Fused quinoline heterocycles VI: Synthesis of 5H‐1‐thia‐3,5,6‐triazaaceanthrylenes and 5H‐1‐thia‐3,4,5,6‐tetraazaaceanthrylenes

Ethyl 3‐amino‐4‐chlorothieno[3,2‐c]quinoline‐2‐carboxylate ( 4 ) is a versatile synthon, prepared by reacting an equimolar amount of 2,4‐dichloroquinoline‐3‐carbonitrile ( 1 ) with ethyl mercaptoacetate ( 2 ). Ethyl 5‐alkyl‐5H‐1‐thia‐3,5,6‐triazaaceanfhrylene‐2‐carboxylates 9a‐c , novel perianellated tetracyclic heteroaro‐matics, were prepared by refluxing 4 with excess of primary amines 7a‐c to yield the corresponding amino‐thieno[3,2‐c]quinolines 8a‐c . Subsequent reaction with an excess of triethyl orthoformate (TEO) furnished 9a‐c . Reaction of 4 with TEO in Ac₂O at reflux, gave the simple acetylated compounds, thieno[3,2‐c]‐quinolines 12 and 13 . Refluxing 4 with benzylamine ( 7d ) gave 10 , and subsequent treatment with TEO gave the tetracyclic compound 11 . Refluxing 13 with an excess of alkylamines 7a‐d gave the fhieno[3,2‐c]quino‐lines 15 . Refluxing the aminothienoquinolines 8b with an excess of triethyl orthoacetate gave thieno[3,2‐c]quinoline 17 , while heating with Ac₂O gave 18 and 19 , with small amounts of 16 . Reaction of 8a,b with ethyl chloroformate and phenylisothiocyanate generated the new 1‐thia‐3,5,6‐triazaaceanthrylenes 20a,b and 21a,b , respectively. Diazotization of 8a‐c afforded the novel tetracyclic ethyl 5‐alkyl‐5H‐1‐fhia‐3,4,5,6‐tetraazaaceanthrylene‐2‐carboxylates 22a‐c in good yields.     

Synthesis of novel thia‐oxadiazolophanes

The novel thia‐1,3,4‐oxadiazolophanes were synthesized regioselectively from 1,4‐bis(5‐mercapto‐1,3,4‐oxadiazol‐2‐yl)butane and various 1,ω‐dihaloalkanes in presence of potassium hydroxide. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:273–275, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10141     

Synthesis and Characterization of 5,10‐ and 5,15‐Disubstituted Porphodimethenes

The four porphodimethene isomers, 5,10‐ and 5,15‐disubstituted, have been synthesized in a one‐pot reaction by the Lindsey protocol. Three of them have been characterized by X‐ray crystallography. Structures show that two of them are 5,15‐porphodimethenes: one is syn‐equatorial, another is anti‐configuration; the third one is 5,10‐porphodimethene. In the 5,10‐porphodimethene, the tripyrrane subunit remains planar conformation. ¹H NMR and UV‐vis spectra have also been characterized. Both spectra reveal remarkable difference between 5,10‐ and 5,15‐disubstituted isomers.     

C‐phosphorylation of 5,10‐dimethyl‐5,10‐dihydrophenazine and its carbo‐ and heteroanalogs

This study covers phosphorylation of heterocyclic analogues of N‐methyldiphenylamine with phosphorus tribromide in pyridine solution. The reaction is found to proceed regioselectively in accordance with the orienting effect of the amino group. Mono and bis‐phosphorylated derivatives of the heterocycles have been isolated and characterized. It is pointed out that the heterocyclic systems under study exhibit reduced reactivity in electrophilic phosphorylation as compared to N‐methyldiphenylamine. The results of calculations by the PM3 method are reported for the starting molecules and their σ‐complexes. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:652–657, 2001     

Synthesis and characterization of novel (9H‐fluoren‐9‐ylamino) carbonylaminomethylphosphonic acid

The new α‐aminophosphonic acids are synthesized, reacting (9H‐fluoren‐9‐yl)urea with formaldehyde and phosphorus trichloride. (9H‐Fluoren‐9‐yl)urea was prepared from spiro(fluoren‐9,4′‐imidazolidine)‐2′,5′‐dione by alkaline hydrolysis with Ba(OH)₂. The structure of the title compounds was proved by means of IR, ¹H, ¹³C, and ³¹P NMR spectroscopy. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:719–722, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20500     

Synthesis,molecular and crystal structure,and properties of 10‐propylthio‐5,10‐dihydrophenarsazine

10‐Propylthio‐5,10‐dihydrophenarsazine 2 was obtained by the reaction of 10‐chloro‐5,10‐dihydrophenarsazine 1 with propanethiol in the presence of triethylamine under mild conditions. The structure of 2 was established by X‐ray single crystal diffraction. The reaction of 2 with 2,4‐bis(ethylthio)‐1,3,2,4‐dithiadiphosphetane‐2,4‐disulfide 3 at room temperature affords a novel route to S‐10(5,10‐dihydrophenarsazine) S′‐ethyl‐S″‐propyltetrathiophosphate 4 . © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:287–291, 2000     

Synthesis and biological evaluation of novel methylene‐bis‐[1,5]‐benzodiazepines

A series of novel methylene‐bis‐chalcones 3 was prepared by the reaction of 5‐(3‐formyl‐4‐hydroxybenzyl)‐2‐hydroxy benzaldehyde 2 with different acetophenones, subsequent treatment of compound 3 with an appropriate o‐phenylenediamine gave the corresponding methylene‐bis‐[1,5]‐benzodiazepines 4/5 in good yields. Characterization of the new compounds has been done by means of IR, ¹H NMR, MS and elemental analyses. The antibacterial and antifungal activity of the compounds has also been evaluated.     

Regiodirected Synthesis and Stereochemistry of 2,4,8‐Trialkyl‐3‐thia‐1,5‐diazabicyclo[3.2.1]octanes and α,ω‐Bis(2,4,6‐trialkyl‐1,3,5‐dithiazinane‐5‐yl)alkanes

2,4,8‐Trialkyl‐3‐thia‐1,5‐diazabicyclo[3.2.1]octanes have been obtained by the regioselective and stereoselective cyclocondensation of 1,2‐ethanediamine with aldehydes RCHO (R═Me, Et, Prⁿ, Buⁿ, Pentⁿ) and H₂S at molar ratio 1:3:2 at 0°C. The increase in molar ratio of thiomethylation mixture RCHO–H₂S (6:4) at 40°C resulted in selective formation of bis‐(2,4,6‐trialkyl‐1,3,5‐dithiazinane‐5‐yl)ethanes. Cyclothiomethylation of aliphatic α,ω‐diamines with aldehydes RCHO (R═Me, Et) and H₂S at molar ratio 1:6:4 and at 40°С led to α,ω‐bis(2,4,6‐trialkyl‐1,3,5‐dithiazinane‐5‐yl)alkanes. Stereochemistry of 2,4,8‐trialkyl‐3‐thia‐1,5‐diazabicyclo[3.2.1]octanes have been determined by means of ¹H and ¹³С NMR spectroscopy and further supported by DFT calculations at the B3LYP/6‐31G(d,p) level. The structure of α,ω‐bis(2,4,6‐trialkyl‐1,3,5‐dithiazinane‐5‐yl)alkanes was confirmed by single‐crystal X‐ray diffraction study.     

Synthesis of 3‐Ω‐aminohydantoins

Several 3‐Ω‐amino monosubstituted hydantoins have been obtained in the reaction of isocyanate of glycine ethyl ester with the appropriate aliphatic or aromatic diamine. It was found, that the 3‐(aminoaryl) monosubstituted hydantoins may be diazotized and their diazonium salts may be coupled and hydrolysed without changes in the hydantoin ring.     

Synthesis of 9‐Halogenated 9‐Deazaguanine N7‐(2′‐Deoxyribonucleosides)

The syntheses of N⁷‐glycosylated 9‐deazaguanine 1a as well as of its 9‐bromo and 9‐iodo derivatives 1b , c are described. The regioselective 9‐halogenation with N‐bromosuccinimide (NBS) and N‐iodosuccinimide (NIS) was accomplished at the protected nucleobase 4a (2‐{[(dimethylamino)methylidene]amino}‐3,5‐dihydro‐3‐[(pivaloyloxy)methyl]‐4H‐pyrrolo[3,2‐d]pyrimidin‐4‐one). Nucleobase‐anion glycosylation of 4a – c with 2‐deoxy‐3,5‐di‐O‐(p‐toluoyl)‐α‐D ‐erythro‐pentofuranosyl chloride ( 5 ) furnished the fully protected intermediates 6a – c (Scheme 2). They were deprotected with 0.01M NaOMe yielding the sugar‐deprotected derivatives 8a – c (Scheme 3). At higher concentrations (0.1M NaOMe), also the pivaloyloxymethyl group was removed to give 7a – c , while conc. aq. NH₃ solution furnished the nucleosides 1a – c . In D₂O, the sugar conformation was always biased towards S (67–61%).     

Palladium‐Catalyzed Asymmetric Synthesis of Silicon‐Stereogenic 5,10‐Dihydrophenazasilines via Enantioselective 1,5‐Palladium Migration

A palladium‐catalyzed asymmetric synthesis of silicon‐stereogenic 5,10‐dihydrophenazasilines was developed that proceeds via an unprecedented enantioselective 1,5‐palladium migration. High enantioselectivity was achieved by employing 4,4′‐bis(trimethylsilyl) (R )‐Binap as the chiral ligand, and a series of mechanistic investigations were carried out to probe the catalytic cycle of this process.     

Synthesis and anti‐inflammatory activity of 8H‐1‐thia‐8‐aza‐dibenzo[e,h]azulenes

Synthesis of a novel class of fused heterotetracyclic compounds, 8H‐1‐thia‐8‐aza‐dibenzo[e,h]azulenes ( VII ), is described. Starting N‐benzoyl‐protected 5H‐dibenzo[b,f]azepine ( XI , PG = Bz) was oxidized to 5‐benzoyl‐10,11‐epoxy‐10,11‐dihydro‐5H‐dibenzo[b,f]azepine ( 2 ), which subsequently rearranged in Lewis acid‐induced epoxide ring opening to give 5‐benzoyl‐5,11‐dihydro‐10H‐dibenzo[b,f]azepin‐10‐one ( 3 ). Vilsmeier reaction of 3 provided β‐chlorovinyl aldehyde 4 that readily cyclized with ethyl 2‐mercaptoacetate to form dibenzazepino[4,5]‐fused thiophene structure 5 . Further transformation of substituent at C‐2 position of 5 and N‐deprotection led to final aminoalkoxy derivatives 9 . All compounds with tetracyclic skeleton were tested in vitro for their anti‐inflammatory activity. J. Heterocyclic Chem., (2011).     

Synthesis and hydrolysis of p‐toluoyl and acetyl 9‐triptycyl diselenides: A study on generation of triptycene‐9‐selenenoselenoic acid

p‐Toluoyl 9‐triptycyl diselenide ( 9 ) was prepared by reaction of Se‐9‐triptycyl triptycene‐9‐selenoseleninate ( 7 ) with p‐toluenecarboselenoic acid ( 8 ) and by reaction of triptycene‐9‐selenenoselenolate salt with p‐toluoyl chloride. Acetyl 9‐triptycyl diselenide ( 13 ) was prepared by reaction of triptycene‐9‐selenenoselenolate salt with acetyl chloride. Hydrolysis of the two diselenides, 9 and 13 , provided triptycene‐9‐selenol ( 10 ) and di‐9‐triptycyl triselenide ( 12 ), suggesting the generation of triptycene‐9‐selenenoselenoic acid ( 3 ). © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:525–528, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20155     

Synthesis and biological activity evaluation of differently substituted 1,4‐dioxo‐3,4‐dihydrophthalazine‐2(1H)‐carboxamides and ‐carbothioamides

Differently substituted phthalic anhydrides can react either with semicarbazide or thiosemicarbazide to give respectively 1,4‐dioxo‐3,4‐dihydrophthalazine‐2(1H)‐carboxamides or 1,4‐dioxo‐3,4‐dihydrophthal‐azine‐2(1H)‐carbothioamides under mild conditions and generally with good yields. These compounds have been tested in order to evaluate their anti‐microbial activity. Furthermore a new synthetic pathway to phtha‐lazino[2,3‐b]phthalazine‐5,7,12,14‐tetraone has been devised.     

Synthesis and X‐ray study of cis and trans isomers of 6‐cyano‐2‐oxa‐10‐thia‐1‐phosphabicyclo[4.4.0]decane‐1‐oxide

Intramolecular cyclization of bis(3‐chloropropyl)‐diethoxythiophosphorylacetonitrile 7, taking place under distillation in vacuo, yields 6‐cyano‐2‐oxa‐10‐thia‐1‐phosphabicyclo[4.4.0]decane‐1‐oxide 10 as a mixture of cis and trans isomers in a 2.3:1 ratio. The isomers were separated chromatographically. For both isomers, single crystals with nonequivalent enantiomeric ratios were obtained under crystallization. The structures of both isomers of bicyclophostone 10 are confirmed by X‐ray study of single crystals. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:163–170, 2000     

New heterocycles from 8‐hydroxyquinoline via dipolar 1,3‐cycloadditions: Synthesis & biological evaluation

Diarylnitrilimine and arylnitriloxide dipoles react with two 8‐hydroxyquinoline substrates to give respectively pyrazolinic and isoxazolinic derivatives. The structure of these new heterocycles was established on the basis of their spectroscopic data and by chemical methods. The inhibition activity of one of these heterocycles was evaluated in vitro against 8 pathogenic μ‐organisms.     

Synthesis of 3‐Ω‐amino‐2‐thiohydantoins

In the reaction of ethyl isothiocyanatoacetate with diamines, followed by cyclization of the intermediate product, 3‐monosubstituted thiohydantoins have been obtained. It was found that the reaction course depends on the purity of the isothiocyanate used and also, in the case of dialkylaminoamines, the self‐cyclization occurs. Besides the dialkylamino derivatives of 3‐monosubstituted 2‐thiohydantoins also new monoalkylamino, amino and heterocyclic derivatives were synthesized. The aryldiazonium derivative of 3‐monosubstituted 2‐thiohydantoin yielded both respective phenol derivative after hydrolysis and the product of coupling with 2‐naphthol.     

Synthesis and characterization of low‐band‐gap conjugated polymers containing phenothiazine and benzo‐2,1,3‐thia‐/seleno‐diazole

Two phenothiazine‐based conjugated polymers, poly(3, 7‐divinylene‐N‐octyl‐phenothiazine‐alt‐benzo‐2,1,3‐ thiadiazole) (PQS) and poly(3,7‐divinylene‐N‐octyl‐phenothiazine‐alt‐benzo‐2,1,3‐selenodiazole) (PQSe) were synthesized by Heck coupling reaction. The chemical structures of the two polymers were confirmed by ¹H‐NMR and Ft‐IR. They showed good solubility in some common organic solvents such as tetrahydrofuran (THF), chloroform. The weight‐average molecular weight (Mw) of the polymers determined by GPC in THF against polystyrene standards was 3.7 × 10³ for PQS and 1.9 × 10³ for PQSe, respectively. The temperatures of 5% weight loss (T₅) were 385.0°C for PQS and 324.0°C for PQSe, respectively, determined by TGA measurements under nitrogen ambience. UV–vis absorption spectra of the polymer films showed the absorption maxima at 537 nm for PQS and 539 nm for PQSe, with the full width at half maximum (FWHM) of 190 and 230 nm, respectively. The optical band gaps ( ) of the polymer films are 1.86 eV for PQS and 1.80 eV for PQSe, respectively. As the polymers have low‐band‐gap and broad absorption in the visible region, they may be used as potential light‐harvesting materials for photovoltaic devices (PVDs). Furthermore, photoluminescence (PL) spectra of the polymer solutions showed the emission maxima at 698 nm for PQS and 709 nm for PQSe, with FWHM of 152 nm and 167 nm, respectively, which revealed that these two polymers may be used as red and near infrared light‐emitting materials for polymeric light‐emitting diodes (PLEDs). Copyright © 2009 John Wiley & Sons, Ltd.     

4‐Vinyl­benzoic acid and 9‐vinyl­anthracene

The crystal structures of two styrene analogues, 4‐vinyl­benzoic acid, C₉H₈O₂, (I), and 9‐vinyl­anthracene, C₁₆H₁₂, (II), were determined by X‐ray analyses at 108 and 293 K for (I) and at 123 and 293 K for (II). In (I), a pair of mol­ecules around an inversion center form a dimer connected by two carboxyl groups. The anthracene planes of two mol­ecules in (II) are antiparallel to each other around an inversion center. The vinyl group of (I) is almost coplanar with the phenyl ring, whereas the vinyl group of (II) is nearly perpendicular to the anthracene plane. In (I), the bond length of the vinyl group at 293 K is significantly shorter than that at 108 K [1.288 (2) versus 1.3248 (14) Å] suggesting a bias of the thermal motion, whereas the bond lengths are not so different between the two temperatures in (II) [1.3266 (15) versus 1.310 (2) Å].