Note Cite This: J. Org. Chem. 2019, 84, 417−422
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Synthesis of Unsymmetrical Heterobenzisapphyrins Sunit Kumar, Kishor G. Thorat, and Mangalampalli Ravikanth* Indian Institute of Technology, Powai, Mumbai, 400076, India
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ABSTRACT: Two examples of highly unsymmetrical heterobenzisapphyrins containing one benzene, two pyrroles, one furan, and one thiophene ring connected via four meso-carbons and one direct bond were prepared over a sequence of five steps in 8−9% yields. The X-ray structure revealed that the furan ring was inverted from the macrocyclic framework and the macrocycle was nearly planar. Spectral and electrochemical studies indicated that the macrocycle was nonaromatic in nature due to lack of conjugation.
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of highly unsymmetrical heterobenzisapphyrins 1a and 1b containing one benzene, one thiophene, one furan, and two pyrroles connected via four meso-carbons and one direct benzene−thiophene link which involves multistep synthesis as depicted in Scheme 1. The single crystal structure analysis of one of the heterobenzisapphyrins 1b revealed that the furan ring was inverted from the macrocyclic framework, and the spectral and electrochemical studies supported the nonaromatic nature of the heterobenzisapphyrins 1a and 1b.
apphyrins are 22π electron aromatic macrocycles containing five pyrrole rings connected via four meso-carbons and one direct pyrrole−pyrrole link. Sapphyrins were serendipitously discovered by Woodward and co-workers during their early investigations into the total synthesis of vitamin B12.1 Although some initial synthetic reports were available on sapphyrins, these pentapyrrolic macrocycles have received tremendous attention only after their accidental discovery as good receptors for anions by Sessler and co-workers.2 Thus, Sessler and co-workers in the early 1990s revived the interest in sapphyrin macrocycles and showed their potential applications in viral photoeradication,3 as photosensitizers in photodynamic therapy,4 in anion binding/sensing,5 ligand for metal coordination, and in material science.6 Over the years, new analogues of sapphyrins such as heterosapphyrins resulted from the replacement of one or more pyrrole rings with thiophene, furan, and selenophene. N- or X-confused heterosapphyrins in which pyrrole or heterocycle is inverted were synthesized, and their properties were studied. 7 Carbasapphyrins in which one or two pyrrole rings are replaced by carbacycles,8 polycyclic aromatic moieties embedded sapphyrins such as biphenyl sapphyrins and phenanthrene sapphyrins,9 and so on were prepared, and were explored for their properties and applications in various fields.8 Interestingly, among carbasapphyrins, the reports on phenylene containing sapphyrins are very rare, though a significant amount of work has been done on benzene containing porphyrins.10 The benzene containing porphyrin analogues have been used to understand aromaticity and conjugation since the characteristics of these macrocycles vary from nonaromatic to highly aromatic and few examples of antiaromatic structures are also known.11 The benzene containing porphyrinoids readily form organometallic derivatives and can be used as chemical sensors and also in molecular recognition studies.12 To date there are only limited reports available on benzene containing expanded porphyrinoids. However, more examples on benzene containing heterosapphyrins are required to understand their physico-chemical and coordination properties. In this paper, we report two examples © 2018 American Chemical Society
Scheme 1. Synthesis of Heterobenzisapphyrins (1a/1b)
Received: October 10, 2018 Published: November 30, 2018 417
DOI: 10.1021/acs.joc.8b02616 J. Org. Chem. 2019, 84, 417−422
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The Journal of Organic Chemistry The unsymmetrical heterobenzisapphyrins 1a and 1b were synthesized as shown in Scheme 1. m-Bromobenzaldehyde was reacted with thiophene 2-boronic acid under Suzuki coupling reaction conditions (Experimental Section), followed by silica gel column chromatographic purification, afforded m-thienylbenzaldehyde 2 as a yellow oily liquid in 78% yield. The compound 2 was subjected to Grignard reaction by treating it with ArMgBr in THF, followed by column chromatographic purification, to afford the corresponding mono-carbinol 3a/3b as a white solid in 50−53% yields. The appropriate monocarbinol 3a/3b was treated first with 1.2 equiv of n-BuLi, followed by the addition of 1.2 equiv of 4-methyl benzaldehyde in dry THF at 0 °C. After workup, the crude compound was subjected to silica gel column chromatographic purification and afforded the respective dicarbinols 4a/4b as pale white solids in 45−53% yields. The dicarbinols 4a/4b were treated with excess pyrrole in 1,2-dichloroethane in the presence of a catalytic amount of BF3·OEt2, and the resulting crude compounds were purified by silica gel column chromatography to afford the respective pure tetrapyranes 5a/5b as pale yellow oily pastes in 56−63% yields (Scheme 1). The other required intermediate, 2,5-bis(p-tolyl)hydroxymethylfuran 6, was prepared by using the reported method.13 The unsymmetrical heterobenzisapphyrins 1a/1b were synthesized by 1:1 condensation of the appropriate tetrapyrrane (5a/ 5b) and furan dicarbinol 6 in CH2Cl2 in the presence of a catalytic amount of TFA at room temperature for 1 h under an inert atmosphere, followed by oxidation with 2,3-dichloro-1,4benzoquinone (DDQ) in open air for an additional 30 min (Scheme 1). The crude reaction mixtures were subjected to alumina column chromatography, and the major brown band was collected to afford the desired heterobenzisapphyrins 1a/ 1b as brown solids in 8−9% yields. Attempts to condense the 5a/5b with other thiophene/selenophene diols to obtain the corresponding unsymmetrical heterobenzisapphyrins were unsuccessful. The heterobenzisapphyrins 1a/1b were characterized by HR-MS, 1D/2D NMR spectroscopy, and X-ray crystallography. The respective molecular ion peak in HR-MS confirmed the identities of heterobenzisapphyrins 1a and 1b. The 1H and 1H−1H COSY NMR spectra of macrocycle 1a are shown in Figure 1. The macrocycle showed a greater number of resonances due to its asymmetric nature, and the Xray structure also showed that the furan ring was inverted from the macrocyclic framework (Figure 2). Thus, we identified and assigned all resonances based on location, integration, coupling constant, and cross-peak correlations in COSY and NOESY spectra. In the 1H NMR spectrum of macrocycle 1a, the anisyl −OCH3 protons (type I) appeared as a singlet resonance at 3.91 ppm and showed NOE correlation with a doublet at 7.20 ppm which we identified as type l protons of the meso-anisyl group. The multiplet in the region of 7.35−7.38 ppm was assigned to type m protons of the meso-anisyl group based on its cross-peak correlation with type l protons. The inner −CH proton of the o-phenylene unit was observed as broad singlet at 8.16 ppm. The doublet at 7.85 ppm was assigned to the type b proton of the m-phenylene unit based on its NOE correlation with the type m proton. The type b proton showed cross-peak correlation with the type c proton of the m-phenylene unit which appeared along with type m protons as a multiplet in the region of 7.35−7.38 ppm. The type d proton of m-phenylene was also identified based on its cross-peak correlation with the type c proton, and it appeared as a multiplet in the region of 7.14−7.16 ppm. The type II −CH3 protons of the meso-tolyl
Figure 1. 1D and 2D NMR spectra for compound 1a recorded in CDCl3 at room temperature.
Figure 2. X-ray structure of heterobenzisapphyrin 1b with 50% thermal ellipsoid probability: (a) front view and (b) side view. All the meso-aryl groups and hydrogen atoms are omitted for clarity.
group appeared as a singlet at 2.49 ppm and showed NOE correlation with a doublet at 7.31 ppm (type n) which in turn showed cross-peak correlation with type o protons which appeared as a multiplet in the region of 7.48−7.52 ppm. The type f proton of thiophene which appeared as a doublet at 7.07 ppm was identified based on NOE correlation with type o protons. The type e proton appeared as multiplet in the region of 7.48−7.52 ppm along with type o protons which was identified since it showed cross-peak correlation with type f protons. The two doublets at 6.91 and 6.97 ppm were identified as type g and type h protons of the pyrrole I ring based on their cross-peak correlations. The pyrrole II ring j protons appeared as a doublet at 6.88 ppm, whereas the type k protons appeared as a multiplet along with type d protons. The inverted furan ring type i and type i′ protons which appeared as two sets of doublets at 7.24 and 7.41 ppm, respectively, were also identified based on similar correlations in 2D NMR spectra. The other meso-tolyl protons were also similarly identified and assigned. Similarly, all the resonances in compound 1b were also identified and assigned using 1D and 2D NMR spectroscopy. Thus, although the benzisapphyrin macrocycles 1a and 1b were asymmetric, 1D and 2D 418
DOI: 10.1021/acs.joc.8b02616 J. Org. Chem. 2019, 84, 417−422
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reported hetero-m-benzisapphyrins.10b Upon protonation of 1a (2 × 10−5 M), by systematic addition of TFA (0−2.0 equiv, 2 × 10−2 M), a change in the color of the solution was noticed from green to yellow and the absorption bands experienced bathochromic shifts (456 to 486 and 683 to 948 nm) with clear isosbestic points (360, 423, 466, and 770 nm) as shown in Figure 3. Compound 1b and its dicationic species 1b·2H2+ also showed similar absorption features (Figure S31). The systematic protonation studies were also followed by 1H NMR spectroscopy which showed the upfield shifts of all benzene, pyrrole, furan, and thiophene protons along with the appearance of two inner −NH protons at 8.96 and 11.34 ppm due to formation of 1a·2H2+ (Figures S32 and S33). The redox properties of 1a/1b were investigated by cyclic voltammetry and differential pulse voltammetry in CH2Cl2 containing TBAP (0.1 M) as supporting electrolyte. The cyclic voltammograms along with differential pulse voltammograms of 1a and 1b are shown in Figure 4. Macrocycles 1a and 1b
NMR spectroscopy was very useful in deducing the molecular structure of macrocycles. We obtained the molecular structure of heterobenzisapphyrin 1b as shown in Figure 2, and crystallographic data are given in Tables S1 and S2. Suitable single crystals of compound 1b were obtained by slow evaporation of a chloroform/pet-ether solution at room temperature over a period of 1 week, and the macrocycle crystallizes in a orthorhombic system with a Fdd2 space group. The crystal structure revealed that the macrocycle core heteroatoms and benzene inner carbon atom (N1, N2, S1, O1, and C6) were almost in the plane, whereas the two pyrrole rings, furan, thiophene, and benzene rings were deviated alternately in upward and downward directions with dihedral angles of 6.87°, 15.57°, 30.92°, 11.65°, and 14.80° with respect to the mean plane (C11-C16-C21-C26). The furan ring was found inverted from the macrocyclic framework to get relief from electrostatic repulsions between electron lone pairs on N1, N2, and O1. The phenylene moiety in macrocycle 1b retained its benzene like features as seen from analysis of C−C bond lengths within the ring (1.360(16)−1.411(14) Å) except for the C4−C5 bond (1.429(15) Å) possessing single bond characteristic features, which indicates the absence of conjugation. However, the remaining C−C, C−S, C−O, and C−N bond lengths in the rest of the macrocyclic core other than the m-phenylene ring display typical conjugated bond behavior within the macrocycle. All the meso substituents in 1b were arranged in orthogonal fashion with respect to the plane of the macrocycle. Overall, the crystal structure analysis revealed that the heterobenzisapphyrin 1b adopts almost planar geometry with inversion of the furan ring toward the macrocyclic framework and also supported nonaromatic character due to lack of conjugation. We have studied the absorption properties of heterobenzisapphyrins 1a/1b and their diprotonated forms 1a·2H2+/1b· 2H2+ which were generated by addition of excess amounts of TFA (Figure S31). The absorption spectra of 1a upon systematic addition of TFA to generate its protonated derivative 1a·2H2+ is shown in Figure 3. The absorption spectrum of 1a showed one broad absorption band at 683 nm and two relatively sharp bands at 456 and 393 nm. The unsymmetrical heterobenzisapphyrins 1a and 1b were found to show blue-shifted absorption maxima compared to our recently
Figure 4. Comparison of cyclic voltammograms of compound 1a (black line) and compound 1b (red line) and the differential pulse voltammogram (dotted blue line) recorded in CH2Cl2 with 0.1 M TBAP as the supporting electrolyte at a scan rate of 50 mV s−1.
exhibit three irreversible oxidations, one reversible reduction, and one irreversible reduction. For example, the heterobenzisapphyrin macrocycle 1a showed three irreversible oxidations at 0.89, 1.15, and 1.41 V, one reversible reduction at −0.68 V, and one irreversible reduction at −1.53 V. The ease of reduction of macrocycles 1a/1b supports the electrondeficient nature of heterobenzisapphyrins. Also, these macrocycles were found to be difficult to oxidize compared to heterom-benzisapphyrins reported by our group.10b Further, the density functional theory (DFT) calculations were carried out for 1b and its diprotonated form 1b·2H2+ to understand the changes in structural, spectral, and electrochemical properties of 1b before and after protonation. The S0 (ground) state optimized geometries are presented in Figure S35. The DFT study showed a very similar structure for 1b as obtained by X-ray and predicted a more distorted structure for its diprotonated form 1b·2H2+. The optimized geometry of the compound 1b·2H2+ indicated that the heterocyclic rings were deviated more from the plane of the macrocycle compared to its nonprotonated form 1b. Analysis of selected frontier molecular orbitals (FMOs) of the compounds 1b and 1b·2H2+ suggested that the HOMOs in both were localized mainly on the furan ring and meso substituents adjacent to the furan ring (Figure S36). The LUMOs were distributed essentially all over the macrocyclic core, leaving no orbital densities on meso substituents. In 1b·2H2+, the FMOs were stabilized to a greater extent and there was a decrease in band gap, suggesting
Figure 3. Change in the absorption spectra of 1a (2 × 10−5 M) upon the systematic addition of (2 × 10−2 M) trifluoroacetic acid in CHCl3 at room temperature. 419
DOI: 10.1021/acs.joc.8b02616 J. Org. Chem. 2019, 84, 417−422
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29.8, 55.4, 75.8, 114.1, 123.4, 124.0, 125.0, 125.2, 125.7, 128.1, 128.2, 129.1, 134.7, 136.1, 144.4, 144.8, 159.3 ppm; HRMS (ESI-TOF) m/ z: [M − OH]+ calcd for C18H15OS 279.0838, found 279.0834. Phenyl(3-(thiophen-2-yl)phenyl)methanol (3b). Phenyl(3(thiophen-2-yl)phenyl)methanol 3b was prepared by following the same procedure as given for compound 3a by using 3-(thiophen-2yl)benzaldehyde 2 (2.00 g, 0.472 mmol) and PhMgBr (17.1 mL of a 3 M solution in Et2O, 53.12 mmol). The crude compound was purified by silica gel column chromatography and obtained the desired compound 3b using petroleum ether/ethyl acetate (90:10) as a white solid (1.50 g, 53% yield). mp: 100−102 °C; 1H NMR (500 MHz, CDCl3): 2.25 (bs, 1H), 5.88 (s, 1H), 7.06 (dd, J = 3.6 Hz, 1H), 7.26− 7.31 (m, 4H), 7.33−7.36 (t, 3H), 7.40−7.42 (m, 2H), 7.51−7.52 (m, 1H), 7.66 (t, J = 1.7 Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3): δ = 76.3, 123.4, 124.2, 125.1, 125.4, 125.8, 126.7, 128.1, 128.7, 129.2, 134.8, 143.8, 143.7, 144.4, 144.6 ppm; HRMS (ESI-TOF) m/z: [M − OH]+ calcd for C17H13S 249.0732, found 249.0732. (5-(3-(Hydroxy(4-methoxyphenyl)methyl)phenyl)thiophen2-yl)(p-tolyl)methanol (4a). A sample of benzene thia mono-ol 3a (1 g, 3.37 mmol) in 30 mL of diethyl ether in a three-neck roundbottom flask under a N2 atmosphere was cooled to −10 °C. Tetramethylethylenediamine (TMEDA) (0.98 g, 1.26 mL, 8.43 mmol) and n-butyl lithium (5.27 mL, 1.6 M solution in hexane) were added to the stirred solution. The resulting mixture was vigorously stirred at 0 °C for 1.5 h. Then, to the reaction mixture, an ice cold solution of p-tolualdehyde (0.80 mL, 6.74 mmol) in dry THF (40 mL) was added, and stirring was continued for an additional 15 min at 0 °C. The reaction was quenched by adding an ice-cold NH4Cl solution (50 mL, ca. 1 M). The organic layer was diluted with diethyl ether and washed 2−3 times with water, and brine and dried over anhydrous sodium sulfate. The crude compound obtained after removal of solvent was subjected to silica gel column chromatography using petroleum ether/ethyl acetate (70:30) which afforded 4a as a white solid (0.75 g, 53% yield). mp: 114−116 °C; 1H NMR (500 MHz, CDCl3): 2.27 (bs, 1H), 2.38 (s, 3H), 2.48 (bs, 1H), 3.81 (s, 3H), 5.82 (s, 1H), 6.01 (s, 1H), 6.85−6.89 (m, 3H), 7.15 (d, J = 3.6 Hz, 1H), 7.20 (d, J = 7.9 Hz, 2H), 7.25−7.34 (m, 4H), 7.37 (d, J = 7.9 Hz, 2H), 7.46−7.47 (m, 1H), 7.60 (bs, 1H); 13C{1H} NMR (125 MHz, CDCl3): δ = 21.2, 21.3, 55.4, 60.5, 72.6, 114.1, 122.9, 123.7, 124.9, 125.6, 125.8, 126.4, 128.1, 129.1, 129.4, 134.6, 136.0, 138.0, 140.2, 144.3, 144.8, 147.9, 153.3 ppm; HRMS (ESI-TOF) m/z: [M − OH]+ calcd for C26H23O2S 399.1413, found 399.1414. (3-(5-(Hydroxy(p-tolyl)methyl)thiophen-2-yl)phenyl)(phenyl)methanol (4b). Compound 4b was prepared by following the same procedure as given for compound 4a by using phenyl(3(thiophen-2-yl)phenyl)methanol 3b (1.00 g, 3.35 mmol), tetramethylethylenediamine (TMEDA) (1.09 g, 1.40 mL, 9.38 mmol), nbutyl lithium (5.86 mL of 1.6 M solution in hexane), and ptolualdehyde (0.90 mL 7.5 mmol). The crude compound was purified by silica gel column chromatography and obtained the desired compound 4b using petroleum ether/ethyl acetate (75:25) as a white solid (0.80 g, 45% yield). mp: 110−112 °C 1H NMR (400 MHz, CDCl3): 2.29 (bs, 1H), 2.36 (s, 3H), 2.42 (bs, 1H), 5.84 (s, 1H), 5.99 (s, 1H), 6.83 (dd, J = 3.7 Hz, 1H), 7.12 (d, J = 3.7 Hz, 1H), 7.18 (d, J = 7.8 Hz, 2H), 7.23−7.39 (m, 9H), 7.43−7.46 (m, 1H), 7.60 (t, J = 1.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ = 21.3, 72.6, 76.3, 122.9, 123.9, 125.0, 125.8, 125.9, 126.4, 127.8, 129.1, 129.4, 134.7, 138.0, 140.2, 143.7, 144.2, 144.6, 148.0 ppm; HRMS (ESI-TOF) m/ z: [M − OH]+ calcd for C25H21OS 369.1308, found 369.1308. 2-((3-(5-((1H-Pyrrol-2-yl)(p-tolyl)methyl)thiophen-2-yl)phenyl)(phenyl)methyl)-1H-pyrrole (5a). To a solution of (5-(3(hydroxy(4-methoxyphenyl)methyl)phenyl)thiophen-2-yl)(p-tolyl)methanol 4a (1.00 g, 2.40 mmol) and pyrrole (1.61 g, 24.01 mmol) in 1,2-dichloroethane (150 mL) under nitrogen, after 15 min, BF3·OEt2 (68.15 mg, 0.48 mmol) was added, and the resulting mixture was stirred under reflux for 6 h. The solution was cooled to room temperature, and the solvent was evaporated on a rotatory evaporator. The product was purified by silica gel column chromatography by eluting with a mixture of pet ether/ethyl acetate in a ratio of 85:15. Evaporation of the product fractions gave the benzitetrapyrrane 5a as
formation of electron-deficient species and supporting the bathochromic shift in absorption upon protonation of 1b. In conclusion, we have synthesized two examples of new highly unsymmetrical heterobenzisapphyrins over a sequence of steps. The heterobenzisapphyrins reported here are quite different in structure and properties compared to some known heterobenzisapphyrins.10 The crystal structure revealed that the heterobenzisapphyrin adopts an almost planar conformation with inversion of the furan ring from the macrocyclic framework. The NMR and absorption studies support the asymmetric and nonaromatic nature of the macrocycles. The redox studies indicated the macrocycles were electrondeficient.
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EXPERIMENTAL SECTION
General Experimental. 3-Bromobenzaldehyde, thiophene, pyrrole, trimethylborate, BF3·OEt2, trifluoroacetic acid (TFA), and 2,3dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) were used as obtained from Sigma-Aldrich. All other chemicals used for the synthesis were reagent grade unless otherwise specified. The spectral, electrochemical, and X-ray single crystal structure analyses were performed as previously described.14 For UV−vis, the solutions for all compounds (2 × 10−5 M) were prepared by using spectroscopic grade CHCl3 solvent. The X-ray data for compound 1b (CCDC 1871885) can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Computational Details. DFT calculations for the compound 1b and its diprotonated form 1b·2H2+ in unrestricted mode were performed using the Gaussian 09 program package15 as described previously.14 3-(Thiophen-2-yl)benzaldehyde (2). Thiophene-2-boronic acid (5.19 g, 40.54 mol) was added to the solution of 3-bromobenzaldehyde (5.00 g, 27.02 mmol) and Pd(PPh3)4 (312 mg, 2.70 mmol) in 50 mL of 1,2-dimethoxyethane under a nitrogen atmosphere at room temperature. Subsequently, an aqueous solution of sodium carbonate (20 mL, 2 M) was added to the reaction. The resulting mixture was heated at reflux for 12 h, with vigorous stirring under a nitrogen atmosphere. Then the reaction mixture was allowed to cool to room temperature and poured into water, and extracted with diethyl ether. The combined organic layers were washed with water, and brine, and dried over sodium sulfate. The crude product obtained after removal of solvent was subjected to silica gel column chromatography using a petroleum ether/ethyl acetate (95:5) solvent mixture, which afforded 3-(thiophen-2-yl)benzaldehyde 2 as a pale yellow oily liquid (4.10 g, 78% yield). 1H NMR (400 MHz, CDCl3): 7.10 (dd, J = 3.6 Hz, 1H), 7.35 (dd, J = 3.6 Hz, 1H), 7.40 (dd, J = 3.6 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.77−7.80 (m, 1H), 7.85−7.88 (m, 1H), 8.10 (t, J = 1.6 Hz, 1H), 10.06 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ = 124.2, 125.9, 126.8, 128.4, 128.8, 129.8, 131.7, 135.6, 137.1, 142.8, 192.2 ppm; HRMS (ESI-TOF) m/z: [M − H]+ calcd for C11H7OS 187.0212, found 187.0203. (4-Methoxyphenyl)(3-(thiophen-2-yl)phenyl)methanol (3a). 3-(Thiophen-2-yl)benzaldehyde 2 (2.00 g, 10.62 mmol) was dissolved in dry degassed THF (100 mL), and the freshly prepared PhMgBr (17.1 mL of a 3 M solution in Et2O, 53.12 mmol) was added to the reaction mixture. The resulting mixture was stirred for 8 h at room temperature. The reaction mixture was slowly quenched with NH4Cl and extracted with diethyl ether. The extracts were washed twice with water and dried over sodium sulfate, and the solvent was removed under reduced pressure. The crude compound was purified by silica gel column chromatography using petroleum ether/ethyl acetate (85:15). The evaporation of solvent on a rotary evaporator under reduced pressure gave the desired compound (4-methoxyphenyl)(3-(thiophen-2-yl)phenyl)methanol 3a as a white solid (1.60 g, 50% yield). mp: 105−107 °C; 1H NMR (400 MHz, CDCl3): 2.16 (d, J = 3.2 Hz, 1H), 3.72 (s, 3H), 5.76 (d, J = 2.4 Hz, 1H), 6.15 (d, J = 8.4 Hz, 2H), 6.99 (dd, J = 3.6 Hz, 1H), 7.18−7.28 (m, 6H), 7.42− 7.44 (m, 1H), 7.58 (bs, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ = 420
DOI: 10.1021/acs.joc.8b02616 J. Org. Chem. 2019, 84, 417−422
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The Journal of Organic Chemistry
Phenylene); 13C{1H} NMR (100 MHz, CDCl3): δ = 21.5, 29.8, 114.1, 116.0, 123.8, 124.3, 127.6, 127.7, 128.4, 128.6, 128.7, 129.0, 129.1, 129.2, 130.2, 130.4, 130.5, 130.9, 131.3, 132.1, 132.4, 134.2, 134.3, 135.2, 135.3, 135.8, 137.2, 137.3, 137.4, 138.9, 139.1, 142.0, 142.3, 142.7, 146.0, 151.5, 154.7, 155.1, 163.9, 168.0, 173.3 ppm; UV−vis (in CHCl3, λmax/nm, log ε) = 275 (4.5), 454 (4.7), 673 (4.1) and 941 (3.4); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C53H39N2OS 751.2778, found 751.2773.
a pale-colored oil (0.70 g, 56% yield) that was stored in the freezer. 1 H NMR (500 MHz, CDCl3): 2.37 (s, 3H), 3.81 (s, 3H), 5.43 (s, 1H), 5.62 (s, 1H), 5.83 (bs, 1H), 6.00 (bs, 1H), 6.17−6.20 (m, 2H), 6.72 (bs, 2H), 6.73 (d, J = 3.5 Hz, 1H), 6.88 (d, J = 8.5 Hz, 2H), 7.06−7.21 (m, 8H), 7.27−7.30 (m, 1H), 7.40−7.43 (m, 2H), 7.83 (bs, 1H), 7.95 (bs, 1H); 13C{1H} NMR (125 MHz, CDCl3): δ = 21.2, 45.8, 49.8, 55.4, 107.6, 108.0, 108.4, 108.5, 113.0, 114.0, 117.3, 117.4, 122.8, 124.0, 126.1, 126.8, 127.8, 128.4, 129.1, 129.5, 129.9, 131.4, 133.2, 133.8, 134.7, 135.0, 136.9, 139.7, 143.3, 144.1, 146.9, 158.5 ppm; HRMS (ESI-TOF) m/z: [M + K]+ calcd for C34H30N2OSK 553.1710, found 553.1715. 2-((3-(5-((1H-Pyrrol-2-yl)(p-tolyl)methyl)thiophen-2-yl)phenyl)(phenyl)methyl)-1H-pyrrole (5b). The benzitetrapyrrane 5b was prepared by following the same procedure as given for compound 5a by using (3-(5-(hydroxy(p-tolyl)methyl)thiophen-2yl)phenyl)(phenyl)methanol 4b (1.00 g, 2.59 mmol), pyrrole (1.74 g, 25.87 mmol), and BF3·OEt2 (73.44 mg, 0.51 mmol). The crude compound was purified by alumina column chromatography and obtained the desired compound 5b using petroleum ether/ethyl acetate (90:10) as a pale-colored oil (0.80 g, 63% yield). 1H NMR (400 MHz, CDCl3): 2.34 (s, 3H), 5.45 (s, 1H), 5.60 (s, 1H), 5.81 (bs, 1H), 5.97 (bs, 1H), 6.14−6.16 (m, 2H), 6.71 (bs, 2H), 6.73 (dd, J = 3.6 Hz, 1H), 7.03−7.05 (m, 1H), 7.08 (d, J = 3.6 Hz, 1H), 7.12− 7.25 (m, 8H), 7.28−7.32 (m, 3H), 7.38−7.41(m, 2H), 7.81 (bs, 1H), 7.92 (bs, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ = 21.2, 45.6, 50.55, 107.5, 108.0, 108.3, 108.4, 117.2, 122.6, 124.0, 126.0, 126.7, 127.7, 128.2, 128.5, 128.8, 129.0, 129.3, 133.0, 133.2, 134.6, 136.8, 139.6, 142.7, 143.2, 143.6, 146.8 ppm; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H29N2S 485.2046, found 485.2051. Compound 1a. A sample of benzitetrapyrrane 5a (100 mg, 0.19 mmol) and furan-2,5-diylbis(p-tolylmethanol) 6 (64 mg, 0.19 mmol) were dissolved in 70 mL of CH2Cl2 under a nitrogen atmosphere. Then to this was added 10 μL of TFA (0.02 mmol), and the reaction mixture was allowed to stir at room temperature for 1 h. After 1 h, DDQ (107 mg, 0.24 mmol) was added and the reaction mixture was stirred in open air for an additional 30 min. The solvent was removed under reduced pressure, and the crude compound was purified by basic alumina column chromatography using petroleum ether/ethyl acetate (85:15), which afforded 1a as a dark green colored solid (12 mg, 8% yield). mp: decomposes at ∼120 °C; 1H NMR (500 MHz, CDCl3): δ = 2.38 (s, 3H, −CH3), 2.40 (s, 3H, −CH3), 2.49 (s, 3H, −CH3), 3.91 (s, 3H, -OCH3), 6.88 (d, J = 4.5 Hz, 2H, β-Py), 6.91 (d, J = 4.0 Hz, 2H, β-Py), 6.97 (d, J = 4.0 Hz, 2H, β-Py), 7.07 (d, J = 8.7 Hz, 2H, Ar), 7.07 (d, J = 5.4 Hz, 2H, β-Th), 7.14−7.16 (m, 3H, β-Py and Phenylene), 7.18−7.22 (m, 5H, β-Oxa, Ar), 7.31 (d, J = 8.7 Hz, 2H, Ar), 7.35−7.38 (m, 3H, Phenylene and Ar), 7.41 (d, J = 4.1 Hz, 2H, β-Oxa), 7.49−7.55 (m, 7H, β-Thia, and Ar), 7.85−7.86 (m, 1H, Phenylene), 8.16 (bs, 1H, Phenylene); 13C{1H} NMR (100 MHz, CDCl3): δ = 21.5, 29.8, 55.6, 113.1, 114.1, 115.7, 124.0, 124.3, 127.6, 128.5, 128.7, 129.0, 129.1, 129.2, 129.5, 130.0, 130.3, 130.5, 130.8, 131.3, 132.4, 132.5, 133.8, 134.2, 134.3, 134.5, 135.1, 135.2, 135.3, 135.6, 137.0, 137.1, 137.3, 138.9, 139.5, 142.2, 142.7, 146.7, 151.5, 154.3, 155.27, 160.2, 12.5, 164.0, 168.0, 172.8 ppm; UV−vis (in CHCl3, λmax/nm, log ε) = 275 (4.7), 454 (4.7) and 673 (4.1); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C54H41N2O2S 781.2883, found 781.2884. Compound 1b. Compound 1b was prepared by following the same procedure as given for compound 1a by using benzitetrapyrrane 5b (100 mg, 0.20 mmol), furan-2,5-diylbis(p-tolylmethanol) 6 (64 mg, 0.20 mmol), TFA (0.01 mL, 0.02 mmol), and DDQ (107 mg, 0.24 mmol). The crude compound was purified by alumina column chromatography and obtained the desired compound 1a using petroleum ether/ethyl acetate (90:10) as dark green colored solid (14 mg, 9% yield). mp: decomposes at ∼120 °C; 1H NMR (500 MHz, CDCl3): δ = 2.38 (s, 3H, −CH3), 2.40 (s, 3H, −CH3), 2.49 (s, 3H, −CH3), 6.87 (d, J = 4.6 Hz, 2H, β-Py), 6.92 (d, J = 4.4 Hz, 2H, βPy), 6.98 (d, J = 4.4 Hz, 2H, β-Py), 7.06 (d, J = 4.6 Hz, 2H, β-Py), 7.12−7.15 (m, 3H, β-Th and Phenylene), 7.19−7.24 (m, 5H, β-Oxa, Ar), 7.31−7.38 (m, 4H, β-Th, Phenylene and Ar), 7.43−7.55 (m, 12H, β-Oxa, and Ar), 7.87−7.89 (m, 1H, Phenylene), 8.29 (bs, 1H,
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b02616. Characterization data (including HRMS, 1H, and 13 NMR spectra) for all the reported compounds, absorption, and crystallographic data (PDF) Crystallographic data for 1b (CIF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Fax: 91-22-5723480. Tel: 91-22-5767176. ORCID
Mangalampalli Ravikanth: 0000-0003-0193-6081 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This paper is dedicated to Professor C. P. Rao, IIT Bombay. M.R. thanks the Department of Science and Technology, Govt. of India (File No. EMR/2015/002196 to M.R), S.K. thanks the UGC (ref. No. 23/12/2012(ii)EU-V) for a fellowship, and K.G.T. thanks the IIT Bombay, India, for an Institute Postdoctoral Fellowship.
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REFERENCES
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