Beilstein Arch. 2026, 202636. https://doi.org/10.3762/bxiv.2026.36.v1
Published 09 Oct 2026
Physical-AI robotic systems are being developed as platforms for autonomous organic synthesis. However, solvent handling remains a practical challenge in robotic operations, as the use of organic solvents imposes requirements on equipment materials, fluid delivery, and product recovery. Here, we introduce Kneading Chemistry, a semi-solid reaction method with controlled solvent content designed for robotic organic synthesis. We investigated the reduction of ketones with NaBH₄ under semi-solid conditions using a robotic kneading system equipped with force monitoring and programmable motion control. The amounts of solvent and silica gel were adjusted according to the substrate. Silica gel serves as both a reaction medium and a reservoir for protic solvents, helping maintain the semi-solid reaction environment during kneading. A structurally diverse range of ketones was reduced in moderate to good yields with reduced solvent use. Products were recovered directly from the silica gel reaction mixture by elution, without conventional aqueous work-up.
Keywords: Kneading Chemistry; Semi-solid reaction; Mechanochemistry; Robotic organic synthesis; Sodium borohydride reduction
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Nishihori, Y.; Nakajima, Y.; Ono, K.; Takebe, H.; Matsubara, S. Beilstein Arch. 2026, 202636. doi:10.3762/bxiv.2026.36.v1
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