HETEROCYCLES

Paper | Special issue | Vol. 84, No. 1, 2012, pp. 537-554
Received, 29th April, 2011, Accepted, 17th August, 2011, Published online, 19th August, 2011.
DOI: 10.3987/COM-11-S(P)17

■ Synthesis and Reactivity of Novel 1H-Isochromeno[3,4-d]imidazol-1-onium Salts

Bart I. Roman, Marie Guégan, Nils De Vos, Cedric Maton, and Christian V. Stevens*

Faculty of Bioscience Engineering, Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium

Abstract

A straightforward and convenient preparation of 25 novel imidazolium salts from the corresponding 1H-isochromeno[3,4-d]imidazolones is described, employing either a quaternization or a quaternization/anion metathesis strategy. The nature of the anion has a major influence on the melting point of these imidazolium salts (BF4 > I, PF6 > N(Tf)2, N(CN)2 > OTf).

INTRODUCTION
The synthesis of highly functionalized organic substances very often involves the intermediacy of polyfunctionalized compounds. Multicomponent reactions (MCRs) can offer efficient, short routes from readily accessible starting materials to such complex molecular scaffolds. Our research group has recently illustrated this rationale in the continuous flow synthesis of 3,4-diamino-1H-isochromen-1-ones 2 (Scheme 1).1 Furthermore, we prepared the corresponding 1H-isochromeno[3,4-d]imidazol-1-ones 3 in one extra step.2
Having these imidazoles in hand, we were intrigued to investigate their conversion into imidazolium salts. Today, this class of compounds receives a tremendous amount of attention because of their application as ionic liquids. The latter non-volatile organic solvent surrogates may play a key role in green chemistry in the near future, although their supposed benignness recently became the topic of a lively debate.3,4 Moreover, imidazolium salts are often used as precursors to stable N-heterocyclic carbenes (NHCs),5 highly interesting species that show useful application in organocatalysis6 or as ancillary ligands in various metal containing complex catalysts.7 Such metal-NHC complexes also exhibit promising pharmacological properties, which could render them useful as novel antibacterial and antitumor drugs.8 The present paper provides an efficient protocol for the conversion of isochromeno[3,4-d]imidazol-1-ones into an array of corresponding imidazolium salts and evaluates the influence of the nature of the counter ion on the melting point of these substances.

RESULTS AND DISCUSSION
PREPARATION OF IMIDAZOLIUM HALIDES
The study of the potential of 1H-isochromeno[3,4-d]imidazol-1-ones to form imidazolium salts via alkylation of N(3) was initiated by the treatment of imidazole 3a with methyl iodide as a model reaction (Scheme 2). An overview of the evaluated conditions and the corresponding yields of imidazolium salt 4a is depicted in Table 1.
In an initial attempt, imidazole 3a was treated with 4 equivalents of methyl iodide in acetonitrile at reflux temperature (Entry 1). After 2 h, imidazolium salt 4a was obtained as a precipitate in a disappointing yield of 6%. Prolongation of the reaction time to 12 h did not significantly alter the reaction outcome (Entry 2).
Since the solubility of the substrate in acetonitrile (MeCN) was particularly low, a subsequent trial was carried out in dimethylformamide (DMF, Entry 3). As this solvent was used to synthesize imidazole 3a in a microreactor environment, solubility issues were obviously overcome in this manner. Furthermore, the transformation was carried out in a sealed vessel at 180 °C in an attempt to enhance the reaction rate and to avoid boil-off of methyl iodide. Under these conditions, precipitated crystals of imidazolium salt 4a in a yield of 29% were obtained after 5 h. Isolation of further amounts of the salt from the mother liquor proved tedious.
Unfortunately, prolongation of the reaction time caused degradation (Entry 4). Though all starting material in the mother liquor was apparently consumed, the precipitated crystals of 4a represented a mere yield of 12%. Moreover, removal of residual DMF from these crystals engendered a significant product loss. Subsequent attempts to alkylate imidazole 3a with a large excess of n-butyl bromide or iodide (10 equiv) were somewhat more successful, but again DMF removal proved impractical. Clearly, the use of DMF as a solvent deemed problematic and was hence abandoned.
In a final attempt (Entry 5), the solvent was switched back to MeCN while maintaining the pressure vessel set-up. In order to avoid excessive pressure build-up of the more volatile acetonitrile, the reaction temperature was lowered to 150 °C. After 8 h of heating, the pressure vessel was stored at -15 °C. To our delight, this caused the formation of a copious amount of crystals, which were easily isolated by filtration. Furthermore, removal of solvent traces under a high vacuum atmosphere proved swift, and imidazolium salt 4a was obtained in 75% yield. The mother liquor did not contain starting material, but isolation of further amounts of the desired salt from this mixture was uneconomical.

These optimized conditions were subsequently employed to prepare a library of imidazolium salts 4a-n, the majority of which were obtained in good to excellent yields (Table 2). Only in the case of product 4c, a prolonged reaction time of 24 h was required to obtain an acceptable yield. The discrepancy in yield between products 4c and 4d clearly indicates that, as could be expected, alkyl iodides are a better electrophilic partner in the reaction compared to the corresponding alkyl bromides. The somewhat lower yields reported for imidazolium salts 4b, 4f and 4k are due to an extra recrystallization step in acetonitrile, required to obtain the pure substances.

As displayed in Table 2, halides 4a-n possess relatively high melting points, which can appear surprising given the general opinion that larger imidazolium cations tend to produce relatively low melting points. However, the isochromenone moiety provides ample possibility for intermolecular interactions, thus increasing the melting points dramatically. Still, the alkyl chain length seems to bear no or very little influence on the efficiency of ion packing, and thus on the melting point (comparing the values for compounds 4a and 4d, 4b and 4c, 4g and 4h, etc.)
It is well-accepted that simple halides generally inflict high melting points, while organic (e.g. triflate, tosylate) and larger inorganic (e.g. tetrafluoroborate, hexafluorophosphate) anions tend to give lower melting points. To investigate the validity of this rule for our isochromeno imidazolium salts, we prepared an array of salts 5, possessing different anions Y-, both via anion metathesis and a direct quaternization approach (Scheme 4).

PREPARATION OF IMIDAZOLIUM SALTS VIA ANION METATHESIS
The investigation was started with the anion metathesis of imidazolium iodide 4a via treatment with one equivalent of lithium bis(trifluoromethanesulfonyl)imide (lithium bistriflimide, LiNTf2) at room temperature.9 To facilitate analysis of the reaction mixture via 1H NMR spectroscopy, D2O was chosen as a solvent. During the course of the reaction a white precipitate formed, which was isolated via filtration. MS and 19F NMR analyses confirmed that this was indeed the desired imidazolium bistriflimide 5a, which was obtained in 58% yield (Scheme 5, Table 3). Moreover, no traces of imidazolium salts could be detected in the filtrate (D2O phase). These results were confirmed by mass spectrometry and infrared spectroscopy.
In a similar manner, fluorinated analogue 5b was obtained. The use of 2 equivalents of LiNTf2 did not significantly augment the yield. In our opinion, the conversion to 5a and 5b is complete, but an appreciable amount of product is lost in the filtration step, given the small scale on which the experiments were conducted. This is evidenced by comparing the yields for entries 2 and 3 in Table 3.

Next, the preparation of the corresponding imidazolium dicyanamides via the same protocol was evaluated (Scheme 6, Table 4). Employing silver dicyanamide, however, a complex reaction mixture (Entry 1) or a sticky brown precipitate of different salts was formed (Entry 2). To our delight, utilizing NaN(CN)2, the desired imidazolium dicyanamides were formed as a white precipitate in the reaction mixture, and could readily be isolated by filtration and thorough drying (Entries 3, 4). Indeed, the solubility of silver iodide in water is extremely low (3x10-9 g.mL-1 at 20 °C) when compared to its lithium (1.51 g.mL-1) or sodium counterparts (1.79 g.mL-1).
Identical observations were made for the tetrafluoroborate salts (Entries 5-9). The yield of these imidazolium dicyanamides and tetrafluoroborates 5c-f is moderate due to the small scale of the reaction set-up and the according respectable losses in the filtration step. This is apparent when comparing the yields of 5e for Entries 7 and 8.

Subsequently, we investigated the preparation of imidazolium hexafluorophosphates.10 Treatment of the corresponding iodides with aqueous HPF6 at room temperature yielded a white precipitate. Upon isolation via filtration, washing to neutrality of the residue and thorough drying, NMR and MS analyses proved that the desired salts 5g-h were indeed obtained.

PREPARATION OF IMIDAZOLIUM SALTS VIA DIRECT ALKYLATION OF N(3)
Next, we wanted to evaluate the potential of methyl triflate in the direct alkylation of the imidazoles. Moreover, the inclusion of the triflate anion was also appealing in the light of our melting point study. Treatment of isochromeno imidazolones 3 with excess methyl triflate under dry conditions furnished the corresponding imidazolium triflates 5i-j in a fast, exothermic reaction, while solvent and remaining alkylating reagent were easily removed by evaporation (Scheme 8). Oddly, these imidazolium triflates, unlike all other salts obtained in this study, proved unstable in their pure solid state even when kept at -15 °C. It should also be noted that compounds 5c and 5h were unstable upon prolonged dissolution in DMSO-d6, i.e. during the recording of their 13C NMR spectra.

STUDY OF THE MELTING BEHAVIOR
Having an array of imidazolium salts in our hands, we were intrigued to evaluate the influence of the counter ion on their melting behaviour. Chart 1 provides an overview of the observed melting points. The high values recorded for the bistriflimides, dicyanamides, tetrafluoroborates, hexafluorophosphates and triflates are consonant with those already mentioned earlier for the imidazolium halides and can again be explained by the ample possibility for intermolecular interactions offered by the molecular skeleton. As a consequence, none of the synthesized salts can be used as an ionic liquid. Nevertheless, some interesting conclusions can be made from these data.

Firstly, substitution of iodide for hexafluorophosphate does not alter the melting point. Moreover, the imidazolium tetrafluoroborates possess even higher melting points than the corresponding iodides. The latter observation can appear surprising when considering the popular, somewhat oversimplified rule stating that a reduction in the melting point can straightforwardly be obtained by increasing the size of the anion, or that of the cation. Indeed, this should reduce Coulombic attraction contributions to the lattice energy of the crystal, and increase the covalence of the ions. Yet, the contributions of anions and cations should not be considered separately, and simplistic predictions of melting point changes are thus questionable.11-13 Our case supports this statement: the melting points of the hexafluorophosphate and tetrafluoroborate salts are higher than, or in the same range as those of the much smaller and less covalent iodide salts.
A moderate reduction in melting point (15-30 °C) can be observed for imidazolium bistriflimides and dicyanamides, while the largest difference was recorded for the triflates 5i and 5j. The latter salts melt at a temperature 58 °C to 53 °C lower than the corresponding iodides. These observations are in agreement with the general observation that highly fluorinated organic anions tend to give lower melting salts. In this context, the bistriflimide salts were also lower melting than the starting iodides. The most common explanation for this behaviour is the largely delocalized character of these anions due to the presence of the strongly electron-withdrawing CF3-moiety.14 The consequent weak coordination ability and absence of strong H-bonding contributes significantly to reduction of the melting point. An analogous rationale can be pursued for the dicyanamide anion, since the nitrile groups exhibits a similar, albeit weaker, electron withdrawing behavior.

CONCLUSIONS
A synthetic route was developed furnishing an entry to novel isochromeno imidazolonium salts. Starting from the straightforwardly obtainable 1H-isochromeno[3,4-d]imidazol-1-ones 3, the corresponding imidazolium halides were prepared via a straightforward and convenient alkylation of the N(3) atom in a pressure vessel. Anion metathesis subsequently furnished the analogous tetrafluoroborates, hexafluorophosphates, bistriflimides and dicyanamides. The corresponding triflates were prepared upon treatment of the imidazolones with methyl triflate under mild conditions.
The imidazolium halide, tetrafluoroborate and hexafluorophosphate salts possess high melting points (MP~230 °C). With either bistriflimide or dicyanamide as a counter ion, lower melting salts were obtained (MP~200 °C). The largest reduction in melting point was recorded for the strongly delocalized triflate anion (MP~170 °C).

EXPERIMENTAL
All reagents were purchased from commercial sources (Aldrich, Acros) and used without further purification. Solvents were purchased from commercial sources (Aldrich) and employed as is. Crude reaction mixtures were analyzed on LC/MS/UV. Thin layer chromatography was carried out on silica gel 60F254 plates (Merck).
High resolution 1H (300 MHz), 13C (75 MHz), 31P (121 MHz) and 19F (282 MHz) magnetic resonance (NMR) spectra were recorded on a Jeol Eclipse+300 FT NMR spectrometer in deuterated solvents. Chemical shifts are reported using TMS and/or CFCl3 as an internal reference, unless otherwise indicated. Peak assignments were obtained with the aid of DEPT, HSQC, HMBC and COSY spectra. Attenuated total reflection (ATR) IR spectra were recorded on a Perkin Elmer Spectrum BX spectrometer, equipped with a ZnSe-crystal, at room temperature. Low-resolution mass spectra were recorded on an Agilent 1100 series VL mass spectrometer (ES, 70 eV). Melting points were measured with a Büchi B-540 apparatus and are uncorrected.
SYNTHESIS OF IMIDAZOLIUM SALTS 4a-n
1H-Isochromeno[3,4-d]imidazolone 3 (0.5 mmol) and an appropriate alkyl halide (5 mmol, 10 equiv) were added to a 10 mL pressure vessel containing 2.5 ml of MeCN. The vessel was subsequently sealed and heated in an oil bath at 150 °C for 8 h, under continuous stirring. Next, the mixture was stored overnight at -15 °C to induce crystallization. Imidazolium salt 4 was isolated in crystalline form upon filtration and removal of residual solvent traces under a high vacuum atmosphere. In some cases, an extra recrystallization step in MeCN was necessary to obtain a sufficient degree of purity.
1-Phenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4a
1H NMR (DMSO-d6, 300 MHz, ppm): δ = 4.01 (s, 3H, CH3); 6.80 (d, 1H, J = 7.70 Hz, H9); 7.70 (td, 1H, Jvic = 7.7 Hz, Jallyl = 1.1 Hz, H7); 7.79-7.78 (m, 6H, 6 x Har); 8.37 (d, 1H, J = 7.7 Hz, H6); 9,70 (s, 1H, H2); 13C NMR (DMSO-d6, 75 MHz, ppm): δ = 32.45 (CH3); 109.69 (C9b); 118.36 (C5a); 119.57 (C9); 126.67 (C2’, C6’); 127.10 (C9a); 129.49 (C7); 130.73 (C3’, C5’); 132.03 (C4’); 132.21 (C6); 133.65 (C1’); 134.88 (C2); 136.56 (C8); 140.44 (C3a); 157.22 (C=O); IR (ATR, cm-1): ν = 1760 (C=O); 1515 (C=C); MS (ES+): m/z (%): 277.2 (M+, 100); MP: 230.2-230.3 °C; Yield = 75%; pale yellow crystals; MW = 404.20.
1-Phenyl-3-ethyl-1H-isochromeno[3,4-d]imidazol-5-onium bromide 4b
1H NMR (DMSO-d6, 300 MHz, ppm): δ = 1.60 (t, 3H, J = 7.3 Hz, CH3); 4.43 (q, 2H, J = 7.3 Hz, NCH2); 6.82 (d, 1H, J = 8.3 Hz, H9); 7.67-7.89 (m, 7H, 7 x CHar); 8.38 (d, 1H, J = 7.7 Hz, H6); 9.79 (s, 1H, H2); 13C NMR (DMSO-d6, 75 MHz, ppm): δ = 13.57 (CH3); 41.76 (NCH2); 109.69 (Cq,ar); 118.28 (CHar); 119.46 (CHar); 126.60 (CH2’ar); 126.96 (Cq,ar); 129.34 (Cq,ar); 130.53 (CH3’ar); 131.87 (CHar); 132.07 (CHar); 133.60 (Cq,ar); 134.05 (CHar); 136.44 (Cq,ar); 139.96 (Cq,ar); 157.77 (C=O); IR (ATR, cm-1): ν = 1759 (C = O); 765; MS (ES+): m/z (%): 291.3 (M+, 100); MP: 216.8-220.8 °C; Yield = 40%; white crystals; MW = 371.23.
1-Phenyl-3-butyl-1H-isochromeno[3,4-d]imidazol-5-onium bromide 4c
1H NMR (DMSO-d6, 300 MHz, ppm): δ = 0.97 (t, 3H, J = 7.4 Hz, CH3); 1.46 (sextet, 2H, J = 7.4 Hz, CH2-CH3); 1.96 (p, 2H, J = 7.4 Hz, NCH2-CH2); 4.39 (t, 2H, J = 7.4 Hz, NCH2); 6.82 (d, 1H, J = 7.7 Hz, H9); 7.67-7.88 (m, 7H, 7x CHar); 8.38 (dd, 1H, Jvic = 7.7 Hz, Jallyl = 1.1 Hz, CH6ar); 9.80 (s, 1H, CH2ar); 13C NMR (DMSO-d6, 75 MHz, ppm): δ = 13.27 (CH3); 18.81 (CH2); 29.96 (CH2); 46.06 (NCH2); 109.82 (C9b); 118.44 (C5a); 119.46 (C9); 126.65 (C2’, C6’); 127.05 (C9a); 129.35 (C7); 130.54 (C3’, C5’); 131.89 (C4’); 132.02 (C6); 133.61 (C1’); 134.24 (C2); 136.36 (C8); 140.01 (C3a); 157.83 (C=O); IR (ATR, cm-1): ν = 2953 (CH=CH); 1766 (C=O); MS (ES+): m/z (%): 319.2 (M+, 100); MP: 220.6-222.7 °C; Yield = 65%; yellow crystals; MW = 399.28.
1-Phenyl-3-butyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4d
1H NMR (DMSO-d6, 300 MHz, ppm): δ = 0.97 (t, 3H, J = 7,4 Hz, CH3); 1.46 (sextet, 2H, J = 7.4 Hz, CH2-CH3); 1.96 (p, 2H, J = 7.4 Hz, NCH2-CH2); 4.39 (t, 2H, J = 7.4 Hz, NCH2); 6.82 (d, 1H, J = 7.7 Hz, H9); 7.71 (dxt, 1H, Jvic = 7.7 Hz, Jallyl = 1,1 Hz, H7); 7.77-7.89 (m, 7H, 7 x CHar); 8.37 (dd, 1H, Jvic = 7.2 Hz, Jallyl = 1.1 Hz, H6); 9.76 (s, 1H, H2); 13C NMR (DMSO-d6, 75 MHz, ppm): δ = 13.37 (CH3); 18.94 (CH2); 29.99 (CH2); 46.22 (N-CH2); 110.03 (C9b); 118.55 (C5a); 119.57 (C9); 126.75 (C2’, C6’); 127.16 (C9a); 129.46 (C7); 130.64 (C3’, C5’); 132.00 (C4’); 132.12 (C6); 133.71 (C1’); 134.23 (C2); 136.46 (C8); 140.11 (C3a); 157.92 (C=O); IR (ATR, cm-1): ν = 1766 (C=O); MS (ES+): m/z (%): 319.2 (M+, 100); MP: 214.2-223.5 °C; Yield = 86%; gray crystals; MW = 446.28.
1-m-Methylphenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4e
1H NMR (DMSO-d6, 300 MHz, ppm): δ = 2.48 (s, 3H, C3’-CH3); 4.01 (s, 3H, NCH3); 6.86 (d, 1H, J = 8.0 Hz, H9); 7.58-7.75 (m, 5H, 5 x Har); 7.85 (td, 1H, Jvic = 8.0 Hz, Jallyl = 1.7 Hz, H8); 8.38 (dd, 1H, Jvic = 8.3 Hz, Jallyl = 1,1 Hz, H6); 9.67 (s, 1H, H2); 13C NMR (DMSO-d6, 75 MHz, ppm): δ = 20.86 (Car-CH3); 32.47 (NCH3); 109.65 (C9b); 118.35 (C5a); 119.66 (C9); 123.68 (CHar); 126.84 (CHar); 127.13 (C9a); 129.48 (C7); 130.47 (C5’); 132.20, 132.58 (C6, C4’); 133.60 (C1’); 134.78 (C2); 136.61 (C8); 140.43, 140.69 (C3a en C3’); 157.97 (C=O); MS (ES+): m/z (%): 291.3 (M+, 100); IR (ATR, cm-1): ν = 1759 (C=O); 1517 (C=C); MP: 200.0-205.7 °C; Yield = 94%; yellow crystals; MW = 418.23.
1-m-Methylphenyl-3-butyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4f
1H NMR (DMSO-d6, 300 MHz, ppm): δ = 0.94 (t, 3H, J = 7.1 Hz, CH3); 1.42 (sextet, 2H, J = 7.1 Hz, CH2-CH3); 1.94 (p, 2H, J = 7.1 Hz, NCH2-CH2); 2.45 (s, 3H, Car-CH3); 4.34 (t, 3H, J = 7.1 Hz, NCH2); 6.83 (d, 1H, J = 8.3 Hz, H9); 7.56-7.71 (m, 5H, 5 x CHar); 7.81 (td, 1H, Jvic = 7.8 Hz, Jallyl = 1.3 Hz, CHar); 8.34 (d, 1H, J = 7.7 Hz; H6); 9.71 (s, 1H, H2); 13C NMR (DMSO-d6, 75 MHz, ppm): δ = 13.40 (CH3); 18.94 (CH2); 20.83 (Car-CH3); 30.05 (CH2); 46.21 (NCH2); 109.92 (C9b); 118.58 (C5a); 119.68 (C9); 123.74 (CHar); 126.88 (CHar); 127.14 (C9a); 129.50 (C7); 130.41 (C5’); 132.14 (C6); 132.55 (C4’); 133.65 (C1’); 134.18 (C2); 136.53 (C8); 140.09 (C3a); 140.64 (C3’); 157.95 (C=O); IR (ATR, cm-1): ν = 2956 (CH=CH); 1766 (C=O); MS (ES+): m/z (%) : 333.3 (M+, 100); MP: 213.2-214.2 °C; Yield = 37%; yellow crystals; MW = 460.31.
1-p-Fluorophenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4g
1H NMR (DMSO-d6, 300 MHz, ppm): δ = 4.01 (s, 3H, NCH3); 6.85 (d, 1H, J =7.7 Hz, H9); 7.63-7.97 (m, 6H, 6 x CHar); 8.38 (d, 1H, J =7.7 Hz, H6); 9.69 (s, 1H, H2); 13C NMR (DMSO-d6, 75 MHz, ppm): δ = 32.34 (N-CH3); 109.79 (C9b); 117.53 (CHar); 117.84 (CHar); 117.89 (CHar); 119.63 (C9); 126.92 (C9a); 129.18 (C7); 129.36 (d, J = 8.1 Hz, Car); 129.80 (d, J = 2.3 Hz, Car); 132.10 (C6); 136.59 (C8); 140.09 (C3a); 157.80 (C=O); 161.72 (C4’); IR (ATR, cm-1): ν = 2981 (CH=CH); 1748 (C=O); 1514 (C=C); MS (ES+): m/z (%): 295.2 (M+, 100); MP: 221-222 °C; Yield = 73%; yellow crystals; MW = 422.19.
1-p-Fluorophenyl-3-butyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4h
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 0.97 (t, 3H, J = 7.2 Hz, CH3); 1.46 (sextet, 2H, J = 7.2 Hz, CH2-CH3); 1.97 (p, 2H, J = 7.2 Hz, NCH2-CH2); 4.39 (t, 2H, J = 7.2 Hz, NCH2); 6.86 (d, 1H, J =7.2 Hz, H9); 7.64-7.98 (m, 6H, 6 x CHar); 8.38 (dd, 1H, Jvic = 7.7 Hz, Jallyl = 1.1 Hz, H6); 9.77 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 13.27 (CH3); 18.81 (CH2); 29.94 (CH2); 46.13 (NCH2); 110.10 (C9b); 117.47 (CHar); 117.78 (CHar); 118.40 (C5a); 119.64 (C9); 126.97 (C9a); 129.28 (C7); 129.41 (CHar); 129.88 (d, J = 3.5 Hz, Car); 132.05 (C6); 134.45 (Car); 136.53 (C8); 139.87 (C3a); 157.80 (C=O); 161.78 (C4’); IR (ATR, cm-1): ν = 2999 (CH=CH); 1753 (C=O); 1515 (C=C); MS (ES+): m/z (%): 337.2 (M+, 100); MS (ES-): 591.0; 127.2 (I-); MP: 219.8-221.5 °C; Yield = 71%; yellow crystals; MW = 464.27.
1-p-Methoxyphenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4i
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 3.93 (s, 3H, OCH3); 4.00 (s, 3H, NCH3); 6.86 (d, 1H, J = 7.7 Hz, H9); 7.33 (~dt, 2H, Jvic = 8.8 Hz, Jallyl = 2.8 Hz, H2’, H6’); 7.68-7.89 (m, 4H, 4 x CHar); 8.37 (dd, 1H, Jvic = 8.3 Hz, Jallyl = 1.1 Hz, H6); 9.67 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.29 (N-CH3); 55.82 (OCH3); 109.82 (C9b); 115.55 (C2’, C6’); 118.21 (C5a); 119.49 (C9); 125,95 (C1’); 127.12 (C9a); 127.98 (C3’, C5’); 129.32 (C7); 132.04 (C6); 134.88 (C2); 136.50 (C8); 140.16 (C3a); 157.86 (C=O); 161.27 (C4’); IR (ATR, cm-1): ν = 3030 (CH=CH); 1762 (C=O); 1513 (C=C); MS (ES+): m/z (%): 307.3 (M+, 100); MP: 226.5-233.1 °C; Yield = 95%, yellow crystals; MW = 434.23.
1-p-Methoxyphenyl-3-butyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4j
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 0.97 (t, 3H, J = 7.3 Hz, CH3), 1.46 (sextet, 2H, J = 7.3 Hz, CH2-CH3), 1.96 (p, 2H, J = 7,3 Hz, NCH2-CH2), 3.93 (s, 3H, OCH3), 4.38 (t, 2H, J = 7.3 Hz, NCH2), 6.88 (d, 1H, J =8.3 Hz, H9), 7.33 (~dt, 2H, Jvic = 9.4 Hz, Jallyl = 2.8 Hz, H2’, H6’), 7.67-7.99 (m, 4H, 4 x CHar), 8.37 (d, 1H, J = 7.7 Hz, CH6ar), 9.72 (d, 1H, J = 1.7 Hz, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 13.25 (CH3), 18.83 (CH2), 29.97 (CH2), 46.03 (NCH2), 55.82 (OCH3), 110.01 (C9b), 115.49 (C2’, C6’), 118.42 (C5a), 119.50 (C9), 126.01 (C1’), 127.15 (C9a), 128.05 (C3’, C5’), 129.32 (C7), 131.98 (C6), 134.27 (C2), 136.42 (C8), 139.82 (C3a), 157.86 (C=O), 161.23 (C4’); IR (ATR, cm-1): ν = 1752 (C=O), 1514 (C=C); MS (ES+): m/z (%): 349.2 (M+, 100); MP: 216.9-219.5 °C; Yield = 73%; yellow crystals; MW = 476.31.
1-p-Methylphenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4k
1H NMR (DMSO-d6, 300 MHz, ppm): δ = 2.51 (s, 3H, CH3C4’), 4.01 (s, 3H, NCH3), 6.86 (d, 1H, J = 7.7 Hz, H9), 7.58-7.74 (m, 5H, 5 x CHar), 7.85 (t, 1H, J = 7.4 Hz, CHar), 8.38 (d, 1H, J = 7.7 Hz, H6), 9.65 (s, 1H, H2); 13C NMR (DMSO-d6, 75 MHz, ppm): δ = 20.86 (CH3Cq,ar), 32.29 (NCH3), 109.56 (C9b), 118.24 (C5a), 119.47 (C9), 126.27 (C2’, C6’), 127.05 (C9a), 129.35 (C7), 130.94 (C3’, C5’), 131.03 (C1’), 132.07 (C6), 134.74 (C2), 136.45 (C8), 140.30 (C3a), 141.92 (C4’), 157.83 (C=O); IR (ATR, cm-1): ν = 1766 (C=O), 1516 (C=C); MS (ES+): m/z (%): 291.3 (M+, 100); MP: 234.8-241.7 °C; Yield = 67%, yellow crystals; MW = 418.23.
1-p-Methylphenyl-3-butyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4l
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 0.97 (t, 3H, J = 7.4 Hz, CH3), 1.46 (sextet, 2H, J = 7.4 Hz, CH2-CH3), 1.96 (p, 2H, J = 7.4 Hz, NCH2-CH2), 2.52 (s, 3H, CH3C4’), 4.38 (t, 2H, J = 7.4 Hz, NCH2), 6.86 (d, 1H, J =8.0 Hz, H9), 7.62 (d; 2H, J = 8.3 Hz, H3’ en H5’), 7.70 (td, 1H, Jvic = 8.0 Hz, Jallyl = 1.1 Hz, H7), 7.74 (d, 2H, J = 8.3 Hz, H2’ en H6’), 7.85 (td, 1H, Jvic = 7.8 Hz, Jallyl = 1.1 Hz, H8), 8.37 (d, 1H, J = 8.0 Hz, H6), 9.75 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 13.27 (CH3), 18.84 (CH2), 20.87 (C4’-CH3); 29.94 (CH2); 46.09 (NCH2); 109.95 (C9b); 118.43 (C5a); 119.49 (C9); 126.36 (C2’, C6’), 127.11 (C9a), 129.32 (C7), 130.86 (C3’, C5’), 131.11 (C1’), 131.99 (C6), 134.10 (C2), 136.37 (C8), 139.96 (C3a), 141.89 (C4’), 157.83 (C=O); IR (ATR, cm-1): ν = 1752 (C=O), 1517 (C=C); MS (ES+): m/z (%): 333.3 (M+, 100); MP: 224.3-227.8 °C; Yield = 71%; yellow crystals; MW = 460.31.
1-m-Methoxyphenyl-3-butyl-1H-isochromeno[3,4-d]imidazol-5-onium jodide 4m
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 0.98 (t, 3H, J = 7.2 Hz, CH3), 1.47 (sextet, 2H, J = 7.2 Hz, CH2-CH3), 1.97 (p, 2H, J = 7.2 Hz, NCH2-CH2), 3.87 (s, 3H, OCH3), 4.39 (t, 2H, J = 7.2 Hz, NCH2), 6.92 (d, 1H, J = 7.7 Hz, H9), 7.42 (d, 2H, J = 7.7 Hz, 2 x CHar), 7.52 (d, 1H, J = 1.7 Hz, CH2’ar), 7.67-7.77 (m, 2H, 2 x CHar), 7,87 (t, 1H, J = 7.4 Hz, CHar), 8.38 (d, 1H, J = 7.7 Hz, CH6ar), 9.79 (d, 1H, J = 2.2 Hz, CH2ar); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 13.27 (CH3), 18.84 (CH2), 29.94 (CH2), 46.13 (NCH2), 55.90 (OCH3), 109.89 (C9b), 112.31 (C2’), 117.61 (CHar), 118.39 (Car), 118.47 (Car), 119.69 (C9), 127.03 (C9a), 129.37 (C7), 131.41 (C5’), 131.98 (C6), 134.13 (C2), 134.53 (C1’), 136.44 (C8), 139.89 (C3a), 157.80 (C=O), 160.19 (C3’); IR (ATR, cm-1): ν = 1765 (C=O); MS (ES+): m/z (%): 349.2 (M+, 100); MP: 214.6-218.9 °C; Yield = 74%; yellow crystals; MW = 476.31.
1-Phenyl-2-methyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium iodide 4n
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.57 (s, 3H, Car-CH3), 3.95 (s, 3H, NCH3), 6.50 (d, 1H, J = 7.7 Hz, H9), 7,65 (t, 1H, J = 7.4 Hz, CHar), 7.73-7.92 (m, 6H, 6 x CHar), 8.36 (d, 1H, J = 7.7 Hz, H6); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 10.38 (Car-CH3), 30.90 (NCH3), 108.55 (Cq,ar), 118.08 (Cq,ar), 118.75 (CHar), 127.01 (Cq,ar), 127.30 (CH2’ar), 128.86 (Cq,ar), 131.00 (CH3’ar), 132.10 (CHar), 132.69 (CHar), 136.42 (CHar), 139.64 (Cq,ar), 143.99 (Cq,ar), 157.79 (C=O); IR (ATR, cm-1): ν = 1761 (C=O), MS (ES+): m/z (%): 291.3 (M+, 100); MP: 230.4-239.1 °C; Yield = 96%; yellow crystals; MW = 418.23.
SYNTHESIS OF IMIDAZOLIUM BISTRIFLIMIDES 5a-b.
A solution of 4a or 4g (100 mg) and LiNTf2 (2 equiv) in water (3 mL) was stirred at room temperature for 1 h, during which time a white precipitate of 5a or 5b, respectively, formed. This precipitate was isolated by filtration, washed with water (3 x 2 mL) and dried under vacuum for 1 h.
1-Phenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium bistriflimide 5a
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.49 (s, DMSO), 3.36 (s, H2O), 4.00 (s, 3H, NMe), 6.80 (d, 1H, Jvic = 8.3 Hz, H9), 7.70 (t, 1H, H7), 7.77-7.86 (m, 6H, H3’, H5’, H2’, H6’, H8, H4), 8.37 (d, 1H, Jvic = 8.3 Hz, H6), 9.67 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.43 (NMe), 39.54 (DMSO-d6), 109.67 (C9b), 118.39 (C5a), 119.59 (C9), 126.68 (C2’, C6’), 127.09 (C9a), 129.52 (C7), 130.75 (C3’, C5’), 132.05 (C4’), 132.23 (C6), 133.65 (C1’), 134.91 (C2), 136.59 (C8), 140.45 (C3a), 157.93 (C=O), no CF3 peak visible; 19F-NMR (DMSO-d6, 292 MHz, ppm): δ = (-)78.60 (s, 6F, CF3); IR (ATR, cm-1): ν = 1134.44 (C-F), 1196.67 (C-O), 1517.23 (C=C), 1655.44 (C=N), 1759.78 (C=O), 3152.20 (=C-H); MS (ES+): m/z (%): 277.3 (M+, 100), 278.3 ([M+1]+, 19); MS (ES-): m/z (%): 280.0 ([N(Tf)2]-, 100), 281 ([N(Tf)2]-, 5), 282 ([N(Tf)2]-, 10), 582.8 (7); MP: 198-200 °C; Yield = 58%; beige powder; MW = 557.44.
1-p-Fluorophenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium bistriflimide 5b
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.51 (s, DMSO), 3.37 (s, H2O), 4.01 (s, 3H, NMe), 6.84 (d, 1H, Jvic = 7.7 Hz, H9), 7.68 (t, 2H, H3’, H5’), 7.71 (t, 1H, H7), 7.85 (t, 1H, Jvic = 7.7 Hz, H8) 7.92 (dd, 2H, JH-F = 5.0Hz, Jvic = 8.8 Hz, H2’, H6’), 8.38 (d, 1H, Jvic = 8.3 Hz, H6), 9.68 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.35 (NMe), 39.52 (DMSO-d6), 109.81 (C9b), 116.73 (q, 2C, JC-F = 333.4 Hz, CF3), 117.69 (d, JC-F = 24.2 Hz, C3’, C5’), 118.22 (C5a), 119.64 (C9), 126.94 (C9a), 129.27 (d, JC-F = 10.4 Hz, C2’, C6’), 129.43 (C7), 129.82 (d, JC-F = 3.5 Hz, C1’), 132.11 (C6), 135.04 (C2), 136.59 (C8), 140.22 (C3a), 157.81 (C5=O), 163.42 (d, JC-F = 249.2 Hz, C4’); 19F-NMR (DMSO-d6, 292 MHz, ppm): δ = (-)107.9-(-)107.8 (m), (-)78.61 (s, 6F, CF3); IR (ATR, cm-1): ν = 1191.51 (C-F), 1211.48 (C-O), 1514.22 (C=C), 1656.90 (C=N), 1746.22 (C=O), 3133.83 (=C-H); MS (ES+): m/z (%): 295.3 (M+, 100), 296.3 ([M+1]+, 19); MS (ES-): m/z (%): 280.0 ([N(Tf)2]-, 100), 282 ([N(Tf)2]-, 10), 548.8 (7); MP: 201-205 °C; Yield = 48%; beige powder; MW = 575.43.
SYNTHESIS OF IMIDAZOLIUM DICYANAMIDES 5c-d.
A solution of 4a or 4g (100 mg) and NaN(CN)2 (3 equiv) in water (3 mL) was stirred at room temperature for 1 h, during which time a white precipitate of 5c or 5d, respectively, formed. This precipitate was isolated by filtration, washed with water (3 x 2 mL) and dried under vacuum for 1 h.
1-Phenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium dicyanamide 5c
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.50 (s, DMSO), 3.35 (s, H2O), 4.01 (s, 3H, NMe), 6.81 (d, 1H, Jvic = 7.7 Hz, H9), 7.71 (t, 1H, H7), 7.78-7.88 (m, 6H, H3’, H5’, H2’, H6’, H8, H4), 8.38 (d, 1H, Jvic = 8.3 Hz, H6), 9.70 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.40 (NMe), 39.42 (DMSO-d6), 109.64 (C9b), 117.32 (CN), 118.21 (C5a), 119.43 (C9), 126.56 (C2’, C6’), 127.00 (C9a), 129.34 (C7), 130.57 (C3’, C5’), 131.89 (C4’), 132.07 (C6), 133.52 (C1’), 134.73 (C2), 136.41 (C8), 140.31 (C3a), 157.80 (C=O); IR (ATR, cm-1): ν = 1192, 1213 (C-O), 1498, 1519 (C=C), 1598, 1742 (C=O), 2189 (CN); MS (ES+): m/z (%): 277.3 (M+, 100), 278.3 ([M+1]+, 19); MP: 233.5-234.5 °C; Yield = 62%; off-white powder; MW = 343.34. The product proved unstable upon prolonged dissolution in DMSO-d6. Hence, breakdown was observed in the 13C NMR spectrum.
1-p-Fluorophenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium dicyanamide 5d
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.50 (s, DMSO), 3.36 (s, H2O), 4.01 (s, 3H, NMe), 6.85 (d, 1H, Jvic = 7.7 Hz, H9), 7.64-7.77 (m, 3H, H3’, H5’, H7), 7.80-7.98 (m, 3H, H2’, H6’, H8), 8.38 (d, 1H, Jvic = 8.3 Hz, H6), 9.69 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.44 (NMe), 39.52 (DMSO-d6), 109.90 (C9b), 117.81 (d, JC-F = 23.1Hz, C3’, C5’), 118.32 (C5a), 119.05 (CN), 119.76 (C9), 127.01 (C9a),129.36 (d, JC-F = 9.2Hz, C2’, C6’), 129.53 (C7), 129.92 (d, JC-F =2.31Hz, C1’), 132.22 (C6), 135.17 (C2), 136.71 (C8), 140.33 (C3a), 157.92 (C5=O), 163.53 (d, JC-F = 249.2Hz, C4’); 19F-NMR (DMSO-d6, 292 MHz, ppm): δ = (-)107.79-(-)107.91(m); IR (ATR, cm-1): ν = 1158.00 (C-F), 1217.88 (C-O), 1516.97 (C=C), 1650.48 (C=N), 1746.73 (C=O), 2135.02 (CN), 3113.68 (=C-H); MS (ES+): m/z (%): 295.3 (M+, 100), 296.3 ([M+1]+, 22); MP: 197-199 °C; Yield = 47%; white powder; MW = 361.33.
SYNTHESIS OF IMIDAZOLIUM TETRAFLUOROBORATES 5e-f.
A solution of 4a or 4g (200 mg) and LiBF4 (2 equiv) in water (6 mL) was stirred at room temperature for 1 h, during which time a white precipitate of 5e or 5f, respectively, formed. This precipitate was isolated by filtration, washed with water (3 x 4 mL) and dried under vacuum for 1 h.
1-Phenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium tetrafluoroborate 5e
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.50 (s, DMSO), 3.39 (s, H2O), 4.02 (s, 3H, NMe), 6.82 (d, 1H, Jvic = 7.7 Hz, H9), 7.69 (t, 1H, H7), 7.77-7.87 (m, 6H, H3’, H5’, H2’, H6’, H8, H4), 8.38 (d, 1H, Jvic = 7.7 Hz, H6), 9.68 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.38 (NMe), 39.53 (DMSO-d6), 110.21 (C9b), 118.39 (C5a), 119.59 (C9), 126.66 (C2’, C6’), 127.09 (C9a), 129.52 (C7), 130.76 (C3’, C5’), 132.05 (C4’), 132.24 (C6), 133.66 (C1’), 134.91 (C2), 136.57 (C8), 140.45 (C3a), 157.95 (C5=O); 19F-NMR (DMSO-d6, 292 MHz, ppm): δ = (-)71.91(s), (-)148.18 (s, [11BF4]-), (-)148.13 (s, [10BF4]-); IR (ATR, cm-1): ν = 1049.44 (C-F), 1220.95 (C-O), 1508.96 (C=C), 1643.38(C=N), 1759.53 (C=O), 3080.44 (=C-H); MS (ES+): m/z (%): 277.3 (M+, 100), 278.3 ([M+1]+, 19); MS (ES-): m/z (%): 86.3 ([10BF4]-, 30), 87.3 ([11BF4]-, 100), 197 (69); MP: 242-245 °C; Yield = 44%; beige powder; MW = 364.10.
1-p-Fluorophenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium tetrafluoroborate 5f
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.50 (s, DMSO), 3.38 (s, H2O), 4.02 (s, 3H, NMe), 6.86 (d, 1H, Jvic = 7.7 Hz, H9), 7.61-7.76 (m, 3H, H3’, H5’, H7), 7.81-7.94 (m, 3H, H2’, H6’, H8), 8.38 (d, 1H, Jvic = 7.7 Hz, H6), 9.66 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.39 (NMe), 39.52 (DMSO-d6), 109.86 (C9b), 117.82 (d, JC-F = 24.2Hz, C3’, C5’), 118.33 (C5a), 119.75 (C9), 127.02 (C9a), 129.36 (d, JC-F = 9.2 Hz, C2’, C6’), 129.54 (C7), 129.94 (d, JC-F = 2.3Hz, C1’), 132.21 (C6), 135.16 (C2), 136.70 (C8), 140.34 (C3a), 157.93 (C5=O), 163.56 (d, JC-F = 249.2Hz, C4’); 19F-NMR (DMSO-d6, 292 MHz, ppm): δ = (-)107.4-(-)107.6 (m), (-)148.08 (s, [11BF4]-), (-)148.02 (s, [10BF4]-); IR (ATR, cm-1): ν = 1059.77 (C-F), 1214.65 (C-O), 1511.36 (C=C), 1651.92 (C=N), 1757.10 (C=O), 3126.61 (=C-H); MS (ES+): m/z (%): 295.3 (M+, 100), 296.3 ([M+1]+, 22); MS (ES-): m/z (%): 86.3 ([10BF4]-, 22), 87.3 ([11BF4]-, 92), 468 (57), 469.0 (100); MP: 237-239 °C; Yield = 65%; beige powder; MW = 382.09.
SYNTHESIS OF IMIDAZOLIUM HEXAFLUOROPHOSPHATES 5g-h.
Hexafluorophosphoric acid (65 wt% in water, 1.3 equiv, ~0.1 mL) was added to a suspension of 4a or 4g (0.5 mmol) in water (5 mL). The resulting mixture was stirred at room temperature for 8 h, during which time a precipitate of 5g or 5h, respectively, formed. This precipitate was isolated by filtration, washed with water until neutral, and dried under vacuum for 1 h.
1-Phenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium hexafluorophosphate 5g
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.50 (s, DMSO), 3.36 (s, H2O), 4.01 (s, 3H, NMe), 6.81 (d, 1H, Jvic = 7.8 Hz, H9), 7.71 (t, 1H, Jvic = 7.8 Hz, H7), 7.77-7.91 (m, 6H, H3’, H5’, H2’, H6’,H8, H4’), 8.38 (d, 1H, Jvic = 7.8 Hz, H6), 9.69 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.31 (NMe), 39.41 (DMSO-d6), 109.56 (C9b), 118.24 (C5a), 119.46 (C9), 126.54 (C2’, C6’), 126.98 (C9a), 129.37 (C7), 130.60 (C3’, C5’), 131.92 (C4’), 132.08 (C6), 133.53 (C1’), 134.76 (C2), 136.44 (C8), 140.32 (C3a), 157.81 (C5=O); 19F-NMR (DMSO-d6, 292 MHz, ppm): δ = (-)70.40 (d, JP-F = 710.3 Hz, [PF6]-); IR (ATR, cm-1): ν = 835.05, 1214.41 (C-O), 1520.75 (C=C), 1657.33 (C=N), 1742.69 (C=O), 3152.20 (=C-H); MS (ES+): m/z (%): 277.3 (M+, 100), 278.3 ([M+1]+, 19); MS (ES-): m/z (%): 127.0 (I-, 13), 145.0 ([PF6]-, 100), 293.3 (16), 313.0 (59); MP: 224-227 °C; Yield = 57%; white powder; MW = 422.26.
1-p-Fluorophenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium hexafluorophosphate 5h
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.50 (s, DMSO), 3.35 (s, H2O), 4.01 (s, 3H, NMe), 6.86 (d, 1H, Jvic = 8.3Hz, H9), 7.64-7.75 (m, 3H, H3’, H5’, H7), 7.82-7.92 (m, 3H, H2’, H6’, H8), 8.39 (d, 1H, Jvic = 8.3Hz, H6), 9.65 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.28 (NMe), 39.45 (DMSO-d6), 109.75 (C9b), 117.73 (d, JC-F = 23.1 Hz, C3’, C5’), 118.24 (C5a), 119.69 (C9), 126.92 (C9a), 129.24 (d, JC-F = 9.2Hz, C2’, C6’), 129.46 (C7), 129.82 (d, JC-F = 2.3 Hz, C1’), 132.15 (C6), 135.12 (C2), 136.62 (C8), 140.25 (C3a), 157.80 (C5=O), 163.48 (d, JC-F = 250.3 Hz, C4’); 19F-NMR (DMSO-d6, 292 MHz, ppm): δ = (-)70.01 (d, JP-F = 718.2 Hz, [PF6]-), (-)107.85-(-)107.88 (m); IR (ATR, cm-1): ν = 835.05, 1220.23 (C-O),1320.26 (C-F), 1517.99 (C=C), 1660.90 (C=N), 1746.28 (C=O), 3156.01 (=C-H); MS (ES+): m/z (%): 295.0 (M+, 100), 296.3 ([M+1]+, 18); MS (ES-): m/z (%): 145.0 ([PF6]-, 100), 280.0 (35), 313.0 (18); MP: 226-228 °C; Yield = 40%; white powder; MW = 440.25. The product proved unstable upon prolonged dissolution in DMSO. Hence, breakdown was observed in the 13C NMR spectrum.
SYNTHESIS OF IMIDAZOLIUM TRIFLATES 5i-j.
1H-Isochromeno[3,4-d]imidazol-1-one 3a or 3b (1 mmol), methyl triflate (2 equiv) and MeCN (5.5 mL) were quickly added to a flame-dried round bottom flask equipped with a stirring bar. The resulting mixture was kept under an N2 atmosphere and stirred at room temperature for 30 min. Reaction progress was monitored using TLC. The desired imidazolium triflates 5i or 5j were obtained via evaporation of the solvent and excess alkylating agent. Finally, the obtained salts were dried under vacuum for 1 h. If impurities should be present, the product can be recrystallized from acetonitrile at -15 °C.
1-Phenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium triflate 5i
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.50 (s, DMSO), 3.46 (s, H2O), 4.01 (s, 3H, NMe), 6.81 (d, 1H, Jvic = 7.7 Hz, H9), 7.70 (t, 1H, H7), 7.79-7.88 (m, 6H, H3’, H5’, H2’, H6’,H8, H4’), 8.38 (d, 1H, Jvic = 7.7 Hz, H6), 9.67 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.38 (NMe), 39.41 (DMSO-d6), 109.69 (C9b), 118.43 (C5a), 119.62 (C9), 121.20 (q, JC-F = 321.9, CF3), 126.70 (C2’, C6’), 127.13 (C9a), 129.48 (C7), 130.75 (C3’, C5’), 132.06 (C4’), 132.23 (C6), 133.71 (C1’), 134.92 (C2), 136.55 (C8), 140.50 (C3a), 157.97 (C5=O); 19F-NMR (DMSO-d6, 292 MHz, ppm): δ = 77.64 (s, 3F, CF3); IR (ATR, cm-1): ν = 1143.45 (C-F), 1258.59 (C-O), 1517.42 (C=C), 1647.93 (C=N), 1758.54 (C=O), 3043.88 (=C-H); MS (ES+): m/z (%): 277.3 (M+, 100), 278.3 ([M+1]+, 21); MS (ES-): m/z (%): 149.0 ([OTf]-, 100), 151 (6), 316.0 (18), 321.0 (6), 575.0 (6); MP: 170-173 °C; Yield = 85%; brown powder; MW = 426.37.
1-p-Fluorophenyl-3-methyl-1H-isochromeno[3,4-d]imidazol-5-onium triflate 5j
1H-NMR (DMSO-d6, 300 MHz, ppm): δ = 2.50 (s, DMSO), 3.38 (s, H2O), 4.02 (s, 3H, NMe), 6.86 (d, 1H, Jvic = 8.3 Hz, H9), 7.63-7.74 (m, 3H, H3’, H5’, H7), 7.81-7.92 (m, 3H, H2’, H6’, H8), 8.38 (d, 1H, Jvic = 7.7 Hz, H6), 9.65 (s, 1H, H2); 13C-NMR (DMSO-d6, 75 MHz, ppm): δ = 32.54 (NMe), 39.52 (DMSO-d6), 110.26 (C9b), 118.03 (d, JC-F = 23.1 Hz, C3’, C5’), 118.61 (C5a), 119.96 (C9), 120.89 (q, JC-F = 321.9 Hz, CF3), 127.36 (C9a), 129.59 (d, JC-F = 9.2Hz, C2’, C6’), 130.26 (d, JC-F = 2.3 Hz, C1’), 130.63 (C7), 132.38 (C6), 135.33 (C2), 136.80 (C8), 140.70 (C3a), 158.25 (C5=O), 163.89 (d, JC-F = 249.2 Hz, C4’); 19F-NMR (DMSO-d6, 292 MHz, ppm): δ = (-)107.94-(-)107.82 (m), (-)77.69 (s, 3F, CF3); IR (ATR, cm-1): ν = 1028.61 (C-F), 1245.02 (C-O), 1509.37 (C=C), 1650.80 (C=N), 1759.04 (C=O), 3045.96 (=C-H): MS (ES+): m/z (%): 295.0 (M+, 100), 296.3 ([M+1]+, 18); MS (ES-): m/z (%): 149.0 ([OTf]-, 100), 321.0 (20), 593.0 (50); MP: 167-170 °C; Yield = 94%; brown powder; MW = 444.36.

ACKNOWLEDGEMENTS
Bart I. Roman thanks the Research Foundation – Flanders (Fonds voor Wetenschappelijk Onderzoek – Vlaanderen) for financial support for this research.

References

1. D. R. J. Acke and C. V. Stevens, Green Chem., 2007, 9, 386.. CrossRef
2. D. R. J. Acke, C. V. Stevens, and B. I. Roman, Org. Proc. Res. Dev., 2008, 12, 921. CrossRef
3. R. P. Swatloski, J. D Holbrey, and R. D. Rogers, Green Chem., 2003, 5, 361. CrossRef
4. P. J. Scammells, J. L. Scott, and R. D. Singer, Austr. J. Chem., 2005, 58, 155. CrossRef
5. L. Benhamou, E. Chardon, G. Lavigne, S. Bellemin-Laponnaz, and V. César, Chem. Rev., 2011, 111, 2705. CrossRef
6. D. Enders, O. Niemeier, and A. Henseler, Chem. Rev., 2007, 107, 5606. CrossRef
7. D. Bourissou, O. Guerret, F. P. Gabbaï, and G. Bertrand, Chem. Rev., 2000, 100, 39. CrossRef
8. G. Gasser, I. Ott, and N. Metzler-Nolte, J. Med. Chem., 2011, 54, 3. CrossRef
9. D. Zhao, Z. Fei, W. H. Ang, and P. J. Dyson, Int. J. Mol. Sci., 2007, 8, 304. CrossRef
10. J. G. Huddleston, H. D. Willauer, R. P. Swatloski, A. E. Visser, and R. D. Rogers, Chem. Commun., 1998, 1765. CrossRef
11. J. D. Holbrey and R. D. Rogers, In Ionic Liquids in Synthesis; ed. by P. Wasserscheid and T. Welton, Wiley-VCH: Weinheim, 2003, 4.
12. A. Elaiwi, P. B. Hitchcock, K. R. Seddon, N. Srinivasan, Y. M. Tan, T. Welton, and J. A. Zora, J. Chem. Soc., Dalton Trans., 1995, 3467. CrossRef
13. J. Fuller, R. T. Carlin, H. C. De Long, and D. Haworth, Chem. Commun., 1994, 299. CrossRef
14. C. Chiappe, A. Marra, and A. Mele, Top. Curr. Chem., 2010, 295, 177. CrossRef