Abstract: 1,2,3,4-Tetrahydroisoquinoline (THIQ) derivatives represent an important class of nitrogencontaining heterocycles that have attracted considerable interest owing to their structural diversity, synthetic versatility, and broad range of reported biological activities. Their structural resemblance to naturally occurring alkaloids and the ease of functionalization at different positions of the THIQ framework make them valuable scaffolds for the development of structurally diverse bioactive molecules. This review summarizes recent advances (2019-2025) in the chemistry of THIQ derivatives with particular emphasis on synthetic strategies, structural modification, representative lead molecules, and Structure-Activity Relationship (SAR) studies associated with diverse biological activities. In addition, recent developments in molecular hybridization, scaffold design, and emerging synthetic approaches for the preparation of THIQ derivatives are critically discussed. This review also highlights current research trends, key structural features governing biological performance, and future opportunities for the chemical development and functional diversification of THIQ-based scaffolds. Overall, this review provides a comprehensive resource for researchers working in heterocyclic, synthetic, and medicinal chemistry involving tetrahydroisoquinoline derivatives.
Abstract: Pd-catalyzed C-H bond activation has greatly revolutionized the field of organic synthesis over the past two decades. A deep mechanistic understanding of this process is crucial for the rational design of new reactions. This review summarizes recent advances in the combination of experimental and computational approaches toward understanding Pd-catalyzed C-H bond activation mechanisms. Density Functional Theory (DFT) serves as a key tool for studying the mechanisms of organic reactions. In this review, a range of mechanistic pathways for Pd-catalyzed C-H bond activation and functionalization reactions were described. The widely recognized concerted metalation and deprotonation pathway, which occurred through a monometallic Pd complex or a bimetallic PdAg complex with acetate/amidate as the base, was highlighted. Oxidative addition, carbometalation and elimination, electrophilic aromatic substitution, and σ-bond metathesis, along with 1,2-addition, were also included. This paper presents a systematic framework for understanding the mechanisms of Pd-catalyzed C-H bond activation, offering valuable insights for researchers engaged in mechanistic studies and reaction development in this field.
Abstract: Colorectal cancer (CRC) continues to pose a pressing challenge to global health, with rising incidence rates and treatment outcomes frequently impeded by drug resistance, systemic toxicity, and limited selectivity in current chemotherapy regimens. In this context, heterocyclic compounds, particularly pyrazole derivatives, have emerged as promising candidates in the quest for more effective anticancer agents. This review explores advancements in the design, synthetic methodologies, and development of structurally diverse pyrazole-based molecules for CRC therapy, highlighting their biological activity, mechanisms of action, and the critical role of structure-activity relationship (SAR) studies in optimizing therapeutic performance. The exponential growth of academic literature suggests that strategic modifications to the core pyrazole structure can significantly enhance both potency and selectivity against key CRC cell lines, such as HCT116, HT29, and SW620. This review aims to collate literature work reported by researchers (from 2010 to 2025) to provide an overview of the potential of pyrazole-based derivatives, especially against CRC. Unlike broader oncology reviews, this work focuses exclusively on the role of pyrazole in colorectal cancer (CRC). By systematically sourcing literature from verified databases, including PubMed and Google Scholar, we comprehensively compile and elaborate on SAR reported between 2010 and 2025, providing a targeted resource for CRC drug discovery.
Knoevenagel Condensation (KC) revolutionizes the classical carbon-carbon bond formation strategy by providing an adaptable and efficient route to generate C=C linkages from carbonyl compounds and active methylene substrates. Despite its synthetic versatility and wide applicability in the preparation of pharmaceuticals and functional materials, traditional methods have several drawbacks, including the use of harmful solvents, harsh reaction conditions, toxic catalysts or reagents, waste generation, lengthy and complex work-up, lower sustainability, and safety risks. These disadvantages emphasize the need to switch to more eco-friendly, efficient, and greener options. This review critically surveys advancements in green synthetic methodologies developed for the Knoevenagel condensation, focusing on innovations such as heterogeneous catalysis, ionic liquid-mediated systems, solvent-free conditions, microwave-assisted techniques, and the utilization of benign solvents like water and ethanol. A comparative discussion of these methodologies highlights their efficiency, product yields, reduced reaction times, and catalyst recyclability. Additionally, these green protocols typically do not require complex extraction or extensive work-up procedures to isolate the product, making the process simpler, cleaner, and more efficient compared to conventional methods. Furthermore, they offer greater environmental compatibility than the former strategies. Overall, this review emphasizes that green Knoevenagel protocols not only provide sustainable alternatives but also open new opportunities for the large-scale, environmentally friendly synthesis of valuable organic intermediates.
Abstract: Polyhydroquinolines (PHQs) are important nitrogen-containing heterocycles because of their wide range of pharmacological activities and potential for future pharmaceutical developments. The current review focuses on critically discussing recent advances in the green and sustainable multicomponent synthesis of PHQ derivatives. The scope includes energy-efficient approaches, such as microwave-, ultrasound-, and solarassisted synthesis, along with the implementation of sustainable catalysts such as organocatalysts, photocatalysts, nanocatalysts, transition-metal catalysts, and biodegradable composites for the synthesis of PHQ derivatives. Furthermore, the review highlights the importance of solvent selection, especially under neat conditions, and the use of green solvents as less-toxic, recyclable medium. The reviewed studies indicate that several advanced methodologies can reduce reaction time, improve synthetic efficiency, enable catalyst recycling, and minimise hazardous solvent use; however, limitations remain, including the use of expensive catalysts, a restricted substrate scope, challenges in catalyst separation, and scale-up, as well as specialised energy sources. Where available, green chemistry metrics including atom economy, E-factor, Process Mass Intensity (PMI), and Eco-Scale are evaluated to compare the environmental performance of reported methodologies beyond isolated yield. Overall, the review highlights recent progress towards PHQ synthesis, identifies gaps that limit the widespread use of pharmaceuticals and industrial applications, and suggests future research directions for scalable, economical, and reproducible synthetic methodologies.
