New synthesis and reactivity of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one with binucleophilic amines

3‐(Bromoacetyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one was synthesized by the reaction of dehydroacetic acid (DHAA) with bromine in glacial acetic acid. Novel heterocyclic products were synthesized from the reaction of bromo‐DHAA with alkanediamines, phenylhydrazines, ortho‐phenylenediamines, and ortho‐aminobenzenethiol. The obtained new products 3‐(2‐N‐substituted‐acetyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐ones, 4‐hydroxy‐3‐[1‐hydroxy‐2‐(2‐phenylhydrazinyl)vinyl]‐6‐methyl‐2H‐pyran‐2‐one, 1‐(2,4‐dinitrophenyl)‐7‐methyl‐2,3‐dihydro‐1H‐pyrano[4,3‐c]pyridazine‐4,5‐dione, 3‐(3,4‐dihydroquinoxalin‐2‐yl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one/3‐(3,4‐dihydroquinoxalin‐2‐yl)‐6‐methyl‐2H‐pyran‐2,4(3H)‐dione, 6‐methyl‐3‐(3,4‐dihydroquinoxalin‐2‐yl)‐2H‐pyran‐2,4(3H)‐dione, and (E)‐3‐(2H‐benzo[b][1,4]thiazin‐3(4H)‐ylidene)‐6‐methyl‐2H‐pyran‐2,4(3H)‐dione were fully characterized by IR, ¹H and ¹³C NMR, and mass spectra. J. Heterocyclic Chem., 2011.     

New succinyl‐spaced pyrazoles: Regioselective synthesis of 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones

The facile and convenient access by a conventional procedure in ethanol as solvent to a new series of succinyl‐spaced pyrazoles including 1,4‐bis[5‐(trichloromethyl)‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones (64–82%) and the respective dehydrated derivatives as 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones in 57–82% yields, from the regioselective cyclocondensation reactions of 4‐substituted 4‐methoxy‐1,1,1‐trichloroalk‐3‐en‐2‐ones with succinic acid dihydrazide, where the 4‐substituents are Me, Ph, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐NO₂C₆H₄, 2‐furyl, and 2‐thienyl, is reported. J. Heterocyclic Chem., 2011.     

Cocrystals of diastereoisomers of 1,4‐dihydro­pyridine derivatives

A mixture of the RR/SS and RS/SR diastereoisomeric pairs of methyl 4‐(2,4‐dichloro­phen­yl)‐2,7‐dimethyl‐5‐oxo‐1,4,5,6,7,8‐hexa­hydro­quinoline‐3‐carboxyl­ate, C₁₉H₁₉Cl₂NO₃, forms cocrystals in which there is one unique mol­ecule in the asymmetric unit, but the mol­ecule displays disorder in the region of the 7‐position of the quinoline ring system as a result of the random occurrence of the diastereoisomers at the same crystallographic site. A similar arrangement exists in the monohydrate cocrystals that form from a mixture of the RR/SS and RS/SR diastereoisomeric pairs of methyl 4‐(2,4‐dichloro­phen­yl)‐2‐methyl‐7‐phenyl‐5‐oxo‐1,4,5,6,7,8‐hexa­hydro­quinoline‐3‐carboxyl­ate monohydrate, C₂₄H₂₁Cl₂NO₃·H₂O. These compounds belong to a class of 1,4‐dihydro­pyridines whose members have calcium modulatory properties. The 1,4‐dihydro­pyridine rings have the usual shallow boat conformation. In each structure, the 2,4‐dichloro­phenyl ring is oriented such that the 2‐chloro substituent is in a synperi­planar orientation with respect to the 1,4‐dihydro­pyridine ring plane. In each crystal structure, the mol­ecules are linked into chains by N—H⋯O hydrogen‐bonding inter­actions.     

Solution 1H and 13C NMR of new chiral 1,4‐oxazepinium heterocycles and their intermediates from the reaction of 2,4‐pentanedione with α‐L‐amino acids and (R)‐(—)‐2‐phenylglycinol

The reaction of 2,4‐pentanedione ( 1 ) with (R)‐(—)‐2‐phenylglycine methyl ester ( 2 ), (R)‐(—)‐2‐phenylglycinol ( 3 ) and the proteinogenic amino acids (2S,3R)‐(—)‐2‐amino‐3‐hydroxybutyric acid (L ‐threonine) ( 4 ) and (R)‐(—)‐2‐amino‐3‐mercaptopropionic acid (L ‐cysteine) ( 5 ) methyl esters was investigated. The corresponding enamines 6 , 7 and 8 were isolated and characterized spectroscopically whereas 9 , which is unstable, was transformed in situ into 13 . Treatment of 7 , 8 and 9 with boron trifluoride etherate afforded the new [1,4]oxazepines 10 , 11 and [1,4]thiazepine ( 12 ) as their BF₃O^? salts. The structures of the enamines and their corresponding seven‐membered heterocycles were assessed by 1D and 2D NMR spectroscopy. Variable‐temperature experiments revealed different molecular mobility behavior among these heterocycles. Copyright © 2003 John Wiley & Sons, Ltd.     

Poly[bis(μ‐benzene‐1,4‐dicarboxylato)bis[μ‐6‐(4‐pyridyl)‐5H‐imidazolo[4,5‐f][1,10]phenanthroline]dilead(II)]: an interpenetrating α‐Po net

The asymmetric unit of the title compound, [Pb₂(C₈H₄O₄)₂(C₁₈H₁₁N₅)₂]_n, contains two Pb^II atoms, two benzene‐1,4‐dicarboxylate (1,4‐bdc) dianions and two 6‐(4‐pyridyl)‐5H‐imidazolo[4,5‐f][1,10]phenanthroline (L) ligands. Each Pb^II atom is eight‐coordinated by three N atoms from two different L ligands and five carboxylate O atoms from three different 1,4‐bdc dianions. The two 1,4‐bdc dianions (1,4‐bdc₁ and 1,4‐bdc₂) show different coordination modes. Each 1,4‐bdc₁ coordinates to two Pb^II atoms in a chelating bis‐bidentate mode. Each carboxylate group of the 1,4‐bdc₂ anion connects two Pb^II atoms in a chelating–bridging tridentate mode to form a dinuclear unit. Neighbouring dinuclear units are connected together by the aromatic backbone of the 1,4‐bdc dianions and the L ligands into a three‐dimensional six‐connected α‐polonium framework. The most striking feature is that two identical three‐dimensional single α‐polonium nets are interlocked with each other, thus leading directly to the formation of a twofold interpenetrated three‐dimensional α‐polonium architecture. The framework is held together in part by strong N—H...O hydrogen bonds between the imidazole NH groups of the L ligands and the carboxylate O atoms of 1,4‐bdc dianions within different α‐polonium nets.     

Catenation of 1,3‐Diphosphacyclobutane‐2,4‐diyl Units Having 2,4,6‐Tri‐tert‐butylphenyl Protecting Groups and a P‐sec‐Butyl Group in the Ring

Two and three stable 1‐sec‐butyl‐2,4‐bis(2,4,6‐tri‐tert‐butylphenyl)‐1,3‐diphosphacyclobutane‐2,4‐diyl units were catenated to construct multi‐biradical derivatives by utilizing 1,3‐di‐, 1,4‐di‐, and 1,3,5‐trimethylenebenzenes as bridging groups, respectively. UV/Vis spectroscopic and cyclovoltammetric (CV) properties of the multi‐biradicals indicate a non‐conjugative interaction between the concatenated biradical units.     

Racemic isopropyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(6‐methyl‐2‐pyridyl)‐3‐nitropyridine‐5‐carboxylate hemi­benzene solvate

This analysis establishes the rotameric orientation of the pyridyl‐ring N atom of the title compound, C₁₇H₂₁N₃O₄·0.5C₆H₆, as antiperiplanar (ap) to the 1,4‐dihydropyridine H‐4, the absence of an intramolecular hydrogen bond between the 1,4‐dihydropyridine NH and the pyridyl‐N atom, and the unusual planarity of the 1,4‐dihydropyridine ring.     

Synthesis of 2‐amino‐7,8‐dihydro‐6(5H)‐quinazolinone, 2,4‐diamino‐7,8‐dihydro‐6(5H)‐quinazolinone, 5,6,7,8‐tetrahydro‐2,6‐quinazoline‐diamine and 5,6,7,8‐tetrahydro‐2,4,6‐quinazolinetriamine derivatives

N‐(2‐Amino‐5,6,7,8‐tetrahydro‐6‐quinazolinyl)acetamide ( 9 ) and N‐(2,4‐diamino‐5,6,7,8‐tetrahydro‐6‐quinazolinyl)acetamide ( 6 ) were synthesized from N‐(4‐oxocyclohexyl)acetamide ( 5 ) as novel peptidomimetic building blocks. With similar purpose, N‐(6‐oxo‐5,6,7,8‐tetrahydro‐2‐quinazolinyl)acetamide ( 18 ) and N‐[2‐(acetylamino)‐6‐oxo‐5,6,7,8‐tetrahydro‐4‐quinazolinyl]acetamide ( 14 ) were prepared from cyclohexane‐1,4‐dione monoethylene ketal ( 11 ).     

Asymmetric Hydroformylation of 4‐Vinyl‐1,3‐dioxolan‐2‐one

A chiral cyclic carbonate, 4‐vinyl‐1,3‐dioxolan‐2‐one was used as racemic substrate in asymmetric hydroformylation. The catalysts were formed in situ from “pre‐formed” PtCl₂(diphosphine) and tin(II) chloride. (2S,4S )‐2,4‐Bis(diphenylphosphinopentane ((S,S )‐BDPP)), (S,S )‐2,3‐O‐izopropylidine‐2,3‐dihydroxy‐1,4‐bis(diphenylphosphino)butane ((S,S )‐DIOP)), and (R )‐2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl ((R )‐BINAP)) were used as optically active diphosphine ligands. The platinum‐containing catalytic systems provided surprisingly high activity. The hydroformylation selectivities of up to 97% were accompanied by perfect regioselectivity towards the dioxolane‐based linear aldehyde. The enantiomeric composition of all components in the reaction mixture was determined and followed throughout the reaction. The unreacted 4‐vinyl‐1,3‐dioxolan‐2‐one was recovered in optically active form. The kinetic resolution was rationalized using the enantiomeric composition of the substrate and the products.     

A convenient synthesis of 2‐(1H‐1,2,4‐triazol‐1‐yl)‐2H‐1,4‐benzothiazine derivatives

A series of 2‐(1H‐1,2,4‐triazol‐1‐yl)‐2H‐1,4‐benzothiazines were designed and synthesized by condensation of 1,2,4‐triazole‐substituted ω‐bromoacetophenones and o‐aminothiophenols with the aid of K₂CO₃ under mild conditions with moderate to high yields. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:332–336, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20434     

Two hydrazones derived from 1‐aryl‐3‐(p‐substituted phenyl)prop‐2‐en‐1‐one: synthesis,crystal structure,Hirshfeld surface analysis and in vitro biological properties

Two chalcones were synthesized by the aldolic condensation of enolizable aromatic ketones with substituted benzaldehydes under Claisen–Schmidt reaction conditions and then treated with 2,4‐dinitrophenylhydrazine to yield their corresponding hydrazones. The two (E,Z)‐2,4‐dinitrophenylhydrazone structures, namely (Z)‐1‐(2,4‐dinitrophenyl)‐2‐[(E)‐3‐(4‐methylphenyl)‐1‐phenylallylidene]hydrazine, C₂₂H₁₈N₄O₄, ( H1 ), and (Z)‐1‐[(E)‐3‐(4‐chlorophenyl)‐1‐(naphthalen‐1‐yl)allylidene]‐2‐(2,4‐dinitrophenyl)hydrazine, C₂₅H₁₇ClN₄O₄, ( H2 ), were isolated by recrystallization and characterized by FT–IR, UV–Vis, single‐crystal and powder X‐ray diffraction methods. The UV–Vis spectra of the hydrazones have been studied in two organic solvents of different polarity. It was found that ( H2 ) has a molar extinction coefficient larger than 40000. Single‐crystal X‐ray diffraction analysis reveals that the molecular zigzag chains of ( H1 ) and ( H2 ) are interconnected through noncovalent contacts. A quantitative analysis of the intermolecular interactions in the crystal structures has been performed using Hirshfeld surface analysis. All the synthesized chalcones and hydrazones were evaluated for their antibacterial and antioxidant activities. Results indicate that the studied compounds show significant activity against Gram negative Escherichia coli strain and the chalcone 3‐(4‐methylphenyl)‐1‐phenylprop‐2‐en‐1‐one, ( C1 ), was the most effective. In addition, only hydrazone ( H1 ) displayed a moderate DPPH (2,2‐diphenyl‐1‐picryl hydrazyl) scavenging efficiency.     

Linking Deltahedral Zintl Clusters with Conjugated Organic Building Blocks: Synthesis and Characterization of the Zintl Triad [R‐Ge9‐CHCHCHCH‐Ge9‐R]4−

The accessibility of triads with deltahedral Zintl clusters in analogy to fullerene–linker–fullerene triads is another example for the close relationship between fullerenes and Zintl clusters. The compound {[K(2.2.2‐crypt)]₄[RGe₉‐CH?CH? CH?CH‐Ge₉R]}(toluene)₂ (R=(2Z,4E)‐7‐amino‐5‐aza‐hepta‐2,4‐dien‐2‐yl), containing two deltahedral [Ge₉] clusters linked by a conjugated (1Z,3Z)‐buta‐1,3‐dien‐1,4‐diyl bridge, was synthesized through the reaction of 1,4‐bis(trimethylsilyl)butadiyne with K₄Ge₉ in ethylenediamine and crystallized after the addition of 2.2.2‐cryptand and toluene. The compound was characterized by single‐crystal structure analysis as well asNMR and IR spectroscopy.     

(E)‐1‐(2′‐Deoxy‐β‐d‐ribo­furan­osyl)‐2,4‐di­fluoro‐5‐(2‐iodo­vinyl)­benzene

This analysis of the title compound, C₁₃H₁₃F₂IO₃, establishes the orientation of (E)‐5‐(CH=CH—I) as antiperiplanar (ap) to the C—C bond (5–6 position) of the 2,4‐di­fluoro­phenyl ring system, with the (E)‐5‐(CH=CH—I) H atom located in close proximity (2.17 Å) to the F4 atom of the 2,4‐di­fluoro­phenyl moiety.     

Poly[[μ2‐1,3‐bis(pyridin‐4‐yl)propane](μ3‐1,4‐phenylenediacetato)cadmium]

Solvothermal reaction between Cd(NO₃)₂, 1,4‐phenylenediacetate (1,4‐PDA) and 1,3‐bis(pyridin‐4‐yl)propane (bpp) afforded the title complex, [Cd(C₁₀H₈O₄)(C₁₃H₁₄N₂)]_n. Adjacent carboxylate‐bridged Cd^II ions are related by an inversion centre. The 1,4‐PDA ligands adopt a cis conformation and connect the Cd^II ions to form a one‐dimensional chain extending along the c axis. These chains are in turn linked into a two‐dimensional network through bpp bridges. The bpp ligands adopt an anti–gauche conformation. From a topological point of view, each bpp ligand and each pair of 1,4‐PDA ligands can be considered as linkers, while the dinuclear Cd^II unit can be regarded as a 6‐connecting node. Thus, the structure can be simplified to a two‐dimensional 6‐connected network.     

1‐Chloro‐3,6‐di­methoxy‐2,5‐di­methyl­benzene and 1‐chloro‐3,6‐di­methoxy‐2,4‐di­methyl­benzene

The title compounds, 1‐chloro‐3,6‐di­methoxy‐2,5‐di­methyl­benzene, (IIIa), and 1‐­chloro‐3,6‐di­methoxy‐2,4‐di­methyl­benzene, (IIIb), both C₁₀H₁₃ClO₂, were obtained from 2,5‐ and 2,6‐di­methyl‐1,4‐benzo­quinone, respectively, and are intermediates in the synthesis of ammonium quinone derivatives. The isomers have different substituents around the methoxy groups and crystallize in different space groups. In both mol­ecules, the methoxy groups each have different orientations with respect to the benzene ring. In both cases, one methoxy group lies in the plane of the ring and can participate in conjugation with the aromatic system, while the second is almost perpendicular to the plane of the aromatic ring. The C—O—C bond angles around these substituents are also different: 117.5 (4) and 118.2 (3)° in (IIIa) and (IIIb), respectively, when the methoxy groups lie in the plane of the ring, and 114.7 (3) and 113.6 (3)° in (IIIa) and (IIIb), respectively, when they are out of the plane of the ring.     

The Synthesis of 1,4‐Bis[N‐(4/6‐Substituted Benzothiazole‐2‐yl)‐N′‐Glycosylguanidino]Benzenes

The starting material O‐protected glycosyl isothiocyanate ( 1?3 ) was refluxed with 1,4‐diaminobenzene in CHCl₃ under nitrogen atmosphere to give 1,4‐bis(N‐glycosyl)thioureidobenzene ( 4?6 ). Then 1,4‐bis[N‐(4/6‐substituted benzothiazole‐2‐yl)‐N′‐glycosylguanidino]benzenes ( 8a?8e , 9a?9e , 10a?10e ) were obtained in good yield by reaction of compounds ( 4?6 ) with 2‐amino‐4/6‐benzothizoles ( 7a?7e ) and HgCl₂ in the presence of TEA in DMF. The structures of all 18 new compounds were confirmed by IR, ¹H NMR, LC‐MS and elemental analysis. The bioactivity of anti‐HIV‐1 protease (HIV‐1 PR) and against angiotensin converting enzyme (ACE) have been evaluated.     

Quinolone analogues 1. A convenient synthesis of 1‐alkyl‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxaline‐3‐carboxylic acids

The reaction of the alkylhydrazinoquinoxaline N‐oxides 2a‐d with dimethyl acetylenedicarboxylate gave the dimethyl 1‐alkyl‐1,5‐dihydropyridazino[3,4‐b]qumoxaline‐3,4‐dicarboxylates 3a‐d , whose reaction with nitrous acid effected the C₄‐oxidation to afford the dimethyl 1‐alkyl‐4‐hydroxy‐1,4‐dihydropyridazino‐[3,4‐b]quinoxaline‐3,4‐dicarboxylates 4a‐d , respectively. The reaction of compounds 4a‐d with 1,8‐diazabicyclo[5.4.0]‐7‐undecene in ethanol provided the ethyl 1‐alkyl‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxa‐line‐3‐carboxylates 5a‐d , while the reaction of compounds 4a‐d with potassium hydroxide furnished the 1‐alkyl‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxaline‐3‐carboxylic acids 6a‐d , respectively. Compounds 6c,d were also obtained by the reaction of compounds 5c,d with potassium hydroxide, respectively.     

Poly[[(μ2‐biphenyl‐2,4′‐dicarboxylato)[μ2‐1,4‐bis(imidazol‐1‐ylmethyl)benzene]cadmium(II)] 0.15‐hydrate]

The asymmetric unit of the title two‐dimensional coordination polymer, {[Cd(C₁₄H₈O₄)(C₁₄H₁₄N₄)]·0.15H₂O}_n, is composed of one Cd^II cation, one biphenyl‐2,4′‐dicarboxylate (bpdc) anion, one 1,4‐bis(imidazol‐1‐ylmethyl)benzene (bix) ligand and 0.15 solvent water molecules. The coordination environment of the Cd^II cation is defined by four carboxylate O atoms from two different bpdc anions in a chelating mode and two N atoms from two distinct bix ligands, constructing a distorted trigonal prism polyhedron. Two inversion‐related Cd^II cations are bridged together by two positionally disordered bpdc anions, forming a 22‐membered ring with a Cd...Cd distance of 9.1966 (9) Å. These rings are then further linked by two bix ligands, extending into a two‐dimensional layer along (102) with 6³ topology.     

A synchrotron radiation study of the one‐dimensional complex of sodium with (1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d‐ribitol,a member of the 'immucillin' family

The sodium salt of [immucillin‐A–CO₂H]⁻ (Imm‐A), namely catena‐poly[[[triaquadisodium(I)](μ‐aqua)[μ‐(1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d ‐ribitol][triaquadisodium(I)][μ‐(1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d ‐ribitol]] tetrahydrate], {[Na₂(C₁₂H₁₃N₄O₆)₂(H₂O)₇]·4H₂O}_n, (I), forms a polymeric chain via Na⁺—O interactions involving the carboxylate and keto O atoms of two independent Imm‐A molecules. Extensive N,O—H...O hydrogen bonding utilizing all water H atoms, including four waters of crystallization, provides crystal packing. The structural definition of this novel compound was made possible through the use of synchrotron radiation utilizing a minute fragment (volume ∼2.4 × 10⁻⁵ mm⁻³) on a beamline optimized for protein data collection. A summary of intra‐ring conformations for immucillin structures indicates considerable flexibility while retaining similar intra‐ring orientations.