1-Isocyano-5-aminonaphthalene
Chemical compound
From Wikipedia, the free encyclopedia
1-Isocyano-5-aminonaphthalene (commonly ICAN) is a substituted naphthalene bearing an isocyano (âNâ¡C) group and an amino (âNH2) group in a 1,5-relationship. The pushâpull 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.[1][2] 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.[3]
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| Names | |
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| Preferred IUPAC name
5-Isocyanonaphthalen-1-amine | |
| Other names
5-Amino-1-isocyanonaphthalene; ICAN | |
| Identifiers | |
3D model (JSmol) |
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| ChemSpider | |
PubChem CID |
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| Properties | |
| C11H8N2 | |
| Molar mass | 168.199 g·molâ1 |
| Appearance | Yellowâorange solid (reported) |
| Low in water; soluble in organic solvents | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Structure and photophysics
The 1,5-arrangement of âNH2 and âNâ¡C on the naphthalene core creates a donorâacceptor 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.[1][2]
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.[4][1]
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).[5][6]
Properties and uses
Fluorescence and solvatochromism
ICAN's emission shifts from blueâgreen in less polar media toward orangeâred in polar/protic media; it has been applied as an environment-sensitive probe and as a reference pushâpull dye in photophysics.[1][2]
Chemical sensing
ICAN-type dyes have been used in complexation/ion-sensing studies (e.g., silver(I) detection) and for background reduction in biolabelling.[7]
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 0.04â1.25 μg·mLâ1 against clinical isolates and improved survival in a neutropenic mouse model of invasive candidiasis (5 mg/kg i.p.).[3]
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 [citation needed]. In general, many low-molecular isocyanides are strongly malodorous, although exceptions exist.[8]
Derivatives
| Abbrev. | Substituents (1;5) | Photophysical notes (qual.) | Antifungal notes |
|---|---|---|---|
| ICAN | âNâ¡C; âNH2 | Strong ICT; pronounced solvatochromism | Active vs Candida spp. (μg/mL range[clarification needed]).[3] |
| MICAN | âNâ¡C; âNHCH3 | Emission shifted vs ICAN | Active; improved MICs vs ICAN.[3] |
| DIMICAN | âNâ¡C; âN(CH3)2 | Red-shifted emission; strong ICT | Most potent in set; MIC 0.04â1.25 μg/mL; in-vivo efficacy in mice.[3] |
| DIN | âNâ¡C; âNâ¡C | Rigid, lower aqueous solubility | Low MICs in vitro; solubility limits addressed by formulation.[3] |