* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Compound 30 was synthesized using a modification of the procedure reported by Liu et al. [7]. 3,4-Dihydroxy-3-cyclobutene-1,2-dione (squaric acid, 2.053 g, 18 mmol) was dissolved in anhydrous methanol (18 ml), and trimethyl orthoformate (4 ml, 36.5 mmol) was added to the solution. The reaction mixture was refluxed at 56 °C for 24 h. The crude product was then concentrated under reduced pressure. The pale yellow solid was dissolved in methylene chloride and purified on a silica gel column (EtOAc: Hexanes 1:2) to give 3,4-dimethoxycyclobut-3-ene-1,2-dione (2.29 g, 89.4percent) as a white solid. mp 55-57 °C (lit. 56-58 °C) [7, 8]1H NMR (300 MHz, CD2Cl2) δ 4.34 (6H, s, OCH3) 13C NMR (75 MHz, CD3OD) δ 189.35 (C2, C=O), 189.35 (C1, C=O), 184.35 (C3), 184.35 (C4), 60.29 (OCH3), 60.29 (OCH3) LRMS (EI): 142.03 (100), 114.03 (18), 99.01 (16), 86.01 (54), 67.99 (8), 56.25 (7)
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 2, p. 282 - 287
[2] Organic Syntheses, 1999, vol. 76, p. 189 - 189
[3] Chemistry - A European Journal, 2011, vol. 17, # 49, p. 13698 - 13705
[4] Chemistry - A European Journal, 2017, vol. 23, # 47, p. 11234 - 11238
[5] Chemical Communications, 2018, vol. 54, # 26, p. 3231 - 3234
[6] Organic and Biomolecular Chemistry, 2015, vol. 13, # 22, p. 6225 - 6241
[7] Journal of Organic Chemistry, 2018, vol. 83, # 17, p. 10627 - 10635
[8] RSC Advances, 2018, vol. 8, # 54, p. 30761 - 30776
[9] Patent: WO2008/5570, 2008, A1, . Location in patent: Page/Page column 74-75
[10] Patent: WO2009/5802, 2009, A1, . Location in patent: Page/Page column 20-21
Squaric acid (1.0023g) was dissolved in 30 mL EtOH and refluxed overnight. Then the solution was concentrated and purified by flash column chromatography, giving 0.7430 g squaric ethyl ester in 50percent yield.A solution of squraic ethyl ester, 2-amino pyridine (100 mg, 0.588 mmol) and Et3N (10 drops) in CH2Cl2 (10 mL) was stirred at room temperature overnight. Then it was concentrated under reduced pressure and purified by flash column chromatography (PE/EA 2:1) to give compound 6 as a white solid. The yield was 73percent. 1H NMR (400 MHz, Acetone-d6) δ 10.26 (s, 1H), 8.50 - 8.29 (m, 1H), 7.98 - 7.78 (m, 1H), 7.68 (d, J = 8.3 Hz, 1H), 7.14 (dd, J = 6.9, 5.3 Hz, 1H), 4.85 (q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR (100MHz, Acetone-d6) δ 186.42, 180.83, 170.33, 166.86, 152.22, 149.33, 139.43, 120.17, 113.63, 70.65, 16.06.
48%
for 12 h; Heating / reflux
For 12 h, 0.15 mol of 3,4-dihydroxy-3-cyclobutene-1,2-dione in 150 mL of absolute ethanol is heated under reflux.The reaction mixture is concentrated.The oil is purified by column chromatography.Mobile phase: methyl tert-butyl ether/iso-octane 50:50Stationary phase: AMICON 35-70 mic.Yield: 48percent
Reference：
[1] Journal of Materials Chemistry A, 2015, vol. 3, # 6, p. 2883 - 2894
[2] Angewandte Chemie - International Edition, 2017, vol. 56, # 22, p. 6181 - 6186[3] Angew. Chem., 2017, vol. 129, # 22, p. 6277 - 6282,6
[4] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 2, p. 263 - 272
[5] Chemical Communications, 2013, vol. 49, # 89, p. 10465 - 10467
[6] Heterocyclic Communications, 2012, vol. 18, # 3, p. 113 - 116
[7] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 13, p. 3793 - 3797
[8] Patent: US6995262, 2006, B1, . Location in patent: Page/Page column 61
[9] Journal of Organic Chemistry, 1976, vol. 41, p. 3904 - 3909
[10] Tetrahedron, 2001, vol. 57, # 45, p. 9325 - 9333
[11] Journal of the American Chemical Society, 2007, vol. 129, # 34, p. 10320 - 10321
[12] RSC Advances, 2013, vol. 3, # 39, p. 18055 - 18061
[13] Journal of Medicinal Chemistry, 2014, vol. 57, # 3, p. 987 - 999
[14] Patent: CN103214410, 2016, B, . Location in patent: Paragraph 0051
10
[ 122-51-0 ]
[ 2892-51-5 ]
[ 5231-87-8 ]
Reference：
[1] Arkivoc, 2014, vol. 2014, # 5, p. 351 - 364
[2] Angewandte Chemie - International Edition, 2012, vol. 51, # 18, p. 4426 - 4430
[3] Synthetic Communications, 2007, vol. 37, # 15, p. 2527 - 2542
[4] Journal of Organic Chemistry, 2007, vol. 72, # 10, p. 3976 - 3979
11
[ 64-17-5 ]
[ 122-51-0 ]
[ 2892-51-5 ]
[ 5231-87-8 ]
Reference：
[1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 39, p. 9322 - 9330
[2] Synthetic Communications, 1997, vol. 27, # 12, p. 2177 - 2180
12
[ 389-27-5 ]
[ 2892-51-5 ]
Reference：
[1] Journal of the American Chemical Society, 1959, vol. 81, p. 3480
[2] Journal of the American Chemical Society, 1962, vol. 84, p. 2919,2921
A solution of squaric acid (1) (2.00 g, 17.54 mmol) in n-BuOH (50 mL) was refluxed under stirring for 3 h. After cooling on an ice bath, 50 mL of diethyl ether (Et2O) was added to the mixture, which was sequentially washed with cold distilled water, cold saturated aqueous NaHCO3, and cold distilled water. The organic layer, after separation, was dried over anhydrous sodium sulphate and the solvent removed under reduced pressure. The resulting brownish oil (2.92 g, 74percent yield) was chromatographically pure and used in the next reaction without further purification. Yield: 74percent.
Reference：
[1] Canadian Journal of Chemistry, 1986, vol. 64, p. 2267 - 2273
[2] Bulletin de la Societe Chimique de France, 1990, # 3, p. 367 - 374
[3] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 14, p. 3803 - 3814
[4] Journal of Molecular Structure, 2009, vol. 936, # 1-3, p. 239 - 249
[5] Comptes Rendus Chimie, 2012, vol. 15, # 5, p. 454 - 462
[6] Justus Liebigs Annalen der Chemie, 1965, vol. 686, p. 55 - 63
[7] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1990, vol. 45, # 4, p. 490 - 496
[8] Tetrahedron, 2001, vol. 57, # 45, p. 9325 - 9333
[9] Patent: US4927970, 1990, A,
[10] Patent: US4927970, 1990, A,
[11] Patent: US4927970, 1990, A,
[12] Chemistry - A European Journal, 2016, vol. 22, # 29, p. 10179 - 10186
[13] Dyes and Pigments, 2017, vol. 147, p. 120 - 129
3,4-Diisopropoxycyclobut-3-ene-1,2-dione (diisopropyl squarate) was prepared by the heatingof <strong>[2892-51-5]squaric acid</strong> (1.14 g, 10 mmol) in 2-propanol and benzene (1:1 v/v) for 5 days using a Dean-Stark968 HETEROCYCLES, Vol. 99, No. 2, 2019apparatus (1.82 g, 92% yield), mp 43 C (lit,9 mp 43-44 C).
81%
With sulfuric acid; In isopropyl alcohol; for 3h;Reflux;
A mixture of <strong>[2892-51-5]squaric acid</strong> (2.00 g, 17.5 mmol), isopropanol (20 mL)and a drop of concentrated H2SO4 was refluxed for 3 h, and the solventwas evaporated under reduced pressure. Then isopropanol was added,the mixture was refluxed for 30 min and the solvent was evaporatedagain. The crude product was purified by silica gel column chromatography(petroleum ether:ethyl acetate=81:1()2.t8o0 ga,f8o1r%d)as white solid. M.p. 42-45 C. 1H NMR (400 MHz, CDCl3, ppm) ;5.39-5.29 (m, 2H, CH), 1.45 (d, J=6.4 Hz, 12H, CH3).
Add 20 mL of ethanol to a 50 mL round bottom flask, then add 2.00 g of <strong>[2892-51-5]squaric acid</strong> (17.6 mmol) and reflux at 80 C.After 3 hours, after the <strong>[2892-51-5]squaric acid</strong> is completely dissolved, the ethanol is removed by steaming under reduced pressure, and the reaction is repeated three times and then refluxed for 24 hours.At the end of the reaction, silica gel column chromatography was carried out using petroleum ether: ethyl acetate as 2:1 (v/v) as eluent.Light yellow oily liquid product 2.09 g, yield 70%
70%
at 80℃; for 12h;
In a 50 mL round bottom flask, 20 mL of ethanol was added first, then 2.00 g of <strong>[2892-51-5]squaric acid</strong> (17.6 mmol) was added, and the reaction was refluxed at 80 C for 3 hours. After all the <strong>[2892-51-5]squaric acid</strong> is dissolved, the ethanol is removed by vacuum distillation under reduced pressure, and the reaction is repeated three times and then refluxed at 80 C for 12 hours. After the reaction is completed. Silica gel column chromatography using petroleum ether: ethyl acetate = 2:1 (v/v) as eluent to afford the product as a pale yellow oily product (yield: 70%).
50%
Reflux;
Squaric acid (1.0023g) was dissolved in 30 mL EtOH and refluxed overnight. Then the solution was concentrated and purified by flash column chromatography, giving 0.7430 g squaric ethyl ester in 50% yield.A solution of squraic ethyl ester, 2-amino pyridine (100 mg, 0.588 mmol) and Et3N (10 drops) in CH2Cl2 (10 mL) was stirred at room temperature overnight. Then it was concentrated under reduced pressure and purified by flash column chromatography (PE/EA 2:1) to give compound 6 as a white solid. The yield was 73%. 1H NMR (400 MHz, Acetone-d6) delta 10.26 (s, 1H), 8.50 - 8.29 (m, 1H), 7.98 - 7.78 (m, 1H), 7.68 (d, J = 8.3 Hz, 1H), 7.14 (dd, J = 6.9, 5.3 Hz, 1H), 4.85 (q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H); 13C NMR (100MHz, Acetone-d6) delta 186.42, 180.83, 170.33, 166.86, 152.22, 149.33, 139.43, 120.17, 113.63, 70.65, 16.06.
48%
for 12h;Heating / reflux;
For 12 h, 0.15 mol of 3,4-dihydroxy-3-cyclobutene-1,2-dione in 150 mL of absolute ethanol is heated under reflux.The reaction mixture is concentrated.The oil is purified by column chromatography.Mobile phase: methyl tert-butyl ether/iso-octane 50:50Stationary phase: AMICON 35-70 mic.Yield: 48%
A solution of squaric acid (1) (2.00 g, 17.54 mmol) in n-BuOH (50 mL) was refluxed under stirring for 3 h. After cooling on an ice bath, 50 mL of diethyl ether (Et2O) was added to the mixture, which was sequentially washed with cold distilled water, cold saturated aqueous NaHCO3, and cold distilled water. The organic layer, after separation, was dried over anhydrous sodium sulphate and the solvent removed under reduced pressure. The resulting brownish oil (2.92 g, 74% yield) was chromatographically pure and used in the next reaction without further purification. Yield: 74%.
In water; toluene;
A. 1,2-Dibutoxy-1-cyclobutene-3,4-dione Protected by a nitrogen atmosphere, a mixture of 1-butanol (64 mL), toluene (42 mL), and 1,2-dihydroxy-1-cyclobutene-3,4-dione (21.43 g, 0.1878 mole) was heated under reflux with stirring under a Dean-Stark water separator until water stopped passing(7.6 mL of water was collected). Reflux was continued for a further 30 minutes, then the excess toluene and butanol were distilled off under reduced pressure (50-100 mm Hg) to give the title compound as a yellow liquid. The concentrate was diluted with 25 mL of methanol.
In toluene;
A. 1,2-Dibutoxy-1-cyclobutene -3,4-dione A mixture of 1-butanol (48 mL), toluene (32 mL), and 1,2-dihydroxy-l-cyclobutene-3,4-dione (16.0 g, 0.1402 mole) was heated at reflux under a nitrogen atmosphere with stirring under a Dean-Stark water separator until water stopped passing over. The resulting solution of the title compound was cooled to 0-5 C.
In toluene;
A. 1,2-Dibutoxy-1-cyclobutene-3,4-dione A mixture of 1-butanol (3 L), toluene (2 L) and 1,2-dihydroxy-1-cyclobutene-3,4-dione (1 kg; 8.767 moles) was refluxed with stirring under a Dean-Stark separator until water stopped passing(theory:0.316 L). The excess toluene and butanol were then removed by distillation under reduced pressure to give the title compound as a yellow liquid. The concentrate was diluted with methanol (1.5L) and used in the next step.
Squaric acid (0.570 g, 5 mmol) and 3-(Diethylamino)phenol (1.652g, 10 mmol) were refluxed under nitrogen for one day in a 40 ml mixture of n-butanol/toluene (1:1/v:v). The reaction mixture was cooled to room temperature. The formed precipitate was filtered and washed with methanol several times (1.895 g, yield: 92.8%). 1H NMR (600 MHz,DMSO-d6) 1.16(t, 12H), 3.52(q, 8H), 6.16(s, 2H), 6.60(d,2H), 7.73(d,2H); m.p.: 278 C
With oxalyl dichloride; N,N-dimethyl-formamide; In tetrachloromethane; at 50℃; for 4h;
Experimental procedure taken from LUNELLI et al. [B. Lunelli, Tetrahedron Lett. 2007, 3595-3597]. Finely powdered squahc acid (1 1 .4 g, 0.10 mol) was suspended in anhydrous carbon tetrachloride (50 mL). After addition of anhydrous Lambda/,/V-dimethylformamide (0.400 mL) and oxalyl chloride (18.0 mL, 0.200 mol), the reaction mixture was heated at 50 C for four hours. After cooling to room temperature, the mixture was filtered, and the filtrate was evaporated under reduced pressure. The resulting oily residue crystallized in the refrigerator. Subsequently, the spontaneously precipitated, light yellow, easily sublimating crystals were separated, washed with petroleum ether and stored in the refrigerator. The product (Yield: 79%) was used without any further purification. Mp = 50 - 53 C. (53 C [B. Lunelli, Tetrahedron Lett. 2007, 3595-3597]).
54%
With thionyl chloride; In N,N-dimethyl-formamide; benzene; at 60℃; for 6h;
A mixture of <strong>[2892-51-5]squaric acid</strong> (1.14 g, 10 mmol),thionyl dichloride (1.8 mL, 20 mmol) and DMF (200 uL) in dry benzene (10 mL) was refluxed for 6 h at 60. The solvent was evaporated in vacuo and hexane (20 mL) was added, then the soluble products were separated from gummy precipitates. Concentrating and cooling to give yellow crystalline which was used in the next step without further purification (0.82 g,5.4mmol), yield 54%.
52%
With oxalyl dichloride;N,N-dimethyl-formamide; In tetrachloromethane; at 20 - 50℃;Inert atmosphere;
L Synthesis of Precursor 3 (3,4-dichlorocyclobut-3-ene-l,2-dione)A suspension of <strong>[2892-51-5]squaric acid</strong> (3,4-dihydroxycyclobut-3-ene-l,2-dione; 1.14 g, 10 mmol) in carbon tetrachloride (5 ml) with DMF (2 drops) under nitrogen was frozen by immersion in liquid nitrogen. Oxalyl chloride (2.54 g, 20 mmol) was introduced at once and the flask was allowed to warm up to RT. It was then heated to 500C for lhr and the reaction mixture was filtered. The residue was washed with CCl4 and the filtrate was evaporated in vacuo to give pale yellow crystals, yielding 785 mg of Precursor 3 (52%).
48%
With thionyl chloride; In tetrahydrofuran; toluene; at 20 - 95℃; for 2h;
Squaric acid (114 mg, 1 mM), thionyl chloride (238 mg, 2 mM) and anhydrous tetrahydrofuran (20 muL) were stirred in anhydrous toluene at room temperature, and then the temperature was raised and stirred at 95 C for 2 hours. The mixture was cooled to room temperature and washed with 2 mL of anhydrous toluene to synthesize 3,4-dichlorocyclobut-3-ene-1,2-diene. At this time, the yield was 48%.
18%
With thionyl chloride; N,N-dimethyl-formamide; In benzene; at 90℃; for 12h;Inert atmosphere;
Example 1 Synthesis of Dye [0028] Squaric acid (2.28 g, 40.0 mmole) was charged in a reaction bottle (100 mL). The reaction bottle was then purged by argon and vacuumed for several cycles to remove moisture therein. Benzene (17.5 mL) was then injected into the reaction bottle, and 8 drops of anhydrous DMF was then injected into the reaction bottle. Thionyl chloride (3.6 mL, 40 mmole) was then slowly injected into the reaction bottle to react with the <strong>[2892-51-5]squaric acid</strong>, and the reaction was heated to 90 C. to reflux for 12 hours. The resulting mixture was cooled to room temperature, and a major part of organic solvents thereof was removed by a rotary evaporator to obtain a condensed mixture. The condensed mixture was extracted by hexane, and then purified by re-crystallization and sublimation to obtain a yellow needle-shaped solid (0.8 g, yield=18%). The above reaction is shown in Formula 24, and the spectrum data of the product in Formula 24 is shown as follows. 13C-NMR (CDCl3, 300 MHz, deltaC/ppm): 188.1 (2C, s); 189.41 (2C, s).
With thionyl chloride; In N,N-dimethyl-formamide; for 3h;Reflux;
A mixture of <strong>[2892-51-5]squaric acid</strong> (0.55 g, 4.8 mmol), thionyl dichloride (0.88 ml, 9.7 mmol) and DMF (5 drops) was heated at reflux for 3 h.The resultant mixture was cooled to 0 C. Anhydrous methylenechloride (6 ml) and anhydrous AlCl3 (0.64 g, 4.8 mmol) were added to the reaction mixture. Then anisole (0.52 g, 4.8 mmol) was added to the mixture dropwise. The mixture was stirred at 0 C for 1.5 h.The resultant mixture was poured onto crushed ice and extracted with CH2Cl2 (2 15 ml), the combined organic layer was washed with water (15 ml) followed by brine (15 ml) and concentrated under reduced pressure to give crude product, which was further purified by column chromatography on silica gel using hexane/EtOAc (5:1) as eluent to afford title compound as yellow solid(1.02 g, 72%).
With thionyl chloride; N,N-dimethyl-formamide; In toluene; at 25℃; for 6h;Reflux;
1) After dissolving 3,4-dihydroxy-3-cyclobutene-1,2-dione (5 g, 43.5 mmol) in a sufficient amount of toluene,Added chlorosulfoxide (total 10.4g),When you join half the amount,Add 20uL anhydrous DMF (dimethylformamide),Then at room temperature (25C,Continue to add thionyl chloride under the sameAfter the addition,The mixture is refluxed for 6 hoursRemove the solvent,The residue dissolves in hexane,Store in the refrigerator,Isolated pale yellow crystals,
With thionyl chloride; In N,N-dimethyl-formamide; benzene; for 6h;Reflux;
3,4-dichlorocyclobut-3-ene-1,2-dione was synthesized by taking a solution of thionyl chloride(1.8 mL, 20 mmol), DMF (0.1 mL) and <strong>[2892-51-5]squaric acid</strong> (1.14 g, 10 mmol) inbenzene (20 mL). The mixture was heated under reflux for 6 h. Aftersolution was concentrated by rotary evaporation and then n-hexane(20 mL) was added. After handling undesirable colloid, the remainingsolvent was removed by evaporation and the remaining residue wascooled to produce crystals which were used without further purification.
With oxalyl dichloride; In tetrachloromethane; N,N-dimethyl-formamide; at 50℃; for 4h;
Weigh 3.4g (about 0.0300mol) of <strong>[2892-51-5]squaric acid</strong> and weigh 16mL of carbon tetrachloride and 80muL of N,N-dimethylformamideAdd it together in a three-necked flask,Cool to below 10 C with an ice water bath.Amount of 10.2 g of oxalyl chloride was added to the flask, and bubbles were immediately generated.A reflux condenser was placed and placed in a water bath at 50 C with heating and stirring, and a large amount of bubbles overflowed with the reaction.After 1 h of reaction, the solution turned bright yellow.After the reaction was continued for 3 hours, the white solid (squaraine) was completely reacted, and the bubbles were no longer generated, and the reaction was stopped.The product is steamed to give a yellow liquid which is cooled in an ice water bath.Soon the liquid solidifies into a yellow crystal, a crude product of succinyl chloride.
2-[3,3-Dimethyl-5-nitro-1,3-dihydro-indol-(2E)-ylidenemethyl]-4-[1-(3,3-dimethyl-5-nitro-3H-indol-2-yl)-meth-(Z)-ylidene]-3-hydroxy-cyclobut-2-enone[ No CAS ]
2-[5-Amino-3,3-dimethyl-1,3-dihydro-indol-(2E)-ylidenemethyl]-4-[1-(5-amino-3,3-dimethyl-3H-indol-2-yl)-meth-(Z)-ylidene]-3-hydroxy-cyclobut-2-enone[ No CAS ]
Compound 30 was synthesized using a modification of the procedure reported by Liu et al. [7]. 3,4-Dihydroxy-3-cyclobutene-1,2-dione (<strong>[2892-51-5]squaric acid</strong>, 2.053 g, 18 mmol) was dissolved in anhydrous methanol (18 ml), and trimethyl orthoformate (4 ml, 36.5 mmol) was added to the solution. The reaction mixture was refluxed at 56 C for 24 h. The crude product was then concentrated under reduced pressure. The pale yellow solid was dissolved in methylene chloride and purified on a silica gel column (EtOAc: Hexanes 1:2) to give 3,4-dimethoxycyclobut-3-ene-1,2-dione (2.29 g, 89.4%) as a white solid. mp 55-57 C (lit. 56-58 C) [7, 8]1H NMR (300 MHz, CD2Cl2) delta 4.34 (6H, s, OCH3) 13C NMR (75 MHz, CD3OD) delta 189.35 (C2, C=O), 189.35 (C1, C=O), 184.35 (C3), 184.35 (C4), 60.29 (OCH3), 60.29 (OCH3) LRMS (EI): 142.03 (100), 114.03 (18), 99.01 (16), 86.01 (54), 67.99 (8), 56.25 (7)
With trifluoroacetic acid; In methanol;Heating / reflux;
Preparative Example 5; Preparation of Compound 209A; Charged 9.5 kg of the compound of formula 214 to 50 gallon glass reactor equipped with a thermocouple, N2 inlet and feed tank. Charged 65 liters dry methanol (KF < 0.1 %) followed by 20 liters trimethylorthoformate and 0.2 kg trifluroracetic acid. Heated the batch to reflux and maintained for about one hour. Concentrated the batch at one atmosphere until the internal temperature exceeded 7O0C. Maintained the batch at reflux for about four hours. Adjusted the batch to a temperature between 40 and 500C and charged 26 liters dry methanol. Adjusted the temperature to about 20 to 30C. Charged 78 liters of dry methanol and adjusted the batch to a temperature between -5 and 5C. Charged 13.0 kg of the compound of formula V. Over about 4 hours, charged 11.1 kg triethylamine (TEA) to the batch while maintaining the batch at a temperature between -5 and 50C. About one and a half hours after the start of the <n="76"/>TEA charge, seeded the batch with 130 grams of compound (209A) added as a solid. After the addition of TEA was completed, agitated the batch for about 30 minutes at a temperature between -5 and 5C. Charged 12 liters acetic acid while maintaining the batch at a temperature between -5 and 50C. Heated the batch to a temperature between 60 and 700C and maintained this temperature for about 1 hour. Adjusted the temperature to about 25 to 350C over about 1 hour. Adjusted the temperature to about -5 to 50C over about 1 hour. Filtered the batch and washed the filter cake with 65 liters (5 x) methanol. Dried the batch in a vacuum oven for at least 24 hours at 60 to 700C. Yield 14.5 kg , 81%. 1HNMR (CD3CN) 8.07 (1 H, s); 7.56 (1 H, d); 7.28 (1H, d); 6.99 (1 H, t); 4.35 (3H, s); 3.10 (6H1 s)
With trifluoroacetic acid; In methanol; for 5h;Heating / reflux;
Example Ia - In Situ Preparation of Dimethyl Squarate (2A2) and Reaction With Compound (2B) to Form Compound (2Ca). Into a 50 gallon glass reactor equipped with a thermocouple, N2 inlet and feed tank was charged 9.5 kg of the compound of Formula 2A. The reactor was then charged with 65 liters dry methanol (Karl Fischer titration "KF" indicates water present at < 0.1 %) followed by 20 liters trimethylorthoformate and 0.2 kg trifluroracetic acid. The reaction mixture was heated to reflux and maintained for about one hour. The reaction mixture was concentrated at one atmosphere until the internal temperature exceeded 700C. The reaction mixture was maintained at reflux for about four hours then the temperature was adjusted to a temperature between 40 0C and 50 0C. The reactor was charged with 26 liters dry methanol and the reaction mixture temperature was adjusted to about 20 0C to 30 C. The reactor was charged with 78 liters of dry methanol and the reaction mixture temperature was adjusted to a temperature between -5 0C and 50C. The reactor was charged with 13.0 kg of the compound of Formula 2B. Triethylamine (TEA), 11.1 kg, was charged into the reactor over 4 hours while maintaining the batch at a temperature between -5 and 50C. About one and a half hours after the start of the TEA charge, the reaction mixture was seeded with 130 grams of the compound 2C. After the addition of TEA was completed the reaction mixture was agitated for about 30 minutes maintaining the batch temperature between -5 and 50C. Acetic acid, 12 liters was charged into the reactor while maintaining the batch at a temperature between -5 and 50C. The reaction mixture was heated to a temperature between 60 and 7O0C and maintained in this temperature range for about 1 hour. After about 1 hour the temperature was adjusted to a temperature in the range of 25 0C to 35 0C and maintained at that temperature range for about 1 hour, then the temperature was readjusted to a temperature in the range of [-5 0C] to [+50C] over about 1 hour. The reaction mixture was filtered and the filter cake washed with 65 liters methanol. The solids collected were dried in a vacuum oven for about 24 hours with the oven temperature maintained at 600C to 7O0C. Yield was 14.5 kg , about 81% based on the amount of the compound of Formula 2C employed. 1HNMR (CD3CN) 8.07 (1H, s); 7.56 (1H1 d); 7.28 (1H, d); 6.99 (1H, t); 4.35 (3H, s); 3.10 (6H, s)
With quinoline; butan-1-ol; In benzene; for 24 - 36h;Heating / reflux; azeotropic distillation of water;
EXAMPLE 2 General Procedure for Preparation of Compounds Represented by the General Formula 2 A mixture of the corresponding quinaldinium salt (1 mmol), and <strong>[2892-51-5]squaric acid</strong> (0.5 mmol) and quinoline (0.5 mL) was refluxed in a mixture of n-butanol and benzene (6-9 mL each, 1:1) with azeotropic distillation of water for 24-36 h. The solvent was distilled off under reduced pressure to obtain a residue, which was chromatographed over silica gel. Elution of the column with a mixture (1:9) of methanol and chloroform gave the corresponding squaraine dyes of the general formula 2. The physiochemical properties of compound of the general formula 2, (wherein, X=Br, Y=H, R2=CH3, 90-95%), mp 336-338 C., IR (KBr) numax 3056, 1613, 1580 cm-1. 1H-NMR (DMSO-d6) delta 9.31 (1H, d, J=9.5 Hz), 9.28 (1H, d, J=9.3 Hz), 7.3-8.4 (8H, m, aromatic), 5.86 (1H, s, vinylic), 5.78(1H, s, vinylic), 3.85 (3H, s); 3.78 (3H, s); FAB-MS: m/z=550.246 (calcd 550.248 for C26H18Br2N2O2).
5-carboxyl-2,3,3-trimethyl-1-octyl-3H-indol-1-ium iodide[ No CAS ]
[ 2892-51-5 ]
[ 1351395-51-1 ]
Yield
Reaction Conditions
Operation in experiment
81%
In toluene; butan-1-ol; for 30h;Reflux; Dean-Stark;
5-Carboxy-2,3,3-trimethyl-1-octyl-3H-indolium iodide (0.85 g, 1.9 mmol) and 3,4-dihydroxycyclobut-3-ene-1,2-dione (0.1 g, 0.87 mmol) were dissolved in a mixture of n-butanol (6 ml) and toluene. The reaction mixture was heated under reflux for 30 h using a Dean-Stark apparatus to remove the water. After removing the solvent, the product was purified by column chromatography on a silica gel column with ethyl ether: methanol (V/V: 1:1). The product was obtained as a dark blue solid. Yield: 81%. 1H NMR (300 MHz, DMSO-d6): delta; 7.92 (s, 2H), 7.90 (d, J = 8.7 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 5.81 (s, 2H), 4.04 (t, J = 7.5 Hz, 4H), 1.67 (s, 12H), 1.33-1.23 (m, 12H), 0.83 (t, J = 5.5 Hz, 3H). Calculated for C44H56N2O6 (708.32); Found: 708.1. Anal.: C44H56N2O6 (708.32); Calcd.: C 74.55, H 7.96, N 3.95, O 13.54; Found: C 74.09, H 8.03, N 3.93, O 13.66.
With quinoline; In butan-1-ol; benzene; for 15h;Reflux;
Synthesis Example 1; Carboxyindolenine was synthesized using 4-hydrazinobenzoic acid and methyl isopropyl ketone. 78.87 mmol of 4-hydrazinobenzoic acid, 160.92 mmol of sodium acetate, and 123.46 mmol of methyl isopropyl ketone were added to 180 ml of glacial acetic acid, and the mixture was subjected to a reaction under nitrogen at 120 C. for 7 hours. Acetic acid was distilled off and the resultant solid was dispersed in a solution of water:methanol=9:1 and filtered. The solid was added to 70 g of methanol and the mixture was heated to 30 C. and filtered. 160 g of water were added to the filtrate for crystallization and the crystal was filtrated. The resultant solid was washed with 35 ml of a solution of water:methanol=9:1 and dried in vacuum to afford 37.7 mmol of carboxyindolenine.In order to synthesize an N-n-alkylcarboxyindolenine salt, 0.1 mol of 2,3,3-trimethyl-5-carboxy-indolenine and 1-iodooctane were dissolved in 20 ml of ethanol and the mixture was subjected to a reaction for 7 hours while being refluxed. The solid was filtered to afford 1-n-octyl-2,3,3-trimethyl-5-carboxy-indolenium iodide in a yield of 55%.In order to synthesize a squarylium dye, 0.7 mmol of 1-n-octyl-2,3,3-trimethyl-5-carboxy-indolenium iodide and 3 mmol of <strong>[2892-51-5]squaric acid</strong> were dissolved in a solvent obtained by adding 1 ml of quinoline to 40 ml of a solvent of benzene:butanol=1:4 (volume ratio) and the mixture was refluxed while removing water and subjected to a reaction for 15 hours. The mixture was cooled to room temperature, and the solid was filtered. The solid was washed with diethyl ether to afford a squarylium dye D-4. The IR spectrum, MS spectrum, and 1H-NMR spectrum (solvent: DMSO-d6) of the squarylium dye D-4 were measured. FIG. 2 shows the IR spectrum.
4-[(1-ethyl-3,3-dimethyl-3H-indol-1-ium-2-yl)methylidene]-2-[(1-ethyl-3,3-dimethylindolin-2-ylidene)methyl]-3-oxocyclobut-1-en-1-olate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With pyridine In toluene; butan-1-ol for 3h; Reflux;
55%
In toluene; butan-1-ol for 10h; Dean-Stark; Reflux;
Synthesis of SQIND2
A mixture of compounds 1-ethyl-2, 3, 3-trimethyl-3H-indol- 1-ium iodide (1.7 g, 0.0 054 mmol) and 3,4-dihydroxycyclobut- 3-ene-1,2-dione (0.31 g, 0.0027 mmol) was taken 40 ml of dry n-butanol/toluene 1:1 (v/v). The reaction was refluxed for 10 h using Dean-Stark trap for azeotropic removal of water. It was cooled to rt and the solvent was removed. The product was filtered and washed with hexane. The dye was recrystallized with methanol and hexane to give SQIND2 as green dye solid in 55% yield (see Scheme 1). 1HNMR (400 MHz-CDCl3) spectrum recorded at δ 1.20(t, 3H, J = 6.6 Hz, CH3), 1.35(t, 3H, J = 7.2 Hz,CH3), 1.78(s, 6H, 2CH3), 3.45(q, 2H, J = 7.2 Hz, CH2), 5.9(s, 1H, C = CH), 7.5(s, 1H, C = CH), 7.31-7.39(td, 1H, J = 7.2 Hz, Ar-H), 7.93(t, 1H, J = 7.8 Hz, Ar-H), 8.05(dd, 1H, = 5.4 Hz, Ar-H), 8.12(t, 1H, J = 7.2 Hz, Ar-H), 8.2(d, 1H, J = 8.4 Hz, Ar-H), 8.65(d, 1H, J = 8.4 Hz, Ar-H), 8.92(d, 1H, J = 8.4 Hz, Ar-H), 9.3(d, 1H, J = 4.8 Hz, Ar-H). 13CNMR (MHz-CDCl3) spectrum recorded at 12.09, 27.03, 38.46, 49.37, 86.30, 109.16, 122.42, 123.76, 127.86, 142.09, 142.36, 169.72.
48%
In toluene; butan-1-ol at 160℃; for 0.25h; Microwave irradiation;
With orthoformic acid triethyl ester In ethanol Inert atmosphere; Reflux;
1.1.2
(2) taking squaric acid (1 mol) in 50 mL of absolute ethanol, adding the catalyst to triethyl orthoformate, heating under reflux with nitrogen until all the squaric acid is dissolved.2.2 mol of the quaternary ammonium salt (I1d) prepared above was added thereto, and heating was continued to reflux.TLC was detected until all the starting materials were reacted, and the solvent was removed by cooling under reduced pressure, and the column chromatography was separated to give a blue solid dye (I1c)
In toluene; butan-1-ol at 160℃; for 0.333333h; Microwave irradiation; Sealed tube;
78%
In toluene; butan-1-ol Reflux;
General procedure.
General procedure: A mixture of quaternized or non-quaternized indolenine (2mmol) and squaric acid or its dicyanomethylene or barbituric derivative was refluxed in 50mL of a butanol-toluene mixture (1:1, v/v). The solvent was removed and the residue was dried in a vacuum desiccator over P2O5. The product was column purified (Silica gel 60, CHCl3-MeOH, gradient).
24%
With quinoline In butan-1-ol; benzene Reflux;
4.2. Synthesis of SQ dyes 13-16 and 19
General procedure: To a butanol/benzene (4:1) mixed solution (30 ml) were added 1-alkyl-2,,3,3-trimethyl-3H-indolenium iodide (3.30 mmol), 3,4-dihydroxy-3-cyclobuten-1,2-dione (170 mg, 1.50 mmol), and quinoline (2 ml). The mixture was refluxed for 1-2 days. After the reaction was completed, the solvent was removed in vacuo. The resulting precipitate was washed with hexane, purified by column chromatography (SiO2, 13: AcOEt, 14, 15, 16, 19: AcOEt/CHCl3=1:1), and recrystallized from ethanol. The physical and spectral data are shown below.
N-(3-sulfonatopropyl)-2,3,3-trimethyl-3H-indolium[ No CAS ]
5-nitroquinolinium-2-(3,3-dimethyl-(1-propan-3-sulphonate)-2-indolinylidenemethyl)-4-(3,3-dimethyl-(1-propan-3-sulfonic acid)-2-indolinylidenemethyl) cyclobutene-1,3-diolate dihydrate[ No CAS ]
N-(3-sulfonatopropyl)-2,3,3-trimethyl-3H-indolium[ No CAS ]
5-nitroisoquinolinium 2-(3,3-dimethyl(1-propan-3-sulphonate)-2-indolinylidenemethyl)-4-(3,3-dimethyl(1-propan-3-sulfonic acid)-2-indolinylidenemethyl)cyclobutene-1,3-diolate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
51%
In toluene; butan-1-ol Reflux; Dean-Stark;
3 5-Nitroisoquinolinium 2-(3,3-dimethyl-(1-propan-3-sulphonate)-2-indolinylidenemethyl)-4-(3,3-dimethyl-(1-propan-3-sulfonic acid)-2-indolinylidenemethyl)cyclobutene-1,3-diolate (5)
General procedure: Same procedure as for 2 except: 5-nitroisoquinoline (613 mg, 3.52 mmol). Upon cooling, a metallic green powder was collected in vaccuo, washed with petroleum ether (60/40), and used following precipitation from chloroform. Yield: 750 mg (51%). UV/Vis (H2O) λmax (log ɛ): 624 (5.44). IR (KBr) νmax: 1598 (C-O). ES-: 319.4 (C32H34N2O8S22-; calc. 638.8). [(C9H7N2O2)+(C32H35N2O8S2)-·H2O] (EA) (% found/calc.): C, 59.11/59.12; H, 5.03/5.32; N, 7.09/6.73.
bis-quinaldinium 2,4-bis-(3,3-dimethyl-(1-propan-3-sulphonate)-2-indolinylidenemethyl)cyclobutene-1,3-diolate[ No CAS ]
[ 2892-51-5 ]
bis-2-aminofluorenium 2,4-bis-(3,3-dimethyl-(1-propan-3-sulphonate)-2-indolinylidenemethyl)cyclobutene-1,3-diolate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
47%
In toluene; butan-1-ol;Reflux; Dean-Stark;
General procedure: Same procedure as for 2 except: <strong>[153-78-6]2-aminofluorene</strong> (638 mg, 3.52 mmol). Upon cooling, a metallic green powder was collected in vaccuo, washed with petroleum ether (60/40), and used without further purification. Yield: 830 g (47%). IR (KBr) numax: 1595 (C-O).
In toluene; butan-1-ol; at 110℃; for 21h;Inert atmosphere;
Under N2 atmosphere, n-butanol/toluene [1:1 (v/v), 5mL], N-methylaniline (3.00g, 27.4mmol), and <strong>[2892-51-5]squaric acid</strong> (1.28g, 11.2mmol) were combined and stirred at 110C for 21h, then cooled to room temperature. The obtained precipitate was filtered, washed with methanol and dried in vacuo to yield an orange powder (2.95g, yield 90.8%). 1H NMR (500MHz, DMSO-d6, TMS, delta, ppm): 7.22 (m, 8H, Ar-H), 7.29 (m, 2H, Ar-H at the para position), 3.84 (s, 6H, N-CH3). 13C NMR (125MHz, CDCl3, TMS, delta, ppm): 177.47, 168.52, (141.24, 141.09), 129.24, 127.27, 123.00, (39.19, 38.73). MALDI-TOF MS: calcd for C18H16N2O2 (MW=292.12): m/z=292.61 [M+]. Elemental anal. calcd for C18H16N2O2: C, 73.95%; H, 5.52%; N, 9.58%. Found: C, 73.93%; H, 5.59%; N, 9.66%. It is worth noting that in 13C NMR spectrum of MePhA-SQD might show peaks based on conformers as shown in the literature describing squalyrium dyes.
In toluene; butan-1-ol; at 110℃; for 25h;Inert atmosphere;
Under N2 atmosphere, n-butanol/toluene [1:1 (v/v), 5mL], N-methylaniline (4.81g, 21.3mmol), and <strong>[2892-51-5]squaric acid</strong> (1.00g, 8.77mmol) were combined and stirred at 110C for 25h, then cooled to room temperature. The obtained precipitate was filtered, washed with methanol and dried in vacuo to yield an orange powder (3.55g, yield 78.4%). 1H NMR (500MHz, DMSO-d6, TMS, delta, ppm): 7.82 [s (br), 6H, Ar-H], 7.71 [s (br), 2H, Ar-H], 7.48 [s (br), 4H, Ar-H], 7.43 (m, 12H, Ar-H). 13C NMR (125MHz, CDCl3, TMS, delta, ppm): 179.40, 168.68, 140.93, 138.21, 133.45, 132.82, 129.41, 128.69, 128.15, 127.25, 127.07, 125.91, 124.54, 123.84. MALDI-TOF MS: calcd for C36H24N2O2 (MW=516.18): m/z=516.93 [M+]. Elemental anal. calcd for C36H24N2O2: C, 83.70%; H, 4.68%; N, 5.42%. Found: C, 83.60%; H, 4.71%; N, 5.49%. In the 13C NMR spectrum of NpPhA-SQD, although 16 peaks were expected on the basis of the chemical structure, only 14 peaks were observed. When the DEPT-135 13C NMR spectrum of NpPhA-SQD in CDCl3 was obtained, six peaks attributable to quaternary carbons disappeared i.e., the peaks at 179.40, 168.68, 140.93, 138.21, 133.45, and 132.82 may have coincided with those of quaternary carbons; therefore, the remaining eight peaks may contain the two lost CH peaks.
[nickel(II)(squarate)(2,2'-bipyridine)(H2O)] monohydrate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With sodium carbonate; In methanol; water; at 20 - 90℃; for 3h;pH 8.0;Reflux;
0.5 mmol <strong>[2892-51-5]squaric acid</strong> (0.05703 g) was dissolved in 10 ml distilled water and neutralized by aqueous solution of sodium carbonate to adjust the pH at 8.0. The nickel(II) nitrate, hexahydrate (0.2908 g, 1.0 mmol) was dissolved in 5 ml distilled water and added to the previous solution. The resultant mixture was stirred at room temperature for 15 min. Then, 10 ml methanolic solution of 2,2'-bipyridine (0.156 g, 1.0 mmol) was added to the previous solution and stirred for another 1 h. The whole mixturewas then refluxed for 2 h at 90 C. It was then allowed to cool to room temperature, the blue precipitate was filtered off and light blue colored filtrate was kept in undisturbed condition. After few days, the block shaped greenish blue colored crystals suitable for single crystal X-ray structural study were obtained and these were separated and dried. Yield 72%. Anal. Calc. for C14H11N2NiO6:C, 46.2; H, 2.5; N, 7.7. Found: C, 46.5; H, 2.4; and N, 7.5%. Selected IR bands (KBr pellet, cm1): m (O-H) stretching 3445 (m); m (CO) 1506 (m), 1524 (s), 1483 (s) and 1445 (w).
A solution of 0.30 g (2.6 mmol) of <strong>[2892-51-5]squaric acid</strong> (1) and 0.80 g(4.1 mmol) of concentrated sulfuric acid in 25 mL of anhydrous methanolin a round-bottomed flask equipped with a reflux condenser washeated until reflux for 24 h. After the reaction was complete, the solutionwas cooled, neutralized with saturated sodium bicarbonate solutionand extracted with 3 × 50 mL of dichloromethane. The organicphase was then dried with anhydrous magnesium sulfate, filtered andevaporated to afford 0.32 g (87%) of a yellow oil. IR (ATR, cm-1): 2996(nuc-H), 1809 (nuC=O), 1638 (nuC=C), 1266 (nuC-O), 735 (deltaC-H)·1H NMR(400 MHz, CDCl3-d1) delta 4.37. 13C NMR (400 MHz, CDCl3-d1) delta 61.22,184.67, 189.39.
5-acetamido-1-ethyl-2,3,3-trimethyl-3H-indol-1-ium iodide[ No CAS ]
5-acetylamino-2-[[3-[(5-acetylamino-1-ethyl-1,3-dihydro-3,3-dimethyl-2H-indol-2-ylidene)methyl]-2-hydroxy-4-oxo-2-cyclobuten-1-ylidene]methyl]-1-ethyl-3,3-dimethyl-3H-indolium inner salt[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
With quinoline; In butan-1-ol; benzene; for 6h;Reflux; Dean-Stark;
A mixture of <strong>[2892-51-5]squaric acid</strong> (114 mg, 1 mmol), 5-acetylamino-2,3,3-trimethyliondoleninium iodide 2 (744 mg, 2 mmol) and quinoline (516 mg, 8 mmol) was refluxed in 30 mL of a 1:1 mixture of n-butanol and benzene with Dean-Stark trap for 6 h. After cooling the volatiles in vacuo the residue was recrystallized from methanol, yielding 475 mg (84%) of 16. 1H NMR (DMSO-d6) delta (ppm) 1.23 (br. t, 6H),1.66 (s,12H), 2.05 (s, 6H), 4.09 (br. s, 4H), 5.73 (s, 2H), 7.25 (d, J = 8.7 Hz, 2H), 7.52 (d, J = 8 Hz, 2H), 7.69 (s, 2H),10.0 (s, 2H). lambdamax (EtOH) = 655 nm ( epsilon = 3.72 x 105 L mol-1 cm-1). ES-MS+ 566.2930 (cal. 566.2893 for C34H38N4O4).
Nipecotic acid and squaric acid were purchased from AldrichChemical Co. To a solution of 1.044 g <strong>[498-95-3]nipecotic acid</strong> in 1 mL ofwater, 0.47 g of squaric acid dissolved in 1 mL of water was added.The solvent was evaporated and the residue was recrystallizedfrom a mixture of methanol-water (3:1), m.p. 188-189 C. Elementalanalysis for C16H24N2O8; calc.: %C, 51.61; %H, 6.50; %N, 7.52;found: %C, 51.47; %H, 6.55; %N, 7.45.
All chemical reagents were analytical grade commercial products. Solvent was purified by conventional methods. Squaric acid (H2Sq; 0.46 g, 4 mmol) and 2-pyridine propanol (0.56 g; 4 mmol) were dissolved in water (25 cm3) mixture in the molar ratio 1:1 and the solution was heated to 50 C in a temperature-controlled bath and stirred for one hour. The reaction mixture was then slowly cooled to room temperature. The crystals formed were filtered and washed with 10 cm3 of water and methanol and dried in air. A few days later, well-formed crystals were selected for X-ray studies. Elemental analysis for 1, (white, yield 61%) C12H13NO5: calc.: C, 57.39; H, 5.45; N, 5.63%. Found: C, 57.37; H,5.22; N, 5.58%. M.p.: 115 C
2-[[3-[(1,3-dihydro-3,3-dimethyl-2H-indol-2-ylidene)methyl]-2-hydroxy-4-oxo-2-cyclobuten-1-ylidene]methyl]-3,3-dimethyl-3H-indole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
In toluene; butan-1-ol Reflux;
General procedure.
General procedure: A mixture of quaternized or non-quaternized indolenine (2mmol) and squaric acid or its dicyanomethylene or barbituric derivative was refluxed in 50mL of a butanol-toluene mixture (1:1, v/v). The solvent was removed and the residue was dried in a vacuum desiccator over P2O5. The product was column purified (Silica gel 60, CHCl3-MeOH, gradient). 2-(3,3-dimethyl-2,3-dihydro-1H-2-indolylidenmethyl)-4-(3,3-dimethyl-3H-2-indoliumylmethylene)-3-oxo-1-cyclobuten-1-olate (nor-SqO): Yield 75%. Dark-blue solid. 1H NMR (400MHz, CDCl3, ppm): Major conformer: δ 12.84 (2H, NH, broad s), 7.27 (2H, arom-ortho, d, J=7.6Hz), 7.25 (2H, arom-meta, m, second order), 7.13 (2H, arom-ortho,d, J=7.8Hz), 7.08 (2H, arom-meta. ddd, J=7.6, 7.5, 0.8Hz), 5.48 (2H, CH, s), 1.453 (12H, CH3, s). Minor conformer: δ 12.54 (2H, NH, broad s), 7.27 (2H, arom-ortho, d, J=7.6Hz), 7.25 (2H, arom-meta, m, second order), 7.13 (2H, arom-ortho,d, J=7.8Hz), 7.08 (2H, arom-meta, ddd, J=7.6, 7.5, 0.8Hz), 5.52 (2H, CH, s), 1.450 (12H, CH3, s). 13C NMR (100MHz, CDCl3, ppm): Major conformer: δ 183.42 (CO), 175.77 (CCNH), 175.14 (CHC(CO)2), 141.96 (arom, C), 139.02 (arom, C), 128.29 (arom, CH), 123.20 (arom, CH), 122.35 (arom, CH), 111.51 (arom, CH), 85.94 (CH), 48.70 (-C(CH3)2), 26.65 (CH3). Minor conformer: 185.59 (CO), 180.31 (CO), 175.91(CCNH), 175.24 (CHC(CO)2), 141.86 (arom, C), 139.02 (arom, C), 128.24 (arom, CH), 123.26 (arom, CH), 122.48 (arom, CH), 111.36 (arom,C), 86.17 (CH), 48.70 (-C(CH3)2), 26.65 (CH3). MALDI-TOF MS, m/z calcd. for [C26H24N2O2]+ 396.2, found: 397.1 [M+H]+, 419.0 [M+Na]+, 434.9 [M+K]+. Anal. calcd. (%) for C26H24N2O2: C, 78.76; H, 6.10; N, 7.07. Found: C, 78.72; H, 6.12; N, 7.12.
69%
With activated montmorillonite K10 In neat (no solvent) at 120℃; for 1h; Irradiation;
67%
In butan-1-ol; benzene at 120℃; for 12h;
61%
In toluene; butan-1-ol at 160℃; for 0.333333h; Microwave irradiation;
41%
In toluene; butan-1-ol at 160℃; for 0.333333h; Microwave irradiation;
4.1.1 Synthesis
General procedure: The starting 5-substitute 2,3,3-trimethylindolium (2a-b) was readily obtained via the condensation of benzohydrazine substitute 1a-b with 3-methylbutan-2-one in glacial acetic, acid as previously reported [15,16] (see Scheme 2). The obtained indolenines were then quaternarized. In a typical experiment, an appropriate iodo-alkane (1:4 M ratio) was placed into a reaction vial with CH3CN and 2a-b. The vessel was then sealed with a crimp cap and heated in the microwave system at 155 °C for 35 min, according to a previously published procedure [15]. The solid formed was isolated by filtration and repeatedly washed under stirring with diethyl ether (3 × 200 ml) and then filtered, giving pure products 3a-b. (0023) A suspension of squaric acid (0.5 mmol) and either indolenine or indolium molecules 3 (1 mmol) in a 1:1 mixture of butanol:toluene (2 ml) was heated at 160 °C in the microwave reactor. The deep blue-green mixture was cooled to room temperature and a shiny purple precipitate was formed. The solvent was removed and the precipitate was washed a few times with diethyl ether. Squaraines were obtained in 41-82% yields.
In toluene; butan-1-ol at 160℃; for 0.5h; Microwave irradiation;
66%
In toluene; butan-1-ol at 160℃; for 0.5h; Microwave irradiation;
4.1.1 Synthesis
General procedure: The starting 5-substitute 2,3,3-trimethylindolium (2a-b) was readily obtained via the condensation of benzohydrazine substitute 1a-b with 3-methylbutan-2-one in glacial acetic, acid as previously reported [15,16] (see Scheme 2). The obtained indolenines were then quaternarized. In a typical experiment, an appropriate iodo-alkane (1:4 M ratio) was placed into a reaction vial with CH3CN and 2a-b. The vessel was then sealed with a crimp cap and heated in the microwave system at 155 °C for 35 min, according to a previously published procedure [15]. The solid formed was isolated by filtration and repeatedly washed under stirring with diethyl ether (3 × 200 ml) and then filtered, giving pure products 3a-b. (0023) A suspension of squaric acid (0.5 mmol) and either indolenine or indolium molecules 3 (1 mmol) in a 1:1 mixture of butanol:toluene (2 ml) was heated at 160 °C in the microwave reactor. The deep blue-green mixture was cooled to room temperature and a shiny purple precipitate was formed. The solvent was removed and the precipitate was washed a few times with diethyl ether. Squaraines were obtained in 41-82% yields. 5-bromine-2-[[3-[(1,3-dihydro-3,3-dimethyl-2H-indol-2-ylidene)methyl]-2-hydroxy-4-oxo-2-cyclobuten-1-ylidene]methyl]-5-bromine-3,3-trimethyl-3H-indole (Br-NH) [15] 5-bromine-2,3,3-trimethyl-3H-indole (3a) (238.1 mg) and squaric acid (57.0 mg) in butanol/toluene solution (1:1, 2 ml) at 160 °C for 30 min gave 183 mg of Br-NH, 0.33 mmol, 66% yield. 1H NMR (CDCl3-d1) δ: 7.26-7.03 (6H, m), 5.52-5.44 (2H, m), 1.44 (12H, s). HRMS (ESI) calcd for C26H22Br2N2O2 [M]+ 553.0048, found 553.0159. Tm: 329.7-331.8 °C. λabs: 655 nm, λem: 668 nm in ethanol.
In toluene; butan-1-ol; at 160℃; for 0.5h;Microwave irradiation;
General procedure: The starting 5-substitute 2,3,3-trimethylindolium (2a-b) was readily obtained via the condensation of benzohydrazine substitute 1a-b with 3-methylbutan-2-one in glacial acetic, acid as previously reported [15,16] (see Scheme 2). The obtained indolenines were then quaternarized. In a typical experiment, an appropriate iodo-alkane (1:4 M ratio) was placed into a reaction vial with CH3CN and 2a-b. The vessel was then sealed with a crimp cap and heated in the microwave system at 155 C for 35 min, according to a previously published procedure [15]. The solid formed was isolated by filtration and repeatedly washed under stirring with diethyl ether (3 × 200 ml) and then filtered, giving pure products 3a-b. (0023) A suspension of <strong>[2892-51-5]squaric acid</strong> (0.5 mmol) and either indolenine or indolium molecules 3 (1 mmol) in a 1:1 mixture of butanol:toluene (2 ml) was heated at 160 C in the microwave reactor. The deep blue-green mixture was cooled to room temperature and a shiny purple precipitate was formed. The solvent was removed and the precipitate was washed a few times with diethyl ether. Squaraines were obtained in 41-82% yields. 5-bromine-2-[[3-[(1,3-dihydro-3,3-dimethyl-1-ethyl-2H-indol-2-ylidene)methyl]-2-hydroxy-4-oxo-2-cyclobuten-1-ylidene]methyl]- 5-bromine-3,3-trimethyl-1- ethyl-3H-indolium (Br-C2) [15] 5-bromine-2,3,3-trimethyl-1-ethyl-3H-indolium iodide salt (3a-C2) (394.1 mg) and <strong>[2892-51-5]squaric acid</strong> (57.0 mg) in butanol/toluene solution (1:1, 2 ml) at 160 C for 30 min gave 250 mg of Br-C2, 0.41 mmol, 82% yield. 1H NMR (CDCl3) delta: 7.45 (2H, s), 7.43 (2H, d, J = 8 Hz), 6.86 (2H, d J = 8 Hz), 5.96 (2H, s), 4.05(4H, m), 1.77 (12H, s), 1.38 (6H, t, J = 7 Hz). 13C NMR (CDCl3): delta 182.3, 180.6, 169.2, 144.4, 141.2, 130.9, 125.9, 116.8, 110.6, 86.9, 77.8, 77.2, 76.5, 49.5, 38.7, 27.1, 12.1 HRMS (ESI) calcd for C30H30Br2N2O2 [M]+ 609.0674, found 609.0824. Tm: 315.8-323.7 C. lambdaabs: 638 nm, lambdaem: 644 nm in ethanol.
The DL-SeriniumHSq was synthesized using the following procedure:0.315 g (3 mmol) of DL-Serine and 0.456 g (3 mmol) of H2Sqwere dissolved in 45 ml of water. The mixture was stirred continuouslyat room temperature for 6 h. After the complete dissolutionof the <strong>[2892-51-5]squaric acid</strong> the reaction mixture was set aside to crystallize.The product was purified by multiple recrystallizations fromdistilled water. The yield of the product was 81%. Crystals suitablefor X-ray diffraction were grown by slow evaporation from amixture of methanol-water (1:3 v/v). After several weeks, colourlesscrystals are isolated, filtered and dried at room temperature.The most intensive signal in the positive ESI mass spectrum ofcompound studied is the peak at m/z, corresponding to the singlycharged cation [C3H9NO2] with a molecular weight of 88.20. TGAanalysis in the range 350e500 K showed an absence of the solventmolecules in the crystal structure.
The compounds [N(C3H7)4](HC4O4) (1) and [N(C4H9)4]2[(C4O4)(H2C4O4)2] (2) were synthesized using similar methods as follows.Firstly, 20 mL of an ethanolic solution containing 280 mg(2.45 mmol) of squaric acid was mixed with 10 mL of a solutioncontaining 832 mg (4.90 mmol) of AgNO3, resulting in the formationstoichiometrically of a precipitate of 804 mg (2.45 mmol)Ag2(C4O4). To this precipitate was added in complete darkness20 mL of a solution containing 1088 mg (4.90 mmol) of [N(C3H7)4]Cl; the white precipitate of AgCl formed was filtered and discardedleaving a solution containing 1188 mg (2.45 mmol) of[N(C3H7)4]2(C4O4), the product of interest. After approximately 30days with the slow evaporation of the solvent, the[N(C3H7)4]2(C4O4) was obtained as a very viscous liquid as previouslyobserved for the croconate of tetrabutylammonium [15].Finally, to obtain a crystalline product a third stagewas necessary inwhich 10 mL of a 50percent (ethanol/water) solution containing 280 mg(2.45 mmol) of squaric acid was added to the product obtained inthe above process. After approximately 25 days with completeevaporation of the solvent the formation of a colourless crystallinematerialwas observed with an overall yield of 42percent in relation to thetetrapropylammonium cation. Elemental analysis for[N(C3H7)4](HC4O4) (1) gave: Calc: C, 64.18percent; H, 9.76percent; N, 4.68percent;Found: C, 65.13percent; H, 10.02percent; N, 4.52percent. For the synthesis of compound2, 20 mL of a solution containing 1360 mg (4.90 mmol) of[N(C4H9)4]Cl was added in the second stage with the resultantformation of a material of high viscosity termed[N(C4H9)4]2Sq.After evaporation of the solvent in the third step,10 mL of a 50percent solution of ethanol/water containing 280 mg(2.45 mmol) of squaric acid was added. Following the slow evaporationof all solvent after 20 days the formation of a colourlesscrystalline material was observed. The yield was 38percent in relation tothe tetrabutylammonium cation. Elemental analysis of[N(C4H9)4]2[(C4O4) (H2C4O4)2] gave (2): Calc: C, 64.05percent; H, 9.28percent; N,3.40percent; Found: C, 66.13percent; H, 9.53; N, 3.51percent.
2-(3-(dibutylamino)phenoxy)ethyl prop-2-enoate[ No CAS ]
[ 2892-51-5 ]
C42H56N2O8[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
In toluene; butan-1-ol;Dean-Stark;
398 mg of squalic acid and 2.23 g of 2- (3- (dibutylamino) phenoxy) ethyl acrylate were placed in a 100 mL three-necked flask, and 40 mL of n-butanol and 20 mL of toluene were added. .Dean-Stark trap set was used to remove the water generated during the reaction and promote the reaction.After completion of the reaction, the reaction mixture was cooled, extracted with methylene chloride, and then subjected to column chromatography to obtain the compound represented by the following formula (3) in a yield of 60%.
60%
In toluene; butan-1-ol; at 120℃; for 5h;Dean-Stark;
Place 398 mg <strong>[2892-51-5]squaric acid</strong> and 2.23 g in a 100 mL 3-neck flaskEthyl 2-(3-(dibutylamino)phenoxy)acrylate,40 mL of n-butanol and 20 mL of toluene were added thereto, and the obtained mixture was heated and refluxed at 120 C. for 5 hours. The Dean-Stark separator group was used to remove water generated during the reaction and promoted the reaction. After the reaction is complete, the resultant from it is cooled and then extracted with dichloromethane and processed by column chromatography.Thus, the compound represented by Chemical Formula Z-1 was obtained with a yield of 60%.Subsequently, 0.72 g (1 mmol) of the compound represented by the chemical formula Z-1 and 2.02 g (1 mmol) of triacetyl beta-cyclodextrin represented by the chemical formula Z-2 (Chemical Abstract Service No. (CAS) 23739-88 were added. - 0, TCI Chemicals) was dissolved in 50 ml of methylene chloride, the solution was stirred at room temperature for about 12 hours, and the residue after complete removal of the solvent was dried under reduced pressure, About 2.7 g of core-shell dye was obtained as a solid.
60%
In toluene; butan-1-ol; at 120℃; for 5h;
Squaric acid (398 mg) and 2-(3-(dibutylamino)phenoxy)ethyl acrylate (2.23 g) were put in a 100 mL 3-necked flask, n-butanol (40 mL) and toluene (20 mL) were added thereto, and the mixture was heated and refluxed at 120 C. for 5 hours. Water produced during the reaction was removed by using a Dean-Stark trap set, and the reaction was promoted. After the reaction, the resultant was cooled down and extracted with methylene chloride, and an extract therefrom was treated through column chromatography to obtain a compound represented by Chemical Formula X (Yield of 60%).
In toluene; butan-1-ol at 160℃; for 0.5h; Microwave irradiation;
4.1.1 Synthesis
General procedure: The starting 5-substitute 2,3,3-trimethylindolium (2a-b) was readily obtained via the condensation of benzohydrazine substitute 1a-b with 3-methylbutan-2-one in glacial acetic, acid as previously reported [15,16] (see Scheme 2). The obtained indolenines were then quaternarized. In a typical experiment, an appropriate iodo-alkane (1:4 M ratio) was placed into a reaction vial with CH3CN and 2a-b. The vessel was then sealed with a crimp cap and heated in the microwave system at 155 °C for 35 min, according to a previously published procedure [15]. The solid formed was isolated by filtration and repeatedly washed under stirring with diethyl ether (3 × 200 ml) and then filtered, giving pure products 3a-b. (0023) A suspension of squaric acid (0.5 mmol) and either indolenine or indolium molecules 3 (1 mmol) in a 1:1 mixture of butanol:toluene (2 ml) was heated at 160 °C in the microwave reactor. The deep blue-green mixture was cooled to room temperature and a shiny purple precipitate was formed. The solvent was removed and the precipitate was washed a few times with diethyl ether. Squaraines were obtained in 41-82% yields.
Squaric acid (0.228g, 2mmol) was added to hot pure water (200mL). While the solution was hot, cobalt(II) carbonate hydrate (CoCO3·xH2O) (0.274g, 2mmol) was added under stirring. The mixture was stirred at 80C for 4h, and then at room temperature for 1day. 1-Vinylimidazole (0.362mL, 4mmol) in ethyl alcohol (20mL) was dropwise added to the mixture at room temperature for the synthesis of the complex. After stirring for one more day at room temperature, the mixture was allowed to rest. The precipitate in the powder form was separated by filtration and then washed with water, ethanol, diethyl ether and dried at room temperature. The pink product was obtained with a yield of 90% (711mg, 1.80mmol). Anal. Calc. for [Co(sq)(vim)2(H2O)2]n (C14H16CoN4O6, MA: 394.9g/mol): C, 42.54; H, 4.05; N, 14.18. Found: C, 41.84; H, 3.99; N, 13.57%. Selected IR peaks (KBr disk/cm-1): upsilon=3320 (m,br) upsilon(O-H); 3146-3008 (m,mt) upsilon(C-H); 1654 (m,sh) upsilon(C=O); 1488 (vs,br) upsilon[(C-O)+(C-C)] cm-1.
With quinoline; In toluene; butan-1-ol; for 18h;Dean-Stark; Reflux;
<strong>[29636-94-0]1-(2-hydroxyethyl)-2,3,3-trimethylindolenine bromide</strong> (2.61 g,9.20 mmol), squaric acid (1.00 g, 4.38 mmol) and quinoline(1.09 mL, 1.19 g, 9.20 mmol) were dissolved in toluene/1-butanol1:1 (125 mL) in a round-bottomed flask equipped with a magneticstirrer, a Dean-Stark trap and a water-jacketed condenser,then the mixture was refluxed 18 h. After cooling down to ambienttemperature, the volatiles were evaporated under vacuum, then Et2O was added, and the resulting precipitate was decanted. Theresidue was redissolved in minimal CH2Cl2, poured into Et2O, thenthe precipitatewas collected by filtration andwashed with H2O andEt2O until the effluent was colorless to yield, after drying, 2.05 gcompound 3 (4.23 mmol, 97%). Tm > 300 C (dec.); FT-IR (KBr/CH2Cl2) 3346, 3054, 2961, 2924, 2870, 1572, 1494, 1455, 1431, 1354,1279, 1241, 1171, 1099, 1055, 1020, 969, 930, 835, 814, 782, 753, 696,682 cm-1; 1H NMR (400 MHz, CDCl3) delta 7.49 (d, 3J = 7.3 Hz, 2H), 7.31(m, 4H), 7.14 (t, 3J = 7.3 Hz, 2H), 5.89 (s, 2H), 4.33 (br s, 2H), 4.16 (t,3J = 5.4 Hz, 4H), 3.77 (t, 3J = 5.4 Hz, 4H), 1.69 (s, 12H) ppm; 13C NMR(100 MHz, CDCl3) delta 180.7, 177.8, 169.7, 142.7, 141.3, 129.2, 129.0,127.6, 123.4, 121.9, 110.6, 86.3, 57.7, 48.6, 45.9, 26.4 ppm; UV-Vis(DMF):lambdamax (epsilon) 641 nm (143000); HRMS (ESI, MNa+) calcd. forC30H32NaN2O4 m/e: 507.2254, found: 507.2258.
With orthoformic acid triethyl ester; In ethanol;Reflux; Inert atmosphere;
(2) taking squaric acid (1 mol) in 50 mL of absolute ethanol, adding the catalyst to triethyl orthoformate, heating under reflux with nitrogen until all the squaric acid is dissolved.2.2 mol of the quaternary ammonium salt (I2d) prepared above was added thereto, and heating was continued to reflux.TLC was detected until all the starting materials were reacted, and the solvent was removed by cooling under reduced pressure, and the column chromatography was separated to give a blue solid dye (I2c)
3-(5-carboxypentyl)-1,1,2-trimethyl-1H-benzo-[e]indol-3-ium bromide[ No CAS ]
C46H48N2O6[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
49%
In a 2: 1 mixture of toluene and n-butanol, <strong>[2892-51-5]squaric acid</strong> and 2 equivalents of carboxypentylbenzoindolium bromide were reacted, JJ25 was synthesized. Specifically, After dissolving carboxypentylbenzoindolium bromide (0.7 g, 1.74 mmol) and squalic acid (0.1 g, 0.87 mmol) in a 2: 1 mixture of toluene and n-butanol and installing a Dean Stark apparatus, and then it was refluxed for 12 hours. After termination of reaction and then The n-butoxyl substituted intermediate was isolated using column chromatography (chloroform: MeOH = 95: 5). To remove the n-butoxyl group, the intermediate was dissolved in methanol (50 ml), 2N sodium hydroxide (5 ml) was added, and the reaction was carried out at 50 C for 6 hours, and then neutralized with 2 N HCl(hydrogen chloride). The solvent was removed and JJ-25 was isolated 620 mg (49%) using column chromatography (silica, EtOAc: MeOH = 90: 10).
2,3,3,8-tetramethyl-3H-pyrrolo[3,2-h]quinoline[ No CAS ]
[ 2892-51-5 ]
(Z)-3-oxo-2-((Z)-(3,3,8-trimethyl-1,3-dihydro-2H-pyrrolo[3,2-h]quinolin-2-ylidene)methyl)-4-((3,3,8-trimethyl-3H-pyrrolo[3,2-h]quinolin-1-ium-2-yl)methylene)cyclobut-1-en-1-olate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
With quinoline; In toluene; butan-1-ol; at 120℃; for 6h;
To the azeotropic mixture of n-BuOH: toluene (20 ml 1:1 v/v) wereadded 2, 3, 3, 8-tetramethyl-3H-pyrrolo [3, 2-h] quinoline 3 (0.5 g,2.2 mmol), 3, 4-dihydroxy-3-cyclobuten-1, 2-dione 4 (0.127 g,1.1 mmol) and quinoline (1 ml). The mixture was then refluxed for6 h. After completion of the reaction, the solvent was removed undervacuo. The crude product obtained was purified by column chromatography(eluent system: dichloromethane: methanol, 9:1) to give greencoloured solid (0.8 g, 68%).
1-ethyl-2,3,3,8-tetramethyl-3H-pyrrolo [3,2-h]quinolin-1-ium iodide[ No CAS ]
[ 2892-51-5 ]
(Z)-2-((Z)-(1-ethyl-3,3,8-trimethyl-1,3-dihydro-2H-pyrrolo[3,2-h]quinolin-2-ylidene)methyl)-4-((1-ethyl-3,3,8-trimethyl-3H-pyrrolo[3,2-h]quinolin-1-ium-2-yl)methylene)-3-oxocyclobut-1-en-1-olate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65%
With quinoline; In toluene; butan-1-ol; at 120℃; for 6h;
To the azeotropic mixture of n-BuOH: toluene (20 ml 1:1 v/v) wereadded 1-ethyl 2, 3, 3, 8-tetramethyl-3H-pyrrolo [3, 2-h] quinoline 5(0.5 g, 1.3 mmol), 3, 4-dihydroxy-3-cyclobuten-1, 2-dione 4 (0.074 g,0.6 mmol) and quinoline (1 ml). The mixture was then refluxed for6 h.After completion of reaction solvent was removed under vacuo.The crude product obtained was purified by column chromatography(eluent system: dichloromethane: methanol, 9:1) to give greencoloured solid (0.5 g, 65%).
With pyridine; In toluene; butan-1-ol; at 115℃; for 24h;Inert atmosphere;
1.35 g (3 mmol) of porphyrin derivative with 171 mg (1.59 mmol) of 3,4-dihydroxy-3-cyclobutene-1,2-dione (<strong>[2892-51-5]squaric acid</strong>) was added to a mixed solvent of 10 mL of toluene n-butanol (1:1 by volume). And add 5mL of pyridine, Under the protection of nitrogen, The temperature was slowly raised to 115 C, and after 24 hours, it was precipitated with diethyl ether to obtain 805 mg (0.98 mmol) of the intermediate product squaraine derivative, yield 65%.
3-ethyl-6-iodo-2-methylbenzothiazol-3-ium iodide[ No CAS ]
[ 2892-51-5 ]
4-[(3-ethyl-6-iodobenzothiazol-3-ium-2-yl)methylidene]-2-[(3-ethyl-6-iodo-3H-benzothiazol-2-ylidene)methyl]-3-oxocyclobut-1-en-1-olate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
With pyridine; In butan-1-ol; for 4h;Reflux;
A mixture of benzothiazolium salt 2 (2.00 g, 4.64 mmol) and <strong>[2892-51-5]squaric acid</strong> (0.27 g, 2.32 mmol) inn-BuOH/pyridine [9/1 (v/v)] (230 mL) was heated under reflux for about 4 h. The reaction mixturewas then cooled in an ice bath, the resulting precipitate was collected by filtration under reducedpressure and washed thoroughly with water and Et2O to afford chromatographically pure greencrystals. Yield: 93%. M.p. > 300 C. UV/Vis [MeOH/CH2Cl2, 99/1 (v/v)] max (log "): 660 (4.85);1H-NMR (DMSO-d6) : 8.22 (2H, s, ArH), 7.72 (2H, d, J = 8.0, ArH), 7.32 (2H, d, J = 8.0, ArH), 5.78(2H, s, CH=C), 4.25 (4H, d, J = 6.8, NCH2CH3), 1.35-1.30 (6H, m, NCH2CH3). HRMS (ESI-TOF) m/z:683.88936 ([M I]+, calc. for C24H20I2N3O2S2: 683.88761).
In toluene; butan-1-ol at 125℃; for 16h; Dean-Stark;
1 Synthesis Example 1
3.5 parts of the compound represented by the formula (1-1) and 0.57 parts of 3,4-dihydroxy-3-cyclobutene-1,2-dione,201 parts of 1-butanol and 134 parts of toluene were mixed.For the resulting mixture, the formed water was removed using a Dean-Stark tube.Stir at 125 ° C for 16 hours.The crystals formed after cooling were filtered, washed twice with 80 parts of hexane, and the crystals were dried under reduced pressure at 60 ° C to obtain 3.3 parts of the compound represented by formula (I-10).
In toluene; butan-1-ol at 100℃; for 3h; Dean-Stark;
3 (Example 3) Synthesis of squarylium compound 3
Compound 4 (0.53 g) and Compound 2 (0.15 g)20 mL of toluene and 20 mL of n-butanolAdded to the mixed solvent ofHeat and stir at 100 ° C for 3 hours by the Dean-Stark methodThe Subsequently, filtration was performed, and the obtained solid was washed with toluene and dried under vacuum to obtain 0.46 g of squarylium compound 3.
1,3-bis(p-piperazinephenylamino)squaraine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90.4%
General procedure: Squaraine dyes were synthesized by the reaction of squaric acidwith p-substituted anilines according by the general method: 1,2- dihydroxycyclobuten-3,4-dione (2.5 mmol) was heated under reflux in amixture of 1-butanol (40 mL) and toluene (20 mL), and water was distilledoffi azeotropically using a Dean-Stark trap. Affiter 1 h, an appropriatep-substituted aniline (5 mmol) was added and the reaction mixturerefluxed for additional 4 h. Reaction mixture was cooled and thesolvent removed on a Buechner funnel. The solid was dried at roomtemperature [18,19]. The p-substituted derivatives of aniline used inthe synthesis were: p-aminobiphenyl, p-aminothiophenol, p-methoxyaniline,p-isopropylaniline, p-tert-butylaniline, <strong>[67455-41-8]1-(p-aminophenyl)piperazine</strong>and p-propylaniline.
General procedure: Squaraine dyes were synthesized by the reaction of squaric acidwith p-substituted anilines according by the general method: 1,2- dihydroxycyclobuten-3,4-dione (2.5 mmol) was heated under reflux in amixture of 1-butanol (40 mL) and toluene (20 mL), and water was distilledoffi azeotropically using a Dean-Stark trap. Affiter 1 h, an appropriatep-substituted aniline (5 mmol) was added and the reaction mixturerefluxed for additional 4 h. Reaction mixture was cooled and thesolvent removed on a Buechner funnel. The solid was dried at roomtemperature [18,19]. The p-substituted derivatives of aniline used inthe synthesis were: p-aminobiphenyl, p-aminothiophenol, p-methoxyaniline,p-isopropylaniline, p-tert-butylaniline, 1-(p-aminophenyl)piperazineand p-propylaniline.
Stage #1: 4,5,6,7-tetrahydroindole With potassium hydroxide In dimethyl sulfoxide for 0.833333h; Inert atmosphere;
Stage #2: methyl iodide In dimethyl sulfoxide for 2h;
Stage #3: squaric acid In ethanol at 85℃; for 1.25h;
1.3 Example 1.3 (Synthesis of SQL-3)
Pulverized 740 mg of potassium hydroxide, placed it into a reactor, and established an argon atmosphere. Added 400 mg 4,5,6,7-tetrahydroindole in 6 mL of DMSO and stirred for 50 minutes. Added 0.41 mL methyl iodide and stirred for 2 h. Added 20 mL water, extracted with 30 mL hexane, and washed the extract twice with 20 mL portions of water. Dried the extract with sodium sulfate and concentrated in vacuo to 380 mg of oil. Dissolved the oil in 5 mL ethanol and poured the resulting solution onto 156 mg of squaric acid in a vial. Stirred and heated the contents of the vial in an 85 °C-block until boiling then capped the vial and stirred for 1 hour and 15 minutes. Cooled to room temperature and filtered, washing the filter cake twice with 2 mL portions of ethanol. Dried the filter cake in vacuo at 70 °C to 315 mg of purple powder product. *H N MR (400 MHz, CDCI3) d 7.53 (s, 1H), 4.11 (s, 3H), 2.70 (t, J = 6.3 Hz, 2H), 2.60 (t, J = 6.2 Hz, 2H), 1.90 (ddt, = 12.2, 8.6, 4.7 Hz, 2H), 1.81 - 1.71 (m, 2H). MS (APCI, positive mode) 349. Film optical data (Amorphous polycarbonate [APC] film): l max = 582 nm, FWHM = 26 nm.
Stage #1: 4,5,6,7-tetrahydroindole With potassium hydroxide In dimethyl sulfoxide for 0.75h; Inert atmosphere;
Stage #2: benzyl bromide In dimethyl sulfoxide for 1h; Cooling with ice;
Stage #3: squaric acid In ethanol at 80℃; for 2h; Sealed tube;
1.4 Example 1.4 (Synthesis of SQL-4)
Loaded 335 mg of pulverized potassium hydroxide into a reactor under an argon atmosphere. Added 3 mL dimethylsulfoxide, stirred, and added 181 mg 4,5,6,7- tetrahydroindole. Stirred for 45 minutes, cooled in an icebath, and dripped in 256 mg benzyl bromide. Removed cooling, stirred for 1 hour, diluted with icewater, and extracted with hexanes. Washed the extracts with water, dried them with brine then sodium sulfate, and concentrated to 430 mg of orange oil pyrrole that was used without further purification. Dissolved this in 5 mL ethanol, combined in a via l along with 83 mg squaric acid, sealed the vial, and stirred and heated the contents at 80 °C for 2 hours. Cooled the slurry, filtered it, and washed the filter cake with ethanol. Dried the filter cake at 70 °C under vacuum for 2 hours to 130 mg of squaraine product. 1H N MR (400 MHz, Chloroform-d) d 7.60 (s, 1H), 7.23 (q, J = 9.0, 7.4 Hz, 3H), 7.02 (d, J = 7.5 Hz, 2H), 5.94 (d, J = 14.8 Hz, 2H), 2.60 (q, J = 7.0, 6.0 Hz, 2H), 2.53 (t, J = 6.3 Hz, 2H), 1.79 (p, J = 6.3, 5.8 Hz, 2H), 1.71 (q, J = 5.5, 4.9 Hz, 2H). LC-MS (APCI, +) 501. Amorphous polycarbonate film: l max = 585 nm, FWH M = 26 nm.
Stage #1: 4,5,6,7-tetrahydroindole With potassium hydroxide In dimethyl sulfoxide for 1h; Inert atmosphere;
Stage #2: p-methoxybenzyl chloride In dimethyl sulfoxide for 0.75h;
Stage #3: squaric acid In ethanol at 80℃; for 2h; Sealed tube;
1.5 Example 1.5 (Synthesis of SQL-5)
Under argon, 110 mg 4,5,6,7-tetrahydroindole was combined with 220 mg of pulverized potassium hydroxide and 2 mL dimethyl sulfoxide and stirred for 1 hour. 142 mg 4-methoxybenzyl chloride was added and the resulting solution stirred for 45 minutes. 4 mL cool water was added and hexanes was used to extract the resulting solution. The extract was washed with water, dried with sodium sulfate, and concentrated to 160 mg of crude pyrrole. This was dissolved in 2 mL ethanol, added to 30 mg squaric acid, stirred, and heated in a sealed vial at 80 °C for 2 hours. The solution was cooled to room temperature and filtered. The filter cake was dried to 13 mg of product squaraine. 1H N MR (400 MHz, Chloroform- ) d 7.59 (s, 1H), 6.98 (d, 7 = 8.1 Hz, 2H), 6.81 (d, J = 8.0 Hz, 2H), 5.86 (s, 2H), 3.77 (s, 3H), 2.57 (dt, J = 12.2, 6.1 Hz, 2H), 1.86 - 1.63 (m, 6H). 13C N MR (101 MHz, Chloroform- ) d 158.72, 129.94, 128.27, 126.73, 114.09, 55.23, 49.70, 23.48, 23.01, 22.62, 22.26. HPLC-MS (APCI, +) 561. Amorphous polycarbonate film: l max = 585 nm, FWH M = 27 nm.
Stage #1: 2-Methylcyclopentanone; phenethylamine at 80℃; for 0.666667h; Inert atmosphere;
Stage #2: ethylene glycol With [RhCl2(p-cymene)]2; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene at 125℃; for 18h;
Stage #3: squaric acid In ethanol at 80℃; for 2h; Sealed tube;
1.21 Example 1.21 (Synthesis of SQL-21)
Established an argon atmosphere within a reactor, then added 2.00 g 1- methylcyclopentanone and 35 mL 3-methyl-3-pentanol. Stirred and added 2.72 g phenethylamine. Heated this mixture in a n 80 °C-oil bath for 40 minutes then added 250 mg dichloro(p-cymene)ruthenium(ll) dimer, 476 mg XantPhos, and 2.50 mL ethylene glycol. Heated the oil bath to 125 °C for 18 hours. Cooled, concentrated, and purified the residue using silica gel chromatography and an ethyl acetate-hexanes gradient. The product pyrrole eluted along with an impurity, but was used without further purification after concentrating it to 880 mg of yellow oil. This was dissolved in 10 mL ethanol and heated at 80 °C, stirred, in a sealed vial along with 222 mg squaric acid. After 2 hours, the mixture was cooled, concentrated and purified using silica gel chromatography and a methanol-dichloromethane gradient, giving 1.16 g of product squaraine. 1H N MR (400 MHz, Chloroform- ) d 7.51 (s, 1H), 7.31 - 7.18 (m, 3H), 7.12 (ddd, 7 = 7.5, 4.7, 1.7 Hz, 2H), 5.33 (dt, 7 = 13.5, 6.1 Hz, 1H), 4.33 (dt, J = 13.4, 7.8 Hz, 1H), 3.10 (dd, J = 7.9, 6.2 Hz, 2H), 2.73 - 2.60 (m, 1H), 2.58 - 2.46 (m, 1H), 2.45 - 2.33 (m, 2H), 1.89 (tt, J = 8.4, 4.2 Hz, 1H), 1.19 - 1.12 (m, 3H). HPLC-MS (APCI, +) 529. 13C N MR (101 MHz, Chloroform-d) d 162.04, 161.93, 138.68, 133.96, 133.93, 131.58, 129.27, 128.46, 126.67, 49.94, 49.90, 38.93, 38.46, 38.44, 32.95, 32.90, 23.35, 18.69. Amorphous polycarbonate film: l max = 593 nm, FWH M = 24 nm.
Stage #1: 2,2-dimethylcyclopentanone; phenethylamine at 80℃; for 0.5h; Inert atmosphere;
Stage #2: ethylene glycol With [RhCl2(p-cymene)]2; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene at 125℃; for 45h;
Stage #3: squaric acid In ethanol at 80℃; for 2h; Sealed tube;
1.23 Example 1.23 (Synthesis of SQL-23)
To a reactor, under argon, was added 0.56 g 2,2-dimethylcyclopentanone and 9 mL 3- methyl-3-pentanol. This solution was stirred, 665 mg phenethylamine added, and the resulting mixture heated in an 80 °C-oil bath for 30 minutes. 61 mg dichloro(p- cymene)ruthenium (I I) dimer, 115 mg XantPhos, and 0.61 mL ethylene glycol were added and the oil bath heated to 125 °C for 45 hours. The solution was concentrated and purified by silica gel chromatography using an ethyl acetate-hexanes gradient, providing 176 mg of impure pyrrole product. This was dissolved in 2 mL ethanol and combined with 42 mg squaric acid in a vial. The solution was stirred and the vial sealed and heated at 80 °C for 2 hours. The resulting slurry was cooled and filtered. The filter cake was washed with ethanol and dried at 70 °C under vacuum to 98 mg of squaraine product. 1H N MR (400 MHz, Chloroform ed) d 7.55 (s, 1H), 7.44 - 7.36 (m, 2H), 7.32 (t, J = 7.4 Hz, 2H), 7.25 (t, J = 7.1 Hz, 1H), 4.81 (dd, J = 9.8, 6.5 Hz, 2H), 3.20 - 3.06 (m, 2H), 2.65 (t, J = 7.0 Hz, 2H), 2.27 (t, J = 7.0 Hz, 2H), 1.37 (s, 6H). 13C N MR (101 MHz, Chloroform- ) d 170.72, 162.46, 138.37, 133.80, 131.95, 129.26, 128.60, 126.64, 49.27, 47.00, 40.67, 39.53, 26.82, 22.51. H PLC-MS (APCI, +) 557. Amorphous polycarbonate film: l max = 594 nm, FWH M = 24 nm.
Stage #1: 2-naphthalen-1-yl-ethylamine; cyclopentanone at 70℃; for 1h; Inert atmosphere;
Stage #2: ethylene glycol With [RhCl2(p-cymene)]2; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene at 125℃; for 19h;
Stage #3: squaric acid In ethanol at 80℃; for 2h; Sealed tube;
1.13 Example 1.13 (Synthesis of SQL-13)
A reactor containing 0.34 g cyclopentanone and 4.5 mL 3-methyl-3-pentanol was prepared and an argon atmosphere established. To this was added a solution of 0.68 g 2- naphthaleneethylamine in 4.5 mL 3-methyl-3-pentanol and the reaction heated in 70 °C-oil for 1 hour. Added 24 mg dichloro(p-cymene)ruthenium (II) dimer, 45 mg XantPhos, and 0.48 mL ethylene glycol and heated the oil bath to 125 °C for 19 hours. Concentrated free of solvent, then purified the residue using silica gel chromatography and an ethyl acetate- hexane gradient. This gave 147 of pyrrole as a yellow oil. It was dissolved in 2 mL ethanol and added into a vial along with 32 mg squaric acid. The vial was sealed and its contents stirred and heated at 80 °C for 2 hours. The solution was cooled, filtered, and the filter cake washed with ethanol then dried under vacuum to 113 mg squaraine product. 1H N MR (400 MHz, Chloroform-d) d 7.84 - 7.78 (m, 1H), 7.74 (t, J = 9.4 Hz, 2H), 7.56 (s, 1H), 7.48 - 7.42 (m, 2H), 7.40 (s, 1H), 7.24 (d, J = 8.4 Hz, 1H), 4.87 (t, J = 6.5 Hz, 2H), 3.27 (t, J = 6.5 Hz, 2H), 2.53 (d, J = 6.9 Hz, 2H), 1.96 (d, J = 7.8 Hz, 4H). 13C N MR (101 MHz, Chloroform- ) d 159.39, 136.24, 134.33, 133.49, 132.28, 131.33, 128.00, 127.87, 127.69, 127.59, 127.47, 126.03, 125.52, 50.76, 38.95, 28.69, 24.90, 24.80. LC-MS(APCI, +) 601. Amorphous polycarbonate film: l max = 592 nm/FWH M = 26 nm.
Stage #1: 2-Methylcyclopentanone; 2-(2,4-dichloro-phenyl)-ethylamine at 80℃; for 0.5h; Inert atmosphere;
Stage #2: ethylene glycol With [RhCl2(p-cymene)]2; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene at 145℃; for 6h;
Stage #3: squaric acid In ethanol at 80℃; for 2h; Sealed tube;
1.28 Example 1.28 (Synthesis of SQL-28)
0.52 g 2-methylcyclopentanone and 10 mL 1-methylcyclohexanol were combined in a reactor under argon and stirred. 1.11 g 2,4-dichlorophenethylamine was added and the solution heated in an 80 °C oil bath for 30 minutes. 32 mg dichloro(p-cymene)ruthenium (I I) dimer, 61 mg XantPhos, and 0.66 mL ethylene glycol were added and the oil bath heated to 145 °C for 6 hours. Concentrated free of most 1-methylcyclohexanol then purified the residue using silica gel chromatography and an ethyl acetate-hexanes gradient. The 414 mg of pyrrole product eluted with an impurity, but was used without further purification. It was dissolved in 3 mL ethanol and combined with 81 mg squaric acid in a vial. The vial was sealed and its contents stirred and heated at 80 °C for 2 hours. The slurry was cooled and filtered. The filter cake was washed with ethanol and dried at 70 °C under vacuum to 361 mg of squaraine product. *H N MR (400 MHz, Chloroform- ) d 7.50 (s, 1H), 7.40 (q, 7 = 1.5 Hz, 1H), 7.15 - 7.10 (m, 2H), 5.34 (tdd, J = 15.2, 7.4, 4.9 Hz, 1H), 4.39 - 4.25 (m, 1H), 3.37 - 3.25 (m, 1H), 3.15 (dtd, J = 13.5, 7.7, 2.0 Hz, 1H), 2.75 - 2.64 (m, 1H), 2.67 - 2.51 (m, 1H), 2.54 - 2.38 (m, 1H), 1.94 (dddd, J = 12.7, 7.4, 5.4, 3.3 Hz, 1H), 1.21 (dd, J = 7.0, 1.6 Hz, 3H). H PLC-MS (APCI, +) 667. Amorphous polycarbonate film: l max = 594 nm, FWH M = 24 nm.
Stage #1: 2-Methylcyclopentanone; (naphth-1-yl)methylamine at 80℃; for 0.666667h; Inert atmosphere;
Stage #2: ethylene glycol With [RhCl2(p-cymene)]2; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene at 145℃; for 24h;
Stage #3: squaric acid In ethanol at 80℃; for 2.5h; Sealed tube;
1.26 Example 1.26 (Synthesis of SQL-26)
0.42 g 2-methylcyclopentanone was dissolved in 10 mL 1-methylcyclohexanol under argon. 0.74 g 1-naphthylmethylamine was added and the resulting solution heated in an 80 °C-oil bath for 40 minutes. 26 mg dichloro(p-cymene)ruthenium (II) dimer, 50 mg XantPhos, and 0.53 mL ethylene glycol were added and the oil bath heated to 145 °C for 24 hours. Concentrated free of most 1-methylcyclohexanol then purified the residue using silica gel chromatography with an ethyl acetate-hexanes gradient. This provided 180 mg of pyrrole product which was dissolved with 2.5 mL ethanol and added to 39 mg squaric acid in a vial. The vial was sealed and its contents stirred and heated at 80 °C for 2.5 hours. The resulting slurry was cooled and filtered. The filter cake was dried under vacuum at 75 °C to 148 mg of squaraine product. HPLC-MS (APCI, +) 601. Amorphous polycarbonate film: l max = 594 nm, FWH M = 23 nm.
With orthoformic acid triethyl ester; In ethanol;Reflux; Inert atmosphere;
(3) taking squaric acid (2 mol) in 100 mL of absolute ethanol, adding the catalyst triethyl orthoformate, heating under reflux with nitrogen until all the squaric acid is dissolved.1 mol of the quaternary ammonium salt (V2d) prepared above and 1 mol of the quaternary ammonium salt (VII2d) were added thereto, and the mixture was further heated to reflux.TLC was detected until all the starting materials were reacted, and the solvent was removed by cooling under reduced pressure, and the column chromatography was separated to give a blue solid dye (VII2c)
With orthoformic acid triethyl ester In ethanol Reflux; Inert atmosphere;
7.1.3
(3) taking squaric acid (2 mol) in 100 mL of absolute ethanol, adding the catalyst triethyl orthoformate, heating under reflux with nitrogen until all the squaric acid is dissolved.1 mol of the quaternary ammonium salt (V1d) prepared above and 1 mol of the quaternary ammonium salt (VII1d) were added thereto, and the mixture was further heated to reflux.TLC was detected until all the starting materials had been reacted, the solvent was removed by cooling under reduced pressure, and the blue solid dye (VII1c) was obtained by column chromatography
With orthoformic acid triethyl ester; In ethanol;Inert atmosphere; Reflux;
(3) taking squaric acid (1 mol) in 100 mL of absolute ethanol, adding the catalyst triethyl orthoformate, heating under reflux with nitrogen until all the squaric acid is dissolved.0.8 mol of the quaternary ammonium salt (I2d) prepared above was added thereto, and heating was continued with 1.2 mol of the quaternary ammonium salt (I3d).TLC was detected until all the starting materials were reacted, and the solvent was removed by cooling under reduced pressure, and the column chromatography was separated to give a blue solid dye (I3c)
With orthoformic acid triethyl ester; In ethanol;Reflux; Inert atmosphere;
(3) taking squaric acid (2 mol) in 100 mL of absolute ethanol, adding the catalyst triethyl orthoformate, heating under reflux with nitrogen until all the squaric acid is dissolved.1 mol of the quaternary ammonium salt (V2d) prepared above and 1 mol of the quaternary ammonium salt (V2d) were added thereto, and the mixture was further heated to reflux.TLC was detected until all the starting materials had been reacted, and the solvent was removed by cooling under reduced pressure, and a blue solid dye (V2c) was obtained by column chromatography
With orthoformic acid triethyl ester; In ethanol;Inert atmosphere; Reflux;
(3) taking squaric acid (2 mol) in 100 mL of absolute ethanol, adding the catalyst triethyl orthoformate, heating under reflux with nitrogen until all the squaric acid is dissolved.1 mol of the quaternary ammonium salt (V2d) prepared above and 1 mol of the quaternary ammonium salt (VI2d) were added thereto, and the mixture was further heated to reflux.TLC was detected until all the starting materials had been reacted, the solvent was removed by cooling under reduced pressure, and the blue solid dye (VI2c) was obtained by column chromatography
With orthoformic acid triethyl ester In ethanol Reflux; Inert atmosphere;
5.1.3
(3) taking squaric acid (2 mol) in 100 mL of absolute ethanol, adding the catalyst triethyl orthoformate, heating under reflux with nitrogen until all the squaric acid is dissolved.1 mol of the quaternary ammonium salt (V1d) prepared above and 1 mol of the quaternary ammonium salt (V1d) were added thereto, and the mixture was further heated to reflux. TLC was detected until all the starting materials had been reacted, and the solvent was removed by cooling under reduced pressure, and a blue solid dye (V1c) was obtained by column chromatography
In toluene; butan-1-ol for 3h; Dean-Stark; Inert atmosphere;
2 Example 2
In the present embodiment, a compound (SQ) having a structure represented by the formula (II) is produced by a compound of the structure represented by the formula (III) and a squaric acid.Under a nitrogen atmosphere, in a Dean-Stark apparatus, squaric acid (0.11 g, 1 mmol) was placed in 10 ml of n-butanol and 10 ml of toluene, and heated under reflux for 1 h.The squaric acid is dissolved in a binary solvent system to obtain a reaction liquid.The compound of the formula (III) (0.57 g, 2 mmol) was dissolved in 5 ml of n-butanol and 5 ml of toluene, and the reaction mixture was added dropwise thereto, and the reaction was stopped after the first reaction for 3 hours.The first reaction product is cooled to precipitate a solid precipitate, and the precipitate is washed by adding n-hexane to filter, and then the precipitate is subjected to dissolution extraction by adding dichloromethane and water.After drying with anhydrous sodium sulfate, rotary evaporation, and purification with a mixed solution of dichloromethane and petroleum ether in a volume ratio of 1:1.The green solid product, 446.1 mg of the compound of the formula (II), was obtained with a purity of 99% and a yield of 68.1%
Synthesis of CF3-SADBE
General procedure: A solution of squaric acid (9 mmol) and alcohol (36 mmol) in toluene (9 ml) was refluxed at 100 °C using Dean-Stork apparatus for 16h. After completion of the reaction toluene was concentrated in vacuo and resulting solution was diluted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution flowed bybrine. The volatile were concentrated in vacuo and purified by column chromatography to yield respective compound.
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