The colourful fluorescence from readily-synthesised 3,4-diaryl-substituted maleimide fluorophores Hsiu-Chih Yeh, Wei-Ching Wu and Chin-Ti Chen* Institute of Chemistry, Academia Sinica, Taipei, Taiwan 11529, R.O.C; Fax: +886-2-783-1237. E-mail: cchen@chem.sinica.edu.tw Received (in Cambridge, UK) 20th November 2002, Accepted 4th December 2002 First published as an Advance Article on the web 20th December 2002 A new synthesis procedure has been developed for a series of maleimide-based fluorophores, exhibiting a large variation of emission spectra spanning the entire visible range. Fluorophores tethered with unsubstituted maleimide, a fluores- cence quencher per se, are thiol-reactive probes for protein labelling 1 or micromorphological probes 2 for monitoring bulk polymerization. On the other hand, 3,4-bisindole-substituted maleimides, the common structure of natural products found for red-fluorescent alkaloids from slime moulds, are of interest as potent inhibitors of protein kinase C (PKC). 3 Unlike the larger members of the carboxylic imide family, such as phthalimides, naphthalimide, and perylenebisimide, aryl-substituted maleimide compounds have received much less attention in the field of colorants or fluorescence dyes. 4 Fluorescence metal sensors based on monoindole-substituted maleimides have recently been reported. 5 Nevertheless, absorp- tion and fluorescence spectroscopic properties of diaryl- substituted maleimide have been neglected and remained unexplored. Just recently, we reported the first efficient and bright red organic light-emitting diode (OLED) based on nondoping red emitter, NPAMLMe, 6 a naphthylphenylamino substituted N-methyl-3,4-diphenylmaleimide. NPAMLMe is a deep red fluorophore with relatively large Stokes shifts (D) in both solution and solid state. 6 Noteworthy, in addition to its unusual spectroscopic behavior, 3,4-bis(4-bromophenyl)malei- mide, a precursor to NPAMLMe, was prepared handily in one- step (similar to that shown in Scheme 1) employing 4-bromo- benzyl cyanide (or 4-bromophenylacetonitrile) as the starting material. In this communication, we apply the newly found one- step synthesis to prepare a series of 3,4-diarylmaleimide compounds carrying varied functionality, employing a broad class of different aryl-substituted acetonitrile as starting materi- als. We examine the spectroscopic properties of these new maleimide derivatives in evaluating further electrooptical application. To our knowledge, there are several synthetic procedures known for preparing either symmetrical or unsymmetrical 3,4-substituted maleimides. 7–10 Among them, the most recog- nized one is through an indirect method of the ammonolysis of maleic anhydrides, which in turn are best prepared from the reaction of glyoxylic acids with acetic acids. 7 However, glyoxylic acid derivatives are not widely available commer- cially. An efficient one-step synthesis of maleimides can be achieved by condensation of glyoxylate esters with acet- amides. 9 Once again, desired glyoxylate esters often require synthetic preparation. In the context of synthesis, it has been known for some time that diphenylmaleimde can be prepared from diphenylfumaronitrile. 10 However, we found that the synthesis of diphenylfumaronitrile from phenylacetonitrile is often troublesome and requires tedious purification. Difficulties or unsatisfactory yields were often reported in preparing diaryl- substituted fumaronitrile. 11 Therefore, to serve the purpose of spectroscopic studies, the direct and one-step synthesis of maleimides reported here is quite valuable, particularly for the symmetrical 3,4-diaryl-substituted fluorescent maleimides. This is because the starting materials, aryl-substituted acetoni- trile derivatives are abundant either commercially available or readily synthesizable. Maleimides MLH, 3-CF 3 MLH, 4-CF 3 MLH, 3-PYDMLH, 2-THPMLH, 4-MeOMLH, 1-NPHMLH, and 2-NPHMLH were synthesized directly from acetonitrile derivatives (Scheme 1). The yields of such direct and one-step syntheses of maleimides are highly dependent on the acetonitrile derivatives. Without optimizing the individual maleimide syntheses, we obtained reaction yields ranging from low (such as < 10% of 2-THPMLH) to reasonably good (such as > 60% of 3-PYDMLH). Following methylation with an excess amount of methyl iodide provided N-methylated deriva- tives MLMe, 3-CF 3 MLMe, 4-CF 3 MLMe, 2-THPMLH, 4-MeOMLMe, 1-NPHMLMe, and 2-NPHMIMe. Diamino- substituted derivatives TPAMLMe, PhAMLMe, and EtAMLMe were obtained by a method similar to that for NPAMLMe by coupling N-methyl-3,4-bis(4-bromophenyl- )maleimide with appropriate secondary amines catalyzed by palladium. 6 All new compounds were purified by column chromatography. They were fully characterized by 1 H and 13 C NMR, FAB-MS, and elemental analysis, and were consistent with proposed structures.† Depending on the substituent on diaryl-substituted mal- eimide, a large variation in fluorescence colour was observed (Fig. 1, Table 1). The emission wavelength maxima (l max em ) of both MLH and MLMe clearly show bathochromic shifts with electron-donating (such as 4-methoxy and 4-diarylamino groups) or electon-rich aryl (such as 2-thienyl) substituents and hypsochromic shifts with electron-withdrawing (such as 4-tri- fluoromethyl) or electron-deficient aryl (such as 3-pyridyl) substituents. Except for the quite similar 3-CF 3 MLH and 3-CF 3 MLMe, all maleimide compounds exhibit larger Stokes Scheme 1 Reagents and conditions: i, I 2 (1 equiv.) in THF, NaOCH 3 (3 equiv.) in CH 3 OH, 2 h at 278 °C, 14 h at 25 °C, then 3% HCl (aq) (7 ~ 65%). ii, CH 3 I (5 equiv.), KOBu t , DMF, 25 °C, 6 ~ 12 h (70 ~ 90%). This journal is © The Royal Society of Chemistry 2003 404 CHEM. COMMUN. , 2003, 404–405 DOI: 10.1039/b211537a