Zinc chloride catalyzed synthesis of 5-substituted 1H-tetrazoles under solvent free condition

Zinc chloride is an efficient and safe catalyst in the [3 ＋ 2] cycloaddition reaction of organic nitriles with sodium azide in solventless condition. The corresponding 5-substituted ^1H tetrazoles were obtained under mild conditions. This method can overcome disadvantages such as： the use of toxic metals and expensive reagents, drastic reaction conditions, water sensitivity and the presence of dangerous hydrazoic acid.

A convenient synthesis of 1-alkyl-5-amino-6-phenylethyluracils as potential non-nucleoside HIV-1RT inhibitors

1-Alkyl-5-amino-6-phenylethyluracils （1a, 1b） were synthesized as potential non-nucleoside HIV-1RT inhibitors. A convenient synthetic procedure was developed for the preparation of 1-alkyl-5-amino or 5-aminosubstituted-6-phenylethyluracils, which were synthesized in three or four steps from 6-methyluracil in good yield. The development of a one-pot reaction that simultaneously removed the benzyl protection group and reduced the nitro group greatly improved the yield of the synthesis. Compounds 1a and 1b are analogs of MKC-442, which is an efficient inhibitor of HIV-1 reverse transcriptase, 1a and 1b were tested for their inhibition of HIV-1RT, and moderate activity was found for 1a.

Effective synthesis of 5-amino-1-pentanol by reductive amination of biomass-derived 2-hydroxytetrahydropyran over supported Ni catalysts

A highly efficient and green process was developed for the synthesis of useful 5-amino-1-pentanol(5-AP)from biomass-derived dihydropyran by coupling the in situ generation of 5-hydroxypentanal(5-HP,via the ring-opening tautomerization of 2-hydroxytetrahydropyran(2-HTHP))and its reductive amination over supported Ni catalysts.The catalytic performances of the supported Ni catalysts on different oxides including SiO2,TiO2,ZrO2,γ-Al2 O3,and MgO as well as several commercial hydrogenation catalysts were investigated.The Ni/ZrO2 catalyst presented the highest 5-AP yield.The characterization results of the oxide-supported Ni catalysts showed that the Ni/ZrO2 catalyst possessed high reducibility and a high surface acid density,which lead to the enhanced activity and selectivity of the catalyst.The effect of reaction parameters on the catalytic performance of the Ni/ZrO2 catalyst was studied,and a high 5-AP yield of 90.8%was achieved in the reductive amination of 2-HTHP aqueous solution under mild conditions of 80℃and 2 MPa H2.The stability of the Ni/ZrO2 catalyst was studied using a continuous flow reactor,and only a slight decrease in the 5-AP yield was observed after a 90-h time-on-stream.Additionally,the reaction pathways for the reductive amination of 2-HTHP to synthesize 5-AP were proposed.

Synthesis of 5-Aryl-1, 2-dihydro-1-pyrrolizinones

In order to search for new potent anti-inflammatory and analgesic agents in pyrrolizinones, the title compounds were designed and synthesized. A series of the compounds were prepared with two different synthetic schemes. Some of the compounds showed remarkable anti-inflammatory and/or analgesic activities on mice.

Synthesis and Crystal Structure of Ag_2(admtrz)_2(CF_3CO_2)_2(admtrz=4-amino-3,5-dimethyl-1,2,4-triazole)

The title compound (Ag2F6O4N8C12H16, Mr = 666.07) was synthesized and its crystal structure was determined by single-crystal X-ray diffraction method. It crystallizes in orthorhombic, space group Fddd with cell parameters: a = 12.2718(1), b = 23.3229(1), c = 29.1918(1) ? V = 8355.10(8) 3, Z = 16, Dc = 2.118 g/cm3, F(000) = 5184 and m = 1.966 mm-1. The structure was solved by direct methods and refined by full-matrix least-squares methods. The final R = 0.0624 and Rw = 0.1699 for 1584 observed reflections with I ≥ 2.0s(I). The molecular structure consists of two trigonal silver atoms bridged by double triazole ligands. The distance between the two silver atoms Ag(1)…Ag(1A) is 3.475(2) ?

Syntheses and Characterization of Two New Alkaline Earth Metal-organic Topological Frameworks with 3-Amino-1H-1,2,4-triazole-5-carboxylate

Two new alkaline earth metal coordination polymers constructed from the deriva-tive of 1,2,4-triazole are presented herein,namely,{[Sr（AmTAZAc）2（H2O）]}（1） and {[Ba（AmTAZAc）2（H2O）]}（2）（AmTAZAc = 3-amino-1H-1,2,4-triazole-5-carboxylate）,which have been synthesized by using the layering method and structurally characterized by elemental analysis,IR,and single-crystal X-ray diffraction.Complexes 1 and 2 are isostructural,and both crystallize in the orthorhombic system,space group Fdd2.X-ray structural analysis shows that 1 or 2 has an intriguing 3-D infinite network of（318.438.510） topology based on a 2-D sheet structure of（4,4） net.The result shows that noncovalent interactions play an important role in strengthening the whole structures of the compounds.

Synthesis of N1-Substituted-3-aryl-4-alkyl-4, 5-dihydro-1H-1-pyra-zolethiocarboxamide as Novel Small Molecule Inhibitors of Cysteine Protease of T.cruzi

A series of N1-substituted-3-aryl-4-alkyl-4, 5-dihydro-1H-1-pyrazolethiocarboxamide were prepared from the Mannich bases of aryl ketones in good yields. Some derivatives were found to be active against the cysteine protease of T.cruzi..

The Synthesis of 1-Aryl-5-Fluorouracil

A series of new type substituted 5-fluorouracil derivatives, 1-aryl-5-fluorouracil (4a-4f), were synthesized via diaryliodonium salts and the structure of the title compound was finally confirmed by IR, UV. H-1-NMR. MS and CHN analysis.

Key Intermediates: A Simple and Highly Selective Synthesis of 5-<i>Amino</i>-1-<i>aryl</i>-1<i>H</i>-<i>pyrazole</i>-4-<i>carbonitriles</i>for Applications in the Crop Protection

A series of six pyrazoles was synthesized by Michael-type addition reaction. The molecules 5-amino-1-aryl-1H-pyrazole-4-carbonitrile (3a-f) were synthesized from (ethoxymethylene)malo-nonitrile (1) and fluorinated and non-fluorinated aryl hydrazines (2a-f) using ethanol and fluorinated ethanol as solvents at reflux. An excellent regio-selectivity was found when pyrazole derivatives were formed as an exclusive product. No other regioisomer or uncyclised hydrazide was observed. Their structures were confirmed by spectroscopy data (1H, 13C, 19F, COSY (correlation spectroscopy), HSQC (heteronuclear single-quantum correlation spectroscopy) and HMBC (heteronuclear multiple-bond correlation spectroscopy);MS (mass-spectrometry). The yields ranged from good to excellent (47% - 93%) under mild reaction conditions. It would indicate a high selectivity in the one-step work procedure. These products (3a-f) and derivatives have a potential academic and industrial use as key intermediates, in special, for application in crop protection.

Synthesis of 2-(N-formyl)-5-aryl/aryloxymethyl-1,3,4-thiadiazoles with potential bioactivity in PEG-400

An environmental benign procedure for synthesis of 2-(N-formyl)-5-aryl/aryloxymethyl-1,3,4-thiadiazoles has been developed by reaction of 2-amino-5-aryl/aryloxymethyl-1,3,4-thiadiazoles with formic acid in PEG-400.The key advantages of this protocol are the shorter reaction time,higher yields,lower cost,simple workup,and environment-friendly compared to conventional organic solvent reaction.The present method does not involve any hazardous organic solvent or catalyst.

Synthesis, Crystal Structure, Antibacterial Activities and Theoretical Computation of 3-(2-Hydroxybenzly)-4-(4-isopropylbenzyl- ideneamino)-(1H)-1,2,4-triazole-5-thione

The title compound C18H18N4OS has been synthesized by the reaction of 3-（2-hydroxy- benzyl）-4-amino-（1H）-1,2,4-triazole-5-thione with 4-isopropylbenzaldehyde in ethanol and characterized by IR, ^1H NMR spectra and elemental analysis. Its structure was determined by X-ray diffraction analysis. The crystal belongs to monoclinic, space group P21/c with a = 11.605（2）, b = 7.401（1）, c = 20.339（2） A, β= 103.05（2）°, V= 1701.8（4） A^3, Z = 4, Mr = 338.42,μ = 0.202 mm^-1, Dc = 1.321 g/cm^3 and F（000） = 712. The structure was solved by direct methods and refined to R = 0.0428 and wR = 0.1069. Due to the intramolecular O-H…N hydrogen bond and π-π stacking interactions between the benzene （C（1）～C（6）） and triazole rings, the two planes are essentially coplanar. Their biological activities have been measured, showing this type of compound has certain antibacterial activity for Staphylococous aureus and Bacillus subtilis. Based on the quantum chemistry calculation at the RHF/6-31G level, the frontier orbitals and electrostatic potential of the title compound were also discussed.

Estrogen affects neuropathic pain through upregulating N-methyl-D-aspartate acid receptor 1 expression in the dorsal root ganglion of rats

Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1（NMDAR1） plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D（-）-2-amino-5-phosphonopentanoic acid（AP-5）,or both once daily for 15 days.Compared with injured drug na？ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity（as assessed by immunohistochemistry） and protein（as determined by western blot assay） in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.

Studies on 3-Amino-4-(1H-tetrazol-5-yl)-furazan:Crystal Structure, Thermal Behavior and Energetic Performance

The structure of 4-amino-3-(5-tetrazolate)-fiirazan(HAFT) was characterized by single crystal X-ray diffraction. The thermal decomposition process of HAFT was investigated by MS-FTIR-DSC-TG coupling technique. The result shows that the exothermic process occurs from 278.7-350℃, with a peak temperature of 324.7℃. The thennal decomposition gaseous products of HAFT are NO2, CO2, HCN, CO, NH3 and H2O. The detonation velocity and detonation pressure of HAFT were calculated by the nitrogen equivalent equation. The detonation velocity of HAFT is 7727.46 m/s, which is higher than that of TNT(7178 m/s). The detonation pressure of HAFT(25.27 GPa) is satisfactory. The sensitivity tests reveal HAFT possesses excellent insensitivities to impact and friction.

Auxiliary Ligands Mediated One- and Two-dimensional Cd(Ⅱ) Coordination Polymers Incorporating Methyl-3- hydroxy-5-carboxy-2-Thiophenecarboxylate Ligand

Two N-donor ligands mediated Cd（Ⅱ） coordination polymers, namely,[Cd（L）（dmpz）2]n （1） and {[Cd（L）（atr）05（H20）]（H2O）}n （2） （H2L = methyl-3-hydroxy-5-carboxy-2-thiophenecarboxylate, dmpz = 3,5-dimethylpyrazole, and atr= 4-amino-l,2,4-triazole）, havebeen produced. Their structures were characterized by single-crystal X-ray diffraction analysis,elemental analyses and infrared spectra. Compound 1 possesses a one-dimensional （1D） chainstructure and is finally extended into a three-dimensional （3D） supramolecular architecturethough hydrogen bonding interactions. Compound 2 features a two-dimensional （2D） networkwith 4-connected sql topology based on dinuclear Cd（Ⅱ） clusters as nodes, which is alsoassembled into a 3D supramolecular architecture through hydrogen bonding interactions.Furthermore, compounds 1 and 2 exhibit high thermal stabilities and intense fluorescent emissionin the solid, and can be explored as potential luminescent materials.

Improved microwave-assisted catalyst-free synthesis of9-aryl-5,9-dihydropyrimido[4,5-d][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-dione derivatives

Agreen regioselective synthesis of some new and known 9-aryl-5,9-dihydropyrimido[4,5-d][l,2,4]triazolo[1,5-a]pyrimidine-6,8（4H,7H）-diones has been described via the microwave-assisted one-pot reaction of 3-amino-1H-1,2,4-triazoles,aromatic aldehydes and barbituric acids under solvent- and catalyst-free conditions.This operationally simple procedure is less laborious and provides a better scope than previously reported procedures.

Methylation of 5-Amino-3-methylthio-1 H-pyrazole Derivatives and Two Related Crystal Structures

5-Amino-3-methylthio-1H-pyrazoles are very important building blocks from which a wide variety of pyrazole de-rivatives can be prepared. When substituted 5-amino-3-methylthio-1H-pyrazole was treated with CH3I, the methy-lation occurres at endocyclic two nitrogens at the same time. The ratio of isomers in products was depended upon the nature of 4-position substituent in the pyrazole ring. The products were characterized by X-ray diffraction analysis, and the ratios of isomer were explained by means of the results of ab inito calculation.

Improvement in the synthesis of 2-(5-amino-1,2,4-thiadiazol-3- yl)-2-(Z)-methoxyiminoacetic acid 2-benzothiazolyl thioester

2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(Z)-meth-oxyiminoacetic acid 2-benzothiazolyl thioester(III),an important intermediate of the fourth generation cephalos-porins,was efficiently synthesized by reacting 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(Z)-methoxyiminoacetic acid(I)with 2,29-dibenzothiazole disulfide(II)in the presence of triphenylphosphine.Effects of reaction time,temperature,solvents,catalysts and feeding molar ratio on the yield and quality of products were investigated,and an im-proved procedure suitable for industrial production was established.Using 1,2-dichloroethane as solvent,triphe-nylphosphine as reducer,and triethylamine as catalyst,n(I):n(II):n(triphenylphosphine)51.0:1.0:1.0,the product was obtained at room temperature in 98.1%yield.The purity of the product without further purification is 98.7%determined by HPLC method.This procedure could be a suitable alternative to the traditional processes because of its easy handling,high yield and low cost.

Synthesis and antitumor activity of some new pyrazolo[1,5-α]pyrimidines

New series of pyrazolo[1,5-α]pyrimidine derivatives 7a-i,11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines,namely colorectal carcinoma（HCT116）,prostate adenocarcinoma（PC-3） and liver carcinoma（HepG-2） using MTT cytotoxicity assay at 100 μg/mL.Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells.Whereas,compounds 7d and 11 a showed better antitumor activity than the rest of the compounds against both cell lines.A structure-activity relationship（SAR） has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data（MS,IR,^1H NMR and ^13C NMR） and elemental analysis.

Glycerol mediated synthesis of 5-substituted lH-tetrazole under catalyst free conditions

We have developed simple,cost effective and environmentally benign protocol for the synthesis of 5-substituted 1H-tetrazoles via[2,3]cycloaddition reaction from organic nitriles and sodium azide in glycerol under catalyst free condition.The corresponding 5-substituted 1H-tetrazoles were obtained with good to excellent yields（68-95%）.

Solvent-free preparation of arylaminotetrazole derivatives using aluminum(Ⅲ) hydrogensulfate as an effective catalyst

An efficient and simple method for the preparation of 5-arylamino-1H-tetrazole and 1-aryl-5-amino-1H-tetrazole derivatives is reported using aluminum（Ⅲ） hydrogensulfate（Al（HSO4）3） as an effective heterogeneous catalyst from secondary arylcyanamides. Generally,when the substitution in arylcyanamide is strongly electron-withdrawing the position of equilibrium would shift toward the isomer of 1-aryl-5-amino-1H-tetrazole（B） and as the electron-donating of substituent increased,the position of equilibrium is shifted toward the isomer of 5-arylamino-1H-tetrazole（A）.The present methodology offers several advantages,such as excellent yields,short reaction times,easy work-up and greener conditions.