Severe liver injury and clinical characteristics of occupational exposure to 2-amino-5-chloro-N,3-dimethylbenzamide: A case series

Background:The 2-amino-5-chloro-N,3-dimethylbenzamide is a key intermediate in the synthesis of pesticides and pharmaceuticals.However,no literature currently exists on 2-amino-5-chloro-N,3-dimethylbenzamide poisoning in humans.This study aimed to reveal the health hazard of this chemical for humans and summarize the clinical characteristics of patients with occupational 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.Methods:This observational study included four patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning from June 2022 to July 2022.The entire course of the incidents was described in detail.Blood 2-amino-5-chloro-N,3-dimethylbenzamide concentrations were detected by a mass spectrometer.Hema-toxylin and eosin staining was performed to assess liver injury,and immunofluorescence was used to evaluate hepatic mitophagy.Results:The 2-amino-5-chloro-N,3-dimethylbenzamide powder(99%purity)entered the human body mainly via the skin and respiratory tract due to poor personal protective measures.The typical course of 2-amino-5-chloro-N,3-dimethylbenzamide poisoning was divided into latency,rash,fever,organic dam-age,and recovery phases in accordance with the clinical evolution.Rash and fever may be the important premonitory symptoms for further organ injuries.The chemical was detected in the blood of all patients and caused multiple organ injuries,predominantly liver injury,including kidney,myocardium,and micro-circulation.Three patients recovered smoothly after comprehensive treatments,including artificial liver therapy,continuous renal replacement therapy,glucocorticoids,and other symptomatic and supportive treatments.One patient survived by liver transplantation.The postoperative pathological findings of the removed liver showed acute liver failure,and immunofluorescence staining confirmed the abundance of mitophagy in residual hepatocytes.Conclusions:This study is the first to elaborate the clinical characteristics of patients with 2-amino-5-chloro-N,3-dimethylbenzamide poisoning.The chemical enters the body through the respiratory tract and skin during industrial production.The 2-amino-5-chloro-N,3-dimethylbenzamide poisoning causes multiple-organ dysfunction with a predominance of liver injury.Liver transplantation may be an effective option for patients with severe liver failure.The mechanisms of liver injury induced by 2-amino-5-chloro-N,3-dimethylbenzamide might involve abnormal mitochondrial function and mitophagy.

Synthesis and Structural Characterization of a Tetranuclear Copper Complex with 2-Amino-1,3-thiazole

The title tetranuclear complex,（μ4-oxo）-hexakis（μ2-chloro）-tetrakis（2-amino-1,3-thiazole-N）-tetra-copper（ii） [Cu4（μ4-O）（μ-Cl）6L4]（1,L=2-amino-1,3-thiazole） was synthesized by the reaction of CuCl2·2H2O with 2-amino-1,3-thiazole in methanol and characterized by IR spectra and X-ray diffraction.Complex 1 crystallizes in triclinic,space group P1 with a=9.7137（2）,b=10.7005（2）,c=14.6505（2）,α=83.9550（10）,β=82.0930（10）,γ=67.1640（10）°,V=1387.84（4）3,Mr=883.43,Z=2,μ=3.927 mm-1,Dc=2.1144 g/cm3,F（000）=868,R=0.0332 and wR=0.0814.The complex contains a tetrahedron of four CuII atoms coordinating to a central μ4-O atom,with the six edges of the tetrahedron bridged by six Cl atoms.The Cu-O bond distances range from 1.910（2） to 1.918（2）,Cu-Cl from 2.3501（11） to 2.5924（10）,and Cu-Cu from 3.1003（6） to 3.1663（6）.The coordination geometries of the four coppers distort from trigonal bipramid to tetragonal pyramid with different distortion factors.The free animo groups of the ligands result in a lot of N-H···Cl and N-H···N intra-and intermolecular hydrogen bonds.

Microwave promoted one-pot synthesis of 3-(2′-amino-3′-cyano-4′-arylpyrid-6′-yl)coumarins

A facile procedure for the synthesis of 3-（2′-amino-3′-cyano-4′-arylpyrid-6′-yl） coumarins are being reported starting from 3- acetylcoumarin, aromatic aldehydes and malononitrile. The reactions were carried out on microwave irradiation in good yield with short time and easy work-up. The structures of all the compounds have been confirmed on the basis of their analytical, IR, ^1H NMR, and mass spectral data.

Synthesis,Crystal Structure and Plant Growth Regulatory Activity of 1-(3-Amino-[1,2,4]triazol-1-yl)-3,3-dimethyl-butan-2-one

The title compound 1-（3-amino-[1,2,4]triazol-1-yl）-3,3-dimethyl-butan-2-one（3） was synthesized by Hofmann-alkylation reaction of 1-chloro-3,3-dimethyl-butan-2-one（1） and ~1H-[1,2,4]triazol-3-ylamine（2） with equal amount of K_2CO_3 as acid acceptor. The structure of compound 3 was characterized by ~1H NMR, 13 C NMR, HRMS and single-crystal X-ray diffraction. The compound crystallizes in the monoclinic system, space group P21/n with a = 5.7227（8）, b = 27.924（4）, c = 6.2282（7） ？, β = 101.892（11）°, V = 973.9（2） ？~3, Z = 4, T = 180.00（10） K, μ（MoKα） = 0.087 mm^（-1）, Dc = 1.243 g/cm^3, 3832 reflections measured（3.648≤θ≤26.022°）, 1916 unique reflections（Rint = 0.0359, Rsigma = 0.0572） used in all calculations. The final R = 0.0557（I 〉 2σ（I）） and w R = 0.1276（all data）. Bioassay showed that 3 displayed excellent activity as plant growth regulator with inducing lateral root formation and enhancing primary root elongation at 0.27 mmol/L（50 ppm） in soybeen（He Feng-50）. Good water solubility was found with 50 mg in 1 m L of water. Therefore, application of 3 in agriculture is more environmentally friendly due to cosolvent-free condition, and results in improved abiotic-stress tolerance by affecting the root growth. And furthermore, it can be used as a precursor to investigate the function of regulating plant root growth.

Synthesis and antiangiogenic activities of 5-amino-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanoic acid derivatives

Based on the structure-activity relationships and antiangiogenic mechanism of RGD-containing peptides, a series of 5-amino- 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. The structures were characterized by ^1H NMR, MS and elementary analysis. There ability to inhibit angiogenesis were evaluated by chick embryo chorioallantoic membrane assay at 10^-5 mol/L. Compounds 7a and 7b displayed obvious antiangiogenic activity.

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.

Mechanism of Excited State Double Proton Transfer in 2-Amino-3-Methoxypyridine and Acetic Acid Complex

The excited-state double-proton transfer （ESDPT） mechanism of 2-amino-3-methoxypyridine and acetic acid com- plex is studied by the density functional theory （DFT） and time-dependent DFT with CAM-B3LYP functional. The complex is connected through two different types of inter-molecular hydrogen bonds. After photo-excitation, both hydrogen bonds get strengthened, which can facilitate the ESDPT reaction. The scanned potential energy curve along the proton transfer coordinate indicates that the ESDPT reaction proceeds in a stepwise pattern.

Facile synthesis of[1,2,4]triazino[4,3-b][1,2,4,5]tetrazepin derivatives by a one-pot reactions using 4-amino-3-hydrazinyl-6-methyl-1,2,4-triazin-5(4H)-one

4-Amino-3-mercapto-6-methyl-l,2,4-triazin-5（4H）-one 1 converted to 4-amino-6-methy-3-（methylthio）-1,2,4-triazin-5（4H）-one by methylation with methyl iodide.Controlled hydrazination of the resulting compound afforded 4-amino-3-hydrazinyl-6- methyl-l,2,4-triazin-5（4H）-one 2 as a building block,to the synthesis of some novel derivatives of[1,2,4]triazino- [4,3,b][1,2,4,5]tetrazepine 3-6,by the reaction with 3-chloropentane-2,4-dione,chloro acetonitrile,1,3-dichloroacetone,and methyl bromoacetate.This general synthetic procedure can be extended to the preparation of wide variety of tetrazepines using 1,2- bielectrophiles derivatives.

Role of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor regulation in stress-induced pain chronification

Persistent postsurgical pain is a serious issue in public health, which has received increased interest in recent years. Previous studies have reported that psychological factors promote the development of chronic postsurgical pain. However, it is unclear how chronification of postsurgical pain occurs. The α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor(AMPA) phosphorylation in the central nervous system plays a critical role in synaptic plasticity and contributes to central sensitization and chronic pain development. Here, we discuss the role of AMPA receptor regulation in stress-induced pain chronification after surgery.

Synthesis and Evaluation of 2-Amino-4H-Pyran-3-Carbonitrile Derivatives as Antitubercular Agents

A series of 2-amino-4H-pyran-3-carbonitrile derivatives were designed and synthesized. Their antitubercular activities were evaluated against autoluminescent M. tuberculosis H37Ra and standard strain M. tuberculosis H37Rv. No obvious antitubercular activities could be observed (MIC > 10 ug/mL). The results are in sharp contrast with the previously reported data.

Theoretical Study on the Reaction Mechanism of 2-Methoxybenzaldehyde,4-Bromo-indanone,Malononitrile and Ammonium Acetate One-pot to Form 6-(2-Methoxyphenyl)-2-amino-6-bromo-5H-indeno[1,2-b]pyridine-3-carbonitrile

The reaction mechanism of 2-methoxybenzaldehyde, 4-bromo-indanone, malononitrile and ammonium acetate one-pot to form 6-（2-methoxyphenyl）-2-amino-6-bromo-5 Hindeno[1,2-b]pyridine-3-carbonitrile was studied by density functional theory. The geometries of the reactants, transition states, intermediates and products were optimized at the PW91/DNP level. Vibration analysis was carried out to confirm the transition state structure. Reaction pathways were investigated in this study. The result indicates that the reaction Re→ TSB1→IMB1→ TSB2→ IMB2→TSB3→IMB3→TSB4→IMB4→TSB5→IMB5→TSB6→IMB6→TSB7→IMB7→ TSB8→IMB8→TSB9→IMB9→P2 is the main pathway, the activation energy of which is the lowest. The dominant product predicted theoretically is in agreement with the experiment results.

Syntheses of Coordination Compounds of 2-Amino-3-Methylbutanoic Acid Their Mixed Ligand Complexes and Antibacterial Activities

Coordination compounds of 2-amino-3-methylbutanoic acid were synthesized with chromium(III) and oxovanadium(IV) ions. M:L;1:2. Adducts of these complexes using 1,10-phenantroline and ethylenediamine were further synthesized, M:L, (1:2). These compounds were characterized using electronic, infra-red spectrophotometry, magnetic susceptibility measurement and percentage metal analyses. The zones of inhibition and minimum inhibitory concentrations of the compounds against eight microbes were studied. The results obtained indicated an octahedral geometry for the Cr(III) complexes, indicative of additional coordination of two water molecules. On the other hand a square pyramid geometry was obtained for the binary oxovanadium complex and its 1,10-phenantroline adduct. However, for the oxovanadium ethylenediamine adduct a distorted octahedral geometry was proposed. The result for the antibacterial studies indicated that both mixed ligand complexes of 1,10-phenantroline exhibited good antibacterial activity, and in some cases better activity than the standard, streptomycin.

Palladium-Catalyzed Sonogashira Coupling Reaction of 2-Amino-3-Bromopyridines with Terminal Alkynes

Palladium-catalyzed the Sonogashira coupling reaction of 3-halogen-2-aminopyridines 1 with terminal alkynes 2 afforded the corresponding 21 target products 3a-3u in the presence of palladium catalyst. The structure of target products 3a-3u was confirmed and characterized by 1H NMR, 13C NMR, and HRMS. The influences of different kinds of catalyst loading, bases, substrates and temperature were also investigated. Under the optimized conditions, including 2.5 mol% Pd?(CF3COO)2, 5 mol% PPh3 and 5 mol% CuI as additive, 1 mL Et3N, substrate 1 with terminal alkynes 2 for the cross-coupling reactions at 100°C for 3 h in DMF afforded the corresponding products of 2-amino-3-alkynylpyridines 3 in moderate to excellent yields (72%?-?96%). The present methodology has provided an effective synthetic method including operational convenience, high efficiency and wide-application.

豹皮菌中2－Amino－3－（1，2－dicarboxyethylthio）propanoic Acid非对映异构体的分离和鉴定

从豹皮菌中的新鲜子实体的乙醇提取物中分离得到一种ＮＭＤＡ受体格抗剂，经理化常数和波谱数据的测定鉴定为２－Ａｍｉｎｏ－３－（１，２－ｄｉｃａｒｂｏｘｙｅｔｈｙｌｔｈｉｏ）ｐｒｏｐａｎｏｉｃａｃｉｄ非对映异构体的混合物，该化合物是首次从豹皮菌中得到，经进一步分离，得到两种非对映体异构体。

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.

Acylation of 3,4-Diaminofurazan

An acylation method of 3,4-diaminofurazan was developed. Under the catalysts of p-Tolu- enesulfonic acid, 3-amino-4-formylaminofurazan, 3-amino-4-acetylaminofurazan, 3-amino-4-propio- nylaminofurazan, 3-amino-4-butylramino-furazan and 3-amino-4-benzoylaminofurazan were synthe- sized by acylation of 3,4-diaminofurazan with formic acid, acetic acid, propionic acid, butyric acid and benzoic acid respectively. Also, 3,4-diacetylaminofurazan and 3,4-dipropionylaminofurazan were synthesized by acylation of 3,4-diaminofurazan with acetic anhydride and propionic anhydride re- spectively. Compared with the traditional method which uses acyl halogen as reagent, our method reduced the reaction time and increased the yield and purify. The 3-amino-4-acylaminofurazan could be hydrolyzed to 3,4-diaminofurazan in ethanol with acid catalyst.

Synthesis,Crystal Structure and Thermal Properties of Zn（NH3）3（AFT）2

A new coordination compound of Zn(NH3)3(AFT)2(1,ZnC6H13N17O2,AFT =4-amino-3-(5-tetrazolate)-furazan)was synthesized and characterized by elemental analysis and FT-IR spectrum.Its crystal structure was determined by X-ray single-crystal diffraction.This crystal belongs to the orthorhombic system,space group Pnma with a = 18.680(3),b = 6.9438(11),c =12.268(2)A,μ= 1.592 mm-1,V= 1591.3(4)A3,M,= 420.72,Dc=1.756 g·cm^-3,Z= 4,F(000)= 860,the final R = 0.0480 and wR = 0.1262 for the observed reflections with I>2σ(Ⅰ).The zinc(Ⅱ)ion is five-coordinated by N atoms from two AFT"ligands and three NH3 molecules.The thermal decomposition mechanism of compound 1 was tested by differential scanning calorimetry(DSC)and thermogravimetry-derivative thermogravimetry(TG-DTG)methods.The DSC curve exhibits two endothermic and one exothermic processes.In addition,the non-isothermal kinetics parameters were calculated by using the Kissinger s method and Ozawa-Doyle's method.Besides,the entropy of activation(ΔS≠),enthalpy of activation(ΔH≠),free energy of activation(ΔG≠)and impact sensitivity(IS)was also obtained.

A facile synthesis of novel unsymmetrical N-(4-oxo-2-phenyl-3(4H)-quinazolinoyl)-N-(aryl) acetamidines

A series of novel unsymmetrical N-（4-oxo-2-phenyl-3（4H）-quinazolinoyl）-N-（aryl） acetamidines was synthesized by reacting ethyl（1H）-N-（4-oxo-2-phenylquinazolin-3（4H）-y1）ethanimidoate（2） and suitable reactive aromatic amines.Structures＇ determination of the synthesized compounds was carried out using spectroscopic techniques including IR,~1H NMR,and mass spectrometry. Structural effects on reactivity were also studied.

Synthesis and Crystal Structure of Ethyl 2-(6-(1,3-Dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) Butanoate

The title compound ethyl 2-（6-（1,3-dioxo-4,5,6,7-tetrahydro-lH-isoindol-2（3H）- yl）-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4（3H）-yl） butanoate 3 was synthesized by the reaction of ethyl 2-（6-amino-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4（3H）-yl） butanoate with 4,5,6,7- tetraydrophthalic anhydride, and its structure was determined by X-ray single-crystal diffraction. The crystal belongs to the monoclinic system, space group P2 1/n with a = 9.3469（2）, b = 16.7715（5）, c = 13.7153（4） A, β= 104.9680（10）°, μ = 0.107 mm^-1, Mr = 430.42, V= 2077.08（10） ,A3, Z= 4, Dc = 1.376 g/cm3, F（000） = 904, T= 296（2） K, R = 0.0508 and wR = 0.1478.