5‐Acetyl‐2‐amino‐6‐methyl‐4‐(3‐nitrophenyl)‐4H‐pyran‐3‐carbonitrile and 2‐amino‐5‐ethoxycarbonyl‐6‐methyl‐4‐(3‐nitrophenyl)‐4H‐pyrano‐3‐carbonitrile

The structures of the title compounds, C₁₅H₁₃N₃O₄, (I), and C₁₆H₁₅N₃O₅ [IUPAC name: ethyl 6‐amino‐5‐cyano‐2‐methyl‐4‐(3‐nitro­phenyl)‐4H‐pyrano‐3‐carboxyl­ate], (II), are very similar, with the heterocyclic rings adopting boat conformations. The pseudo‐axial m‐nitro­phenyl substituents are rotated by 84.0 (1) and 98.7 (1)° in (I) and (II), respectively, with respect to the four coplanar atoms of the boat. The dihedral angles between the phenyl rings and nitro groups are 12.1 (2) and 8.4 (2)° in (I) and (II), respectively. The two compounds have similar patterns of intermolecular N—H?O and N—H?N hydrogen bonding, which link mol­ecules into infinite tapes along b .     

1‐[4‐(Methyl­sulfonyl)­phenyl]‐5‐phenyl‐1H‐pyrazole derivatives

Three related compounds containing a pyrazole moiety with vicinal phenyl rings featuring a methyl­sulfonyl substituent are described, namely 3‐methyl‐1‐[4‐(methyl­sulfonyl)­phenyl]‐5‐phenyl‐1H‐pyrazole, C₁₇H₁₆N₂O₂S, ethyl 1‐[4‐(methyl­sul­fonyl)­phenyl]‐5‐phenyl‐1H‐pyrazole‐3‐carboxyl­ate, C₁₉H₁₈N₂O₄S, and 1‐[4‐(methyl­sulfonyl)­phenyl]‐3‐[3‐(morpholino)­phenoxy­methyl]‐5‐phenyl‐1H‐pyrazole, C₂₇H₂₇N₃O₄S. The design of these compounds was based on celecoxib, a selective cyclo­oxy­genase‐2 (COX‐2) inhibitor, in order to study the influence of various substituents on COX‐2 and 5‐lipoxy­genase (5‐LOX) inhibition.     

2‐Azido‐2‐deoxycellulose: Synthesis and 1,3‐Dipolar Cycloaddition

Chitosan ( 1 ) was prepared by basic hydrolysis of chitin of an average molecular weight of 70000 Da, ¹H‐NMR spectra indicating almost complete deacetylation. N‐Phthaloylation of 1 yielded the known N‐phthaloylchitosan ( 2 ), which was tritylated to provide 3a and methoxytritylated to 3b . Dephthaloylation of 3a with NH₂NH₂?H₂O gave the 6‐O‐tritylated chitosan 4a . Similarly, 3b gave the 6‐O‐methoxytritylated 4b . CuSO₄‐Catalyzed diazo transfer to 4a yielded 95% of the azide 5a , and uncatalyzed diazo transfer to 4b gave 82% of azide 5b . Further treatment of 5a with CuSO₄ produced 2‐azido‐2‐deoxycellulose ( 7 ). Demethoxytritylation of 5b in HCOOH gave 2‐azido‐2‐deoxy‐3,6‐di‐O‐formylcellulose ( 6 ), which was deformylated to 7 . The 1,3‐dipolar cycloaddition of 7 to a range of phenyl‐, (phenyl)alkyl‐, and alkyl‐monosubstituted alkynes in DMSO in the presence of CuI gave the 1,2,3‐triazoles 8 – 15 in high yields.     

Facile Synthesis of Novel 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one Derivatives as Potential Anticancer Agents

A series of 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 6a – l ) derivatives has been efficiently synthesized by straightforward sequential reactions. Tandem Vilsmeier Hack reaction/cyclization/bromination/Suzuki cross‐coupling reactions were successfully applied to the preparation of title compounds in good‐to‐high yields. In the synthetic sequences, 3‐chloro‐3‐(2‐oxo‐2H‐chromen‐3‐yl)acrylaldehydes ( 2 ) were found to react with ammonium thiocyanate to yield the corresponding 3‐(isothiazol‐5‐yl)‐2H‐chromen‐2‐ones ( 3 ). These derivatives were brominated with N‐bromo succinamide to yield the corresponding regioselective 3‐(4‐bromoisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 4 ). Finally, compound 4 was treated with various phenyl/pyrazole/7H –pyrrolo[2,3‐d]pyrimidinyl boronic acids 5a – l in the presence of K₂CO₃ and Pd catalyst in dimethylformamide to yield the corresponding title derivatives 6a – l . All the synthesized compounds were characterized by analytical and spectral studies. All the final compounds were screened against different cancer cell lines (A549, PC3, SKOV3, and B16F10), and among these compounds, 6b , 6g , 6h , and 6l displayed moderate cytotoxic activity against the tested cell lines.     

1H‐Indazole and 2H‐indazole derivatives of androsta‐5,16‐dien‐3β‐ol

The title compounds, 17‐(1H‐indazol‐1‐yl)androsta‐5,16‐dien‐3β‐ol, (I), and 17‐(2H‐indazol‐2‐yl)androsta‐5,16‐dien‐3β‐ol, (II), both C₂₆H₃₂N₂O, have an indazole substituent at the C17 position. The six‐membered B ring of each compound assumes a half‐chair conformation. A twist of the steroid skeleton is observed and reproduced in quantum‐mechanical ab initio calculations of the isolated molecule using a molecular orbital Hartree–Fock method. In the 1H‐indazole derivative, (I), the molecules are joined in a head‐to‐head fashion via O—H...O hydrogen bonds, forming chains along the a axis. In the 2H‐indazole derivative, (II), the molecules are joined in a head‐to‐tail fashion with one of the N atoms of the indazole ring system acting as the acceptor. The hydrogen‐bond pattern consists of zigzag chains running along the b axis. Substituted steroids have proven to be effective in inhibiting androgen biosynthesis through coordination of the Fe atoms of some enzymes, and this study shows that indazole‐substituted steroids adopt twisted conformations that restrict their intermolecular interactions.     

Two regioisomers of condensed thioheterocyclic triazine synthesized from 6‐phenyl‐3‐thioxo‐2,3,4,5‐tetrahydro‐1,2,4‐triazin‐5‐one

In the crystal structure of 6‐phenyl‐3‐thioxo‐2,3,4,5‐tetrahydro‐1,2,4‐triazin‐5‐one, C₉H₇N₃OS, (I), the 1,2,4‐triazine moieties are connected by face‐to‐face contacts through two kinds of double hydrogen bonds (N—H...O and N—H...S), which form planar ribbons along the a axis. The ribbons are crosslinked through C—H...π interactions between the phenyl rings. The molecular structures of two regioisomeric compounds, namely 6‐phenyl‐2,3‐dihydro‐7H‐1,3‐thiazolo[3,2‐b][1,2,4]triazin‐7‐one, C₁₁H₉N₃OS, (II), and 3‐phenyl‐6,7‐dihydro‐4H‐1,3‐thiazolo[2,3‐c][1,2,4]triazin‐4‐one, C₁₁H₉N₃OS, (III), which were prepared by the condensation reaction of (I) with 1,2‐dibromoethane, have been characterized by X‐ray crystallography and spectroscopic studies. The crystal structures of (II) and (III) both show two crystallographically independent molecules. While the two compounds are isomers, the unit‐cell parameters and crystal packing are quite different and (II) has a chiral crystal structure.     

Five N′‐benzylidene‐N‐methylpyrazine‐2‐carbohydrazides

The compounds N′‐benzylidene‐N‐methylpyrazine‐2‐carbohydrazide, C₁₃H₁₂N₄O, (IIa), N′‐(2‐methoxybenzylidene)‐N‐methylpyrazine‐2‐carbohydrazide, C₁₄H₁₄N₄O₂, (IIb), N′‐(4‐cyanobenzylidene)‐N‐methylpyrazine‐2‐carbohydrazide dihydrate, C₁₄H₁₁N₅O·2H₂O, (IIc), N‐methyl‐N′‐(2‐nitrobenzylidene)pyrazine‐2‐carbohydrazide, C₁₃H₁₁N₅O₃, (IId), and N‐methyl‐N′‐(4‐nitrobenzylidene)pyrazine‐2‐carbohydrazide, C₁₃H₁₁N₅O₃, (IIe), have dihedral angles between the pyrazine rings and the benzene rings in the range 55–78°. These methylated pyrazine‐2‐carbohydrazides have supramolecular structures which are formed by weak C—H...O/N hydrogen bonds, with the exception of (IIc) which is hydrated. There are π–π stacking interactions in all five compounds. Three of these structures are compared with their nonmethylated counterparts, which have dihedral angles between the pyrazine rings and the benzene rings in the range 0–6°.     

2‐Benzoyl‐N‐phenyl‐2‐(1,2,4‐triazol‐1‐yl)­thio­acet­amide and 2‐(4‐methoxy­benzoyl)‐N‐phenyl‐2‐(1,2,4‐triazol‐1‐yl)­thio­acet­amide

In the two title compounds, C₁₇H₁₄N₄OS, (I), and C₁₈H₁₆N₄O₂S, (II), the dihedral angles between the planes of the triazole and N‐phenyl rings and the plane of five of the atoms that link these two rings are 63.5 (8) and 73.2 (6)° for (I), and 65.1 (1) and 72.1 (3)° for (II), respectively. There are some inter‐ and intramolecular interactions in the crystal structure.     

Two seven‐membered heterocycles with 1,2‐diaza ring N atoms: 3,5,7‐triphenyl‐1,2‐diazacyclohepta‐1(7),2‐diene and 3,7‐bis(2‐hydroxyphenyl)‐5‐phenyl‐1,2‐diazacyclohepta‐1(7),2‐diene

The title compounds, 3,5,7‐triphenyl‐1,2‐diazacyclohepta‐1(7),2‐diene, C₂₃H₂₀N₂, (I), and 3,7‐bis(2‐hydroxyphenyl)‐5‐phenyl‐1,2‐diazacyclohepta‐1(7),2‐diene, C₂₃H₂₀N₂O₂, (II), constitute the first structurally characterized examples of seven‐membered heterocycles with 1,2‐diaza ring N atoms. Compound (I) crystallizes in the space group P, with two independent molecules in the asymmetric unit that differ in the conformation of one of the phenyl rings, while (II) crystallizes in the space group C2/c. The C₅N₂ ring in each of (I) and (II) adopts a twist‐boat conformation. Compound (I) exhibits neither C—H...π interactions nor π–π stacking interactions, whereas (II) shows both intramolecular O—H...N hydrogen bonds and a C—H...π interaction that joins the molecules into an infinite chain in the [010] direction.     

Direct Synthesis and Characterization of New Copper(II) and Zinc(II) 5‐R‐Tetrazolato Complexes [R = Me,Ph, 4‐Py] with Ethylenediamine and DMSO as Coligands

Three novel 5‐R‐tetrazolato complexes (R = Me, Ph, 4‐Py), namely [Zn₂(MeCN₄)₄(DMSO)₂] ( 1 ), [Cu₂(PhCN₄)₄(en)₂] · 2DMSO ( 2 ), and [Cu(4‐PyCN₄)₂(DMSO)₂] · 4DMSO ( 3 ), were isolated as unexpected products under attempts to prepare heterometallic tetrazolates using a direct synthesis strategy in the Cu⁰‐ZnO‐en‐RCN₄H‐DMSO system (en = ethylenediamine). The prepared compounds were characterized by elemental, single‐crystal X‐ray, and thermal analyses, and IR spectroscopy. Variation of the 5‐substituent of the tetrazole ring causes different composition of complexes 1 – 3 and diverse coordination modes of 5‐R‐tetrazolato ligands. Complex 1 is a 3D coordination polymer due to N1, N4‐bridging of 5‐methyltetrazolato anions. Complex 2 , with en as a coligand, has a dinuclear structure with two copper atoms linked together by two 5‐phenyltetrazolato ligands by tetrazole N2, N3 bridges. Complex 3 represents a 2D coordination polymer, formed due to 5‐(4‐pyridyl)tetrazolato bridges between adjacent copper atoms (with the tetrazole and pyridine rings nitrogen atoms as coordination centers). DMSO molecules, included in all the compounds, are solvate and/or coordinated ones.     

Two (Z)‐N‐aryl‐3‐benzylideneisoindolin‐1‐ones

Two isoindolin‐1‐one derivatives, (Z)‐3‐benzyl­idene‐N‐phenyl­isoindolin‐1‐one, C₂₁H₁₅NO, (II), and (Z)‐3‐benzyl­idene‐N‐(4‐methoxy­phenyl)­isoindolin‐1‐one, C₂₂H₁₇NO₂, (III), were synthesized by the palladium‐catalysed heteroannulation. The mol­ecules of both compounds have a Z configuration. The interplanar angles between the five‐ and six‐membered rings of the isoindolinone moiety in (II) and (III) are 1.66 (11) and 2.26 (7)°, respectively. The phenyl rings at the N‐position in (II) and (III) are twisted out of the C₄N ring plane by 62.77 (11) and 67.10 (7)°, respectively. The substitutions at the N and C‐3 positions of the isoindolinone system have little influence on the molecular dimensions of the resulting compounds.     

2‐[(E)‐(4‐Chloro­phenyl)­methyl­ene­amino]‐N‐(X‐methyl­phenyl)‐4,5,6,7‐tetra­hydro‐1‐benzo­thio­phene‐3‐carbox­amide,where X = 2 and 3

The title compounds, both C₂₃H₂₁ClN₂OS, are isomeric, with (I) and (II) being the N‐3‐methyl­phenyl and N‐2‐methyl­phenyl derivatives, respectively. The dihedral angle between the 4‐chloro­phenyl group and the thio­phene ring in (II) [38.1 (1)°] is larger than that in (I) [7.1 (1)°], indicating steric repulsion between the chloro­phenyl and o‐toluidine groups in (II). In both compounds, an intramolecular N—H⋯N hydrogen bond forms a pseudo‐six‐membered ring, thus locking the molecular conformation. In the crystal structures, mol­ecules are connected via N—H⋯O hydrogen bonds, forming chains along the b axis in (I) and along the c axis in (II). Intermolecular C—H⋯O/S and π–π interactions are also observed in (II), but not in (I).     

2‐Phenyl­malonpiperadide and 2‐phenyl­malonmorpholide

The structures of 2‐phenyl­malonpiperadide [systematic name: 2‐phenyl‐1,3‐bis­(piperidin‐1‐yl)­propane‐1,3‐dione, C₁₉H₂₆N₂O₂, (I)] and 2‐phenyl­malonmorpholide [systematic name: 1,3‐dimorpholino‐2‐phenyl­propane‐1,3‐dione, C₁₇H₂₂N₂O₄, (II)], have been determined and both their molecular conformations and packing arrangements compared. Although chemically similar, compounds (I) and (II) exhibit different molecular conformations. The only general conformational similarities are that their respective carbonyl groups are orientated in the same direction and the heterocyclic rings exist in the chair arrangement. General similarities in the packing arrangements arise due to both compounds having the same space group (P2₁2₁2₁) and a similar alignment of their phenyl‐substituted backbone with respect to the c axis. Similar C—H⋯O hydrogen‐bonding associations are listed for the carbonyl O atoms, while only one of the morpholine O atoms is involved in any such association.     

邻-(N-芳酰基-N-甲氨基苯)-二硫化合物的合成：通过N-甲基-2-单芳基苯并噻唑啉在溶剂中的自发偶联反应和它们的血管内皮生长因子抑制活性

N-甲基-2-单芳基苯并噻唑啉 (1) 在固体状态时可以稳定地储藏在空气中。但是,它们在不同溶剂中却表现出了不同的行为。在醇溶液或二甲亚砜-水的体系中,1相对稳定;而在其它有机溶剂如：丙酮,氯仿,二氯甲烷和乙酸乙酯等溶剂中,会发生自发偶联反应生成相应的邻-(N-芳酰基-N-甲氨基苯)-二硫化合物 (2)。对这些新的化合物 (1) 和 (2) 进行了体外人乳腺癌细胞 (MDA-MB-231) 血管内皮生长因子靶点筛选,大部分化合物都表现出了抑制活性。实验结果表明这两类化合物 (1) 和 (2) 作为血管内皮生长因子抑制剂值得进行深入研究。     

Synthesis and Characterization of Novel N‐Alkylamine‐ and N‐Cycloalkylamine‐Derived 2‐Benzoyl‐N‐aminohydrazinecarbothioamides, 1,3,4‐Thiadiazoles and 1,2,4‐Triazole‐5(4H)thiones

4‐Aminomorpholine, 1‐aminopiperidine, and 1,1‐dimethylhydrazine were carried out in the corresponding methyl dithiocarbamates and those in turn in aminohydrazinethioamides, which under the influence of acid chlorides (benzoyl, 4‐chlorobenzoyl, 4‐fluorobenzoyl, 4‐methoxybenzoyl and 2‐furoyl) gave arylcarbonyl derivatives. Those compounds were cyclized in concentrated H₂SO₄ to 2‐(N‐cycloalkylamino‐ and N‐dimethylamino)‐amino‐5‐phenyl‐1,3,4‐thiadiazole derivatives and in 10% NaOH aqueous solution to 4‐cycloalkylamino‐ and 4‐dimethylamino‐3‐phenyl‐1,2,4‐triazole‐5(4H)‐thiones.     

Kinetics of N‐bromination of 2‐oxazolidinone

The kinetics of N‐bromination of 2‐oxazolidinone by transfer of Br from sodium hypobromite, N‐bromosuccinimide (NBS), or N‐bromoacetamide (NBA) were determined spectrophotometrically, at pH between 4.6 and 12.45 (depending on the brominating agent). The reaction with hypobromite was of first order with respect to both the hypobromite and the substrate. The bromination of oxazolidinone with NBS (or NBA) has been found to be a reversible process of order one with respect to both NBA (or NBA) and oxazolidinone in the forward direction, and order one with respect to SI (or ACAM) and the resulting N‐bromo‐oxazolidinone in the other. The pH dependence of the reaction rate was in keeping with a mechanism in which all the brominating agents (HOBr, BrO^?, NBS and NBA) react predominantly with the anion of the substrate. Bimolecular bromination rate constants increased in the order BrO^? < NBA < NBS < HOBr. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 642–649, 2004     

Hydrogen‐bonded ribbons in ethyl (E)‐3‐[2‐amino‐4,6‐bis(dimethylamino)pyrimidin‐5‐yl]‐2‐cyanoacrylate and 2‐[(2‐amino‐4,6‐di‐1‐piperidylpyrimidin‐5‐yl)methylene]malononitrile

The pyrimidine rings in ethyl (E)‐3‐[2‐amino‐4,6‐bis(dimethylamino)pyrimidin‐5‐yl]‐2‐cyanoacrylate, C₁₄H₂₀N₆O₂, (I), and 2‐[(2‐amino‐4,6‐di‐1‐piperidylpyrimidin‐5‐yl)methylene]malononitrile, C₁₈H₂₃N₇, (II), which crystallizes with Z′ = 2 in the space group, are both nonplanar with boat conformations. The molecules of (I) are linked by a combination of N—H...N and N—H...O hydrogen bonds into chains of edge‐fused R₂²(8) and R₄⁴(20) rings, while the two independent molecules in (II) are linked by four N—H...N hydrogen bonds into chains of edge‐fused R₂²(8) and R₂²(20) rings. This study illustrates both the readiness with which highly‐substituted pyrimidine rings can be distorted from planarity and the significant differences between the supramolecular aggregation in two rather similar compounds.     

Hydrogen‐bonding patterns in three substituted N‐benzyl‐N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)acetamides

The molecules of N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐2‐chloro‐N‐(4‐methoxybenzyl)acetamide, C₂₃H₂₆ClN₃O₂, are linked into a chain of edge‐fused centrosymmetric rings by a combination of one C—H...O hydrogen bond and one C—H...π(arene) hydrogen bond. In N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐2‐chloro‐N‐(4‐chlorobenzyl)acetamide, C₂₂H₂₃Cl₂N₃O, a combination of one C—H...O hydrogen bond and two C—H...π(arene) hydrogen bonds, which utilize different aryl rings as the acceptors, link the molecules into sheets. The molecules of S‐[N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐N‐(4‐methylbenzyl)carbamoyl]methyl O‐ethyl carbonodithioate, C₂₆H₃₁N₃O₂S₂, are also linked into sheets, now by a combination of two C—H...O hydrogen bonds, both of which utilize the amide O atom as the acceptor, and two C—H...π(arene) hydrogen bonds, which utilize different aryl groups as the acceptors.     

2‐Amino­thia­zole and 2‐amino­thiazolinone derivatives

The reaction of different substituted α‐cyano­oxiranes with thio­urea resulted in the formation of the 2‐amino­thia­zolinone derivative 2‐amino‐5‐(2,5‐di­methoxy­phenyl)‐1,3‐thia­zol‐4(5H)‐one, C₁₁H₁₂N₂O₃S, (I), and the 2‐amino­thia­zole derivative ethyl 2‐amino‐5‐(2,5‐di­methoxy­phenyl)‐1,3‐thia­zole‐4‐carboxyl­ate, C₁₄H₁₆N₂O₄S, (II). The geometries of the two crystallographically independent mol­ecules in (II) are nearly identical but mirror related. The crystal structures of both compounds contain two types of intermolecular hydrogen bonds.     

Two 5‐oxa‐2,6‐diazaspiro[3.4]octan‐1‐one derivatives from the [3+2] cyclo­addition of methylenelactams with nitrones

The two title 5‐oxa‐2,6‐di­aza­spiro­[3.4]­octan‐1‐one adducts, 7‐benzoyl‐2‐(4‐methoxy­phenyl)‐6‐phenyl‐5‐oxa‐2,6‐di­aza­spiro­[3.4]­octan‐1‐one, C₂₅H₂₂N₂O₄, (III), and 6‐tert‐butyl‐2‐(4‐methyl­phenyl)‐7‐phenyl‐5‐oxa‐2,6‐di­aza­spiro­[3.4]­octan‐1‐one, C₂₂H₂₆N₂O₂, (IV), were obtained from a stereospecific [3+2] 1,3‐cyclo­addition of 3‐methyl­ene azetidin‐2‐ones as dipolaro­philes with nitro­nes. The lactam ring is conjugated with the p‐­methoxy­phenyl or p‐methyl­phenyl moiety. The envelope conformations of the isoxazolidine rings in (III) and (IV) are different, leading the substituents to be pseudo‐axial in (III) and pseudo‐equatorial in (IV).