Аннотация
For over a century, synthetic chemistry demanded the rigorous exclusion of water, relying on toxic, volatile organic solvents. This paradigm, while successful, is environmentally and economically costly. This review advocates for a fundamental shift: adopting water not just as a green solvent, but as a transformative medium that reshapes our understanding of reactivity and bridges chemistry with biology. Aqueous phase organic synthesis (APOS) has evolved from accidental observations to a deliberate discipline. Water’s unique properties—its high polarity, hydrogen-bonding capacity, and the hydrophobic effect—make it an active participant. This effect drives reactant aggregation and stabilizes transition states, leading to dramatic rate enhancements in pericyclic and condensation reactions. A broad range of reactions thrive in water, including classical carbon–carbon bond-forming reactions like the aldol and Diels–Alder, and modern cross-couplings (e.g., Suzuki–Miyaura) enabled by water-tolerant catalysts. Multicomponent and click chemistries are particularly powerful. Challenges like poor solubility are addressed with micellar catalysis, water-soluble ligands, and precise control of the reaction microenvironment. Beyond sustainability, APOS drives discovery, often yielding improved selectivities, new pathways, and streamlined syntheses of complex targets like pharmaceuticals. Its greatest promise lies in interfacing with biology. Bioorthogonal reactions, such as azide–alkyne cycloadditions, enable labeling and imaging in living organisms. Aqueous compatibility is essential for in situ therapeutic strategies, chemical biology, and advanced bioconjugation techniques for modifying biomolecules. The future converges with emerging technologies: machine learning to navigate complex aqueous systems, flow chemistry for scalability, and the integration of enzymatic with synthetic catalysis. This points toward a unified chemical-biological engineering paradigm. In conclusion, APOS is a mature, versatile field. It is a cornerstone of green chemistry and a critical bridge to biology, accelerating progress in medicine and materials science. Embracing water is both an environmental imperative and a strategic pathway to the next generation of scientific discovery. Introduction: The Solvent Problem in Organic Synthesis For generations, organic synthesis has been defined by precise control over molecular structure carried out in rigorously dried environments. Since the emergence of modern organic chemistry in the nineteenth century, water – the very medium that sustains life – has been regarded as an obstacle to chemical transformation. This long-standing assumption has shaped laboratory routines, industrial manufacturing, and chemical education, reinforcing the idea that successful synthesis depends on strict exclusion of moisture. This introduction revisits that historical mindset, evaluates its environmental and economic consequences, and presents the case for a fundamental transition toward aqueous phase organic synthesis (APOS) as a more suitable platform for future chemical and biological innovation.