Scalability gaps in Chemistry

Representative open questions

Showing 18 of 19 — one per source paper, highest-quality first.

• WITHDRAWN: Combinatorial Chemistry Online Volume 15, Issue 11, November 2013 (2013) · doi

  Solid-phase synthesis of glycopeptides using Shoda's unprotected carbohydrates has been reported by Novoa et al., but the scalability of this protocol for generating large combinatorial glycopeptide libraries with varying carbohydrate complexity and peptide lengths remains undemonstrated.

• Bis (N-Heterocyclic Carbene) Palladium Complex Immobilized Onto Fe3o4@Sio2 as a Catalyst for Sonogashira (Amine/Copper Free) and Hiyama Coupling of Arbr/Cl in Green Media (2026) · doi

  The optimal reaction conditions use 20 mg of catalyst in 2 mL water; however, the paper does not evaluate scalability to gram-scale or multi-gram syntheses. Testing the heterogeneous Pd-NHC/Fe3O4@SiO2 catalyst at increased reaction volumes (10-100 mL) and substrate quantities would determine whether heat transfer limitations or mass transfer constraints arise during scale-up of Sonogashira and Hiyama coupling reactions.

• My journey in the CO2-chemistry wonderland (2017) · doi

  The production scalability of cyclic carbonates from olefins, CO2, and air is limited by the current availability of epoxides (ca. 600 kt/y using H2O2 routes) not matching commodity chemical market demands of several Mt/y. Alternative epoxide production routes with higher throughput capacity and lower cost than H2O2 oxidation must be developed and evaluated for integration with the oxidative carboxylation process.

• Organometallic Chemistry of Heterocycles (2010) · doi

  Ring expansion and ring contraction reactions have enabled preparation of metal-containing rings (closo-ruthenacyclopentadienes, ruthenabenzofuran, iridabenzothiophene, azanickelacyclopentadienes) with various substituents, but the scope and limitations of these ring-forming processes with respect to substituent electronic properties and steric demands remain incompletely defined.

• Multicomponent reactions in crop protection chemistry (2020) · doi

  The synthesis of α-aminophosphonate derivatives containing pyrimidinyl and benzothiazolyl moieties has been demonstrated at laboratory scale, but the scalability of multicomponent phosphonate reactions to industrial crop protection manufacturing processes has not been systematically evaluated.

• Flow Chemistry as a Drug Discovery Tool: A Medicinal Chemistry Perspective (2018) · doi

  The MACOS microwave-heated thin-film catalysis system (Scheme 22) achieves temperatures exceeding 900°C on copper or gold-coated capillaries for multicomponent propargyl amine synthesis, but the paper does not specify the thermal stability limits of the capillary coatings, their reusability/lifetime, temperature uniformity across the reaction zone, or applicability to other metal films (e.g., platinum, nickel).

• Flow Chemistry in Drug Discovery: Challenges and Opportunities (2021) · doi

  While the paper mentions that microfluidic cell-chips can execute 1,500 chemical combinations per day with real-time analysis, there is no investigation of how reaction scaling from microfluidic chip conditions to preparative flow reactor scales affects yield, selectivity, and consistency when using the same AI-optimized parameters.

• Water extract rice husk as an efficient catalyst to synthesis of p-thymol tailored 1,2,4-triazole sulfanyls as potential antidiabetic candidates (2026) · doi

  The rice husk water extract catalyst is employed for synthesis, but the paper does not compare catalytic efficiency, yield optimization, or sustainability metrics against conventional synthetic methods or other green catalysts for 1,2,4-triazole sulfanyl compound synthesis, limiting assessment of the proposed catalyst's practical scalability.

• Sustainable Biginelli chemistry: Indian contributions to green multicomponent synthesis (2026) · doi

  While the phosphotungstic acid-Jeffamine hybrid catalyst demonstrated scalable DHPM synthesis in water at near-neutral pH (7.5), the paper does not specify minimum or maximum batch scale feasibility, catalyst loading optimization for industrial production, or cost-benefit analysis compared to Fe(III)/bent and IL2@Fe3O4 systems.

• Asymmetric Organocatalysis at the Service of Medicinal Chemistry (2014) · doi

  While enamine-catalysed organocatalytic reactions achieve gram-scale synthesis of oseltamivir, the relatively high catalyst loading and long reaction times for asymmetric organocatalysis in medicinal chemistry applications require optimization to improve practical scalability and reaction efficiency.

• Flow Chemistry in Medicinal Chemistry: Applications to <scp>Bcr</scp> ‐ <scp>Abl</scp> Kinase Inhibitors (2022) · doi

  The platform was limited to two-step reaction sequences (with optional third deprotection step); integration of longer multi-step synthesis sequences with inline intermediate workup and purification for Bcr-Abl kinase inhibitor scaffold elaboration remains out of scope and requires development of automated workup protocols.

• Chiral configurations in cyclophosphazene chemistry (2015) · doi

  The scope of the 31P NMR/CSA method has been tested only for spiranes with up to four additional centers of chirality in cyclophosphazenes. Investigation of whether this method can effectively characterize spirane-bridged cyclophosphazene compounds with six or more chiral centers, and at what separation distance the CSA complexation becomes completely ineffective, remains unexplored.

• Synthesis and spectroscopic characterization of homoleptic triorganopnictogen(III) compounds – useful precursors for functionalized materials. Molecular structure of [4-{(CH2O)2CH}C6H4]3Sb (2025) · doi

  No discussion is provided regarding the scalability of synthesis or potential industrial applications of these homoleptic triorganopnictogen(III) compounds.

• Lu2CrMnO6–Pm-g-C3N4 supported dendritic nanosilica as a recyclable green catalyst for eco-friendly synthesis of N-[(2-hydroxyethoxy)carbonyl] glycine from carbon dioxide (2026) · doi

  While the study demonstrates recyclability over ten consecutive cycles, long-term stability and performance over extended periods or in industrial-scale operations have not been investigated.

• Integrating integrated circuit wastewater into the metal catalyst supply chain (2026) · doi

  The paper demonstrates successful catalyst synthesis and testing at laboratory scale but does not address scaling up the ammonia vaporization method or the catalytic process to industrial or commercial production levels.

• Chemistry Teacher International, Best Practices in Chemistry Education (2020) · doi

  It is now important that the continuity of Chemistry Teacher International is insured through regional editors in different parts of the world to help obtain new articles for the journal and share good practices from all parts of the world.

• Organometallic Chemistry (2024) · doi

  The paper lacks discussion on scalability, industrial applications, or practical considerations for preparing and using carbenes and carbenoids on larger scales.

• Catalysts in Green Chemistry (2026) · doi

  While the paper discusses green catalysts in pharmaceutical and fine chemical industries, scalability of these catalytic systems from laboratory to industrial production scale is not addressed.