* 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.
Reference：
[1] Oriental Journal of Chemistry, 2011, vol. 27, # 3, p. 1261 - 1264
5
[ 610-27-5 ]
[ 3682-14-2 ]
Reference：
[1] Journal of the Chemical Society, 1937, p. 26,31
[2] Patent: CN106810501, 2017, A,
6
[ 610-27-5 ]
[ 5466-84-2 ]
Yield
Reaction Conditions
Operation in experiment
88%
With oxalyl dichloride; N,N-dimethyl-formamide In toluene for 3 h; Inert atmosphere; Reflux
General procedure: Dicarboxylic acid 2 (1 mmol) and oxalyl chloride (1.2 mmol) were combined in dry toluene (5 mL) and a drop of freshly distilled DMF was added. The reaction vessel was purged with argon and the reaction was heated under stirring for 3 h. The stirring was stopped and the toluene solution was decanted off the oily residue and filtered. Evaporation of the volatiles provided the analytically pure target product which, if necessary, was transformed intro crystalline form by trituration with diethyl ether. In some cases (see ESI) additional crystallization or trituration with 1:2 v/v hexane-toluene mixture was used. .
Reference：
[1] Patent: US3979416, 1976, A,
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1994, # 20, p. 2967 - 2974
[3] Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 9, p. 1817 - 1821
[4] Tetrahedron Letters, 2017, vol. 58, # 32, p. 3160 - 3163
[5] Bulletin des Societes Chimiques Belges, 1996, vol. 105, # 1, p. 55 - 56
[6] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 19, p. 5722 - 5726
[7] Patent: US7759468, 2010, B1,
[8] Chemische Berichte, 1878, vol. 11, p. 393[9] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1878, vol. 10, p. 196
[10] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 230
[11] Journal of the Chemical Society, 1909, vol. 95, p. 208
[12] Journal of the Indian Chemical Society, 1930, vol. 7, p. 619,624
[13] Journal of the Chemical Society, 1925, vol. 127, p. 1794
[14] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 1834 - 1840
[15] Synthetic Communications, 2003, vol. 33, # 9, p. 1499 - 1507
[16] Patent: US3979416, 1976, A,
[17] Letters in Organic Chemistry, 2013, vol. 10, # 7, p. 496 - 501
[18] Patent: CN105418442, 2016, A, . Location in patent: Paragraph 0006
7
[ 610-27-5 ]
[ 108-24-7 ]
[ 5466-84-2 ]
Reference：
[1] Journal of the Chemical Society, 1937, p. 26,31
8
[ 610-27-5 ]
[ 89-40-7 ]
Reference：
[1] Synthetic Communications, 2003, vol. 33, # 9, p. 1499 - 1507
[2] Journal of the Chemical Society, 1937, p. 26,31
[3] Oriental Journal of Chemistry, 2011, vol. 27, # 3, p. 1261 - 1264
[4] Patent: CN106810501, 2017, A, . Location in patent: Paragraph 0048
9
[ 46053-72-9 ]
[ 89-40-7 ]
[ 610-27-5 ]
Reference：
[1] Chemische Berichte, 1900, vol. 33, p. 2811
10
[ 610-27-5 ]
[ 320-97-8 ]
Reference：
[1] Patent: CN108516930, 2018, A,
11
[ 56-23-5 ]
[ 610-27-5 ]
[ 89-20-3 ]
Reference：
[1] Ukrainskii Khimicheskii Zhurnal (Russian Edition), 1958, vol. 24, p. 68[2] Chem.Abstr., 1958, p. 18325
12
[ 610-27-5 ]
[ 31643-49-9 ]
Reference：
[1] Chemical Physics Letters, 2006, vol. 423, # 4-6, p. 306 - 311
13
[ 31643-49-9 ]
[ 610-27-5 ]
Yield
Reaction Conditions
Operation in experiment
95%
at 60 - 65℃; for 2.45 h; Green chemistry
General procedure: Aromatic or aliphatic nitriles (2 mmol) were dissolved in 5 ml of [bmim]HSO4 and the reaction mixture was heated at 60-65 °C for 1-3 h. The progress of reaction was monitored by TLC. After completion of reaction, as checked by TLC, the reaction mixture was poured into water containing crushed ice. The product was precipitated out, filtered and dried. The yield of the final product was high (>90percent) in all cases. All final products obtained were found sufficiently pure so it didn’t need further purification.The filtrate was concentrated under vacuum, washed with diethylether twice and concentrated under high vacuum. After proper drying under reduced pressure, approximately 95percent ionic liquid was recovered from the reaction and compared with the original ionic liquid to check its authenticity. The efficiency of recovered ionic liquid in conversion of nitriles to acids was found unchanged in comparison to the original one and we reused it up to 5-6 cycles without any significant loss of its activity.
Reference：
[1] Asian Journal of Chemistry, 2012, vol. 24, # 7, p. 3033 - 3038
[2] Journal of the American Chemical Society, 1901, vol. 23, p. 751
[3] Journal fuer Praktische Chemie (Leipzig), 1896, vol. <2> 53, p. 383
[4] Dissertation <Freiburg 1891>, S. 9,
[5] Monatshefte fuer Chemie, 1902, vol. 23, p. 418
[6] Kogyo Kagaku Zasshi, Spl. 36 <1933> 121, [7] Chem. Zentralbl., 1933, vol. 104, # II, p. 216
[8] Kogyo Kagaku Zasshi, 1933, vol. 36, p. 391,394
[9] Journal of the American Chemical Society, 1901, vol. 23, p. 751
[10] Journal fuer Praktische Chemie (Leipzig), 1896, vol. <2> 53, p. 383
[11] Monatshefte fuer Chemie, 1902, vol. 23, p. 418
[12] Dissertation <Freiburg 1891>, S. 9,
[13] Chemische Berichte, 1881, vol. 14, p. 1330 Anm.
[14] Letters in Organic Chemistry, 2013, vol. 10, # 7, p. 496 - 501
15
[ 85-44-9 ]
[ 610-27-5 ]
Reference：
[1] Journal of the Chemical Society, 1931, p. 79,81
[2] Letters in Drug Design and Discovery, 2013, vol. 10, # 9, p. 872 - 878
[3] Patent: CN105418442, 2016, A, . Location in patent: Paragraph 0006
Reference：
[1] Monatshefte fuer Chemie, 1900, vol. 21, p. 794
[2] Monatshefte fuer Chemie, 1900, vol. 21, p. 794
[3] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1994, # 20, p. 2967 - 2974
[4] Patent: WO2006/93728, 2006, A2, . Location in patent: Page/Page column 34-35; 38-39
[5] Patent: WO2006/93728, 2006, A2, . Location in patent: Page/Page column 35-36; 37-38
[6] Patent: WO2011/5731, 2011, A2, . Location in patent: Page/Page column 49-50
[7] Dyes and Pigments, 2015, vol. 113, p. 189 - 199
[8] Dyes and Pigments, 2015, vol. 117, p. 49 - 60
56
[ 67-56-1 ]
[ 610-27-5 ]
[ 610-22-0 ]
[ 90072-77-8 ]
Reference：
[1] Monatshefte fuer Chemie, 1900, vol. 21, p. 794
57
[ 610-27-5 ]
[ 5411-50-7 ]
Yield
Reaction Conditions
Operation in experiment
32%
at 120℃; for 2 h; UV-irradiation
EXAMPLE 7 Bromodecarboxylation of arenedicarboxylic acids induced by bromoisocyanurate (0393) (0394) [00164] Round bottom flask equipped with Dimroth condenser (chilled to 10 °C) was charged with arenedicarboxylic acid RC6H3(C02H)2 (1 mmol), bromoisocyanurate, additive and solvent (10 mL). The mixture was magnetically stirred and heated in an oil bath at 120 °C under florescent room light irradiation (FL) for 60 h. The cooled reaction mixture was filtered through short silica gel pad, washed with 1 M aq Na2S03, dried over Na2S04, filtered and concentrated in vacuo to give crude dibromoarene RC6H3Br2. Optionally, the crude dibromide was purified by chromatography on silica gel. The results are presented in Table 6.
Reference：
[1] Journal of the American Chemical Society, 1940, vol. 62, p. 2799,2800
59
[ 610-27-5 ]
[ 13138-53-9 ]
Reference：
[1] Chemical Physics Letters, 2006, vol. 423, # 4-6, p. 306 - 311
60
[ 610-27-5 ]
[ 5434-21-9 ]
Yield
Reaction Conditions
Operation in experiment
96%
With hydrogen In ethanol at 20℃; for 3 h;
1 g (4.73 mmol) of 4-nitrophthalic acid is dissolved in 10 ml of anhydrous ethanol. The solution is stirred at room temperature and degassed under argon. 50 mg of 5percent palladium/carbon are added all at once and hydrogen is bubbled through the solution. After 3 hours, the solution is filtered on celite and then evaporated. [00347] Orange-coloured oil. m=820 mg. Y=96percent. 1H NMR (DMSO): 3.32 (1H, s), 5.95 (1H, s), 6.49-6.53 (2H, m), 7.46-7.50 (1H, d, J=8.8 Hz), 12.33 (2H, COOH, s).
96%
With hydrogen In ethanol at 20℃; for 3 h;
1 g (4.73 mmol) of 4-nitrophthalic acid is dissolved in 10 mL of anhydrous ethanol. The solution is stirred at room temperature and degassed under argon. 50 mg of palladium/charcoal (5percent) are added in a single portion and hydrogen is bubbled into the solution. After 3 hours, the solution is filtered through Celite and then evaporated. [00137] Orange-coloured oil. m=820 mg. Y=96percent. 1H NMR (DMSO): 3.32 (1H, s), 5.95 (1H, s), 6.49-6.53 (2H, m), 7.46-7.50 (1H, d, J=8.8 Hz), 12.33 (2H, COOH, s).
Reference：
[1] Patent: US6689922, 2004, B1, . Location in patent: Page column 20
[2] Patent: US6706725, 2004, B1, . Location in patent: Page column 11
[3] Chemical Communications, 2017, vol. 53, # 62, p. 8751 - 8754
[4] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 230
[5] Journal of the American Chemical Society, 1908, vol. 30, p. 1143
[6] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1878, vol. 10, p. 192[7] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 225
[8] Chemische Berichte, 1901, vol. 34, p. 4352
[9] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 230
[10] Journal of the American Chemical Society, 1908, vol. 30, p. 1143
[11] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1878, vol. 10, p. 192[12] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 225
[13] Journal of medicinal chemistry, 1966, vol. 9, # 1, p. 165 - 168
[14] Letters in Drug Design and Discovery, 2013, vol. 10, # 9, p. 872 - 878
acro-reticular strong acid ion exchange resin (FPC-22); at 101 - 105℃; for 1.41667 - 22h;Conversion of starting material;
Example 2; Solid Acid Resin-Catalyzed Esterification; A 1 gallon autoclave contains a macro-reticular strong acid ion exchange resin (FPC-22). The initial charge of resin to the autoclave was 1070 ml of resin (water wet volume) or about 495 g of resin (net dry weight). The resin was used to catalyze three prior esterification reactions, without any regeneration cycles, prior to this experiment. 117O g Nitro-iso-Phthalic Acid (NlPA) and 710 ml of Methanol was added to the autoclave. The mixture was heated to an operating temperature of 101 - 105C over one hour and then EPO <DP n="36"/>held an additional 25 minutes. After which, 81 ml/min of anhydrous methanol was fed to a vaporizer and then sparged into the reactor as methanol gas. The methanol gas was continuously removed from the reactor over 6 hours to maintain the reactor at a constant weight and in the desired temperature range of 101 - 1050C. Pressure in the reactor varied from 28 psig at the beginning of the methanol sparge to 34 - 36 psig at the end of the methanol sparge. The methanol gas from the reactor was condensed and analyzed for water by Karl Fischer. The water content of the condensed methanol varied from 6.8 % wt/wt at the beginning of the methanol sparge to 0.4 % wt/wt at the end of the sparge. The autoclave was unloaded through a sintered metal frit to separate the reaction mixture from the resin, which remained in the autoclave for subsequent experiments. The reaction mixture was allowed to slowly cool overnight to room temperature. The total product (liquid and solids) from the autoclave weighed 2.00 kg. Solids from the unloading pot analyzed 74 % dry solids. The dry solids contained 0.29 % NIPA, determined by base titration. The liquid from the unloading pot contained 3.4 % dissolved solids. The dissolved solids analyzed 32 % NIPA, also by base titration. The overall conversion of NIPA (MW = 211) to diester (MW=239) was about 99.5 % as illustrated in the summary material balance table:Starting Amount 1170 g NIPAReaction Conversion 99.5% by Trial & ErrorLiquors as % of Total Mass 11 % by Trial & ErrorTotalOverall Balance Liquors Solids as NIPA6 NIPA 2 4 61318 Diester 5 1313 1164676 MeOH 213 4632000 Total 220 1780 1170Analysis % Solids 3.4% 74%% NIPA in dry solids 32% 0.29%; Example 5; Solvent Drying Following Separation of Reaction Mixture from Solid AcidCatalyst; The invention is exemplified as in example 2, except that the reaction mixture was sparged with anhydrous solvent after separation of the solid acid catalyst. A 1 gallon autoclave contains a macro-reticular strong acid ion exchange resin (FPC-22). The initial charge of resin to the autoclave was 1070 ml of resin (water wet volume) or about 495 g of resin (net dry weight). The resin has been used to catalyze six prior esterification reactions, without any regeneration cycles, prior to the upcoming experiment. 117O g Nitro-iso- Phthalic Acid (NIPA) and 710 ml of Methanol was added to the autoclave. The mixture was heated to an operating temperature of 101 - 1050C over two hours, and then held an additional 30 minutes. After which, 91 ml/min of anhydrous methanol was fed to a vaporizer and then sparged into the reactor as methanol gas. The methanol gas was continuously removed from the reactor over 6 hours to maintain the reactor at a constant weight and in the desired temperature range of 101 - 1050C. Pressure in the reactor varied from 30 psig at the beginning of the methanol sparge to 34 - 35 psig at the end of the methanol sparge. The methanol gas from the reactor was condensed and analyzed for water by Karl Fischer. The water content of the condensed methanol varied from 6.6 % wt/wt at the beginning of the methanol sparge to 0.4 % wt/wt at the end of the sparge. The water content of the EPO <DP n="40"/>condensed methanol was substantially not changing with time for approximately one hour, as illustrated by the following measurements:The autoclave was unloaded through a sintered metal frit to separate the reaction mixture from the resin, which remained in the autoclave for subsequent experiments. The reaction mixture was then sparged with anhydrous methanol gas at the same rate as previous for an additional 25 minutes after separation from the resin. The water content of the condensed methanol rapidly decreased with time, as illustrated by the following measurements:After the second sparge was complete, the mixture was allowed to slowly cool overnight to room temperature. The total product (liquid and solids) from the autoclave weighed 2.05 kg. Solids from the unloading pot analyzed 92.6 % Dry Solids. The dry solids contained 0.108 % NIPA, determined by base titration. The liquid from the unloading pot contained 1.56 % dissolved solids. The dissolved solids analyzed 23.4 % NIPA, also by base titration. The overall conversion of NIPA (MW = 211 ) to diester (MW=239) was about 99.7 % as illustrated in the summary material balance table:Starting Amount 1170 g NIPA Reaction Conver...
at 101 - 125℃; under 2208.1 - 2932.13 Torr; for 1.25 - 3h;Conversion of starting material;
Example 3; Comparative Isothermal Esterification with No Solid Acid Catalyst; EPO <DP n="37"/>In this example, the esterification was conducted at 120-1250C without solid acid catalyst as compared to 101-1050C with solid acid catalyst as in Example 2. The addition of solid acid catalyst as in Example 2 increases the conversion of the NIPA to diester. 1755 g Nitro-iso-Phthalic Acid (NIPA) and 925 ml of methanol was added to a 1 gallon autoclave. The mixture was heated to an operating temperature of 120 - 125C over two hours, and then held an additional hour. After which, 37 ml/min of anhydrous methanol was fed to a vaporizer, and then sparged into the reactor as methanol gas. The methanol gas was continuously removed from the reactor over 31 hours, to maintain the reactor at a constant weight and in the desired temperature range of 120 - 125C. Pressure in the reactor varied from 52 psig at the beginning of the methanol sparge to 70 - 75 psig at the end of the methanol sparge. The methanol gas from the reactor was condensed and analyzed for water by Karl Fischer. The water content of the condensed methanol varied from 5.2 % wt/wt at the beginning of the methanol sparge to 0.07 % wt/wt at the end of the sparge. The autoclave was unloaded and the mixture allowed to slowly cool overnight to room temperature. The total product (liquid and solids) from the autoclave weighed 2.65 kg. Solids from the unloading pot analyzed 80% dry solids. The dry solids contained 6% NIPA, determined by base titration. For simplicity, any half ester of NIPA is included as part of the % NIPA value determined by the base titration. The liquid from the unloading pot contained 29 % dissolved solids. The dissolved solids analyzed 46 % NIPA, also by base titration. The overall conversion of NIPA (MW = 211) to dimethyl-5-nitrophthalate (diester; MW=239) was about 91 % as illustrated in the summary material balance table:Starting Amount 1755 g NIPA Reaction Conversion 91% by Trial & Error Liquors as % of Total Mass 11% by Trial & ErrorTotalOverall Balance Liquors Solids as I vJIPA153 NIPA 40 113 153 1815 Diester 47 1768 1602682 MeOH 212 470 2650 Total 299 2351 1755Analysis % Solids 29% 80%% NIPA in dry solids 46% 6%; Example 4; Comparative lsobaric Esterification with No Solid Acid Catalyst; In this example, the esterification was conducted at an operating pressure of 40 - 42 PSIG without solid acid catalyst as compared to an operating temperature of 101-1050C with solid acid catalyst as in Example 2. The addition of solid acid catalyst as in Example 2 increases the conversion of NIPA to diester. 3540 g Nitro-iso-Phthalic Acid (NIPA) and 2210 g of methanol was added to a 2 gallon reactor. The mixture was heated to an operating pressure of 40 - 42 PSIG over 40 minutes, and then held an additional 35 minutes. After which, 1.0 gallon per hour of anhydrous methanol was fed to a vaporizer, and then sparged into the reactor as methanol gas. The methanol gas was continuously removed from the reactor over 770 minutes, to maintain the reactor at a constant weight and in the desired pressure range of 40 - 42 PSIG. Temperature in the reactor varied from, 113C at the beginning of the methanol sparge to 110C at the end of the methanol sparge. The methanol gas from the reactor was condensed and analyzed for water by Karl Fischer. The water content of the condensed methanol varied from 2.2 % wt/wt at the beginning of the methanol sparge to 0.29 % wt/wt at the end of the sparge. The reactor was unloaded and the mixture allowed to slowly cool overnight to room temperature. The total product (liquid and solids) from the reactor weighed 6.05 kg. Solids from the unloading pot analyzed 68 % dry solids. The dry solids contained 27 % NIPA, determined by base titration. The liquid from the unloading pot contained 54 % dissolved solids. The dissolved solids analyzed 52 % NIPA, also by base titration. The overall conversion of NIPA (MW = 211 ) to diester (MW=239) was about 63 % as illustrated in the summary material balance table: EPO <DP n="39"/>Starting Amount 3540 g NIPAReaction Conversion 63% by Trial & ErrorLiquors as % of Total Mass 33% by Trial & ErrorTotalOverall Balance Liquors Solids as NIPA1319 NIPA 556 747 13032516 Diester 513 2020 22372215 MeOH 911 13026050 Total 1980 4070 3540Analysis % Solids 54% 68%% NIPA in dry solids 52% 27%
With methanesulfonic acid; at 80℃; for 16h;Inert atmosphere; Industry scale;
EXAMPLE 1Step 1 : One-pot esterification-reduction4-Nitrophthalic acid was dissolved in 26 L MeOH (slightly endothermic) and 3.62 kg of MsOH (exothermic). The solution was heated under nitrogen at 80 0C in thehydrogenation vessel for 16 h (if preferred, the reaction can also be carried out at reflux in a regular vessel). The solution was cooled to 40 0C and sampled to ensure <6% of remaining monomethyl ester.The solution was further cooled to 20 0C and seeded (seeds can be readily prepared by taking out ca. 50OmL of the solution and stirred at rt with traces of seeds that form on simple evaporation on a spatula) to form a very thick slurry.10% Pd/C was charged with ca. 1 L MeOH and the slurry at rt was carefully stirred under 60 psi of H2 gas to maintain temp <40 0C.After complete reduction of the nitro group, the mixture became a solution containing the catalyst. An additional 16 L of MeOH was added to the mixture to ensure product stays in solution (without this, some product crystallized out after 3 days); if the vessel volume permits, this 16 L of MeOH can be added at the beginning of the reaction to dilute the exotherm of the hydrogenation.The reaction was repeated at the same scale. The two batches were combined and the catalyst was filtered off with MeOH rinse. The filtrate was concentrated to 25 L to give a slurry. EtOAc (44 L) was added followed by a slow addition of aq K3PO4 (made from 16 kg solid + 32 L water, solution ca. 36 L, used all but 1 L) to keep temp <25 0C. The mixture became very thick after 2-4L addition, but then lightened. The pH of the mixture should be about 9 (otherwise adjust with more K3PO4 or 1 N HCl). The bottom aq. layer (ca. 50 L, 0.3% loss) was cut away. The organic layer was washed with 32 L water (aq loss ca 2%), concentrated, solvent switched to toluene to a target volume of ca. 36 L with <4 L EtOAc left. Seed if necessary to induce crystallization. Heptane (20 L) was then added. The slurry was aged at rt for >2 h when LC revealed <3% loss in the mother liquor. The crystals were collected by filtration and rinsing with 1/1 toluene/heptane (18 L) and then heptane (6 L). Drying gave the product in 84% yield (8.85 kg).
A 250 g of phthalic anhydride and 325 mL of concentratedsulphuric acid were placed in the flask and heated untilthe temperature of the mixture raised to 80C. The waterbath was cooled, and 105 mL of fuming nitric acid wasadded slowly from the dropping funnel at such a rate so as tomaintain the temperature of the stirred mixture at 100-110C(about 1 hr). A 450 mL of concentrated nitric acid was addedas rapidly as possible without causing the temperature to riseabove 110C. The mixture was heated on the water or steambath, with stirring, for 2 hrs. The reaction mixture was allowedto stand overnight and then poured into 750 mL ofcold water contained in a 2 L beaker. The mixture of 3- and4-nitro phthalic acids was cooled and filtered through a sinteredglass funnel. The wet cake of acids was returned to therinsed-out beaker and it was stirred thoroughly with 100 mLof water, which dissolved a large amount of the 4-nitrophthalic acid. It was filtered again at the pump and thesolid was dissolved in 100-150 mL of boiling water. The hotsolution was filtered and stirred mechanically until crystallizationcommences and then left overnight until crystallizationwas completed. It was filtered again with suction and this 3-nitro phthalic acid was dried upon filter paper (m.p.206-208C). It was recrystallized from about 250 mL of boilingwater (m.p. 214- 216C) [11].The characterization of products was carried out by meltingpoint determination, FT-IR and NMR spectroscopy asshown in Table 1. The mother liquors from the washings andrecrystallizations were saved for recovery of the 4-nitrophthalic acid. The combined mother liquors were concentratedto a small bulk and the acid was extracted withether. Upon esterification by the Fischer - Speier method, the3-nitro acid formed only the acid ester and was removed byshaking the product with sodium carbonate solution, whilstthe neutral ester of 4-iiitrophthalic acid remained unaffected.Hydrolysis of the neutral ester gave the product, 4-nitrophthalic acid (m. p. 164C).
EXAMPLE 2 A mixture of 21.1. g of 4-nitrophthalic acid and 50.0 g of acetic anhydride were heated at reflux for 6 hours, following which the acetic acid was removed by distillation at atmospheric pressure. The excess acetic anhydride was removed by distillation at 15 mm Hg pressure with the flask temperature not exceeding 120C, leaving a quantitative yield of crude 4-nitrophthalic anhydride, m.p. 114-116C. The product was recrystallized from chloroform to afford a 93% yield of product, m.p. 123-124C, identical to that of Example 1.
88%
With oxalyl dichloride; N,N-dimethyl-formamide; In toluene; for 3h;Inert atmosphere; Reflux;
General procedure: Dicarboxylic acid 2 (1 mmol) and oxalyl chloride (1.2 mmol) were combined in dry toluene (5 mL) and a drop of freshly distilled DMF was added. The reaction vessel was purged with argon and the reaction was heated under stirring for 3 h. The stirring was stopped and the toluene solution was decanted off the oily residue and filtered. Evaporation of the volatiles provided the analytically pure target product which, if necessary, was transformed intro crystalline form by trituration with diethyl ether. In some cases (see ESI) additional crystallization or trituration with 1:2 v/v hexane-toluene mixture was used. .
88%
With acetic anhydride; for 1h;Reflux;
General procedure: A mixture of 3- or 4-nitrophthalic acid (10 g, 0.047 mol) and acetic anhydride (24 mL) was stirredat reflux for 1h. After cooling, volatiles were evaporated (repeated addition of toluene andevaporation facilitated the procedure). The anhydride precipitated out of the residue upon additionof diethyl ether as sub-white powder (3-nitrophthalic anhydride 4a: 7.90 g (90%), 4-nitrophthalicanhydride 4b: 8.00 g (88%)). The anhydrides were used in the next step without characterization.
51%
In acetic anhydride; toluene;
Next, 4-nitrophthalic acid (21.1 g, 0.1 mole) in a round-bottomed flask was admixed with acetic anhydride (40 ml) and refluxed for 1 hour. The mixture was brought to room temperature and acetic anhydride was removed under vacuum. The concentrated mixture was allowed to stand overnight, and the solid obtained was recrystallized using toluene to give 4-nitrophthalic anhydride ((9.9 g (51%), Mp 119 C.)).
37%
With thionyl chloride; trifluoro-N-(oxo-lambda4-sulfanylidene)methanesulfonamide; at 90 - 95℃; for 0.666667h;
4-Nitrophthalic acid(8), 0.21 g (1.00 mmol), and thionyl chloride, 0.1 mL,were added to 0.40 g (2.05 mmol) of compound 1. Themixture was stirred for 40 min at 90-95C, cooled, andevaporated under reduced pressure. The residue wasdissolved in a small amount of acetone, and the product(5-nitro-2-benzofuran-1,3-dione) was precipitated withhexane, filtered off, washed with diethyl ether, anddried. Yield 0.072 g (37%). IR spectrum (film), nu,cm-1: 3111, 1852, 1791, 1545, 1348, 1258, 1126, 929,899, 710. 1H NMR spectrum (CD3CN), delta, ppm: 8.19 d(1H, 7-H, J = 8.4 Hz), 8.59 d (1H, 6-H, J = 8.4 Hz),8.61 s (1H, 4-H); published data [6]: delta, ppm: 8.28 d(J = 8.2 Hz), 8.79 d.d (J = 8.2, 1.8 Hz), 8.86 d (J =1.4 Hz). 13C NMR spectrum (CD3CN), deltaC, ppm:121.65, 127.99, 132.19, 133.91, 136.80, 153.90,162.22, 162.49.
In deoxygenated nitrogen; toluene;
EXAMPLE 1 In a 100-ml round-bottom flask equipped with an inlet tube for deoxygenated nitrogen, a gas outlet tube, a thermometer extending to the bottom of the flask and an electric heating mantle, was placed 21.1 g of 4-nitrophthalic acid and the apparatus was flushed with nitrogen. The mass was heated under a slow flow of nitrogen for 4 hours at 165-170C, and then allowed to cool to room temperature. The crude product was added to toluene, heated to reflux, and filtered while hot. The filtrate was cooled to 0C, the solid precipitate recovered by filtration, recrystallized from chloroform and dried to constant weight at 35C in a vacuum oven, to yield 11.08 g of 4-nitrophthalic anhydride, m.p. 123-124C, whose percent elemental analysis of C, 49.81; H, 1.53; N, 7.22 is in excellent agreement with the theoretical values.
With acetic anhydride;Reflux;
General procedure: A 75 g of 3 or 4-nitro phthalic acid and 70 g (65 mL) ofredistilled acetic anhydride were placed in a 250 mL roundbottomedflask, fitted with a reflux condenser. The mixturewas heated to gentle boiling until a clear solution was obtained.The hot mixture was poured into the into a large porcelaindish and allowed to cool. The crystalline mass wasgrinded thoroughly in a mortar and filtered at the pumpthrough a sintered glass funnel. The crystals were returned tothe mortar and grinded with 50 mL of sodium-dried etherand filtered. Again the crystals were returned to the mortarand washed once more with 50 mL of dry, alcohol-free ether.It was dried in the air for a short time (m. p. 162C). Thecharacterization of products was carried out by melting pointdetermination, FT-IR and NMR spectroscopy as shown inTable 1.
With acetic anhydride; at 90 - 120℃; for 2h;
First, 80 g of phthalic anhydride was added to a 500 mL four-necked flask, and 180 mL of concentrated sulfuric acid was slowly added thereto. After stirring for 10 minutes, the mixture was placed in a water bath and 60 g of fuming nitric acid was added dropwise at 70 C. After the completion of the dropwise addition, the reaction was stirred at 70 C for 1 hour. After completion of the reaction, the reaction mixture was cooled to room temperature with an ice bath and filtered. The residue was washed three times with water and then dissolved in 100 mL of distilled water. Keeping at 55 C for 1 h, filtering, drying the residue to obtain 4-nitrophthalic acid; 100g of 4-nitro phthalic acid added to four-necked flask, to which was added 30mL of acetic anhydride, stirred until solid was completely dissolved at 90 deg.] C, temperature was raised to 120 deg.] C and dissolved,Stirring at 90 C until all the solid dissolved, dissolved and heated to 120 C and maintained at this temperature for 2h, and side reaction while stirring, after cooling the reaction to room temperature, filtration, take the filter cake washed with ether 2, Dried at 40 C for 4 hours to obtain 4-nitrophthalic anhydride; 20 g of urea was added to a 500-mL three-necked flask, placed in a water bath, and the 4-nitrophthalic anhydride was added to the flask in 3 portions at a controlled temperature of 5 C, And the temperature was gradually raised to 70 C after the completion of the addition, so that 4-nitrophthalic anhydride was completely dissolved, and the temperature was lowered to 45 C. The flask was evacuated and 10 mL of the solid was precipitated when no more solid precipitated And then the mixture was stirred for 20 min at 400 rpm. After stirring, the mixture was cooled to room temperature, filtered, washed with distilled water and dried at 50 C. Giving 4-nitro-2-carbamoylbenzoic acid; To a 500 mL four-necked flask, 40 mL of a 10% aqueous solution of sodium hypochlorite was placed in an ice bath, and 100 g of the 4-nitro-2-carbamoylbenzoic acid obtained above was added thereto at 0 C. The temperature was increased to 30 C, After the reaction, the reaction was cooled to -5 C, and immediately after cooling, the mixture was suction filtered and the residue was dried at 60 C to obtain 2-amino-4-nitrobenzoic acid. To a 250 mL three-necked flask, 15 g of the 2-amino-4-nitrobenzoic acid obtained above was added, and 90 mL of absolute ethanol was added thereto. The mixture was refluxed at 100 C for 1 hour. After refluxing, 50 mL of 9% Ammonium sulfate solution, in the 800W microwave heating continue to return under 5min, hot filter, wash the residue to pH 7, the combined filtrate, pour 50g ice water and stir quickly, standing 5min after the crude product precipitation, with the quality The crude product was dissolved in 30% hydrochloric acid and filtered. The filtrate with 30% ammonia water quality adjusted to pH 3, solid precipitation after the filter, the residue placed 60 drying, can be 2,4-diaminobenzoic acid.
With hydrogen;5%-palladium/activated carbon; In ethanol; at 20℃; for 3h;
1 g (4.73 mmol) of 4-nitrophthalic acid is dissolved in 10 ml of anhydrous ethanol. The solution is stirred at room temperature and degassed under argon. 50 mg of 5% palladium/carbon are added all at once and hydrogen is bubbled through the solution. After 3 hours, the solution is filtered on celite and then evaporated. [00347] Orange-coloured oil. m=820 mg. Y=96%. 1H NMR (DMSO): 3.32 (1H, s), 5.95 (1H, s), 6.49-6.53 (2H, m), 7.46-7.50 (1H, d, J=8.8 Hz), 12.33 (2H, COOH, s).
96%
With hydrogen;5%-palladium/activated carbon; In ethanol; at 20℃; for 3h;
1 g (4.73 mmol) of 4-nitrophthalic acid is dissolved in 10 mL of anhydrous ethanol. The solution is stirred at room temperature and degassed under argon. 50 mg of palladium/charcoal (5%) are added in a single portion and hydrogen is bubbled into the solution. After 3 hours, the solution is filtered through Celite and then evaporated. [00137] Orange-coloured oil. m=820 mg. Y=96%. 1H NMR (DMSO): 3.32 (1H, s), 5.95 (1H, s), 6.49-6.53 (2H, m), 7.46-7.50 (1H, d, J=8.8 Hz), 12.33 (2H, COOH, s).
With methanesulfonic acid at 20 - 100℃; Inert atmosphere;
1
Example 1; Preparation of 5-/6-nitrofluorescein; Reactor 1; A reactor previously made inert with nitrogen was charged with methanesulphonic acid (2.43 L). 4-nitrophthalic acid (600 g) was added, and the temperature maintained between 20 -25 0C. Following agitation for 10 minutes, resorcinol (benzene-1 ,3-diol) (657 g) was added and the reaction mixture heated cautiously to 70 0C then to 95-100 0C. The reaction mixture was stirred at 95-1000C and stirring and heating was continued for a minimum of 2 hours. The reaction mixture was sampled every 2 hours for in-process analysis. Following reaction completion, indicated by a limit of not greater than 2% 4-nitrophthalic acid by HPLC, the reaction was cooled to 60 - 70 0C.; Reactor 2; A second reactor was charged with cold (0-10 0C), deionised water (7.2 L). The reaction mixture at 60-70 °C was charged to the cold water, keeping the temperature of the solution at less than 30 0C. The mixture was agitated for a minimum of 30 minutes and the precipitated product isolated by filtration. The isolated material was washed with deionised water (0.36 L) and pulled dry under vacuum.The damp product was recharged to the reactor, deionised water (4.8 L) added and the mixture heated to 95-100 0C with agitation for 30 minutes. The suspension was cooled to 20-30 0C and the solid product isolated by filtration, washed with deionised water (0.48 L) and pulled dry. The damp product was analysed by proton NMR to determine the methanesulphonic acid ester content. A methanesulphonic acid ester content of less than 5 % relative to the product is preferred. The hydrolysis procedure was repeated until the ester content was within this limit. The solid was transferred to a vacuum oven and dried at 65-70 0C until constant weight to give the product as a dark orange solid. m.p = 346-349 0C1H (DMSO-D6) 6.54-6.58 (6H, m, 6-isomer) 6.58-6.72 (6H, m, 5-isomer), 7.57 (1 H, d, 5-isomer), 8.1 (1 H, d, 6-isomer), 8.26 (1 H, d, 6-isomer), 8.5 (1 H, dd, 6-isomer), 8.57 (1 H, dd, 5-isomer), 8.66 (1 H, d, 5-isomer), (1 H, m), 4.15 (1 H, d) m/z = 378.1 (M+1 )
2
First, the compound (54) was synthesized using the compounds (52) and (53). 4.37 parts of the compound (52), 8.09 parts of the compound (53) and 0.0600 parts of tetraisopropoxytitanium were added, And the mixture was stirred at 150 ° C. for 4 hours. After completion of the reaction, the unreacted compound (53) was distilled off by distillation under reduced pressure, The mixture was extracted with chloroform and concentrated to obtain 8.20 parts of Compound (54) (yield 91.1%).
86%
With titanium(IV) isopropylate at 150℃; for 4h;
2
[0121] Synthesis Example 2[0122] Synthesis of compound (39):A compound (39) in which, in the formula (1) , Ri to R4, R6, R7/ R9, R11 , i4 and R15 are hydrogen atoms, R12 and Ri3 are LiR2o groups, where Li is a carboxylate group and R20 is a 2-ethylhexyl group, R5 and R8 are COORi7 groups, and Rio , 16 and R17 are methyl groups was synthesized according to the following synthesis scheme. [0123] First, a compound (65) was synthesized by using compounds (63) and (64). 8.74 parts of the compound (63), 16.18 parts of the compound (64) and 0.12 part of tetraisopropoxytitanium were put together, and the mixture obtained was stirred at 150°C for 4 hours.After the reaction was completed, any unreactedcompound (64) was separated off by distillation under reduced pressure, and thereafter the reaction product obtained was extracted with chloroform, and thenconcentrated to obtain 15.30 parts of the compound (65) (yield: 86.0%) .
With sodium hydroxide; In water; at 150℃; for 48h;Autoclave;
A mixture of Co(NO3)2·6H2O (0.116 g, 0.40 mmol), 1,4-bis(1,2,4-triazol-1-ylmethyl) benzene (0.024 g, 0.10 mmol), 4-nitrophthalic acid (0.042 g, 0.20 mmol), NaOH (0.008 g, 0.20 mmol) and H2O (10 mL) was sealed in a 25 mL Teflon-lined stainless steel vessel and heated at 150 C for 2 days, and then cooled to room temperature. Red block-shaped crystals were filtered off, washed with water and dried in air. Yield: 73% based on btx. Anal. Calc. for C14H13CoN4O8 (424.21): C, 39.64; H, 3.09; N, 13.21. Found: C, 39.78; H, 3.00; N, 12.98%.
Step A: Dimethyl 4-aminobenzene-l,2-dicarboxylate Materials FW Mass Volume mol Equiv. (1 (g/niL) MeOH 26 L 10% Pd/C 159 g (wet) K3PO4 212 8.0 kg 37.7 1.5 EtOAc 27 L 4-Nitrophthalic acid was dissolved in 26 L MeOH (slightly endothermic) and 3.62 kg of methanesulfonic acid (MsOH, exothermic). The solution was heated under nitrogen at 80 C in the hydrogenation vessel for 16 h (if preferred, the reaction can also be carried out at reflux in a regular vessel). The solution was cooled to 40 C and sampled to ensure The solution was further cooled to 20 C and seeded (seeds can be readily prepared by taking out ca. 500 mL of the solution and stirred at 23 C with traces of seeds that form on simple evaporation on a spatula) to form a very thick slurry. 10% Pd/C was charged with ca. 1 L MeOH and the slurry at 23 C was carefully stirred under 60 psi of gas to maintain temp After complete reduction of the nitro group, the mixture became a solution containing the catalyst. An additional 16 L of MeOH was added to the mixture to ensure product stays in solution (without this, some product crystallized out after 3 days); if the vessel volume permits, this 16 L of MeOH can be added at the beginning of the reaction to dilute the exotherm of the hydrogenation. The reaction was repeated at the same scale. The two batches were combined and the catalyst was filtered off with MeOH rinse. The filtrate was concentrated to 25 L to give a slurry. EtOAc (44 L) was added followed by a slow addition of aq K3PO4 (made from 16 kg solid + 32 L water, solution ca. 36 L, used all but 1 L) to keep temp 2 h The mixture became very thick after 2-4 L addition, but then lightened. The pH of the mixture should be about 9 (otherwise adjust with more K3PO4 or 1 N HC1). The bottom aqueous layer (ca. 50 L, 0.3% loss) was cut away. The organic layer was washed with 32 L water (aq loss ca 2%), concentrated, solvent switched to toluene to a target volume of ca. 36 L with 2 h when LC revealed < 3% loss in the mother liquor. The crystals were collected by filtration and rinsing with 1/1 toluene/heptane (18 L) and then heptane (6 L), and dried to give the title product.
Step A: Dimethyl 4-aminobenzene-l,2-dicarboxylate Materials FW Mass Volume mol Equiv. (1 (g/niL) (wet) K3PO4 212 8.0 kg 37.7 1.5 EtOAc 27 L 4-Nitrophthalic acid was dissolved in 26 L MeOH (slightly endothermic) and 3.62 kg of methanesulfonic acid (MsOH, exothermic). The solution was heated under nitrogen at 80 C in the hydrogenation vessel for 16 h (if preferred, the reaction can also be carried out at reflux in a regular vessel). The solution was cooled to 40 C and sampled to ensure The solution was further cooled to 20 C and seeded (seeds can be readily prepared by taking out ca. 500 mL of the solution and stirred at 23 C with traces of seeds that form on simple evaporation on a spatula) to form a very thick slurry. 10% Pd/C was charged with ca. 1 L MeOH and the slurry at 23 C was carefully stirred under 60 psi of gas to maintain temp After complete reduction of the nitro group, the mixture became a solution containing the catalyst. An additional 16 L of MeOH was added to the mixture to ensure product stays in solution (without this, some product crystallized out after 3 days); if the vessel volume permits, this 16 L of MeOH can be added at the beginning of the reaction to dilute the exotherm of the hydrogenation. The reaction was repeated at the same scale. The two batches were combined and the catalyst was filtered off with MeOH rinse. The filtrate was concentrated to 25 L to give a slurry. EtOAc (44 L) was added followed by a slow addition of aq K3PO4 (made from 16 kg solid + 32 L water, solution ca. 36 L, used all but 1 L) to keep temp 2 h when LC revealed
5-AF 9 was synthesized according to the method as illustrated in Figure 2. 4-nitrophthalic acid 5 (10 g, 45 mmol), resorcinol 4 (12.44 g, 113 mmol), and zinc chloride (13.62 g, 100 mmol) were heated at 120 C for melting. The mixture was stirred at 150 C for 2 h until the material solidified. The mixture was pulverized and boiled in 150 mL 1M HCl for 1 h. The solid was collected on a frit, washed several times with hot water, and dried in vacuo to obtain an orange precipitate 5(6)-nitrofluorescein 6. 5(6)-nitrofluorescein 6 (7.6 g, 20 mmol), sodium hydrosulfide (8.2 g, 146 mmol) and 250 mL sodium sulfide (17.5 g, 73mmol) solution were mixed and refluxed for 24 h. The solution was cooled down to the room temperature and a red-brown precipitate was collected by adding acetic acid to the solution. The precipitate was refluxed for 6 h with 300 mL diluted hydrochloric acid and filtered to get rid of the sulfur. The filtrate was cooled at 4 C for 24 h to obtain 5-AF. The crude was purified by column chromatography on silica gel (MeOH/CH2Cl2, 1:15) to give 9 (2.94 g, yield 40%). 1H NMR (400 MHz, DMSO-d6) (delta, ppm): 10.04 (s, 2H), 6.97 (s, 1H), 6.94 (d, J = 8.3 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H), 6.63 (s, 2H), 6.58 (d, J = 8.4 Hz, 2H), 6.53 (d, J = 8.6Hz, 2H), 5.72 (s, 2H); 13C NMR (400 MHz, DMSO-d6) (delta, ppm): 170.20, 159.56, 152.39, 150.72, 139.85, 129.35, 127.79, 124.55, 122.47, 112.94, 111.07, 106.89, 102.61, 83.28; FT-IR (KBr) (cm-1): 3424.24, 1715.09, 1601.22, 1467.70, 1388.70, 1318.80, 1274.35, 1174.71, 849.48; MS (ESI): m/z = 345.9 (M-H)-, calcd. 347.08.
4-Nitrophthalic acid was dissolved in 26 L MeOH (slightly endothermic) and 3.62 kg of methanesulfonic acid (MsOH, exothermic). The solution was heated under nitrogen at 80 C. in the hydrogenation vessel for 16 h (if preferred, the reaction can also be carried out at reflux in a regular vessel). The solution was cooled to 40 C. and sampled to ensure (0188) The solution was further cooled to 20 C. and seeded (seeds can be readily prepared by taking out ca. 500 mL of the solution and stirred at 23 C. with traces of seeds that form on simple evaporation on a spatula) to form a very thick slurry.
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;
1.1 General procedure to synthesize substrate 1a-1n, 1s, 1t, 4a-4e through esterification.
General procedure: To a stirred solution of the corresponding alcohol and the carboxylic acid in dry dichloromethane(0.2 M) was added EDC.HCl (3 equiv. according to limiting reagent) and 4-dimethylaminopyridine (DMAP, 1 equiv.) at room temperature. The reaction mixture was stirredat room temperature and monitored by TLC. Upon the complete conversion of the startingmaterial, the crude reaction mixture was washed by H2O and Brine. The organic layer was driedby Mg2SO4. The solvent was removed under reduced pressure and the residue was purified byflash chromatography on silica gel to give desired product.
In water; N,N-dimethyl-formamide at 95℃; for 336h;
Synthesis of [Zn(npa)(L1)]2H2O}n (1)
A mixture of Zn(OAc)22H2O (0.1 mmol), L1 (0.1 mmol), and np a(0.1 mmol) and H2O/DMF (4 ml/2 ml) was added in a 15 ml Teflon-lined stainless steel reactor at 95 °C, left for two weeks, and then slowly cooled to room temperature. Colorless blocks of single crystals suitable for the X-ray data collection were obtained by filtration, washed with H2O/MeOH (4/1), and air-dried. Yield: 81 % (based on bipmo). Elemental analyses: chemical formula [C27H21N5O9Zn]; calculated, %: C 51.90, H 3.39, N 11.21. Found, %: C 51.78, H 3.28, N 11.29. IR(KBr, cm-1): 3140, 3117, 2974, 2929, 2897, 1658, 1634, 1605, 1574, 1522, 1482, 1430, 1392, 1346, 1312, 1283, 1259, 1186,1161, 1122, 1091, 1068, 1049, 963, 930, 881, 859, 835, 790, 766, 736, 710, 673, 656, 616, 523, 464
To a solution of 4-nitrophthalic acid (10.6 g, 50.2 mmol) in methanol (50 ml) was added methanesulfonic acid (7.2 g, 75.3 mmol). The reaction mixture was heated at refluxovernight. After cooling to room temperature, Pd/C (1 g in 5 ml of water) was added and the reaction mixture was stirred at 37C for 9 h. Ethyl acetate (50 ml) was then added and Pd/C was removed by filtration. Volatiles were removed under vacuum to dryness and the crude product was dissolved in ethyl acetate (-100 ml) and the organic phase was washed with water, dried over magnesium sulfate and filtered. Volatiles were removed under vacuumgive 10.5 g (100%) of the desired product. This product was used directly in next step withoutfurther purification.1H NMR (CDCI3, 400 MHz) O 3.85 (5, 3H), 3.92 (5, 3H), 6.69 (d, 1H), 6.75 (5, 1H), 7.74 (d,1 H).
d. (isonicotinamide): (4-nitrophthalic acid) [(HL + ) ·(Hnpta -)] (4)
A solution of 4-nitrophthalic acid (21.1 mg, 0.1 mmol) in methanol (14 mL) was added dropwise to a vigorously stirred solution of isonicotinamide (12.2 mg, 0.1 mmol) in methanol (3 mL) over 5 min. The solution was stirred for a few minutes, filtered into a test tube, and left standing at room tempera- ture for 10 days. Light yellow block crystals were isolated after slow evaporation of the methanol solution in air. The crys- tals were collected and dried in air to give [(HL + ) ·(Hnpta -)] (4) . (yield: 26 mg, 78.02%). mp 161-162 °C. Elemental analy- sis: Calc. for C 14 H 11 N 3 O 7 (333.26): C, 50.41; H, 3.30; N, 12.60. Found: C, 50.30; H, 3.16; N, 12.46. Infrared spectrum (cm -1 ): 36 80s( (OH)), 344 9s( as (NH)), 3372s( s (NH)), 3256m, 3134m, 3070m, 2988m, 2944m, 2835m, 1729s( (C = O)), 1673s( as (C = O)), 1620s( as (CO 2 -)), 1608m( (C = C)), 1531s( as (NO 2 )), 1486m, 14 4 4m( (C = N)), 1398s( s (CO 2 -)), 1327s( s (NO 2 )), 1288s( s (C- O)), 1246m, 1204m, 1163m, 1120m, 1078m, 1035m, 992m, 950m, 909m, 866m, 823m, 777m, 734m, 690m, 650m, 626m, 610m.
With chlorine; potassium carbonate; molybdenum; In 1,2-dichloro-benzene; at 90 - 190℃; for 8h;
Put 105.6g (0.5mol) 4-nitrophthalic acid and 211.2g o-dichlorobenzene into a 500ml four-necked reaction flask equipped with condenser, reflux water separator, thermometer and stirring, stir to dissolve, and heat to 170C-190C, reflux dehydration, when there is no more water out, cool to 90C-100, put 2.112g molybdenum powder and 37.95g anhydrous potassium carbonate; Raise the temperature to 180C-190C, control the flow rate, pass 10.56g Cl2 into the reaction solution at a constant speed, keep the temperature for 8h, take samples, HPLC detects that the content of 4-nitrophthalic acid is less than 1%, stop the reaction, and lower the temperature to 90C-100C, add water, distill to recover the solvent, and cool to 0C-10C after steaming to obtain crude 4,4'-diphenyl ether tetracarboxylic acid; Add the obtained crude product to a 3-5% hydrochloric acid solution, raise the temperature to 90C-100C, hold for 2h, lower the temperature to 0-10C, and filter to obtain 4,4'-biphenyltetracarboxylic acid fine product; Then put the 4,4'-biphenyltetracarboxylic acid product into pure water, raise the temperature to reflux for 2h, cool to 0C-10, and filter to obtain white to off-white 3,3',4,4'-diphenyl ether tetracarboxylic acid Refined product; The refined product of 3,3'4,4'-diphenyl ether tetracarboxylic acid is heated and dehydrated at 210C-230C to obtain 4,4'-diphenyl ether tetracarboxylic dianhydride.
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