1 Introduction
Fulgide family compounds are the subject of numerous publications, mainly due to their photochromic properties and applications in the synthesis of lignans [1,2]. From the fulgide-related compounds, fulgimides appear to be the most interesting for data storage applications because of their increased fatigue resistance, higher chemical stability compared to the parent fulgides and the possibility of functionalisation at the nitrogen atom.
N-substituted fulgimides can be synthesized by functionalisation of simple N-H imides or by the dehydratation of related succinamic acids. The latter can be obtained either by the reaction of a fulgide with a primary amine or by the reaction of a succinic half-ester with the Grignard salt of the amine [1,3].
Amongst available dehydrating agents, the most common is acetyl chloride [4], acetic anhydride [5] and thionyl chloride [6] but there are also literature reports about the use of carbonyldiimidazole (CDI) [7], carbodiimides [1,8] and recently also hexamethyldisilazane (HMDS) [9].
It is known that DCC (N,N’-dicyclohexylcarbodiimide) and CDI (1,1’-carbonyldiimidazole) may give unsatisfactory results due to the formation of isofulgimides instead of fulgimides [1,8].
The use of acetyl chloride or acetic anhydride proved not always effective due to the formation of acidic byproducts, which can lead to decomposition of the material.
Otto et al. [10] have developed another interesting method for fulgimide formation, where the succinamic acid is esterified to give a phenacyl ester, which is then cyclized to the imide by treatment with a base. The disadvantage of this approach is that it requires additional steps and the treatment with a strong base (t-BuLi) is sometimes necessary. Nevertheless, the obtained yields are much better compared to other methods.
We have already successfully used benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP; Castro's reagent) for the coupling of amines or alcohols with carboxylates, and we usually obtained excellent results [11,12].
As none of the methods described in the literature proved successful in the case of the synthesis of chiral imide 2e due to its instability, we decided to employ BOP. The good yield of dehydratation and a short reaction time encouraged us to check this method on a broader scope of substrates.
2 Results and discussion
The used synthetic procedure is presented in Scheme 1. Fulgides 1a and 1b were prepared according to the literature protocols [2b, 2h], involving a double Stobbe condensation followed by saponification of the 2,3-bisarylidene succinic acid ester and subsequent treatment with acetyl chloride. It is noteworthy that BOP could also successfully be used for the dehydratation of fulgenic acids to produce fulgides. The yield obtained using this methodology was always higher than obtained by the treatment with acetyl chloride and similar to those observed when DCC was used. In contrast to DCC, the purification process was much easier. Nevertheless, in the case of most fulgides, the use of somewhat more expensive and toxic BOP does not seem to be reasonable.
General procedure for the BOP-mediated synthesis of fulgimides 2a-f.
Fulgides react almost quantitatively with primary amines in the presence of one equivalent of tertiary amine (triethylamine, TEA). TEA can compete in salt formation between the succinamic acid and the primary amine, thus its addition was found to be beneficial to the rate of the reaction and the obtained yield.
Rigorous drying of the resulted amide acid is essential for the next step, since even traces of residual humidity significantly lowers the yield of the BOP-mediated reactions. The mixture of the amide acid with 1.05 eq of BOP in dry tetrahydrofuran (THF) was then treated with 1.1 eq of TEA, first at −45 °C and then at room temperature. We found that final warming up of the reaction mixture to 35 °C slightly increased the yield. The usual work-up affords the product pure enough to crystallize out of the ethereal solution without additional purification by column chromatography. However, in the case of the oily imide 2e, this operation was necessary.
The described method proved to be the only applicable for the synthesis of this compound.
Attempted synthesis using acetyl chloride or DCC gave only trace amounts of the product 2e.
It is also noteworthy that in the case of N-(4-bromo)phenyl fulgimide 2d, the yield was increased significantly, comparing to the obtained by traditional methods (48%). We found p-bromophenyl fulgimides of particular interest due to a possibility to introduce other structural modifications at the N-phenyl ring e.g. via the Suzuki-Miyaura cross coupling. The X-ray structure of fulgimide 2d proves the (E,E) configuration of the double bonds which causes helical chirality of the molecule (Fig. 1), that can be further elaborated in stereoselective transformations [12].
Oak Ridge Thermal Ellipsoid Plot (ORTEP) diagram of molecule 2d.
The described method will be evaluated for the synthesis of thermally irreversible heterocyclic fulgimides.
3 Conclusion
We have developed a mild method for the preparation of fulgimides which can be used for the synthesis of bisarylidenefulgimides having different N-substituents. The yields are superior to those obtained with traditional dehydratation with AcCl or CDI. For unstable fulgimide 2e, the BOP-mediated dehydratation proved to be the only applicable procedure.
4 Experimental
The NMR spectra were recorded on a Varian Unity Plus spectrometer operating at 200 MHz for 1H NMR and at 50 MHz for 13C NMR. The spectra were measured in CDCl3 and are given as δ values (in ppm) relative to TMS. Mass spectra were collected on Quattro LC Micromass and LCT Micromass TOF HiRes apparatus. Optical rotations were measured on Perkin-Elmer 241 polarimeter. TLC analyses were performed on silica gel plates (Merck Silica Gel 60 F254) and visualized using UV-light. Column chromatography was carried out at atmospheric pressure using Silica Gel 60 (230–400 mesh, Merck). Melting points were determined by a Boetius hot-plate microscope and were uncorrected. Solvents used in the reactions were anhydrous. CH2Cl2 was dried with anhydrous CaCl2. THF was dried with CaH2 and distilled under argon directly into the reaction vessel. The single-crystal X-ray measurements were carried out on Oxford Diffraction Xcalibur R κ-axis diffractometer with CCD Ruby detector. In all cases, Cu Kα characteristic radiation was applied. After initial corrections and data reduction, intensities of reflections were used to solve and consecutively refine structures using SHELXS97 [13] and SHELXL97 [14] programs. Further absorption corrections were applied in final steps of refinement. BOP and all other reactants were purchased from Aldrich.
The anhydrides 1a and 1b were prepared according to literature protocols, via double Stobbe condensation/esterification sequences, followed by saponification and dehydratation with AcCl at reflux. The analytical data were in accordance with those presented in the literature for 1a [2b] and 1b [2g].
4.1 General synthesis of fulgimides 2
Fulgide 1a (100 mg, 0.22 mmol) or 1b (100 mg, 0.36 mmol) was dissolved in a minimal amount of CH2Cl2 and 1.05 eq of primary amine was added in dry CH2Cl2. In the case of the synthesis of 2a, methylamine was cooled to −78 °C, and 2.5 eq were added directly to the cooled solution of the fulgide in dry CH2Cl2. It was not necessary to use TEA in this preparation. In all other cases, 2 eq of TEA were added and the solution was stirred at room temperature or refluxed until bleaching of the solution indicated complete turnover of the coloured fulgide. The solvents were evaporated, and the residue dissolved in AcOEt and washed with 10% aqueous citric acid solution and brine. The organic layer was dried with Na2SO4, filtered and evaporated in vacuo to give the appropriate succinamic acid as an oily residue. Dry THF was distilled directly into the reaction mixture (approx. 1 mL/20 mg) and 1.05 eq of BOP was added under argon. The mixture was stirred and cooled to −45 °C. Then 1.1 eq of TEA was added at this temperature and the solution was left to reach room temperature and then was warmed to 35 °C. During the time of the reaction, a color change from slightly yellow to deep yellow or deep orange was observed. After 30 more minutes of reaction time, the solvent was evaporated, the residue dissolved in AcOEt and washed with 10% citric acid solution (2 ×), then 5% NaHCO3 solution (4 ×), water (1 ×) and brine (1 ×). The solution was dried over Na2SO4, filtered and evaporated to dryness.
Fulgimides 2a–d and 2f started to crystallize after immediate treatment with diethyl ether.
Fulgimide 2e was subjected to flash column chromatography on Al2O3 (it decomposed immediately on silica) using diethyl ether as an eluent.
Yields and analytical data for fulgimides 2a–f are presented in Table 1.
Structure of products 2a–f, the obtained yields and analytical data.
| Compound | Isolated yield and analytical data |
| 2a | 76%, 78 mg of dense, deep yellow oil, which slowly solidifies to form dark yellow crystals; Mp 152–154 °C 1H NMR: 3.25 (s, 3H), 3.64 (s, 12H), 3.76 (s, 6H); 6.29 (s, 4H), 7.68 (s, 2H), 13C NMR: 25.09, 55.93, 61.43, 107.87, 122.47, 130.14, 134.65, 140.53, 152.28, 170.67 HRMS: m/z [M + Na]+ calcd for C25H27NNaO8 492.1634; found 492.1626 |
| 2b | 92%, 107 mg of fine yellow crystals; Mp 174–175 °C 1H NMR: 3.66 (s, 12H), 3.78 (s, 6H), 6.35 (s, 4H), 7.51 (m, 5H), 7.79 (s, 2H) 13C NMR: 55.89, 61.41, 107.93, 122.07, 126.65, 128.59, 129.27, 130.11, 132.16, 135.44, 140.66, 152.24, 169.53 HRMS: m/z [M + Na]+ calcd for C30H29NNaO8 554.1791; found 554.1782 |
| 2c | 94%; 116 mg of fine yellow crystals; Mp 217–219 °C 1H NMR: 3.65 (s, 12H), 3.78 (s, 6H), 3.87 (s, 3H), 6.34 (s, 4H), 7.05 (d, J = 4.5 Hz, 2H), 7.41 (d, J = 4.5 Hz, 2H), 7.77 (s, 2H) 13C NMR: 55.67, 55.93, 61.41, 108.00, 114.63, 122.20, 124.82, 127.89, 130.16, 135.26, 140.69, 152.28, 159.59, 169.82, HRMS: m/z [M + Na]+ calcd for C31H31NNaO9 584.1897; found 584.1901 |
| 2d | 82%; 110 mg of fine yellow crystals; Mp 190–191 °C 1H NMR: 3.63 (s, 12H), 3.76 (s, 6H); 6.31 (s, 4H); 7.42 (d, J = 4.4 Hz, 2H), 7.66 (d, J = 4.4 Hz, 2H), 7.76 (s, 2H) 13C NMR: 55.92, 61.44, 108.00, 121.79, 122.35, 128.10, 130.00, 131.19, 132.43, 135.77, 140.81, 152.27, 169.21 HRMS: m/z [M + Na]+ calcd for C30H28BrNNaO8 632.0896; found 632.0878 CCDC nr 847340 |
| 2e | 73%, 89 mg of dense, deep yellow oil; [α]D20 +94 (c 1, CHCl3) 1H NMR: 1.97 (d, J = 7.4 Hz, 3H), 3.62 (s, 12H); 3.75 (s, 6H); 5.25 (q, J = 7.4 Hz, 1H); 6.25 (s, 4H); 7.26–7.42 (m, 3H); 7.58 (m, 2H); 7.61 (s, 2H) 13C NMR: 27.58, 50.59, 55.97, 61.47, 107.88, 117.13, 122.47, 127.89, 127.91, 128.69, 130.24, 134.66, 140.90, 152.28, 171.20 HRMS: m/z [M + Na]+ calcd for C32H33NNaO8 582.2104; found 582.2099 |
| 2f | 60%, 87 mg of fine, yellowish crystals; Mp 234–237 °C 1H NMR: 6.80–6.95 (m, 8H), 7.04–7.13 (m, 2H), 7.51–7.56 (m, 2H), 7.62 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1H), 7.87–7.97 (m, 2H), 7.93 (s, 2H), 7.99 (d, J = 8.6 Hz, 1H), 8.03 (d, J = 1.8 Hz, 1H) 13C NMR: 122.59, 124.18, 125.74, 126.66, 126.90, 127.25, 127.89, 128.43, 129.05, 129.66, 129.87, 129.99, 132.90, 133.35, 134.81, 135.87, 169.71 HRMS: m/z [M + Na]+ calcd for C28H19NNaO2 424.1313; found 424.1313 |
Acknowledgment
The authors kindly acknowledge the financial support from the Polish Ministry of Science and Higher Education (grant No. N204 030636).