* 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.
Stage #1: With sodium hydrogencarbonate In toluene at 80 - 90℃; for 10.5 h; Stage #2: With sodium hydroxide In water at 70 - 80℃; for 8.5 h; Reflux
In the flask was added 282g four iminodiacetic acid (2. lmol, content 99percent), 300ml of toluene, stirring and dissolving the sodium bicarbonate catalyst was added 101g (l. 2mol), warmed to 80 ° C, was added dropwise dichloroethane burn lOOg (lmol), 4h addition was completed, then 80-90 ° C insulation reaction 6. 5h, cooling filter back; In the reaction flask 604g32percent sodium hydroxide was added 800ml of water, heated to boiling under reflux condition, followed by the above-mentioned substituted condensate uniformly added dropwise to liquid caustic soda, 3. 5h completion of the addition, and then at that temperature insulation 4. 5h, cooled to 70-80 ° C was added 0.5percent by weight stock solution of the activated carbon decolorization 0. 5h, filtered; was added 31percent hydrochloric acid to a pH of between 1-2 can, to cool 30-40 ° C, centrifuging, then drying the acquired EDTA products 557g, content of 99.53percent, a yield of 95.29percent.
While stirring at 0 ° C into ethanol, slowly add the thionyl chloride and keep stirring until the temperature has reached about room temperature for about half an hour. Iminodiacetic acid (Formula 4, 3.33 g, 25 mmol) was then added and the temperature was raised to reflux overnight. After cooling to room temperature, the reaction was quenched with saturated sodium bicarbonate solution (20 mL) and solid sodium bicarbonate added to adjust the pH to neutral. After most of the ethanol was distilled off under reduced pressure, it was extracted three times with ethyl acetate (3 × 20 mL). The organic phases are combined, washed once with brine, filtered through a pad of magnesium sulfate and dried, Diethyl iminodiacetate (formula 5, 4.15 g, 88percent yield) was obtained by distillation under reduced pressure (recovery of organic solvent)
9.04 g
for 24 h; Reflux
About 11 g of iminodiacetic acid (0.0826 mol) was dispersedin 75 ml of absolute ethanol. To this 6 ml of concentrated sulfu-ric acid was added dropwise over time and the reaction mixturewas refluxed for 24 h. Then the mixture was allowed to cool downto room temperature and the excess acid was neutralized with 1 Msodium hydroxide. The organic layer was collected by filtration andthe filtrate was diluted with 200 ml of dichloromethane. This wasthen washed three times with 50 ml brine solution in each step.The organic layer was evaporated under vacuum to get a yellowishliquid. Yield: 9.04 g.
44.7 g
Inert atmosphere; Cooling with ice; Reflux
Diethyliminodiacetate 1 was purchased from Aldrich or prepared using a procedure adapted from the literature (Kuehn, T.; Schwalbe, H. J. Am. Chem. Soc. 2000, 122, 6169). An oven-dried 2-neck round bottom flask containing a magnetic stir bar was fitted with a pressure equalizing addition funnel and reflux condenser with a nitrogen inlet adapter. Anhydrous ethanol (EtOH, 750 mL) was added to the flask; the flask was immersed in an ice-water bath. The addition funnel was charged with thionyl chloride (SOCl2, 110 mL, 1503 mmol); SOCl2 was added drop-wise to the EtOH with stirring. Once SOCl2 addition was complete, iminodiacetic acid (50 g, 376 mmol) was added to the reaction mixture. The flask was transferred into a heated oil bath; the suspension was heated to reflux; the white suspension gradually became more translucent, ultimately becoming clear and colorless. The reaction mixture was refluxed overnight. The flask was removed from the oil bath, and the mixture was allowed to cool to room temperature. 2.5percent aq. sodium bicarbonate (NaHCO3, 200 mL) was added cautiously to the reaction mixture with vigorous stirring. Small portions of anhydrous NaHCO3 were then added to the stirred mixture until gas evolution ceased. The mixture was vacuum filtered through paper and concentrated by rotary evaporation yielding an oil floating on a clear, aqueous solution. The biphasic mixture was transferred into a reparatory funnel with 1:1 saturated aq. NaCl (brine)/H2O (200 mL). The aqueous layer was extracted with dichloromethane (CH2Cl2, 1×100 mL, then 2×50 mL). The CH2Cl2 layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered through paper and concentrated by rotary evaporation to a pale tan oil. This oil was distilled under reduced pressure (95° C. distillate at 0.65 torr) affording diethyliminodiacetate (1, 44.7 g) as a clear oil. 1H NMR (400 MHz, CDCl3) δ ppm 4.20 (q, J=7.2 Hz, 4H), 3.46 (s, 4H), 2.04 (br. s., 1H), 1.28 (t, J=7.1 Hz, 6H).
Reference：
[1] Journal of Organic Chemistry, 1988, vol. 53, # 9, p. 1966 - 1969
[2] Journal of the American Chemical Society, 2000, vol. 122, # 26, p. 6169 - 6174
[3] Patent: CN105949080, 2016, A, . Location in patent: Paragraph 0018
[4] Tetrahedron Letters, 2008, vol. 49, # 36, p. 5293 - 5296
[5] Helvetica Chimica Acta, 1993, vol. 76, # 2, p. 893 - 899
[6] Polish Journal of Chemistry, 1990, vol. 64, # 1-6, p. 333 - 338
[7] Journal of the American Chemical Society, 1999, vol. 121, # 1, p. 8 - 13
[8] European Journal of Inorganic Chemistry, 2011, # 27, p. 4168 - 4174
[9] Journal of Organic Chemistry USSR (English Translation), 1974, vol. 10, # 3, p. 462 - 464[10] Zhurnal Organicheskoi Khimii, 1974, vol. 10, # 3, p. 457 - 460
[11] Inorganic Chemistry Communications, 2013, vol. 35, p. 311 - 314
[12] Electrochimica Acta, 2014, vol. 137, p. 557 - 563
[13] Langmuir, 2016, vol. 32, # 47, p. 12476 - 12487
[14] Patent: US9469725, 2016, B2, . Location in patent: Page/Page column 9; 10; 11
4
[ 142-73-4 ]
[ 6290-05-7 ]
Yield
Reaction Conditions
Operation in experiment
92%
With trifluoroborane diethyl ether In ethanol
5. To a magnetically stirred suspension of iminodiacetic acid (50 g, 0.376 mol) in absolute ethanol (1000 ml) under N2 was added boron trifluoride etherate (100 g, 1.127 mmol). The reaction mixture was refluxed for 3 days and concentrated in vacuo to a volume of 150 ml. A saturated NH4 Cl solution (500 ml) was added and the reaction mixture was extracted with CH2 Cl2 (3*250 ml). The combined organic layers were dried and concentrated in vacuo. The crude product was distilled at 10 mm Hg to give 65.2 g (92percent yield) of iminodiacetic acid, diethyl ester as a colorless liquid.
Reference：
[1] Patent: US4981985, 1991, A,
5
[ 142-73-4 ]
[ 6290-05-7 ]
Reference：
[1] Patent: US4389528, 1983, A,
6
[ 50-00-0 ]
[ 72-48-0 ]
[ 142-73-4 ]
[ 3952-78-1 ]
Reference：
[1] Journal of the Chemical Society, 1958, p. 2390,2392
7
[ 67-56-1 ]
[ 142-73-4 ]
[ 39987-25-2 ]
Yield
Reaction Conditions
Operation in experiment
81%
Stage #1: at -20 - -10℃; Stage #2: at -20 - 20℃; for 72 h;
Methanol (500 mL) was cooled to –20 °C, and SOCl2 (36 mL, 0.5 mol) was added dropwise under vigorous stirring while maintaining the temperature of the reaction mixture below –10 °C. Iminodiacetic acid(13.3 g, 0.1 mol) was then added in one portion. The reaction mixture was stirred for 24 h at r.t. and then left to stand at r.t. for two days.The volatiles were evaporated, and the residue were crystallized from methanol. Yield: 16 g (81percent); white crystalline solid.1H NMR (300 MHz, D2O): δ = 4.13 (s, 4 H), 3.85 (s, 6 H).13C NMR (75 MHz, D2O): δ = 168.08, 54.12, 47.66. Anal. Calcd for C6H12ClNO4: C, 36.47; H, 6.12; N, 7.09. Found: C, 36.52;H, 6.01; N, 6.98.
With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 48 h;
A mixture of iminodiacetic acid (5.1 g, 38.3 mmol) and sodium hydrogen carbonate (NaHCO3, 12.9 g, 153 mmol) were dissolved in 50 mL of water. Once the bubbling subsided, 50 mL of THF was added followed by 10.0 g (46.0 mmol) of BOC2O. The mixture was stirred at ambient temperature for 2 days when starting materials were completely consumed as detected by ESI. The reaction was worked up by removing THF and washing the aqueous layer with Et2O twice. The pH of the aqueous layer was then adjusted to 1 using conc. HCl. The product was extracted with EtOAc and solvent removed in vacuo to provide the product as a white solid. The product was purified by crystallization from EtOAc to give 8.04 g (90percent) of clear crystals of 27. ES MS [M-H]-232. 1.
90%
With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 48 h;
A mixture of iminodiacetic acid (5.1 g, 38.3 mmol) and sodium hydrogen carbonate (NaHC03, 12.9 g, 153 mmol) were dissolved in 50 mL of water. Once the bubbling subsided, 50 mL of THF was added followed by 10.0 g (46.0 mmol) of BOC20. The mixture was stirred at ambient temperature for 2 days when starting materials were completely consumed as detected by ESI. The reaction was worked up by removing THF and washing the aqueous layer with Et2O twice. The pH of the aqueous layer was then adjusted to 1 using conc. HCI. The product was extracted with EtOAc and solvent removed in vacuo to provide the product as a white solid. The product was purified by crystallization from EtOAc to give 8.04 g (90percent) of clear crystals of 27. ES MS [M-H]- 232.1.
67%
With sodium hydroxide In 1,4-dioxane at 0 - 20℃;
To a stirred solution of iminodiacetic acid (2 g, 15 mmol) in a dioxane/H2O (3/1, 40 mL) mixture, were added at 0 °C, Boc2O (3.93 g, 18 mmol) and 10 mL of 2 N NaOH solution. The mixture was stirred at room temperature and dioxane was evaporated under reduced pressure. The aqueous layer was acidified with a 20percent citric acid solution and extracted with AcOEt. The organic layer was dried over MgSO4 and evaporated to give 17a (67percent), as a white solid directly used in the next step.
44%
With sodium hydroxide In 1,4-dioxane; water at 20℃; for 72 h;
Iminodiacetic acid (13.3g, lOOmmol), dioxane (200mfc), and NaOH (8g, 200mmol) dissolved in 200mNo. of water were added into a 1 .pound.fiask, and stirred until the mixture formed a uniform solution. Di-t-butyldicarbonate (25 va.1, HOmmol) was added into the solution, which was stirred for 72h at room temperature. Then, the reaction mixture was washed with ether (2χl00ml).The aqueous layer was acidified with 10percent aqueous HCl (100m.pound.), and extracted with ethylacetate (3x150m.pound.). The collected organic layer was washed with saturated aqueous NaCl (2χ150mNo.), from which moisture was removed with Na2SO4. And, the resulting mixture was recrystallized (ethylacetate : hexane = 1 : 2) to obtain colorless crystal.Yield: 10.33g (44percent)1H-NMR(Acetone-d6, 400MHz) : 4.12 and 4.08(two s, 4H), 1.4(s, 9H)
Reference：
[1] Journal of Medicinal Chemistry, 1996, vol. 39, # 8, p. 1601 - 1608
[2] Patent: WO2004/35576, 2004, A2, . Location in patent: Page 170
[3] Patent: WO2005/117904, 2005, A2, . Location in patent: Page/Page column 404-405
[4] Tetrahedron, 1996, vol. 52, # 29, p. 9793 - 9804
[5] Bioorganic and Medicinal Chemistry, 1998, vol. 6, # 8, p. 1347 - 1378
[6] Pharmazie, 2001, vol. 56, # 1, p. 58 - 60
[7] Tetrahedron Letters, 1994, vol. 35, # 12, p. 1863 - 1866
[8] European Journal of Medicinal Chemistry, 2015, vol. 90, p. 547 - 567
[9] Bioorganic and Medicinal Chemistry, 2001, vol. 9, # 4, p. 837 - 846
[10] Organic Letters, 2015, vol. 17, # 15, p. 3930 - 3933
[11] Patent: WO2007/108566, 2007, A1, . Location in patent: Page/Page column 7; 9-10
[12] Patent: EP1443046, 2004, A1, . Location in patent: Page 42
[13] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 4, p. 708 - 712
[14] Patent: CN106631879, 2017, A, . Location in patent: Paragraph 0025-0027
Example 1 Compound 2: N-t-Boc-iminodiacetic Acid A mixture of iminodiacetic acid (1, 2 g, 15.03 mmol), di-t-butyl dicarbonate (3.9 g, 18.0 mmol), and sodium hydroxide (0.721 g, 18.0 mmol) in water (50 mL) was stirred at room temperature for 18 hours. The reaction solution was washed with 20 mL of methylene chloride (CH2Cl2) followed by adjusting pH to 2.5 with 6 N HCl. The resulting mixture was extracted with ethyl acetate (2*300 mL) and the combined organic layer was dried over anhydrous magnesium sulfate (MgSO4). The solvent was removed in vacuo to give 1.0 g (29percent) of 2. 1H NMR (270 MHz, DMSO-d6) δ1.36 (s, 9H), 3.88 (s, 2H), 3.92 (s, 2H), 13.69 (bs, 2H). 13C NMR (67.80 MHz, DMSO-d6) δ27.84, 49.12, 49.64, 79.59, 154.79, 171.20.
Reference：
[1] Patent: US6395266, 2002, B1,
11
[ 24424-99-5 ]
[ 142-73-4 ]
[ 56074-20-5 ]
Yield
Reaction Conditions
Operation in experiment
29%
With hydrogenchloride; sodium hydroxide In water
Example 1 Compound 2: N-t-Boc-iminodiacetic Acid A mixture of iminodiacetic acid (1, 2 g, 15.03 mmol), di-t-butyl dicarbonate (3.9 g, 18.0 mmol), and sodium hydroxide (0.721 g, 18.0 mmol) in water (50 mL) was stirred at room temperature for 18 hours. The reaction solution was washed with 20 mL of methylene chloride (CH2 Cl2) followed by adjusting pH to 2.5 with 6 N HCl. The resulting mixture was extracted with ethyl acetate (2*300 mL) and the combined organic layer was dried over anhydrous magnesium sulfate (MgSO4). The solvent was removed in vacuo to give 1.0 g (29percent) of 2. 1 H NMR (270 MHz, DMSO-d6)δ 1.36 (s, 9H), 3.88 (s, 2H), 3.92 (s, 2H), 13.69 (bs, 2H). 13 C NMR (67.80 MHz, DMSO-d6) δ 27.84, 49.12, 49.64, 79.59, 154.79, 171.20.
Reference：
[1] Patent: US6153655, 2000, A,
12
[ 142-73-4 ]
[ 56074-20-5 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 7, p. 2404 - 2406
13
[ 142-73-4 ]
[ 75-65-0 ]
[ 85916-13-8 ]
Reference：
[1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1988, vol. 42, # 6, p. 373 - 377
In the flask was added 282g four iminodiacetic acid (2. lmol, content 99%), 300ml of toluene, stirring and dissolving the sodium bicarbonate catalyst was added 101g (l. 2mol), warmed to 80 C, was added dropwise dichloroethane burn lOOg (lmol), 4h addition was completed, then 80-90 C insulation reaction 6. 5h, cooling filter back; In the reaction flask 604g32% sodium hydroxide was added 800ml of water, heated to boiling under reflux condition, followed by the above-mentioned substituted condensate uniformly added dropwise to liquid caustic soda, 3. 5h completion of the addition, and then at that temperature insulation 4. 5h, cooled to 70-80 C was added 0.5% by weight stock solution of the activated carbon decolorization 0. 5h, filtered; was added 31% hydrochloric acid to a pH of between 1-2 can, to cool 30-40 C, centrifuging, then drying the acquired EDTA products 557g, content of 99.53%, a yield of 95.29%.
Iminodiacetic acid (26.6 g, 0.2 mol) was dissolved in 2 M NaOH (200mL) and the resulting solution was cooled in an ice bath. Benzyloxycarbonyl chloride (37.5 g, 31.4 mL, 0.22 mol) and 2 M NaOH (120 mL) were subsequently added to the stirred solution, the reaction mixture was stirred at r.t. for 6 h and then washed with Et2O (2 × 100 mL). The aqueous phase was acidified with conc. HCl to pH 1-2 and extractedwith Et2O (3 × 200 mL). The organic extract was dried over Na2SO4and evaporated. The product was used in the subsequent reactionswithout further purification. Yield: 51 g (95%); colorless viscous oil. 1H NMR (300 MHz, CDCl3): delta = 10.37 (s, 1 H), 8.53 (s, 1 H), 7.38-7.23(m, 5 H), 5.14 (s, 2 H), 4.16 (s, 2 H), 4.11 (s, 2 H).13C NMR (75 MHz, CDCl3): delta = 174.10, 173.39, 156.09, 135.45, 128.55,128.31, 127.86, 68.50, 50.06, 49.94.
60%
A mixture of 2,2-<strong>[142-73-4]iminodiacetic acid</strong> (150 g, 1.13 mol) and aqueous sodiumhydroxide solution (2 N, 1.5 L, 3 mol) was stirred at 0 C for 30 minutes. After drop-wiseaddition of benzyl chloroformate (211 g, 1.24 mol) at 0 C, the reaction mixture wasstirred at 10 C for 18 hours. The reaction mixture was then washed with ethyl acetate (1 L), and the aqueous layer was acidified to a pH of approximately 2 and extracted with ethyl acetate (2 x 1 L). These two organic layers were combined, dried over sodium sulfate, filtered, and concentrated in vacuo to provide the product as a yellow gum. Yield: 180 g, 0.674 mol, 60%. 1H NMR (400 MHz, CDCI3) oe 8.07 (br s, 2H), 7.27-7.37(m, 5H), 5.16 (5, 2H), 4.19 (br s, 2H), 4.13 (br s, 2H).
With sodium hydroxide; In water; at 0 - 20℃;
To a solution of N- (carboxymethyl) glycine (13. 31 g, 100.00 mmol) in aqueous 2N NaOH (100 mL) was added a solution of benzylchloroformate (18.77 g, 110.00 mmol) in aqueous 2N NaOH (55 mL) at 0 C. The reaction was stirred at room temperature overnight and washed with Et20. The aqueous layer was acidified to pH 2 with aqueous IN HC1 solution and extracted four times with Et2O. The combined organic layers were dried over MgS04, filtered, and concentrated in vacuo to afford the product as a clear oil. 'HNMR (400 MHz, CDC13) 8 10.25 (br s, 1H), 8.71 (br s, 1H), 7.34-7. 17 (m, 5H), 5.14 (s, 2H), 4.16 (s, 2H), 4.11 (s, 2H). ES MS M+1 = 268
With sodium hydroxide; at 20℃; for 2h;Cooling with ice;
To a solution of <strong>[142-73-4]iminodiacetic acid</strong> (266 mg, 2.0 mmol) in 2 N NaOH solution in an ice bath, was added benzyl chloroformate (337 mL, 2.4 mmol). The mixture was stirred at room temperature for 2 h and extracted twice with Et2O. The aqueous layer was acidified to pH 2 and extracted with Et2O (3 times). The organic layers were dried over MgSO4 and evaporated under reduced pressure to give 24a as a colourless oil directly used in the next step. Yield 64%. tR, LCMS 3.49 min, Purity 98%; MS (ESI): m/z 266(MH).
While stirring at 0 C into ethanol, slowly add the thionyl chloride and keep stirring until the temperature has reached about room temperature for about half an hour. Iminodiacetic acid (Formula 4, 3.33 g, 25 mmol) was then added and the temperature was raised to reflux overnight. After cooling to room temperature, the reaction was quenched with saturated sodium bicarbonate solution (20 mL) and solid sodium bicarbonate added to adjust the pH to neutral. After most of the ethanol was distilled off under reduced pressure, it was extracted three times with ethyl acetate (3 × 20 mL). The organic phases are combined, washed once with brine, filtered through a pad of magnesium sulfate and dried, Diethyl iminodiacetate (formula 5, 4.15 g, 88% yield) was obtained by distillation under reduced pressure (recovery of organic solvent)
9.04 g
With sulfuric acid; for 24h;Reflux;
About 11 g of iminodiacetic acid (0.0826 mol) was dispersedin 75 ml of absolute ethanol. To this 6 ml of concentrated sulfu-ric acid was added dropwise over time and the reaction mixturewas refluxed for 24 h. Then the mixture was allowed to cool downto room temperature and the excess acid was neutralized with 1 Msodium hydroxide. The organic layer was collected by filtration andthe filtrate was diluted with 200 ml of dichloromethane. This wasthen washed three times with 50 ml brine solution in each step.The organic layer was evaporated under vacuum to get a yellowishliquid. Yield: 9.04 g.
44.7 g
With thionyl chloride;Inert atmosphere; Cooling with ice; Reflux;
Diethyliminodiacetate 1 was purchased from Aldrich or prepared using a procedure adapted from the literature (Kuehn, T.; Schwalbe, H. J. Am. Chem. Soc. 2000, 122, 6169). An oven-dried 2-neck round bottom flask containing a magnetic stir bar was fitted with a pressure equalizing addition funnel and reflux condenser with a nitrogen inlet adapter. Anhydrous ethanol (EtOH, 750 mL) was added to the flask; the flask was immersed in an ice-water bath. The addition funnel was charged with thionyl chloride (SOCl2, 110 mL, 1503 mmol); SOCl2 was added drop-wise to the EtOH with stirring. Once SOCl2 addition was complete, iminodiacetic acid (50 g, 376 mmol) was added to the reaction mixture. The flask was transferred into a heated oil bath; the suspension was heated to reflux; the white suspension gradually became more translucent, ultimately becoming clear and colorless. The reaction mixture was refluxed overnight. The flask was removed from the oil bath, and the mixture was allowed to cool to room temperature. 2.5% aq. sodium bicarbonate (NaHCO3, 200 mL) was added cautiously to the reaction mixture with vigorous stirring. Small portions of anhydrous NaHCO3 were then added to the stirred mixture until gas evolution ceased. The mixture was vacuum filtered through paper and concentrated by rotary evaporation yielding an oil floating on a clear, aqueous solution. The biphasic mixture was transferred into a reparatory funnel with 1:1 saturated aq. NaCl (brine)/H2O (200 mL). The aqueous layer was extracted with dichloromethane (CH2Cl2, 1×100 mL, then 2×50 mL). The CH2Cl2 layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered through paper and concentrated by rotary evaporation to a pale tan oil. This oil was distilled under reduced pressure (95 C. distillate at 0.65 torr) affording diethyliminodiacetate (1, 44.7 g) as a clear oil. 1H NMR (400 MHz, CDCl3) delta ppm 4.20 (q, J=7.2 Hz, 4H), 3.46 (s, 4H), 2.04 (br. s., 1H), 1.28 (t, J=7.1 Hz, 6H).
General procedure: Iminodiaceticacid (13.6 g 100 mM) and 1,2-phenylenediamine (21.6 g, 200 mM)were refluxed for 24 h in 4 N HCl (80 mL), the resulting solutionwascooled to isolate the hydrochloride of the compound, then it wasneutralized using aqueous ammonia. The product obtained was recrystallizedfrom aqueous methanol. Yield: 72%, M.P 248 ± 2 C.Elemental analysis for C16H15N5; Calc C 69.30, H 5.45, N.25.30;found: C 69.18; H, 5.32, N. 25.24. MS (IE, m/z %): 275 [M], 276[M1], 132 (100) [C8H8N2], 118 (8.9) [C7H6N2], 146 (24.6%)[C8H8N3]: 1H NMR (300, MHz, CD3OD): d 3.310e4.111 (m, 4H,bzimeCH2eN.), 4.917 (s, H, eCH2eNHeCH2e) and 7.200e7.550 (m,8H, bzim-rings). 13C NMR (300, MHz, CD3OD): d 48.860e49.428(CH2eNe) and 123.628e155.124 (bzim-rings).
66%
In ethylene glycol; at 200℃;
The ligands were synthesised using a modified version of the conditions detailed by V. O. Rodionov et.al. ( J . Am. Chem. Soc., 129 (42), (2007), 12696-704). o-Phenylenediamine (4.55 g, 42.1 mmols), nitrilodiacetic acid (2.80 g, 20.9 mmols) and ethylene glycol (45 ml) were all added to an appropriate round bottom flask, which was then heated to 200C under stirring, at which point the brown solution became purple. The reaction was left overnight under reflux using a waterless condenser. The flask was removed from the heat and left to cool to room temperature. Once cooled, the contents were transferred to a beaker and ice water was added, forming a precipitate. The mixture was stirred for 5 minutes at room temperature, after which it was filtered in vacuo to give a pink solid. The precipitate was left to dry overnight. The crude product was recrystallized from ethanol/water and left to dry in air, affording a pure light brown solid. Yield 66%. dH/ppm (400 MHz, DMSO) 12.27 (s, 2H), 7.54-7.50 (m, 4H), 7.16-7.07 (m, 4H), 3.98 (s, 4H); m/z (ES-ToF); 278.14 ([M+H]+).
32.3%
With hydrogenchloride; In water; for 72h;Reflux;
The ligand was prepared according to Matthews et al. [45]. Iminodiacetic acid (6.65 g, 50 mmol) ando-phenylenediamine (10.82 g, 100 mmol) were mixed in a solution of 18% HCl (100 mL).The solution was heated under reflux for 3 days. A green precipitate formed after cooling was dissolvedafter the addition of water (300 mL). The solution was stirred and ammonia (28%) was added until thepH of the solution became 9. During the addition of ammonia, a light brown precipitate was obtained.The precipitate was collected on a frit, washed several times with water and dried at 40 C. Yield: 32.3%.Anal. Calcd. for abb·4H2O: C, 55.0; H, 6.6; N, 20.0; S, 0.0. Found: C, 55.0; H, 6.6; N, 19.5; S, 0.0%.IR (cm-1): 405w, 447w, 480w, 533w, 742vs, 767m, 876m, 1015m, 1110m, 1222m, 1273vs, 1310w,1331m, 1438vs, 1454s, 1532w, 1623m, 2851m, 3055s, 3226s, 3368m. UV-Vis (MeOH/nm): 324,378, 428.
In ethylene glycol; at 200℃; for 8h;
<strong>[142-73-4]iminodiacetic acid</strong> (0.1 mol, 13.3 g) and o-phenylenediamine (0.2 mol, 21.6 g),With 100mL of ethylene glycol as solvent, the reaction was refluxed at 200 C for about 8 hours until no water vapor bubbles were released. After cooling to room temperature, the reaction mixture was poured into 200mL of distilled water and cooled to room temperature to give a white viscous solid An excess of absolute ethanol was added, allowed to stand overnight, filtered to give an off-white solid product which was washed with a small amount of acetone, filtered with suction and recrystallized from anhydrous methanol to giveN, N-bis (2-benzimidazolylmethyl)Imine (IDB).
Synthesis of Compound 7 Iminodiacetate (10.0 g, 75.1 mmol) and BF3·OEt2 (22 ml, 173 mmol) were dissolved in anhydrous methanol (50 ml) and flown for 5 hours under argon atmosphere. Then, the mixture solution was neutralized with a saturated aqueous sodium bicarbonate solution, and extraction with chloroform was performed. Triethylamine was added to an aqueous phase until the pH thereof becomes 9, and extraction with chloroform was performed again. The extract was dried with an anhydrous sodium sulfate as a drying agent. Thereafter, the drying agent was filtered out from the dried residue to obtain a filtrate. The filtrate was concentrated under reduced pressure to obtain a yellow oily object serving as Compound 7 (9.61 g, yield of 79 %). 1H-NMR (400 MHz, CDCl3) measurement was conducted on Compound 7 so obtained to find that delta3.74 (6H, s, OMe), 3.48 (4H, s, CH2N), 2.00 (1H, s, NH). An ESI-MS (positive) measurement was conducted on Compound 7 to find that the m/z was 162.1[(M+H)+]. This could examine a structure of Compound 7. It is to be noted that a molecular mass of the Compound 7 is C6H11NO2: 161.07.
With thionyl chloride;
Iminodiacetic acid was stirred overnight in an 80/20 MeOH/SOCl2 mixture. The diester obtained after evaporation under reduced pressure (300 mg, 1.52 mmol) was dissolved in CH2Cl2 (10 mL) and DIEA (792 muL, 4.56 mmol) and benzoylchloride (176 muL, 1.52 mmol) were added. The mixture was stirred overnight at room temperature and washed with HCl 0.5 N and NaHCO3 10% solutions. The organic layer was dried over MgSO4 and evaporated to give the desired diester as a colourless oil (99%). The former compound (400 mg, 1.5 mmol) was saponified with NaOH (6 mmol) in MeOH (5 mL) and H2O (1 mL). After evaporation of MeOH under reduced pressure, HCl 1 N was added to the residue and the aqueous layer was extracted 3 times with AcOEt to give (benzoyl-carboxymethyl-amino)acetic acid (20a) directly used in the next step. White powder. Yield 98 Purity 98%; MS (ESI+): m/z = 238 (M+H)+.
With sodium hydrogencarbonate; In tetrahydrofuran; water; at 20℃; for 48h;
A mixture of <strong>[142-73-4]iminodiacetic acid</strong> (5.1 g, 38.3 mmol) and sodium hydrogen carbonate (NaHCO3, 12.9 g, 153 mmol) were dissolved in 50 mL of water. Once the bubbling subsided, 50 mL of THF was added followed by 10.0 g (46.0 mmol) of BOC2O. The mixture was stirred at ambient temperature for 2 days when starting materials were completely consumed as detected by ESI. The reaction was worked up by removing THF and washing the aqueous layer with Et2O twice. The pH of the aqueous layer was then adjusted to 1 using conc. HCl. The product was extracted with EtOAc and solvent removed in vacuo to provide the product as a white solid. The product was purified by crystallization from EtOAc to give 8.04 g (90%) of clear crystals of 27. ES MS [M-H]-232. 1.
90%
With sodium hydrogencarbonate; In tetrahydrofuran; water; at 20℃; for 48h;
A mixture of <strong>[142-73-4]iminodiacetic acid</strong> (5.1 g, 38.3 mmol) and sodium hydrogen carbonate (NaHC03, 12.9 g, 153 mmol) were dissolved in 50 mL of water. Once the bubbling subsided, 50 mL of THF was added followed by 10.0 g (46.0 mmol) of BOC20. The mixture was stirred at ambient temperature for 2 days when starting materials were completely consumed as detected by ESI. The reaction was worked up by removing THF and washing the aqueous layer with Et2O twice. The pH of the aqueous layer was then adjusted to 1 using conc. HCI. The product was extracted with EtOAc and solvent removed in vacuo to provide the product as a white solid. The product was purified by crystallization from EtOAc to give 8.04 g (90%) of clear crystals of 27. ES MS [M-H]- 232.1.
67%
With sodium hydroxide; In 1,4-dioxane; at 0 - 20℃;
To a stirred solution of <strong>[142-73-4]iminodiacetic acid</strong> (2 g, 15 mmol) in a dioxane/H2O (3/1, 40 mL) mixture, were added at 0 C, Boc2O (3.93 g, 18 mmol) and 10 mL of 2 N NaOH solution. The mixture was stirred at room temperature and dioxane was evaporated under reduced pressure. The aqueous layer was acidified with a 20% citric acid solution and extracted with AcOEt. The organic layer was dried over MgSO4 and evaporated to give 17a (67%), as a white solid directly used in the next step.
44%
With sodium hydroxide; In 1,4-dioxane; water; at 20℃; for 72h;
Iminodiacetic acid (13.3g, lOOmmol), dioxane (200mfc), and NaOH (8g, 200mmol) dissolved in 200mNo. of water were added into a 1 £fiask, and stirred until the mixture formed a uniform solution. Di-t-butyldicarbonate (25 va.1, HOmmol) was added into the solution, which was stirred for 72h at room temperature. Then, the reaction mixture was washed with ether (2chil00ml).The aqueous layer was acidified with 10% aqueous HCl (100m£), and extracted with ethylacetate (3x150m£). The collected organic layer was washed with saturated aqueous NaCl (2chi150mNo.), from which moisture was removed with Na2SO4. And, the resulting mixture was recrystallized (ethylacetate : hexane = 1 : 2) to obtain colorless crystal.Yield: 10.33g (44%)1H-NMR(Acetone-d6, 400MHz) : 4.12 and 4.08(two s, 4H), 1.4(s, 9H)
With sodium hydroxide; In 1,4-dioxane; water; at 20℃; for 22h;
<strong>[142-73-4]iminodiacetic acid</strong> (10.00 g) was dissolved in a mixed solution of 1, 4-dioxane (160 ML) and water (80 ML).. To this were added a 1N aqueous sodium hydroxide solution (160 ML) and then di-tert-butyl dicarbonate (18.04 g).. The solution was stirred at room temperature for 22 hours.. The solution was concentrated under reduced pressure, made to PH 3 by addition of a 5% potassium hydrogen sulfate solution and then extracted with 25% ethanol/chloroform.. The extract was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure.. The resulting residue was washed with hexane to give the title compound (4.25 g).1H-NMR (DMSO-d6) delta:F1.37 (s, 9H), 3.88 (s, 2H), 3.91 (s, 2H).
With sodium hydroxide; In 1,4-dioxane; water; for 72h;
In <strong>[142-73-4]iminodiacetic acid</strong> as initial starting material, <strong>[142-73-4]iminodiacetic acid</strong> in an aqueous 4% NaOH, in dioxane as solvent, the reaction 72 h, after dicarbonate ((Boc)2) Of protecting an imino group, ethyl acetate and n-hexane in a volume ratio of (1: 2 under recrystallized) conditions, to obtain pure diacetate containing tert-butoxycarbonyl (Boc) group protected.Then, to obtain the Boc protected diacetate and then to N, N - dimethylformamide (DMF) as solvent, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride ( EDCI), 1- hydroxybenzotriazole (HOBt), as a catalyst, under nitrogen, for 24 h the reaction 0-25 deg.] C, was added di-n-octylamine, amidation reaction.After completion of the reaction, the product was extracted after addition of ethyl acetate, and then by saturated citric acid, saturated sodium bicarbonate, washed three times with saturated saline solution successively, the organic solvent was removed by filtration and dried to obtain a crude product, the crude product was purified by column in this layer analysis, ethyl acetate: petroleum ether (1:10) as eluent and purified to obtain a diamide compound containing a Boc protecting group; finally, the diamide compound and then the Boc protecting group by trifluoroacetic acid: dichloromethane methane (v: v = 1: 1), 24 h the reaction de-Boc protecting group at 0-25 deg.] C, the solvent was removed by distillation and trifluoroacetic acid, and then sequentially passes through saturated sodium bicarbonate solution and saturated brine, sulfuric acid A secondary amine intermediate was filtered to give the magnesium sulfate8Preparation of intermediate dibromide and bromoacetyl bromide is 1,6-diamine as raw materials, water and chloroform as solvent, the reaction for 2 h at 5 , a white precipitate appeared bottom of the flask, the white precipitate was washed continuously with distilled water several times, and dried in vacuo to obtain the 60 pure B5A yield of 80 - 96% Ready.Finally, the preparation of the intermediate secondary amine under conditions dibromide in acetonitrile as a solvent, 40 - 85 Reaction 3 - 5 h.After the completion of the reaction, the solvent was removed, and the product extracted with ethyl acetate, successively 5% aqueous hydrochloric acid, saturated sodium bicarbonate solution, three times with saturated brine solution through, then dried over anhydrous sodium sulfate the solvent was removed, dried over deg.] C and dried to obtain pure 60 L3-58.In addition, L3-14Extractant (R = nC4H9, M = 1); L3-34Extractant (R = nC4H9, M = 3); L3-54Extractant (R = nC4H9, M = 5), and synthetic methods and steps L3-58Consistent yield of 80--99%.
With sodium hydrogencarbonate In 1,4-dioxane for 0.333333h; Ambient temperature;
2.38 g (87%)
In sodium hydrogencarbonate; acetone
15 Example 15
Example 15 N-FMOC-Iminodiacetic acid. Iminodiacetic acid (2.19 g, 16.5 mmol, Sigma Chemical Co., St. Louis, Mo.) was dissolved in a mixture of 1 M sodium bicarbonate (40 ml) and acetone (30 ml). 9-Fluorenemethyl chloroformate (2.0 g, 7.7 mmol) was dissolved in acetone (10 ml) and added to the above solution. After 6 hours reaction, the mixture was treated with brine, acidified with 1N HCl, and extracted with ethyl acetate. The yield was 2.38 g (87%), mp 213°-215.5° C. The mass spectrum (CI-NH3) showed a peak at 373 corresponding to m+1+NH3. Analysis (C19H17N06): calc. 64.22% C, 4.82% H, 3.94% N; found 64.15% C, 4.83% H, 3.909% N.
With toluene-4-sulfonic acid; In toluene; at 80℃; for 18h;
To a 250 ml three-necked flask, 60 ml of toluene, 95 ml of benzyl alcohol,6g <strong>[142-73-4]iminodiacetic acid</strong> and 10.3g toluene-4-sulfonic acid,The reaction mixture was reacted at 80 C for 18h,The solution turned cloudy from milky white to clear,After the white solid was precipitated, the white solid was dissolved in 100 ml after filtrationTrichloromethane, to which triethylamine was added dropwise with stirring until the solution was clear,The solution was washed once with 500 mL of saturated aqueous sodium bicarbonate,Dried over anhydrous magnesium sulfate,After drying in vacuo, 13.6 g of a colorless transparent oil was obtained in a yield of 96% by weight.
Thionyl chloride (16 ml, 225.39 mmol, 1.64 g/ml) the addition was completed, iminodiacetic acid3(10 g, 75.13 mmol) was added and the reaction was transferred to room temperature,stiringovernight. Methanol was removed under vacuum to give the compound4(14.70 g, 99 %) as a white solid.1H NMR (400 MHz, DMSO) delta10.05 (s, 2H), 4.01 (s, 4H), 3.74 (s, 6H). HRMS (ESI) (m/z):calcdfor C6H11NO4[M+H]+ 162.0755, found. 162.0766.
99%
With thionyl chloride; at -10 - 20℃;
At -10 , pressure-equalizing dropping funnel was added thionyl chloride (16ml, 225.39mmol, 1.64g / ml)To 100 ml of methanol, add imine diacetate (10 g, 75.13 mmol),The reaction solution was transferred to room temperature and stirred overnight. The reaction solution was swirled to remove methanol to obtain Compound 3 (14.70 g, 99%) as a white solid.
81%
Methanol (500 mL) was cooled to -20 C, and SOCl2 (36 mL, 0.5 mol) was added dropwise under vigorous stirring while maintaining the temperature of the reaction mixture below -10 C. Iminodiacetic acid(13.3 g, 0.1 mol) was then added in one portion. The reaction mixture was stirred for 24 h at r.t. and then left to stand at r.t. for two days.The volatiles were evaporated, and the residue were crystallized from methanol. Yield: 16 g (81%); white crystalline solid.1H NMR (300 MHz, D2O): delta = 4.13 (s, 4 H), 3.85 (s, 6 H).13C NMR (75 MHz, D2O): delta = 168.08, 54.12, 47.66. Anal. Calcd for C6H12ClNO4: C, 36.47; H, 6.12; N, 7.09. Found: C, 36.52;H, 6.01; N, 6.98.
4 Preparation of MGDA trisodium salt from crude iminodiacetic acid mixture (route b)
Example 4 Preparation of MGDA trisodium salt from crude iminodiacetic acid mixture (route b) 95 g of iminodiacetonitrile were introduced into 420 g of 50% by weight aqueous sodium hydroxide solution at 40° C. and, after 2 h, the mixture was heated at 95° C. for 5 h. The resulting disodium iminodiacetate solution was then adjusted to pH 6 with 49 g of sulfuric acid (98% by weight) and subsequently, at 30° C., 28.5 g of hydrocyanic acid (99.3% by weight) and 46 g of acetaldehyde were simultaneously added dropwise, after which the mixture was stirred at 60° C. for 8 h.
5. To a magnetically stirred suspension of iminodiacetic acid (50 g, 0.376 mol) in absolute ethanol (1000 ml) under N2 was added boron trifluoride etherate (100 g, 1.127 mmol). The reaction mixture was refluxed for 3 days and concentrated in vacuo to a volume of 150 ml. A saturated NH4 Cl solution (500 ml) was added and the reaction mixture was extracted with CH2 Cl2 (3*250 ml). The combined organic layers were dried and concentrated in vacuo. The crude product was distilled at 10 mm Hg to give 65.2 g (92% yield) of iminodiacetic acid, diethyl ester as a colorless liquid.
With acetic acid In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; water
1 EXAMPLE 1
EXAMPLE 1 A stirred mixture of 36 g (0.5 mole) of acrylic acid, 66.5 g (0.5 mole) of iminodiacetic acid, 130 ml of water and 20 ml of anhydrous acetic acid was kept at 100° C. for 3 hours. After the mixture had been cooled to room temperature, 50 ml of water and acetic acid were removed under reduced pressure (0.02 atm). The reaction mixture was then cooled to 5° C., after which the product precipitated in crystalline form was filtered off and washed with 60 ml of ice water. Yield: 100.5 g (0.49 mole) of β-alaninediacetic acid = 98.5%. Purity: 99.5% by weight.
With sodium hydroxide; In water; at 160℃; for 0.5h;Catalytic behavior;
10 g Diethanolamine, 2 g catalyst, and 8.5 g sodium hydroxide (dissolved in 80 mL deionized water) were added to a high-pressure reactor. The airtightness of the reactor was checked, and then N2 was passed and emptied 5-6 times before pressurizing to 1 MPa. The temperature was raised to 160 C at a heating rate of 4 C/min, and stirring was carried out at a speed of 400 rpm. The volume of hydrogen discharged was measured by a rotameter. The exhaust valve was opened when the air pressure reached 1.5 MPa and then closed when the pressure dropped to 1 MPa. The volume and exhaust temperature of each exhaust were recorded. During reactions, if the pressure in the reactor did not change for 20 min, the reaction was regarded as complete. Liquid chromatography was used for qualitative analysis. The yield of iminodiacetic acid was calculated using a strong anion exchange column (Hypersil SEX, 5 mum, 4.6 mm × 250 mm). The calculation of the yield of iminodiacetic acid is described in detail in the Supporting Information.
90.2%
With nitrogen; hydrogen;copper; In sodium hydroxide; water;
Example 1 In a flameproof, 2-litre capacity, stainless steel autoclave reactor (AISI 316), are loaded in the following order and with stirring: 263.7 g of 97% sodium hydroxide; 640 g of demineralized water; 326.4 g of 98% pure diethanolamine; 45.7 g of Raney copper with an approximate moisture content of 30%, which effectively means using 32 g net of catalyst in the trial, and, finally, an additional 40 g of demineralized water to wash away any trace of the previous reagents. The inside of the reactor is then flushed twice with nitrogen (10 kg/cm2) and twice more with hydrogen (10 kg/cm2). The last sweep of hydrogen is depressurized to 2 kg/cm2 and, with the reactor closed, heating of the reactants is commenced. Once 14-16 kg/cm2 has been reached inside the reactor, it is depressurized to 10 kg/cm2 and, with the vent open but maintaining the said internal pressure, heating is continued to 170-175C, when the timing of the reaction begins. After four hours from the start of the reaction, it is considered finished and cooled to 90C, filtered through a Buchner and Kitasato, and the Raney copper catalyst recovered. After washing well, it is stored under formic acid so that once it has been regenerated it may be reused in successive reactions. After analysis, the reaction solution provides a yield of 90.2% IDA in the form of its disodium salt which, when submitted to conventional electrodialysis, results in an almost quantitative recovery of free IDA with a purity above 98%.
With copper; sodium hydroxide; In water; at 160℃; for 6.33333h;Inert atmosphere;
Disodium iminodiacetate was synthesized using an expanded sponge copper catalyst as follows. Specifically, 80 g of diethanolamine (manufactured by Nippon Shokubai Co., Ltd.), 64 g of sodium hydroxide (manufactured by Wako Pure Chemical Industries, Ltd., first class reagent), 170 g of ion exchanged water, and 1 g of a developed sponge copper catalyst (CDT-60 manufactured by Kawaken Fine Chemicals Co., ) Was placed in a nickel autoclave having an internal capacity of 500 ml and equipped with a supernatant withdrawal pipe and a pressure regulating valve, and internal replacement was performed 3 times with nitrogen gas. The reaction temperature was raised to 160 C. at a rate of 4 C./min. While stirring at a reaction pressure of 10 kg / cm 2 G, 200 rpm, the reaction was carried out until hydrogen evolution ceased. Gas discharged from the pressure regulating valve was led to a gas flow rate accumulator, and the amount of generated hydrogen was measured (actually generated hydrogen amount). Based on the actual amount of generated hydrogen, the conversion was calculated in the same manner as in Example 1, and the conversion was 98.2%. The time required for the reaction was 350 minutes after raising the temperature to 160 C. After completion of the reaction, the temperature was lowered to 80 C., stirring was stopped, and the mixture was allowed to stand at this temperature for 5 minutes. Then, using a Kiriyama Roto filter paper (Nihon Rikagaku Kikai Co., Ltd., acid resistant alkali, No. 704) while withdrawing the supernatant The filtrate and the catalyst were separated by filtration.With respect to the above filtrate, analysis by ICP-MS was carried out in the same manner as in Example 1, and as a result, the respective element amounts of Cu, Si, Al and Fe were 5 ppm, 27 ppm, 256 ppm and 41 ppm, respectively.The obtained filtrate was transferred to a polypropylene container and stored under air (Air) atmosphere for 3 days. As a result, adhesion of a large amount of coloring components to the container was observed.
2-[(benzyloxy)carbonyl](carboxymethyl)amino}acetic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
Step 1 To the solution of <strong>[142-73-4]iminodiacetic acid</strong> XLV (10 g, 75.13 mmol) and K2CO3 (41.53 g, 300.52 mmol) in water (225 mL) was added a solution of CBzOsu (20.6 g, 82.64 mmol) in acetone (150 mL). The mixture was stirred at r.t. overnight. The acetone was evaporated under reduced pressure and the remaining water was washed with ethyl ether (2*). The aqueous layer was acidified to pH=2 with 2 M aq. HCl and then saturated with NaCl, washed with EtOAc (3*). The combined EtOAc was dried over MgSO4 and evaporated under reduced pressure to give 2-[(benzyloxy)carbonyl](carboxymethyl)amino}acetic acid XLVI (15 g, 56.17 mmol, 75% yield). ESIMS found for C12H13NO6 m/z 290 (M+Na).
With potassium hydroxide; In tetrahydrofuran; water; at 20℃; for 72h;
Compound 5d has successfully been prepared by direct coupling of 4-(4-bromo-phenoxy)-benzenesulphonyl chloride (3d) to unprotected <strong>[142-73-4]IDA</strong> following originally described procedure (Santos et al., 2006). Briefly, to a solution of <strong>[142-73-4]IDA</strong> (0.93 g, 7.02 mmol) and KOH (1.36 g, 24.2 mmol) in water (5 mL) was added a solution of 4-(4-bromophenoxy)benzenesulphonyl chloride (3d) (2.70 g, 7.80 mmol) in THF (25 mL), and the resulting suspension was stirred for 3 days at room temperature. The organic solvent was evaporated, the residue dissolved in 5 % aqueous NaOH (40 mL), and the insoluble white solids were filtered off. The aqueous solution was washed with DCM (3 × 40 mL), acidified to pH 1 with concentrated aqueous HCl, and extracted with EtOAc (6 × 40 mL). The combined EtOAc-layers were dried over anhydrous MgSO4, filtered and evaporated in vacuo to give the pure product. Yield: 1.90 g, 4.30 mmol, 61 % (white solid). 1H-NMR (DMSO-d6): delta 7.82 (d, J = 8.8 Hz, 2H, ArH), 7.64 (d, J = 8.8 Hz, 2H, ArH), 7.17-7.07 (m, 4H, ArH), 3.96 (s, 4H, 2 × CH2CO2H).
General procedure: A solution of amino acid (1.94 mmol) and NaOH (0.22 g, 5.40 mmol) in H2O (1 mL) was added dropwise into a 20 mL test tube containing a 1 mL aqueous solution of TCT (0.1 g, 0.54 mmol) at 0 C. The mixture was allowed to warm to room temperature, boiling chips were added and the reaction vessel was placed on the center of the turn-table in a domestic microwave oven (Samsung GB872, 850 W, 2.54 GHz). The mixture was then irradiated at the specified power for the prescribed time. After the microwave was switched off, the reaction mixture was cooled and acidified with concentrated HCl. The precipitate was collected by filtration, washed successively with H2O and EtOH before drying at 80 C to afford the pure product. Novel compounds 1b-e and 1j were fully characterized by 1H NMR, 13C NMR, FT-IR, and HRMS analyses. Spectroscopic data for known compounds 1a, 1f-i and 1k were consistent with those reported in the literature.
65%
With sodium hydroxide; In water; at 110℃;
12.64 g (95mmol) <strong>[142-73-4]iminodiacetic acid</strong> and 12.00 g (30mmol) NaOH were dissolved in 40 mL deionized water and stirred to get a clear solution (a), 5.53 g (30mmol) of cyanuric chloride was dissolved in 40mL of deionized water to obtain solution (b). Solution (b) was added to solution (a) slowly and drop by drop within one hour under the ice bath condition, and then the mixture was returned to room temperature and continued to be stirred for 120 min then reflux overnight at 110. After the refluxed solution was cooled to room temperature, the pH was adjusted to 1-2 with an acid solution, at which time a large amount of white solid was precipitated, and finally washed with an ethanol solution, suction filtered, and dried to give a final product, namely1,3, 5-triazine-2,4, 6-triaminohexaacetic acid (H6TTHA), mass is 8.5 g, yield is 65%.
di[2-(perfluorooctyl)ethyl] iminodiacetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
69%
With boron trifluoride diethyl etherate; for 96h;Inert atmosphere;
2-(Perfluorooctyl)ethanol (65 g, 140 mmol) was melt withiminodiacetic acid 26 (3.72 g, 28 mmol) in a round-bottomedflask under argon. BF3*Et2O (10.6 mL) was slowly added and themixture was stirred for 96 h. After addition of ethyl acetate, thesolution was washed with an aqueous solution of ammoniumchloride. Residual alcohol was eliminated by sublimation (110 C,0.5 mm Hg) and the crude mixture was purified by flashchromatography over silica gel to furnish 27 as a white solid(19.8 g, 69%)
In N,N-dimethyl-formamide; at 70℃; for 18h;Inert atmosphere;
A mixture of EDTA dianhydride (0.51 g, 1.99 mmol), iminodiacetic acid (0.53 g, 3.98 mmol), in dry DMF (20 mL) was heated at 70 C under stirring under argon. After 18 h the brown mixture was concentrated, 5 mL methanol were added, then 50 mL acetone to give a white solid. The supernatant was taken off; the residue was triturated twice with 50 mL acetone to give after filtration and drying under vacuum compound 1f (0.77 g, 74%) as white crystals.1H NMR (D2O, 300 MHz, 25 C) delta=4.29 (s, 4H, N-CH2-CO), 3.94 (s, 4H, N-CH2-CO), 3.56 (s, 4H, N-CH2-CO), 3.41 (s, 4H, N-CH2-CO), 2.78 (s, 4H, N-CH2-CH2-N). 13C NMR (D2O, 75 MHz, 25 C) delta=172.3 (CO), 171.4 (CO), 170.8 (CO), 170.5 (CO), 55.4 (CH2), 54.8 (CH2), 51.2 (CH2), 50.3 (CH2), 49.3 (CH2). HRMS (ESI): calcd for C18H26N4O14Na+: 545.1338; found: 545.1340. Anal. Calcd (%) for C18H26N4O14: C, 41.38; H, 5.02; N, 10.72; O, 42.88; found: C, 41.27; H, 4.89; N, 10.97.
1
A solution of iminodiacetonitrile (100 g, 95%, lmol) was treated with sodium hydroxide solution (585 g, 15%, 2.2 mol) at 60-65 ° C Hydrolysis, hydrolysis after heating to l0 ° C, insulation lh, cooling to 60 ° C, Add ammonium sulfate in part to adjust ρΗ = 9.5, the reaction released The ammonia gas absorbed, continue to drop 93wt% Of sulfuric acid to pH value of 2.0, cooled to 40 ° C insulation lh, filtration, The filter cake was washed with 15 ml of water and dried to give a white iminodiacetic acid solid. The resulting filtrate was concentrated by steaming and the sulfur was separated Sodium, the filtrate applied to the next batch, continuous application of three batches, Apply the following three batches of data as shown in the table below..
90%
With water; calcium hydroxide at 25℃; for 5h;
Example
47.55 g (0.5 mol) of iminodiacetonitrile was suspended in 190 g of water and 40.7 g (0.55 mol) of calcium hydroxide was added.After that,The reaction product was allowed to stand at 25 DEG C for 5 hours for hydrolysis reaction.After the reaction was completed, 108 g (1.1 mol) of 37% hydrochloric acid was added to neutralize it.After that,The reaction solution was concentrated in vacuo to a weight of 100 g,When the concentration was completed, 300 ml of methanol was added to precipitate crystals.The precipitated crystals were filtered, washed with 20 ml of methanol,And dried in a 60 ° C vacuum dryer for 24 hours to obtain 66.5 g of iminodiacetic acid.The yield of iminodiacetic acid obtained was 90% by weight (weight of iminodiacetic acid obtained / weight of iminodiacetic acid which can be theoretically obtained x 100), purity on HPLC (high-performance liquid chromatography) was 99.2% The concentration of Cl ion was 0.01 in ion chromatography.
With Alcaligenes faecalis ZJUTBX11 cells encapsulated in alginate-chitosan-alginate membrane liquid core capsules In aq. buffer at 35℃; Enzymatic reaction;
With water In aq. buffer at 35℃; Microbiological reaction; Enzymatic reaction;
502.1 g
With hydrogenchloride; sulfuric acid In water at 80 - 160℃; for 6h; Inert atmosphere; Autoclave;
1
A 1 L kettle was charged with 100 g of 7 K,273 g of hydrochloric acid having a mass fraction of 30%Mass fraction of 98% concentrated sulfuric acid 55g,Then 100g of iminodiacetonitrile with 95% mass fraction was added slowly.After the nitrogen to 0. 2Mpa replacement kettle gas, and then emptied.The reaction vessel was sealed and heated to 160 ° C.The inside of the autoclave was purged with nitrogen to a pressure of IMpa.After the heat 6 hours, after the end of the cooling temperature, until the temperature dropped to 80 ° C, pressure relief, the material into a 1000ml four-necked flask, weighing, testing.The weight was 502.1g and the IDA content was 25. 81%.
With water In aq. phosphate buffer at 37℃; for 1h; Green chemistry; Enzymatic reaction;
2.5. Biocatalytic nitrile conversion by selected nitrilases
General procedure: A typical reaction mixture (5 mL in 25 mL shake flask) contained thenitrile substrate and appropriate amount of E. coli cell mass expressingthe selected nitrilase suspended in 100mM phosphate buffer pH 7. Inthe case of mandelonitrile, conversion experiments were performed inaqueous buffer containing 10 % methanol to aid substrate solubility.The catalytic reaction was performed at 37 °C with agitation at 150 rpmin an incubator shaker. Aliquots (100 μl) were withdrawn at regularpredetermined time intervals and quenched with 10 μl of 1M HCl. Thereaction mixture was centrifuged and filtered using a 0.45 μm syringefilter, and the product formed was monitored through HPLC analysis.
2,2'-((3-sulfopropyl)azanediyl)diacetic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100%
In water; at 85℃; for 4h;
Example 1 Synthesis of 2,2'-((3-sulfopropyl)azanediyl)diacetic acid 2,2'-azanediyldiacetic acid 15.5 g, 116 mol) and 1,2-oxathiolane-2,2-dioxide 14.2 g, 116 mol) were combined in 35 mL water. The mixture was stirred at 85 C. for 4 h. Reaction monitored by NMR and completion was verified by disappearance of NMR resonances of starting material. The resulting aqueous solution contained 2,2'-((3-sulfopropyl)azanediyl)diacetic acid in essentially quantitative yield as determined by NMR. The solution was used without purification or further manipulation.
In water; at 85℃; for 4h;
The sulfonated <strong>[142-73-4]iminodiacetic acid</strong> was synthesized as generally shown in Reaction 2 above. 15.5 g of <strong>[142-73-4]iminodiacetic acid</strong> (116 mmol) and 14.2 g of 1,2-oxathiolane 2,2-dioxide (116 mmol) were combined in 35 mL water. The reaction mixture was stirred at 85C for 4 hours, and reaction progress was monitored by NMR until the resonances of the starting materials disappeared. The resulting aqueous solution was used without purification orfurther manipulation.
With water; at 85℃; for 4h;
15.5 g of <strong>[142-73-4]iminodiacetic acid</strong> (116 mmol) and 14.2 g of 1,2-oxathiolane 2,2-dioxide (116 mmol) were combined in 35 mL water. The reaction mixture was stirred at 85 C. for 4 hours, and reaction progress was monitored by NMR until the resonances of the starting materials disappeared. The resulting aqueous solution was used without purification or further manipulation.
With sodium hydroxide; In ethanol; water; at 90℃; for 11h;Reflux;
Example 2: Preparation of DHE-<strong>[142-73-4]IDA</strong> DHE-<strong>[142-73-4]IDA</strong> was prepared by a base catalyzed condensation of commercially available DHE, <strong>[142-73-4]iminodiacetic acid</strong> (<strong>[142-73-4]IDA</strong>) and formaldehyde. DHE (20 mmol), 37% formaldehyde solution (22 mmol), <strong>[142-73-4]IDA</strong> (22 mmol) and 2 molar equivalent of NaOH were added in 40 mL water-ethanol solvent (1:2 v/v) in a 100 mL round bottom flask. The mixture was heated with continuous stirring to dissolve <strong>[142-73-4]IDA</strong> and NaOH, and then refluxed at 90 C for 11 h. The color of the reaction mixture initially changed to light purple within 30 minutes, and then gradually changed to light brownish as the reaction progressed. After about 6 h of reflux, the reaction mixture became colloidal as white solid started to form. After refluxing for another 3 h, the solution became thick with white solid which was cooled down to room temperature, neutralized with 3 M HCl and kept in a refrigerator for about 2 h. White product was filtered, washed and dried in an oven at 50 C to obtain DHE<strong>[142-73-4]IDA</strong> with 95% yield (5.6 g). The purity of the product was confirmed by 1H-NMR (Figure 8). 1H-HMR (400 MHz, DMSO- d6): delta (ppm) 6.89 (s, 1H), 6.66 (s, 1H), 4.03 (s, 3H), 3.61 (s, 4H), 3.41 (s, 4H), 2.43 (t, 2H), 1.55 (q, 2H), 0.83 (t, 3H).
2,2'-[(diisopropoxyphosphoryl)methyl]azanediyl}-diacetic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Ca. 100%
A mixture of 21.02 g (0.158 mol) of imidodiacetic acid, 4.513 g (0.165 mol) of paraformaldehyde,2.10 g (0.016 mol) of imidodiacetic acid hydrochloride, and 50 mL of acetonitrile was heated for 1.5 h at 60C. Diisopropyl phosphonate, 25 g(0.150 mol), was then added, and the mixture was heated for 5 h at 80C until its 31P NMR spectrum displayed only one signal at deltaP 22.1 ppm, corresponding to phosphonate 1.
Example-1: 20 mmol of cyanuric chloride was added to 200 mL of ice water and the ice bath was added. And then add 10mmo1 4,4 '- diaminodystyrene _2,2'_ disulfonic acid (DSD acid) and 200mL distilled water mixture (plus 20mmol Na2C03), stirring, 0 ~ 5 C, reaction 2h. Raise the temperature to 30 ~ 40 C, add 20mmol Na2C03. And then add 20mmol tetradecyl dimethyl tert-amine and 10mL DMF mixture, temperature control reaction l0h. Heating to 80 ~ 90 C, adding 20mmol of <strong>[142-73-4]iminodiacetic acid</strong>, dropping 10% Na2C03 solution to maintain the system pH 8 ~ 9, temperature control reaction 8h. Cooling to room temperature, adding 60 g of sodium chloride, stirring, suction filtration, vacuum drying tetracarboxylic acid heavy calcium carbonate powder fluorescent whitening agent, the yield of 88%
[VO(IDA)(4,4'-dimethoxy-2,2'-dipyridyl)]*2H2O[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
at 70℃; for 0.416667h;
General procedure: The solutions contained 1) VO(acac)2 (5.3 g, 20.0 mmol), H2IDA (2.66 g, 20.0 mmol) and dmbipy (3.68 g, 17.0 mmol) in water (100 mL) and 2) VO(acac)2 (5.3 g, 20.0 mmol), mH2IDA (2.94 g,20.0 mmol) and dmbipy (3.68 g, 17.0 mmol) in water (100 mL) were heated about 25 min at 70°C in a heating mantle. Then, after several days, dark green crystals of [VO(mIDA)(dmbipy)*]1.5H2O and the grey-green powder of [VO(IDA)(dmbipy)]*2H2O were obtained. The composition of the studied compounds was established on the basis of the elemental analysis of carbon, hydrogen and nitrogen (CARBO ERBA type CHNS e O 1108). Anal. Calcd for [VO(mIDA)(dmbipy)]*1.5H2O (percent): C, 42.20, H, 4.84, N, 9.23. Found:C, 42.54, H, 4.94, N, 9.03. Anal. Calcd for [VO(IDA)(dmbipy)]*2H2O(percent): C, 42.67, H, 4.67, N, 9.33. Found: C, 42.43, H, 4.78, N, 9.17.
In a dry four-necked flask (250 ml) equipped with an electric stirrer, a thermometer, a reflux condenser, and a nitrogen conduit, The dry nitrogen drains the air from the four bottles. 30 g of water, 13.3 g of <strong>[142-73-4]iminodiacetic acid</strong>, 0.1 g of hydrochloric acid (mass percent concentration) 36%) was added to a four-necked flask and heated to 90 C. Slowly dropping the mass percentage of 25% formaldehyde solution 120g, Paul Stir for 3 h. After distilling off the water under reduced pressure, 30 g of toluene was added, and 20.2 g of diphenylphosphine oxide was slowly added, and the mixture was charged Reaction for 1h, the solvent toluene distillation, the product, the yield of 89%, HPLC content of 99.4%. The product was found by infrared test= O, P-C, -COOH, indicating that the target product was obtained.
(2,2'-(2-dioctylamino)-2-oxoethylazanediyl) diacetic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77.8%
With sodium hydroxide; In ethanol; water; at 20 - 85℃; for 17.5h;Inert atmosphere;
3.3 g (80 mmol) of sodium hydroxide was dissolved in 250 mL of ultrapure water,Further, 10.65 g (80 mmol) of <strong>[142-73-4]iminodiacetic acid</strong> was dissolved.After dissolution, 12 mL of a 5 mol / L sodium hydroxide aqueous solution was added until the pH test paper became blue, 230 mL of ethanol was further added and the mixture was stirred.12.7 g (40 mmol) of ClDOAA was dissolved in 20 mL of ethanol, after purging with argon, it was slowly added dropwise with stirring at room temperature.After the dropwise addition, the mixture was refluxed at 85 C. for 17.5 hours. During the refluxing, a 5 mol / L sodium hydroxide aqueous solution was added at any time so that the pH was about 11, and the same volume of ethanol was added.Only ethanol was distilled off from the reaction solution by an evaporator.The remaining aqueous solution was subjected to liquid separation three times with 100 mL of diethyl ether.While stirring the obtained aqueous solution, 30 mL of 3 mol / L hydrochloric acid was added, and the resulting white precipitate was recovered by filtration.The obtained precipitate was washed twice with 100 mL of ultrapure water, vacuum dried and then purified by reprecipitation using acetone and hexane to obtain 12.9 g (yield: 77.8%) of a white powder .The resulting compound was analyzed by nuclear magnetic resonance (NMR), elemental analysis,Was identified using matrix-assisted laser desorption ionization time-of-flight mass analyzer (MALDI-TOF / MS),It was confirmed to be 2,2 '- (2- (dioctylamino) -2-oxoethylazanediyl) diacetic acid (DONTAMA).
0.2 part of trade name: Leocol RTMTD 90 (surfactant) manufactured by Lion Corporation was added to 410 parts of ice water, and the mixture was vigorously stirred, 5.9 parts of cyanuric chloride was added thereto, and the mixture was stirred at 0 to 5 C. for 30 minutes to obtain a suspension .Subsequently, 90 parts of the wet cake of the compound represented by the above formula (9) was dissolved in 180 parts of water to obtain a solution.This solution was added dropwise to the above suspension over 30 minutes.After completion of the dropwise addition, the mixture was stirred at pH 6 to 8 at 25 to 45 C. for 6 hours. 8.5 parts of <strong>[142-73-4]iminodiacetic acid</strong> was added to the obtained reaction solution, and the mixture was stirred at pH 7 to 9 at 75 to 90 C. for 6 hours.After cooling the obtained reaction solution to 20 to 25 C., 2000 parts of 2-propanol was added to the reaction solution, and the mixture was stirred at 20 to 25 C. for 2 hours.The precipitated solid was separated by filtration to obtain 92.1 parts of a wet cake. The sodium salt of the water-soluble azo compound of the present invention represented by the following formula by the wet cake is dried at 80 C. in a hot air dryer (10) (lambdamax: 402.0nm) to obtain 26 parts.
N-(4-nitrophenyl)iminodiacetic acid disodium salt[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
Iminodiacetic acid (1.33 g, 10 mmol) was treated with anequimolar amount of sodium methoxide, obtained by dissolvingmetallic sodium (0.46 g, 20 mmol) in dry methanol (20 mL),and the mixture was distilled in vacuo (Rotavapor). The residue was dissolved in dry DMSO (10 mL), then, 4-nitrofluorobenzene(1.41 g, 10 mmol) and anhydrous Na2CO3 (1.06 g,10 mmol) were added. The reaction mixture was kept at 70 Cunder stirring for 18 hours. Afterwards, the resulting slurry was dissolved in water (200 mL) and the solution was extractedtwice with ethyl acetate (ca. 70 mL each). Then, the aqueousphase was acidified with HCl (6 M) up to pH 2, and the desiredproduct was extracted thrice with ethyl acetate (100 mL each).The organic extracts were dried over Na2SO4 and distilled invacuo (Rotavapor) to afford the crude product, which was dissolvedin a methanolic solution of sodium methoxide (2 M,10 mL). Diethyl ether (80 mL) was then added to precipitate thepure product, which was finally filtered off. Yield 60% (1.79 g).IR (nujol) nu (cm-1): 1597, 1516, 1339; 1H NMR (300 MHz,D2O) delta (ppm) 3.95 (s, 4H, -CH2-), 6.47 and 8.03 (2d,J = 9.5 Hz, 2H + 2H, p-NO2-C6H4-N<); Anal. calcd forC10H8N2O6Na2: C, 40.28; H, 2.70; N, 9.40; Na, 15.42; found:C, 40.24; H, 2.73; N, 9.39; Na, 15.43.
Stage #1: [2,2]bipyridinyl; water; iminodiacetic acid at 20℃; for 1h;
Stage #2: manganous acetylacetonate In methanol at 20℃; Reflux;
2.5.3 Synthesis of [Co(imda)(bipy)(H2O)]·4H2O (3)
To an aqueous solution of iminodiacetic acid (2mmol, 0.266g), 2,2′-bipyridne (2mmol, 0.312g) was added in small batches and stirred for 1hat room temperature forming a homogeneous clear solution. A methanolic solution of Co(acac)2(H2O)2 (2mmol, 0.586g) was added drop wise to the above mixture. The stirring was continued overnight followed by refluxing for 24h. Solution was left standing in air in a beaker at room temperature. Crystals of complex (3) were collected as above. However, the obtained crystals were not suitable for crystallography.
Stage #1: 1-amino-4-bromo-9,10-dioxoanthracene-2-sulphonic acid; iminodiacetic acid With sodium carbonate; copper(II) sulfate In water at 80℃; for 12h;
Stage #2: Iron(III) nitrate nonahydrate In water
[Cu(iminodiacetate)(3-methyladenine)(H2O)2]*3H2O[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Ca. 63%
General procedure: In a Kitasato flask, Cu2CO3(OH)2 (0.25 mmol) was reacted with0.5 mmol of the corresponding iminodiacetic-like acids H2IDA (1,4,11),H2MIDA (5,10,12), H2EIDA (13), H2FurIDA (8), H2NBzIDA (6,14),H2MEBIDA (15), H2CBIDA (2,9,16) and H2NamIDA (3,7) in 60 mL ofdistilled water with heating (50 C), stirring and moderate vacuum.Once a clear blue solution of the binary chelate was obtained, thecorresponding Meade ligand (0.5 mmol) was added: 1Meade (1-3),3Meade (4-9), 7Meade (10), 9Meade (11-16). The solution was leftreacting for one hour. Afterwards, it was filtered in a crystallizationdevice (to remove possible un-reacted materials) and stood at r.t. coveredwith a plastic film to control the evaporation of the solvents.
2-hydroxyethyliminodiacetic acid, sodium salt[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
(1) preparing a first reaction solution containing sodium iminodiacetate250 g of <strong>[142-73-4]iminodiacetic acid</strong> was placed in a clean 2 L autoclave, and 150 g of water was added thereto to stir and dissolve. Under stirring, 320 g of a 50 wt% sodium hydroxide solution was added dropwise to the sodium iminodiacetate solution, and the temperature was controlled to be 35-40 C during the dropwise addition. After the completion of the dropwise addition, the temperature was controlled from 40 C to 45 C for 1.5 h, and sodium <strong>[142-73-4]iminodiacetic acid</strong> reacted with sodium hydroxide to form sodium iminodiacetate.(2) Preparation of disodium hydroxyethyl<strong>[142-73-4]iminodiacetic acid</strong>Adding 18-crown ether-6 to 0.03 g to the first reaction solution containing sodium <strong>[142-73-4]iminodiacetic acid</strong>, and then introducing 100 g of ethylene oxide, controlling the temperature at 60 C to 65 C, and maintaining the reaction for 4 hours to obtain a hydroxyl group. A second reaction solution of disodium <strong>[142-73-4]iminodiacetic acid</strong>.The pressure in the reaction vessel was adjusted to be zero, and the second reaction liquid was concentrated under reduced pressure at the end of the heat retention, and a large amount of white solid precipitated. Then, the temperature was lowered to 30 C, 80 ml of methanol was added dropwise to the second reaction liquid with a white solid precipitated, and the temperature was further lowered to 5-10 C, and the mixture was stirred for 2 hours, and the mixture was suction filtered, and the filter cake was rinsed with a small amount of cold methanol. After drying for 4 hours, 465 g of disodium hydroxyethyliminodiacetate was obtained in a yield of 93%.
[Cu(iminodiacetic acid)(9-methyladenine)(H2O)2]*3H2O[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Stage #1: copper (II) carbonate hydroxide; water; iminodiacetic acid at 50℃;
Stage #2: 3-methyladenine at 50℃; for 1h;
2.3.1. General synthetic procedure
General procedure: In a Kitasato flask, Cu2CO3(OH)2 (0.25 mmol) was reacted with0.5 mmol of the corresponding iminodiacetic-like acids H2IDA (1,4,11),H2MIDA (5,10,12), H2EIDA (13), H2FurIDA (8), H2NBzIDA (6,14),H2MEBIDA (15), H2CBIDA (2,9,16) and H2NamIDA (3,7) in 60 mL ofdistilled water with heating (50 °C), stirring and moderate vacuum.Once a clear blue solution of the binary chelate was obtained, thecorresponding Meade ligand (0.5 mmol) was added: 1Meade (1-3),3Meade (4-9), 7Meade (10), 9Meade (11-16). The solution was leftreacting for one hour. Afterwards, it was filtered in a crystallizationdevice (to remove possible un-reacted materials) and stood at r.t. coveredwith a plastic film to control the evaporation of the solvents.
Stage #1: maleic acid With sodium hydroxide In water at 45 - 55℃; for 0.25h;
Stage #2: With sodium tungstate In water for 2.25h;
Stage #3: iminodiacetic acid Further stages;
2; 5 Example 2:
Add 232g of maleic acid to a 2000mL four-neck flask, then add 200g of deionized water, and stir at 45°C for 1 hour.Then use 50% (mass fraction) of NaOH solution to adjust the pH of the reaction system to 5.0-6.5, and maintain the temperature not to exceed 55°C. After the addition is complete, the temperature is raised to 55°C and stirred for 15 minutes.Add 16 g of sodium tungstate to the reaction system and stir for 45 minutes. In 90 minutes, the 30% hydrogen peroxide solution was added dropwise, and 50% NaOH was added to the system to adjust the pH.During the reaction, pH=6.0-7.0, and temperature does not exceed 75°C. After the addition of hydrogen peroxide is completed, the temperature is raised to 60-65°C and stirred for 3 hours, then 266 g of iminodiacetic acid is added and stirred for 1 hour.Add 160g of solid sodium hydroxide, then heat to 90°C, react for 8h, and cool to obtain a solution of N,N-diethylcarboxylic acid-3-hydroxydisuccinic acid tetrasodium salt, which is a solution of the chelating agent represented by formula Ia , Yield: 96.12%.
Stage #1: (2E)-but-2-enedioic acid With sodium hydroxide In water at 45 - 55℃; for 0.25h;
Stage #2: With sodium tungstate In water for 2.25h;
Stage #3: iminodiacetic acid Further stages;
3 Example 3:
Add 232g of fumaric acid to a 2000mL four-necked flask, then add 200g of deionized water, and stir at 45°C for 1 hour. Then use 50% (mass fraction) of NaOH solution to adjust the pH of the reaction system to 5.0-6.5, and maintain the temperature not to exceed 55°C. After the addition is complete, the temperature is raised to 55°C and stirred for 15 minutes. Add 20 g of sodium tungstate into the reaction system and stir for 45 minutes. In 90 minutes, the 30% hydrogen peroxide solution was added dropwise, and 50% NaOH was added to the system to adjust the pH. During the reaction, pH=6.0-7.0, and temperature does not exceed 75°C. After the addition of hydrogen peroxide is completed, the temperature is increased to 60-65°C, stirred for 3h, then 266g iminodiacetic acid is added, stirred for 1h, 160g solid sodium hydroxide is added, then the temperature is raised to 90°C, the reaction is 8h, and the temperature is reduced to obtain N,N-di A solution of tetrasodium acetoxy-3-hydroxydisuccinic acid, that is, a solution of a chelating agent represented by formula Ia, yield: 85.12%.
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