Synthesis of certain pyrrolo[2,3-b]pyridine-5-carboxylic acid derivatives as potential antimicrobial agents

Summary A synthetic approach to new 1-benzyl-7-alkyl-2,3-dimethyl-4-oxopyrrolo[2,3-b]pyridine-5-carboxylic acids using 5,6-dimethyl-2,4-dioxopyrrolo[2,3-d][1,3]oxazine as the starting material is reported. The antimicrobial activity of these compound is reported.

---

Synthese von Pyrrolo[2,3-b]pyridin-5-carbonsäure-Derivaten als potentielle antimikrobielle Substanzen

Zusammenfassung Die Synthese von neuen 1-Benzyl-7-alkyl-2,3-dimethyl-4-oxopyrrolo[2,3-b]pyridin-5-carbonsäuren durch Verwendung von 5,6-Dimethyl-2,4-dioxopyrrolo[2,3-d][1,3]oxazinen als Ausgangsmaterial wird beschrieben. Die antimikrobielle Aktivität dieser Substanzen wurde geprüft.

     

Phthalazinone in Heterocyclic Synthesis: Synthesis of Some s-Triazole,s-Triazolothiadiazine,s-Triazolothiadiazine,and s-Triazolothiadiazole Derivatives as Pharmaceutical Interest

1(2H)-Oxophthalazine-2-acetic acid ethyl ester was allowed to react with various reagents under different conditions to yield compounds 2-[(4-substituted-5-mercaptotriazol-3-yl) methyl]-1 (2H)-oxophthalzines 5 and 7 which acted as starting materials for the preparation of some new s-triazolo[5,1-b][1,3]thiazine (8), s-triazolo[3,4-b][1,3,4]thiadiazine 9,12,14,20, and s-triazolo[3,4-b][1,3,4]thiadiazole 18,21 derivatives.

     

Condensed isoquinolines. 37.* Heterocyclization using 3-(arylamino)- and 3-(hetarylamino)isoquinolin-1(2H)-ones

The reaction of 3-NHR-isoquinolin-1(2H)-ones (R = Ar) with aromatic aldehydes in the presence of Me3SiCl or in acetic acid leads to the formation of derivatives of dibenzo[b,f][1, 8]naphthyridin-5(6H)- one and benzo[f]isoquino[3,4-b][1, 8]naphthyridine-5,9(6H,7H)-dione. The reaction for R = Het in the presence of Me3SiCl gives derivatives of 5H-pyrido[1',2':1,2]pyrimido[4,5-c]isoquinolin-5-one, benzo[f]isoquinoline[3,4-b][1,8]naphthyridine-5,9[6H,7H]-dione, and derivatives of new heterocyclic systems, 5H-pyrazino[1',2':1,2]pyrimido[4,5-c]isoquinolin-5-one, 5H-[1,3]thiazolo[3',2':1,2]pyrimido- [4,5-c]isoquinolin-5-one, 5-H-benzo[f]pyrazolo[3,4-b][1,8]naphthyridin-5-one, and isoquino[3,4-b]- [1,5]naphthyridin-5(6H)-one. The effect of the structure of substituent R and nature of the substituent in the benzaldehydes on the structure of the reaction products was studied.     

Darstellung und reaktionen eines 2H-pyrrolo[3,4-b]pyridins und eines 2H-pyrrolo[3,4-b]pyrazins

A 2H-pyrrolo[3,4-b]pyridine and a 2H-pyrrolo[3,4-b]pyrazine can be prepared by the electrochemical reduction of N-phenylpyridine- and -pyrazinedicarboxylic imide in the presence of trimethylchlorosilane. These ortho-quinoid heterocyclic compounds 4 and 13 react with dienophiles leading to substituted quinolines and quinoxalines.     

Ionic Liquid-Mediated Facile Synthesis and Antimicrobial Study of Thiazolo [2,3-b]Benzo[h]Quinazolines and Thiazino[2,3-b] Benzo-[h]Quinazolines

Abstract

8-Methoxy-4-phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thione, obtained by the condensation of 2-benzylidene-6-methoxy-3,4-dihydronapthalene-1(2H)-one with thiourea, on reaction with chloroacetic acid and 3-chloropropanoic acid in the presence of the ionic liquid N-methylpyridinium tosylate furnishes 3-methoxy-7-phenyl-7,10-dihydro-5H- benzo[h]thiazolo[2,3-b]quinazoline-9(6H)-one and 3-methoxy-7-phenyl-5,6,10,11-tetrahydro- benzo[h][1,3]thiazino[2,3-b]quinazoline-9(7H)-one. Further, condensation of the thione with 1,2-dibromoethane and 1,3-dibromopropane yields 3-methoxy-7-phenyl-6,7,9,10-tetrahydro-5 H-benzo[h]thiazolo[2,3-b]quinazoline and 3-methoxy-7-phenyl-5,6,7,9,10,11-hexahydrobenzo [h][1,3]thiazino[2,3-b]quinazoline respectively. Arylidene derivatives have been obtained by two routes. The structures of the cyclized compounds have been established on the basis of elemental analysis and spectroscopic data. The synthesized compounds were screened for antimicrobial activity. Some of the compounds showed promising antimicrobial activities.     

Synthesis and Properties of 7-Acetyl-8-aryl-9-cyano-3-hydroxy-6-methyl-3,4-dihydro-2H,8H-pyrido[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazines

7-Acetyl-8-aryl-2-(1-chloro-2-hydroxy-3-propyl)thio-9-cyano-6-methyl-1,4-dihydropyridines were obtained by treatment of 1,4-dihydropyridine-2(3H)-thiones with epichlorohydrin in the presence of sodium bicarbonate. When treated with NaOMe, these compounds are readily intramolecularly alkylated with formation of 7-acetyl-8-aryl-3-hydroxy-9-cyano-6-methyl-3,4-dihydro-2H,8H-pyrido[2,1-b]-[1,3]thiazines. We have studied amination of 2-(1-chloro-2-hydroxy-3-propyl)thio-1,4-dihydropyridines and acylation of 3-hydroxy-3,4-dihydro-2H,8H-pyrido[2,1-b][1,3]thiazines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1394–1399, September, 2005.     

Synthesis of Some New Fused and Polyfused [1,2,4]Triazolo-[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazepines

7-[1,3-Dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine-6,8-dione and 7-[5-oxo-1,3-dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4-b][1,3,4]-thiadiazepine-6,8-diones were obtained by treating 3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo-[3,4-b][1,3,4]thiadiazepine-6,8-diones with CS₂ and chloroacetyl chloride, respectively. Treatment of the above compounds with mercaptoacetic acid gave 1,2-dibromoethane or the corresponding spiro polyfused heterocycles. Some other triazolothiadiazepine derivatives including spiro polyfused compounds were also synthesized. __________ Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1256–1264, August, 2005.     

Synthesis and Antiproliferative Activity of Some Newly Synthesized Pyrazolopyridine Derivatives

Russian Journal of General Chemistry - A series of pyrazolopyridine derivatives is synthesized from emyl-4-amino-6-memyl-1-(mphtha[1,2-d]-[1,3]tmazol-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate...     

Synthesis of disubstituted imidazo[4,5-b]pyridin-2-ones

Regioselective palladium-catalyzed amination of 2-chloro-3-iodopyridine followed by a subsequent palladium-catalyzed amination leads to 2,3-diaminopyridines. Treatment with triphosgene affords highly functionalized unsymmetrical imidazo[4,5-b]pyridin-2-ones in just three synthetic steps. A two-step synthesis of pseudosymmetrically disubstituted imidazo[4,5-b]pyridin-2-ones, 1,4-disubstituted pyrido[2,3-b]pyrazinediones, and 1,3-disubstituted thiadiazolo[3,4-b]pyridin-2-ones is also described.     

Synthesis of pyrazolo[3,4-c]isoquinoline and pyrazolo[3,4-b]pyridine derivatives from azomethines and CH-acidic compounds

Summary Donor substituted arylidene aminopyrazoles1a–c and CH-acidic 1,3-dicarbonyl compounds2a–e give in ethanol in an addition/cyclization reaction pyrazolo[3,4-c]isoquinolines4a–i and pyrazolo[3,4-b]pyridine derivatives5a,b, respectively. Using ethyl cyanoacetate as CH-acidic component, cinnamate6 and the cyano substituted pyrazolo[3,4-b]pyridine7 are formed.

---

Synthese von Pyrazolo[3,4-c]isochinolin- und Pyrazolo[3,4-b]pyridin-Derivaten aus Azomethinen und CH-aciden Verbindungen

Zusammenfassung Die Reaktion der donorsubstituierten Aryliden-aminopyrazole1a–c mit den CH-aciden 1,3-Dicarbonylverbindungen2a–e führt in einer Additions/Cyclisierungsreaktion zu den Pyrazolo[3,4-c]isochinolin-4a–i bzw. Pyrazolo[3,4-b]pyridin-Derivaten5a,b. Verwendet man Cyanessigester als CH-acide Komponente, werden der Zimtsäureester6 und das cyanosubstituierte Pyrazolo[3,4-b]pyridin7 gebildet.

     

Basen-induzierte umwandlung des anellierten pyrrolo-systems in das pyridazin-system

Treatment of substituted 1,3-Bishydrazino-2-tert-butyl-pyrrolo[3,4-b]chinoxalines with aqueous sodium hydroxide leads to the formation of 6-membered 1,2-Dihydro-pyridazino[4,5-b]chinoxalines. The base induced solvolysis is followed by ring opening and ring closure.     

Preparation of new nitrogen-bridged heterocycles. 59. Syntheses and intramolecular interactions of 3-(acylmethylthio)- and 3-[(3-ethoxycarbonyl-2-propenyl)thio]thieno[3,4-b]indolizine derivatives

Various thieno[3,4-b]indolizine derivatives having an acylmethylthio or (3-ethoxycarbonyl-2-propenyl)thio group at the 3-position which could not be obtained by a conventional method were prepared by a new procedure using cyanoethyl group as a protecting group and their intramolecular arene-pi interactions were investigated. In the (1)H-NMR spectra of these thieno[3,4-b]indolizines, the low-field shifts (delta 0.10-0.33 ppm) for the 5-protons were observed in comparison with those of 3-(methylthio)thieno[3,4-b]indolizines as a standard. The UV spectra also exhibited a characteristic absorption band at 425-445 nm attributable to the arene-pi interaction but their intensities were generally lower than those of 3-(arylmethylthio)thieno[3,4-b]indolizines. In their X-ray analyses, the anti conformation for 3-(acylmethylthio)thieno[3,4-b]indolizines and the gauche one for the 3-(3-ethoxycarbonyl-2-propenyl)thio derivatives were exhibited.     

A highly selective fluorescence chemosensor for Pb(II) in neutral buffer aqueous solution

A 3,4-dimethylthieno[2,3-b]thiophene-based fluorogenic probe bearing benzo[d]-thiazole-2-thio unit (sodium 3,4-bis ((benzo[d]thiazol-2-ylthio)methyl) thieno [2, 3-b]thio-phene-2, 5-dicarboxylate) was developed as a novel fluorescent chemosensor with high selectivity towards Pb(II) over other cations tested. The new probe exhibited good water solubility and only sensed Pb(II) among metal ions examined in neutral 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer solution. The selectivity and sensitivity of fluorogenic probe to Pb(II) were discussed on the basis of experimental results.     

C–H Arylation using acyl thiourea ligands: Applications in the synthesis of 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles

Synthesis of a series of new 3,6-diaryl-[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazoles(5a–o) was achieved by phophine free, C–H arylative cross-coupling of 6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles(4a–o)with suitably substituted iodoanilines using 1-(2-naphthoyl)-3-(4-bromophenyl)thiourea as a ligand.The requisite triazolothiadiazoles(4a–o) were obtained by the condensation of 4-amino-1,2,4-triazole-3-thiol(3) with suitably substituted aromatic acids in the presence of phosphoryl chloride.     

Regioselectivity of cyclization of 3-allyl(propargyl)sulfanyl-5<Emphasis Type="Italic">H</Emphasis>-[1,2,4]triazino[5,6-<Emphasis Type="Italic">b</Emphasis>]indoles

The interaction of 3-allylsulfanyl-5H-[1,2,4]triazino[5,6-b]indole with iodine led to 1-iodomethyl-1,2-dihydro[1,3]thiazolo[2',3':3,4][1,2,4]triazino[5,6-b]indol-11-ium pentaiodide with an angular structure, on the basis of which 1-iodomethyl-1,2-dihydro[1,3]thiazolo-, 1-methylidene-1,2-di-hydro[1,3]thiazolo, and 1-methyl[1,3]thiazolo derivatives were obtained. The intramolecular cyclization of 3-propargyl(allyl)sulfanyl-5H-[1,2,4]triazino[5,6-b]indoles under the influence of concentrated sulfuric acid led to linear annelated products:3-methyl[1,3]thiazolo[3',2':2,3][1,2,4]tri-azino[5,6-b]indole or its 2,3-dihydro derivative.     

A new route to benzo[4,5]cyclohepta[1,2-b]naphthalenes: synthesis of radermachol

[formula: see text] Condensation of 3-phenylsulfonyl-1,3-isobenzofuranone (3) with benzocyclohept-6,7-en-5-ones such as 4 and 15 provides a straightforward, general method for synthesis of functionalized benzo[4,5]cyclohepta[1,2-b]naphthalenes (e.g., 5 and 16). This finding was used to achieve a brief and efficient preparation of 6,7-benzo-3,4-(1,4-dimethoxy-2,3-naphtho)-1,5-dioxosuberane (2), an established intermediate to the naturally occurring red pigment radermachol (1).     

3,4-二氢-1H-2-苯并吡喃衍生物化合成

3,4-二氢-1 H-2-苯并吡喃也俗称异色满(isochroman)。近年来,将该类化合物引入到药物合成中的研兖引起了人们的兴趣。虽然,已经合成出许多具有镇痛、降血压、抗组胺。和抗肿瘤等药理活性的3,4-二氢-1 H-2-苯并吡喃类化物,合但大都为异色满环上的1,3,4位取代衍生物或者螺环化合物,关于并杂环合成方面的研究至今不多见,作者前     

Synthesis of dihydrodiol metabolites implicated in the mechanism of carcinogenesis of phenanthro[4,3-b][1]benzothiophene and phenanthro[3,4-b][1]benzothiophene,the polycyclic sulfur heterocycles with a "Fjord" structure

Dihydrodiols, which are potential proximate carcinogens of phenanthro[4,3-b][1]benzothiophene (3) and phenanthro[3,4-b][1]benzothiophene (4) and possess a "fjord" structure, were synthesized. The dihydrodiols synthesized were trans-3,4-dihydroxy-3,4-dihydrophenanthro[4,3-b][1]benzothiophene (5) and trans-3,4-dihydroxy-3,4-dihydrophenanthro[3,4-b][1]benzothiophene (6). The precursors to the dihydrodiols 5 and 6 were 3-methoxyphenanthro[4,3-b][1]benzothiophene (11) and 3-methoxyphenanthro[3,4-b][1]benzothiophene (16). Compound 11 was obtained via Suzuki cross-coupling reaction of easily accessible starting materials. However, this synthetic strategy utilizing Suzuki reaction for the preparation of 16 was comparatively less productive than that described previously due to time-consuming synthesis of the starting material(s), and extremely poor yield associated with cyclization of the epoxide 15 to 16. The methoxy derivatives 11 and 16 were converted to the corresponding dihydrodiols 5 and 6 by a sequence involving demethylation, oxidation, and reduction. The trans-stereochemistry of the dihydrodiols was established by (1)H NMR, which indicated a large coupling constant between vicinal carbinol protons. The UV spectra of the dihydrodiols 5 and 6 are presented.     

Synthesis of Some 3-Substituted 1,2-Dihydroindoles

The reaction of 4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6-methyl carboxylate 2 with hydrazine hydrate in methanol gave 4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6-carbonylhydrazine 3. Furthermore, the reaction of 3 with carbon disulfide and then hydrazine hydrate afforded 3-[6-(4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4-oxo-1,3-thiazin-2-yl] hydrazone-1,3-dihydroindol-2-one 5. the latest reacted with DMAD to give {6-hydroxy-3-[4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6yl]-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-7-ylidene}methoxycarbonylmethylene 6.     

Some cyclization reactions of 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one: preparation and computational analysis of non symmetrical zwitterionic biscyanines

Regioselective nucleophilic addition of bisnucleophiles 1,2-benzenediamine, 2-amino-benzenethiol, and N-phenyl-1,2-benzenediamine to 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (1) at C6 followed by intramolecular cyclocondensation at the C7 carbonyl afforded highly coloured tetracenes 1,3-diphenyl-1,6-dihydro-[1,2,4]triazino[5,6-b]phenazin-4-ium 4-methylbenzenesulfonate (12), 1,3-diphenyl-1H-[1,2,4]triazino[6,5-b]phenothiazine (14) and 1,3,11-triphenyl-1,6-dihydro-[1,2,4]triazino[5,6-b]phenazin-11-ium 4-methylbenzenesulfonate (15), respectively. Neutralization of the latter with alkali gave the free base 1,3,11-triphenyl-1H-[1,2,4]triazino[5,6-b]phenazin-11-ium-6-ide (16). Furthermore, the benzotriazinone 1 reacts with dimethyl malonate to give 6-(methoxycarbonyl)-7-oxo-1,3-diphenyl-7H-benzofuro[5,6-e][1,2,4]triazin-1-ium-4-ide (17) in 74% yield, while with S(4)N(4) [5,6-c]-thiadiazolo-7-oxo-1,3-diphenyl-1,2,4-benzotriazine (22) was formed in 15% yield. The free bases 16 and 17 display negative solvatochromism, which supports charge separated ground states similar to those of zwitterionic biscyanines, and DFT calculations at the UB3LYP/6-31G(d) level afford ΔE(ST) values of -13.6 and -18.7 kcal mol(-1), respectively that strongly favour the singlet ground state. All ring systems described are new and fully characterized.