Synthesis of Some Novel Pyrido[2,3‐d]pyrimidine and Pyrido[3,2‐e][1,3,4]triazolo and Tetrazolo[1,5‐c]pyrimidine Derivatives as Potential Antimicrobial and Anticancer Agents

A novel series of pyrido[2,3‐d]pyrimidines 3a – d , 4a – d , 5a – d , 6a – d , and 7a – d ; pyrido[3,2‐e][1,3,4]triazolo; and tetrazolo[1,5‐c]pyrimidines 10a – d and 11a – d was synthesized through different chemical reactions starting from 2‐amino‐3‐cyano‐4,6‐diarylpyridines. The newly synthesized heterocycles were characterized by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and mass spectral data. Compounds have been screened for their antibacterial and antifungal activities. The data showed that the presence of electron‐donating group such as p‐methoxyphenyl increases the antimicrobial activity. Also, the compounds have shown anticancer activity for colon and liver cancer cells.     

Synthesis of Biologically Active[4-(4-Bromophenyl)-2-thiazolyl]hydrazones and their D-Galactose Derivatives

Benzaldehyde [4‐(4‐bromophenyl)thiazol‐2‐yl]hydrazones 5a – 5d were prepared by reacting the thiosemicarbazones 2a – 2d with 2,4′‐dibromoacetophenone ( 1 ) in absolute ethanol. Acetylation of 5a and 5b with Ac₂O/Py at room temperature gave the N‐acetyl derivatives 6a and 6b . 4‐Methyl‐2‐pentanone/cyclopentanone [4‐(4‐bromo‐phenyl)thiazol‐2‐yl]hydrazones ( 8a ) and ( 8b ) were similarly obtained from the reaction of 1 with the thiosemicarbazones 7a and 7b , respectively. Cyclization of D‐galactose thiosemicarbazone ( 9 ) and its tautomers 10 and 11 with 1 afforded an equilibrium mixture of the acyclic 2‐thiazolylhydrazone 12 , together with its respective cyclic galactosyl derivatives 13 and 14 , whose structures were studied by using ¹H and ¹³C NMR spectra. The antimicrobial activity of the synthesized thiazole derivatives was evaluated in vitro by using an agar diffusion technique, and some of these compounds showed potential activity against Candida albicans.     

Structure elucidation of [1,3]oxazolo[4,5‐e][2,1]benzisoxazole and naphtho[1,2‐d][1,3]‐ and phenanthro[9,10‐d]oxazoles using gradient selected gHMBC,gHMQC and gHMQC‐TOCSY NMR techniques

Structure elucidation of compounds in the benzisoxazole series ( 1 – 6 ) and naphtho[1,2‐d][1,3]‐ ( 7 – 10 ) and phenanthro[9,10‐d][1,3]oxazole ( 11 – 14 ) series was accomplished using extensive 2D NMR spectroscopic studies including ¹H–¹H COSY, long‐ range ¹H–¹H COSY, ¹H–¹³C COSY, gHMQC, gHMBC and gHMQC‐TOCSY experiments. The distinction between oxazole and isoxazole rings was made on the basis of the magnitude of heteronuclear one‐bond ¹J_{C2, H2} (or ¹J_{C3, H3}) coupling constants. Complete analysis of the ¹H NMR spectra of 11 – 14 was achieved by iterative calculations. Gradient selected gHMQC‐TOCSY spectra of phenanthro[9,10‐d][1,3]oxazoles 11 – 14 were obtained at different mixing times (12, 24, 36, 48 and 80 ms) to identify the spin system where the protons of phenanthrene ring at H‐5, H‐6 and at H‐9 and H‐7 and H‐8 were highly overlapping. Copyright © 2003 John Wiley & Sons, Ltd.     

Syntheses and Properties of Graphyne Fragments: Trigonally Expanded Dehydrobenzo[12]annulenes

We present herein the synthesis and properties of the largest hitherto unknown graphyne fragment, namely trigonally expanded tetrakis(dehydrobenzo[12]annulene)s (tetrakis‐DBAs). Intramolecular three‐fold alkyne metathesis reactions of hexakis(arylethynyl)DBAs 9 a and 9 b using Fürstner’s Mo catalyst furnished tetrakis‐DBAs 8 a and 8 b substituted with tert‐butyl or branched alkyl ester groups in moderate and fair yields, respectively, demonstrating that the metathesis reaction of this protocol is a powerful tool for the construction of graphyne fragment backbones. For comparison, hexakis(arylethynyl)DBAs 9 c – g have also been prepared. The one‐photon absorption spectrum of tetrakis‐DBA 8 a bearing tert‐butyl groups revealed a remarkable bathochromic shift of the absorption cut‐off (λ_cutoff) compared with those of previously reported graphyne fragments due to extended π‐conjugation. Moreover, in the two‐photon absorption spectrum, 8 a showed a large cross‐section for a pure hydrocarbon because of the planar para‐phenylene‐ethynylene conjugation pathways. Hexakis(arylethynyl)‐DBAs 9 c – e and 9 g and tetrakis‐DBA 8 b bearing electron‐withdrawing groups aggregated in chloroform solutions. Comparison between the free energies of 9 e and 8 b bearing the same substituents revealed the more favorable association of the latter due to stronger π–π interactions between the extended π‐cores. Polarized optical microscopy observations, DSC, and XRD measurements showed that 8 b and 9 e with branched alkyl ester groups displayed columnar rectangular mesophases. By the time‐resolved microwave conductivity method, the columnar rectangular phase of 8 b was shown to exhibit a moderate charge‐carrier mobility of 0.12 cm² V^?1 s^?1. These results indicate that large graphyne fragments can serve as good organic semiconductors.     

Reversible Mechanical Interlocking of D‐Shaped Molecular Karabiners bearing Coordination‐Bond Loaded Gates: Route to Self‐Assembled [2]Catenanes

Complexation of 1,4‐phenylenebis(methylene) diisonicotinate, L1 , with cis‐protected Pd^II components, [Pd( L′ )(NO₃)₂], in an equimolar ratio yielded binuclear complexes, 1 a – d of [Pd₂( L′ )₂( L1 )₂](NO₃)₄ formulation where L′ stands for ethylenediamine (en), tetramethylethylenediamine (tmeda), 2,2′‐bipyridine (bpy), and phenanthroline (phen). The combination of 4,4′‐bipyridine, L2 , with the cis‐protected Pd^II units is known to yield molecular squares, 2 a – d . However, 2 b – d coexist with the corresponding molecular triangles, 3 b – d . Combination of an equivalent each of the ligands L1 and L2 with two equivalents of cis‐protected Pd^II components in DMSO resulted in the D ‐shaped heteroligated complexes [Pd₂( L′ )₂( L1 )( L2 )](NO₃)₄, 4 a – d . Two units of the D ‐shaped complexes interlock, in a concentration dependent fashion, to form the corresponding [2]catenanes [Pd₂( L′ )₂( L1 )( L2 )]₂(NO₃)₈, 5 a – d under aqueous conditions. Crystal structures of the macrocycle [Pd₂(tmeda)₂( L1 )( L2 )](PF₆)₄, 4 b′′ , and the catenane [Pd₂(bpy)₂( L1 )( L2 )]₂(NO₃)₈, 5 c , provide unequivocal support for the proposed molecular architectures.     

Einkristalle von La[AsO4] im Monazit‐ und Sm[AsO4] im Xenotim‐Typ

Single Crystals of La[AsO₄] with Monazite‐ and Sm[AsO₄] with Xenotime‐Type Structure Brick‐shaped, transparent single crystals of colourless monazite‐type La[AsO₄] (monoclinic, P2₁/n, a = 676.15(4), b = 721.03(4), c = 700.56(4) pm, β =104.507(4)°, Z = 4) and pale yellow xenotime‐type Sm[AsO₄] (tetragonal, I4₁/amd, a = 718.57(4), c = 639.06(4) pm, Z = 4) emerge as by‐products from alkali and rare‐earth metal chloride fluxes whenever the synthesis of lanthanide(III) oxoarsenate(III) derivatives from admixtures of the corresponding sesquioxides in sealed, evacuated silica ampoules is accompanied by air intrusion and subsequent oxidation. Nine oxygen atoms from seven discrete [AsO₄]^3? tetrahedra recruit the rather irregular coordination sphere of La³⁺ (d(La³⁺?O^2?) = 248 – 266 pm plus 291 pm) and even a tenth ligand could be considered at a distance of 332 pm. The trigonal dodecahedral figure of coordination consisting of eight oxygen atoms at distances of 236 and 248 pm (4× each) about Sm³⁺ is provided by only six isolated tetrahedral [AsO₄]^3? units. Alternating trans‐edge condensation of the latter with the [LaO₉₊₁] polyhedra of monazite‐type La[AsO₄] and the [SmO₈] polyhedra of xenotime‐type Sm[AsO₄] constitutes the main structural chain features along [100] or [001], respectively. The bond distances and angles of the complex [AsO₄]^3? anions range within common intervals (d(As⁵⁺?O^2?) = 167 – 169 pm, ?(O–As–O) = 100 – 116°) for both lanthanide(III) oxoarsenates(V) presented here.     

Tetramethylcyclotetraarsoxane Bridged Copper(I) Halides with Porous Sheet and Framework Structures [CuX{cyclo-(MeAsO)4}] (X=Cl,Br, I) and [Cu3X3{cyclo-(MeAsO)4}2] (X=Cl,Br)

Open sheet and framework structures [CuX{cyclo-(MeAsO)₄}] (X=Cl, Br, I) 1 – 3 and [Cu₃X₃{cyclo-(MeAsO)₄}₂] (X=Cl, Br) 4 and 5 may be prepared by self-assembly from CuX and methylcycloarsoxane (MeAsO)_n in acetonitrile solution. 1 – 3 exhibit 4⁴ nets in which (CuX)₂ units are connected through μ-1 _KAs¹ : 2 _KAs³ coordinated (MeAsO)₄ ligands into large 28-membered rings. In contrast, adjacent [CuX] chains in 4 and 5 are connected into sheets by μ₄-K⁴ As coordinated (MeAsO)₄ building blocks, with μ-1 _KAs¹ : 2 _KAs³ bridging of these layers by independent (MeAsO)₄ cyclotetramers leading to the generation of a porous framework structure. 1 – 5 were characterised by X-ray structural analysis.     

Molecular Design of Calixarene,Part 4, Synthesis of Novel Double‐Armed p‐(tert‐Butyl)calix[4]arene‐Derived Amides and Their Lead(II)(Pb2+)‐Selective‐Electrode Properties

A series of novel double‐armed p‐(tert‐butyl)calix[4]arenes, carrying benzoylamido, 4‐nitrobenzoylamido, isonicotinamido, α‐naphthamido, acetamido, propionamido, or butyramido groups (see 2 – 8 , resp.) were synthesized in 80 – 86% yield by the reaction of the lower‐rim 1,3‐bis(aminoethoxy)‐substituted calix[4]arenediol 1 with the corresponding acylating agents. Their structures were established by elemental analysis, mass, IR, UV, and ¹H‐NMR spectroscopy. Ion‐selective electrodes (ISEs) for Pb²⁺, carrying 2 – 8 in a PVC membrane as neutral ionophore, were prepared, and their selectivity coefficients for Pb²⁺ (K) were determined against other heavy‐metal ions, alkali and alkaline earth metal ions, and ammonium ions by means of the separate‐solution method. The results obtained indicated that the electrodes based on the calix[4]arene‐derived amides 2 – 8 as the neutral ionophores were all Pb²⁺ selective and exhibited almost theoretical Nernstian slopes, except for 3 and 4 . Typically, the Pb²⁺‐selective electrode based on 6 – 8 exhibited almost Nernstian slopes for Pb²⁺ over a relatively wide concentration range and had a fast response time as well as a long lifetime, although the silver ion interfered strongly. These ISEs based on 6 – 8 showed a relatively good Pb²⁺ selectivity against most of the interfering cations examined, except for Ag⁺. The effect of the side‐arm functions of calix[4]arene derivatives 2 – 8 on the Nernstian slopes and on the selectivity coefficients for Pb²⁺ obtained with the Pb²⁺ ISEs based on 2 – 8 is discussed.     

Synthesis and biological activities of substituted dihydrobenzo[h]-pyrimido[4,5-b]quinolines as tetracyclic 5-deaza nonclassical folates

Novel tetracyclic compounds 1–4 have been synthesized via a regiospecific cyclocondensation reaction between substituted 6-aminopyrimidines 5– 7 and chlorovinyl aldehydes 13 and 14 . The linear structures of these compounds were established by ¹H nmr and ¹³C nmr spectral data and also by synthesis of the compounds via an unambiguous route. The growth of Manca human lymphoma cells was inhibited 50% by 1 and 4 at 4.5 × 10^?6 M and 1.2 × 10^?6 M respectively. These compounds also inhibited human dihydrofolate reductase (DHFR)by 50% at 4.4 × 10^?6 M and 1.4 × 10^?6 irrespectively and L. casei DHFR at 1.9 × 10^?5 M and 1.1 × 10^?5 M respectively. Compound 16 , a positional isomer of 1 , was the most potent of the compounds studied, it inhibited the growth of Manca human lymphoma cells by 50% at 9 × 10^?8 M. The IC₅₀ values of 16 for the inhibition of human DHFR and L. casei DHFR were 8 × 10^?8 M and 1.9 × 10^?5 M respectively.     

The Cluster Compounds Ag[W6Br14] and Ag2[W6Br14]

The reaction of W₆Br₁₂ with AgBr in evacuated silica tubes (temperature gradient 925 K/915 K) yielded brownish black octahedra of Ag[W₆Br₁₄] ( I ) and yellowish green platelets of Ag₂[W₆Br₁₄] ( II ) both in the low temperature zone. ( I ) crystallizes cubically (Pn3 (no. 201); a = 13.355 Å, Z = 4) and ( II ) monoclinically (P2₁/c (no. 14); a = 9.384 Å, b = 15.383 Å, c = 9.522 Å, β = 117.34°, Z = 2). Both crystal structures contain isolated cluster anions, namely [(W₆Brⁱ₈)Br^a₆]^1– and [(W₆Brⁱ₈)Br^a₆])]^2–, respectively, with the mean distances and angles: ( I ) d(W–W) = 2.648 Å, d(W–Brⁱ) = 2.617 Å, d(W–Br^a) = 2.575 Å, d(Brⁱ…Brⁱ) = 3.700 Å, d(Brⁱ…Br^a) = 3.692 Å, ∠W–Brⁱ–W = 60.78°. ( II ) d(W–W) = 2.633 Å, d(W–Brⁱ) = 2.624 Å, d(W–Br^a) = 2.613 Å, d(Brⁱ…Brⁱ) = 3.710 Å, d(Brⁱ…Br^a) = 3.707 Å, ∠W–Brⁱ–W = 60.23°. The Ag⁺ cations are trigonal antiprismatically coordinated in ( I ) with d(Ag–Br) = 2.855 Å, but distorted trigonally planar in ( II ) with d(Ag–Br) = 2.588–2.672 Å. The structural details of hitherto known compounds with [W₆Br₁₄] anions will be discussed.     

Photochemische Reaktionen. 62. Mitteilung [1]. Die Photofragmentierung von O-acetyljervin

On ultraviolet irradiation O-acetyljervine ( 1 ) is subjected to several parallel fragmentations. From the complex reaction mixtures obtained in a variety of solvents (dioxan, tetrahydrofuran, acetonitrile, iso-octane, benzene) the major alicyclic products 6 – 8 and the heterocyclic compounds 12 – 16 have been isolated. Products 6 – 8 undergo further photochemical changes, e.g., decarbonylation of 7 to 9 and hydrolytic cleavage of 8 to 10 . These photofragmentations are initiated almost specifically upon selective π → π* excitation at 2537 Å with a quantum yield of Φ²⁵³⁷ = 0.145 for conversion of starting material. Reaction upon irradiation in the long-wavelength n → π* absorption band is very much less efficient (Φ³⁶⁶⁰ = 0.611 · 10^?3, both determinations for O-trimethylsilyl-jervine ( 2 ) in tetrahydrofuran). A high degree of photostability is observed also at 2537 Å on N-protonation of O-acetyljervine ( 1 ) in acetic acid. Furthermore, reactivity is greatly reduced for the N-methyl ( 3 ) and N-acetyl ( 4 ) derivatives in neutral solvents at 2537 Å. N-Chloro-O-acetyljervine ( 5 ) in dioxan at 2537 Å gave preferentially O-acetyljervine hydrochloride.     

On the Purported Structure of Cyclodeca[1,2,3-de: 6,7,8-d′e′]dinaphthalene

The reaction of the bis(sulfonium salt) 7 in a solution of Na₂CO₃ in H₂O/EtOH yielded three main products 8 – 10 . The spectroscopic data of 8 were identical to those which led Mithcell and Sondheimer to assign them to cyclodeca[1,2,3-de: 6,7,8-d′e′]dinaphthalene ( 3 ). Our investigations show, however, that the correct structural assignment leads to the structure of 7,7a-dihydrodibenzo[de,mn]naphthacene ( 8 ).     

Diphosphapodanden, [12]‐, [15]‐ und [18]Diphosphacoronanden,Diphosphacryptand‐8 und Alkalimetall‐Komplexe

Diphosphapodands, [12]‐, [15]‐, and [18]Diphosphacoronands, Diphosphacryptand‐8, and Alkali‐Metal Complexes The cyclizing bis‐phosphonium‐salt formation of the open‐chain bis‐phosphine 17a (1,1,7,7‐tetrabenzyl〈P.O.P‐podand‐7〉) with diethylene glycol derived dibromide 13a yields the 12‐membered cyclic bis‐phosphonium salt 20 (4,4,10,10‐tetrabenzyl‐12〈O.P.O.P‐coronand‐4〉‐4,10‐diium dibromide) in yields as high as 50–60%. The 1,1,10,10‐tetrabenzyl〈P.O₂.P‐podand‐10〉 17b forms with 13a the 15‐membered cyclic bis‐phosphonium salt 21 (7,7,13,13‐tetrabenzyl‐15〈O₂.P.O.P‐coronand‐5〉‐7,13‐diium dibromide) with the same high yield. By quaternization of the bis‐phosphine 17b with triethylene glycol derived dibromide 13b , the 18‐membered 7,7,16,16‐tetrabenzyl‐18〈O₂.P.O₂.P‐coronand‐6〉‐7,16‐diium dibromide 24 is obtained in 50% yield, too. The Wittig reaction of the cyclic phosphonium salts with benzaldehyde yields the 12‐, 15‐, and 18‐membered cyclic bis‐benzylphosphine dioxides 9, 10 , and 11 as cis‐ and trans‐isomers beside trans‐stilbene. The 7,13‐dioxido‐7,13‐dibenzyl‐15〈O₂.P.O₂.P‐coronand‐5〉 10 forms a crystalline 1 : 1 Na‐complex 23 , which exists as a dimer. The structure of 23 was established by an X‐ray analysis and spectroscopic data. The 7,16‐dibenzyl‐18〈O₂.P.O₂.P‐coronand‐6〉 28 that is available by reduction of 11 with CeCl₃/LiAlH₄ reacts with triethylene glycol derived dibromide 13b under Ruggly Ziegler‐dilution conditions to give the bicyclic bis‐phosphonium salt 29 (1,10‐dibenzyl〈P[O₂]₃.P‐cryptand‐8〉‐1,10‐diium dibromide) in 18% yield. Again, by the Wittig procedure with benzaldehyde, the 7,16‐dioxido〈P[O₂]₃P‐cryptand‐8〉 12 is obtained as the first diphosphacryptand. The FD‐MS (CH₂Cl₂) of the cyclic bis‐phosphine dioxides 10 – 12 show that they exist as [2M+Na]⁺ complexes. The complex formation constants K_a of 9 – 11 with alkali‐metal cations are studied and compared with the complex formation of corresponding crown ethers.     

Oligoporphyrin Arrays Conjugated to [60]Fullerene: Preparation,NMR Analysis,and Photophysical and Electrochemical Properties

We report the synthesis and physical properties of novel fullerene–oligoporphyrin dyads. In these systems, the C‐spheres are singly linked to the terminal tetrapyrrolic macrocycles of rod‐like meso,meso‐linked or triply‐linked oligoporphyrin arrays. Monofullerene–mono(Zn^II porphyrin) conjugate 3 was synthesized to establish a general protocol for the preparation of the target molecules (Scheme 1). The synthesis of the meso,meso‐linked oligopophyrin–bisfullerene conjugates 4 – 6 , extending in size up to 4.1 nm ( 6 ), was accomplished by functionalization (iodination followed by Suzuki cross‐coupling) of the two free meso‐positions in oligomers 21 – 23 (Schemes 2 and 3). The attractive interactions between a fullerene and a Zn^II porphyrin chromophore in these dyads was quantified as ΔG=−3.3 kcal mol⁻¹ by variable‐temperature (VT) ¹H‐NMR spectroscopy (Table 1). As a result of this interaction, the C‐spheres adopt a close tangential orientation relative to the plane of the adjacent porphyrin nucleus, as was unambiguously established by ¹H‐ and ¹³C‐NMR (Figs. 9 and 10), and UV/VIS spectroscopy (Figs. 13–15). The synthesis of triply‐linked diporphyrin–bis[60]fullerene conjugate 8 was accomplished by Bingel cyclopropanation of bis‐malonate 45 with two C₆₀ molecules (Scheme 5). Contrary to the meso,meso‐linked systems 4 – 6 , only a weak chromophoric interaction was observed for 8 by UV/VIS spectroscopy (Fig. 16 and Table 2), and the ¹H‐NMR spectra did not provide any evidence for distinct orientational preferences of the C‐spheres. Comprehensive steady‐state and time‐resolved UV/VIS absorption and emission studies demonstrated that the photophysical properties of 8 differ completely from those of 4 – 6 and the many other known porphyrin–fullerene dyads: photoexcitation of the methano[60]fullerene moieties results in quantitative sensitization of the lowest singlet level of the porphyrin tape, which is low‐lying and very short lived. The meso,meso‐linked oligoporphyrins exhibit ¹O₂ sensitization capability, whereas the triply‐fused systems are unable to sensitize the formation of ¹O₂ because of the low energy content of their lowest excited states (Fig. 18). Electrochemical investigations (Table 3, and Figs. 19 and 20) revealed that all oligoporphyrin arrays, with or without appended methano[60]fullerene moieties, have an exceptional multicharge storage capacity due to the large number of electrons that can be reversibly exchanged. Some of the Zn^II porphyrins prepared in this study form infinite, one‐dimensional supramolecular networks in the solid state, in which the macrocycles interact with each other either through H‐bonding or metal ion coordination (Figs. 6 and 7).     

Synthesis and Reactions of Pyrido[2,1‐a]isoquinolin‐4‐yl Formimidate Derivatives and Antimicrobial Activities of Isolated Products

Treatment of arylidene malononitriles 2A – C with 1‐cyanomethylisoquinoline 1 afforded 4‐amino‐2‐arylpyrido[2,1‐a ]isoquinoline‐1,3‐dicarbonitrile derivatives 5A – C , which converted to formimidates 6A – C via reaction with triethylorthoformate. Treatment of the latter compounds with hydrazine hydrate gave the corresponding amino–imino compounds 7A – C , which underwent Dimroth rearrangement to afford 13‐aryl‐1‐hydrazinylpyrimido[5′,4′:5,6]pyrido[2,1‐a ]isoquinoline‐12‐carbonitrile 8A – C . The latter reacted with aldehyde to give 9a – i . Oxidative cyclization of the latter compounds 9a – i gave [1,2,4]triazolo[4″,3″:1′,6′]‐pyrimido[5′,4′:5,6]pyrido[2,1‐a ]isoquinolines 10a , d , g . Such compounds isomerized to the thermodynamically more stable isomers [1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:5,6]‐pyrido[2,1‐a ]isoquinolines 11a , d , g . Antimicrobial activities for some compounds were studied.     

Synthesis and Complexation Properties of a New Class of Receptors based on a cone-configurated tetra-p-(tert-butyl)calix[4]arene and bipyridyl subunits

0The bipyridyl-armed tetra-p-(tert-butyl)calix[4]arenes 1 – 5 were synthesized from tetra-p-(tert-butyl)-calix[4]arene A and 6-(bromomethyl)-6′-methyl-2,2′-bipyridine ( B ) by direct base-strength-driven regioselective O-alkylation or by stepwise procedures. Preliminary complexation studies of the ligands 1 – 3 with Cu^I affording the complexes 6 – 8 are described.     

Structural Elucidation and Antimicrobial Evaluation of Novel [1,2,4]Triazolo[4,3‐a]pyrimidines and Pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidinones

1,3‐Di(thiophen‐2‐yl)prop‐2‐en‐1‐one ( 1 ) was utilized in the synthesis of 4,6‐di(thiophen‐2‐yl)‐3,4‐dihydropyrimidine‐2(1H)‐thione ( 2 ) and 5,7‐di(thiophen‐2‐yl)‐2‐thioxo‐2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐one ( 4 ). The latter thiones were used in the synthesis of two new series of [1,2,4]triazolo[4,3‐a]pyrimidines 10a – i and pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidinones 5a – i via reaction with the appropriate hydrazonoyl halides using triethylamine as a basic catalyst in dioxane. The mechanism of formation of the synthesized compounds was discussed, and the assigned structure was established via microanalysis, spectral data (infrared, ¹H NMR, and Mass), and density functional calculations. Moreover, the newly synthesized products were evaluated for their antimicrobial activities, and the results show that some derivatives have been well with mild activities. Finally, quantum chemistry calculations confirmed the mechanism and structure of the products.     

Nitrogen‐Rich Compounds of the Lanthanoids: The 5,5′‐Azobis[1H‐tetrazol‐1‐ides] of some Yttric Earths (Tb,Dy, Ho,Er, Tm,Yb, and Lu)

A set of N‐rich salts, 3 – 9 , of the heavy lanthanoids (terbium, 3 ; dysprosium, 4 ; holmium 5 ; erbium, 6 ; thulium, 7 ; ytterbium, 8 ; lutetium, 9 ) based on the energetic 5,5′‐azobis[1H‐tetrazole] (H₂ZT) was synthesized and characterized by elemental analysis, vibrational (IR and Raman) spectroscopy, and X‐ray structure determination. The synthesis of the lanthanoid salts 3 – 9 was performed by crystallization from concentrated aqueous solutions of disodium 5,5′‐azobis[1H‐tetrazol‐1‐ide] dihydrate (Na₂ZT?2 H₂O; 1 ) and the respective Ln(NO₃)₃?5 H₂O and yielded large rhombic crystals of the type [Ln(H₂O)₈]₂(ZT)₃?6 H₂O in ca. 70% of the theoretical yield. The compounds 3 – 9 are isostructural (triclinic space group P ) to the previously published yttrium salt 2 ; they show, however, a clear lanthanoid contraction of several crystallographic parameters, e.g., the cell volume or the Ln? O bond lengths of the Ln³⁺ ions and the coordinating H₂O molecules. The lanthanoid contraction influences the strengths of the H‐bonds, which can be observed as a red shift by 4 cm^?1 in the characteristic IR band, in particular from 3595 cm^?1 ( 3 ) to 3599 cm^?1 ( 9 ). In good agreement with previous works, 2 – 9 are purely salt‐like compounds without a coordinative bond between the tetrazolide anion and the Ln³⁺ cation.     

Formation of Heptaleno[1,2-c]furans and Heptaleno[1,2-c]furanones

The dehydrogenation reaction of the heptalene-4,5-dimethanols 4a and 4d , which do not undergo the double-bond-shift (DBS) process at ambient temperature, with basic MnO₂ in CH₂Cl₂ at room temperature, leads to the formation of the corresponding heptaleno[1,2-c]furans 6a and 6d , respectively, as well as to the corresponding heptaleno[1,2-c]furan-3-ones 7a and 7d , respectively (cf. Scheme 2 and 8). The formation of both product types necessarily involves a DBS process (cf. Scheme 7). The dehydrogenation reaction of the DBS isomer of 4a , i.e., 5a , with MnO₂ in CH₂Cl₂ at room temperature results, in addition to 6a and 7a , in the formation of the heptaleno[1,2-c]-furan-1-one 8a and, in small amounts, of the heptalene-4,5-dicarbaldehyde 9a (cf. Scheme 3). The benzo[a]heptalene-6,7-dimethanol 4c with a fixed position of the C?C bonds of the heptalene skeleton, on dehydrogenation with MnO₂ in CH₂Cl₂, gives only the corresponding furanone 11b (Scheme 4). By [²H₂]-labelling of the methanol function at C(7), it could be shown that the furanone formation takes place at the stage of the corresponding lactol [3-²H₂]- 15b (cf. Scheme 6). Heptalene-1,2-dimethanols 4c and 4e , which are, at room temperature, in thermal equilibrium with their corresponding DBS forms 5c and 5e , respectively, are dehydrogenated by MnO₂ in CH₂Cl₂ to give the corresponding heptaleno[1,2-c]furans 6c and 6e as well as the heptaleno[1,2-c]furan-3-ones 7c and 7e and, again, in small amounts, the heptaleno[1,2-c]furan-1-ones 8c and 8e , respectively (cf. Scheme 8). Therefore, it seems that the heptalene-1,2-dimethanols are responsible for the formation of the furan-1-ones (cf. Scheme 7). The methylenation of the furan-3-ones 7a and 7e with Tebbe's reagent leads to the formation of the 3-methyl-substituted heptaleno[1,2-c]furans 23a and 23e , respectively (cf. Scheme 9). The heptaleno[1,2-c]furans 6a, 6d , and 23a can be resolved into their antipodes on a Chiralcel OD column. The (P)-configuration is assigned to the heptaleno[1,2-c]furans showing a negative Cotton effect at ca. 320 nm in the CD spectrum in hexane (cf. Figs. 3–5 as well as Table 7). The (P)-configuration of (–)- 6a is correlated with the established (P)-configuration of the dimethanol (–)- 5a via dehydrogenation with MnO₂. The degree of twisting of the heptalene skeleton of 6 and 23 is determined by the Me-substitution pattern (cf. Table 9). The larger the heptalene gauche torsion angles are, the more hypsochromically shifted is the heptalene absorption band above 300 nm (cf. Table 7 and 8, as well as Figs. 6–9).     

2,4-Disubstituted Pyrrolo[2,3-d]pyrimidine α-D- and β-D-Ribofuranosides Related to 7-Deazaguanosine

Nucleobase-anion glycosylation (KOH, tris[2-(2-methoxyethoxy)ethyl]amine (TDA-1), MeCN) of the pyrrolo[2,3-d]pyrimidines 4a – d with 5-O-[(1,1-dimethylethyl)dimethylsilyl]-2,3-O-(1-methylethylidene)-α-D -ribo-furanosyl chloride ( 5 ) gave the protected β-D -nucleosides 6a – d stereoselectively (Scheme 1). Contrary, the β-D -halogenose 8 yielded the corresponding α-D -nucleosides ( 9a and 9b ) apart from minor amounts of the β-D -anomers. The deprotected nucleosides 10a and 11a were converted into 4-substituted 2-aminopyrrolo[2,3-d]-pyrimidine β-D -ribofuranosides 1 . 10c , 12 , 14 , and 16 and into their α-D -anomers, respectively (Scheme 2). From the reaction of 4b with 5 , the glycosylation product 7 was isolated, containing two nucleobase moieties.