Evaluation of N‐hydroxymethylphthalimide in alkaline medium: Novel entry to the tricyclic [1,3]oxazepine core via an intramolecular π and O‐cationic cyclization

Fused isoindolo[1,3]benzo(or thieno)oxazepines 8a,b and one of their positional isomers aromatic tricyclic N,O‐acetals 13b are reported to occur efficiently in a three‐step sequence from N‐hydroxy‐methylphthalimide (6) . The key step of this methodology is the intramolecular arylation of an endocyclic and/or exocyclic N‐acyliminium cation. The mechanism leading to these species, in particular to a tricyclic lactam 13b , is discussed.     

Synthesis of Novel 7‐methylene‐6,7‐dihyrobenzo[f]Benzo[4,5]Imidazo[1,2‐d][1,4]Oxazepines via Base‐mediated Regioselective Intramolecular Hydroamination

A versatile and transition metal‐free approach for the synthesis of new 7‐methylene‐6,7‐dihyrobenzo[f]benzo[4,5]imidazo[1,2‐d][1,4]oxazepines were developed by an efficient 7‐exo‐dig regioselective hydroamination of 2‐(2‐(prop‐2‐yn‐1‐yloxy)phenyl)‐1H‐benzo[d]imidazole in the presence of potassium carbonate in DMF at 90°C.     

Highly Site Selective Formal [5+2] and [4+2] Annulations of Isoxazoles with Heterosubstituted Alkynes by Platinum Catalysis: Rapid Access to Functionalized 1,3‐Oxazepines and 2,5‐Dihydropyridines

Platinum‐catalyzed formal [5+2] and [4+2] annulations of isoxazoles with heterosubstituted alkynes enabled the atom‐economical synthesis of valuable 1,3‐oxazepines and 2,5‐dihydropyridines, respectively. Importantly, this Pt catalysis not only led to unique reactivity dramatically divergent from that observed under Au catalysis, but also proceeded via unprecedented α‐imino platinum carbene intermediates.     

Novel calix[4]cryptands: “Mappemonde II” and “Mill II”

Two novel calix[4]cryptands were synthesized from 1,3‐alternate calix[4]bis‐azacrown. “Mappemonde II” consists of one 1,3‐calix[4]bis‐azacrown wrapped by a benzo‐crown ether loop. “Mill II” is composed of two 1,3‐calix[4]bis‐azacrowns linked by two benzo‐crown ether strands.     

Synthesis of Spiro[benzo[h]chromene-4,3′-indoles] and Spiro[benzo[f]chromene-1,3′-indoles]

Russian Journal of Organic Chemistry - New spiro heterocycles, spiro[benzo[h]chromene-4,3′-indoles] and spiro[benzo[f]chromene-1,3′-indoles], have been synthesized in 50–60% yield...     

New synthetic approaches to polycyclic aromatic hydrocarbons and their carcinogenic oxidized metabolites: derivatives of benzo[s]picene, benzo[rst]pentaphene, and dibenzo[b,def]chrysene

A new synthetic approach to polycyclic aromatic compounds is described that entails in the key steps double Suzuki coupling of PAH bisboronic acid derivatives with o-bromoaryl aldehydes to furnish aryl dialdehydes that are converted to larger polycyclic aromatic ring systems by either (a) conversion to diolefins by Wittig reaction followed by photocyclization or (b) reductive cyclization with triflic acid and 1,3-propanediol. This synthetic method provides convenient access to as many as three different polycyclic aromatic ring systems from a single Suzuki coupled intermediate. It was utilized to synthesize substituted derivatives of benzo[s]picene, benzo[rst]pentaphene, dibenzo[b,def]chrysene, and 13,14-dihydro-benz[g]indeno[2,1-a]fluorene, as well as the putative carcinogenic bisdihydrodiol metabolites of benzo[s]picene, benzo[rst]pentaphene, and dibenzo[b,def]chrysene.     

Synthesis of 1,3-disubstituted benzo[c]thiophene analogs containing benzo[b]thiophene/benzo[b]pyrrole

The synthesis of 1,3-disubstituted benzo[c]thiophene analogs incorporating benzo[b]thiophene/benzo[b]pyrrole units is described.     

Synthesis and cytotoxic activity of benzopyranoxanthone analogues of benz.

Condensation of 3-hydroxy-2-naphthalenecarboxylic acid with phloroglucinol afforded 1,3-dihydroxy-12H-benzo[b]xanthen-12-one. Construction of an additional dimethylpyran ring onto this skeleton, by alkylation with 3-chloro-3-methyl-1-butyne followed by Claisen rearrangement, gave access to a series of benzo[b]pyrano[2,3-i]xanthen-6-ones and benzo[b]pyrano[3,2-h]xanthen-7-ones related to psorospermine and benzo[b]acronycine. In contrast with what is observed in the pyridoacridone and benzopyridoacridone series, the linear benzo[b]-pyrano[2,3-i]xanthen-6-one derivatives were more potent than their angular benzo[b]pyrano[3,2-h]xanthen-7-one isomers. cis-3,4-Diacetoxy-5-methoxy-2,2-dimethyl-3,4-dihydro-2H,6H-benzo[b]pyrano[2,3-i]xanthen-6-one, the most active among the new compounds, was more potent than acronycine in inhibiting the proliferation of L1210 murine leukemia cells.     

Synthesis and reactions of 2,4-disubstituted benzo[b]furano-, benzo[b]thieno- and indolo[3,2-d]-1,3-oxazinium salts

Under acid catalyzed acylation 3-acetamidobenzo[b]furan, -benzo[b]tkiophene, and indole undergo heterocyclization to condensed 1,3-oxazinium salts. Treatment of the salts with ammonium acetate in acetic acid gives the corresponding benzo[b]furano- and benzo[b]thieno[3,2-d]pyrimidines and 2-acetyl-3-acetamidoindole gives pyrimido [5,4-d] indole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1569–1571, November, 1990.     

Benzo[g]isoquinolinium benzoylmethylids

Stable benzo[g]isoquinolinium methylids were obtained from N-phenacylbenzo[g]isoquinolinium bromides and two of its benzene ring-substituted analogs. The first of these quaternary salts was converted to benzo[g]isoquinolinium dibenzoylmethylid. 3-Benzoyl-l,2-dicarbomethoxynaphth[2,3-g]indolizine was obtained from the same salt with dimethyl acetylenedicarboxylate (via a 1,3-dipolar cycloaddition reaction). Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 806–807, June, 1980     

Synthesis and characterization of benzo[c]thiophene analogs incorporating benzo[b]thiophene/1-hexylindole/benzo[b]furan

Synthesis of 1,3-disubstituted benzo[c]thiophene analogs incorporating heterocycles such as benzo[b]thiophene/1-hexylindole/benzo[b]furan and thiophene units is described. Optical and electrochemical studies of the benzo[c]thiophene analogs are also reported.     

The synthesis and cytotoxic evaluation of a series of benzodioxole substituted titanocenes

Using 6‐benzo[1,3]dioxolefulvene ( 1a ), a series of benzodioxole substituted titanocenes was synthesized. The benzyl‐substituted titanocene bis[(benzo[1,3]dioxole)‐5‐methylcyclopentadienyl] titanium (IV) dichloride ( 2a ) was synthesized from the reaction of Super Hydride with 1a . An X‐ray determined crystal structure was obtained for 2a . The ansa‐titanocene {1,2‐di(cyclopentadienyl)‐1,2‐di‐(benzo[1,3]dioxole)‐ethanediyl} titanium(IV) dichloride ( 2b ) was synthesized by reductive dimerisation of 1a with titanium dichloride. The diarylmethyl substituted titanocene bis(di‐(benzo[1,3]dioxole)‐5‐methylcyclopentadienyl) titanium(IV) dichloride ( 2c ) was synthesized by reacting 1a with the para‐lithiated benzodioxole followed by transmetallation with titanium tetrachloride. When titanocenes 2a–c were tested against pig kidney (LLC‐PK) cells inhibitory concentrations (IC₅₀) of 2.8 × 10^?4, 1.6 × 10^?4 and 7.6 × 10^?5 M , respectively, were observed. These values represent improved cytotoxicity against LLC‐PK, when compared with unsubstituted titanocene dichloride, but are not as impressive as values obtained for titanocenes previously synthesized using the above methods. Copyright © 2006 John Wiley & Sons, Ltd.     

One ‐ pot synthesis of novel sulfur and selenium heterocycles by directed ortho‐lithiation

A procedure for the synthesis of benzo[e][1,3]thiazine‐2,4‐diones from benzamides by directed lithiation and sequential treatment with sulfur and phosgene is reported. Use of thiophosgene afforded 2‐thioxo‐2,3‐dihydro‐benzo[e][1,3] thiazin‐4‐ones. Application of this methodology to benzenesulfonamides afforded the previously unknown 1,1‐dioxo‐1,2‐dihydro‐1,4‐dithia‐2‐aza‐naphthalen‐3‐one ring system with phosgene and the 1,2‐dioxo‐2‐phenyl‐2,3‐dihydrobenzo[e][1,4,2]dithiazine‐3‐one ring system with thiophosgene. Use of selenium in place of sulfur afforded the novel analogous selenium heterocycles, however in the case of benzamides the use of selenium and phosgene afforded benzo[d]isoselenazol‐3‐ones unexpectedly.     

Theophylline as a new and green catalyst for the one-pot synthesis of spiro[benzo[a]pyrano[2,3-c]phenazine] and benzo[a]pyrano[2,3-c]phenazine derivatives under solvent-free conditions

A green, convenient, high yielding and one-pot procedure for the synthesis of novel spiro[benzo[a]pyrano[2,3-c]phenazine] derivatives by domino multi-component condensation reaction between 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamines, ninhydrine, and malononitrile in the presence of a catalytic amount of 1,3-dimethyl-7H-purine-2,6-dione (theophylline) as an expedient, eco-friendly and reusable solid base catalyst under thermal, microwave irradiation and solvent-free conditions. This procedure has also been applied successfully for the synthesis of benzo[a]pyrano[2,3-c]phenazines.     

Tandem Pummerer-Diels-Alder Reaction Sequence. A Novel Cascade Process for the Preparation of 1-Arylnaphthalene Lignans

The alpha-thiocarbocation generated from the Pummerer reaction of an o-benzoyl-substituted sulfoxide is intercepted by the adjacent keto group to produce an alpha-thio isobenzofuran as a transient intermediate which undergoes a subsequent Diels-Alder cycloaddition with added dienophiles. Acid-catalyzed ring-opening of the cycloadduct followed by aromatization gave an arylnaphthalene derivative. With acetylenic dienophiles, the tandem cyclization-cycloaddition sequence provided tetralones which result from a pinacol-type rearrangement of the primary cycloadducts. The versatility of the approach is highlighted through the synthesis of taiwanin C and E and justicidin E. The alpha-thiocarbocation generated from the Pummerer reaction of benzo[1,3]dioxol-5-yl-[6-[(ethylsulfinyl)methyl]benzo[1,3]dioxol-5-yl)methanone is intercepted by the adjacent keto group to produce an alpha-thioisobenzofuran as a transient intermediate which undergoes a subsequent Diels-Alder cycloaddition with dimethyl maleate. The initially formed Diels-Alder cycloadduct was readily converted to 5-benzo[1,3]dioxol-5-yl-8-(ethylthio)naphtho[2,3-d][1,3]dioxole-6,7-dicarboxylic acid dimethyl ester by loss of water on treatment with p-toluenesulfonic acid. Desulfurization of the thionaphthalene with Ra/Ni followed by hydrolysis of the less hindered methyl ester afforded 5-benzo[1,3]dioxol-5-ylnaphtho[2,3-d][1,3]dioxole-6,7-dicarboxylic acid 6-methyl ester which was further transformed into taiwanin C and justicidin E in good yield. Oxidation of the initial Diels-Alder cycloadduct with NaIO(4) in the presence of RuCl(3) followed by extrusion of ethyl sulfinate gave a naphthol derivative which can be converted into taiwanin E.     

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.     

Condensation of fluorosubstituted benzaldehydes with amines and cyclic 1,3-diketones

Condensation of fluorosubstituted benzaldehydes with 2-naphthyl or 6-quinolylamine and cyclic β-diketones (,3-cyclohexanedione, dimedone, and 1,3-indandione) provided new fluoroderivatives of benzo[a]-acridine, 4,7-phenanthroline, and benzo[f]indeno[1,2-b]quinoline. Forming in the course of the reaction fluorophenylmethylene-2-naphthyl-(or 6-quinolyl)amines, arylbis(cyclohexane-1,3-dion-2-yl)methanes, and 2-(fluorophenylmethylene)-1,3-indandiones were isolated.     

2-substituted benzofuran fragment ion formation in the electron ionization mass spectra of 6-alkyl- and 6-aryldibenzo(d,f)(1,3)dioxepine derivatives. 1. Spirocyclization of the molecular ions in the gas phase

The formation of 2-substituted benzo[b]furan ions in the electron ionization (EI) mass spectra of a series of 6-alkyl- and 6-aryldibenzo(d,f)(1,3)dioxepines has been studied by means of exact mass measurements and multiple-stage mass spectrometry conditions using an ion trap mass spectrometer. The proposed mechanism of formation of benzo[b]furan ions requires the formation of a spirocyclic cyclohexadienone system, which undergoes elimination of a cyclopentadienone molecule. A parallel with the chemical conversion of arylmethyl-substituted dibenzo(d,f)(1,3)dioxepines into an analogous spirocyclic system was also underlined.     

Na‐Y Zeolite,a convenient and recyclable catalyst for the facile one‐pot synthesis of spiro dibenzo[b,e][1,4]oxazepine scaffolds

A new method for the synthesis of Spiro dibenzo[b,e][1,4]oxazepines that involves a three‐component reaction of isatins, 2‐amino phenols and cyclic‐1,3‐diketones has been developed. This protocol employs Na‐Y zeolite nanopowder as a heterogeneous catalyst and does not require the presence of any additivies or strong acid–base condition. Na‐Y zeolite nanopowder was synthesized through a simple hydrothermal procedure and it was characterized using different array of shophisticated techniques. Key features of the reaction include a recyclable catalyst and a wide scope of possible substrates.     

Benzo‐Annulated Steroids: Synthesis of Octahydro‐indeno‐phenanthrenes by Formal [3+3] Cyclocondensation Reaction with 1,3‐Bis[(trimethylsilyl)oxy]buta‐1,3‐dienes

Octahydro‐indeno‐phenanthrenes, benzo‐annulated steroids, were prepared by formal [3+3] cyclocondensation reaction of 1,3‐bis[(trimethylsilyl)oxy]buta‐1,3‐dienes with the silyl enol ether of 16‐formylestrone methyl ether.