Facile Route to the Synthesis of 1,3-Diazahetero-Cycle-Fused [1,2-a]Quinoline Derivatives via Cascade Reactions.
ABSTRACT: A one-step protocol without transition-metal catalysts with simple post-treatment for the synthesis of 1,3-diazaheterocycle-fused [1,2-a]quinoline derivatives via the cascade reaction of 2-fluorobenzaldehyde (1) and heterocyclic ketene aminals (2) was developed. In the one-step cascade reaction, C=C and C-N bonds were constructed, and the targeted compound can be efficiently obtained by filtering without column chromatography. This protocol describes a valuable route to concisely and feasibly obtain 1,3-diazaheterocycle-fused [1,2-a]quinoline derivatives. The synthetic methodology is particularly attractive because of the following features: low-cost solvent, mild temperature, atom economy, high yield, and potential biological activity of the product.
Project description:An efficient and convenient method to synthesize highly functionalized 3,7'-bisindole derivatives has been developed via a Michael addition and cyclic condensation reaction of heterocyclic ketene aminals (HKAs) with 2-(1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione derivatives in ethanol-based solvents at room temperature. This strategy provides an efficient, environmentally friendly approach for easy access to various novel 3,7'-bisindole derivatives in moderate to good yields.
Project description:The synthesis of new 3-dithiocarbamic flavonoids has been accomplished by the reaction of the corresponding 2-hydroxyaryl dithiocarbamates with aminals. These flavonoids were obtained as a mixture of diastereoisomers, the anti isomer being the major one. The heterocyclization of these compounds provided novel tricyclic flavonoids bearing a 1,3-dithiolium-2-yl ring fused at the 3,4-carbon positions of the benzopyran moiety.
Project description:Neocryptolepine, which is a kind of tetracyclic indoloquinoline alkaloid, exhibits the inhibition of topoisomerase II and shows antiproliferative activity. The present study describes the synthesis and antiproliferative evaluation of several neocryptolepine analogues carrying a branched, functionalized dibasic side chain at C11. These 2-substituted 5-methyl-indolo[2,3-b]quinoline derivatives were prepared by nucleophilic aromatic substitution (SNAr) of 11-chloroneocryptolepines with appropriate 1,2- and 1,3-diamines. Some of the 11-(?-aminoalkylamino) derivatives were further transformed into 11-ureido and thioureido analogues. Many of the prepared neocryptolepine derivatives showed submicromolar antiproliferative activity against the human leukemia MV4-11 cell line. Among them, 11-(3-amino-2-hydroxy)propylamino derivatives 2h and 2k were the most cytotoxic with a mean IC50 value of 0.042 ?M and 0.057 ?M against the MV4-11 cell line, 0.197 ?M and 0.1988 ?M against the A549 cell line, and 0.138 ?M and 0.117 ?M against the BALB/3T3 cell line, respectively.
Project description:The Friedländer reactions of acetylbenzenes and 2-acetylpyridine with 3-aminonaphthalene-2-carbaldehyde afforded the corresponding 2-phenylbenzo[g]quinoline and 2-(pyrid-2-yl)benzo[g]quinoline, respectively. The same reactions of 3-aminonaphthalene-2-carbaldehyde with 1,2-, 1,3-, 1,4-di- and 1,3,5-triacetylbenzenes, however, afforded a series of corresponding (benzo[g]quinolin-2-yl)benzenes as new N,C-bidentate and unexpected benzo[g]quinoline. Crystallinity, thermal properties, absorption and emission spectral properties of the products were studied.
Project description:A one-pot strategy for efficient and facile synthesis of C,B-substituted carborane-fused N-polyheterocycles is reported. A rhodium catalyzed cascade cyclization of carboranyl N-arylimines with vinyl ketones enables the effective construction of three new B-C and C-C bonds in one reaction. Both carboranyl B-H and aryl C-H bonds are sequentially activated, leading to a series of previously unavailable C,B-substituted carborane-fused cyclopenta[b]quinoline derivatives, for potential applications in pharmaceuticals and materials, in a step-economical manner. The successful isolation and structural identification of a key intermediate provide solid evidence for the reaction mechanism, involving a tandem sequence of regioselective B-H activation, alkene insertion, nucleophilic cyclization, C-H activation, nucleophilic cyclization, dehydration and oxidative aromatization.
Project description:Strained azirinium ylides derived from 2H-azirines and ?-diazoketones under Rh(II)-catalysis can undergo either irreversible ring opening across the N-C2 bond to 2-azabuta-1,3-dienes that further cyclize to 2H-1,4-oxazines or reversibly undergo a 1,5-cyclization to dihydroazireno[2,1-b]oxazoles. Dihydroazireno[2,1-b]oxazoles derived from 3-aryl-2H-azirines and 3-diazoacetylacetone or ethyl diazoacetoacetate are able to cycloadd to acetyl(methyl)ketene generated from 3-diazoacetylacetone under Rh(II) catalysis to give 4,6-dioxa-1-azabicyclo[3.2.1]oct-2-ene and/or 5,7-dioxa-1-azabicyclo[4.3.1]deca-3,8-diene-2-one derivatives. According to DFT calculations (B3LYP/6-31+G(d,p)), the cycloaddition can involve two modes of nucleophilic attack of the dihydroazireno[2,1-b]oxazole intermediate on acetyl(methyl)ketene followed by aziridine ring opening into atropoisomeric oxazolium betaines and cyclization. Azirinium ylides generated from 2,3-di- and 2,2,3-triaryl-substituted azirines give rise to only 2-azabuta-1,3-dienes and/or 2H-1,4-oxazines.
Project description:We have synthesized and theoretically calculated 5-methylisoindolo[2,1-<i>a</i>]quinoline derivatives as novel near-infrared absorption dyes via a ruthenium-catalyzed one-pot metathesis/oxidation/1,3-dipolar cycloaddition protocol. The reactivity in 1,3-dipolar cycloaddition was governed by the electronic effect of aromatic ring substituents. Substrates with an electron-withdrawing group on the aromatic ring afforded higher yields. The maximal absorption wavelength of 3,5-dimethyl-11-phenylisoindolo[2,1-<i>a</i>]quinoline-7,10-dione and 11-(4-methoxyphenyl)-5-methylisoindolo[2,1-<i>a</i>]quinoline-7,10-dione in MeOH increased to 736 and 737 nm, although that of <b>3a</b> was 727 nm.
Project description:Domino strategy has been used for the synthesis of 2H-pyrido[1,2-a]pyrimidin-2-ones. Four sequential reactions: aza-Michael addition, water elimination, intramolecular acyl substitution, and [1,3]-H shift were observed in this domino protocol. Hexafluoroisopropanol is used as a promotor and recyclable solvent in this cascade process. Availability of inexpensive 2-aminopyridines and wide variety of Michael acceptors such as commercially available acrylates and unactivated Baylis-Hillman adducts makes this methodology a huge reservoir of novel fused N-heterocycles as bioactive and potential therapeutic agents. The reaction mechanism has been proposed and rationalized by density functional theory calculation. Products are obtained up to 95% yield.
Project description:Rhodium catalyzed synthesis of substituted tetrahydropyridines was accomplished from readily accessible thio-tethered <i>N</i>-sulfonyl-1,2,3-triazoles. The reaction involves tandem rhodium catalyzed 1,2-sulfur migration in ?-thio-?-diazoimines, generated from thio-tethered <i>N</i>-sulfonyl-1,2,3-triazoles, to thio-substituted 1-azadiene and subsequent self aza-Diels-Alder reaction. Interestingly, the methodology was effectively extended to the synthesis of fused tetrahydropyridines, dihydropyridines and cyclohexenes through the <i>in situ</i> trapping of the intermediate, 1-azadiene, with various dienophiles such as enol ether, enamine, ketene <i>S</i>,<i>S</i>-acetal, alkyne, alkene and diene. Furthermore, the direct conversion of propargyl sulfides to (fused)-tetrahydropyridines was also achieved through the successful integration of copper and rhodium catalysts in one-pot.
Project description:An efficient access to the tetracyclic-fused quinoline systems, 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives 4a-l, is described, involving the intramolecular Friedel-Crafts acylation reaction of 2-(phenoxymethyl)-4-phenylquinoline-3-carboxylic acid derivatives 3a-l aided by the treatment with PPA (polyphosphoric acid) or Eaton's reagent. The required starting compound (2) was obtained by Friedländer reaction of 2-aminobenzophenone (1) with 4-chloroethylacetoacetate by using CAN (cerium ammonium nitrate, 10 mol %) as catalyst at room temperature. The substrates 3a-l were prepared through one-pot reaction of ethyl 2-(chloromethyl)-4-phenylquinoline-3-carboxylate (2) and substituted phenols. Our developed strategy, involving a three-step route, offers easy access to tetracyclic-fused quinoline systems in short reaction times, and the products are obtained in moderate to good yields.