes of Monophosphine‐o‐Carborane in the Formation of Iridium and Rhodium Complexes: Synthesis,Reactivity, and Characterization

Monophosphine‐o‐carborane has four competitive coordination modes when it coordinates to metal centers. To explore the structural transitions driven by these competitive coordination modes, a series of monophosphine‐o‐carborane Ir,Rh complexes were synthesized and characterized. [Cp*M(Cl)₂{1‐(PPh₂)‐1,2‐C₂B₁₀H₁₁}] (M=Ir ( 1 a ), Rh ( 1 b ); Cp*=η⁵‐C₅Me₅), [Cp*Ir(H){7‐(PPh₂)‐7,8‐C₂B₉H₁₁}] ( 2 a ), and [1‐(PPh₂)‐3‐(η⁵‐Cp*)‐3,1,2‐MC₂B₉H₁₀] (M=Ir ( 3 a ), Rh ( 3 b )) can be all prepared directly by the reaction of 1‐(PPh₂)‐1,2‐C₂B₁₀H₁₁ with dimeric complexes [(Cp*MCl₂)₂] (M=Ir, Rh) under different conditions. Compound 3 b was treated with AgOTf (OTf=CF₃SO₃^?) to afford the tetranuclear metallacarborane [Ag₂(thf)₂(OTf)₂{1‐(PPh₂)‐3‐(η⁵‐Cp*)‐3,1,2‐RhC₂B₉H₁₀}₂] ( 4 b ). The arylphosphine group in 3 a and 3 b was functionalized by elemental sulfur (1 equiv) in the presence of Et₃N to afford [1‐{(S)PPh₂}‐3‐(η⁵‐Cp*)‐3,1,2‐MC₂B₉H₁₀] (M=Ir ( 5 a ), Rh ( 5 b )). Additionally, the 1‐(PPh₂)‐1,2‐C₂B₁₀H₁₁ ligand was functionalized by elemental sulfur (2 equiv) and then treated with [(Cp*IrCl₂)₂], thus resulting in two 16‐electron complexes [Cp*Ir(7‐{(S)PPh₂}‐8‐S‐7,8‐C₂B₉H₉)] ( 6 a ) and [Cp*Ir(7‐{(S)PPh₂}‐8‐S‐9‐OCH₃‐7,8‐C₂B₉H₉)] ( 7 a ). Compound 6 a further reacted with nBuPPh₂, thereby leading to 18‐electron complex [Cp*Ir(nBuPPh₂)(7‐{(S)PPh₂}‐8‐S‐7,8‐C₂B₉H₁₀)] ( 8 a ). The influences of other factors on structural transitions or the formation of targeted compounds, including reaction temperature and solvent, were also explored.     

Substituent effects of two isophthalate derivatives on the construction of cadmium coordination polymers incorporating a dipyridyl ligand

In recent years, the design and construction of crystalline coordination complexes by the assembly of metal ions with multitopic ligands have attracted considerable attention because of the unique architectures and potential applications of these compounds. Two new coordination polymers, namely poly[[μ‐trans‐1‐(2‐aminopyridin‐3‐yl)‐2‐(pyridin‐4‐yl)ethene‐κ²N:N′](μ₃‐5‐methylisophthalato‐κ⁴O¹,O^1′:O³:O^3′)cadmium(II)], [Cd(C₉H₆O₄)(C₁₂H₁₁N₃)]_n or [Cd(5‐Me‐ip)(2‐NH₂‐3,4‐bpe)]_n, ( I ), and poly[[μ‐trans‐1‐(2‐aminopyridin‐3‐yl)‐2‐(pyridin‐4‐yl)ethene‐κ²N:N′](μ₂‐5‐hydroxyisophthalato‐κ⁴O¹,O^1′:O³:O⁵)cadmium(II)], [Cd(C₈H₄O₅)(C₁₂H₁₁N₃)]_n or [Cd(5‐HO‐ip)(2‐NH₂‐3,4‐bpe)]_n, ( II ), have been prepared hydrothermally by the self‐assembly of Cd(NO₃)₂·4H₂O and trans‐1‐(2‐aminopyridin‐3‐yl)‐2‐(pyridin‐4‐yl)ethene (2‐NH₂‐3,4‐bpe) with two similar dicarboxylic acids, i.e. 5‐methylisophthalic acid (5‐Me‐H₂ip) and 5‐hydroxyisophthalic acid (5‐HO‐H₂ip). The coordination network of ( I ) is a two‐dimensional sql net parallel to (101). Adjacent sql nets are further linked to form a three‐dimensional supramolecular framework via hydrogen‐bonding interactions. Compound ( II ) is a two‐dimensional (3,5)‐connected coordination network parallel to (010) with the point symbol (6³)(5⁵6⁴7). As the other reactants and reaction conditions are the same, the structural differences between ( I ) and ( II ) are undoubtedly determined by the different substituent groups in the 5‐position of isophthalic acid. Both ( I ) and ( II ) exhibit good thermal stabilities and photoluminescence properties.     

Epoxidation of cyclohexene with H2O2 over efficient water‐tolerant heterogeneous catalysts composed of mono‐substituted phosphotungstic acid on co‐functionalized SBA‐15

A series of Keggin‐type heteropolyacid‐based heterogeneous catalysts (Co‐/Fe‐/Cu‐POM‐octyl‐NH₃‐SBA‐15) were synthesized via immobilized transition metal mono‐ substituted phosphotungstic acids (Co‐/Fe‐/Cu‐POM) on octyl‐amino‐co‐functionalized mesoporous silica SBA‐15 (octyl‐NH₂‐SBA‐15). Characterization results indicated that Co‐/Fe‐/Cu‐POM units were highly dispersed in mesochannels of SBA‐15, and both types of Brønsted and Lewis acid sites existed in Co‐/Fe‐/Cu‐POM‐octyl‐NH₃‐SBA‐15 catalysts. Co‐POM‐octyl‐NH₃‐SBA‐15 catalyst showed excellent catalytic performance in H₂O₂‐mediated cyclohexene epoxidation with 83.8% of cyclohexene conversion, 92.8% of cyclohexene oxide selectivity, and 98/2 of epoxidation/allylic oxidation selectivity. The order of catalytic activity was Co‐POM‐octyl‐NH₃‐SBA‐15 > Fe‐POM‐octyl‐NH₃‐SBA‐15 > Cu‐POM‐octyl‐NH₃‐SBA‐15. In order to obtain insights into the role of ‐octyl moieties during catalysis, an octyl‐free catalyst (Co‐POM‐NH₃‐SBA‐15) was also synthesized. In comparison with Co‐POM‐NH₃‐SBA‐15, Co‐POM‐octyl‐NH₃‐SBA‐15 showed enhanced catalytic properties (viz. activity and selectivity) in cyclohexene epoxidation. Strong chemical bonding between ‐NH₃⁺ anchored on the surface of SBA‐15 and heteropolyanions resulted in excellent stability of Co‐POM‐octyl‐NH₃‐SBA‐15 catalyst, and it could be reused six times without considerable loss of activity.     

Influence of the Metal Ions on the Allylic Rearrangement Reaction of 3,4,5,6‐Tetrahydrophthalic Anhydride

To further investigate the influence of metal ions on the allylic rearrangement of 3,4,5,6‐tetrahydrophthalic anhydride during the hydrothermal reaction, metal ions such as manganese(II), zinc(II) and cadmium(II) have been employed in the synthesis, which leads to the formation of three new lamellar coordination polymers, [Mn^II₅(µ₃‐OH)₃(1‐chec)(1,2‐chedc)(2,3‐chedc)₂(H₂O)] ( 3Mn) , [Zn^II₅(µ₃‐OH)₃(1‐chec)(1,2‐chedc)(2,3‐chedc)₂(H₂O)] ( 4Zn ), and [Cd^II₃(µ₃‐OH)₂(1,2‐chedc)₂] ( 5Cd) (1‐chec=cyclohexene‐1‐carboxylate, 1,2‐chedc=cyclohexene‐1,2‐dicarboxylate, 2,3‐chedc=cyclohexene‐1,2‐dicarboxylate). Interestingly, the allylic rearrangement reaction is metal‐dependent, which occurs only in 3Mn and 4Zn , resulting in the formation of one chiral carbon atom of the corresponding dicarboxylate ligands in both compounds. In addition, the magnetic property of compound 3Mn was studied, which revealed strong antiferromagnetic interactions between the metal centers.     

Synthesis,Structure and Reactivity of some 2,6‐Disubstituted Dimethylsilylbenzenes

Syntheses are described of a number of 2,6‐difunctionalized dimethylsilylbenzenes, namely, 1‐(HMe₂Si)‐2,6‐Cl₂C₆H₃ ( 13 ), 1‐(HMe₂Si)‐2,6‐Br₂C₆H₃ ( 14 ), 1,2,3‐(HMe₂Si)₃C₆H₃ ( 15 ), 1,2‐(HMe₂Si)₂‐6‐ClC₆H₃ ( 16 ), 1,2‐(HMe₂Si)₂‐6‐BrC₆H₃ ( 17 ), 1‐(HMe₂Si)‐2‐(Ph₂P)‐6‐BrC₆H₃ ( 18 ), diphenyl(1,1,3,3‐tetramethyl‐1,3‐dihydrobenzo[c][1,2,5]oxadisilol‐4‐yl)phosphine oxide ( 19 ) and 8‐Brom‐1,1,3,3‐tetramethyl‐2,2,2,2,‐tetracarbonyl‐1,3‐dihydro‐benzo[d][2,1,3]ferra disilol ( 20 ). Compounds 13 – 20 were characterized by multinuclear NMR spectroscopy and in case of 18 – 20 also by single crystal X‐ray diffraction.     

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.