Journal of Heterocyclic Chemistry最新文献

A formal [3 + 3] cycloaddition of 4-hydroxycoumarins with propargylicalcohols was established under mild conditions. This strategy utilizes diazonium tetrafluoroborate as the Lewis acid catalyst and provides a practical approach for delivering pyranocoumarin derivatives in moderate to high yield. The structure of the cycloadduct was unequivocally confirmed by single-crystal x-ray diffraction. The potential synthetic applications of this strategy were also highlighted by the scale-up experiment and further synthetic transformation.

Synthesis of 18 tryptanthrin-triazole hybrid molecules by employing Cu(I)-catalyzed azide-alkyne [3 + 2] cycloaddition (CuAAC) between tryptanthrin oxime O-propargyl ether and aromatic azides is described here. The exclusive formation of E-triazoles was confirmed by theoretical studies using the M06-2x/6–311++G(d,p) level. From the synthesized triazoles, four of them have been selected and were subjected to in vitro anticancer activity studies against selected cell lines. Furthermore, in silico studies have been conducted for the most active compound, 5h, and it suggested that various noncovalent interactions and one conventional hydrogen bond enhance the stability of the complex (binding affinity = −11.29 kcal/mol). ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) studies also prove the increased biological potency of 5h.

Quinazolines and their derivatives occur in various natural products and pharmaceuticals, and thus, various methods of synthesizing quinazolines have been explored. They have traditionally been synthesized via two-component reactions, but these strategies often suffer from the unavailability of the starting materials and limited substrate scopes. To overcome these problems, three-component reactions using additional N sources were developed. Aldehydes were initially used in these reactions, but alcohols are greener and less toxic than aldehydes. However, the previously reported methods involving the use of alcohols require the utilization of transition metal catalysts, ultrahigh temperatures, and extended durations. Thus, an efficient, practical method of synthesizing quinazolines using alcohol is desirable. A facile one-pot three-component method of synthesizing quinazolines utilizing alcohols, 2-aminobenzoketones, and ammonium acetate is reported for the first time, using active MnO₂ and tert-butyl hydrogen peroxide (TBHP) as synergistic oxidants. MnO₂ and TBHP play dual roles: First, they oxidize the alcohol to the aldehyde and then facilitate the transformation of the intermediate into the product. During alcohol oxidation, the synergistic effect of MnO₂ and TBHP is particularly evident. The aldehydes generated in situ via alcohol oxidation undergo immediate subsequent reactions, thereby minimizing their volatilization and side reactions, such as oxidation and polymerization.

This study describes a simple, inexpensive, and effective method for the synthesis of new 5-imino-7-aryle-5H-thiazolo[3,2-a]pyrimidine-3-carbonitrile derivatives 4a-e using a green procedure that does not require the use of heat or a base, creating a strategy that meets both economic and environmental demands. Various synthesized products were characterized via diverse techniques such as ¹H-NMR, infrared (FT-IR), Mass spectroscopy (MS), and single crystal X-ray diffraction. Using a fluorescence spectrometer, the 5-imino-7-phenyle-5H-thiazolo[3.2-a]pyrimidine-3-carbonitrile 4a has been tested as a potent fluorescent agent in mixture of DMSO/Water at 10⁻⁴ M in one hand, and on the other hand the results of our fluorescence evaluation studies with metal ions (Pb(II), Ba(II), Cd(II), Ni(II), Mn(II), Hg(II), Zn(II), Fe(II), Co(II), Cu(II), La(II), Cr(III), and Fe(III)) have shown that this compound exhibits a turn-on and turn-off of the fluorescence to 4a compound with these metals, what forms poor to good interaction by these ions. This result represents the emergence of a new potential ligand for the two heavy cations Cd(II) and Pb(II), which are toxic and polluting, and whose detection is currently of high interest. As well, In the molecular docking evaluation study, it was determined that the 4e molecule has an exceptional ability to inhibit the binding energy of the tubulin protein by −9.13 kcal/mmol, compared to other compounds. The results demonstrate the possibilities for a novel oral medication application.

Imidazole moiety when fused with other heterocyclic system form numerous compounds with different types of pharmacological and biological activities. In this review, we discussed a comprehensive analysis of the synthetic methodologies and reaction mechanisms for imidazo-fused heterocyclic molecules. These molecules represent a crucial class of compounds due to their significant applications and versatile chemical reactivity. This article meticulously examined various synthetic routes for the construction of imidazo-fused heterocycles, ranging from traditional methods to modern approaches such as microwave-assisted reactions, NPs-catalyzed reactions, light-mediated synthesis, electrochemical reactions, and transition metal-free synthesis routes. By consolidating the current knowledge and highlighting future directions, this review aims to serve as a treasure for research community in the fields of organic chemistry, medicinal chemistry, and material science.

We have described herein a simple and formal two-step synthesis of 3-(4,6-diaryl-1,3,5-triazin-2-yl)-2-aryl quinolines from 2-chloro-3-(4,6-diaryl-1,3,5-triazin-2-yl) quinolines and boronic acids under the Suzuki–Miyaura conditions. This protocol provides the C-2 arylation of 2-chloro-3-(4,6-diaryl-1,3,5-triazin-2-yl) quinolines under the mild reaction conditions. These newly formed chemo-types may be useful in drug discovery programs or in material chemistry.

A straightforward and efficient method has been developed to access a variety of benzothiazole derivatives via cascade reductive annulation. Iodine mediated, one-pot three-component reaction of o-chloronitroarenes, aryl aldehydes, and elemental sulfur effectively produce benzothiazoles. Moreover, the metal-free strategy allows the facile synthesis of diverse 2-substituted benzothiazoles through multiple carbon–heteroatom bonds in good yields. The present protocol features a greener approach, readily accessible reagents, broad substrate scope, high product yields, and operational simplicity.

A general strategy was developed for the synthesis of new fully decorated 1,2,3-triazoles (4a–4m and 5a–5g) containing quinazolines from 1-(4-nitrophenyl)-2-(quinazolin-8-ylsulfonyl) ethan-1-one and several azides using Ramachary organocatalytic azide-ketone cycloaddition method. This reaction is reported for the synthesis of fully substituted sulfonyl-1,2,3-triazolyl quinazolins at a temperature of 100°C and the yields of the products produced are satisfactory to excellent. In vitro anticancer activity of all these derivatives demonstrated that six compounds, 4d, 4f, 4i, 4j, 5d, and 5e, were effective against two human breast cancer cell lines, MCF-7 and MDA-MB-231. Compounds 4f, 4j, and 5d had more action against both cell lines than Erlotinib. Later, the findings of inhibitory assays of potent compounds 4d, 4f, 4i, 4j, 5d, and 5e against the tyrosine kinase EGFR revealed that compound 5d proved more potent than the reference erlotinib, while 4f and 4j had comparable efficacy. In silico molecular docking studies were also performed on six strong medicines to identify interactions with the EGFR receptor, and the energy estimations were shown to be comparable with the observed IC₅₀ values. Ultimately, using SWISS/ADME and pkCSM, the in silico pharmacokinetic profile of potent compounds 4d, 4f, 4i, 4j, 5d, and 5e was predicted. All of the compounds precisely followed the principles established by Lipinski, Veber, Egan, and Muegge.

Straightforward synthetic access to bis -pyrazole derivatives has presented. The titled bis -pyrazole derivative: 3′,5-diphenyl-1′,2- bis (5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)-1′H,2H-[3,4′- bis pyrazol]-5′-ol 3 was obtained from the reaction of pyran-2,4-dione 1 and 4-hydrazineyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine 2 in ethanol in a one-step reaction. The other bis-pyrazole derivative: 5,5′-diphenyl-1′H,2H-[3,4′-bispyrazol]-3′-ol 5 formed from hydrazinolysis of pyran-2,4-dione 1 or (E)-3-((allylamino)(phenyl)methylene)-6-phenyl-2H-pyran-2,4(3H)-dione 4 in ethanol. The molecular structure of both compounds elucidated by X-ray crystallographic identification and spectrophotometric tools. The supramolecular structure of 3 could be described as a hydrogen bonded dimer via O–H…N interactions which are further connected by π…π contacts. Hirshfeld analysis showed the significance of the N…H, O…H, C…H, C…C, N…N, C…O and H…H interactions. These contacts contributed by 14.4%, 3.2%, 16.4%, 3.9%, 1.0%, 0.4% and 42.7%, respectively from the whole interactions occurred in the crystal. The d _norm, shape index and curvedness maps revealed the importance of π–π stacking interactions in the molecular packing where the % C…C is 3.9%. In case of 5, the short N…H, C…H, and H…H contacts contributed by 15.5%–17.0%, 28.3%–36.7% and 37.8%–45%, respectively in the molecular packing.