New chromogens of the ferroin-type--II. Pyrido and pyridyl derivatives of phenazine and quinoxaline

Eleven pyrido and pyridyl derivatives of phenazine (6) and quinoxaline (5) have been examined as chromogens of the ferroin type for iron(II) and copper(I). Three of the quinoxaline derivatives show promise as reagents for iron(II) but are expensive and difficult to prepare.     

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.     

Synthesis,Characterization, and Antiproliferative Activity of Novel Chiral [QuinoxP*AuCl2]+ Complexes

Herein is reported the synthesis of two Au(III) complexes bearing the (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (R,R-QuinoxP*) or (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (S,S-QuinoxP*) ligands. By reacting two stoichiometric equivalents of HAuCl₄.3H₂O to one equivalent of the corresponding QuinoxP* ligand, (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (1) and (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (2) were formed, respectively, in moderate yields. The structure of (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (2) was further confirmed by X-ray crystallography. The antiproliferative activities of the two compounds were evaluated in a panel of cell lines and exhibited promising results comparable to auranofin and cisplatin with IC₅₀ values between 1.08 and 4.83 µM. It is noteworthy that in comparison to other platinum and ruthenium enantiomeric complexes, the two enantiomers (1 and 2) do not exhibit different cytotoxic effects. The compounds exhibited stability in biologically relevant media over 48 h as well as inert reactivity to excess glutathione at 37 °C. These results demonstrate that the Au(III) atom, stabilized by the QuinoxP* ligand, can provide exciting compounds for novel anticancer drugs. These complexes provide a new scaffold to further develop a robust and diverse library of chiral phosphorus Au(III) complexes.     

A comparison of some pyridyl-substituted pyrazines as analytical reagents

A comparative study of six 2-pyridyl and 2-(6-methyl-pyridyl) derivatives of pyrazine as chromogenic reagents of the ferroin and cuproin types has established 2,3,5,6-tetrakis(2'-pyridyl)pyrazine as a highly sensitive reagent for iron(II); 2,3-bis(2'-pyridyl)-5,6-dihydropyrazine and 2,3-bis[2'-(6'-methyl pyridyl)]-5,6-dihydropyazine both show high sensitivity and characteristic high selectivity in their reactions with iron(II) and copper(I) respectively-the reaction with copper(I) being almost as sensitive as that given by bathocuproine. The ease with which the highly coloured metal chelates can be extracted into immiscible solvents to give stable solutions makes these reagents useful for the determination of traces of iron and copper.     

Complexation Properties and Synthesis of 1,2-Bis(2,2'-bipyridinyl)ethylene and 1,2-Bis(2,2' -bipyridinyl)ethane Ligands with Cu(I)

l,2-Bis(2,2'-bipyridinyl)ethylene(1) ligand was synthesized by Wittig-Horner reaction and 1, 2-Bis(2, 2'-bipyridinyl)ethane(2) ligand(which can be obtained via another route ) was prepared by hydrogenation of (1). The formation of complexes of (1) and (2) with copper (I) has been studied. The influence of the different bridge chains (CH =CH, CH2CH2) on complexation is discussed on the basis of 1H NMR spectra. Keywords Dipyridine aldehyde, Dipyridine derivative, Copper complex     

Facile route to 3,5-disubstituted morpholines: enantioselective synthesis of O-protected trans-3,5-bis(hydroxymethyl)morpholines

[reaction: see text] (3R,5R)-1 R1 & R2 = TBDPS, (3S,5R)-2 R1 = Bn,R2 = TBDPS, (3S,5S)-3 R2 & R2 = Bn. trans-3,5-Bis(benzyl/tert-butyldiphenylsilyloxymethyl)morpholines, promising candidates for the C(2)-symmetric class of chiral reagents, were prepared with excellent optical purity. A key step in the synthesis is the coupling of a serinol derivative with 2,3-O-isopropylideneglycerol triflate or its equivalent. This methodology was extended to the synthesis of chiral trans-3-(benzyloxymethyl)-5-(tert-butyldiphenylsilyloxymethyl)morpholine, a potentially useful chiral building block.     

Novel synthesis of 2,3-diarylbuta-1,3-dienes from 1,4-dimethoxybutyne-2

It was found that 2,3-diarylbuta-1,3-dienes were readily obtained in good to excellent yields through the S_N-2′ type substitution of 1,4-dimethoxybutyne-2 with aryl Grignard reagents in the presence of a copper(I) salt.     

Derivatives of 5‐Oxy‐pyrido[2,3‐b]quinoxaline‐9‐carboxylic acid: A tricyclic system useful for the synthesis of potential intercalators

The synthesis of a new series of 5‐oxy‐pyrido[2,3‐b]quinoxaline‐9‐carboxamides 4a‐i and N¹,N²‐Bis(5‐oxy‐pyrido[2,3‐b]quinoxaline‐9‐benzoyl)ethylenediamine ( 5 ) is reported starting from 2‐chloro‐3‐nitropyri‐dine. Fundamental steps of the synthetic pathway are i) preparation of 2‐(3‐nitro‐pyridin‐2‐ylamino)benzoic acid ( 1 ) via copper‐catalyzed condensation of 2‐chloro‐3‐nitropyridine with o‐anthranilic acid, ii) intramolecular cyclization of the acid 1 to 5‐oxy‐pyrido[2,3‐b]quinoxaline‐9‐carboxylic acid ( 2b ) upon treatment with concentrated sulfuric acid and oleum and iii) conversion of the acid 2 to the desired amides 4a‐i and 5 . Compounds 4a‐i and 5 are oxygenated azaanalogs of phenazines, a wellknown series of intercalators with cytotoxic activity.     

Benchtop synthesis and crystal structure determination of a monomeric N-heterocyclic carbene complex of copper(I) chloride

(1,3-Bis(2,4,6-trimethylphenyl)imidazol-2-ylidene)copper(I) chloride (1) was prepared by the reaction of 1,3-bis(2,4,6-trimethylphenyl)imidazolium chloride and copper(I) oxide in refluxing tetrahydrofuran. In contrast to previously published methods of preparation of N-heterocyclic carbene complexes of copper(I) halides, this synthesis requires neither an inert atmosphere nor scrupulously dry solvents. The structure of 1 was determined by elemental analysis, ¹H and ¹³C NMR, and a single-crystal X-ray diffraction study. The X-ray crystal data reveal linear coordination about the copper(I) center and linear chains of molecules formed with intermolecular head-to-tail C–H···Cl interactions.     

Control of helical chirality of poly(quinoxaline‐2,3‐diyl)s based on postpolymerization modification of the terminal group by small chiral molecules

Poly(quinoxaline‐2,3‐diyl)s having a terminal formyl or boronyl group were prepared by living polymerization of 1,2‐diisocyanobenzenes using organopalladium initiators bearing a protected formyl or boronyl group. Poly(quinoxaline‐2,3‐diyl)s were successfully deracemized by reacting them with small optically active molecules at their terminal formyl or boronyl group, leading to the induction of optically active helical structures. Poly(quinoxaline‐2,3‐diyl) having terminal formyl groups was converted to one‐handed helical polymer, in which the screw‐sense excess was 68% (84:16). The helix sense of the boronyl‐terminated poly(quinoxaline‐2,3‐diyl) was reversibly controlled by attaching and removing the chiral group. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Unusual hydrothermal synthesis of a heteroaromatic macrocyclic complex

Hydrothermal treatment of 2,3-bis(2′,6″-bipyridyl)quinoxaline, molybdenum trioxide, cupric acetate and water unexpectedly forms the Cu(II) complex of a planar, macrocyclic 2-acyl-6,2′-bipyridyl dimer, imbedded within a copper benzotrizolate-octamolybtate matrix. X-ray crystallographic characterization of this material, and scalar relativistic ZORA DFT modeling of the complex dication are presented.     

Quinoxaline-2,3-dithiol in reactions with propargyl bromide and 1,3-dibromopropyne

Propargyl bromide with quinoxaline-2,3-dithiol in DMSO in the presence of K₂CO₃ affords 2,3-bis-(2-propynylsulfanyl)quinoxaline in good yield whereas in absolute methanol in the presence of sodium methoxide at 20°C a 1:2 mixture of 2,3-bis(2-propynylsulfanyl)quinoxaline and 3-(2-propynylsulfanyl)-2(1H)-quinoxalinethione is formed. Individual 3-(2-propynylsulfanyl)-2(1H)-quinoxalinethione was obtained by crystallization of this mixture from ether. The reaction of 1,3-dibromopropyne with quinoxaline-2,3-dithiol in ethanol in the presence of NaOH at heating results in 2-bromomethylidene-1,4-(3H)-dithiino[2,3-b]quinoxaline in 77% yield. Performing this reaction in methanol in the presence of sodium methoxide during long heating (16 h) led to 2,3-bis[(3-bromo-2-propynyl)sulfanyl]quinoxaline in 72% yield.     

Quinoxalino[2,3-c]cinnolines and their 5-N-oxide: alkoxylation of methyl-substituted quinoxalino[2,3-c]cinnolines to acetals and orthoesters

We report the alkoxylation of methyl-substituted quinoxalino[2,3-c]cinnolines to give acetals and orthoesters in high yields. Routes to the precursors of this alkoxylation reaction as well as other quinoxalino[2,3-c]cinnoline and their 5-oxide derivatives are reported. Most of these quinoxalino[2,3-c]cinnolines were prepared by cyclization of the corresponding 2-amino-3-(2-nitrophenyl)quinoxaline, which, in turn, result from an unusual Beirut reaction from benzofurazan oxides plus 2-nitrobenzylcyanides. Mechanistic explanations for these intriguing reactions are presented.     

Synthesis and Structure of 2,3-Bis(5-tert-butyl-2-methoxyphenyl)buta-1,3-diene by Bromine Elimination of (Z)-1,4-Dibromo-2,3-bis(5-tert-butyl-2-methoxyphenyl)-2-butene

2,3-Bis(5-tert-butyl-2-methoxyphenyl)buta-1,3-diene was prepared by bromination of (Z)- and (E)-2,3-bis(5-tert-butyl-2-methoxyphenyl)-2-butene followed by treatment with zinc powder in a mixture of CH₂Cl₂ and acetic acid, which was converted to the corresponding o-terphenyl skeleton by the condensation with dimethyl acetylenedicarboxylate followed by oxidation with 2,3-dichloro-5,6-dicyanobenzoquinone.     

Synthesis of 6-alkylidene-2,3-benzo-1,4-diaza-7-oxabicyclo[4.3.0]non-2-enes by cyclization of 1,3-bis(silyl enol ethers) with quinoxalines

6-Alkylidene-2,3-benzo-1,4-diaza-7-oxabicyclo[4.3.0]non-2-enes were prepared by cyclization of 1,3-bis(silyl enol ethers) with quinoxaline.     

A spectrochemical study of quinoxaline-2,3-dithiol C8H6N2S2 and its monobasic salts M·C8H5N2S2, oxidation product (C8H5N2S2)2 and the related compound (C8H4N2S)2

The new quinoxaline-2,3-dithioderivative (C₈H₅N₂S₂)₂, (HQS₂)₂, was prepared by oxidation of quinoxaline-2,3-dithiol, H₂QS₂, with iodine or oxygen. These substances and the compound (C₈H₄N₂S)₂, Q₂S₂, have different and characteristic electronic spectra in DMF solution; in the presence of air H₂QS₂ 10⁻⁴ M in DMF is transformed within 14 hr into (HQS₂)₂ and this, after 72 hr, into a new stable not isolated compound. (HQS₂)₂, H₂QS₂ and its salts M·HQS₂ (M = K, (CH₃)₂NH₂) do not show any ν(SH) band in the region 2500–2600 cm⁻¹ but show, like 2,3-dihydroxy-quinoxaline, a ν(NH) band at 3125–3150 cm⁻¹ and a NH-vibration band at 730–750 cm⁻¹ which are absent in quinoxaline, 2,3-dimethyl- and 2,3-dichloroquinoxaline and in Q₂S₂. It may be assigned the constitution of quinoxaline-2,3-dithione to H₂QS₂, bis(quinoxaline)-2,2′-di-sulphide-3,3′-dithione to (HQS₂)₂ and bis(quinoxaline)-2,2′-3,3′-dithioether to Q₂S₂. The i.r. spectra of these quinoxaline-2,3-dithioderivatives are compared with those of quinoxaline and its 2,3-disubstituted derivatives and some tentative assignments are given for their ν(NCS) asym., ν(NCS) sym., ν(CS) and δ(NCS) modes.     

Asymmetric hydrogenation catalyzed by rhodium complexes of 2,3-bis(dimenthylphosphino)maleic anhydride and 2,3-bis(dimenthylphosphino)-N-phenylmaleimide

2,3-Bis(dimenthylphosphino)maleic anhydride and the phenylimide derivative have been prepared from 2,3-dichloromaleic anhydride and 2,3-dichloro-N-phenylmaleimide, respectively, and dimenthyl(trimethylsilyl)phosphine. These compounds have been used as ligands for Rh complexes and have been tested in the asymmetric hydrogenation of α-acetamidocinnamic acid, methyl-α-acetamidocinnamate and itaconic acid. Optical yields of up to approximately 70% were obtained with α-acetamidocinnamic acid.     

Synthesis and photoluminescence of linear and hyperbranched polyethers containing phenylquinoxaline units and flexible aliphatic spacers

Ultrahigh‐molecular‐weight linear polyethers were prepared through a reaction between the phenylquinoxaline monomers 2,3‐bis(4‐hydroxyphenyl)‐6‐fluoroquinoxaline and 2,3‐bis(4‐hydroxyphenyl)‐6‐(α,α,α‐trifluoromethyl)quinoxaline and 1,12‐dibromododecane. A new hyperbranched polyether containing a phenylquinoxaline moiety was also prepared from a new self‐polymerizable AB₂ monomer, 2,3‐bis(6‐bromohexyloxyphenyl)‐6‐(4‐hydroxyphenyloxy)quinoxaline. All the polyethers were amorphous and soluble in polar aprotic solvents. Their solution‐cast thin films were light yellow, ductile, and optically transparent. The polymers were thermally stable up to 350 °C and had glass‐transition temperatures in the range of 25–83 °C, which depended on the architecture and monomer structure. The monomers and polymers displayed fluorescence maxima in the blue‐light region in the range of 431–449 nm with relatively narrow peak widths; this indicated that they had pure and intense fluorescence. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3587–3603, 2004     

Reactions of furoxano[3,4-b]quinoxaline with alkynes and alkenes. Synthesis of pyrazino[2,3-b]quinoxaline 1,4-dioxides

Pyrazino[2,3-b]quinoxaline 1,4-dioxides 3a-e were prepared by reacting Furoxano[3,4-b]quinoxaline with alkynes and alkenes.     

The preparation of HCF2CdX and HCF2ZnX via direct insertion into the carbon halogen bond of CF2HY (Y = Br, I)

The difluoromethylcadmium and zinc reagents have been prepared in DMF via direct insertion of Cd⁰ into the carbon halogen bond of CF₂HY (Y = Br, I). These reagents are stable at 65-75 °C and exhibit prolonged stability and activity at room temperature. Metathesis of the difluoromethylcadmium reagents with Cu(I)X (X = Br, Cl) at −55 °C rapidly produces difluoromethylcopper. The copper reagent is significantly less stable than the cadmium or zinc reagent and rapidly decomposes at room temperature. The difluoromethylcadmium and copper reagents exhibit good reactivity with allylic halides, propargylic derivatives and 1-iodoalkynes to provide good yields of the corresponding difluoromethylalkenes, difluoromethylallenes and difluoromethyl-2-alkynes. Alkylation is successful only with reactive alkyl halides. Generally, the difluoromethylcopper reagent is more reactive than the difluoromethylcadmium reagent and generally exhibits higher regioselectivity in reactions that can occur by either α- or γ-attack.