There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 81-88-9 | MDL No. : | MFCD00011931 |
Formula : | C28H31ClN2O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PYWVYCXTNDRMGF-UHFFFAOYSA-N |
M.W : | 479.01 | Pubchem ID : | 6694 |
Synonyms : |
Basic Violet 10;Brilliant Pink B;Basonyl Red 545.;Symulex Magenta F;NSC 10475;Tetraethylrhodamine;Rhodamine O
|
Signal Word: | Danger | Class: | N/A |
Precautionary Statements: | P264-P270-P280-P330-P305+P351+P338-P310-P403-P501 | UN#: | N/A |
Hazard Statements: | H302-H318-H412 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35 g | Stage #1: at 175℃; for 13 h; Stage #2: at 25℃; for 0.5 h; Stage #3: With hydrogenchloride; sodium chloride In water at 80℃; for 1 h; |
10063] Synthesis Example[Chemical Formula 4]10064] (1) Afier adding phthalic anhydride (15.7 g) and3-(N,N-dimethylamino)phenol (18.0 g) to 1 ,2-dichloroben- zene (57.0 g) in a reactor, the resulting mixture was stirred at 175° C. for 1 hout 1 hour later, 3-(N,N-diethylamino)phenol (12.1 g) was added in three aliquots. Afier the addition was completed, the mixture was stirred at 175° C. for 12 hours. Upon completion of reaction, the mixture was cooled to below 25°C. and, afier adding 3percent sodium hydroxide aqueous solution (100 g), stirred for 30 minutes. After separating the organic layer and adding 4.5percent sulfuric acid (330 g), the mixture was stirred for 30 minutes. Afier separating the aqueous layer and adding 35percent hydrochloric acid (30 g) and sodium chloride (15 g), the mixture was stirred at 80° C. for 1 hour. After cooling to room temperature, the resulting crystals were filtered, washed with 2percent: hydrochloric acid (300 g) and dried at 80° C. to obtain a compound of [Chemical Formula Di (35 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: ethanol; rhodamine B With dmap; camphor-10-sulfonic acid In chloroform for 0.5h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 20℃; for 2h; | 2 For rhodamine B (Tokyo chemical industrial (unit) manufacturing) 25.0 parts added in anhydrous chloroform (Guandong-chemical (unit) manufacturing) 200 parts, camphor sulfonic acid (Aldrich (unit) manufacturing) 1.5 parts, 4 - (N, N-dimethyl amino) pyridine (Tokyo chemical industrial (unit) manufacturing) 1.6 parts, ethanol (Tokyo chemical industrial (unit) manufacturing) 12.1 parts, stirring for about 30 minutes. Thereafter, is slowly added to the 1-ethyl-3 - (3-dimethyl amino propyl) imine hydrochloride carbon two acyls (and optical pure medicine industrial (unit) manufacturing) 14.5 parts of anhydrous chloroform added to 55.3 parts and the pre-dissolving the same after the solution, stirring at room temperature for about 2 hours. Using 1 N hydrochloric acid aqueous solution 150 of 2 time after the operation the liquid, in order to 10% salt water 150 the organic layer by washing 2 times. Then added anhydrous magnesium sulfate 43 portions, stirring for about 30 minutes, filter the desiccant, distillation to remove the solvent, the (g-2) obtains the type the rhodamine compound expressed by 23.1 parts (yield 87%). |
69% | Stage #1: ethanol; rhodamine B With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 4h; Inert atmosphere; Darkness; Stage #2: With hydrogenchloride In dichloromethane; water | |
54% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 72h; |
With sulfuric acid at 50℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With thionyl chloride at 20℃; Inert atmosphere; | |
99% | With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; | Rhodamine B chloride (= N-(9-(2-(chlorocarbonyl)phenyl)-6-(diethylamino)-3H-xanthen-3-ylidene)-Nethylethanaminiumchloride) The fluorescent dye rhodamine B (10.0 g, 22.3 mmol) wasdissolved in dry CH2Cl2 (250 mL), treated with oxalylchloride (8.84 mL) at 0 °C. One drop of dry DMF wasadded, and the solution was allowed to warm up to roomtemperature. After completion of the reaction, the solventwas removed under reduced pressure. The residue wasdissolved in dry CH2Cl2 (50 mL), and the solution wasconcentrated again to remove excess oxalyl chloride.Yielding rhodamine B chloride (11.0 g, 99%) as a purplesolid which is used without further purification |
98% | With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 2h; | 4.3.1. Synthesis of the rhodamine B acyl chloride A Rhodamine B (2.0 g, 4.2 mmol) was dissolved in dry DCM(200 mL). At 0 °C oxalyl chloride (1 mL, 11.8 mmol) and DMF(100 mL, 1.3 mmol) were added and the reaction was allowed towarm to room temperature. The reaction progression was monitoredby observing the gas evolution. After 2 h, the volatiles wereremoved under reduced pressure, and the residue was for redissolved2 times each with DCM (100 mL) and evaporated todryness to remove the excess of oxalyl chloride. The resulting acylchloride was obtained as violet solid (2.04 g, 98%). |
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Heating; | ||
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Heating; | ||
With trichlorophosphate for 24h; Reflux; | ||
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Reflux; | ||
With thionyl chloride at 20℃; | ||
With trichlorophosphate In 1,2-dichloro-ethane Reflux; | ||
With trichlorophosphate In 1,2-dichloro-ethane at 94℃; for 4h; Inert atmosphere; | Synthesis of 6b. Rhodamine B (4b) (0.14 g, 0.292 mmol) was dissolved in 1,2-dichloroethane (10 mL), and phosphorus oxychloride (83.9 mL, 0.900 mmol) was added. The mixture was refluxed at 94 °C for 4 hours under an argon atmosphere, then cooled to room temperature. The solvent was removed under reduced pressure to afford the acid chloride. The residue was dissolved in CH3CN (10 mL), and N-methylaniline (65.0 mL, 0.597 mmol) in CH3CN (5 mL) was added dropwise over 10 minutes. The mixture was stirred at room temperature overnight under an argon atmosphere, then refluxed at 93 °C for 1 hour. The reaction mixture was cooled to room temperature and evaporated to dryness. The residue was purified by silica gel chromatography with AcOEt/MeOH/AcOH (79/20/1). The purified product was dissolved in an aqueous solution of saturated sodium hydrogen carbonate, and extracted with CH2Cl2 three times. The organic layer was washed with 2 N HCl aqueous solution twice, and dried over anhydrous Na2SO4. The solution was filtered and evaporated to dryness to afford 6b as a dark green solid (0.099 g, 60 %). | |
With trichlorophosphate In 1,2-dichloro-ethane at 20℃; for 8.08333h; Reflux; | ||
With trichlorophosphate In 1,2-dichloro-ethane at 20℃; Reflux; | ||
With oxalyl dichloride In dichloromethane at 20℃; for 1h; | ||
With trichlorophosphate Reflux; | The rhodamine B-benzenesulfonamides conjugates 3-6 were synthesized as follows: Rhodamine B (1 mmol) 1 was dissolved in phosphorus oxychloride POCl3 (27 mmol). The mixture was refluxed overnight. After cooling at room temperature, the solvent was evaporated under reduced pressure. The obtained rhodamine B acid chloride was dissolved in acetonitrile. (10 mL). Benzenesulfonamide (2.5 mmol) derivatives 2 and triethylamine (3.6 mmol) were added to the solution and stirred at room temperature overnight under N2. The mixture was then concentrated under reduced pressure, water was added to the residue, and the aqueous phase was extracted with methylene chloride (2 x 40 mL). The organic layer was washed twice with water, dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was subjected to column chromatography (silica, CH2Cl2/MeOH, 99:1). | |
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Reflux; | 2.2. Synthesis of 1 To a solution of rhodamine B (1.0 g, 2.3 mmol) in dry 1,2-dichloroethane (8.0 mL), phosphorus oxychloride (1.1 g, 6.9 mmol) was added dropwise at room temperature within 5 min. After being refluxed for 4 h, the reaction mixture was cooled and concentrated under vacuum to give rhodamine B acid chloride. The crude product was used directly in the next reaction without purification. | |
With trichlorophosphate for 24h; Reflux; Inert atmosphere; | ||
0.9 mmol | With thionyl chloride In 1,2-dichloro-ethane for 8h; Reflux; | |
With trichlorophosphate In 1,2-dichloro-ethane for 6h; Reflux; | ||
With trichlorophosphate In dichloromethane for 6h; Reflux; | ||
With trichlorophosphate In 1,2-dichloro-ethane at 25℃; for 3h; | Celecoxib-Rhodamine B Conjugate (28) Phosphorus oxychloride (0.25 mL, 2.68 mmol) was slowly added to a stirred solution of rhodamine B 26 (0.07 g, 0.15 mmol) in 1,2-dichloroethane (10 mL) with stirring at 25 °C, and this mixture was refluxed for 3 h. The reaction mixture was cooled to 25 °C, and the solvent was removed in vacuo to give rhodamine B acid chloride 27 that was used immediately in the next step of this reaction sequence. N-BOC deprotection of compound 24 was carried out using a procedure similar to that used to prepare compound 25. The amino compound obtained after N-BOC deprotection was dissolved in dry DCM (10 mL) and dry TEA (0.08 mL, 0.60 mmol) was added. A solution of unpurified rhodamine B acid chloride 27 described above in dry DCM (10 mL) was added drop wise over 20 min to the amino compound, and the reaction was allowed to proceed for 16 h at 25 °C with stirring. Removal of the solvent in vacuo afforded a viscous residue that was dissolved in chloroform (25 mL), the chloroform solution was washed water (10 mL), the chloroform fraction was dried (Na2SO4), and the solvent was removed in vacuo. The residue obtained was purified by elution from a Combiflash silica gold column using ethyl acetate-isopropyl alcohol (10:1, v/v) as eluent to give the product that was recrystallized from methanol to give the title compound 28 in 33 % yield as a pale pink solid; mp 198-200 °C; 1H NMR (600 MHz, CDCl3): δ 1.24-1.33 (m, 12H, four CH2CH3), 2.34 (s, 3H, CH3), 3.12 and 3.42 (two t, J = 5.1 Hz, 2H each, SO2NHCH2CH2N), 3.60 (q, J = 7.2 Hz, 8H total, four CH2CH3), 6.74-6.83 (m, 5H total, 4H of rhodamine B and pyrazole H-4), 7.09-7.29 (m, 8H, ArHs), 7.42-7.44 (m, 2H, ArHs), 7.55-7.73 (m, 2H, ArHs), 7.85 (d, J = 8.4 Hz, 2H, ArHs), 8.23 (br s, 1H, NH); 13C NMR (150 MHz, CDCl3): δ 12.51 (four CH2CH3), 21.25 (CH3), 40.23 and 41.93 (SO2NHCH2CH2N), 46.06 (four CH2CH3), 60.36 (rhodamine B C•), 96.05 and 96.33 (rhodamine B ArCH), 105.94 (two rhodamine B ArCH), 106.61 (pyrazole C-4), 119.39 (q, 1JC,F = 267 Hz, CF3), 123.72 (phenylsulfonyl C-3, C-5), 125.58 (phenylsulfonyl C-2, C-6), 125.70 and 125.85 (rhodamine B ArC•), 127.50 (rhodamine B ArCH), 128.14 (4-methylphenyl C-2, C-6), 128.57, 128.59 and 129.30 (rhodamine B ArCH), 129.51 (4-methylphenyl C-3, C-5), 129.70 and 131.22 (rhodamine B ArCH), 133.50 (4-methylphenyl C-1), 135.20 (rhodamine B ArC•), 139.60 and 139.73 (4-methylphenyl C-4 and phenylsulfonyl C-4), 140.07 (rhodamine B ArC•), 141.90 (rhodamine B two ArC•), 143.40 (sulfonylphenyl C-1), 143.43 (q, 2JC,F = 36 Hz, pyrazole C-3), 145.21 (pyrazole C-5), 157.73 and 157. 81 (rhodamine B ArC•), 160.50 (CO) ppm; IR (film) ṽ: 3310, 2985, 1686, 1349, 1159 cm-1; fluorescence (1% DMSO in PBS buffer); lex = 554 nm, lem = 580 nm; ESI-MS: 849 [M-H]-; Anal. calcd for C47H47F3N6O4S : C 66.49, H 5.58, S 3.78, N 9.90, found: C 66.40, H 5.50, S 3.85, N 9.82. | |
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Reflux; | ||
With trichlorophosphate for 24h; Reflux; | ||
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 3h; | 4.1.16 N-(9-(2-((3-Azidopropoxy)carbonyl)phenyl)-6-(diethylamino)-3H-xanthen-3-ylidene)-N-ethylethanaminium (16) To a solution of rhodamine B (4.79 g, 10 mmol) in CH2Cl2 (30 mL) with a trace of DMF (0.5 mL) was added oxalyl chloride (0.86 mL, 20 mmol), and the resulting mixture was stirred at rt for 3 h the reaction mixture was concentrated in vacuo and further dried azeotropically with benzene. The residue was dissolved in anhydrous CH2Cl2 (30 mL) under nitrogen and to the solution were added 6-azidohexan-1-ol (2.86 g, 20 mmol) and TEA (4.18 mL, 30 mmol). The resulting mixture was stirred at rt for 2 h and then evaporated under vacuo to give a yellow oil. The oil was purified by flash chromatography to give 16 (3.58 g, 68%) as red oil. | |
With oxalyl dichloride; N,N-dimethyl-formamide at 20℃; for 0.833333h; | Synthesis of RB-PE-1 General procedure: To the solution of rhodamine B (3.5 g) in anhydrous dichloromethane (30 ml) was added oxalyl chloride (2.5 ml) and a drop of dimethylformamide (DMF). The solution was stirred at room temperature for 50 min and then evaporated in vacuo. The residue was dissolved in anhydrous dichloromethane (30 ml) containing 3-butyn-2-ol (1 g). Then triethylamine (4 ml) was added dropwise to the solution. The reaction mixture was stirred at room temperature for 30 min and then concentrated. The residue was purified by silica gel column chromatography using ethyl acetate/triethylamine (19:1v/v) as the eluent to give the desired product in 70 % yield (2.1 g). | |
With trichlorophosphate In 1,2-dichloro-ethane for 8h; Reflux; | ||
With trichlorophosphate Reflux; | ||
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Reflux; | ||
With thionyl chloride In dichloromethane for 4h; Reflux; | Probe 1: A solution of rhodamine B (288.13mg, 0.6mmol) in dichloromethane (12mL) was stirred, and thionyl chloride (0.187mL, 2.5mmol) was added dropwise over 5 min. The solution was heated under reflux for 4 h. The reaction mixture was cooled and evaporated in vacuum to give rhodamine B acid chloride. A solution of 2,2′-thiobis(ethylamine) (36.06 mg, 0.3 mmol) in acetonitrile (10 mL) was added dropwise to a solution of the crude rhodamine B acid chloride (0.6mmol) dissolved in acetonitrile (30 mL) over 1h in an ice bath. After the addition was completed, the reaction mixture was stirred at room temperature overnight. Solvent was removed under reduced pressure, and the residue was washed with water (20mL×4). Then the resulting purple solid was dried and purified by silica gel column chromatography (CH2Cl2: CH3OH=10: 1, v/v). The first pink band was collected and dried to give the 185.43mg of 1 (yield: 64%). | |
With trichlorophosphate In 1,2-dichloro-ethane for 5h; Reflux; | ||
With trichlorophosphate In 1,2-dichloro-ethane for 1h; Reflux; | ||
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Reflux; | ||
With thionyl chloride In 1,2-dichloro-ethane at 0℃; for 8h; Reflux; | ||
With trichlorophosphate at 110℃; for 4h; | ||
With trichlorophosphate In 1,2-dichloro-ethane at 20℃; for 2h; Reflux; | ||
With trichlorophosphate In 1,2-dichloro-ethane at 0℃; for 4h; Reflux; | ||
With pyridine; thionyl chloride In benzene at 20℃; for 12h; | ||
With trichlorophosphate In 1,2-dichloro-ethane for 8h; Reflux; | 4.2. Synthesis and characterization Through similar procedures as published in the literature, fourcompounds AeD was synthesized and showed the same meltingpoint as in the literature.38 Synthesis of compounds LI-L4,39 inbrief, to a stirred solution of rhodamine hydrochloride (1.0 g,2 mmol) and 2-dichloroethane (5 mL), phosphorus oxychloride(1 mL) was added. The solution was refluxed for 8 h and concentratedby evaporation. The obtained crude acid chloride was dissolvedin 10 mL acetonitrile. Then, a solution of the thiadiazolederivatives (4 mmol) and triethylamine (1 mL) in acetonitrile(10 mL) was added dropwise in 30 min and refluxed for 24 h. Aftercooling to room temperature, the resulting solution was pouredinto 50 mL cold water, and extracted with methylene chloride. Theorganic layer was washed with aqueous NaOH solution and driedover anhydrous MgSO4. Then the solvent was removed under reducedpressure and the residue was purified by silica gel column chromatography with DCM/PE (1:1, v/v) as eluent to give L1-L4. | |
With trichlorophosphate In 1,2-dichloro-ethane at 20℃; for 8h; Reflux; | ||
With trichlorophosphate Reflux; | ||
With trichlorophosphate In 1,2-dichloro-ethane for 8h; Reflux; | Compound 2 was synthesized in two consecutive steps. To asolution of Rhodamine B base (2.21 g, 5.00 mmol) in 1,2-dichloroethane (25 mL) was added POCl3 (1.5 mL) dropwiseover 15 min. The reaction mixture was refluxed for 8 h. At theend of this time, the reaction mixture was cooled to roomtemperature and the solvent was evaporated under reducedpressure to give crude rhodamine B acid chloride. The cruderhodamine B acid chloride and triethylamine (3.5 mL) wasdissolved in dry THF (50 mL). A solution of propargyl amine(0.33 g, 6.00 mmol) in dry THF (10 mL) was added dropwiseto the above solution over 1 h at 0 °C. The reaction mixturewas then stirred at room temperature for 24 h. At the end ofthis time, the insoluble salts were filtered and the solvent wasevaporated under reduced pressure. The dark-red crude productwas purified by silica-gel column chromatography withEtOAc: Hexane (2:8) solvent mixture to give the 2.07 g ofwhite crystaline solid (yield 87 %). | |
105 mg | With thionyl chloride In N,N-dimethyl-formamide for 3h; Inert atmosphere; Reflux; | |
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Reflux; | ||
With trichlorophosphate In 1,2-dichloro-ethane for 8h; Reflux; | Synthesis of DW1: To a stirred solution of rhodamine hydrochloride (0.48g, 1mmol) and 2-dichloroethane (5mL), and phosphorus oxychloride (1 mL) was added. The solution was heated under reflux for 8h and concentrated by evaporation. The obtained crude acid chloride was dissolved in acetonitrile (5mL). Then, a solution of 9,9-dimethyl-9H-fluoren-2-amine (0.209g, 1mmol) and triethylamine (1mL) in acetonitrile (5mL) was added dropwise in 15min. After refluxing for 8h, the solvent was removed under reduced pressure to give a violet oil. The mixture of water and dichloromethane (1:1, v/v) was then added to the mixture, and the aqueous phase was extracted with dichloromethane (5mL×3). The organic layer was washed with water, dried over anhydrous MgSO4, and filtered. Purification of the products was by column chromatography on silica gel (eluant: CH2Cl2:CH3OH=60:1) to give 0.48g white powder with a yield of 75.8%. | |
With trichlorophosphate In 1,2-dichloro-ethane at 80℃; for 3h; Reflux; | Synthesis of1 To a solution of rhodamine B (1.0 g, 2.3 mmol) in dry 1,2-dichloroethane (12 ml) was added phosphorus oxychloride (0.6 ml) dropwise over 5 min. The solution was stirred for 3 h at 80 C under reflux conditions. After cooling, the mixture was evaporated in vacuo to give rhodamine B acid chloride as dark oil, which was used for the next step without further purification. | |
With oxalyl dichloride In dichloromethane at 20℃; for 2h; Inert atmosphere; | ||
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Reflux; | ||
105 mg | With thionyl chloride In N,N-dimethyl-formamide for 3h; Reflux; Inert atmosphere; | |
With trichlorophosphate In 1,2-dichloro-ethane at 0 - 90℃; for 3h; | ||
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Reflux; | Synthesis of compound R1 Rhodamine B (1.59 g, 3 mmol) was dissolved in dry 1,2-dichloroethane(15 mL), followed by addition of phosphorus oxychloride (5 mL). After being heated to reflux for 4 h, the solvent and excess amount of phosphorusoxychloride was removed by evaporation to give the corresponding acid chloride,which was dissolved in acetonitrile without further purification. Then a solution of 2(0.474 g, 3 mmol), triethylamine (2 mL) in acetonitrile (20 mL) was added.After refluxing for 12h, the solvent was removed under reduced pressure to givea violent-oil. Water was then added to the mixture and the aqueous was extracted with dichloromethane (30 mL ). The organic layer was dried over anhydrous MgSO4 and filtered. The crude product was purified bysilica gel column chromatography to give R1(white solid) in 71.2% yield. | |
With trichlorophosphate In 1,2-dichloro-ethane for 4h; Reflux; | Synthesis of compounds R2 General procedure: Rh-B (1.59g, 3 mmol) wasdissolved in 20 mL 2-dichloroethane, and then phosphorus oxychloride (2 mL) was added in. The solution was refluxed for 4 h and concentrated by evaporation.The obtained crude acid chloride 1 was dissolved in 10 mL acetonitrile. Then, asolution of 6-chloropyridazin-3-amine (0.4g,3mmol) and triethylamine (2 mL) in acetonitrile (10 mL) was added dropwise in30 min and refluxed for 24 h. After cooling to room temperature, the resulting solution was poured into 50 mL saturated brine, and extracted with methylenechloride. The organic layer was dried over anhydrous MgSO4. Then the solvent was removed under reduced pressure and the residue was purified bysilica gel column chromatography with PE/ DCM/ EA (4:1:1, v/v) as eluent togive R2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.3% | In ethanol for 36h; Reflux; | 1 The specific preparation method of the probe is as follows: Tris (2-aminoethyl) amine (4.0 g, 27.36 mmol), Rhodamine B (1.638 g, 3.42 mmol), 60 ml of absolute ethanol, The mixture was refluxed for 36 h under reduced pressure. The ethanol was distilled off under reduced pressure and extracted with CH 2 Cl 2 (3 × 100 ml). The organic phase was dried overnight over anhydrous magnesium sulfate. The solvent was evaporated to give a red viscous product. The residue was chromatographed on silica gel. Methanol / trichloromethane / triethylamine in a volume ratio of 9/1/1 gave 1.71 g of a colorless, viscous intermediate in a yield of 87.3%. |
87.3% | In ethanol for 24h; Reflux; Inert atmosphere; | |
87.3% | In ethanol for 24h; Reflux; Inert atmosphere; |
85% | In methanol for 4h; Heating; | |
85% | In methanol at 80℃; | |
85% | In ethanol for 24h; Reflux; | 2.1.1.1 Synthesis of N-(rhodamine B)lactam-ethylenediamine (1 and 2) General procedure: Rhodamine B (0.20g, 0.42mmol) was dissolved in 30mL of ethanol, and diethylenetriamine or tris(2-aminoethyl)amine (0.22mL, excess) were added dropwise to the solution and refluxed overnight (24h) until the solution lost its red color. The solvent was removed by evaporation. Water (20mL) was added to the residue and the solution was extracted with CH2Cl2 (20mL×2). The combined organic phase was washed twice with water and dried over anhydrous Na2SO4. The solvent was removed by evaporation, and the product was dried in vacuo, affording pale-yellow solids of 1 and 2. |
85% | at 80℃; Inert atmosphere; | |
82% | In methanol for 4h; Reflux; | |
79% | In methanol for 4h; Heating; | |
78.5% | In methanol at 80℃; | Synthesis of spirolactam rhodamine (RHB-NH2) (compound 1) The spirolactam Rhodamine B derivative (compound 1) was synthesized as follows[24]. 3.13 mmol rhodamine B was dissolved in 30 mL anhydrous methanol,followed by adding 4.8 mmol tris (2-amino ethyl) amine. Then, the mixture washeated to 80 C. After cooling down to the room temperature, the methanol solutionwas removed by rotary evaporation. The organic layer was washed several times,dried with anhydrous magnesium sulfate and purified by column chromatography onsilica gel (CH2Cl2/MeOH/Et3N = 40:2:1) to give a grayish white powder with ayield of 78.5 %. The synthesis process was shown in Scheme S1. The product wascharacterized by NMR and MS shown in Figure S1-S2. 1H NMR (CDCl3,400 MHz) d:7.90 - 7.87 (m, 1H), 7.47 - 7.39 (m, 2H), 7.12 - 7.08 (m, 1H),6.42 - 6.35 (m, 4H), 6.29 - 6.26 (m, 2H), 3.37 - 3.30 (m, 8H), 3.18 - 3.14 (m,2H), 2.58 - 2.53 (t, 4H), 2.37 - 2.35 (t, 4H), 2.25 - 2.21 (t, 2H), 2.14 - 2.08 (t,4H), 1.19 - 1.15 (t, 12H). ESI m/z [M?H?] = 571.6. |
77% | In methanol at 84.84℃; | |
In methanol at 79.84℃; Inert atmosphere; | ||
In ethanol Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.6% | In methanol for 13h; Reflux; | |
91% | In ethanol at 80℃; Inert atmosphere; | |
91% | In ethanol for 24h; Reflux; | 2.1.1.1 Synthesis of N-(rhodamine B)lactam-ethylenediamine (1 and 2) General procedure: Rhodamine B (0.20g, 0.42mmol) was dissolved in 30mL of ethanol, and diethylenetriamine or tris(2-aminoethyl)amine (0.22mL, excess) were added dropwise to the solution and refluxed overnight (24h) until the solution lost its red color. The solvent was removed by evaporation. Water (20mL) was added to the residue and the solution was extracted with CH2Cl2 (20mL×2). The combined organic phase was washed twice with water and dried over anhydrous Na2SO4. The solvent was removed by evaporation, and the product was dried in vacuo, affording pale-yellow solids of 1 and 2. (0007) 1: (0.20g, yield 91%). 1H NMR (400MHz, CDCl3) δ 7.90 - 7.88 (m, 1H, ArH), 7.44 - 7.42 (m, 2H, ArH), 7.09 - 7.07 (m, 1H, ArH), 6.43 (s, 1H, ArH), 6.41 (s, 1H, ArH) 6.37 (s, 2H, ArH), 6.28 - 6.25 (m, 2H, ArH), 3.32 (q, J=6.8Hz, 8H, NCH2CH3), 3.26 (t, J=6.8Hz, 2H, NCH2CH2), 2.59 (t, J=6.0Hz, 2H, NCH2CH2NH), 2.44 -2.38 (m, 4H, NCH2CH2NH), 1.70 (s, 3H, NCH2CH2NH and CH2CH2NH2) and 1.16 (t, J=7.2Hz, 12H, NCH2CH3). MS (MALDI-TOF); Calcd for [C32H41N5O2]+: m/z 527.33. Found: m/z 528.95 [M+H]+. |
91% | at 80℃; Inert atmosphere; | |
86% | In ethanol at 90℃; for 32h; | 2.1 (1) 1.0 mmol of Rhodamine B (0.48 g) was added to a 100 mL three-necked flask containing 15 mL of absolute ethanol, and stirred to completely dissolve.Then 1 g of diethylenetriamine (10.0 mmol) was added dropwise.Stirring at 90 ° C for 32 h,The color of the solution is lightened, the reaction is terminated, and after cooling to room temperature, the solvent is removed by steaming.Then add water and dichloromethane to extract and wash 3 times (shared 20 mL of water and 30 mL of dichloromethane).The organic phase after extraction and washing was collected 3 times, and the solvent was removed by rotary evaporation. The mixture was mixed with dichloromethane and ethanol at a volume ratio of 6:0.2 to 6:0.8 (gradient elution, adjusting the volume ratio according to the TLC dot plate). Separated and purified by column chromatography,Obtaining an amino group-containing rhodamine B derivative intermediate RhB-NH2 in a yield of 86%,Pink powder, |
83% | In methanol Heating; | |
83% | In methanol at 80℃; | |
79% | In methanol at 40 - 70℃; for 10h; Inert atmosphere; | |
64.3% | In ethanol for 12h; Reflux; | Synthesis of Compound 2: Rhodamine B (0.988 g, 2.1 mmol) and diethylenetriamine (2 mL, 18.6 mmol) were dissolved in ethanol (20 mL). The reaction mixture was stirred and refluxed for 12 h. The crude product was purified by silica gel column chromatography using CH2Cl2/C2H5OH (10/1, v/v) as eluent to afford a pink solid product. Yield: 0.753 g (64.3%). |
64% | In ethanol at 70℃; for 24h; | |
46.8% | In ethanol at 84℃; for 20h; | 1 Synthesis of Rhodamine Derivatives Into a 100 mL three-necked flask, 4.8 g (10 mmol) of rhodamine B and 40 mL of ethanol were added, and after stirring at room temperature for half an hour, 10 mL of diethylenetriamine was added, and the mixture was refluxed at 84° C. for 20 hours.After the reaction was stopped, the insolubles were filtered off, the filtrate was concentrated under reduced pressure, 30 mL of deionized water was added, and extracted twice with 50 mL of dichloromethane.The organic phases were combined, washed twice with 20 mL of saturated sodium chloride solution, and dried by adding an appropriate amount of anhydrous sodium sulfate for 8 hours.The obtained solution was concentrated under reduced pressure, recrystallized with a volume ratio of dichloromethane:methanol=20:1, and the product was vacuum-dried at 60° C. for 6 hours, with a yield of 46.8%. The synthetic route of rhodamine derivatives is shown below: |
6.4% | In ethanol for 24h; Reflux; | 1 Synthesis of Compound 1: Rhodamine B (2.0 g, 4.18 mmol) was added to a 100 mL round bottom flask containing 50 mL of ethanol,After completely dissolving the solution appears purple,Stir under the dropDiethylenetriamine(10.0 mL, 92.00 mmol) was added to the above reaction system and refluxed for 24 h.The solvent was removed by distillation under reduced pressure. The crude product was chromatographed on a 10: 1 (v / v) eluting with dichloromethane / ethanol as a yellow solid (Compound 1) (0.15 g, yield: 6.40%). |
In ethanol for 24h; Reflux; | 1.2 2, rhodamine B (2 g, 4.16 mmol)Placed in a three-necked flask,100 ml of ethanol was added and heated to reflux,After Rhodamine is completely dissolved,Dimethylenetriamine (0.646 g, 6.26 mmol) was slowly added dropwise,Heating to reflux reaction for 24h; to be finished to the end of the reaction to the room temperature, to the reaction by adding step 1 prepared by the intermediate 1, room temperature stirring reaction 15h; reaction is completed by adding 50mL of dichloromethane reaction solution dissolved And extracted three times with 30 mL of water to give an organic phase which was obtained by column chromatography 200-300 mesh silica gel (eluent ethyl acetate: methanol = 10: 1, ν / ν) to give the desired productRN3 0.6 g, 25% yield. | |
In ethanol at 70℃; for 24h; Inert atmosphere; | ||
In methanol at 65℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In ethanol for 16h; Reflux; | |
95% | In ethanol for 12h; Reflux; | |
95% | In ethanol for 12h; Reflux; Inert atmosphere; Schlenk technique; | 2.2 Synthesis of 2-(2-aminoethyl)-30,60-bis(diethylamino)spiro-[isoindoline-1,90- xanthen]-3-one (6) Ethane-1, 2-diamine (4.46mL, 10 equiv.) was added to a solution of rhodamine B (3.2g, 6.68mmol) in ethanol (80mL). The mixture was refluxed for 12h and then evaporated to dryness under a vacuum. The crude solid was dissolved in CH2Cl2 and then washed with H2O and brine. The organic layer was dried with MgSO4. After removal of the solvent, flash chromatography (silica gel; MeOH/CH2Cl2, 3:97 v/v) of the residue yielded 6 as a pink solid (3.1g, 95%). Mp. 217-219°C. IR(KBr, cm-1): υNH, 3417.5; υasCH, 2907.1, 2927.6; υC=O, 1685.6; υC=C, 1616.2, 1513.9; υC-N, 1394.4; υasC-O-C, 1222.7, 1118.6. 1H NMR (CDCl3): δ 8.12-7.78 (m, 1H), 7.64-7.34 (m, 2H), 7.19-6.96 (m, 1H), 6.43 (d, 2H, J=8.9Hz), 6.37 (d, J=2.5Hz, 2H), 6.27 (dd, J1=2.6, J2=2.5Hz, 2H), 3.66-3.24 (m, 8H), 3.28-2.91 (m, 2H), 2.41 (t, J1=6.7Hz, J2=6.6Hz, 2H), 1.40 (s, 2H), 1.16 (t, J1=7.0Hz, J2=7.1Hz, 12H) ppm. 13C NMR (CDCl3): δ 168.59, 153.43, 153.26, 148.79, 132.37, 131.20, 128.64, 128.01, 123.79, 122.70, 108.13, 105.64, 97.71, 77.38, 77.13, 76.88, 64.91, 44.31, 43.80, 40.73, 12.56ppm. |
95% | In ethanol at 80℃; for 12h; | 1.2 2. Synthesis of Compound 5 A mixture of rhodamine B (800 mg, 1.67 mmol) and ethylenediamine (1.12 mL, 16.70 mmol) in absolute ethanol (20 mL), the reaction temperature was controlled at 80 ° C, reaction time was 12 h, after completion of the reaction, the solvent was removed under reduced pressure, extraction, column chromatography on silica gel yielded a yellowish solid (768 mg, 95%). Compound 51H NMR and 13C NMR are shown in Fig. 3 and Fig. 4, respectively. |
95% | In ethanol for 12h; Reflux; Inert atmosphere; Schlenk technique; | Synthesis of 2-(2-aminoethyl)-3',6'-bis(diethylamino)spiro[isoindoline-1,9'-xanthen]-3-one (compound 1) To a solution of rhodamine B (3.2 g, 6.68 mmol) in ethanol (80 mL) was added ethane-1, 2-diamine (4.46 mL, 10 equiv). The mixture was refluxed for 12 h and then taken to dryness under vacuum. The crude solid was dissolved in CH2Cl2 and then washed with H2O and brine. The organic layer was dried with MgSO4. After the removal of the solvent, flash chromatography (silica gel; MeOH/CH2Cl2, 3:97; v/v) of the residue yielded 2 as a pink solid (3.1 g, 95%). 1H NMR (500 MHz, CDCl3): δ 8.12-7.78 (m, 1H), 7.64-7.34 (m, 2H), 7.19-6.96 (m, 1H), 6.43 (d, 2H, J = 8.9 Hz), 6.37 (d, J = 2.5 Hz, 2H), 6.27 (dd, J1 = 2.6, J2 = 2.5 Hz, 2H), 3.66-3.24 (m, 8H), 3.28-2.91 (m, 2H), 2.41 (t, J1 = 6.7 Hz, J2 = 6.6 Hz, 2H), 1.40 (s, 2H), 1.16 (t, J1 = 7.0 Hz, J2 = 7.1 Hz, 12H) ppm. 13C NMR (125 MHz, CDCl3): δ 168.59, 153.43, 153.26, 148.79, 132.37, 131.20, 128.64, 128.01, 123.79, 122.70, 108.13, 105.64, 97.71, 77.38, 77.13, 76.88, 64.91, 44.31, 43.80, 40.73, 12.56 ppm. |
93% | In ethanol for 7h; Reflux; | |
93% | In ethanol for 7h; Reflux; | |
93% | In methanol for 24h; Reflux; | |
92% | In ethanol at 40 - 85℃; for 24h; | |
92% | In ethanol at 80℃; for 12h; | 1.1 1. Synthesis of Compound 1 Rhodamine B (960 mg, 2 mmol)With ethylenediamine (1.3 ml, 20 mmol) in absolute ethanol (40 ml),The reaction temperature was controlled at 80 °C and the reaction time was 12 h. After completion of the reaction, the solvent was removed under reduced pressure, extracted and separated on a silica gel column to give a pale yellow solid (880 mg, 92%). Compound 11H NMR, 13C NMR are shown in Figure 1 and Figure 2, respectively. |
92% | In ethanol at 80℃; for 12h; | 1.1 1. Synthesis of Compound 1 Rhodamine B (960 mg, 2 mmol) was added to a 100 mL round bottom flask, and 40 mL of absolute ethanol was added, followed by dropwise addition of ethylenediamine (1.3 mL, 20 mmol) to the above solution. After the completion of the dropwise addition, the reaction temperature was raised to 80 ° C, and the reaction was refluxed for 12 hours. After the reaction was completed, the ethanol was concentrated by spin. It was then extracted three times with CH2Cl2/saturated brine at room temperature and back-extracted once. The organic phase was dried over anhydrous magnesium sulfate, filtered, and evaporated and evaporated,Isolated by silica gel column to give a pale yellow solid (880mg, 92%).Compound 1H NMR, 13C NMR are shown in Figure 1, Figure 2, respectively. |
92% | In ethanol at 80℃; for 12h; | 1.1 1. Synthesis of Compound 1 Rhodamine B (960 mg, 2 mmol) was added to a 100 mL round bottom flask, and 40 mL of absolute ethanol was added, followed by dropwise addition of ethylenediamine (1.3 mL, 20 mmol) to the above solution.After the completion of the dropwise addition, the reaction temperature was raised to 80 ° C, and the reaction was refluxed for 12 hours. After the reaction is completed,The ethanol was removed by rotary concentration. Then, it was extracted three times with CH 2 Cl 2 /saturated brine at room temperature.Back extraction once. After drying the organic phase with anhydrous magnesium sulfate,Filtration, distillation under reduced pressure, extraction,Separated by silica gel column to give a pale yellow solid(880 mg, 92%). |
92% | In ethanol at 80℃; for 12h; | 1.1 1. Synthesis of Compound 1 Rhodamine B (960 mg, 2 mmol) was added to a 100 mL round bottom flask, and 40 mL of absolute ethanol was added, followed by dropwise addition of ethylenediamine (1.3 mL, 20 mmol) to the above solution. After the completion of the dropwise addition, the reaction temperature was raised to 80 ° C, and the reaction was refluxed for 12 hours. After the reaction was completed, the ethanol was concentrated by spin. Then extracted three times with CH2Cl2/saturated brine at room temperature, reversedExtract once. The organic phase was dried over anhydrous magnesium sulfate, filtered, and then evaporated.Extraction, separation by silica gel column to give a pale yellow solid(880 mg, 92%).Compound 1 1H NMR is shown in Figure 1. |
92% | In ethanol for 12h; Inert atmosphere; Schlenk technique; Reflux; | Synthesis of Compound 1 Ethylenediamine (1.3mL, 20mmol) was added to a solution of rhodamine B (960mg, 2 mmol) in ethanol (20 mL).The mixture was refluxed for 12h and then evaporated to dryness under a vacuum. The residue was dissolved in CH2Cl2 and then washed with H2O and brine. The organic layer was dried with MgSO4. After removal of the solvent, flash chromatography (silica gel; MeOH/CH2Cl2= 3/97, v/v) of the residue yielded 1 as a pink solid (880mg, 92%).1H NMR(CDCl3), δ7.90 (dd, J=5.5, 3.3Hz, 1H), 7.44 (dd, J=5.7, 3.0Hz, 2H), 7.10-7.07 (m, 1H), 6.44 (s, 1H), 6.42 (s, 1H), 6.37(d, J=2.5Hz, 2H), 6.27 (dd, J=8.9, 2.6Hz, 2H), 3.38-3.27 (m, 8H), 3.19 (t, J1=6.65Hz, J2=6.6Hz, 2H), 2.41 (t, J1=6.65Hz, J2=6.6Hz, 2H), 1.38-1.25 (m, 2H), 1.16 (t, J1=7.1Hz, J2=7.0Hz, 12H) ppm. |
92% | In ethanol at 80℃; | 1.1 1. Synthesis of Compound 1 Rhodamine B (960 mg, 2 mmol) and ethylenediamine (1.3 ml, 20 mmol) in dry ethanol (40 ml) were used to control the reaction temperature at 80 ° C, and the reaction time was 12-13 h. After the reaction is completed,The solvent was removed under reduced pressure and extracted.Separated by silica gel column to give a pale yellow solid(880 mg, 92%). |
92% | In ethanol at 80℃; for 12h; | 1.1 1. Synthesis of Compound 1 Rhodamine B (960 mg, 2 mmol) was added to a 100 mL round bottom flask, and 40 mL of absolute ethanol was added, followed by dropwise addition of ethylenediamine (1.3 mL, 20 mmol) to the above solution.After the completion of the dropwise addition, the reaction temperature was raised to 80 ° C, and the reaction was refluxed for 12 hours. After the reaction was completed, the ethanol was concentrated by spin. Then, it was extracted three times with CH 2 Cl 2 /saturated brine at room temperature. Back extraction once. After drying the organic phase over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure, extraction, column separation on silica gel to give a pale yellow solid (880mg, 92%). Compound 1 1H NMR, 13C NMR are shown in Figure 1, Figure 2, respectively. |
90% | In ethanol for 24h; Reflux; | |
90% | In ethanol for 16h; Reflux; Inert atmosphere; | |
88% | In ethanol for 24h; Reflux; | |
87% | In ethanol for 9h; Reflux; | |
86.2% | In ethanol for 12h; Reflux; | 2.2.1 Synthesis of compound 1 To a solution of rhodamine B (300 mg, 0.67 mmol) in EtOH (10 mL) was added ethylenediamine (0.40 mL, 6.7 mmol) over 10 min. The solution was refluxed for 12 h, cooled to room temperature, and the precipitates were filtered and washed with EtOH (3×10 mL). The product was dried in vacuo to give 280 mg of 1 (86.2 %). 1H NMR (400 MHz,CDCl3) δ 7.89 (dt, J=7.5, 3.3 Hz, 1H), 7.48-7.40 (m, 2H),7.12-7.06 (m, 1H), 6.43 (d, J=8.8 Hz, 2H), 6.37 (d, J=2.5 Hz, 2H), 6.28 (d, J=2.6 Hz,1H), 6.26 (d, J=2.6 Hz, 1H),3.33 (q, J=7.1 Hz, 8H), 3.21 (t, J=6.2 Hz, 2H), 2.51 (t, J=6.2 Hz, 2H), 2.44-2.12 (m, 2H), 1.16 (t, J=7.0 Hz, 12H). 13CNMR (101 MHz, CDCl3) δ 168.61, 153.50, 153.29, 148.82,132.38, 131.27, 128.70, 128.03, 123.83, 122.76, 108.16,105.70, 97.73, 64.92, 44.35, 43.91, 40.87. MS (ESI), m/z: Calcd. for C30H37N4O2: 485.2816, found, 485.2921 [M+H]+. |
86.3% | In ethanol at 80℃; for 24h; Inert atmosphere; | To a stirred solution of rhodamine B (0.5 g,1.13 mmol) in ethanol (15 mL), ethylenediamine (0.5 mL, 7.5 mmol) was added and the mixture was refluxed overnight under N2 protection. After cooled to the room temperature, the solvent was removed under reduced pressure and then the residue was dissolved in 20 mL dichloromethane (DCM). The organic solution was washed with water twice, and DCM was removed by evaporation. Earthy yellow solid RE1N2 (0.4703 g, yield 86.3%) was obtained after dried in vacuo. |
86% | With triethylamine In methanol for 24h; Reflux; | |
85% | In methanol at 80℃; for 5h; Inert atmosphere; | Compound 1 Under nitrogen, a solution of rhodamine B (0.5g, 1.0mmol), ethanediamine (90mg, 1.5mmol) and methanol (40mL) was heated at 80°C for 5h. After cooling to room temperature, the solvent was evaporated under reduced pressure. Then, the resulting mixture was dissolved by adding CH2Cl2 (100mL) and water (200mL). After removing the organic layer, the residue was dried over anhydrous Na2SO4 and filtered. The solvent was evaporated under reduced pressure, and the crude product was purified by column chromatography (ethyl acetate:ethanol=1:3) to give 0.43g of saffron yellow 1 in 85% yield. 1H NMR (300MHz, CDCl3) δ 7.91 (dd, J=5.6, 3.0Hz, 1H), 7.45 (dd, J=5.6, 3.1Hz, 2H), 7.10 (dd, J=5.5, 3.0Hz, 1H), 6.43 (d, J=8.8Hz, 2H), 6.37 (d, J=2.4Hz, 2H), 6.27 (dd, J=8.8, 2.5Hz, 2H), 3.33 (q, J=7.1Hz, 8H), 3.19 (t, J=6.6Hz, 2H), 2.39 (t, J=6.6Hz, 2H), 1.16 (t, J=7.0Hz, 12H). |
85% | In ethanol at 80℃; for 7h; | 3 Synthesis of amino-functional rhodamine B Rhodamine B 5.0 g (11.2 mmol) and ethylenediamine 9.0 mL (134.8 mmol) were dissolved in ethanol (50 mL) in a 250 mL flask, then the mixture was heated at 80 °C for 7 h. After ethanol was removed under vacuum, the residue was purified by column chromatography on silica gel (CH2Cl2/MeOH, 10:1) to give 3 as a pale yellow powder 4.7 g, yield: 85%. M.p. 216∼218 °C (the reference value 217∼219 °C), yield: 75%. 1H NMR (CDCl3, ppm): δ 7.89 (m, 1H), 7.42 (m, 2H), 7.07 (m, 1H), 6.40 (dd, 4H, J = 8.9, 2.6 Hz), 6.26 (dd, 2H, J = 8.8, 2.7 Hz), 3.32 (m, 8H), 3.18 (t, 2H, J = 6.6 Hz), 2.40 (t, 2H, J = 6.6 Hz), 1.15 (t, 12H, J = 6.9 Hz). |
85% | In ethanol for 12h; Reflux; | 2.2 Synthesis of Compound 1 To a solution of rhodamine B (3.8g, 7.95mmol) in 100mL of ethanol was added ethane-1,2-diamine (5 mL, 10equiv). The mixture was refluxed for 12h and then taken to dryness under vacuum. The residue was dissolved in CH2Cl2 and then washed with H2O and brine. The organic layer was dried with MgSO4. After the removal of the solvent, flash chromatography (silica gel; MeOH/CH2Cl2, 3:97; v/v) of the residue yielded Compound 1 as a pink solid (3.3g, 85%). 1H NMR (500MHz, CDCl3, 298K, TMS) δ (ppm): 7.90 (dd J1=3.0, J2=3.0Hz, 1H), 7.46-7.43 (m, 2H), 7.09 (dd, J1=3.0, J2=3.0Hz, 1H), 6.43 (d, J=8.8Hz, 2H), 6.37 (d, J=2.5Hz, 2H), 6.27 (dd, J=8.9, 2.6Hz, 2H), 3.38-3.27 (m, 8H), 3.19 (t, J1=6.65Hz, J2=6.6Hz, 2H), 2.41 (t, J1=6.65Hz, J2=6.6Hz, 2H), 1.16 (t, J1=7.0Hz, J2=7.1Hz, 12H) 13C NMR (126MHz, CDCl3, 298K, TMS) δ (ppm): 168.59, 153.43, 153.26, 148.79, 132.37, 131.20, 128.64, 128.01, 123.79, 122.70, 108.13, 105.64, 97.71, 77.38, 77.13, 76.88, 64.91, 44.31, 43.80, 40.73, 12.56. HRMS (M+H)+ found, 485.2925; calcd for C30H36N4O2, 484.2838. |
85% | at 20℃; for 24h; Sealed tube; | |
85% | In ethanol at 80℃; for 12h; Inert atmosphere; Schlenk technique; | 3.1 Synthesis of compound N-(rhodamine B)lactam-1,2-ethylenediamine (1) 2.3.1 Synthesis of compound N-(rhodamine B)lactam-1,2-ethylenediamine (1) A mixture of rhodamine B (4.78 g, 10 mmol) and 1,2-ethylenediamine (3.25 mL, 50 mmol) in 100 mL ethanol was stirred at 80 °C for 12 h, when TLC analysis indicated completion of reaction. After cooling to room temperature, the organic solvent was evaporated under reduced pressure. The residue was dissolved in CH2Cl2 and then washed with H2O and brine. The organic layer was dried with anhydrous magnesium sulfate. After removal of the solvent, the crude product was purified by column chromatography with MeOH-CH2Cl2 (5:95, v/v) to afford the pure product 1 (pink solid, 4.11 mg, 85%). 1H NMR (CDCl3), δ 7.90 (dd, J = 5.6, 3.0 Hz, 1H), 7.61-7.38 (m, 2H), 7.09 (dd, J = 5.6, 2.9 Hz, 1H), 6.43 (d, J = 8.8 Hz, 2H), 6.37 (d, J = 2.5 Hz, 2H), 6.27 (dd, J = 8.9, 2.6 Hz, 2H), 3.38-3.27 (m, 8H), 3.19 (t, J1 = 6.65 Hz, J2 = 6.6 Hz, 2H), 2.41 (t, J1 = 6.65 Hz, J2 = 6.6 Hz, 2H), 1.16 (t, J1 = 7.0 Hz, J2 = 7.1 Hz, 12H) ppm. 13C NMR (CDCl3), δ 168.59, 153.35, 148.79, 132.38, 131.20, 128.64, 128.02, 123.80, 122.71, 108.13, 105.65, 97, 64.91, 44.36, 44.06, 40.73, 12.56 ppm. |
85% | In ethanol for 10h; Reflux; | 9.3 Synthesis of intermediate 13 Rhodamine B (50.0 mg, 0.104 mmol) was dissolved in ethanol (4 mL). Ethylenediamine (0.1 mL, 1.50 mmol) was added and refluxed for 10 h. The solvent was removed by evaporation. 10 mL water was added to the resultant and extracted with CHCl3 (10 mL × 3). The combined organic phase was washed with brine (5 mL × 3), dried with Na2SO4, filtrated and the solvent was removed and dried in vacuo, affording a pink solid of 13 (42.9 mg) in 85% yield. 1H NMR (400 MHz, CDCl3): δ 7.89-7.91 (m, 1H), 7.41-7.45 (m, 2H), 7.07-7.10 (m, 1H), 6.36-6.46 (m, 4H), 6.24-6.29 (m, 2H), 3.30-3.36 (m, 8H), 3.19 (t, 2H, J = 6.6 Hz), 2.42 (t, 2H, J = 6.4 Hz), 1.13-1.18 (m, 12H); 13C NMR (100 MHz, CDCl3): δ 168.54, 153.42, 153.22, 148.75, 132.31, 131.18, 128.62, 127.95, 123.76, 122.68, 108.09, 105.63, 97.67, 64.86, 44.27, 43.80, 40.80, 12.52. |
84% | In ethanol for 24h; Reflux; | |
84% | In ethanol at 80℃; Inert atmosphere; | |
84% | at 80℃; Inert atmosphere; | |
84% | In ethanol for 15h; Reflux; | |
84% | In ethanol for 2h; Reflux; | |
84% | In methanol for 72h; Reflux; Inert atmosphere; | |
84% | In ethanol Reflux; | 1.3 Weigh 2 grams of Rhodamine B and dissolve it in 30 ml of ethanol, then slowly add it dropwise to 1.4 ml of anhydrous ethylene diamine, the mixture was heated to reflux overnight, and the fluorescence of the solution disappeared. After the reaction is completed, cool to room temperature, spin the solution to dryness to obtain the crude product. Then add 1.0M HCl solution to dissolve the crude product, after adding 1.0M NaOH solution, a light pink precipitate precipitated out. The precipitate is filtered and washed with water, after drying the pale pink solid, the rhodamine ethylenediamine compound (Compound 3) was obtained with a yield of 84%. |
84% | In ethanol for 12h; Reflux; | 1 Example 1: Synthesis of Probe RHC First, rhodamine B (0.44 g, 1 mmol) was dissolved in 50 mL of ethanol, heated to reflux until rhodamine B was completely dissolved, and then 500 μL of ethylenediamine was slowly added dropwise to the above solution.After heating under reflux for 12 hours, the reaction solution was cooled to room temperature, and a large amount of solution was spin-dried. A large amount of distilled water was added to the remaining small amount of liquid to produce a large amount of pink precipitate. The treatment can be used directly in the next step with a yield of 84%. |
83% | In ethanol for 12h; Reflux; | 2 Synthesis of 2-(2-aminoethyl)-3',6'-bis(diethylamino)spiro[isoindoline-1,9'-xant hen]-3-one (1) To a solution of Rhodamine B (3.8 g, 7.95 mmol) in 100 mL of ethanol was added ethane-1, 2-diamine (5 mL, 10 equiv). The mixture was refluxed for 12 h and then taken to dryness under vacuum. The residue was dissolved in CH2Cl2 and then washed with H2O and brine. The organic layer was dried with MgSO4. After the removal of the solvent, flash chromatography (silica gel; MeOH/CH2Cl2, 3:97; v/v) of the residue yielded 1 as a pink solid (3.2 g, 83%). 1H NMR(CDCl3), δ 8.12-7.78 (m, 1H), 7.64-7.34 (m, 2H), 7.19-6.96 (m, 1H), 6.43 (d, 2H, J = 8.9 Hz), 6.37 (d, 2H, J = 2.5 Hz), 6.27(dd, 2H, J1 = 2.6, J2 = 2.5 Hz), 3.66-3.24 (m, 8H), 3.28-2.91(m, 2H), 2.41 (t, 2H, J1 = 6.7 Hz, J2 = 6.6 Hz), 1.40 (s, 2H), 1.16 (t, 12H, J1 = 7.0 Hz, J2 = 7.1 Hz) ppm. 13C NMR (CDCl3), δ 168.59, 153.43, 153.26, 148.79, 132.37, 131.20,128.64, 128.01, 123.79, 122.70, 108.13, 105.64, 97.71, 77.38, 77.13, 76.88, 64.91, 44.31, 43.80, 40.73, 12.56 ppm. ESI-MS (M++1) found, 485.13; calcd for C30H37N4O2+, 485.29. |
83% | In ethanol for 12h; Reflux; | 2.2.4 Compound 2 2-(2-aminoethyl)-3′, 6′-bis (diethylamino) spiro [isoindoline- 1,9′- xant-hen]-3-one A solution of Rhodamine B (2 g, 4.499mmol) in ethyl alcohol (30mL) was heated for 20min, then ethanediamine (3.0mL, 44.98mmol), the mixture was refluxed for 12h. The mixture was evaporated in reduced pressure, the distilled water was added to the residue, and the mixture was extracted with dichloromethane (50mL×3), then the organic phase was combined, washed with saturated brine, and dried with Na2SO4, then filtered, Removal of the solvents under reduced pressure gave a crude product, which was purified by silica gel chromatography (eluent: MeOH:DCM 1:50) to produce a light yellow powder (1.81g, 83%).1H NMR (CDCl3, 400MHz) δ 7.97 - 7.87 (m, 1H), 7.51 - 7.44 (m, 2H), 7.16 - 7.07 (m, 1H), 6.45 (d, J=8.8Hz, 2H), 6.39 (d, J=2.6Hz, 2H), 6.29 (dd, J=8.9, 2.6Hz, 2H), 3.35 (q, J=7.1Hz, 8H), 3.21 (t, J=6.6Hz, 2H), 2.45 (t, J=6.6Hz, 2H), 1.65 (s, 2H), 1.18 (t, J=7.0Hz, 12H). ESI-MS: calcd. for [M+H]+ 485.28; found, 485.3. |
83% | Stage #1: rhodamine B In ethanol for 0.333333h; Heating; Stage #2: ethylenediamine In ethanol at 80℃; for 12h; | 2.3.1 Synthesis of compound 1 Rhodamine B (2g, 4.499mmol) was added into 30mL of anhydrous ethanol and was heated for 20min, and ethanediamine (3.0mL, 44.98mmol) was added. The mixture was stirred at 80°C for 12h. After the complete consumption of the starting material monitored using TLC, the mixture was cooled to room temperature. Then the mixture was evaporated in reduced pressure, and the residue was dissolved in distilled water. Next the mixture was extracted with dichloromethane three times, and the organic phase was washed with saturated saline, and dried with anhydrous sodium sulfate. After filtered, the solvent was removed under reduced pressure and crude product was obtained. The crude product was purified by silica gel chromatography using MeOH/DCM (v/v, 1/50) to produce compound 1 as light yellow powder (1.81g, yield 83%). 1H NMR (CDCl3, 400MHz) δ 7.97-7.87 (m, 1H), 7.51-7.44 (m, 2H), 7.16-7.07 (m, 1H), 6.45 (d, J=8.8Hz, 2H), 6.39 (d, J=2.6Hz, 2H), 6.29 (dd, J=8.9, 2.6Hz, 2H), 3.35 (q, J=7.1Hz, 8H), 3.21 (t, J=6.6Hz, 2H), 2.45 (t, J=6.6Hz, 2H), 1.65 (s, 2H), 1.18 (t, J=7.0Hz, 12H). ESI-MS: calcd. for [M+H]+ 485.28; found, 485.3. |
80% | In ethanol Reflux; | |
80% | In ethanol for 12h; Reflux; | |
80% | In ethanol for 24h; Reflux; | Synthesis of compound I Compound I was synthesized according to the reported method.25,26 Rhodamine B (1.2 g, 2.5 mmol) was dissolved in ethanol (50 mL) and ethylenediamine (3.4 mL) was added dropwise with vigorous stirring. The reaction mixturewas refluxed for 24 h. The solvent was removed unde rreduced pressure, then water (100 mL) was added. The mixture was extracted with CH2Cl2 (3×100 mL) and the combined organic layer was dried over Na2SO4 and evaporated.The residue was dissolved in hydrochloric acid(1 mol/L, 100 mL), then sodium hydroxide solution(1 mol/L) was added until a pink solid formed. Pure compoundI (0.97 g) was obtained following filtration, water and then drying. 2-(2-Aminoethyl)-3’,6’-bis(diethylamino)spiro[isoindoline-1,9’-xanthen]-3-one (I). Pink solid, yield 80%, m.p. 213-214 °C (lit. m.p. 217-219 °C)25; 1H NMR(400 MHz, CDCl3): δ = 7.85-7.81 (m, 1H, ArH), 7.39-7.35(m, 2H, ArH), 7.03-7.01 (m, 1H, ArH), 6.36 (d, J = 8.8 Hz,2H, ArH), 6.30 (d, J = 2.4 Hz, 2H, ArH), 6.19 (dd, J = 2.4Hz, 8.8 Hz, 2H, ArH), 3.26 (q, J = 7.2 Hz, 8H, NCH2), 3.13(t, J = 6.8 Hz, 2H, NCH2), 2.37 (t, J = 6.8 Hz, 2H, NH2CH2),1.08 (t, J = 7.0 Hz, 12H, CH3); ESI-MS: m/z calcd forC30H36N4O2 [M+H]+: 485.29; found: 485.29. |
79% | In ethanol for 15h; Heating; | |
79% | In ethanol Reflux; | |
79% | In ethanol for 15h; Reflux; | 1.1 Step 1: Rhodamine B (4.8 g, 10 mmol) was dissolved in 30 mL of ethanol.Then 5 mL of excess ethylenediamine was added dropwise to the solution.It was then refluxed for 15 h until the color of the solution lost color.Excess solvent is then removed by rotary evaporation.20 mL of distilled water (20 mL × 2, CH 2 Cl 2 ) was added to the product for extraction.The organic layer was washed twice with the same volume of water,Drying was carried out using anhydrous Na 2 SO 4 . Finally the solvent is removed by rotary evaporation.Drying in a vacuum oven,A slightly pink solid rhodamine-ethylenediamine (3.8 g, yield, 79%) was obtained. |
79% | In methanol for 15h; Reflux; | Synthesis of 1 Rhodamine B (2.40 g, 5 mmol) was dissolved in methanol (20 mL). Ethylene diamine (5 mL, excess) was added drop-wise to the solution and refluxed overnight (15 h) until the solution loses its red color. The solvent was removed by evaporation. Water (20 mL) was added to the resultant and extracted with CH2Cl2 (20 mL* 2). The combined organic phase was washed twice with water and dried over Na2SO4. The solvent was removed by evaporation and dried in vacuum, affording a pale-pink solid of 1 (3.80 g,yield, 79%). |
78% | In methanol at 80℃; for 20h; | |
75% | In ethanol at 90℃; for 8h; | RD was synthesised by two procedures (Scheme S1). The first step, RB (2.51g, 5.2mmol) was dissolved in ethanol (50mL), then 5mL ethylenediamine was added in dropwise to the flask and the reaction mixture was stirred at 90°C for 8h. After the solution was cooled to room temperature, the solution was concentrated under reduced pressure and the residue was purified by column chromatography (DCM: MeOH=10: 1, v/v) to afford a light yellow solid R2 in 75% yield. 1H NMR (400MHz, CDCl3), δ 7.89 (m, 1H), 7.60-7.33 (m, 2H), 7.18-7.00 (m, 1H), 6.58-6.12 (m, 6H), 3.50-3.23 (m, 8H), 3.23 (t, J=6.6Hz, 2H), 2.45 (t, J=6.6Hz, 2H), 1.17 (t, J=7.0Hz, 12H). MS: (M+H)+, calcd: m/z=485.29, found: m/z=485.27. |
73.6% | In ethanol for 24h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.16% | Stage #1: rhodamine B With pyridine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at -20℃; Stage #2: tetraethylenepentamine β-cyclodextrin With pyridine In N,N-dimethyl-formamide at -20 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With trichlorophosphate In 1,2-dichloro-ethane at 85℃; Inert atmosphere; Reflux; | |
74% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In dichloromethane at 20℃; | |
74% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In dichloromethane at 20℃; | 3',6'-bis (diethylamino)-2-(prop-2-ynyl) spiro [isoindoline-1, 9'-xanthen]-3-one (probe 1) To a solution of rhodamine B (5.76 g, 12 mmol) in 20 mL anhydrous dichloromethane was sequentially added 2-(1H-Benzotriazol-1-yl)-1, 1, 3, 3-tetramethyluronium- hexafluoro-phosphate, HBTU) (5.45 g, 14.4 mmol), propargylamine (0.925 mL, 14.4 mmol) and tri-ethylamine (2.5 mL, 14.4 mmol). The reaction mixture was stirred at room temperature overnight until TLC analysis indicated that the starting material had been consumed. The reaction mixture was diluted with dichloromethane and then washed with brine. The combined organic layers were dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (Hexane : EtOAc, 4:1) to yield compound 1 as a light pink solid (4.25g, 8.85mmol) in 74 % yield. 1H NMR (400 MHz, CDCl3) δ ppm 1.14 (t, J = 7.2, 12 H), 1.74 (t, J = 2.4, 1H), 3.32 (q, J = 7.2 Hz, 8H), 3.93 (d, J = 2.4 Hz, 2H), 6.25 (dd, J = 2.8, 8.8, 2H), 6.37 (d, J = 2.8 Hz, 2H), 6.45 (d, J = 8.8 Hz, 2H), 7.10 (m, 1H), 7.41 (m, 2H), 7.91 (m, 1H). 13C NMR (100 MHz, CDCl3) δ ppm 12.5, 28.5, 44.3, 64.8, 70.0, 78.2, 97.8, 105.1, 108.0, 123.0, 123.7, 127.9, 129.1, 130.4, 132.6, 148.8, 153.4, 153.7, 167.4. |
73% | Stage #1: rhodamine B With thionyl chloride In dichloromethane for 2h; Inert atmosphere; Reflux; Stage #2: Propargylamine In acetonitrile at 20℃; for 2h; Inert atmosphere; | |
70% | Stage #1: rhodamine B With trichlorophosphate In 1,2-dichloro-ethane at 80℃; for 6h; Stage #2: Propargylamine With triethylamine In tetrahydrofuran at 25℃; for 12h; | |
68% | Stage #1: rhodamine B With trichlorophosphate In water; 1,2-dichloro-ethane at 80℃; for 6h; Stage #2: Propargylamine With triethylamine at 20℃; for 16h; | |
62% | With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 18h; | |
50% | Stage #1: rhodamine B With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In 1,2-dichloro-ethane at 20℃; for 2h; Stage #2: Propargylamine In 1,2-dichloro-ethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.8% | In ethanol at 80℃; for 12h; | 1 (0.42 mmol) of rhodamine B was dissolved in ethanol, and then 956 yL (5.04 mmol) of tetraethylenepentamine was added dropwise with ethanol as a solvent. The reaction was stopped by heating to 80 ° C for 12 h, The solvent was removed by a rotary evaporator and washed three times with water and dried to give a yellow solid, i.e., intermediate RTPA. The yield was 90.8%. |
87% | In ethanol at 80℃; Inert atmosphere; | |
87% | at 80℃; Inert atmosphere; |
72% | In ethanol for 12h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | In methanol at 100℃; for 1h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sodium hydroxide In water for 2h; Inert atmosphere; | |
90% | With sodium hydroxide In water | 1 Example 1 Preparation of Compound 2 Rhodamine B was dissolved in 1 mol·L-1 sodium hydroxide aqueous solution and stirred overnight. Ethyl acetate extraction, combined withThe organic phase was washed with 1 mol·L-1 aqueous sodium hydroxide solution and brine, dried, and concentrated to give compound 2 in a yield of 90%. |
90.2% | With sodium hydroxide | 11 Synthesis of Rhodamine B 4-(3-Hydroxylpropyl) Piperazine Amide Example 11 Synthesis of Rhodamine B 4-(3-Hydroxylpropyl) Piperazine Amide The rhodamine B 4-(3-hydroxylpropyl) piperazine amide was obtained using a multistep procedure adapted from Nguyen, T.; Francis, M. B., "Practical Synthetic Route to Functionalized Rhodamine Dyes." Org. Lett. 2003, 5 (18), 3245-3248, the disclosure of which is incorporated herein by reference in its entirety. First, rhodamine B base was synthesized as follows: 15 g of rhodamine B (31.3 mmol) was dissolved in 1 M NaOH and extracted with multiple portions of EtOAc. The combined organic layers were washed with 1 M NaOH (3*) and brine (3*), then stirred over Na2SO4 and dried under vacuum. The product was isolated as a pink foam (12.5 g, 90.2% yield). 1H-NMR (300 MHz, 303K, CDCl3): δ=1.18 (t, 3HH-H=7.0 Hz, 12H), 3.37 (q, 3JH-H=7.0 Hz, 8H), 6.35 (dd, 3JH-H=8.9, 2.5 Hz, 2H), 6.46 (d, 3JH-H=2.4 Hz, 2H), 6.59 (d, 3JH-H=8.9 Hz, 2H), 7.21 (d, 3JH-H=7.5 Hz, 1H), 7.53-7.68 (m, 2H), 8.01 (d, 3JH-H=6.9 Hz, 1H) ppm (). |
With sodium hydroxide In ethyl acetate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 16.5h; | 2 Example 2: Synthesis of Rhodamine Ligand Monomers To a solution of rhodamine B 5.27 g (11 mmol), N,N′-dicyclohexylcarbodimide 2.88 g (14 mmol) and 4-dimethylaminopyridine 134 mg (1.1 mmol) in 75 mL CH2Cl2 was added 2-hydroxyethyl methacrylate 1.82 g (14 mmol) at 0 degrees C. After 30 min, the ice bath was removed and the reaction mixture was stirred at room temperature for 16 h. After filtering off the byproduct dicyclohexylurea, the solvent was evaporated under reduced pressure. The residue was redissolved in 30 mL acetonitrile and the insoluble materials were filtered off. The crude product obtained after evaporating acetonitrile was purified by flash column chromatography using 6% methanol in chloroform. Yield: 5.89 g (91%). An exemplary 1H-NMR spectrum of Rhodamine monomer is shown in FIG. 6B. |
91% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 16h; | 2 Synthesis of Additional Ligand Monomers In this example, the synthesis of ligand monomers, in addition to the fluorescein monomer described in Example 1 and useful in embodiments of the technology described herein is described. Rhodamine-HEMA monomer Synthesis is illustrated schematically in FIG. 11A. To a solution of rhodamine B 5.27 g (11 mmol), N,N′-dicyclohexylcarbodimide 2.88 g (14 mmol) and 4-dimethylaminopyridine 134 mg (1.1 mmol) in 75 mL CH2Cl2 was added 2-hydroxyethyl methacrylate 1.82 g (14 mmol) at 0° C. After 30 min, the ice bath was removed and the reaction mixture was stirred at room temperature for 16 h. After filtering off the byproduct dicyclohexylurea, the solvent was evaporated under reduced pressure. The residue was redissolved in 30 mL acetonitrile and the insoluble materials were filtered off. The crude product obtained after evaporating acetonitrile was purified by flash column chromatography using 6% methanol in chloroform. Yield: 5.89 g (91%). An exemplary 1H-NMR spectrum of Rhodamine monomer is shown in FIG. 11B. |
90% | Stage #1: 2-methyl-2-propenoic acid 2-hydroxyethyl ester; rhodamine B With dmap; camphor-10-sulfonic acid In chloroform for 0.5h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 20℃; for 2h; | 1 Basic violet 10 (18 parts by mass) Anhydrous chloroform (170 parts by mass), Camphorsulfonic acid (1.0 part by mass), 4- (N, N-dimethylamino) pyridine (1.4 parts by mass), 2-Hydroxyethyl methacrylate (18 parts by mass) was added and stirred for about 30 minutes. Thereafter, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (10.5 parts by mass) Anhydrous chloroform (47 parts by mass) Was added and the solution previously dissolved was slowly added, And the mixture was stirred at room temperature for about 2 hours. The liquid separation operation was carried out twice with a 1N hydrochloric acid aqueous solution (150 parts by mass) The organic layer was washed twice with 10% saline (150 parts by mass). Subsequently, 43 parts by mass of anhydrous magnesium sulfate was added and the mixture was stirred for about 30 minutes, The drying agent was filtered, By distilling off the solvent, a compound represented by the following formula (A1) 20.6 parts by mass (Yield 90%). The obtained compound is referred to as a colorant (A-1). |
79% | Stage #1: 2-methyl-2-propenoic acid 2-hydroxyethyl ester; rhodamine B With dmap; dicyclohexyl-carbodiimide In 1,2-dichloro-ethane at 20℃; for 32h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In 1,2-dichloro-ethane for 40h; Inert atmosphere; | |
74.6% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; | 1 Synthesis of Dye Monomer M-1 (0149) To 2 L round-bottom flask equipped with stirrer, 47.9 g of rhodamine B (0.10 mol, produced by Wako Pure Chem. Ind., Ltd.), 500 ml of dichloromethane, 15.6 g of hydroxyethyl methacrylate (0.12 mol, produced by Wako Pure Chem. Ind., Ltd.). 4.9 g of 4-dimethylaminopyridine (0.04 mol, produced by Wako Pure Chem. Ind., Ltd.), 32.6 g of I-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.17 mol, produced by TOYOBO Co., Ltd.) were added, and reacted by stirring at room temperature for 24 hours. After completion of reaction, organic layer was washed with about 500 ml of ion-exchanged water. Then, 50 g of sodium sulfate was added to dehydrate, and 10 mg of p-methoxyphenol (produced by Wako Pure Chem. Ind., Ltd.) was added as polymerization inhibitor, distilled under reduced pressure to remove solvent, to obtain 44 g of red solid (yield: 74.6%). This is referred to dye monomer M-1. |
With thionyl chloride In dichloromethane at 25 - 60℃; for 12h; | ||
Stage #1: 2-methyl-2-propenoic acid 2-hydroxyethyl ester; rhodamine B With dmap; (1S)-10-camphorsulfonic acid In chloroform for 0.5h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 20℃; for 2h; | A-1 Synthesis of Example A-1 In the 18 parts by mass of the alkali purple 10 (basic violet 10) add in 170 parts by weight of the anhydrous chloroform, 1.0 parts by mass of the camphor sulfonic acid, 1.4 parts by mass of the 4 - (N, N-dimethyl amino) pyridine and 18 parts by mass of the methyl acrylic acid 2-hydroxyethyl methacrylate, and stirring for about 30 minutes. Subsequently, the slowly adding 10.5 parts by mass of 1-ethyl-3 - (3-dimethyl amino propyl) imine hydrochloride carbon two acyls adding 47 parts by mass of pre-dissolving the anhydrous chloroform and the solution, while stirring the mixture at room temperature for about 2 hours. Using 150 parts by mass of a 1N hydrochloric acid aqueous solution to 2 times after the separating operation, with 150 parts by mass of a 10% salt water cleaning organic layer 2 times. Furthermore, by adding 43 parts by mass of magnesium sulfate anhydrous stirring for about 30 minutes, filtration of the drying agent, the solvent the distill goes, can obtain 20.6 parts by mass of the represented by formula (A1) said (recovery rate of 90%) of a compound (hereinafter referred to as dye A-1). | |
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 20℃; for 24h; | 1 Into a round-bottom flask equipped with a stirring apparatus, 47.9 g of rhodamine B (compound 18) (0.10 mol, produced by Wako Pure Chemical Industries, Ltd.), 500 mL of methylene chloride, 15.6 g of hydroxyethyl methacrylate (compound 19) (0.12 mol, produced by Wako Pure Chemical Industries, Ltd.), 4.9 g of 4-dimethylaminopyridine (0.04 mol, produced by Wako Pure Chemical Industries, Ltd.), and 32.6 g of 1 -ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.17 mol, produced by Toyobo Co., Ltd.) were added and stirred at room temperature for 24 hours to carry out a reaction. Afier completion of the reaction, theorganic layer was washed with about 500 mE of ion- exchanged water. Next, 50 g of sodium sulfate was added for dehydration, and 10 mg of p-methoxyphenol (produced by Wako Pure Chemical Industries, Ltd.) was added as a polymerization inhibitor, and the solvent was removed under reduced pressure to obtain 44 g (yield: 74.6%) of red solid (compound 20). This was referred to as the dye monomer 5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h; | Synthesis of Benzyl 3-(3',6'-bis(diethylamino)-3-oxospiro[isoindoline-1,9'-xanthen]-2-yl) propanoate (RBAP) A solution of 2 (2.00 g, 10 mmol) and Et3N (1.5 mL, 10.8 mmol) in 20 mL CH2Cl2 was added to a solution of Rhodamine B (4.00 g, 8.3 mmol) and HOBt (1.2 g, 8.9 mmol) in 30 mL CH2Cl2. The reaction mixture was stirred at room temperature for 12 h, filtered through a pad of Celite and then dried under vacuum. Flash chromatography (silica gel; MeOH/DCM, 2/98, v/v; Rf = 0.3) of the residue gave RBAP as a bright-red solid (4.51 g, 90%). 1H-NMR (acetone-d6/D2O): δ = 7.94-7.92 (m, 1H), 7.58-7.56 (m, 2H), 7.36-7.29 (m, 5H), 7.03-7.01 (m, 1H), 6.43-6.39 (m, 6H), 4.98 (s, 2H), 3.45-3.37 (m, 10H), 2.30 (t, J = 7.75 Hz, 2H), 1.15 (t, J = 7.0 Hz, 12H) ppm. 13C-NMR (126 MHz, CDCl3, 298 K): δ = 171.6, 168.2, 153.9, 153.4, 148.9, 136.0, 132.5, 130.9, 128.9, 128.5, 128.2, 128.0, 123.8, 122.9, 108.3, 105.4, 98.2, 66.2, 65.0, 44.5, 35.9, 32.9, 29.8, 12.7 ppm. ESI-MS (m/s): Calculated for [M + H]+ C38H42N3O4 +, 604.3170; HRMS found, 604.3180. (Supporting Materials, Figures S1-S3). |
90% | With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h; | 2.3 Synthesis of Benzyl3-(3′,6′-bis(diethylamino)-3-oxospiro[isoindoline-1,9′-xanth en]-2-yl)propanoate (3) A solution of compound 2 (2.00g, 10mmol) and triethylamine (1.5mL, 10.8mmol) dissolved in 20mL of CH2Cl2 was added to a solution of Rhodamine B (4.00g, 8.3mmol) and HOBt (1.2g, 8.9mmol) in 30mL of CH2Cl2. After the reaction mixture was stirred at room temperature for 12h, the solution was filtered through a pad of Celite and then dried under vacuum. The crude mixture was purified by column chromatography using CH2Cl2/ MeOH (v/v, 98:2) as the eluent to give compound 3 (4.51g, 90%) as a bright-red solid. 1H NMR (500MHz, acetone-d6/D2O, 298K): δ=7.94-7.92 (m, 1H), 7.58-7.56 (m, 2H), 7.36-7.29 (m, 5H), 7.03-7.01 (m, 1H), 6.43-6.39 (m, 6H), 4.98 (s, 2H), 3.45-3.37 (m, 10H), 2.30 (t, J=7.75Hz, 2H), 1.15 (t, J=7.0Hz, 12H) ppm. 13C NMR (126MHz, acetone- d6/D2O, 298K): δ=171.6, 168.2, 153.9, 153.4, 148.9, 136.0, 132.5, 130.9, 128.9, 128.5, 128.2, 128.0, 123.8, 122.9, 108.3, 105.4, 98.2, 66.2, 65.0, 44.5, 35.9, 32.9, 29.8, 12.7ppm. HRMS (m/z): [M+H]+ found at 604.3180; calculated for C38H42N3O4+, 604.3170. |
81% | With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With trichlorophosphate In 1,2-dichloro-ethane at 0 - 85℃; for 5.25h; Inert atmosphere; | |
79% | With trichlorophosphate In acetonitrile at 90℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.2% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In dichloromethane at 20℃; for 2h; | 4.2; 28.i Rhodamine B Boc-piperazine Amide (2). To a stirring solution of Rhodamine B (1, 2.00 g, 4.18 mmol), Boc-piperizine (0.78 g, 4.18 mmol) and Et3N (1.02 g, 10.04 mmol) in CH2CI2 (50 mL), was added HBTU (1.90 g, 5.02 mmol). The mixture was stirred for 2 h at room temperature and diluted in CH2CI2 (50 mL). The solution was washed with brine (50 mL x 2), dried on anhydrous Na2S04, filtered and concentrated. Flash column chromatography of the residue on silica gel (CLLC MeOH, 20: 1) afforded the compound (2) as a purple foam (2.28 g, 91.2%). 1H NMR (400 MHz, CDC13) δ ppm 7.62-7.57 (m, 2H), 7.48-7.44 (m, 1H), 7.25 (m, 1H), 7.16-7.1 1 (m, 2H), 6.84 (d, J=9.0 Hz, 2H), 6.69 (d, J=2.4 Hz, 2H), 3.54 (h, J=7.8 Hz, 8H), 3.29 (s, 4H), 3.19 (s, 4H), 1.33 (s, 9H), 1.22 (t, J=7.8 Hz, 12H). 13C NMR (100 MHz, CDC13) δ ppm 167.84, 157.87, 155.95, 155.78, 154.63, 135.23, 132.13, 130.92, 130.47, 130.26, 127.75, 114.23, 1 13.84, 96.44, 80.54, 46.22, 28.43, 12.70. |
80% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; | |
80% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; | 1.3 Rhodamine-N-piperazine-N-Boc To rhodamine B (0.20 mmol) DMF (5 mL) solution, N-Boc piperazine (0.41 mmol), HOBt (0.25 mmol) and EDC (0.41 mmol) were added sequentially . Stir at room temperature and monitor the reaction by TLC. After the reaction was completed, water (30 mL) was added, extracted with EtOAc (3 × 30 mL), and washed with water. The organic phase was dried over Na 2 SO 4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using methanol / dichloromethane (v / v, 1:50) as the eluent to obtain the target compound as a pink solid (87 mg) with a yield of 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.1% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In dichloromethane at 20℃; | 1.4; 25 Rhodamine B 4-(propargyl)piperazine amide (4). To a stirring solution of Rhodamine B (2.50 g, 5.22 mmol) in DCM (20 mL) was sequentially added compound 3 (0.83g, 6.68 mmol), O-benzotriazole-N,N,N',N'-tetramethyl-uronium-hexafluoro-phosphate(HBTU) (2.2 g, 5.80 mmol), and triethylamine (0.87 niL, 5.80 mmol). The resulting mixture was stirred overnight at room temperature until TLC indicated that the starting material disappeared. The reaction mixture was diluted with DCM (50 mL) and then washed with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. This crude residue was purified by flash column chromatography on silica gel (DCM:MeOH, 20: 1) to give compound 4 as purple solid (2.27 g, 79.1 % yield). 1H NMR (400 MHz, CDC13) δ 1.30 (t, J=7.2, 12H), 2.20 (t, J=2.4, 1H), 2.35 (br s, 4H), 3.23 (d, J=2.4, 2H), 3.32 (br s, 2H), 3.42 (br s, 2H), 3.59 (q, J=7.2, 8H), 6.75-6.76 (m, 2H), 6.89-6.92 (m, 2H), 7.22-7.24 (m, 2H), 7.30-7.32 (m, 1H), 7.51-7.53 (m, 1H), 7.63-7.66 (m, 2H). 13C NMR (100 MHz, CDC13) δ 12.50, 41.31, 46.00, 46.44, 47.17, 50.86, 51.45, 74.12, 96.28, 1 13.72, 1 14.05, 127.61, 129.88, 130.16, 130.44, 132.10, 135.35, 155.63, 157.74, 167.50. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.1% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In dichloromethane at 20℃; | RhodamineB 4-(propargyl)piperazine amide (4) To a stirring solution of Rhodamine B (2.50 g, 5.22 mmol) in DCM (20 mL) was sequentially added compound 3 (0.83 g, 6.68 mmol), O-benzotriazole-N,N,N’,N’-tetramethyl-uronium-hexafluoro-phosphate (HBTU) (2.2 g, 5.80 mmol), and triethylamine (0.87 mL, 5.80 mmol). The resulting mixture was stirred overnight at room temperature until TLC indicated that the starting material disappeared. The reaction mixture was diluted with DCM (50 mL) and then washed with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. This crude residue was purified by flash column chromatographyon silica gel (DCM:MeOH, 20:1) to give compound 4 as purple solid (2.27 g, 79.1 % yield). 1H NMR (400 MHz, CDCl3) δ 1.30 (t, J=7.2, 12 H), 2.20 (t, J=2.4, 1H), 2.35 (br s, 4H), 3.23 (d, J=2.4, 2H), 3.32 (br s, 2H), 3.42 (br s, 2H), 3.59 (q, J= 7.2, 8H), 6.75-6.76 (m, 2H), 6.89-6.92 (m, 2H), 7.22-7.24 (m, 2H), 7.30-7.32 (m, 1H), 7.51-7.53 (m, 1H), 7.63-7.66 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 12.50, 41.31, 46.00, 46.44, 47.17, 50.86, 51.45, 74.12, 96.28, 113.72, 114.05, 127.61, 129.88, 130.16, 130.44, 132.10, 135.35, 155.63, 157.74, 167.50. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane for 0.75h; | Synthesis of Rho B/CHA CT complex The solid CT complex product of rhodamine B and chloranilic acid was synthesized by adding 1 mmol of Rho B to 1 mmol of CHA and stirred in 50 ml of methylene chloride for 45 min. The mixture was allowed to evaporate slowly at room temperature. The deep red color CT complex was precipitated as a solid powder. The separated complex was filtered off, washed well with a little amount of methylene chloride, and then collected and dried under vacuum over anhydrous calcium chloride for 48 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.2% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h; | 5 Synthesis of Dye Monomer M-10 (0159) To the round-bottom 2 L flask equipped with stirrer, 47.9 g of rhodamine B (0.10 mol, produced by Wako Pure Chem. Ind., Ltd.), 500 ml of dichloromethane, 17.3 g of hydroxybutyl acrylate (0.12 mol, produced by Wako Pure Chem. Ind., Ltd.), 4.9 g of 4-dimethylaminopyridine (0.04 mol, produced by Wako Pure Chem. Ind., Ltd.), 32.6 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.17 mol, produced by TOYOBO Co., Ltd.) were added, and reacted by stirring at room temperature for 24 hours. After completion of reaction, organic layer was washed with about 500 ml of ion-exchanged water. Then, 50 g of sodium sulfate was added to dehydrate, 10 mg of p-methoxyphenol as polymerization inhibitor (produced by Wako Pure Chem. Ind., Ltd.) was added, and distilled off the solvent under reduced pressure to obtain 48.5 g of red solid (yield, 80.2%). This is referred to dye monomer M-10. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In dichloromethane at 25℃; for 1h; | 1 Synthesis Example 1 Synthesis of Intermediate (Compound 2) Rhodamine B (2.0 g (3.9 mmol)) (compound 1: produced by Wako Pure Chemical Industries, Ltd.), 2.7 g (3.9 mmol) of a lithium salt of tetrakis(pentafluorophenyl)boron (IV) (LiFABA) (produced by Tosoh Finechem Corporation), and 30 ml of dichloromethane were put into a round-bottom flask equipped with a stirring device, and reacted for 1 hour at 25° C. The reaction solution was diluted with dichloromethane and then washed with water. The solvent was distilled away from the reaction solution by concentration under reduced pressure, thereby obtaining 4.1 g (yield: 100%) of a carboxylic acid substance (compound 2) of reddish-violet solids having a tetrakis(pentafluorophenyl)boron (IV) anion. |
94% | With water In dichloromethane at 20℃; for 0.5h; | 6 Synthesis of Dye Monomer M-12 (B(C6F5)4 salt of Rhodamine B) (0161) To 500 ml round-bottom flask equipped with stirrer, 9.6 g of rhodamine B (0.020 mol), 13.7 g of lithium tetrakis(pentafluorophenyl)borate (0.020 mol, produced by Tosoh-Finechem. Corp.), 150 ml of dichloromethane, 150 ml of ion-exchanged water were added, then, salt exchanging reaction was carried out by stirring at room temperature for 30 minutes. After completion of reaction, organic layer was washed with about 150 ml of ion-exchanged water 4 times. Then, concentrated under reduced pressure, 21.1 g of red solid (yield, 94.0%) in which a chloride ion of rhodamine B was exchanged to tetrakis(pentafluorophenyl)borate anion was obtained. This is referred to dye monomer M-12. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.8% | In ethanol for 12h; Reflux; | RPTU The intermediate RTPA was synthesized following the references [5,6]. RB (0.2 g, 0.416 mmol) was dissolved in EtOH (10 mL) and then TEPA (760 μL, 4.01 mmol) was added in dropwise. The solution was heated to reflux for 12 h until losing its red color. The solvent was removed under reduced pressure. Water was added to the residue and the solution was extracted with CH2Cl2. The organic phase was washed three times with water, evaporated the solvent, and dried in vacuo to afford RTPA as a yellow solid (0.232 g, 90.8%). Next, to a stirring solution of RTPA (50 mg, 0.08 mmol) in CH3CN (10 mL), PITC (117 μL, 0.96 mmol) was added dropwise and the resulted mixture reacted under room temperature for 6 h. After stirred for another 6 h, the solvent was removed under reduced pressure. The crude product was purified by sillica-gel column chromatography with ethyl acetate/petroleum ether (1/5, v/v) as eluent to afford RPTU as a white solid (0.034 g, 36.2%). m.p. 192.6 oC. 1H NMR (400 MHz, CDCl3) (Fig. S9), δ /ppm:1.16 (t, 12H, J=6.8 Hz), 3.34 (q, 8H, J=6.8 Hz), 3.43 (t, 2H, J=4.8 Hz), 3.50 (s, 4H), 3.73 (t, 10H, J=5.6 Hz), 3.84 (t, 2H, J=4.8 Hz), 4.06 (t, 2H, J=5.6 Hz), 6.31(d, 2H, J=7.2 Hz), 6.41-6.43(m, 4H), 7.13-7.18 (m, 12H), 7.35-7.40 (m, 3H), 7.49 (q, 8H, J=7.2 Hz), 7.87 (d, 1H, J=7.2 Hz), 9.55 (s, 1H). 13C NMR (300 MHz, CDCl3) (Fig. S10), δ /ppm: 12.62 (4C, a), 29.69 (2C, t, q), 38.20 (5C, r), 44.45 (4C, b), 49.52 (1C, s), 65.55 (1C, i), 97.98 (2C, d), 104.10 (2C, f), 108.40 (2C, h), 122.88 (1C, n), 124.08 (8C, w), 125.72 (1C, k), 126.09 (4C, y), 126.45 (2C, g), 127.66 (1C, m), 128.23 (8C, x), 128.55 (1C, l), 130.10 (1C, o), 130.37 (4C, v), 133.12 (1C, j), 139.71 (2C, e), 149.04 (2C, c), 153.37 (1C, p), 181.43 (1C, u), 181.78 (3C, z). LC-MS (Fig. S11): [M+Na]+=1175.86. FTIR (cm-1) (Fig. S12): v(NH) 3455.87, 3212.88; v(CH3) 2927.46; v(CH2) 2861.89; v(C=O) 1654.65; v(ArH) 1600.65, 1546.66, 1527.37. Elemental analysis: Calculated for C64H71N11O2S4 (%):C, 66.58; N, 13.34; H, 6.20. Found (%): C, 66.43; N, 12.92; H, 6.00. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium tetrahydroborate; iodine In tetrahydrofuran at 0 - 20℃; for 1h; | |
55% | With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 48h; Inert atmosphere; | 3 To a solution of rhodamine B (10.0 g, 20.9 mmol) in dry THF (50 mL) at 0° C. was added LiAlH4 (4.0 g, 105.4 mmol) portion by portion under argon atmosphere. The resulting mixture was stirred at room temperature for 48 h, then quenched with ethyl acetate (50 mL) carefully. The resulting mixture was diluted with water and CHCl3, and extracted with CHCl3 for 3 times. The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The target compound HJ-3-247 [1491155-13-5] was isolated a sticky pink solid by flash chromatography on silica gel using EtOAc:Hexane (1:4) as an eluent. Yield: 4.93 g (55%). 1H NMR (400 MHz, CDCl3) δ 7.55-7.45 (m, 1H), 7.38-7.27 (m, 3H), 6.81 (d, J=8.6 Hz, 2H), 6.54 (s, 2H), 6.37 (d, J=7.8 Hz, 2H), 5.47 (s, 1H), 4.69 (s, 2H), 3.40 (q, J=6.9 Hz, 8H), 2.38 (brs, 1H), 1.25 (t, J=7.0 Hz, 12H); 13C NMR (100 MHz, CDCl3) δ 151.6, 147.5, 144.9, 138.3, 131.1, 130.0, 128.9, 127.8, 126.5, 111.5, 107.4, 98.7, 62.7, 44.3, 39.2, 12.5. |
26% | With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; Inert atmosphere; |
10% | With sodium tetrahydroborate; iodine In tetrahydrofuran at 60℃; for 48h; | To the stirred solution of fluorescein (1.0 mmol) in THF (4 mL),NaBH4 (6.0 mmol) was added portion-wise. When the gas evolutionstopped, I2 (3.0 mmol) was added slowly, where the reaction temperaturewas then raised to 60 C. After 48 h, the reaction mixture was cooledto room temperature, followed by adding Na2S2O35H2O (1.0 eq to I2)and then saturated NaHCO3 slowly. Then, the pH of the mixture wasadjusted to pH 5 using 2 M AcOH, the aqueous layer was extracted withEtOAc (4 30 mL), the combined organic phase was washed withsaturated NaCl, dried over Na2SO4 and concentrated under reducedpressure, the residue was purified by column chromatography usinggradient MEOH/DCM as eluent (Scheme 2). |
With sodium tetrahydroborate; water In dimethyl sulfoxide at 100℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: rhodamine B; 2,2'-[1,2-ethanediylbis(oxy)]bisethanol With dmap; camphor-10-sulfonic acid In chloroform for 0.5h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 20℃; for 2h; | 3 To 18 parts of Rhodamine B (Tokyo Kasei Kogyo Co., Ltd.), 170 parts of anhydrous chloroform (manufactured by Kanto Chemical Co.), 1.0 parts of camphorsulfonic acid (manufactured by Aldrich Co.), 1.4 parts of 4- (N, N-dimethyl amino) pyridine (manufactured by Tokyo Kasei Kogyo Co., Ltd.), 18 parts of triethylene glycol (manufactured by Wako Pure Chemical Industries, Ltd.) were added and stirred approximately for 30 minutes. Thereafter, a solution prepared by dissolving in advance anhydrous chloroform 47 parts to 10.5 parts of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (manufactured by Wako Pure Chemical Industries, Ltd.) was added slowly, then the mixture was stirred for about 2 hours at room temperature. After performing twice a liquid separation operation with 1N hydrochloric acid aqueous solution (150 parts), the organic layer was washed twice with 150 parts of 10% brine. Then 43 parts of anhydrous magnesium sulfate was added and stirred for about 30 minutes, then the drying agent was filtered and the solvent was evaporated to give 20.6 parts of compound of formula (g-1) (90% yield). |
90% | Stage #1: rhodamine B; 2,2'-[1,2-ethanediylbis(oxy)]bisethanol With dmap; camphor-10-sulfonic acid In chloroform for 0.5h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 20℃; for 2h; | 3 To 18 parts of Rhodamine B (manufactured by Tokyo Chemical Industry Co., Ltd.), 170 parts of anhydrous chloroform (manufactured by Kanto Chemical Co., Inc.), 1.0 part of camphorsulfonic acid (manufactured by Aldrich Corp.) Amino) pyridine (manufactured by Tokyo Chemical Industry Co., Ltd.) and 18 parts of triethylene glycol (manufactured by Wako Pure Chemical Industries, Ltd.) were added and stirred for about 30 minutes. Thereafter, a solution prepared by adding 47 parts of anhydrous chloroform to 10.5 parts of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (manufactured by Wako Pure Chemical Industries, Ltd.) and dissolving it in advance was slowly added Followed by stirring at room temperature for about 2 hours. After performing separation operation twice with 150 parts of 1N hydrochloric acid aqueous solution, the organic layer was washed twice with 150 parts of 10% saline. 43 parts of anhydrous magnesium sulfate was added and stirred for about 30 minutes, then the desiccant was filtered, The solvent was distilled off to obtain 20.6 parts (yield 90%) of the compound represented by the formula (g-1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18 g | Stage #1: rhodamine B With trichlorophosphate In chloroform at 65℃; for 3h; Stage #2: 2-methyl-2-propenoic acid 2-hydroxyethyl ester With triethylamine In chloroform at 20℃; for 3h; Stage #3: tetrabutylammonium trifluoromethylsulfonate In methanol | 20.0 g (41.8 mmol) of rhodamine B was dissolved in 125 g of chloroform, and 9.6 g (62.6 mmol) of phosphorus oxychloride was added dropwise while cooling with an ice bath. Thereafter, the mixture was cooled to 20 deg. C which had been heated at an external temperature of 65°C. C for 3 hours, and then 9.8 g (75.2 mmol) of 2-hydroxyethyl methacrylate was added while cooling with an ice bath and 30.8 g (304 mmol) of triethylamine was added . After the internal temperature was adjusted to 20°C and stirred for 3 hours, 100 g of chloroform was added, followed by partitioning with water, and then the chloroform layer was concentrated.The resulting concentrate was added to 100 mL of methanol, and 16.4 g (41.8 mmol) of tetrabutylammonium trifluoromethylsulfonate was added. The mixture was partitioned between ethyl acetate (200 mL) and water (100 mL), and the ethyl acetate layer was concentrated to obtain 18.0 g of monomer X. |
18 g | Stage #1: rhodamine B With trichlorophosphate In chloroform at 20 - 65℃; for 3h; Cooling with ice; Stage #2: 2-methyl-2-propenoic acid 2-hydroxyethyl ester With triethylamine In chloroform at 20℃; for 3h; Cooling with ice; Stage #3: tetrabutylammonium trifluoromethylsulfonate In methanol | 20.0 g (41.8 mmol) of rhodamine B was dissolved in 125 g of chloroform, and 9.6 g (62.6 mmol) of phosphorus oxychloride was added dropwise while cooling with an ice bath. Thereafter, the mixture was cooled to 20° C which had been heated at an external temperature of 65° C for 3 hours, and then 9.8 g (75.2 mmol) of 2-hydroxyethyl methacrylate was added while cooling with an ice bath and 30.8 g (304 mmol) of triethylamine was added . After the internal temperature was adjusted to 20° C and stirred for 3 hours, 100 g of chloroform was added, followed by partitioning with water, and then the chloroform layer was concentrated. The resulting concentrate was added to 100 mL of methanol, and 16.4 g (41.8 mmol) of tetrabutylammonium trifluoromethylsulfonate was added. The mixture was partitioned between ethyl acetate (200 mL) and water (100 mL), and the ethyl acetate layer was concentrated to obtain 18.0 g of monomer X. |
18 g | Stage #1: rhodamine B With trichlorophosphate In chloroform at 20 - 65℃; for 3h; Cooling with ice; Stage #2: 2-methyl-2-propenoic acid 2-hydroxyethyl ester; tetrabutylammonium trifluoromethylsulfonate With triethylamine In chloroform for 3h; Cooling with ice; | 1 Rhodamine B (20.0 g, 41.8 mmol)Was dissolved in 125 g of chloroform,While cooling with an ice bath, 9.6 g (62.6 mmol) of phosphorus oxychlorideWas added.After that,After cooling to 20 deg. C heated at an outside temperature of 65 deg. C for 3 hours,While cooling with an ice bath, 9.8 g (75.2 mmol) of 2-hydroxyethyl methacrylate,Lt; / RTI & gt;30.8 g (304 mmol) of triethylamine,Was added. The inner temperature was adjusted to 20 ° C for 3 hoursAfter stirring, 100 g of chloroform was added, After separating with water, The chloroform layer was concentrated.The resulting concentrate was added to 100 mL of methanol,16.4 g (41.8 mmol) of tetrabutylammonium trifluoromethylsulfonate were added,Was added.200 mL of ethyl acetate,The mixture was separated into 100 mL of water,By concentrating the ethyl acetate layer, 18.0 g of monomer X was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.3 g | In water at 20℃; for 3h; | 3 Synthesis of Compound 3-3 1.198 g (0.0025 mol) of Rhodamine B was dissolved in 220 ml of water,While dissolving and stirring, a solution of 0.581 g (0.003 mol, 1.2 equivalents) of the lithium salt of bisoxalate borate in 15 ml of water was slowly added at room temperature. After stirring for 3 hours, the precipitated crystals were filtered, washed with water and dried to obtain 1.3 g of purple crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.7% | With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In dichloromethane at 20℃; for 4h; | 1. Synthesis of rhodamine-o-phenylenediamine The conjugation of rhodamine and o-phenylenediamine was carried out by dissolving rhodamine B (1.00 g, 2.1 mmol) in 50 mL of CH2Cl2 then 10 mL of triethylamine (0.6 mL, 4.2 mmol) solution in CH2Cl2 was added dropwise to the rhodamine solution and stirred for 30 min. The mixture of hydroxybenzotriazole (HOBT, 297.3 mg, 2.2 mmol) and o-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborat (TBTU, 706.4 mg, 2.2 mmol) in CH2Cl2 was added into the rhodamine solution and stirred for 30 min. Subsequently, the solution of o-phenylenediamine (324.4 mg, 3.0 mmol) in 5 mL CH2Cl2 was added into the reaction and stirred for 4 h at room temperature. The color of the solution changed from magenta to light orange. The reaction mixture was quenched by addition of water then extracted with distilled water (3 x 15 mL). The combined organic phase was dried using anhydrous Na2SO4. The organic solvent was removed under reduced pressure. The crude reaction was purified by Si-gel column chromatography using 50% EtOAc-hexane to yield a pale yellow solid (957.7 mg, 81.7 %yield) of the desired product. |
73% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate In dichloromethane at 20℃; | 1 The synthetic route is shown in Figure 1.Synthesis of compound RB-OPD: Rhodamine B (0.48 g, 1.0 mmol) was added to a 100 mL round bottom flask containing 30 mL of dichloromethane.O-phenylenediamine (0.54 g, 5.0 mmol) andCarter condensing agent (0.44g, 1.0mmol),Stirred for 10 to 14 hours at room temperature, the solvent was removed by distillation under reduced pressure, the crude product was a volume ratio of about 5: 1 to 3: 1, the column eluent CH2Cl2 / CH3COOC2H5 chromatographic separation to give a white solid (0.39 g of, yield :73%),That is, the compound RB-OPD. |
46.4% | Stage #1: rhodamine B With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 16h; Stage #2: 1,2-diamino-benzene With triethylamine In dichloromethane at 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | As shown in Supplementary Figure 12, rhodamine B (Aldrich) (144 mg,0.3 mmol, 1.0 eq) was dissolved in DMF (2 mL) with HATU (115 mg, 0.3 mmol,1.0 eq) and iPr2NEt (0.5 mL, 3.0 mmol, 10 eq) under an atmosphere of argon. The reaction mixture was stirred at room temperature for 10 min before the addition of N-methyl,N-Boc-ethylenediamine (160 mg, 0.9 mmol, 3.0 eq) in DMF (0.5 mL). The reaction was stirred for 22 h and concentrated under reduced pressure, and the residue subjected to flash column chromatography [100:0 (CHCl3:EtOAc): CH3OH/(CHCl3:EtOAc):CH3OH 80:20] to yield RhoB-NHBoc as a pink solid (75 mg, 39%). Two isomers were visible by 1H and 13C NMR in a ratio of ~3:1; 1H NMR (600 MHz, CD3CN): delta (p.p.m.) = 7.70(tt, J = 2.1, 5.2 Hz, 2H), 7.65 - 7.61 (m, 1H), 7.46 - 7.43 (m, 1H), 7.19 (d, J = 9.5 Hz, 2H), 6.97 (dd, J = 2.6, 9.6 Hz, 2H), 6.81 (d, J = 2.4 Hz, 2H),5.12 (s, 1H), 3.62 (qd, J = 3.2, 7.3 Hz, 8H), 3.20 (t, J = 6.3 Hz, 2H), 2.94 (s, 3H), 2.83 - 2.78 (m, 2H), 1.37 (s, 9H), 1.25 (t, J = 7.1 Hz, 12H); 13C NMR (151 MHz, CD3CN): delta (p.p.m.) = 169.5, 158.7, 156.6, 137.4, 133.1, 132.9, 131.9, 131.0, 130.6, 130.4, 130.2, 128.6, 128.3, 114.9, 96.9, 79.3, 47.8, 46.6, 38.6, 38.5, 28.6, 12.7; isolated signals of the minor conformer 1H, 13C: 1H NMR (600 MHz, CD3CN): delta (p.p.m.) = 7.59 (dd, J = 1.8, 7.3 Hz, 1H), 7.40 - 7.38 (m, 1H), 5.34 (s, 1H), 3.11 (s, 2H), 2.61 (s, 3H), 1.41 (s, 9H); 13C NMR (151 MHz, CD3CN): delta (p.p.m.) = 169.6, 158.8, 157.4, 156.6, 137.4, 130.9, 130.8, 114.6, 96.9, 79.6, 51.5, 38.8, 32.5; HRMS (ESI): m/z calculated for C36H47N4O4 [M]+ 599.3592, found 599.3568. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triethylamine; HATU In N,N-dimethyl-formamide at 20℃; for 16h; | 3.2. Synthesis of 3',6'-Bis(diethylamino)-2-(3-ethynylphenyl)spiro[isoindoline-1,9'-xanthen]-3-one (1) 3-Ethynyl-benzenamin (351.4 mg, 3 mmol) was added to a suspension of Rhodamine B (956.0 mg,2 mmol), HATU (1.141 g, 3 mmol), and Et3N (809.5 mg, 8 mmol) in DMF (15 mL) at room temperaturefor 16 h. Then, ethyl acetate and water were added. The separated aqueous phase was extracted withethyl acetate (3 30 mL). The combined organic phases were washed with water, dried with Na2SO4,and evaporated to dryness. Purication was carried out with silica gel (hexane/ethyl acetate = 4:1) toget the white solid 1. ESI/MS: 542.29 [M + H]+. 1H-NMR (400 MHz, DMSO-d6) δ 7.85 (d, J = 7.9 Hz, 1H), 7.53 (d, J = 1.9 Hz, 2H), 7.15 (s, 2H), 7.04 (d, J = 8.6 Hz, 1H), 6.92 (s, 1H), 6.82-6.74 (m, 1H), 6.51 (d,J = 8.7 Hz, 2H), 6.35 (d, J = 11.5 Hz, 2H), 6.26 (s, 2H), 4.08 (s, 1H), 3.26 (m, 8H), 1.05-1.00 (m, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With triethylamine; HATU In N,N-dimethyl-formamide at 20℃; for 16h; | 3.4. Synthesis of 2-(4-(But-3-yn-1-yloxy)butyl)-3',6'-bis(diethylamino)spiro[isoindoline-1,9'-xanthen]-3-one (2) The intermediate 9 2-(4-(but-3-yn-1-yloxy)butyl)isoindoline-1,3-dione (542.2 mg, 2 mmol) wasdissolved in EtOH (10 mL). Hydrazine hydrate (981.1 mg, 20 mmol) was added dropwise and thereaction was heated to reflux for 30 min until the white solid was not increased. The solvent wasremoved under reduction in vacuo. Then, ethyl acetate and water were added. The water layer wasadjusted to pH 3; the water phase was then collected and adjusted to pH 9 and extracted with ethylacetate (3 30 mL). The combined organic phases were washed with water, dried with Na2SO4,and evaporated to get the crude primary amine 4-(but-3-yn-1-yloxy)butan-1-amine. The primaryamine (253.8 mg, 1.5 mmol) was added to a suspension of Rhodamine B (956.0 mg, 2 mmol), HATU(1.141 g, 3 mmol), and Et3N (809.5 mg, 8 mmol) in DMF (15 mL) at room temperature for 16 h.Then, ethyl acetate and water were added. The separated aqueous phase was extracted with ethylacetate (3 x 30 mL). The combined organic phases were washed with water, dried with Na2SO4, andevaporated to dryness. Purication was carried out with silica gel (hexane/ethyl acetate = 5:1) to getthe pink solid 2. ESI/MS: 566.33 [M + H]+. 1H-NMR (400 MHz, Chloroform-d) δ 7.88 (d, J = 4.6 Hz,1H), 7.44-7.37 (m, 2H), 7.05 (d, J = 4.6 Hz, 1H), 6.45-6.34 (m, 4H), 6.25 (d, J = 8.8 Hz, 2H), 3.42-3.36 (m,2H), 3.36-3.27 (m, 8H), 3.24-3.18 (m, 2H), 3.13 (d, J = 8.1 Hz, 2H), 2.38-2.29 (m, 2H), 1.91 (s, 1H), 1.34 (t,J = 4.3 Hz, 2H), 1.25-1.17 (m, 2H), 1.15 (s, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With titanium(IV) oxide In water at 25℃; for 4h; UV-irradiation; | Photocatalytic degradation of the synthetic pollutant dye mixture was carried out in a digital photocatalytic reactor with some customized modifications as described in the supplementary information sheet (Section S2). The reaction volume was 50 ml with a 1-g/l photocatalyst dose of bare TiO2 or TiO2-PC composite. The suspension was magnetically stirred (at 500 RPM) at room temperature (25 ± 2 °C) for a preinitial 30 min under dark conditions to achieve the adsorption-desorption equilibrium on the photocatalysts. The stirring was continued for a further 240 min under constant UV exposure. Two milliliters of test solution were taken out at differenttime intervals (0, 30, 60, 90, 120, 150, 180 and 240 min) and centrifuged, and 1 ml of each was diluted with 2 ml of Millipore water for UV-visible spectroscopy scans. The experiments were repeated at least three times on consecutive days. However, the median data set was used for kinetic analyses. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: rhodamine B With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: 1,6-hexanediol With dmap In dichloromethane at 20℃; for 24h; | 1.1 1) Synthesis of rhodamine hexandiol 1 In a 50 mL three-neck round bottom flask,Rhodamine B 960 mg (2.01 mmol) was added,Dichloromethane 15mL as solvent,Add at room temperatureDicyclohexyl diimine 420 mg (2.04 mmol),Stirring at room temperature about reaction 1h;Additional hexanediol 240 mg (2.03 mmol) was added, and 248 mg (2.03 mmol) of 4,4-dimethylaminopyridine was added.Reaction at room temperature for 24h;The area where the LC-MS detected the most amount is the target product.The last band is hexyl glycol dihydroxy esterification material. Post-processing:It is not necessary to remove the solvent and wet it directly. Silica gel column chromatography,Gradient elution with a mixture of dichloromethane (EtOH) and ethanol (DCM)First use 40:1 to wash down the small polar substances and change to 20:1.The most concentrated elution of purple is the product,Spin-dry to a purple-red sticky solid. TLC is a characteristic spike with strong purple-red fluorescence.Rf = 0.15 (DCM/EtOH = 20:1).Rhodamine B: Rf=0.05(DCM/EtOH=20:1).Yield 70.0% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | rhodamine B (1000mg, 2.09mmol) was dissolved in DCM (50mL), oxalyl chloride (0.40mL, 4.44mmol) and 69 DMF (cat.) were added at 0C. After 2h of stirring the solvent was removed under diminished pressure. The residue was dissolved in DCM (50mL), 70 TEA (0.30mL, 2.15mmol), 71 DMAP (cat.) and 23 dehydroabietylamine (500mg, 1.75mmol) were added. After 12h stirring the solution was diluted with DCM (25mL), washed with HCl (2m, 3 x 30mL), water (2 x 30mL) and brine (30mL), and the organic phase was dried over MgSO4. The solvent was removed under diminished pressure. Column chromatography (silica gel, n-hexane/ethyl acetate, 8:2) gave 11 compound 17a (1052mg, 86%); RF=0.45 (silica gel, n-hexane/ethyl acetate, 8:2); mp=137-140C; [alpha]D=-19.1 (c=0.33, CHCl3); IR (KBr): v=3444s, 2966s, 2926m, 2868m, 1694s, 1634s, 1616vs, 1550m, 1514vs, 1466m, 1462m, 1376s, 1358s, 1328m, 1306m, 1266m1220s, 1118s, 756mcm-1; UV-vis (CHCl3): lambdamax (log epsilon)=278nm (4.46); 1H NMR (400MHz, CDCl3): delta=7.91-7.85 (m, 1H, 23-H), 7.46-7.38 (m, 2H, 25-H+26-H), 7.08-7.00 (m, 2H, 24-H+12-H), 6.90 (dd, J=8.1, 1.8Hz, 1H, 11-H), 6.85 (d, J=1.4Hz, 1H, 14-H), 6.39-6.23 (m, 5H, 30-H+31-H+31?-H+33-H+33?-H), 6.16 (dd, J=8.9, 2.5Hz, 1H, 30?-H), 3.36-3.23 (m, 8H, 35-H+35?-H), 3.15 (d, J=14.5Hz, 1H, 18-Ha), 2.88 (d, J=14.9Hz, 1H, 18-Hb), 2.85-2.73 (m, 3H, 7-Ha+7-Hb+15-H), 2.07-1.95 (m, 2H, 1-Ha+6-Ha), 1.70-1.57 (m, 1H, 6-Hb), 1.48-1.34 (m, 1H, 2-Ha), 1.28-1.21 (m, 1H, 2-Hb), 1.21 (d, J=6.9Hz, 6H, 16-H+17-H), 1.18-1.11 (m, 12H, 36-H+36?-H), 1.07 (s, 3H, 20-H), 1.06-0.99 (m, 1H, 1-Hb), 0.91-0.81 (m, 2H, 3-Ha+3-Hb), 0.72 (s, 3H, 19-H) ppm; 13C NMR (100MHz, CDCl3): delta=171.0 (C-21), 154.3 (C-27), 153.6 (C-34), 153.6 (C-34?), 148.8 (C-32), 148.8 (C-32?), 147.9 (C-9), 145.3 (C-13), 135.3 (C-8), 132.4 (C-25), 131.2 (C-22), 129.8 (C-31), 129.7 (C-31?), 128.0 (C-26), 126.9 (C-14), 124.3 (C-24), 123.9 (C-12), 123.5 (C-11), 122.7 (C-23), 108.3 (C-30), 108.3 (C-30?), 106.8 (C-29), 106.7 (C-29?), 98.0 (C-33), 97.8 (C-33?), 66.6 (C-28), 54.3 (C-18), 46.5 (C-5), 44.5 (C-35), 44.5 (C-35?), 38.2 (C-4), 37.9 (C-1), 37.7 (C-10), 37.0 (C-3), 33.6 (C-15), 30.3 (C-7), 25.7 (C-20), 24.2 (C-16), 24.1 (C-17), 19.6 (C-6), 19.0 (C-2), 19.0 (C-19), 12.7 (C-36), 12.7 (C-36?) ppm; MS (ESI, MeOH): m/z (%)=710.5 ([M+H]+, 100); analysis calculated for C48H59N3O2 (710.00): C 81.20, H 8.38, N 5.92; found: C 81.01, H 8.57, N 5.77. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 24h; | In a reaction vessel equipped with a stirrer,Rhodamine B 16.1 parts by mass,200 parts by mass of dichloromethane,Add 21.7 parts by mass of Alonics M-305 (manufactured by Toagosei Co., Ltd.) and 11.0 parts by mass of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, and stir at room temperature for 24 hours. It was made to react. After completion of the reaction, the organic layer was washed with ion exchanged water and dried by adding sodium sulfate. The solvent was removed under reduced pressure, the residue was purified by silica gel cam chromatography, a small amount of p-methoxyphenol was added as a polymerization inhibitor, and the solvent was evaporated under reduced pressure to obtain a dye A |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1,2-Diaminoethanetrityl resin (0.050g, 0.06mmol) was initially swelled in DCM (5mL) followed by DMF (5mL). N-Fmoc-Asp(OtBu)-OH (0.061g, 0.15mmol), PyBOP (0.078g, 0.15mmol) and DIPEA (0.10mL, 0.60mmol) in 0.5mL DMF was added to the peptide vessel containing resin beads and the coupling reaction was continued for 6h. The resin beads were washed with DMF (3×3mL) followed by washing with isopropanol (3×3mL). Completion of peptide coupling reaction was confirmed by performing the Kaiser test (KT). Then a solution of 20% piperidine in DMF (1×4mL; 2×3mL) was added to the peptide vessel to cleave NHFmoc protecting group. Resin beads were washed with DMF (3×3mL) followed by isopropanol (3×3mL) and the formation of free amine was confirmed by the Kaiser test. A series of amino acids such as <strong>[76265-69-5]Fmoc-Lys(Tfa)-OH</strong> (0.070g, 0.15mmol), Fmoc-8-aminocaprylic acid (0.057g, 0.15mmol), Fmoc-Phe-OH (0.058g, 0.15mmol), Fmoc-Phe-OH (0.058g, 0.15mmol) and Fmoc-8-aminocaprylic acid (0.057g, 0.15mmol) were coupled to the growing peptide chain in a similar way as mentioned before. After the deprotection of Fmoc group from the last amino acid, Fmoc-8-aminocaprylic acid, tris-tert-butylcarboxylic protected CYUE precursor 10 (0.052g, 0.09mmol), PyBOP (0.078g, 0.15mmol) and DIPEA (0.10mL, 0.6mmol) in 0.5mL DMF was added to the vessel and reacted for 6h. The completion of reaction was again confirmed by the Kaiser test. Finally, the trifluoroacetyl group of lysine was cleaved by 6-12h treatment with 2M aqueous piperidine at room temperature and the complete deprotection of Tfa was confirmed by the Kaiser test. Rhodamine B dye (0.043g, 0.09mmol), PyBOP (0.078g, 0.15mmol) and DIPEA (0.01mL, 0.6mmol) in 0.5mL DMF was added to the peptide vessel and swelled for 6h at room temperature. The completion of rhodamine B coupling reaction was confirmed by the Kaiser test. 4.2.3.5 General procedure for peptide cleavage from resin beads A mixture of 9.5mL trifluoroacetic acid (TFA), 0.25mL triisopropylsilane (TIPS), and 0.25mL H2O was prepared, and 5mL of this cocktail solution was added to resin beads and nitrogen was bubbled through the solution for 30min. Same procedure was repeated twice using 2.5mL (15min each) of cocktail solution. The collected mother liquor from cleavage was evaporated under reduced pressure and the concentrated viscous liquid was precipitated in ice cold diethyl ether. The precipitated product was dried under nitrogen atmosphere, the crude product was purified through HPLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A 200 ml four-necked flask was charged with 9.6 parts of Rhodamine B (manufactured by Tokyo Chemical Industry Co., Ltd.), 32 parts of DMF, 10 parts of benzyl bromide (manufactured by Tokyo Chemical Industry Co., Ltd.) and 3.3 parts of potassium carbonate, and 2 at 90C. Stir for hours. After cooling the reaction solution, 6.4 parts of potassium salt of bistrifluoromethanesulfonylimide (manufactured by Morita Chemical Industry Co., Ltd.) was further stirred for 1 hour. The obtained reaction solution was poured into water, and the precipitated crystals were collected by filtration, washed and dried,In the above specific example 20 parts of a xanthene compound represented by No. 3. | ||
A 200 ml four-necked flask was charged with 9.6 parts of Rhodamine B (manufactured by Tokyo Chemical Industry Co., Ltd.), 32 parts of DMF, 10 parts of benzyl bromide (manufactured by Tokyo Chemical Industry Co., Ltd.) and 3.3 parts of potassium carbonate were put,The mixture was stirred at 90C for 2 hours. After cooling the reaction solution, 6.4 parts of potassium salt of bistrifluoromethanesulfonylimide (manufactured by Morita Chemical Industry Co., Ltd.) was further stirred for 1 hour. The obtained reaction solution was poured into water, and the precipitated crystals were collected by filtration, washed and dried to give the above-mentioned specific example.No. Three20 parts of a xanthene compound represented by No.3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: rhodamine B With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In 1,2-dichloro-ethane at 20℃; for 2h; Stage #2: 2-Hydroxybenzylamine In 1,2-dichloro-ethane for 24h; | 12.1 Step 1: A method for preparing rhodamine fluorescent probes, dissolving 0.01-100 mol rhodamine B, 0.01-100 mol benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate in Add 0.01-100 mol of triethylamine to 5-500 mL of anhydrous 1,2-dichloroethane. Stir at room temperature for 2 hours, then add 0.005-100 mol 2-hydroxybenzylamine and react for 24 hours. The reaction solution is concentrated, and the solid fluorescent probe molecule A-2 is obtained after column chromatography. The yield was 65%. |
65% | Stage #1: rhodamine B With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In 1,2-dichloro-ethane at 20℃; for 2h; Stage #2: 2-Hydroxybenzylamine In 1,2-dichloro-ethane at 20℃; |
Tags: 81-88-9 synthesis path| 81-88-9 SDS| 81-88-9 COA| 81-88-9 purity| 81-88-9 application| 81-88-9 NMR| 81-88-9 COA| 81-88-9 structure
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :