The calculation of sensitometric properties of 1,2,4-triazolo[1,5-a]pyrimidines

Quantitative structure–property relationships were proposed by using artificial neural networks and information received from ¹³C NMR spectra. The suitability of 1,2,4-triazolo[1,5-a]pyrimidines as stabilizers in photographic silver halide materials was determined from their chemical structures. For the numeric coding of the chemical structures of differently substituted 1,2,4-triazolo[1,5-a]pyrimidines 1 – 44 only information available from their ¹³C NMR spectra was used. Even an assignment of the ¹³C NMR chemical shift values to the carbons was not necessary. The best results were achieved by combination of the ¹³C NMR chemical shifts of carbons of the basic heterocycle and the relative fog D_rel using a feed-forward two-layer neural network. For some compounds with a good stabilizing effect the calculated results strongly differ from experimental values giving indication of a mechanism which is not covered by the ¹³C NMR chemical shifts.     

一类新型三唑并嘧啶联噻二唑杂环化合物的合成及杀菌活性

以5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶-2-甲酰肼为原料,设计合成了8个新型的2-(5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶)-1,3,4-噻二唑.5.硫醚类化合物.通过1HNMR、MS和元素分析对所合成的化合物进行了结构表征.初步的生物活性测试结果表明,所合成的化合物均具有较好的杀菌活性.     

Syntheses and biological activities of novel diheterocyclic compounds containing 1,2,4‐triazolo[1,5‐a]pyrimidine and 1,3,4‐oxadiazole

In a search for novel agrochemicals with high activity and low toxicity, a series of diheterocyclic compounds containing 1,2,4‐triazolo[1,5‐a]pyrimidine and 1,3,4‐oxadiazole rings were designed and synthesized by a four‐step synthetic route starting from 2‐mercapto‐5,7‐dimethyl‐1,2,4‐triazolo[1,5‐a]pyrimidine. The structures of all the compounds synthesized were confirmed by ¹H NMR, mass spectroscopy and elemental analysis. The preliminary bioassay against Brassica campestris L and Echinochloa crusgalli Beavu indicated that the title compounds displayed herbicidal activity at the concentration of 100 ppm and that compounds 5a (R = CH₃), 5d (R = C₂H₅) and 5f (R = i‐Bu) were found to have particularly high activities. In addition, the results of an in vivo test at a concentration of 50 ppm showed that all the compounds prepared were highly active against Rhizoctonia slain, but not active against Fusarium oxysporum, Gibberella zeave and Phoma sparagi. A further in vivo test showed that compound 5j possessed better fungicidal activity against Rhizoctonia solani at a concentration of 200 ppm than Carbendazim and Validamycin A, which are well known for their fungicidal activity against Rhizoctonia solani. To our knowledge, this is the first report that 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives display fungicidal activity against Rhizoctonia solani. © 2001 Society of Chemical Industry     

Tandem Ring-Opening/Double Ring-Closing Synthesis of 1,2,4-Triazolo[1,5-a]pyridines from Chromone-Containing Acrylonitriles

We studied a reaction of chromone-containing acrylonitriles and cyanoacrylates with acid hydrazides. This reaction turned out to be a method for the synthesis of salicyloyl-substituted 1,2,4-triazolo[1,5-a]pyridines. The synthesis developed is a tandem ring-opening/double ring-closing process. This synthetic approach is characterized by low toxic solvents (ethanol, butanol) and mediator (Et₃N), 37–84% yields, non-chromatographic isolation of products, and substrate tolerance (59 examples).     

A novel synthesis of indeno[2',1': 5,6] pyrido[2,3- d ][1,2,4]triazolo[4,3- a ]pyrimidines

Reaction of 5-(4-chlorophenyl)-2-thioxo-2,3-dihydro-1H-indeno[2',1':5,6] pyrido[2,3-d]pyrimidine-4,6-dione with hydrazonoyl chlorides gave 1,2,4-triazolo[4,3-a]pyrimidine derivatives regioselectively in good yields. The structures of the newly synthesized compounds are established on the basis of chemical and spectroscopic evidence as well as their synthesis by alternative methods.     

2-氨基-5,7-二甲氧基-1,2,4-三嗪并[1,5-a]嘧啶的合成及工艺优化

2-氨基-5,7-二甲氧基-1,2,4-三嗪并[1,5-a]嘧啶的合成及工艺优化。以4,6-二甲氧基嘧啶-2-胺为主要原料,经两步反应制得2-氨基-5,7-二甲氧基-1,2,4-三嗪并[1,5-a]嘧啶;并考察了第二步合成工艺。通过熔点测定和1HNMR确证了2-氨基-5,7-二甲氧基-1,2,4-三嗪并[1,5-a]嘧啶;找到了最佳合成工艺,总收率81%。该合成方法具有反应条件温和、成本低、适合工业生产等优点。     

Synthesis and characterization of Cu(I) and Zn(II) complexes with new sulfur-bearing isoxazole- or pyrazole-based ligands

The synthesis of the new ligands 6-(5-methyl-1,2-oxazol-3-yl)-2,3-dihydro-5H-[1,4] dithiino[2,3-c]pyrrole-5,7(6H)-dione (isox′) and 6-(3-methyl-1H-pyrazol-5-yl)-2,3-dihydro-5H-[1,4]dithiino[2,3-c]pyrrole-5,7(6H)-dione (pyraz′) and their coordination chemistry toward Cu(I) and Zn(II), was studied. The ligands and their complexes were characterized using a combination of either multinuclear NMR (¹H and ¹³C{¹H}), HRMS, FTIR or Uv–Vis spectroscopy. The solid state structures of ligand isox′ and complexes [Cu(pyraz′)₂]OTf and [Zn(OOCCF₃)₂(pyraz′)₂] were determined. Interestingly, isox′ presents a yellow luminescence in its free form. Additionally, the ability of isox′ to coordinate as an N–O bidentate ligand or as an N–S bridge between two copper centers, forming a coordination polymer, is studied. The solid state structure of this Cu(I)-isox′ 1D coordination polymer is also reported.     

Dechema corrosion handbook Vol. 3 Edited by D. Behrens,VCH Verlagsgesellschaft,Weinheim Frankfurt am Main, 1988. pp. ix + 282, price £286.00 (subscription price to series £238.00 per volume) ISBN 3-527-26654-2

4-Phenyl-5-aminopyrazole 2 obtained from phenylcyanoacetaldehyde 1 and hydrazine hydrate reacted with diethyl malonate to give 3-phenyl-5,7-dioxopyrazolo[1,5-a]pyrimidine 3 , used as the key compound in the synthesis of arylazo dyes. The key compound 3 was coupled with various aryldiazonium salts 4 to yield 3-phenyl-7-hydroxy-6-arylazopyrazolo[1,5-a]pyrimid-5-ones 5. The resulting arylazo dyes (5) were refluxed in phosphorus oxychloride to give 3-phenyl-5,7-dichloro-6-arylazo-pyrazolo[1,5-a]pyrimidines 6 , which subsequently reacted with refluxing morpholine and piperidine to yield 3-phenyl-5,7-bis(morpholino and piperidino)-6-aryiazopyrazolo[1,5-a]pyrimidines 7. The arylazo dyes 5 and 7 were applied to polyester fibres as disperse dyes and the arylazo dyes 6 were applied to polyamide fibres as disperse reactive dyes. The spectral and dyeing properties of the dyes were studied.     

Separation of iridium from platinum using a modified glycidyl methacrylate copolymer with diethylamino groups

A macroporous glycidyl methacrylate — ethylene dimethacrylate copolymer with sorption-active diethylamino groups proved to suit well for the separation of two component mixtures of chloro complexes [lrCl₆]^2- and [PtCl₆]^2-. A method for the separation was worked out, based on the reduction of the two complex ions with an aqueous solution of SO₂, after which iridium(III) is easy to elute (1 M HCI) where as platinum(II) is only eluted with 5 M HCI. The reaction patterns are given, supported by spectroscopic evidence.     

Transition metal α-carbonyl diazoalkane coordination chemistry: structures derived from a side-on diazomalonate platinum complex

The labile side-on α-carbonyl diazoalkane platinum complex (dtbpm-κ²P)Pt[N₂C(CO₂Me)₂-κ²N,N′] (2) displays nucleophilic as well as electrophilic reactivity patterns. H₂O is added stoichiometrically, forming the hydrazonido hydroxo platinum(II) complex (dtbpm-κ²P)Pt(OH)[NHNC(CO₂Me)₂] (3). Protonation of 2 with BF₃·OEt₂ and MeOH yields [(dtbpm-κ²P)Pt{NHNC(CO₂Me)₂-κN,κO}]⁺[BF₄]⁻ ([4]⁺[BF₄]⁻). Both new complexes have been fully characterized spectroscopically and by single crystal X-ray diffraction.     

Tautomerism and Reactions of 1H-1,2,4-Triazole-5-thiones with Hydrazonoyl Halides

The acid dissociation constants (K_a) of a series of 3,4-diaryl-1H-1,2,4-triazole-5-thiones ( 1 ) were determined and were found to correlated linearly with Hammett substituent constants; log K_a = 1.06 σ_x − 11.01. Such a result indicates that 1 exists essentially in one tautomeric form namely the thione form. Reactions of 1 with hydrazonoyl chlorides 2 gave the thiohydrazides 5 . Similiar reaction of 3-phenyl-1H(4H)- 1,2,4-triazole-5-thione 1g with 2a gave the thiohydrazide 5h which was converted into 1,3,5-triphenyl-1,2,4-triazolo[3,4-c]-1,2,4-triazole ( 9 ). The latter was also prepared from 3-phenyl-5-methylthio-4H-1,2,4-triazole ( 6 ) and 2a . The mechanism of the reaction of 1 with 2 is discussed.     

Embrace interlocking of dipyrazinylpyridine complexes involving N⋯π interactions

Fe(II) and Ni(II) complexes of 4-p-tolyl-2,6-di(2-pyrazinyl)pyridine (tdpzpy) have been synthesized and characterized. The N?π interaction involving the uncoordinated pyrazinyl N atom, which is stronger than the corresponding C–H?π hydrogen bonding in a similar 4-p-tolyl-2,2′:6′,2″-terpyridine complex, was distinguished as a supramolecular motif. It acts as an edge-to-face force in assembling cations of [Fe(tdpzpy)₂]²⁺ or [Ni(tdpzpy)₂]²⁺ into chains via embrace interlocking. C–H?π hydrogen bonds further link the chains into higher dimension net. The electronic absorption and emission properties of [Fe(tdpzpy)₂]²⁺ and [Ni(tdpzpy)₂]²⁺ are largely ligand-centered. [Fe(tdpzpy)₂]²⁺ displays an MLCT absorption at 567 nm. The fluorescence of [Ni(tdpzpy)₂]²⁺ is different markedly in methanol and acetonitrile. The ligand-based fluorescence is quenched to some extent by coordination to the d-orbital unfulfilled Fe(II) or Ni(II) atom.     

5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶-2-芳磺酸酯新型化合物的合成及生物活性

三唑类化合物具有广泛的生物活性。以2-羟基-5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶为原料,在缚酸剂存在下,于室温分别和苯磺酰氯、对甲苯磺酰氯进行酯化反应,合成了两个新型的5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶-2-芳磺酸酯化合物a和b。产物经质谱、红外光谱、核磁共振谱确证。初步生物活性表明,该化合物具有一定的杀菌活性和除草活性,其中a有较高除草活性,而b对禾本科植物有较好的促进生长活性。     

Synthesis, Crystal Structure and Antitumor Activity of Ca(II) Coordination Polymer Based on 1,5-Naphthalenedisulfonate

A novel Ca(II) coordination polymer, [CaL(H₂O)₂] _n (L = 1,5-naphthalenedisulfonate), was synthesized by reaction of calcium perchlorate with 1,5-naphthalenedisulfonic acid sodium in CH₃CH₂OH/H₂O. It was characterized by elemental analysis, IR, ¹HNMR and thermal analysis. X-ray crystallographic reveals that the Ca(II) coordination polymer belongs to triclinic system, with space group P-1. The geometry of the Ca(II) ion is a distorted CaO₆ octahedron coordination environment, arising from its coordination by two water molecules, and four oxygen atoms from two l ligands. The Ca(II) ions are linked through the O atoms of 1,5-naphthalenedisulfonate ligands to form 1D chain structure. And then a 2D layered structure is constructed by hydrogen bonds and π–π stacking. The antitumor activity of 1,5-naphthalenedisulfonic acid sodium ligand and its Ca(II) coordination polymer against human hepatoma smmc-7721 cell line and human lung adenocarcinoma A549 cell line have been investigated.     

Exploration of Pyrazolo[1,5-a]pyrimidines as Membrane-Bound Pyrophosphatase Inhibitors

Inhibition of membrane-bound pyrophosphatase (mPPase) with small molecules offer a new approach in the fight against pathogenic protozoan parasites. mPPases are absent in humans, but essential for many protists as they couple pyrophosphate hydrolysis to the active transport of protons or sodium ions across acidocalcisomal membranes. So far, only few nonphosphorus inhibitors have been reported. Here, we explore the chemical space around previous hits using a combination of screening and synthetic medicinal chemistry, identifying compounds with low micromolar inhibitory activities in the Thermotoga maritima mPPase test system. We furthermore provide early structure-activity relationships around a new scaffold having a pyrazolo[1,5-a]pyrimidine core. The most promising pyrazolo[1,5-a]pyrimidine congener was further investigated and found to inhibit Plasmodium falciparum mPPase in membranes as well as the growth of P. falciparum in an ex vivo survival assay.     

Formation of an unusual copper(II) complex from the degradation of a novel tricopper(II) carbohydrazone complex

An unusual copper(II) complex [Cu(L^1a)₂Cl₂] CH₃OH·H₂O·H₃O⁺Cl⁻ (1a) was isolated from a solution of a novel tricopper(II) complex [Cu₃(HL¹)Cl₂]Cl₃·2H₂O (1) in methanol, where L^1a is 3-(2-pyridyl)triazolo[1,5-a]-pyridine, and characterized with single crystal X-ray diffraction study. The tricopper(II) complex of potential ligand 1,5-bis(di-2-pyridyl ketone) carbohydrazone (H₂L¹) was synthesized and physico-chemically characterized, while the formation of the complex 1a was followed by time-dependant monitoring of the UV–visible spectra, which reveals degradation of ligand backbone as intensity loss of bands corresponding to O → Cu(II) charge transfer.     

Increased Lipophilicity of Halogenated Ruthenium(II) Polypyridyl Complexes Leads to Decreased Phototoxicity in vitro when Used as Photosensitizers for Photodynamic Therapy

In the fight against cancer, photodynamic therapy is generating great interest thanks to its ability to selectively kill cancer cells without harming healthy tissues. In this field, ruthenium(II) polypyridyl complexes, and more specifically, complexes with dipyrido[3,2-a:2’,3’-c]phenazine (dppz) as a ligand are of particular interest due to their DNA-binding and photocleaving properties. However, ruthenium(II) polypyridyl complexes can sometimes suffer from low lipophilicity, which hampers cellular internalisation through passive diffusion. In this study, four new [Ru(dppz-X₂)₃]²⁺ complexes (X=H, F, Cl, Br, I) were synthesized and their lipophilicity (logP), cytotoxicity and phototoxicity on cancerous and noncancerous cell lines were assessed. This study shows that, counterintuitively, the phototoxicity of these complexes decreases as their lipophilicity increases; this could be due solely to the atomic radius of the halogen substituents.     

Structure of the first dinuclear Ni(II) complex with an azapurine derivative (the anionic form of 4,6-dimethyl-1,2,3-triazolo[4,5-d]pyrimidin-5,7-dione)

The first dinuclear nickel complex with an azapurine derivative is reported. The crystal structure consists of discrete [Ni₂(dmax)₃(H₂O)₂(dben)₂]⁺ cations, the charge of which is balanced by interstitial dmax anions, where dmax = 4,6-dimethyl-1,2,3-triazolo[4,5-d]pyrimidin-5,7-dionato and dben = N,N′-dibenzylethylenediamine. The nickel centres are bridged by three heterocyclic anions through two nitrogen atoms of their triazole ring. The presence of the bulky auxiliary ligand clearly favours the bridging behaviour of the main ligand, probably by hindering the formation of H-bonds with dmax N atoms as acceptors. H-bonding is however, the main packing interaction, with eight different well defined intermolecular H-bonds that build a 3-D network that is analysed.     

Palladium‐Catalyzed Direct Arylations of 1,2‐Azolo[1,5‐a]pyridines using Copper(I) Chloride as a Lewis Acid Activator and the Synthesis of 2,6‐Disubstituted Pyridines

A direct method for the arylation of 1,2‐azolo[1,5‐a]pyridines has been developed. In the process, the fused pyridines react with aryl halides in the presence of the palladium complex Pd(OAc)₂(Phen) as a catalyst and copper(I) chloride (CuCl) as a Lewis acid to form arylated derivatives. While pyrazolo[1,5‐a]pyridines and [1,2,4]triazolo[1,5‐a]pyridines are arylated at ortho‐positions of their pyridine rings using this method, in situ ring‐opening of the formed C‐7 arylated [1,5‐a]pyridine takes place to generate the 2,6‐disubstituted pyridine. Also, upon treatment with lithium diisopropylamide (LDA), C‐7 arylated pyrazolo[1,5‐a]pyridine‐3‐carboxylates react to produce diversely substituted 2,6‐disubstituted pyridines. Finally, a sequential C‐3 arylation was accomplished through a two‐step sequence involving hydrolysis of pyrazolo[1,5‐a]pyridine‐3‐carboxylates followed by the bimetallic Pd/Cu‐catalyzed decarboxylative coupling reaction with aryl bromide.

     

2-巯基-5，7-二甲基-1，2，4-三唑并[1，5—α]嘧啶的合成

2-巯基-5,7-二甲基-1,2,4-三唑并[1,5—α]嘧啶是合成三唑并嘧啶类衍生物的重要中间体。实验研究了以5-氨基-3-巯基-1,2,4-嘧啶为原料,与乙酰丙酮环合制备2-巯基-5,7-二甲基-1,2,4-三唑并[1,5-α]嘧啶的工艺条件,研究结果表明,在AMZ与乙酰丙酮物质的量比为1：1．1、反应温度为120℃、反应时间为10h时,2-巯基-5,7-二甲基-1,2,4-三唑并[1,5-α]嘧啶的收率达到80％。