Efficient Regioselective Synthesis Research Articles

Regioselective synthesis of thiophene fused sultam derivatives via iodocyclization approach and their application towards triazole linker

An efficient regioselective synthesis of 4-iodo-2,3-disubstituted-2H-thieno[3,2-e][1,2]thiazine-1,1-dioxide derivatives via iodocyclization approach using iodine under mild reaction condition described herein. This coupling–iodocyclization strategy tolerated a variety of functional groups such as alkyl, cycloalkyl, phenyl producing the six-membered heterocyclic ring selectively. The resulting 4-iodo-2,3-disubstituted-2H-thieno[3,2-e][1,2]thiazine-1,1-dioxide was coupled with a variety of boronic acids (Suzuki coupling) and activated alkenes (Heck coupling). The iodo group was utilized for Sonogashira coupling followed by efficient transformation to azido precursor, which was used for the synthesis of various thieno-sultam linked with triazole.

Regioselective synthesis of fused imidazo[1,2-a]pyrimidines via intramolecular C-N bond formation/6-endo-dig cycloisomerization.

An efficient regioselective cascade synthesis of N-fused imidazo heterocycles has been developed. This cascade transformation proceeds via a transition-metal (copper/silver) catalyzed coupling reaction between 2-aminobenzimidazole, aldehydes, and alkynes leading to the formation of propargylamine intermediate, which regioselectively undergoes 6-endo-dig cyclization through intramolecular N-H bond activation interceded C-N bond formation leading to highly functionalized imidazo[1,2-a]pyrimidines in good to excellent yields.

Regioselective synthesis of polycyclic aza-oxa and aza-oxa-thia heteroarenes as Colo-205 and HepG2 carcinoma cells growth inhibitors

An efficient regioselective synthesis of polycyclic diheteroaryl[b,d]pyrans and diheteroaryl[c,e][1,2]diazepines has been reported through ring transformation reactions of 2-oxo-2,5-dihydrothiochromeno[4,3-b]pyrans (3,4), 2-oxo-5,6-dihydro-2H-benzo[b]pyrano[2,3-d]oxepine/thiepine (8, 9) and 6-oxo-3,6-dihydro-2H-naphtho[1,2-b]pyrano[2,3-d]oxepine (15) by hydrazine, at ambient and reflux temperature. Nine compounds viz 5a,b; 10a,c,d; 12b; 13b; 16 and 1-methylthio-5,6-dihydrobenzo[f]quinoline (0.1–100 μM) were screened for their cytotoxicity in normal (IEC-6), carcinoma (Colo-205) and HepG2 cell lines. None of the compounds showed cytotoxicity in normal IEC-6 cells while 10a,d and 16 resulted in killing of Colo-205 cells with IC50 ranging 20–60 μM while 10c and 13b caused killing of HepG2 cells with IC50 values ranging 60–80 μM concentration. Further, 10a,d and 16 caused apoptosis through a cascade of mitochondrial pathway in Colo-205 cells indicating anticancerous potential against intestinal cancer. Interestingly, compounds 10c and 13b exhibited apoptosis through mitochondrial pathway in HepG2 cells suggesting anticancer activity against hepatic cancer.

A green, efficient and recyclable Fe+3@K10 catalyst for the synthesis of bioactive pyrazolo[3,4-b]pyridin-6(7H)-ones under "on water" conditions

An efficient regioselective one-pot three-component synthesis of 4-aryl-3-methyl-4,5-dihydro-1H-pyrazolo[3,4-b]pyridin-6(7H)-ones and their bis-derivatives (Table 3 and Fig. 2) catalyzed by Fe+3-K10 montmorillonite (Fe+3@K10) under the Sharpless conditions (“On water” contdiions) is described. This rapid method produced the products in short reaction times (10–15min) and excellent yields (87–95%). The antibacterial activity of the synthesized products was examined. Some products showed promising activities.

Toxicity and genotoxicity of the air polluted with compounds produced by heavy industry

An efficient regioselective one-pot three-component synthesis of 4-aryl-3-methyl-4,5-dihydro-1H-pyrazolo[3,4-b]pyridin-6(7H)-ones and their bis-derivatives (Table 3 and Fig. 2) catalyzed by Fe+3-K10 montmorillonite (Fe+3@K10) under the Sharpless conditions (“On water” contdiions) is described. This rapid method produced the products in short reaction times (10–15 min) and excellent yields (87–95%). The antibacterial activity of the synthesized products was examined. Some products showed promising activities.

DABCO catalyzed highly regioselective synthesis of fused imidazo-heterocycles in aqueous medium

An efficient regioselective synthesis of 3-aryl imidazo[1,2-a]pyridines, 5-aryl imidazo[2,1-b]thiazoles, and 3-aryl benzo[d]imidazo[2,1-b][1,3]thiazoles is described by the reaction of phenacyl bromide with heterocyclic amine in the presence of DABCO under aqueous medium. The method is applicable for a variety of substituted phenacyl bromides as well as 2-amino-heterocycles. An aqueous reaction medium, regioselectivity, mild reaction condition, and high yield of products are the important features of this protocol.

Ultrasonic irradiation assisted efficient regioselective synthesis of CF3-containing pyrazoles catalyzed by Cu(OTf)2/Et3N

BackgroundMost of the known approaches to the synthesis of CF3-containing organic compounds suffer from serious drawbacks. For example the starting materials required for these methods are rather difficult to obtain, or they are fairly toxic and inconvenient to work with and methods for direct fluorination and trifluoromethylation do not always allow the introduction of the CF3-group at the required position of a molecule.ResultsAn efficient and attractive regioselective synthesis of a series of novel pyrazoles containing the trifluromethyl moiety was achieved using Cu(OTf)2/Et3N as an efficient catalytic system under ultrasonic irradiation.ConclusionsCu(OTf)2/Et3N catalyst showed a great advantage over all the investigated catalysts, and the ultrasonic irradiation method offered high yields of pyrazoles in short reaction time compared with classical conditions. gHMBC spectra of the product were used to rationalize the observed regioselectivity.

Investigation of facet effects on the catalytic activity of Cu2O nanocrystals for efficient regioselective synthesis of 3,5-disubstituted isoxazoles

Cubic, octahedral, and rhombic dodecahedral Cu2O nanocrystals bound by respectively {100}, {111}, and {110} facets were successfully employed to catalyze the [3 + 2] cycloaddition reaction for the regioselective synthesis of 3,5-disubstituted isoxazoles. Surfactant-free nanocrystals having the same total surface area were used for the catalysis. Strongly facet-dependent organocatalytic activity has been observed. Rhombic dodecahedra with fully exposed surface copper atoms on the (110) planes are the most efficient catalysts, followed by octahedra and the least active nanocubes. The particles are also recyclable catalysts. Cu2O rhombic dodecahedra were also used for the syntheses of 3,5-disubstituted isoxazoles from a wide variety of aromatic imidoyl chlorides and terminal alkynes in ethanol at 50 °C with excellent yields. Furthermore, a one-pot multi-component synthetic approach was demonstrated to form isoxazoles directly from readily available aldehyde precursors. This work clearly shows that precise facet engineering of Cu2O crystals can lead to significantly improved organocatalytic efficiency.

ChemInform Abstract: Efficient Regioselective Synthesis and Potential Antitumor Evaluation of Isoxazolo[5,4‐b]pyridines and Related Annulated Compounds.

AbstractA variety of isoxazolopyridine derivatives and related compounds are synthesized starting from 5‐amino‐3‐methylisoxazole (I).

Discovery of 3H-imidazo[4,5-c]quinolin-4(5H)-ones as potent and selective dipeptidyl peptidase IV (DPP-4) inhibitors

In recent years, dipeptidyl peptidase IV inhibitors have been noted as valuable agents for treatment of type 2 diabetes. Herein, we report the discovery of a novel potent DPP-4 inhibitor with 3H-imidazo[4,5-c]quinolin-4(5H)-one as skeleton. After efficient optimization of the lead compound 2a at the 7- and 8-positions using a docking study, we found 28 as a novel DPP-4 inhibitor with excellent selectivity against various DPP-4 homologues. Compound 28 showed strong DPP-4 inhibitory activity compared to marketed DPP-4 inhibitors. We also found that a carboxyl group at the 7-position could interact with the residue of Lys554 to form a salt bridge. Additionally, introduction of a carboxyl group to 7-position led to both activity enhancement and reduced risk for hERG channel inhibition and induced phospholipidosis. In our synthesis of compounds with 7-carboxyl group, we achieved efficient regioselective synthesis using bulky ester in the intramolecular palladium coupling reaction.

Efficient Regioselective Synthesis of 3‐Iodoindole N‐Carboximidamides and N‐Carboximidoates by a Sequential Aza‐Wittig/Iodine Induced Cyclization

Abstract3‐Iodoindole N‐carboximidamides and N‐carboximidoates 4 were prepared regioselectively via a sequential aza‐Wittig/iodine induced cyclization, starting from easily accessible 2‐alkynylphenyl iminophosphorane, isocyanates, various nucleophiles and iodine.

ChemInform Abstract: An Efficient Regioselective Synthesis of Highly Functionalized 3‐Oxo‐2,3‐dihydro‐5H‐thiazolo[3,2‐a]pyrimidines via an Isocyanide‐Based Three‐Component Reaction.

AbstractThe uncatalyzed one‐pot reaction offers a direct approach to title compounds (IV), which are of potential synthetic and pharmaceutical interest.

An efficient regioselective sonochemical synthesis of novel 4-aryl-3-methyl-4,5-dihydro-1H-pyrazolo[3,4-b]pyridin-6(7H)-ones

Abstract An efficient ultrasound-assisted preparation of a series of novel 4-aryl-3-methyl-4,5-dihydro-1 H -pyrazolo[3,4-b]pyridin-6(7 H )-ones via the reaction of 5-amino-3-methyl-1 H -pyrazole, Meldrum's acid and various arylaldehydes using one-pot three-component approach is described. This rapid method produced the products in short reaction times (3–4 min) and excellent yields (87–95%).

Efficient Regioselective Synthesis and Potential Antitumor Evaluation of Isoxazolo[5,4‐b]pyridines and Related Annulated Compounds

The reaction of 5-amino-3-methylisoxazole with appropriate α,β-unsaturated ketones gave the corresponding isoxazolo[5,4-b]pyridines. Treatment of 1 with 2,6-dibenzylidenecyclohexanone or 2-benzylidenedimedone afforded the corresponding isoxazolo[5,4-b]quinoline derivatives. 4,6,8,9-Tetrahydroisoxazolo[5,4-b]quinolin-5-one derivative was also obtained by multicomponent condensation reaction of 1 with dimedone and benzaldehyde. Heterocyclic annulation of the isoxazolo[5,4-b]pyridine system was achieved via reaction of 1 with benzylidene derivatives of indandione, quinuclidone, pyrazolone, and oxazolone. A representative of some newly synthesized compounds was evaluated as antitumor agents.

An efficient regioselective synthesis of highly functionalized 3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidines via an isocyanide-based three-component reaction

We present a novel, convenient, and efficient method for synthesizing polysubstituted 3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidines via a three-component reaction. The zwitterions generated from the reaction of isocyanides and dialkyl acetylenedicarboxylates react with 2-imino-1,3-thiazolidin-4-one to produce the title compounds in good yields.

FeF3/I2-Catalyzed Synthesis of 4-Chalcogen-Substituted Arylamines by Direct Thiolation of an Arene C-H Bond

An efficient regioselective synthesis of 4-chalcogen-substituted­ arylamines by FeF3-catalyzed sulfenylation and selenation of arylamines has been developed. In the presence of FeF3 and I2, a variety of arylamines underwent the reaction with disulfides or diselenides to afford the corresponding 4-sulfenyl- or 4-selenenyl­arylamines in moderate to good yields.

ChemInform Abstract: MCM‐41 Catalyzed Efficient Regioselective Synthesis of β‐Aminoalcohol under Solvent‐Free Conditions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Microwave-Assisted Regioselective Synthesis of trans-1-Arenesulfonyl-2-ethoxycarbonyl-3-phenylazetidines

An efficient regioselective synthesis of trans-1-arenesulfonyl-2-ethoxycarbonyl-3-phenylazetidines has been achieved through microwave-assisted reactions of 1-arenesulfonylaziridines with dimethylsulfonium carboethoxymethylide using alumina as solid support.

ChemInform Abstract: Efficient Regioselective Synthesis of Indole N‐Carboximidamides and N‐Carboximidoates by a Sequential Aza‐Wittig/Ag(I)‐Catalyzed Cyclization.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Efficient Regioselective Synthesis of Indole N-Carboximidamides and N-Carboximidoates by a Sequential Aza-Wittig/Ag(I)-Catalyzed Cyclization

An efficient Ag(I)-catalyzed regioselective cyclization of (2-alkynylphenyl)guanidine or (2-alkynylphenyl)isourea to indole N-carboximidamides or N-carboximidoates has been developed. The approach has the advantages of high regioselectivity, mild reaction conditions, easily accessible starting materials, and good yields.