The supramolecular architecture of tris(naphthalene‐1,5‐diaminium) bis(5‐aminonaphthalen‐1‐aminium) octakis[hydrogen (5‐carboxypyridin‐3‐yl)phosphonate]

The asymmetric unit of the title compound, 3C₁₀H₁₂N₂²⁺·2C₁₀H₁₁N₂⁺·8C₆H₅NO₅P⁻, contains one and a half naphthalene‐1,5‐diaminium cations, in which the half‐molecule has inversion symmetry, one 5‐aminonaphthalen‐1‐aminium cation and four hydrogen (5‐carboxypyridin‐3‐yl)phosphonate anions. The crystal structure is layered and consists of hydrogen‐bonded anionic monolayers between which the cations are arranged. The acid monoanions are organized into one‐dimensional chains along the [101] direction via hydrogen bonds established between the phosphonate sites. (C)O—H...N_py hydrogen bonds (py is pyridine) crosslink the chains to form an undulating (010) monolayer. The cations serve both to balance the charge of the anionic network and to connect neighbouring layers via multiple hydrogen bonds to form a three‐dimensional supramolecular architecture.     

Copper‐Catalyzed α‐Amination of Phosphonates and Phosphine Oxides: A Direct Approach to α‐Amino Phosphonic Acids and Derivatives

A direct approach to important α‐amino phosphonic acids and its derivatives has been developed by using copper‐catalyzed electrophilic amination of α‐phosphonate zincates with O‐acyl hydroxylamines. This amination provides the first example of C? N bond formation which directly introduces acyclic and cyclic amines to the α‐position of phosphonates in one step. The reaction is readily promoted at room temperature with as little as 0.5 mol % of catalyst, and demonstrates high efficiency on a broad substrate scope.     

Catalytic Asymmetric 1,2‐Addition of α‐Isothiocyanato Phosphonates: Synthesis of Chiral β‐Hydroxy‐ or β‐Amino‐Substituted α‐Amino Phosphonic Acid Derivatives

α‐Amino phosphonic acid derivatives are considered to be the most important structural analogues of α‐amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2‐addition reactions of α‐isothiocyanato phosphonate were developed. Through these processes, derivatives of β‐hydroxy‐α‐amino phosphonic acid and α,β‐diamino phosphonic acid, as well as highly functionalized phosphonate‐substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α‐phosphonic acid derivatives.     

Synthesis and biological activities of quinolone analogues: Pyridazino[3,4‐b]quinoxalin‐4‐one

Quinolone analogues I‐VI with pyridazino[3,4‐b]quinoxaline ring system were synthesized form the (l‐alkylhydrzino)quinoxalina N‐oxides 1 via oxidation of pyridazino[3,4‐b]quinoxalines 2,3,5,7 , quinoxalino[2,3‐c]cinnolines 4 , and 1,2‐dizepino[3,4‐b]quinoxalines 6 . The biological activities of quinolone analogues IVa (N₁‐methyl‐C₃‐methyl), Va (N₁‐methyl‐C₃‐ethyl), and VI (N₁‐methyl‐C₃‐H) were superior to those of quinolone analogues I (N₁‐ethyl‐C₃‐carboxyl), 26b (N₁‐ethyl‐C₃‐carboxylate), and IIIc,d [N₁‐alkyl‐C₃‐(CH₂)₃COOC₂H₅].     

Conformations and resulting hydrogen‐bonded networks of hydrogen {phosphono[(pyridin‐1‐ium‐3‐yl)amino]methyl}phosphonate and related 2‐chloro and 6‐chloro derivatives

In the crystal structures of the conformational isomers hydrogen {phosphono[(pyridin‐1‐ium‐3‐yl)amino]methyl}phosphonate monohydrate (pro‐E), C₆H₁₀N₂O₆P₂·H₂O, (Ia), and hydrogen {phosphono[(pyridin‐1‐ium‐3‐yl)amino]methyl}phosphonate (pro‐Z), C₆H₁₀N₂O₆P₂, (Ib), the related hydrogen {[(2‐chloropyridin‐1‐ium‐3‐yl)amino](phosphono)methyl}phosphonate (pro‐E), C₆H₉ClN₂O₆P₂, (II), and the salt bis(6‐chloropyridin‐3‐aminium) [hydrogen bis({[2‐chloropyridin‐1‐ium‐3‐yl(0.5+)]amino}methylenediphosphonate)] (pro‐Z), 2C₅H₆ClN₂⁺·C₁₂H₁₆Cl₂N₄O₁₂P₄²⁻, (III), chain–chain interactions involving phosphono (–PO₃H₂) and phosphonate (–PO₃H⁻) groups are dominant in determining the crystal packing. The crystals of (Ia) and (III) comprise similar ribbons, which are held together by N—H...O interactions, by water‐ or cation‐mediated contacts, and by π–π interactions between the aromatic rings of adjacent zwitterions in (Ia), and those of the cations and anions in (III). The crystals of (Ib) and (II) have a layered architecture: the former exhibits highly corrugated monolayers perpendicular to the [100] direction, while in the latter, flat bilayers parallel to the (001) plane are formed. In both (Ib) and (II), the interlayer contacts are realised through N—H...O hydrogen bonds and weak C—H...O interactions involving aromatic C atoms.     

(2S)‐1‐Carbamoylpyrrolidine‐2‐carboxylic acid

In the title compound, also known as N‐carbamoyl‐l ‐proline, C₆H₁₀N₂O₃, the pyrrolidine ring adopts a half‐chair conformation, whereas the carboxyl group and the mean plane of the ureide group form an angle of 80.1 (2)°. Molecules are joined by N—H...O and O—H...O hydrogen bonds into cyclic structures with graph‐set R²₂(8), forming chains in the b‐axis direction that are further connected via N—H...O hydrogen bonds into a three‐dimensional network.     

Synthesis and Structure of O,O‐Diethyl N‐[(trans‐4‐Aryl‐5,5‐dimethyl‐2‐oxido‐2λ5‐1,3,2‐dioxaphosphorinan‐2‐yl)methyl]phosphoramidothioates

A study on the synthesis of the novel N‐(cyclic phosphonate)‐substituted phosphoramidothioates, i.e., O,O‐diethyl N‐[(trans‐4‐aryl‐5,5‐dimethyl‐2‐oxido‐2λ⁵‐1,3,2‐dioxaphosphorinan‐2‐yl)methyl]phosphoramidothioates 4a – l , from O,O‐diethyl phosphoramidothioate ( 1 ), a benzaldehyde or ketone 2 , and a 1,3,2‐dioxaphosphorinane 2‐oxide 3 was carried out (Scheme 1 and Table 1). Some of their stereoisomers were isolated, and their structure was established. The presence of acetyl chloride was essential for this reaction and accelerated the process of intramolecular dehydration of intermediate 5 forming the corresponding Schiff base 7 (Scheme 2).     

Dimers linked by type‐I C—F...F—C contacts in (Z)‐3‐methyl‐4‐[2‐(4‐methylphenyl)hydrazinylidene]‐1‐(pentafluorophenyl)‐1H‐pyrazol‐5(4H)‐one

The title compound, C₁₇H₁₁F₅N₄O, is described and compared with two closely related analogues in the literature. There are two independent molecules in the asymmetric unit, linked by N—H...O hydrogen bonds and π–π interactions into dimeric entities, presenting a noticeable noncrystallographic C₂ symmetry. These dimers are in turn linked by a medium‐strength type‐I C—F...F—C interaction into elongated tetramers. Much weaker C—H...F contacts link the tetramers into broad two‐dimensional substructures parallel to (101).     

Conformational isomers of the [(5‐methyl‐2‐pyridinio)aminomethylene]diphosphonate dianion and [(5‐methyl‐2‐pyridyl)aminomethylene]diphosphonate trianion in salts with 4‐aminopyridine and ammonia

The crystal structures of two salts, products of the reactions between [(5‐methyl‐2‐pyridyl)aminomethylene]bis(phosphonic acid) and 4‐aminopyridine or ammonia, namely bis(4‐aminopyridinium) hydrogen [(5‐methyl‐2‐pyridinio)aminomethylene]diphosphonate 2.4‐hydrate, 2C₅H₇N₂⁺·C₇H₁₀N₂O₆P₂²⁻·2.4H₂O, (I), and triammonium hydrogen [(5‐methyl‐2‐pyridyl)aminomethylene]diphosphonate monohydrate, 3NH₄⁺·C₇H₉N₂O₆P₂³⁻·H₂O, (II), have been determined. In (I), the Z configuration of the ring N—C and amino N—H bonds of the bisphosphonate dianion with respect to the C_ring—N_amino bond is consistent with that of the parent zwitterion. Removing the H atom from the pyridyl N atom results in the opposite E configuration of the bisphosphonate trianion in (II). Compound (I) exhibits a three‐dimensional hydrogen‐bonded network, in which 4‐aminopyridinium cations and water molecules are joined to ribbons composed of anionic dimers linked by O—H...O and N—H...O hydrogen bonds. The supramolecular motif resulting from a combination of these three interactions is a common phenomenon in crystals of all of the Z‐isomeric zwitterions of 4‐ and 5‐substituted (2‐pyridylaminomethylene)bis(phosphonic acid)s studied to date. In (II), ammonium cations and water molecules are linked to chains of trianions, resulting in the formation of double layers.     

Hydrogen‐bonded dimers in 3‐amino‐4‐anilino‐1H‐isochromen‐1‐one and a hydrogen‐bonded sheet in 3‐amino‐4‐[methyl(phenyl)amino]‐1H‐isochromen‐1‐one

The molecules of 3‐amino‐4‐anilino‐1H‐isochromen‐1‐one, C₁₅H₁₂N₂O₂, (I), and 3‐amino‐4‐[methyl(phenyl)amino]‐1H‐isochromen‐1‐one, C₁₆H₁₄N₂O₂, (II), adopt very similar conformations, with the substituted amino group PhNR, where R = H in (I) and R = Me in (II), almost orthogonal to the adjacent heterocyclic ring. The molecules of (I) are linked into cyclic centrosymmetric dimers by pairs of N—H...O hydrogen bonds, while those of (II) are linked into complex sheets by a combination of one three‐centre N—H...(O)₂ hydrogen bond, one two‐centre C—H...O hydrogen bond and two C—H...π(arene) hydrogen bonds.     

“Reduced” Coumarin Dyes with an O‐Phosphorylated 2,2‐Dimethyl‐4‐(hydroxymethyl)‐1,2,3,4‐tetrahydroquinoline Fragment: Synthesis,Spectra, and STED Microscopy

Large Stokes‐shift coumarin dyes with an O‐phosphorylated 4‐(hydroxymethyl)‐2,2‐dimethyl‐1,2,3,4‐tetrahydroquinoline fragment emitting in the blue, green, and red regions of the visible spectrum were synthesized. For this purpose, N‐substituted and O‐protected 1,2‐dihydro‐7‐hydroxy‐2,2,4‐trimethylquinoline was oxidized with SeO₂ to the corresponding α,β‐unsaturated aldehyde and then reduced with NaBH₄ in a “one‐pot” fashion to yield N‐substituted and 7‐O‐protected 4‐(hydroxymethyl)‐7‐hydroxy‐2,2‐dimethyl‐1,2,3,4‐tetrahydroquinoline as a common precursor to all the coumarin dyes reported here. The photophysical properties of the new dyes (“reduced coumarins”) and 1,2‐dihydroquinoline analogues (formal precursors) with a trisubstituted C=C bond were compared. The “reduced coumarins” were found to be more photoresistant and brighter than their 1,2‐dihydroquinoline counterparts. Free carboxylate analogues, as well as their antibody conjugates (obtained from N‐hydroxysuccinimidyl esters) were also prepared. All studied conjugates with secondary antibodies afforded high specificity and were suitable for fluorescence microscopy. The red‐emitting coumarin dye bearing a betaine fragment at the C‐3‐position showed excellent performance in stimulation emission depletion (STED) microscopy.     

cis‐(6RS,13RS)‐3,3,10,10‐Tetra­methyl‐6,13‐diphenyl‐1,8‐dioxa‐4,11‐diaza­cyclo­tetra­decane‐2,5,9,12‐tetra­one and two of its precursors

The title macrocycle, C₂₆H₃₀N₂O₆, (VI), was obtained by `direct amide cyclization' from the linear precursor 3‐hydr­oxy‐N‐[1‐methyl‐1‐(N‐methyl‐N‐phenyl­carbamoyl)ethyl]‐2‐phenylpropanamide, the N‐methyl­anilide of rac‐2‐methyl‐2‐[(3‐hydroxy‐2‐phenyl­propanoyl)­amino]­propanoic acid, C₁₃H₁₇NO₄, (IV). The reaction proceeds via the inter­mediate rac‐2‐(2‐hydroxy‐1‐phenyl­ethyl)‐4,4‐dimethyl‐1,3‐oxazol‐5(4H)‐one, C₁₃H₁₅NO₃, (V), which was synthesized independently and whose structure was also established. Unlike all previously described analogues, the title macrocycle has the cis‐diphenyl configuration. The 14‐membered ring has a distorted rect­angular diamond‐based [3434] configuration and inter­molecular N—H⋯O hydrogen bonds link the mol­ecules into a three‐dimensional framework. The propanoic acid precursor forms a complex series of inter­molecular hydrogen bonds, each of which involves pairwise association of mol­ecules and which together result in the formation of extended two‐dimensional sheets. The oxazole inter­mediate forms centrosymmetric hydrogen‐bonded dimers in the solid state.     

Tetrakis(diethyl‐phosphonat)‐, Tetrakis(ethyl‐phenylphosphinat)‐ und Tetrakis(diphenylphosphin‐oxid)‐substituierte Phthalocyanine

Tetrakis(diethyl phosphonate), Tetrakis(ethyl phenylphosphinate)‐, and Tetrakis(diphenylphosphine oxide)‐Substituted Phthalocyanines The title compounds 7, 9 , and 11 are obtained by tetramerization of diethyl (3,4‐dicyanophenyl)phosphonate ( 5 ), ethyl (3,4‐dicyanophenyl)phenylphosphinate ( 8 ), and 4‐(diphenylphosphinyl)benzene‐1,2‐dicarbonitrile ( 10 ). The ³¹P‐NMR spectra of the phthalocyanines 7, 9 , and 11 and of their metal complexes present five to eight signals confirming the formation of four constitutional isomers with the expected C_4h, D_2h, C_2v, and C_s symmetry. In the FAB‐MS of the Zn, Cu, and Ni complexes of 7 and 9 , the peaks of dimeric phthalocyanines are observed. By gel‐permeation chromatography, the monomeric complex [Ni( 7 )] and a dimer [Ni( 7 )]₂ can be separated. These dimers differ from the known phthalocyanine dimers, i.e., possibly the P(O)(OEt)₂ and P(O)(Ph)(OEt) substituents in 7 and 9 are involved in complexation. The free phosphonic acid complex [Zn( 12 )] and [Cu( 12 )] are H₂O‐soluble. In the FAB‐MS of [Zn( 12 )], only the peaks of the dimer are present; the ESI‐MS confirms the existence of the dimer and the metal‐free dimer. In the UV/VIS spectrum of [Zn( 12 )], the hypsochromic shift characteristic for the known type of dimers from 660–700 nm to 620–640 nm is observed. As in the FAB‐MS of [Zn( 12 )], the free phosphinic acid complex [Zn( 13 )] shows only the monomer, an ESI‐MS cannot be obtained for solubility problems. The UV/VIS spectrum of [Zn( 13 )] demonstrates the existence of the monomer as well as of the dimer.     

Supramolecular aggregation in three 4‐aryl‐6‐(1H‐indol‐3‐yl)‐3‐methyl‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitriles

Both 6‐(1H‐indol‐3‐yl)‐3‐methyl‐4‐(4‐methylphenyl)‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile and 6‐(1H‐indol‐3‐yl)‐3‐methyl‐4‐(4‐methoxyphenyl)‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile crystallize from dimethylformamide solutions as stoichiometric 1:1 solvates, viz. C₂₉H₂₁N₅·C₃H₇NO, (I), and C₂₉H₂₁N₅O·C₃H₇NO, (II), respectively; however, 6‐(1H‐indol‐3‐yl)‐3‐methyl‐1‐phenyl‐4‐(3,4,5‐trimethoxyphenyl)‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile, C₃₁H₂₅N₅O₃, (III), crystallizes in the unsolvated form. The heterocyclic components of (I) are linked by C—H...π(arene) hydrogen bonds to form cyclic centrosymmetric dimers, from which the solvent molecules are pendent, linked by N—H...O hydrogen bonds. In (II), the heterocyclic components are linked by a combination of C—H...N and C—H...π(arene) hydrogen bonds into chains containing two types of centrosymmetric ring, and the pendent solvent molecules are linked to these chains by N—H...O hydrogen bonds. Molecules of (III) are linked into simple C(12) chains by an N—H...O hydrogen bond, and these chains are weakly linked into pairs by an aromatic π–π stacking interaction.     

Bis[μ3‐cis‐N‐(2‐aminopropyl)‐N′‐(2‐carboxylatophenyl)oxamidato(3–)]bis(2,2′‐bipyridine)dichloridotetracopper(II) dihydrate

The title complex, bis[μ₃‐cis‐N‐(2‐aminopropyl)‐N′‐(2‐carboxylatophenyl)oxamidato(3−)]‐1:2:4κ⁷N,N′,N′′,O:O′,O′′:O′′′;2:3:4κ⁷O′′′:N,N′,N′′,O:O′,O′′‐bis(2,2′‐bipyridine)‐2κ²N,N′;4κ²N,N′‐dichlorido‐1κCl,3κCl‐tetracopper(II) dihydrate, [Cu₄(C₁₂H₁₂N₃O₄)₂Cl₂(C₁₀H₈N₂)₂]·2H₂O, consists of a neutral cyclic tetracopper(II) system having an embedded centre of inversion and two solvent water molecules. The coordination of each Cu^II atom is square‐pyramidal. The separations of Cu^II atoms bridged by cis‐N‐(2‐aminopropyl)‐N′‐(2‐carboxylatophenyl)oxamidate(3−) and carboxyl groups are 5.2096 (4) and 5.1961 (5) Å, respectively. A three‐dimensional supramolecular structure involving hydrogen bonding and aromatic stacking is observed.     

Acrylate based anticorrosion films using novel bis‐phosphonic methacrylates

Two novel phosphonated methacrylate monomers were successfully synthesized and subsequently incorportated into adhesion/anticorrosive coatings. Specifically, they were propyl N,N‐tetramethyl‐bis(phosphonate)‐2‐hydroxyl‐bis(methylene) amine methylmethacrylate (MAC₃NP₂) and 2‐[2,2‐bis(diisopropoxyphosphoryl)ethoxy]‐methylmethacrylate, (MAC₃P₂). The phosphonic forms of each monomer were blended with ～85% w.w acrylates (tripropyleneglycol‐diacrylate and hexanediol‐diacrylate) and 6% w.w of the photo sensitive initiator Darocur®. Along with a monophosphonic monomer synthesized in a previous publication (MAC₃P), they were polymerized on Q‐panels under ultraviolet light, and then subject to the salt spray test (ca. 0.5 mol/L NaCl at 35 °C) for a duration of up to 50 days. The results indicate that acrylate blends with low concentration of the bisphosphonic compound MAC₃P₂ have excellent resistance to corrosion, thus excellent adhesive properties. Importantly, these coatings were formed without the use of a hydrophobic polymer matrix or solvents. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7972–7984, 2008     

Synthesis of novel N1‐(2‐furanidyl)‐5‐fluorouracil derivatives of α‐hydroxy(thio)phosphonates

Several N¹‐(2‐furanidyl)‐5‐fluorouracil derivatives of α‐hydroxythiophosphonates were synthesized via oxidation by Moffatt's method of N¹‐(2‐furanidyl)‐N³‐(hydroxyalkyl)‐5‐fluorouracil, followed by the addition of diethyl thiophosphite. The phosphonate products were obtained by the oxidation of the corresponding thiophosphonates with m‐chloroperoxybenzoic acid. The crystal structure of compound 6a was determined by X‐ray diffraction. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:211–215, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10021     

3‐(1H‐Pyrrol‐2‐yl)‐1H‐pyrazole forms an unusual hydrogen‐bonded two‐dimensional (3,4)‐connected net

The title compound, C₇H₇N₃, is the first crystallographically characterized 1H‐pyrrolyl‐1H‐pyrazole derivative and contains two unique molecules in its asymmetric unit (Z′ = 2). These molecules associate into centrosymmetric tetramers through N—H...N hydrogen bonding, including a cyclic dimerization of one of the two unique pyrazole rings. These tetramers are linked further by two weaker N—H...π contacts to give a novel two‐dimensional (3,4)‐connected net with a (3².8)₂(3.8²)₂ topology.     

Synthesis of 2′‐Deoxy‐1′‐homo‐N‐nucleosides with Anti‐Influenza Activity by Catalytic Methyltrioxorhenium (MTO)/H2O2 Oxyfunctionalization

This paper describes a new route for the synthesis of 1′‐homo‐N‐nucleoside derivatives by means of either methyltrioxorhenium (MTO) or supported MTO catalysts, with H₂O₂ as the primary oxidant. Under these selective conditions, the oxyfunctionalization of the heterocyclic ring and the N heteroatom oxidation were operative processes, regardless of the type of substrate used, that is, purine or pyrimidine derivatives. In addition, the oxidation of 1′‐homo‐N‐thionucleosides, showed the occurrence of site‐specific oxidative nucleophilic substitutions of the heterocyclic ring. The MTO/H₂O₂ system showed, in general, high reactivity under both homogeneous and heterogeneous conditions, affording the final products with high conversion values of substrates and from medium to high yields. Many of the novel 1′‐homo‐N‐nucleoside analogues were active against the influenza A virus, without any cytotoxic effects, retaining their activity in both protected and unprotected forms.