Simple and selective spectrophotometric determination of ruthenium after solid phase extraction with some quinoxaline dyes into microcrystalline p-dichlorobenzene

A simple selective and highly sensitive extraction method has been developed for the determination of ruthenium spectrophotometrically after extraction of its 2,3-dichloro-6-(3-carboxy-2-hydroxy-1-naphthylazo)quinoxaline (I), 2,3-dichloro-6-(2-hydroxy-3,5-dinitrophenylazo)quinoxaline (II) and 2,3-dichloro-6-(2,7-dihydroxy-naphthylazo)quinoxaline (III) complexes into microcrystalline p-dichlorobenzene. The optimization of experimental conditions for the procedure is studied. The solid p-dichlorobenzene containing the ruthenium-reagent (I-III) complexes is separated by filtration and dissolved in N,N-dimethylformamide. The absorbance is measured at lambda(max) 622, 518 and 542 nm against reagents I, II and III, respectively, as blank. Beer's law is obeyed upto 2.5 microg ml(-1) of ruthenium. The molar absorptivity, Sandell sensitivity, detection and quantification limits are calculated, when compared with those parameters without using solid phase extraction method. The interference of various ions has been studied in detail and the statistical evaluation of the experimental results is reported. The proposed methods have been successfully applied for the determination of trace amount of ruthenium in seawater, ore and metallurgy products.     

Iodine-Promoted Domino Oxidative Cyclization for the One-Pot Synthesis of Novel Fused Four-Ring Quinoxaline Fluorophores by sp3 C−H Functionalization

A method for the synthesis of novel fused four-ring quinoxaline skeleton has been described by an I₂ promoted sp³ C−H functionalization between 1,2,3,3-tetramethyl-3H-indolium iodides and 1,2-diamines. This transformation proceeds smoothly under metal- and peroxide-free conditions through a sequential iodination, oxidation, annulation and rearrangement. Moreover, 8,9-dichloro-5,12,12-trimethyl-2-(trifluoromethyl)-5,12-dihydroquinolino[2,3-b]quinoxaline showed good photophysical properties and was used in live cell imaging, indicating the potential value of this skeleton as a fluorophore in probes.     

The chemistry of 1,2,5-thiadiazoles V. Synthesis of 3,4-diamino-1,2,5-thiadiazole and [1,2,5] thiadiazolo[3,4-b]pyrazines

The o-diamine, 3,4-diamino-1,2,5-thiadiazole ( 2 ), was synthesized from 3,4-dichloro-1,2,5-thiadiazole ( 3 ) hy three methods. Aqueous glyoxal cyclized 2 into [1,2,5]thiadiazolo[3,4–6]-pyrazine ( 14 ). 3,4-Dichloro-1,2,5-thiadiazole 1,1-dioxide ( 18 ) reaeted with 2 to give 1,3-dihydro-bis[1,2,5]thiadiazolo[3,4-b:3′,4′-e]pyrazine 2,2-dioxide ( 19 ). The reaction of 2 with selenium oxyehloride led to [1,2,5]selenadiazolo[3,4-c] [1,2,5]thiadiazole ( 12 ). Ring closure of 2,3-diaminoquinoxaline ( 4 ) with thionyl chloride or selenium oxychloride gave [1,2,5]thiadiazolo-[3,4-b]quinoxaline ( 21 ) and [1,2,5]selenadiazolo[3,4-b]quinoxaline ( 22 ), respectively. Sulfurous acid reduced 21 to the 4,9-dihydro derivative 23 , which was reoxidized to 21 with chloranil. Aqueous hase hydrolyzed 21 to 4 via the hydrated intermediate 24 . Aqueous glyoxal cyclized 4 to the covalent hydrate of pyrazino[2,3-b]quinoxaline ( 26 ), 27 , which was dehydrated to 26 . Compound 26 underwent rapid addition of two alcohols in a process analogous to covalent hydration.     

Solid-phase spectrophotometric determination of trace amounts of vanadium using 2,3-dichloro-6(3-carboxy-2- hydroxynaphthylazo)quinoxaline

Solid-phase spectrophotometry (SPS) has been applied to analysis for trace amounts of vanadium in several environmental water (potable and polluted), biological samples (human blood and urine), and soil samples. Vanadium was sorbed in a styrene-divinylbenzene-type anion-exchanger Dowex 1-X8 as a vanadium--2,3-dichloro-6(3-carboxy-2-hydroxynaphthylazo)quinoxaline. Resin phase absorbances at 606 and 800 nm were measured directly which allowed the determination of vanadium in the range 0.03-2.2 ng ml(-1) with a relative standard deviation (R.S.D.) of 1.4%. The comparison of the SPS method and the gallic acid persulphate method shows that the linearity, analytical sensitivity, and precision were better for the SPS method, and that the latter method has lower detection and quantification limits compared with the gallic acid persulphate method.     

Mass spectrometric studies of cis- and trans-1a,3-disubstituted-1, 1-dichloro-4-formyl-1a ,2,3,4-tetrahydro-1H-azirino [ 1,2-a] [1,5] benzodiazepines

The mass spectrometric behaviour of four cis- and trans-la, 3-disubstituted -1,1 -dichloro-4-formyl-1a,2,3,4-tetrahydro-1H-azirino[1, 2-a] [1,5] benzodiazepines has been studied with the aid of mass-analysed ion kinetic energy spectrometry and exact mass measurements under electron impact ioniza-tion. All compounds show a tendency to eliminate a chlorine atom from the aziridine ring, and then eliminate a neutral propene or styrene from the diazepine ring to yield azirino[ 1, 2-6][1,3]benzimidazole ions. These azmno[1,2-a] [1,5]-benzodiazepines can also eliminate HCl, or Cl plus HG simultaneously to undergo a ring enlargement rearrangement to yield 1,6-benzodiazocine ions, which further lose small molecular fragments, propyne or phenylacetylene, with rearrangement to give quinoxaline ions.     

Synthesis,Biological Evaluation,and In Silico Studies of New Acetylcholinesterase Inhibitors Based on Quinoxaline Scaffold

A quinoxaline scaffold exhibits various bioactivities in pharmacotherapeutic interests. In this research, twelve quinoxaline derivatives were synthesized and evaluated as new acetylcholinesterase inhibitors. We found all compounds showed potent inhibitory activity against acetylcholinesterase (AChE) with IC₅₀ values of 0.077 to 50.080 µM, along with promising predicted drug-likeness and blood–brain barrier (BBB) permeation. In addition, potent butyrylcholinesterase (BChE) inhibitory activity with IC₅₀ values of 14.91 to 60.95 µM was observed in some compounds. Enzyme kinetic study revealed the most potent compound (6c) as a mixed-type AChE inhibitor. No cytotoxicity from the quinoxaline derivatives was noticed in the human neuroblastoma cell line (SHSY5Y). In silico study suggested the compounds preferred the peripheral anionic site (PAS) to the catalytic anionic site (CAS), which was different from AChE inhibitors (tacrine and galanthamine). We had proposed the molecular design guided for quinoxaline derivatives targeting the PAS site. Therefore, the quinoxaline derivatives could offer the lead for the newly developed candidate as potential acetylcholinesterase inhibitors.     

Utility of solid-phase spectrophotometry for determination of dissolved iron(II) and iron(III) using 2,3-dichloro-6-(3-carboxy-2-hydroxy-1-naphthylazo)quinoxaline

A new simple, very sensitive, selective and accurate procedure for the determination of trace amounts of iron(II) by solid-phase spectrophotometry (SPS) has been developed. The procedure is based on fixation of iron(II) as 2,3-dichloro-6-(3-carboxy-2-hydroxy-1-naphthylazo)quinoxaline on a styrene-divinylbenzene anion-exchange resin. The absorbance of resin sorbed iron(II) complex is measured directly at 743 and 830nm. Iron(III) was determined by difference measurements after reduction of iron(III) to iron(II) with hydroxylamine hydrochloride. Calibration is linear over the range 1.0-20 microgL(-1) of Fe(II) with relative standard deviation (R.S.D.) of 1.65% (n=10.0). The detection and quantification limits for 100mL sample system are 280 and 950 ngL(-1) using 0.5 g of the exchanger. The molar absorptivity and Sandell sensitivity are also calculated and found to be 2.86 x 10(6)Lmol(-1)cm(-1) and 0.0196 ngcm(-2), respectively. The proposed procedure has been successfully applied to determine iron(II) and iron(III) in tap, mineral and well water samples.     

Benzo[f]isoindole analogs II. Thieno[3,4-b]quinoxaline

The transient existence of thieno[3,4-b]quinoxaline ( 2d ) as a product of dehydration of 1,3-dihydrothieno[3,4-b]quinoxaline 2-oxide ( 5 ) was demonstrated by trapping experiments with N-phenylmaleimide and dimethyl acetylenedicarboxylate. Attempts to isolate 2d from reaction mixtures arising from dehydration of 5 and from dehydrogenation of 1,3-dihydro-thieno[3,4-b]quinoxaline ( 8 ) were unsuccessful.     

Bromination of quinoxaline and derivatives: Effective synthesis of some new brominated quinoxalines

The synthesis of brominated quinoxaline derivatives starting from several kinds of quinoxaline by different bromination strategies was studied. First the synthesis of some brominated quinoxalines was accomplished along with the development of an alternative and effective synthesis of some known compounds. A new, clean, and effective synthetic method for selective reduction of quinoxaline to 1,2,3,4-tetrahydroquinoxaline was also developed. The products obtained were characterized by means of NMR spectroscopy, elemental analyses, and mass spectrometry.     

OH˙ loss and molecular rearrangements of quinoxaline N-oxides studied by interpretation of mass spectra and application of linear discriminant analysis

Quinoxaline N-oxides substituted at the ortho position to the NO group give characteristic [M – OH]⁺ fragments. With the di-N-oxides the peak intensities depend on the electron-withdrawing strength of the 2- and 3-substituents. Linear discriminant analysis was used to study the fragmentation of quinoxaline N-oxides as determined by the number of NO groups. Results of peak selection and discriminant analysis (Fisher quotients and discriminant vector coefficients) were interpreted with regard to the mass spectrometric decomposition of quinoxaline and quinoxaline N-oxide molecules. For the substituted quinoxaline TV-oxides, fragmentations involving molecular rearrangements like those observed for unsubstituted quinoxaline N-oxidles were also found. For these compounds, partial rearrangement to quinoxalinones is confirmed.     

Synthesis of substituted phenols via 1,1-dichloro-2-nitroethene promoted condensation of carbonyl compounds with DMF

A novel and efficient metal-free synthesis of phenolic compounds was developed via coupling cyclization of DMF as a carbon source with active methylene compounds such as 1,3-dicarbonyl compounds with the assistance of 1,1-dichloro-2-nitroethene. The method we used was different from other traditional phenol functionalization methods. In the reaction, the 1,1-dichloro-2-nitroethene as a promoter which unlike our previous research on 1,1-dichloro-2-nitroethene. The method allows the convenient construction of phenolic compounds under mild reaction conditions and moderate yields.     

催化氢化法制备2,4-二氯-5-异丙氧基苯胺

在乙醇溶液中,控制体系中2,4 二氯 5 硝基苯酚、溴化钠、和水的质量分数分别小于0.3%、0.3%和4%的情况下,用雷尼镍作催化剂,13～15大气压下用氢气还原2,4 二氯 5 异丙氧基硝基苯,得到2,4 二氯 5 异丙氧基苯胺,收率达97%.每次更新10%催化剂,循环使用,催化剂活性未见明显下降.     

Synthesis of 5,12-dioxocyclam nickel (II) complexes having quinoxaline substituents at the 6 and 13 positions as potential DNA bis-intercalating and cleaving agents

Several dioxocyclams containing quinoxaline moieties, as well as their nickel(II) complexes were synthesized and studied for their ability to bind and oxidatively cleave DNA. Although no evidence for binding by intercalation was found, the ability of the Ni(II) complexes to cleave DNA in the presence of Oxone was strongly dependent on both the nature and the spatial orientation of the quinoxaline moieties, suggesting at least transient association of these complexes with DNA.     

Synthesis of novel pyridazino[3,4-b]quinoxalines

The pyridazino[3,4-b]quinoxaline 12 was synthesized by the cyclization of the α-arylhydrazonoacyl-hydrazide 11. The reaction of compound 12 with phosphoryl chloride gave pyridazino[3,4-b]quinoxaline 13, whose reactions with sodium azide or cyclic secondary amines provided pyridazino[3,4-b]quinoxalines 14,17 and 18, respectively. The acylhydrazide 15 was also cyclized to pyridazino[3,4-b]quinoxaline 16.     

A facile synthesis of enol type acyl cyanides via a 1,3-dipolar cycloaddition reaction and a cyano group migration

The reaction of 7-chlorotetrazolo[1,5-a]quinoxaline 5-oxide 4a or 7-chloro-1,2,4-triazolo[4,3-a]quinoxaline 5-oxide 4b with 2-chloroacrylonitrile gave 7-chloro-4-(2-cyano-2-hydroxyvinyl)tetrazolo[1,5-a]quinoxaline 5a or 7-chloro-4-(2-cyano-2-hydroxyvinyl)-1,2,4-triazolo[4,3-a]quinoxaline 5b , respectively. Alcoholysis of compound 5a or 5b afforded 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydrotetrazolo[1,5-a]quinoxaline 6a or 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydro-1,2,4-triazolo[4,3-a]quinoxaline 6b , respectively. Compounds 5a,b were found to exist as a syn and anti mixture of the enol form, while compounds 6a,b occurred as the enamine and methylene imine forms. The tautoraeric character and/or D-H exchange of the vinyl protons are described for compounds 5a,b and 6a,b .     

Synthesis and conversion of 2‐(pyrazol‐1‐yl)quinoxaline 4‐oxides

The reaction of 6‐chloro‐2‐hydrazinoquinoxaline 4‐oxide 1b with acetylacetone or benzoylacetone gave 6‐chloro‐2‐(3,5‐dimethylpyrazol‐i‐yl)quinoxaline 4‐oxide 5a or 6‐chloro‐2‐(3‐methyl‐5‐phenylpyrazol‐1‐yl)quinoxaline 4‐oxide 5b , respXectively. Compound 5a or 5b was converted into the pyrrolo[1,5‐a]quinoxaline 6a or 6b , triazolo[4,3‐a]quinoxaline 9a or 9b , and tetrazolo[1,5‐a]quinoxaline 10.     

On the Mechanism of Condensation between 5—Amino—4,6—dichloro—2—methylpyrimidine and 1—Acetyl—2—imidazolin—2—one

The condensation reaction between 5-amino-4,6-dichloro-2-methylprimidine and 1-acetyl-2-imidazolin-2-one using POCl3 as solvent gave 4,6-dichloro-2-methyl-5-(1-acetyl-tetra-hydro-imidazo-2-ylidene)-aminopyrimidine predominantly and 4,6-dichloro-2-methyl-5-{1-1-(2-oxo-tetrahydro-imidazolyl)]-acetene}-aminopyrimidine as by-product. No 4,6-dichloro-2-methyl-5-(1-acetyl-2-imidazolin-2-yl)-aminopyrimidine was found. The result indicated an esterifi-cation-addition-elimination mechanism.     

Tautomeric structure of 1-methyldihydropyridazino-[3,4-b]quinoxalines in solution

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 1 with ethyl 2-ethoxymethylene-2-cyano-acetate or ethoxymethylenemalononitrile gave 6-chloro-2-[2-(2-cyano-2-ethoxycarbonylvinyl)-1-methylhy-drazino]quinoxaline 4-oxide 3a or 6-chloro-2-[2-(2,2-dicyanovinyl)-1-methylhydrazino]quinoxaline 3b , respectively. The reaction of 3a with a base afforded 7-chloro-1-methyl-1,5-dihydropyridazino[3,4-b]quinoxaline 4 . From the NOE spectral data, the 1-methyldihydropyridazino[3,4-b]quinoxalines 2a, 2b and 4 were found to exist as the 1,5-dihydro form in a dimethyl sulfoxide or trifluoroacetic acid/dimethyl sulfoxide solution.     

Regio - and stereospecific halogenation of 7alogenoalkenes in liquid hydrogen fluoride

The products of bromo and chlorofluorination of E and Z-1,2-dichloroethylenes, 1, 3-dichloro-1-propenes, 1, 1-dichloro- ethylene and 1, 3-dichloro-2-fluoro-1-propene by N-bromosuccinimide and hexachloromelamine in anhydrous hydrogen fluoride have been studied. It was found that the reaction was in all cases 100% regio and 93–100% trans-stereospecific with the exception of E-1, 2-dichloro-ethylene, its trans-stereospecificity being 85%.Threo and erithro-1-bromo-1, 2-dichloro-2-fluoroethanes, 2-bromo-1, 3-dichloro-1-fluoropropanes and 1, 2, 3-trichloro-1-fluoro-propanes as well 1, 1, 2-trichloro-2-fluoroethane, 1-bromo-2, 2-dichloro-2-fluoroethane, 1, 2, 2-trichloro-2 fluoroethane, 1-bromo-1, 3-dichloro-2, 2-difluoropropane, and 1, 1, 3-trichloro-2,2-difluoropropane were obtained in 50–70% yield.The bromination of E and Z-1, 3-dichloro-1-propenes with molecular bromine in carbon tetrachloride in the dark is non-stereospecific and gives a mixture of erithro and threo-1, 2-dibromo-1, 3-dichloropropanes in the ratio about 1:1. However, the bromination reaction in anhydrous hydrogen fluoride solution proceeds with a high degree of stereospecificity (94–95%) and gives threo-1, 2-dibromo-1, 3-dichloropropane from Z and erithro-1, 2-dibromo-1, 3-dichloropropane from E-1, 3-dichloro-1-propene.The data obtained are considered in terms of an electrophilic mechanism of halogenoalkene halogenation in anhydrous hydrogen fluoride and a free-radical mechanism in carbon tetrachloride.     

Reaction of azole condensed quinoxaline N-oxides with acetic anhydride

The reaction of 7-chlorotetrazolo[1,5-α]quinoxaline 5-oxide 6a with acetic anhydride gave 7-chloro-5-(7-chlorotetrazolo[1,5-α]quinoxalin-4-yl)-4,5-dihydro-4-oxotetrazolo[1,5-α]quinoxaline 7a , while the reaction of 7-chloro-1,2,4-triazolo[4,3-α]quinoxaline 5-oxide 6b with acetic anhydride afforded 7-chloro-5-(7-chloro-1,2,4-triazolo[4,3-α]quinoxalin-4-yl)-4,5-dihydro-4-oxo-1,2,4-triazolo[4,3-α]quinoxaline 7b and 7-chloro-4,5-dihydro-4-oxo-1,2,4-triazolo[4,3-α]quinoxaline 8b . The reaction of compound 6a or 6b with acetic anhydride/acetic acid provided 7-chloro-4,5-dihydro-4-oxo-tetrazolo[1,5-α]quinoxaline 8a or compound 8b , respectively.