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.

Novel synthesis of 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde:A key intermediate of Losartan

A novel method for synthesis of 2-butyl-5 -chloro-3H-imidazole-4-carbaldehyde 2, a key intermediate of Losartan was reported. The compound 2 was synthesized from starting material dimethyl malonate 6 and n-valeronitrile 8 by six steps with an overall yield of 40%. The key step including the reaction of compound 5 with POCl3/DMF followed by hydrolysis to give compound 2 with the yield of 68%.

Coupling Reaction of 4-Chloro-7-H-Pyrrolo[2,3-d]Pyrimidine with 2,3,5-Tri-O-Acetyl-b-D-Ribofuranosyl Chloride

Coupling reaction of 4-chloro-7-H-pyrrolo[2,3-d]pyrimidine with 2,3,5-tri-O-acetyl -β-D-ribofuranosyl chloride under the basic condition was investigated. An abnormal coupling reaction, in which the heterocyclic base attacked at the carbon of 1,2-O-methylidene moiety instead of anomeric carbon of ribose was observed and the structure of products 5a, 5b were identified by NMR and X-Ray diffraction.

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.

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.

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.

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.

Crystal Structure and Biological Activities of (R)-N′-[2-(4-Methoxy-6-chloro)-pyrimidinyl]-N-[3-methyl-2-(4-chlorophenyl)butyryl]-urea

The title compound （R）-N′-[2-（4-methoxy-6-chloro）-pyrimidyl]-N-[3-methyl-2-（4- chlorophenyl）butyryl]-urea has been synthesized, and its crystal structure and biological behaviors were studied. Crystallographic data： C17H18C12N4O3, Mr = 397.25, monoclinic, space group P21/c, a = 12.331（2）, b = 14.025（3）, c = 23.085（5） A, β = 99.607（4）°, Z = 8, V = 3936.2（13） A3, Dc = 1.341 g/cm^3, F（000） = 1648, R = 0.0718, wR = 0.1585 and/t（MoKα） = 0.353 mm^-1. The preliminary biological tests showed that the title compound has definite insecticidal and fungicidal activities.

Preparation of 2-amino-5,7-dimethoxy-4-aryl/alkyl-4H-chromene-3-carbonitriles using Na_2O-Al_2O_3-P_2O_5 glass–ceramic system

A highly efficient and environmentally benign protocol for the synthesis of 2-amino-5,7-dimethoxy-4- aryl/alkyl-4H-chromene-3-carbonitrile derivatives by one-pot three-component coupling reacting of aromatic aldehydes, malononitrile and 3,5-dimethoxy phenol under reflux condition has been developed in aqueous EtOH media using Na2O-Al2O3-P2O5 glass-ceramic system.

Approach to synthesis of novel chiral 3-chloro-2(5H)- furanone and its application in asymmetric reactions

The synthetic method of the novel chiral synthon, 5-/-menthyloxy-3-chloro-2-(5H)-furanone 5a and its application in asymmetric reactions were investigated. 5a is easily obtained in highly optical purity, and acts as a stable acceptor of Michael addition with oxygen nucleophiles in tandem double Michael addition / internal nucieophilic substitution to offer the spiro-cyclopropane derivative containing four stereogenic centers 8, which it is difficult to obtain by routine methods. The synthetic methods for 5a and 8 are reported in detail and the new compounds are identified on the basis of their analytical data and spectroscopic data, such as UV, IR, H NMR,13 C NMR, MS and elementary analysis. The absolute configuration of the interesting spiro-cyclopropanes, spiro [1-chloro-4-(/-menthyloxy)-5-oxo-6-oxa-biscyclo[3.1.0]hexane-2,3i(4’-/-menthyloxy-5’-/-menthyloxy- butyrolactone)] 8 was established by X-ray crystallography. This result can provide important synthetic strategy in synthesis of some complex

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.

A highly enantioselective synthesis of 5- (ι-menthyloxy) -4-substituted-3-chloro-2(5H) -furanones

In this paper, stereocontrolled tandem Michael addition-elimination reaction of the novel chiral source, S-(ι-menthyloxy)-3,4-dichloro-2(5H)-furanone, with various thiols and amines has been investigated. A series of new enantiomerically pure compounds, 5-(ι-menthyloxy)-4-substituted-3-cnloro-2(5H)-furanones, were obtained in good yields with d. e.(?)98% under mild conditions.

An environmentally friendly synthesis of 1,4-dihydropyrano[2,3-c]pyrazole derivatives catalyzed by tungstate sulfuric acid

An efficient three-component synthesis of 6-amino-4-aryl-5-cyano-3-metriyl-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazoles via a reaction between 3-methyl-1-phenyl-2-pyrazolin-5-one,aromatic aldehydes and malononitrile using tungstate sulfuric acid as a catalyst was described.Mild conditions,good to excellent yields,easily available catalyst and easy work-up are the key features of this method.

马来酸氟吡汀的合成

通过对马来酸氟吡汀的合成研究,确定并打通了马来酸氟吡汀的合成路线,该工艺条件与其他路线比较,具有起始原料易得、产品收率高、操作简便等优点。即以2-氨基-3-硝基-6-氯吡啶为原料与对氟苄胺反应,然后氢化还原后,滤液进行酰化反应得到氟吡汀碱,经五步反应得到马来酸氟吡汀,结构经1H-NMR确认,总收率77%,含量大于99.9%,产品质量符合2010版药典要求。

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.

Mild and Efficient Synthesis of 1-（6-Chloroquinoxalin-2-yl）-2- [4-（trifluoromethyl）-2,6-dinitrophenyl] Hydrazine Derivatives by Microwave Irradiation

Some 1-（6-chloroquinoxalin-2-yl）-2-[4-（trifluoromethyl）-2,6-dinitrophenyl] hydrazine derivatives have been synthesized via both conventional and microwave assisted organic synthesis（MAOS） methods. The MAOS method is more effective on synthesizing these compounds than the conventional method in regard to the higher chemical yields of products（76%-98%） and the shorter reaction time（1-15 min）.

Fast ethylamine gas sensing based on intermolecular charge-transfer complexation

We have investigated the fast ethylamine gas sensing of 2-chloro-3,5-dinitrobenzotrifluoride（CDBF） loaded poly（acrylonitrile） nanofiber based on an intermolecular charge-transfer complexation.Reversible response and recovery were achieved using alternating gas exposure.This system shows a fast ethylamine gas sensing within 0.4 s.