CN110317160B - Novel method for activating sulfonylated 2-phenylisoisatin through C-H - Google Patents
Novel method for activating sulfonylated 2-phenylisoisatin through C-H Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
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Abstract
The invention relates to a novel method for constructing a 2-phenylisoisatin derivative by performing sulfonylation amination on 2-phenylisoisatin through aryl C-H activation reaction catalyzed by transition metal by using sulfonyl azide as a coupling reagent. Compared with the traditional technology, the invention has good functional group tolerance and high yield; low temperature, safety and convenience, and wide application prospect; the by-product is only nitrogen, so that a large amount of by-products are avoided, and the atom utilization rate is improved; the preactivation of a substrate is not needed, the reaction condition is mild, the reaction time is short, and the operation difficulty is reduced.
Description
Technical Field
The invention belongs to the technical field of organic synthetic chemistry, and particularly relates to a novel method for constructing a 2-phenylisoisatin derivative by performing sulfonylation amination on 2-phenylisoisatin through a C-H activation reaction of aryl catalyzed by transition metal by using sulfonyl azide as a coupling reagent.
Background
Isoisatin is an important building block, and its analogs have antibacterial, antifungal and antiproliferative activity[1-4]. Among them, 2-phenylisoisatin compounds have been receiving wide attention in recent years because the 2-phenyl group plays an important role in the activity against plasmodium[1]. Interestingly, it was found that the introduction of amino groups on the phenyl groups enhances the antimalarial activity of this class of compounds[2]. Methods for establishing 2-phenylisatin are numerous[1,3]However, when the phenyl group has a substituent at the ortho-position, the reaction yield is low, and the reaction of such compounds is mainly a cycloaddition reaction, such as with an olefin[3]Olefine aldehyde[4]And indoles[5]The reaction of (3). Therefore, there is a need to develop more efficient and flexible methods for modifying these compounds to obtain more derivatives of 2-phenylisoisatin compounds.
In recent years, the carbon-hydrogen bond functionalization catalyzed by transition metal is widely applied to the construction of C-C bond, C-heteroBond, heterocycle[6]. While N-O is commonly used as a directing group during C-H activation to direct the metal catalyst to a certain C-H bond in the molecule, resulting in its selective cleavage and subsequent functionalization[6]. Theoretically, N-O of the 2-phenylisoisatin can also be used as a guide group for C-H activation reaction to realize the sulfonylation of the ortho-position of the benzene ring of the 2-phenylisoisatin.
Disclosure of Invention
The invention realizes a novel method for constructing the 2-phenylisoindigo red derivative by taking a 2-phenylisoindigo red compound as a raw material and sulfonyl azide as a coupling reagent and performing aryl C-H activation reaction catalyzed by transition metal to perform sulfonamide amination on the 2-phenylisoindigo red. The invention solves the problems of complicated reaction steps, harsh reaction conditions, low atom utilization rate and the like in the traditional synthetic method, reduces the production cost, avoids environmental pollution because the by-product is only nitrogen, and provides a preparation method which is milder, rapid, simple, convenient, safe, effective, low in cost and good in substrate applicability, thereby having wide application prospect.
The technical route of the invention takes 2-phenylisoindigo red compound as a substrate and sulfonyl azide as a coupling reagent, and the 2-phenylisoindigo red compound and the sulfonyl azide are directly coupled in one step at room temperature; the chemical reaction formula is shown as follows:
wherein:
R1is hydrogen, alkyl, alkoxy or ester group;
R2is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl;
R3is alkyl, methylphenyl, methoxyphenyl, halophenyl or nitrophenyl.
The preparation steps are as follows:
(1) adding a 2-phenylisoindigo compound, a sulfonyl azide compound, a silver salt, an acid and a solvent into a clean reactor, and stirring for 1-5 hours at room temperature;
(2) after the reaction is completed, the solvent is removed by reduced pressure distillation, and the residue is separated and purified by silica gel column chromatography to obtain the product.
The catalyst in step (1) is palladium-carbon, tetrakis (triphenylphosphine) palladium, palladium acetate, palladium chloride, bis (acetonitrile) palladium dichloride, bis (benzonitrile) palladium dichloride, 1, 1' -bis (diphenylphosphino) ferrocene palladium dichloride, bis (triphenylphosphine) palladium dichloride, bis (dibenzylideneacetone) palladium, tris (dibenzylideneacetone) dipalladium, allylpalladium (II) chloride dimer, (1, 5-cyclooctadiene) palladium (II) dichloride, rhodium-carbon, rhodium trichloride, rhodium acetate, acetylacetonatocarbonyltriphenylphosphine rhodium, dicyclooctenylrhodium chloride dimer, dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, (bis (hexafluoroantimonic acid) triacetonitrile (pentamethylcyclopentadienyl) rhodium (III)), triphenylphosphine rhodium chloride, ruthenium trichloride, triphenylphosphine ruthenium chloride, dichlorodicarbonylditriphenylphosphine ruthenium chloride, ruthenium trichloride, One or more of bis (2-methallyl) (1, 5-cyclooctadiene) ruthenium (II), p-cymene ruthenium dichloride dimer, cobalt chloride, cobalt acetoacetoxide, dicobalocarbonyl, dichloro (pentamethylcyclopentadienyl) cobalt (III) dimer, pentamethylcyclopentadienyl cobalt diiodide, (bis (hexafluoroantimonate) triacetonitrile (pentamethylcyclopentadienyl) cobalt (III)), iridium trichloride, dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, bis (1, 5-cyclooctadiene) iridium (I) chloride dimer, and methoxy (cyclooctadiene) iridium dimer.
The silver salt in the step (1) is one or more of silver nitrate, silver acetate, silver carbonate, silver sulfate, silver methanesulfonate, silver trifluoromethanesulfonate, silver p-toluenesulfonate, silver bistrifluoromethanesulfonimide, silver trifluoromethanesulfonate, silver hexafluoroantimonate, silver tetrafluoroborate and silver hexafluorophosphate.
The acid in the step (1) is one or more of pivalic acid, adamantane formic acid, acetic acid, trifluoroacetic acid and benzoic acid.
The solvent in the step (1) is trifluoroethanol, hexafluoroisopropanol, dichloromethane, 1, 2-dichloroethane, 1, 4-dioxane, tetrahydrofuran, acetonitrile, ethanol, methanol, toluene and water,N1,N3one or more than one of-disubstituted imidazole ionic liquids.
In the step (1), 2-phenylisoindigo red compounds: sulfonyl azide compounds: catalyst: silver salt: the molar ratio of the acid is 1 (1.1-2.0): (0.01-0.05): (0.08-0.2): (0.5-2.0).
In the step (1), the reaction concentration of the aryl heterocyclic compound is 0.1-0.5 mol/L.
By nuclear magnetic resonance hydrogen spectroscopy (1H NMR), carbon spectrum (13C NMR) and high resolution mass spectrum confirm the structure of the sulfonamide derivative formed by the activation of 2-phenylisoisatin C-H, as shown in the attached figures 1 and 2. Wherein the NMR chart is measured by a Varian INOVA-400 NMR spectrometer, Tetramethylsilane (TMS) is taken as an internal standard (delta 0 ppm), and deuterated dimethyl sulfoxide is taken as a solvent; high resolution mass spectra were determined using an Agilent 1946B mass spectrometer.
Compared with the traditional synthetic method, the method for efficiently forming the C-N bond on the benzene ring of the 2-phenylisoisatin by using the sulfonyl azide compound as the coupling reagent and the aryl C-H coupling reaction catalyzed by the transition metal has a plurality of unique advantages, and is embodied as follows:
1. the C-H coupling reaction takes 2-phenylisoisatin as a substrate, the reaction is rapid under the room temperature condition, a C-N bond is efficiently and rapidly formed on a benzene ring through one-step reaction, the reaction steps and the operation difficulty are reduced, and the cost is saved;
2. the substrate has wide applicability and strong functional group tolerance; the reaction activity of the attack reagent is high, and a wide space is reserved for the development of 2-phenylisoisatin medicaments;
3. the synthetic route of the invention uses sulfonyl azide as a coupling reagent, and only nitrogen is generated as a byproduct in the reaction process, thereby avoiding generating a large amount of waste and having higher atom economy and environmental friendliness.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of Compound 1 of the present invention
FIG. 2 shows nuclear magnetic carbon spectrum of Compound 1 of the present invention
Detailed description of the invention
The present invention will be further described with reference to specific embodiments to assist in understanding the invention. It is not intended that the scope of the invention be limited thereby, but rather that the invention be defined by the claims appended hereto.
Example 1 was carried out: synthesis of Compound 1
(1) 2-Phenylisoisatin (22.3 mg, 0.10 mmol), p-toluenesulfonylazide (39.5 mg, 0.20 mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (2.0 mg, 0.005 mmol), silver bistrifluoromethanesulfonylimide (7.8 mg, 0.02 mmol), acetic acid (12.0 mg, 0.20 mmol), trifluoroethanol (1.0 ml) were sequentially added to a clean reactor, and after argon substitution, the mixture was stirred at room temperature for 5 hours.
(2) After the reaction was completed, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1, v/v) to obtain 35.7 mg of a target product as an orange solid with a yield of 91%;1H NMR (400 MHz, DMSO-d 6 ) δ 9.07 (s, 1H), 7.89– 7.85 (m, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.75 – 7.70 (m, 2H), 7.60 – 7.55 (m, 1H), 7.47 (dd, J = 8.4, 1.6 Hz, 1H), 7.37 (t, J = 7.2 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 2.19 (s, 3H); 13C NMR (100 MHz, DMSO-d 6 ) δ 183.82, 146.91, 143.36, 136.64, 136.10, 135.34, 135.11, 132.16, 131.97, 131.80, 129.60, 125.98, 125.72, 125.65, 122.97, 121.91, 118.74, 114.37, 20.92; HRMS (ESI): m/zcalculated value C21H16N2O4SNa+: 415.0723, found 415.0720.
Example 2 was carried out: synthesis of Compound 1
(1) 2-Phenylisoisatin (22.3 mg, 0.10 mmol), p-toluenesulfonylazide (39.5 mg, 0.20 mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (2.0 mg, 0.005 mmol), silver tetrafluoroborate (3.9 mg, 0.02 mmol), acetic acid (12.0 mg, 0.20 mmol), and trifluoroethanol (1.0 ml) were sequentially added to a clean reactor, and after argon substitution, stirred at room temperature for 5 hours.
(2) After completion of the reaction, the solvent was removed under reduced pressure, and the residue was isolated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1, v/v) to give the objective product 23.5 mg as an orange solid in a yield of 60%.
Example 3 of implementation: synthesis of Compound 1
(1) 2-Phenylisoisatin (22.3 mg, 0.10 mmol), p-toluenesulfonylazide (39.5 mg, 0.20 mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (2.0 mg, 0.005 mmol), silver bistrifluoromethanesulfonylimide (7.8 mg, 0.02 mmol), adamantanecarboxylic acid (36.1 mg, 0.20 mmol), trifluoroethanol (1.0 ml) were added in this order to a clean reactor, and stirred at 90 ℃ for 5 hours after argon substitution.
(2) After the completion of the reaction, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1, v/v) to obtain 30.6 mg of the objective product as an orange solid in a yield of 78%.
Example 4 of implementation: synthesis of Compound 1
(1) 2-Phenylisoisatin (22.3 mg, 0.10 mmol), p-toluenesulfonylazide (39.5 mg, 0.20 mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (2.0 mg, 0.005 mmol), silver bistrifluoromethanesulfonylimide (7.8 mg, 0.02 mmol), adamantanecarboxylic acid (36.1 mg, 0.20 mmol), 1, 2-dichloroethane (1.0 ml) were added in this order to a clean reactor, and stirred at 90 ℃ for 5 hours after argon substitution.
(2) After completion of the reaction, the solvent was removed under reduced pressure, and the residue was isolated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1, v/v) to give the objective product 31.4 mg as an orange solid in a yield of 80%.
Example 5 was carried out: synthesis of Compound 1
(1) 2-Phenylisoisatin (22.3 mg, 0.10 mmol), p-toluenesulfonylazide (39.5 mg, 0.20 mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (2.0 mg, 0.005 mmol), silver bistrifluoromethanesulfonylimide (7.8 mg, 0.02 mmol), adamantanecarboxylic acid (36.1 mg, 0.20 mmol), hexafluoroisopropanol (1.0 ml) were added in this order to a clean reactor, and stirred at 90 ℃ for 5 hours after argon substitution.
(2) After completion of the reaction, the solvent was removed under reduced pressure, and the residue was isolated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1, v/v) to obtain the objective product 27.5 mg as an orange solid in a yield of 70%.
Example 6 of implementation: synthesis of Compound 2
(1) 2-p-Methylphenylisoisatin (23.7 mg, 0.10 mmol), p-toluenesulfonylazide (39.5 mg, 0.20 mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (2.0 mg, 0.005 mmol), silver bistrifluoromethanesulfonylimide (7.8 mg, 0.02 mmol), acetic acid (12.0 mg, 0.20 mmol), trifluoroethanol (1.0 ml) were sequentially added to a clean reactor, and after argon substitution, the mixture was stirred at room temperature for 5 hours.
(2) After the reaction was completed, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1, v/v) to obtain 36.2 mg of the objective product as an orange solid with a yield of 89%;1H NMR (400 MHz, DMSO-d 6) δ 8.92 (s, 1H), 7.90 – 7.83 (m, 1H), 7.76 (d, J = 7.6 Hz, 1H), 7.73 – 7.66 (m, 2H), 7.37 (d, J = 8.0 Hz, 1H), 7.28 – 7.20 (m, 4H), 6.89 (d, J = 8.0 Hz, 2H), 2.37 (s, 3H), 2.15 (s, 3H); 13C NMR (100 MHz, DMSO-d 6) δ 184.10, 147.29, 143.75, 143.05, 136.99, 136.47, 135.92, 135.70, 132.39, 132.17, 129.99, 127.61, 127.50, 126.23, 123.26, 122.41, 116.70, 114.81, 21.56, 21.36; HRMS (ESI): m/zcalculated value C22H18N2O4SNa+: 429.0879, found 429.0882.
Example 7 was carried out: synthesis of Compound 3
(1) 2-p-chlorophenyl isoisatin (25.8 mg, 0.10 mmol), p-toluenesulfonyl azide (39.5 mg, 0.20 mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (2.0 mg, 0.005 mmol), silver bistrifluoromethanesulfonylimide (7.8 mg, 0.02 mmol), acetic acid (12.0 mg, 0.20 mmol), trifluoroethanol (1.0 ml) were added in this order to a clean reactor, and after replacement with argon, the mixture was stirred at room temperature for 5 hours.
(2) After the reaction was completed, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1, v/v) to obtain the target product 32.2 mg as an orange solid with a yield of 75%;1H NMR (400 MHz, DMSO-d 6) δ 9.30 (s, 1H), 7.91 – 7.84 (m, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.74 (d, J= 4.4 Hz, 2H), 7.61 (dd, J = 8.8, 2.4 Hz, 1H), 7.51 (d, J = 2.4 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.8 Hz, 1H), 7.08 (d, J = 8.0 Hz, 2H), 2.23 (s, 3H); 13C NMR (100 MHz, DMSO-d 6) δ 183.76, 146.95, 143.67, 135.97, 135.74, 135.34, 133.87, 132.04, 131.63, 131.44, 129.76, 129.44, 126.26 (2s), 123.11, 122.00, 120.10, 114.49, 20.99; HRMS (ESI): m/zcalculated value C21H15ClN2O4SNa+: 449.0333, found 429.449.0336.
Example 8 was carried out: synthesis of Compound 4
(1) 2-phenylisoisatin (22.3 mg, 0.10 mmol), p-chlorobenzenesulfonyl azide (39.5 mg, 0.20 mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (2.0 mg, 0.005 mmol), silver bistrifluoromethanesulfonylimide (7.8 mg, 0.02 mmol), acetic acid (12.0 mg, 0.20 mmol), trifluoroethanol (1.0 ml) were sequentially added to a clean reactor, and after argon substitution, the mixture was stirred at room temperature for 5 hours.
(2) After the reaction was completed, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1, v/v) to obtain 36.3 mg of the objective product as an orange solid with a yield of 88%;1H NMR (400 MHz, DMSO-d 6) δ 9.38 (s, 1H), 7.91 – 7.84 (m, 1H), 7.77 (d, J = 7.6 Hz, 1H), 7.74 – 7.68 (m, 2H), 7.60 – 7.53 (m, 1H), 7.53 – 7.46 (m, 3H), 7.43 – 7.30 (m, 4H); 13C NMR (100 MHz, DMSO-d 6) δ 184.13, 146.96, 138.03, 137.89, 136.27, 135.41, 135.00, 132.28, 132.05, 131.92, 129.44, 128.07, 125.99, 125.38, 122.94, 122.02, 119.00, 114.42; HRMS (ESI): m/zcalculated value C20H13ClN2O4SNa+: 435.0177, found 435.0178.
Example 9 was carried out: synthesis of Compound 5
(1) 2-Phenylisoisatin (22.3 mg, 0.10 mmol), methanesulfonyl azide (24.2 mg, 0.20 mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (2.0 mg, 0.005 mmol), silver bistrifluoromethanesulfonylimide (7.8 mg, 0.02 mmol), acetic acid (12.0 mg, 0.20 mmol), trifluoroethanol (1.0 ml) were sequentially added to a clean reactor, and after replacement with argon, the mixture was stirred at room temperature for 5 hours.
(2) After the reaction was completed, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1, v/v) to obtain 25.6 mg of the objective product as an orange solid with a yield of 88%;1H NMR (400 MHz, DMSO-d 6) δ 9.27 (s, 1H), 7.84 (t, J = 7.6 Hz, 1H), 7.76-7.67 (m, 4H), 7.56 (t, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H), 3.08 (s, 3H); 13C NMR (100 MHz, DMSO-d 6) δ 185.36, 147.48, 137.67, 134.93, 134.79, 132.25, 131.80, 131.66, 124.06, 123.71, 121.75, 120.91, 116.66, 114.24, 39.73; HRMS (ESI): m/zcalculated value C15H12N2O4SNa+: 339.0410, found 339.0418.
Reference to the literature
1.Nepveu, F.; Kim, S.; Boyer, J.; Chatriant, O.; Ibrahim, H.; Reybier, K.; Monje, M. C. ; Chevalley, S. Perio P.; Lajoie, B. H.; Bouajila, J.; Deharo, E.; Sauvain, M.; Tahar, R.; Basco, L.; Pantaleo, A.; Turini, F.; Arese, P.; Valentin, A.; Thompson, E.; Vivas, L.; Petit, S.; Nallet, J. P. J Med Chem 2010, 53, 699-714.
2.Najahi, E.; Rakotoarivelo, N. V. ; Valentin, A. ; Nepveu, F. Eur J Med Chem 2014, 76, 369-375.
3.Ramana, C. V.; Patel, P.; Vanka, K.; Miao, B.; Degterev, A.; European Journal of Organic Chemistry 2010, 2010, 5955-5966.
4.Ibrahim, H.; Furiga, A.; Najahi, E.; Pigasse Henocq, C.; J. P. Nallet, J. P.; Roques, C. ; Aubouy, A.; Sauvain, M.; Constant, P.; Daffe, M.; Nepveu, F. J Antibiot (Tokyo) 2012, 65, 499-504.
5.Kumar, C.; Ramana, C. V. Org Lett 2015, 17, 2870-2873.
6.X, J.; Hu, S.; Lu, Y.; Dong, Y.; Tang, W.; Lu, T.; Du, D. Advanced Synthesis & Catalysis 2015, 357, 923-927.
7.Liu, R. R.; Ye, S. C.; Lu, C. J.; Zhuang, G. L. Gao, J. R.; Jia, Y. X.; Angew Chem Int Ed Engl 2015, 54, 11205-11208.
8.Sambiagio, C.; Schonbauer, D.; Blieck, R.; Dao-Huy, T.; Pototschnig, G.; Schaaf, P. ; Wiesinger, T.; Zia, M. F.; Wencel-Delord, J.; Besset, T. ; Maes, B. U. W.; Schnurch, M. Chem Soc Rev 2018, 47, 6603-6743。
Claims (4)
1. A method for constructing 2-phenylisoisatin derivatives by using sulfonyl azide as a coupling reagent and performing sulfonylation amination on 2-phenylisoisatin through aryl C-H activation reaction catalyzed by transition metal; the method is characterized in that sulfonyl azide compounds are used as coupling reagents, and C-N bonds are rapidly formed on a benzene ring of 2-phenylisoisatin at room temperature, and the chemical reaction formula is as follows:
wherein:
R1is hydrogen, alkyl, alkoxy or ester group;
R2is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl;
R3is alkyl, methylphenyl, methoxyphenyl, halophenyl or nitrophenyl;
the catalyst is dichloro (pentamethylcyclopentadienyl) iridium (III) dimer;
the silver salt is one or more of bis (trifluoromethane) sulfonyl imide silver and silver tetrafluoroborate;
the acid is one or more of adamantane formic acid and acetic acid.
2. The method for synthesizing 2-phenylisoisatin derivative according to claim 1, which is characterized by using the following preparation steps:
(1) adding a 2-phenylisoindigo red compound, a sulfonyl azide compound, a catalyst, a silver salt, an acid and a solvent into a clean reactor, replacing with argon, and stirring at room temperature for 1-5 hours;
(2) after the reaction is completed, the solvent is removed by reduced pressure distillation, and the residue is separated and purified by silica gel column chromatography to obtain the product.
3. The method according to claim 2, wherein the molar ratio of the 2-phenylisoisatin compound, the sulfonyl azide compound, the catalyst, the silver salt and the acid in step (1) is 1 (1.1-2.0), 0.01-0.05, (0.08-0.2) and (0.5-2.0).
4. The method according to claim 2, wherein the reaction concentration of the 2-phenylisoindigo compound in the step (1) is 0.1 to 0.5 mol/L.
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