{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:00:32Z","timestamp":1785301232404,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Isocyanides constitute a valuable class of organic compounds widely employed in multicomponent reactions (MCRs), heterocycle synthesis, and drug discovery. However, their broader application is limited by low commercial availability and hazardous classical synthetic methods. Herein, we report a greener microwave-assisted protocol for the efficient synthesis of isocyanides through a modified Hofmann carbylamine reaction. The methodology is based on the in situ generation of dichlorocarbene from near-stoichiometric amounts of chloroform and sodium hydroxide, using Span\u00ae 80 (sorbitan monooleate) as a biodegradable phase-transfer catalyst under microwave irradiation. Importantly, the protocol eliminates the need for aqueous workup procedures, thereby reducing waste generation and improving the overall sustainability of the process. A broad range of aliphatic-, aromatic-, and amino-acid-derived isocyanides was obtained in moderate-to-excellent isolated yields (43\u201396%) within 30 min, without isolation of intermediates. Compared with conventional approaches, the proposed methodology avoids toxic dehydrating agents such as POCl3 and phosgene, eliminates the need for formamide precursors, and reduces hazardous by-products associated with dehydration processes. The protocol is operationally simple, scalable, and represents a practical, convergent, and environmentally more benign alternative for isocyanide synthesis.<\/jats:p>","DOI":"10.3390\/molecules31152620","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"2620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microwave-Intensified Hofmann Carbylamine Reaction Enabled by Span\u00ae 80: Rapid Access to Isocyanides in a Biphasic System"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1215-0754","authenticated-orcid":false,"given":"Wender Alves","family":"Silva","sequence":"first","affiliation":[{"name":"Laboratory for Bioactive Compound Synthesis, Institute of Chemistry, University of Brasilia, Campus Universitario Darcy Ribeiro, Brasilia 70904-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7474-666X","authenticated-orcid":false,"given":"Sayuri Cristina Santos","family":"Takada","sequence":"additional","affiliation":[{"name":"Genetic Resources and Biotechnology, Brazilian Agricultural Research Corporation (Embrapa), Brasilia 70770-917, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5512-1649","authenticated-orcid":false,"given":"Saulo Tarso Alves","family":"Passos","sequence":"additional","affiliation":[{"name":"Laboratory for Bioactive Compound Synthesis, Institute of Chemistry, University of Brasilia, Campus Universitario Darcy Ribeiro, Brasilia 70904-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","unstructured":"Ugi, I. 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