Dushyant Singh Raghuvanshi

Regioselective Hydrothiolation of Alkynes by Sulfonyl Hydrazides Using Organic Ionic Base–Brønsted Acid

A practical and novel approach has been developed for the synthesis of vinyl sulfides by the reaction of sulfonyl hydrazides with aryl/heteroarylacetylenes using a DBU-based ionic liquid. The system offers a new sulfur source for hydrothiolation and is endowed with green credentials.

Nickel-Mediated N-Arylation with Arylboronic Acids: An Avenue to Chan–Lam Coupling

An efficient use of NiCl(2)·6H(2)O, for the cross-coupling of arylboronic acids with various N-nucleophiles, has been demonstrated. The method is practical and offers an alternative to the corresponding Cu-mediated Chan-Lam process for the construction of the C-N bond.

Convenient MW-assisted synthesis of unsymmetrical sulfides using sulfonyl hydrazides as aryl thiol surrogate.

An efficient synthesis of unsymmetrical sulfides has been achieved via the cross-coupling reaction of aryl/het-aryl/benzyl halides with stable and easily workable sulfonyl hydrazides as thiol substitutes by means of [DBU][HOAc] and CuI under microwave irradiation.

An Expeditious Synthesis of Tetrahydro-1,2,4-triazolo[5,1-b]quinazolin-8(4H)-ones and Dihydro-1,2,4-triazolo[1,5-a]pyrimidines

There is currently great interest in solid-state reactions as they offer potential reduction in environmental contamination with the elimination of solvents.1,2 One practical approach to achieve this goal is by grinding the solid reactants together using a mortar and pestle, a technique adopted for a number of reactions.3,4 One-pot multi-component reactions (MCRs) have been exploited as a powerful tool for the assembly of large libraries of biologically active compounds.5,6 Among heterocycles, quinazolinones and triazolo-pyrimidines have attracted a great deal of attention due to their therapeutic and pharmacological properties.7,8 Drugs such as fluconazole and itraconazole are notable examples of antifungal molecules possessing the triazole nucleus. In view of the above and considering the fact that ionic liquids have been used as eco-friendly catalysts as well as solvents in organic synthesis,9–13 it was thought worthwhile to utilize the catalytic potential of 1-nbutyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF4) in the synthesis of tetrahydro1,2,4-triazolo[5,1-b]quinazolin-8(4H)-ones and dihydro-1,2,4-triazolo[1,5-a]pyrimidines. Although different strategies have been employed for the synthesis of these compounds,14–18 these methods suffer from drawbacks such as long reaction times, cumbersome isolation of the products and harsh reaction conditions. We now report a facile and efficient ionic liquid-catalyzed multi-component synthesis of tetrahydro-1,2,4-triazolo[5,1-b]quinazolin8(4H)-ones (3) and dihydro-1,2,4-triazolo[1,5-a]pyrimidines (4) in excellent yields from 3-amino-1,2,4-triazole, aldehydes and dimedone (or ethyl acetoacetate), respectively, by simple grinding using a mortar and pestle at room temperature (Scheme 1). In order to optimize the reaction conditions, test reactions of 3-amino-1,2,4-triazole (1), benzaldehyde (2a) and dimedone were carried out in the presence of various ionic liquid catalysts. While there was no observable product in the absence of the catalyst, the addition of various [Bmim] salts, brought about a dramatic change in the reaction profile, the best result being obtained using 15 mol% of [Bmim]BF4 at room temperature in 12 min. Although it was also determined that heating at 70◦C in the presence of 15 mol%

Toxicological and pharmacological evaluation, antioxidant, ADMET and molecular modeling of selected racemic chromenotacrines {11-amino-12-aryl-8,9,10,12-tetrahydro-7H-chromeno[2,3-b]quinolin-3-ols} for the potential prevention and treatment of Alzheimer’s disease

The pharmacological analysis of racemic chromenotacrines (CT) 1-7, bearing the 11-amino-12-aryl-8,9,10,12-tetrahydro-7H-chromeno[2,3-b]quinolin-3-ol ring skeleton, in a series of experiments targeted to explore their potential use for the treatment of Alzheimers disease (AD), is reported. The toxicological evaluation showed that among all these chromenotacrines, CT6 is much less hepatotoxic than tacrine in a range of concentrations from 1 to 300 μM, measured as cell viability in HepG2 cells. Moreover, CT6 did not significantly increase lactate dehydrogenase, aspartate transaminase, and alanine transaminase release in HepG2 cells. Besides, CT6 treatment exerts a high protective effect against the lipid peroxidation induced after H₂O₂-treated SH-SY5Y cells, in a concentration-dependent manner. CT6 showed an excellent antioxidant profile in the AAPH test, and protects against the decrease in cell viability induced by respiratory chain inhibitors (Oligomicyn A/Rotenone) and NO donors in neuronal cultures. This effect could be due to a mixed antiapoptotic and antinecrotic neuroprotective effect at low and intermediate CT6 concentrations, respectively. CT1-7 are potent and selective inhibitors of EeAChE in the submicromolar range. CT3 [IC₅₀ (EeAChE) = 0.007 ± 0.003 μM], and CT6 [IC₅₀ (EeAChE) = 0.041 ± 0.001 μM] are the most potent AChE inhibitors. Kinetic studies on the non-toxic chromenotacrine CT6 showed that this compound behaves as a non-competitive inhibitor (Ki = 0.047 ± 0.003 μM), indicating that CT6 binds at the peripheral anionic site, a fact confirmed by molecular modeling analysis. In silico ADMET analysis showed also that CT6 should have a moderate BBB permeability. Consequently, non-toxic chromenotacrine CT6 can be considered as an attractive multipotent molecule for the potential treatment of AD.

Microwave-Assisted Synthesis of Some Novel Thiazolidinone and Thiohydantoin Derivatives of Isatins

A simple, rapid, and efficient method for the synthesis of some new thiazolidinone and thiohydantoin derivatives of isatins along with some Mannich bases has been achieved in excellent yield from indole-2,3-dione-3-thiosemicarbazone employing microwave irradiation.