1-Isocyano-5-aminonaphthalene

Chemical compound 1,5-ICAN.svg skin-invert-image 150px Structural formula of 1-Isocyano-5-aminonaphthalene (ICAN) 5-Isocyanonaphthalen-1-amine 5-Amino-1-isocyanonaphthalene; ICAN 1620067-61-9 changed CAS 61012044 102102046 1S/C11H8N2/c1-13-11-7-3-4-8-9(11)5-2-6-10(8)12/h2-7H,12H2 ZGMMMIZCNKPHTB-UHFFFAOYSA-N [C-]#[N+]c1cccc2c1cccc(N)2 11 8 2 Yellow–orange solid (reported) Low in water; soluble in organic solvents 1-Isocyano-5-aminonaphthalene (commonly ICAN) is a substituted naphthalene bearing an isocyano (–N≡C) group and an amino (–NH2) group in a 1,5-relationship. The push–pull pairing of an electron donor (amino) and an electron-withdrawing (isocyano) group gives ICAN a pronounced intramolecular charge-transfer (ICT) character, which underlies its strong solvatochromic fluorescence and its use as an environment-sensitive fluorophore.Rácz D. Nagy M. Mándi A. Zsuga M. Kéki S. Solvatochromic properties of a new isocyanonaphthalene based fluorophore Journal of Photochemistry and Photobiology A: Chemistry 2013 270 19–27 10.1016/j.jphotochem.2013.07.007 2013JPPA..270...19R 2437/172817 free Kovács S. L. Nagy M. Fehér P. P. Zsuga M. Kéki S. Effect of the Substitution Position on the Electronic and Solvatochromic Properties of Isocyanoaminonaphthalene (ICAN) Fluorophores Molecules 2019 24 13 2434 10.3390/molecules24132434 free 31284476 6678642 ICAN and several N-alkylated analogues have also been explored as antifungal leads, with reports of low minimum inhibitory concentrations (MICs) against Candida spp. and proof-of-concept efficacy of a dimethylated derivative in a neutropenic mouse model.Nagy M. Szemán-Nagy G. Kiss A. Nagy Z. L. Tálas L. Rácz D. Majoros L. Tóth Z. Szigeti Z. M. Pócsi I. etal Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals Molecules 2020 25 4 903 10.3390/molecules25040903 free 32085460 7070524 Structure and photophysics The 1,5-arrangement of –NH2 and –N≡C on the naphthalene core creates a donor–acceptor system. ICAN exhibits large Stokes shifts and marked solvent-dependent absorption and emission changes; related ICAN isomers (e.g., 1,4-ICAN; 2,6-ICAN) show systematic variations consistent with ICT tuning by the substitution pattern. Synthesis ICAN is prepared by the carbylamine (Hofmann) reaction, in which a primary amine is converted to an isocyanide via in situ dichlorocarbene generated from chloroform and base (often with phase-transfer catalysis). For naphthalene systems, treating the appropriate aromatic diamine under carbylamine conditions affords the mono-isocyanide (ICAN) together with minor amounts of the diisocyanide.Gokel G. W. Widera R. P. Weber W. P. Phase-Transfer Hofmann Carbylamine Reaction: tert-Butyl Isocyanide Organic Syntheses 1976 55 96–99 10.15227/ORGSYN.055.0096 free https://orgsyn.org/demo.aspx?prep=cv6p0232 subscription By contrast, the related 1,5-diisocyanonaphthalene (DIN) is efficiently obtained by formylation of both amines to a diformamide followed by POCl3-based dehydration; under controlled acidic conditions DIN undergoes partial hydrolysis to give the nonsymmetric 1-formamido-5-isocyanonaphthalene (ICNF).Salami S. A. Siwe-Noundou X. Krause R. W. M. A More Sustainable Isocyanide Synthesis from N-Substituted Formamides Using Phosphorus Oxychloride in the Presence of Triethylamine as Solvent Molecules 2022 27 20 6850 10.3390/molecules27206850 free 36296444 9608669 Kopcsik E. Nagy M. Kéki S. Preparation and Optical Study of 1-Formamido-5-Isocyanonaphthalene, the Hydrolysis Product of the Potent Antifungal 1,5-Diisocyanonaphthalene International Journal of Molecular Sciences 2023 24 9 7780 10.3390/ijms24097780 free 37175485 10177923 Properties and uses Fluorescence and solvatochromism ICAN's emission shifts from blue–green in less polar media toward orange–red in polar/protic media; it has been applied as an environment-sensitive probe and as a reference push–pull dye in photophysics. Chemical sensing ICAN-type dyes have been used in complexation/ion-sensing studies (e.g., silver(I) detection) and for background reduction in biolabelling.Nagy M. Rácz D. Nagy Z. L. Fehér P. P. Kalmár J. Fábián I. Kiss A. Zsuga M. Kéki S. Solvatochromic isocyanonaphthalene dyes as ligands for silver(I) complexes, their applicability in silver(I) detection and background reduction in biolabelling Sensors and Actuators B: Chemical 2018 255 2555–2567 10.1016/j.snb.2017.09.061 2018SeAcB.255.2555N free Antifungal research ICAN, its N-alkyl derivatives, and DIN show in vitro activity against Candida spp.; the dimethylated analogue DIMICAN achieved MIC values as low as 0.04–1.25 μg·mL−1 against clinical isolates and improved survival in a neutropenic mouse model of invasive candidiasis (5 mg/kg i.p.). Safety ICAN and related solids are often described as having little or no noticeable odour (likely reflecting low volatility); ICAN and its derivatives are reported as odorless August 2025. In general, many low-molecular isocyanides are strongly malodorous, although exceptions exist.Massarotti Alberto Brunelli Francesca Aprile Silvio Giustiniano Mariateresa Tron Gian Cesare Medicinal Chemistry of Isocyanides Chemical Reviews 2021 121 10 7251–7341 10.1021/acs.chemrev.1c00143 34197077 free Derivatives Abbrev. Substituents (1;5) Photophysical notes (qual.) Antifungal notes ICAN –N≡C; –NH2 Strong ICT; pronounced solvatochromism Active vs Candida spp. (μg/mL rangeOctober 2025). MICAN –N≡C; –NHCH3 Emission shifted vs ICAN Active; improved MICs vs ICAN. DIMICAN –N≡C; –N(CH3)2 Red-shifted emission; strong ICT Most potent in set; MIC 0.04–1.25 μg/mL; in-vivo efficacy in mice. DIN –N≡C; –N≡C Rigid, lower aqueous solubility Low MICs in vitro; solubility limits addressed by formulation. References Category:Naphthalenes Category:Aromatic amines Category:Isocyanides Category:Fluorescent dyes Category:Antifungals