One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P® activation of 3-arylpropiolic acids

In situ activation of 3-arylpropiolic acids with T3P® (n-propylphosphonic acid anhydride) initiates a domino reaction furnishing 4-arylnaphtho[2,3-c]furan-1,3-diones in excellent yields. Upon employing these anhydrides as reactive intermediates blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones are formed by consecutive pseudo three-component syntheses in a one-pot fashion. The Stokes shifts correlate excellently with the Hammett–Taft σR parameter indicating an extended degree of resonance stabilization in the vibrationally relaxed excited singlet state.


4-Phenylnaphtho
Based upon our experience in using propylphosphonic acid anhydride (T3P ® ) [47] as a condensation agent for in situ activation of benzyl alcohols in the synthesis of N-benzylphenothiazine derivatives [48], we reasoned that T3P ® might be equally well suited for furnishing 4-phenylnaphtho[2,3-c]furan-1,3diones, and thereby opening a straightforward entry to 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones in a diversity-oriented one-pot process. Here, we report the development of the onepot synthesis of these title compounds by a consecutive pseudo three-component approach and the investigation of the luminescence behavior by absorption and emission spectroscopy.
Interestingly, in this domino synthesis of 4-phenylnaphtho[2,3c]furan-1,3-diones electron-rich and electro-neutral substrates are equally well tolerated ( Table 2, entries 1-3), while the electron-poor derivative 1d results in a slightly decreased yield of 88% due to the increased formation of side products ( Table 2, entry 4). Expectedly, the products 2 are not stable under acidic aqueous conditions (e.g., hydrochloric acid, silica gel and saturated aqueous solution of ammonium chloride) [49]. After 48 h in the presence of deuterated hydrochloric acid (36% in D 2 O),  Table 3).
In dichloromethane at only slightly elevated temperatures imide 4a is not formed ( Table 3, entry 1). Upon addition of N,Ndimethylformamide as a cosolvent at 80 °C the desired product 4a can be isolated in 15% yield (Table 3, entry 2). The yield of 4a can be increased to 47% upon raising the reaction temperature to 115 °C (Table 3, entry 3), however, higher temperatures, such as 160 °C, cause a significant drop in yield. Finally, at 115 °C with two equivalents of aniline the highest yield can be achieved (Table 3, entry 6).
Besides comprehensive NMR spectroscopic and mass spectrometric characterization the structures of the title compounds 4 were additionally corroborated by a crystal structure determination of compound 4b (Figure 1). The twist angle of the phenyl substituent (ring A) and the 1H-pyrrole-2,5-dionyl moiety is 51.37 (7)°, whereas the p-anisyl substituent (ring B) is considerably twisted against the adjacent six-membered ring by 70.95(7)° ( Figure 1) [50].
The increased amount of the condensation agent T3P ® obviously enables further activation of the initially formed 1H-benzo[f]isoindole-1,3(2H)-dione by electrophilic attack on the sterically easier accessible carbonyl group. As a consequence the imine condensation proceeds also with thermodynamic control giving exclusively the formation of the E-configured product 5. Interestingly the corresponding reaction with ortho-phenylenediamine (3n) gives rise to the regioselective formation of the pentacyclic condensation product 6, where the intramolecular imine formation formally occurred at the sterically more biased carbonyl group (Scheme 7).

Figure 2:
The ORTEP-type plot of the crystal structure 5 (left) and a centrosymmetric dimer formation by π-π interactions (right) (ellipsoids are drawn at the 40% probability level).
In addition to NMR spectroscopic and mass spectrometric characterization the crystal structures of the imine condensation products 5 and 6 were determined (Figure 2 and Figure 3) [50]. In similarity to 4b the twist angles of the phenyl substituents (rings A and B) are 61.1(1)° and 66.8(1)°, respectively ( Figure 2, left part). Interestingly, the crystal structure of 5 shows centrosymmetric dimers, formed by a close π-π interaction of the planar naphthyl moieties (Figure 2, right part). The intermolecular distance of the naphthalene moieties of the two molecules accounts to 3.435 (7) Å.
This intermolecular plane distance of the two adjacent naphthyl moieties (C2-C11) must be understood as a π-π interaction of two fused aromatic systems [51]. The twist angle of the attached phenyl substituent (ring B) of the asymmetric unit of the crystal structure 6 were determined as 62.28(5)° ( Figure 3). The significant difference of the twist angles in 4b, 5, and 6 could be a consequence of packing in the individual crystal structure. The crystal structure of the pentacyclic molecules 6 shows stacks with an antiparallel arrangement of the monomers. The found interplanar distance is 3.437(4) Å. Consequently, π-π interactions must be considered for this structure [51,52]. Bond lengths and angles of the reported crystal structures 4b, 5, and 6 are in the expected range. The tricyclic 1H-benzo[f]isoindole-1,3(2H)-dionyl moiety in 4b, 5 and the corresponding 3-imino-1-oxo-2,3-dihydro-1H-benzo[f]isoindolyl moiety in 6 are absolutely planar.
All 1-aryl-2,3-naphthaleneimides 4 possess two characteristic absorption maxima λ max,abs between 258.5 and 273.5 nm with molar extinction coefficients ε of 55000 L•mol −1 •cm −1 and between 359.0 and 379.0 nm with molar extinction coefficients ε of about 3500 L•mol −1 •cm −1 . While electron-withdrawing substituents R 1 in tendency shift the absorption maxima slightly hypsochromically (Table 6, entries 1, and 3-6) the electron-donating methoxy group (Table 6, entry 2) clearly causes a red shift. The absorption spectra of the imine condensation products 5 and 6 essentially display a similar appearance; however, the pentacycle 6 possesses a considerably more intense longest wavelength absorption, which appears in the spectrum at 388.5 nm as a shoulder with a molar extinction coefficients ε of 21600 L•mol −1 •cm −1 ( Table 6, entry 12).
Although most of the 1H-benzo[f]isoindole-1,3(2H)-diones 4 fluorescence upon excitation with UV light, a closer inspection, by comparing the relative intensities of the emission maxima at identical concentrations, reveals that only the methoxy derivative 4b (Table 6, entry 2) is substantially fluorescent ( Figure 5). With this exception all qualitatively determined emission spectra reveal a broad unstructured maximum followed by a shoulder. This appearance might result from the free rotation of the N-phenyl substituents, furnishing emissive conformers that arise from a coplanar (λ max,em at 468.0 nm as a shoulder for compound 4a) and torsional orientation (λ max,em at 408.5 nm as a maximum for compound 4a) of the N-phenyl substituent in the corresponding excited Franck-Condon states [54]. Qualita-tively, also a red shift of the emission maximum can be detected upon increasing the electron-withdrawing character of the substituent R 1 . In the consanguineous series of 1H-benzo[f]isoindole-1,3(2H)-diones 4a,b,d-f the emission maxima λ max,em are found in a range from 408.5 to 512.5 nm with Stokes shifts lying between 3900 and 2500 cm −1 (Table 6, entries 1, 2 and 4-6, Figure 6).  This electronic substituent effect of R 1 on the Stokes shifts was further corroborated by linear structure-property relationships based upon Hammett-Taft correlations with the consanguineous series 4a,b,d-f. Correlation studies of the longest wavelength absorption maxima λ max,abs , the shortest wavelength emission maxima λ max,em , and the Stokes shifts Δ with the Hammett-Taft parameters σ p , σ R, σ p+ , and σ p− [55] disclose an interesting insight on electronic substituent effects in the electronic ground and excited states (see Table S6 in Supporting Information File 1). Although the linear correlations of λ max,abs with all σ parameters are relatively poor, the correlations of λ max,em with σ R and σ p+ indicate a strong influence of resonance stabilization in the vibrationally relaxed excited state. This is even more the case in the nearly perfect linear correlation of the Stokes shift with σ R (r 2 = 0.989) and can be interpreted as a significant structural change upon photonic excitation and excited state relaxation resulting from a considerable charge transfer character, as supported by the influence of the remote polar substitution (Figure 7). Interestingly, compound 4a, which has a fluorescence quantum yield Φ f of less than 0.01 in dichloromethane solution, experiences an over eightfold increase to 0.08 in the solid state emission as determined from the powder by an integrating sphere.
In comparison to the 1-phenyl-[2,3-c]-naphthaleneimide 5, which is only weakly luminescent, the pentacycle 6 displays a relative enhancement of the greenish emission at 500 nm by a factor of 340 (relative to compound 4a, Figure 8) and can be quantified with a fluorescence quantum yield of 0.10 ( Table 6, entry 12).

Conclusion
3-Arylpropiolic acids can be readily activated with T3P ® (n-propylphosphonic acid anhydride) to initiate a domino reaction furnishing 4-arylnaphtho[2,3-c]furan-1,3-diones in excel- lent yields. These anhydrides can be considered as reactive intermediates for a subsequent imidation with primary amines and, therefore, a one-pot reaction in the sense of a consecutive pseudo three-component process evolved. The resulting 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones are interestingly blue to greenish-blue emissive upon excitation of the longest wavelength absorption bands. The photophysical characterization by absorption and emission spectroscopy revealed that the Stokes shifts are excellently correlated with Hammett-Taft's σ R parameters indicating an extended degree of resonance stabilization as a result of a charge transfer character in the vibrationally relaxed S 1 -state. The fluorescence can be redshifted by employing 1,2-phenylenediamine as a reaction partner in the terminal step of the sequence furnishing a rigidified planar pentacyclic condensation product. The interesting emission properties and the straightforward diversity-oriented synthetic approach are therefore well-suited for the design of covalently ligated, conjugated and non-conjugated bichromophores in a rapid fashion. Studies directed towards the one-pot synthesis of more complex polycyclic emitters are currently underway.

Supporting Information
The Supporting Information contains all experimental procedures, spectroscopic and analytical data as well as copies of NMR spectra of compounds 2, 4, 5, and 6. X-ray structure analyses of compounds 4b, 5, and 6, and Hammett-Taft correlations of compounds 4a,b,d-f are also given.

Supporting Information File 1
Experimental part.