* 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] Bulletin of the Chemical Society of Japan, 1959, vol. 32, p. 691
[2] Patent: CN108164452, 2018, A, . Location in patent: Paragraph 0041; 0042
Reference：
[1] Journal of Organic Chemistry, 1983, vol. 48, # 15, p. 2465 - 2468
[2] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 5, p. 1388 - 1391
[3] Organic Letters, 2010, vol. 12, # 21, p. 4796 - 4799
[4] Chemische Berichte, 1882, vol. 15, p. 320
[5] Oef. Sv., 1881, # 9, p. 10[6] Bulletin de la Societe Chimique de France, 1881, vol. <2> 36, p. 434
[7] Chemische Berichte, 1892, vol. 25, p. 2115
[8] Justus Liebigs Annalen der Chemie, 1886, vol. 233, p. 226[9] Journal of the Chemical Society, 1886, vol. 49, p. 518
[10] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 1834 - 1840
[11] Patent: US5739135, 1998, A,
[12] Patent: US5049682, 1991, A,
7
[ 615-60-1 ]
[ 118-45-6 ]
[ 89-20-3 ]
Reference：
[1] Patent: US4124593, 1978, A,
[2] Patent: US4025505, 1977, A,
8
[ 56047-23-5 ]
[ 118-45-6 ]
Reference：
[1] Canadian Journal of Chemistry, 1985, vol. 63, p. 121 - 128
[2] European Journal of Medicinal Chemistry, 1987, vol. 22, p. 229 - 238
[3] Patent: US2012/46307, 2012, A1, . Location in patent: Page/Page column 45
Reference：
[1] Zhurnal Obshchei Khimii, 1950, vol. 20, p. 469,471[2] Chem.Abstr., 1958, p. 18325
15
[ 2065-70-5 ]
[ 118-45-6 ]
Reference：
[1] Chemische Berichte, 1882, vol. 15, p. 320
16
[ 88-99-3 ]
[ 118-45-6 ]
Reference：
[1] Journal of the Chemical Society, 1929, p. 255
17
[ 56-23-5 ]
[ 5466-84-2 ]
[ 118-45-6 ]
Reference：
[1] Ukrainskii Khimicheskii Zhurnal (Russian Edition), 1958, vol. 24, p. 68[2] Chem.Abstr., 1958, p. 18325
18
[ 85-44-9 ]
[ 118-45-6 ]
[ 117-21-5 ]
[ 942-06-3 ]
[ 51971-64-3 ]
Reference：
[1] Journal of Organic Chemistry, 1983, vol. 48, # 15, p. 2465 - 2468
[2] Journal of Organic Chemistry, 1983, vol. 48, # 15, p. 2465 - 2468
[3] Journal of Organic Chemistry, 1983, vol. 48, # 15, p. 2465 - 2468
19
[ 40604-49-7 ]
[ 118-45-6 ]
Reference：
[1] Chemische Berichte, 1882, vol. 15, p. 320
20
[ 89-20-3 ]
[ 75-36-5 ]
[ 118-45-6 ]
Reference：
[1] Journal of the Chemical Society, 1929, p. 255
21
[ 118-45-6 ]
[ 7439-89-6 ]
[ 86-90-8 ]
Reference：
[1] Patent: US4962206, 1990, A,
22
[ 118-45-6 ]
[ 1823-59-2 ]
Yield
Reaction Conditions
Operation in experiment
85%
With potassium carbonate In water; 1,2-dichloro-benzene for 3.5 h; Heating / reflux
4-Chlorophthalic anhydride, 16 grams (g) (87.7 mmol), was weighed into a 150 milliliter (ml) three-necked flask fitted with a distillation head and containing about 100 ml of distilled o-dichlorobenzene having a water content of less than 5 ppm. The mixture was heated at reflux for 0.5 hour in a nitrogen atmosphere and about 80 ml of o-dichlorobenzene was removed by distillation. [00022] Powdered potassium carbonate, 6.06 g (43.8 mmol), was added to another flask with 50 ml of dry o-dichlorobenzene. The suspension was heated at reflux for 0.5 hour under nitrogen and 40 ml of o-dichlorobenzene was distilled. The 4-chlorophthalic anhydride solution was transferred to the flask containing carbonate. The mixture was stirred and 468 mg (1.77 mmol) of hexaethylguanidinium chloride (in the form of an 18percent solution in o-dichlorobenzene containing less than 15 ppm of water) was added, whereupon the solution turned yellow as refluxing was continued. Periodic analysis of the mixture showed a 93percent yield of the desired 4,4'-ODPA after 3 hours. In a control experiment employing tetraphenylphosphonium bromide at the same mole percent level and powdered potassium carbonate, a period of 13 hours was required to attain the same yield. The procedure of Example 1 was repeated except that granular potassium carbonate was used and the level of hexaethylguanidinium chloride was 2.0 mole percent based on 4-chlorophthalic anhydride. Product formation leveled off after 3 hours at a minimum of about 85percent total yield. [00024] While typical embodiments have been set forth for the purpose of illustration, the foregoing descriptions and examples should not be deemed to be a limitation on the scope of the invention. Accordingly, various modifications, adaptations, and alternatives may occur to one skilled in the art without departing from the spirit and scope of the present invention.
85%
With potassium carbonate; sodium nitrite In N,N-dimethyl acetamide; toluene at 162 - 170℃; for 5 h;
150 g (0 · 82 mol) of 4-chlorophthalic anhydride, 11 g (0 · 08 mol) of potassium carbonate, 22 g of sodium nitrite was placed in a reactor containing 504 g of dimethylacetamide and 144 g of toluene, and the temperature was raised to 162 ° C, the reaction was carried out at 162 ° C to 170 ° C for 5 hours, followed by distillation under reduced pressure to distill the solvent, and distillation was carried out for 20 min, thereafter, 600 g of pure water was added to the vacuum, and the mixture was further stirred and refluxed for 1 to 2 hours, filtered at 102 ° C, and washed with water, the mixture was filtered and dried to obtain 107 g of 3,3',4,4'-diphenyl ether tetracarboxylic dianhydride, the yield was 85percent, mp 226 ° C, and the purity of liquid chromatography was 99.6percent.
82%
Stage #1: With monopotassium carbonate In 2,4-dichlorotoluene for 7.5 h; Heating / reflux; Nitrogen atmosphere Stage #2: Heating / reflux
The procedure of Example 1 was repeated, substituting 2,4-dichlorotoluene for the o-dichlorobenzene and reducing the tetraphenylphosphonium bromide amount to 200 mg. Reflux time was 7.5 hours after the final addition of K2CO3. Product yield was 82percent of theoretical
80%
With monopotassium carbonate In 1,2-dichloro-benzeneHeating / reflux
4-Chlorophthalic anhydride (16 grams [g], 87.7 mmol) was weighed into a 50 milliliter (ml) round-bottomed flask containing about 17 ml of o-dichlorobenzene. The mixture was heated at reflux for 0.5 hour in a nitrogen atmosphere with distillation of solvent until less than 20 ppm of water was present, whereupon about 7 ml of solvent had been removed. Tetraphenylphosphonium bromide, 400 milligrams (mg) (0.95 mmol) was added with stirring, whereupon the solution turned yellow. Potassium bicarbonate, 22 mg (0.22 mmol), was added, followed by 5.45 g (39.5 mmol) of potassium carbonate in a stepwise fashion over 5-10 minutes. The mixture was heated at reflux (bath temperature 200° C.) after the first addition of K2CO3. The mixture was heated under reflux for 17 hours after the final addition of K2CO3. At the end of the reaction, additional o-dichlorobenzene was added to form a 10percent solution and the by-product KCl was removed by filtration while hot. The filtrate was cooled to room temperature, whereupon the desired 4,4'-ODPA precipitated and was collected by suction filtration. 11.56 g of slightly pink-colored powder was obtained. Recrystallization from o-dichlorobenzene afforded 10.87 g of product (80percent of theoretical) as an off-white powder, m.p. 225-226° C. 4-Chlorophthalic anhydride (4800 g, 26.3 moles) and 7836 g of o-dichlorobenzene were charged to a 3.8 liter (L) stainless steel reactor. The mixture was heated at reflux for about 0.5 hour in a nitrogen atmosphere and 1020 g of o-dichlorobenzene was removed to dry the system. With stirring, 120 g (0.29 mole) of tetraphenylphosphonium bromide was added. After mixing, 6.6 g (0.066 mole) of potassium bicarbonate was added, followed by 1650 g (11.95 moles) of potassium carbonate in 7 portions. The mixture was heated under reflux for 27 hours after the last addition of K2CO3 and periodically analyzed. About 60percent of conversion was achieved at this point. To make sure that the reaction went to completion, an additional 50 g (0.119 mole) of tetraphenylphosphonium bromide was added. The mixture was heated overnight, whereupon conversion reached about 90percent. o-Dichlorobenzene, 39,500 g, was added to dilute the reaction mixture and the temperature was brought to 165° C. A hot filtration was performed through a 1-micron filter bag. The filtrate was cooled to room temperature and the desired 4,4'-ODPA was collected in about 80percent crude yield and 95percent purity. Recrystallization from o-dichlorobenzene gave pure product, m.p. 225-226° C. While typical embodiments have been set forth for the purpose of illustration, the foregoing descriptions and examples should not be deemed to be a limitation on the scope of the invention. Accordingly, various modifications, adaptations, and alternatives may occur to one skilled in the art without departing from the spirit and scope of the present invention.
Reference：
[1] Patent: US5153335, 1992, A,
[2] Patent: US5153335, 1992, A,
[3] Patent: US5153335, 1992, A,
[4] Patent: US5153335, 1992, A,
26
[ 118-45-6 ]
[ 2751-90-8 ]
[ 120-82-1 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
27
[ 118-45-6 ]
[ 2751-90-8 ]
[ 120-82-1 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
28
[ 118-45-6 ]
[ 2751-90-8 ]
[ 120-82-1 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
29
[ 118-45-6 ]
[ 2751-90-8 ]
[ 120-82-1 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
30
[ 118-45-6 ]
[ 2751-90-8 ]
[ 120-82-1 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
31
[ 118-45-6 ]
[ 582-25-2 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
32
[ 118-45-6 ]
[ 2751-90-8 ]
[ 50-30-6 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
33
[ 118-45-6 ]
[ 2751-90-8 ]
[ 50-79-3 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
34
[ 118-45-6 ]
[ 2751-90-8 ]
[ 99-94-5 ]
[ 120-82-1 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
35
[ 118-45-6 ]
[ 2751-90-8 ]
[ 118-91-2 ]
[ 120-82-1 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
36
[ 118-45-6 ]
[ 2751-90-8 ]
[ 74-11-3 ]
[ 120-82-1 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
37
[ 118-45-6 ]
[ 19398-61-9 ]
[ 2751-90-8 ]
[ 74-11-3 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
38
[ 118-45-6 ]
[ 95-73-8 ]
[ 2751-90-8 ]
[ 74-11-3 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
39
[ 118-45-6 ]
[ 2751-90-8 ]
[ 95-50-1 ]
[ 74-11-3 ]
[ 1823-59-2 ]
Reference：
[1] Patent: US5153335, 1992, A,
40
[ 118-45-6 ]
[ 117-21-5 ]
[ 36978-41-3 ]
Yield
Reaction Conditions
Operation in experiment
87.7%
at 30℃; for 8 h; Inert atmosphere
In a 1000 ml three-necked flask, 18.3 g (0.1 mol) of 4-chlorophthalic anhydride and 18.3 g (0.1 mol) were added 3-chlorophthalic anhydride, 300 g of anisole as solvent, 0.13 g (0.001 mol) of nickel chloride as a catalyst, 0.198 g (0.001 mol) of C-1 as a catalyst ligand, and 0.03 g (0.0003 mol) of sodium bromide as a catalyst Auxiliary, 13 g (0.2 mol) of zinc powder was used as a reducing agent, and the reaction was stirred at 30 ° C for 8 hours under a nitrogen atmosphere. The reaction solution was filtered to remove insoluble solids in the reaction liquid. 300 g of methanol was added to the filtration mother liquor, and the product was precipitated, filtered, and dried to obtain 25.8 g of the product 2,3,3',4'-biphenyltetracarboxylic dianhydride, yield 87.7percent.
Reference：
[1] Patent: CN108250169, 2018, A, . Location in patent: Paragraph 0010; 0052-0055; 0058; 0061; 0064; 0071
41
[ 615-60-1 ]
[ 118-45-6 ]
[ 89-20-3 ]
Reference：
[1] Patent: US4124593, 1978, A,
[2] Patent: US4025505, 1977, A,
Reference：
[1] Journal of Chemical and Engineering Data, 2009, vol. 54, # 3, p. 1135 - 1137
45
[ 118-45-6 ]
[ 7732-18-5 ]
[ 89-20-3 ]
Reference：
[1] Justus Liebigs Annalen der Chemie, 1886, vol. 233, p. 226[2] Journal of the Chemical Society, 1886, vol. 49, p. 518
46
[ 80-05-7 ]
[ 118-45-6 ]
[ 38103-06-9 ]
Yield
Reaction Conditions
Operation in experiment
85%
Stage #1: With N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide In water at 85 - 172℃; for 15 h; Stage #2: at 130 - 145℃; for 5 h;
79 g (0.63 mol) of a 32percent by weight aqueous sodium hydroxide solution and 62.4 g (0.3 mol) of bisphenol A were charged into the reactor.Stir and dissolve,The temperature rises to 85 ° C and the solution is transparent.Next, 510 g of a trimethylbenzene solvent and 4.2 g of a benzyltriethylammonium chloride catalyst were added.Warming and refluxing,The temperature rose to 172 ° C,Stirring reaction for 15 hours,Then cool down to 130 ° C,108 g (0.6 mol) of 4-chlorophthalic anhydride and 4.86 g of benzyltriethylammonium chloride catalyst were added.Heating from 140 ° C to 145 ° C,Reflow reaction for 5 hours,Then filter hot,Pumping the filtrate into the crystallization kettle,The filtrate is cooled to room temperature.Crystallized for 12 hours,filter,The precipitate is washed with ion-free water,Filtration, precipitation was obtained and washed with 250 g of ethanol.Stirring for 2 hours,filter,Get wet material 125g,After drying, 120 g of bisphenol A diether dianhydride product (yield 85percent),The product is white powder,
Reference：
[1] Patent: CN108148029, 2018, A, . Location in patent: Paragraph 0011; 0012; 0014
47
[ 118-45-6 ]
[ 2444-90-8 ]
[ 38103-06-9 ]
Yield
Reaction Conditions
Operation in experiment
25%
at 180℃; for 5 h;
A dry 100 mL flask was charged with 2.0 g (7.3 mmol) of the disodium salt of bisphenol A, 2.67 g (14.6 mmol) of 4-chlorophthalic anhydride, 4 mL (14 mmol) of hexaethylguanidinium chloride as a 15 weight percent solution in o-dichlorobenzene, 48 g of dry o-dichlorobenzene, and 100 mg of o-terphenyl (internal standard). The flask was immersed in an oil bath maintained at 180° C. and the mixture was stirred magnetically. The reaction was followed as in Example 1. The yield of biphenol dianhydride had reached 25percent after 5 hours.
To a mixture of 4-chlorophthalic acid anhydride (25.3 g) and bromobenzene (200 ml) was added aluminum chloride (37.1 g) at room temperature with stirring and the mixture was stirred at the same temperature for 1 hr. and then stirred at 100C for 30 min. After cooling the reaction mixture, the mixture was diluted with ethyl acetate and was added to ice water. To this mixture, conc. hydrochloric acid (20 ml) was added and the mixture was stirred at room temperature for 1 hr. and the organic layer was partitioned. The organic layer was washed successively with 4N hydrochloric acid, water and saturated brine and dried over magnesium sulfate. The organic layer was concentrated until crystals precipitated, the precipitated crystals were collected by filtration, and recrystallization from toluene was repeated to give 2-(4-bromobenzoyl)-4-chlorobenzoic acid (12 g) as colorless crystals.
5-chloro-2-phenethylisoindoline-1,3-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
64%
In ethanol; for 6h;Reflux;
A mixture of <strong>[118-45-6]5-chloroisobenzofuran-1,3-dione</strong> (36 g, 0.2 mol) and Beta-phenylethylamine (26 g, 0.2 mol) in anhydrous ethanol was refluxed for 6 h. After cooling to room temperature, crystals of 5-chloro-2-phenethylisoindoline-1,3-dione (1, 36.5 g, 64%) separated. These were filtered off, washed with ethanol. The product is pure enough for the next reaction. 1H-NMR (CDCl3, 300 MHz) delta ppm: 2.99 (t, J=7.8 Hz, 2H), 3.93(2H, t, J=7.8 Hz), 7.20-7.31 (5H, m), 7.62-7.63 (2H, m), 7.74 (1H, dd, J1=1.6 J2=3.3 Hz). ESI-MS m/z: 332 [M + H]+.
With carbon disulfide; sulfur; sodium t-butanolate; In dimethyl sulfoxide; at 150℃;
18.2g4- chloro phthalic anhydride was added to the kettle,156g dimethyl sulfoxide,1.3 g sulfur and 17.3 g sodium tert-butoxide,Then, 13 g of carbon disulfide was added dropwise thereto (the molar ratio was <strong>[118-45-6]4-chlorophthalic anhydride</strong>: carbon disulfide: sulfur: sodium t-butoxide: dimethylsulfoxide = 1: 1.7: 0.05: 1.8: 20)After the addition was complete, the reaction was warmed to 150 C until the reaction of the starting material was completed.Decompression recovery part of dimethyl sulfoxide, the remainder added to water, filtered, washed with water,32.3 g of 3,3 ', 4,4'-diphenyl sulfide tetracarboxylic dianhydride was obtained after drying, yield 99.08%.
With choline chloride; urea; at 140℃; for 1h;Green chemistry;
General procedure: DES ChCl/urea was synthesized as described in literature(Abbott et al. 2004). Briefly, choline chloride and urea with the molar ratio of 1:2 were stirred at 80 C for 1 h until a clear and transparent solution was formed (Fig. 1). The obtained DES was used without additional purification. Into a 25-mL round-bottom flask were added ChCl/urea (5.19 g, 20 mmol), phthalic anhydride (1.48 g, 10 mmol) and urea (0.60 g, 10 mmol) in successive, then the mixture was heated at 140 C for 1 h under vigorous stirring. The reaction progress was monitored by GC analysis. After reaction, the reaction mixture was cooled to room temperature, followed by addition of 2 mL of water. The DES was dissolved and the product was precipitated. The solid was collected by filtration and washed thoroughly with water. The white solid was dried thoroughly to afford the product in a yield of 84%. The DES was recovered by evaporation of water under vacuum, and subjected to next run. The product was received in a yield of yield of 95% in the second run.
80.8%
With formamide; at 120℃; for 3h;
10.0 g (54.8 mmol) of 5-chloro-isobenzofuran-1,3-dione and 30 ml of formamide were added to a 100 ml reaction flask and heated at 120 C for 3 hours.After cooling to room temperature, the reaction solution was poured into 100 ml of water, stirred for 10 minutes, filtered, and the filter cake was washed with water and dried to obtain 5-chloroimphthalate. The product was a white powdery solid. Yield 80.8%.
With formamide; at 120℃; for 3h;H;
A solution of 10.0 g of <strong>[118-45-6]4-chlorophthalic anhydride</strong> in 24.6 g of formamide is heated at a temperature in the region of [120C] with stirring for 3 hours and is then cooled to a temperature in the region [OF 20C] and poured into 100 cm3 of water. After stirring for 30 minutes, the mixture is filtered and the precipitate is then dried under vacuum at a temperature in the region of 60C. 10.4 g of 4-chlorophthalimide are thus obtained in the form of a solid melting at [171C.] Rf = 0.07 (thin layer chromatography on silica gel, eluent : dichloromethane).
With formamide; at 120℃; for 3h;
d 4-Chlorophthalimide A solution of 10.0 g of <strong>[118-45-6]4-chlorophthalic anhydride</strong> in 24.6 g of formamide is heated at a temperature in the region of 120 C. with stirring for 3 hours and is then cooled to a temperature in the region of 20 C. and poured into 100 cm3 of water. After stirring for 30 minutes, the mixture is filtered and the precipitate is then dried under vacuum at a temperature in the region of 60 C. 10.4 g of 4-chlorophthalimide are thus obtained in the form of a solid melting at 171 C. Rf=0.07 (thin layer chromatography on silica gel, eluent: dichloromethane).
With formamide; at 150℃; for 1h;
The suspension of <strong>[118-45-6]4-chlorophthalic anhydride</strong> (3 g) in formamide (15 ml) was heated with stirring to 1500C for 1 h. The resulting yellowish solution was cooled to rt and the product was fractionally precipitated by addition of water to yield 4-chlorophthalimide (1.91 g) as colourless crystals.
With formamide; at 150℃; for 1h;
The suspension of <strong>[118-45-6]4-chlorophthalic anhydride</strong> (3 g) in formamide (15 ml) was heated with stirring to 150 C. for 1 h. The resulting yellowish solution was cooled to rt and the product was fractionally precipitated by addition of water to yield 4-chlorophthalimide (1.91 g) as colourless crystals.
With hydrazine; In acetic acid; for 2h;Heating / reflux;
A mixture of <strong>[118-45-6]4-chlorophthalic anhydride</strong> (1.81 g, 10 mmol) and acetic acid (15 mL) was added to a solution of hydrazine hydrate (0.62 mL, 10 mmol) in acetic acid (2mL). The resulting mixture was stirred at reflux for 2 h. The precipitate was collected and dried to give the title compound as a white solid (1.82 g, 95%).1U NMR (400MHz, DMSO-d6): delta = 11.71 (s, 2H), 8.08 (d, J=8.3Hz, IH), 8.02 (s, IH), 7.93 (d, J=8.3Hz, IH).
With potassium carbonate;hexaethylguanidinium chloride; In water; 1,2-dichloro-benzene; for 3.5h;Heating / reflux;
4-Chlorophthalic anhydride, 16 grams (g) (87.7 mmol), was weighed into a 150 milliliter (ml) three-necked flask fitted with a distillation head and containing about 100 ml of distilled o-dichlorobenzene having a water content of less than 5 ppm. The mixture was heated at reflux for 0.5 hour in a nitrogen atmosphere and about 80 ml of o-dichlorobenzene was removed by distillation. [00022] Powdered potassium carbonate, 6.06 g (43.8 mmol), was added to another flask with 50 ml of dry o-dichlorobenzene. The suspension was heated at reflux for 0.5 hour under nitrogen and 40 ml of o-dichlorobenzene was distilled. The <strong>[118-45-6]4-chlorophthalic anhydride</strong> solution was transferred to the flask containing carbonate. The mixture was stirred and 468 mg (1.77 mmol) of hexaethylguanidinium chloride (in the form of an 18% solution in o-dichlorobenzene containing less than 15 ppm of water) was added, whereupon the solution turned yellow as refluxing was continued. Periodic analysis of the mixture showed a 93% yield of the desired 4,4'-ODPA after 3 hours. In a control experiment employing tetraphenylphosphonium bromide at the same mole percent level and powdered potassium carbonate, a period of 13 hours was required to attain the same yield. The procedure of Example 1 was repeated except that granular potassium carbonate was used and the level of hexaethylguanidinium chloride was 2.0 mole percent based on <strong>[118-45-6]4-chlorophthalic anhydride</strong>. Product formation leveled off after 3 hours at a minimum of about 85% total yield. [00024] While typical embodiments have been set forth for the purpose of illustration, the foregoing descriptions and examples should not be deemed to be a limitation on the scope of the invention. Accordingly, various modifications, adaptations, and alternatives may occur to one skilled in the art without departing from the spirit and scope of the present invention.
85%
With potassium carbonate; sodium nitrite; In N,N-dimethyl acetamide; toluene; at 162 - 170℃; for 5h;
150 g (0 · 82 mol) of <strong>[118-45-6]4-chlorophthalic anhydride</strong>, 11 g (0 · 08 mol) of potassium carbonate, 22 g of sodium nitrite was placed in a reactor containing 504 g of dimethylacetamide and 144 g of toluene, and the temperature was raised to 162 C, the reaction was carried out at 162 C to 170 C for 5 hours, followed by distillation under reduced pressure to distill the solvent, and distillation was carried out for 20 min, thereafter, 600 g of pure water was added to the vacuum, and the mixture was further stirred and refluxed for 1 to 2 hours, filtered at 102 C, and washed with water, the mixture was filtered and dried to obtain 107 g of 3,3',4,4'-diphenyl ether tetracarboxylic dianhydride, the yield was 85%, mp 226 C, and the purity of liquid chromatography was 99.6%.
82%
The procedure of Example 1 was repeated, substituting 2,4-dichlorotoluene for the o-dichlorobenzene and reducing the tetraphenylphosphonium bromide amount to 200 mg. Reflux time was 7.5 hours after the final addition of K2CO3. Product yield was 82% of theoretical
80%
With monopotassium carbonate;tetraphenylphosphonium bromide; potassium hydrogencarbonate; In 1,2-dichloro-benzene;Heating / reflux;Conversion of starting material;
4-Chlorophthalic anhydride (16 grams [g], 87.7 mmol) was weighed into a 50 milliliter (ml) round-bottomed flask containing about 17 ml of o-dichlorobenzene. The mixture was heated at reflux for 0.5 hour in a nitrogen atmosphere with distillation of solvent until less than 20 ppm of water was present, whereupon about 7 ml of solvent had been removed. Tetraphenylphosphonium bromide, 400 milligrams (mg) (0.95 mmol) was added with stirring, whereupon the solution turned yellow. Potassium bicarbonate, 22 mg (0.22 mmol), was added, followed by 5.45 g (39.5 mmol) of potassium carbonate in a stepwise fashion over 5-10 minutes. The mixture was heated at reflux (bath temperature 200 C.) after the first addition of K2CO3. The mixture was heated under reflux for 17 hours after the final addition of K2CO3. At the end of the reaction, additional o-dichlorobenzene was added to form a 10% solution and the by-product KCl was removed by filtration while hot. The filtrate was cooled to room temperature, whereupon the desired 4,4'-ODPA precipitated and was collected by suction filtration. 11.56 g of slightly pink-colored powder was obtained. Recrystallization from o-dichlorobenzene afforded 10.87 g of product (80% of theoretical) as an off-white powder, m.p. 225-226 C. 4-Chlorophthalic anhydride (4800 g, 26.3 moles) and 7836 g of o-dichlorobenzene were charged to a 3.8 liter (L) stainless steel reactor. The mixture was heated at reflux for about 0.5 hour in a nitrogen atmosphere and 1020 g of o-dichlorobenzene was removed to dry the system. With stirring, 120 g (0.29 mole) of tetraphenylphosphonium bromide was added. After mixing, 6.6 g (0.066 mole) of potassium bicarbonate was added, followed by 1650 g (11.95 moles) of potassium carbonate in 7 portions. The mixture was heated under reflux for 27 hours after the last addition of K2CO3 and periodically analyzed. About 60% of conversion was achieved at this point. To make sure that the reaction went to completion, an additional 50 g (0.119 mole) of tetraphenylphosphonium bromide was added. The mixture was heated overnight, whereupon conversion reached about 90%. o-Dichlorobenzene, 39,500 g, was added to dilute the reaction mixture and the temperature was brought to 165 C. A hot filtration was performed through a 1-micron filter bag. The filtrate was cooled to room temperature and the desired 4,4'-ODPA was collected in about 80% crude yield and 95% purity. Recrystallization from o-dichlorobenzene gave pure product, m.p. 225-226 C. While typical embodiments have been set forth for the purpose of illustration, the foregoing descriptions and examples should not be deemed to be a limitation on the scope of the invention. Accordingly, various modifications, adaptations, and alternatives may occur to one skilled in the art without departing from the spirit and scope of the present invention.
With 1,1,2,2,3,3-Hexaethylguanidiniumchlorid; potassium carbonate; In 1,2-dichloro-benzene; for 8h;
CO3 Drying in 10-Gallon Stainless Steel Reactor: A 10-Gallon reactor was charged with 4.5 kilograms (kg) of orthodichlorobenzene (ODCB) (PPG grade F) obtained from PPG Industries, Pittsburgh, Pa., USA. The agitator was set at low speed. While stirring, about 2.23 kg of K2CO3 (Aldrich 99% granular) was added to make a 29 weight % (wt %) slurry of K2CO3 in ODCB. The reactor was sealed and then heated to ODCB reflux (180 C.). The ODCB/water azeotrope was distilled overhead through condenser (It should be noted that water came over early in distillation). Distillation was continued until about 1.15 kg of ODCB has been removed, making a 40 wt % slurry of K2CO3 in ODCB. A sample of distillate overhead was taken and its moisture content was determined using Karl Fischer. Distillation was continued until the moisture content in overheads was less than 10 parts per million (ppm), and preferably less than 5 ppm. This amount of drying ensured that water of hydration of K2CO3 had been removed. Then, the K2CO3 slurry was drained out from the 10-Gallon reactor into collection bottles that were previously dried at 110 C. under nitrogen, under nitrogen at 55 C. with slow agitation. Each collection bottle was capped and sealed tightly with Parafilm. About 1.5 kg of pre-dried ODCB that had been stored with dried 4A Molecular Sieves and had been treated at 200 C. under full vacuum to remove water, was used to rinse reactor contents into collection bottles. ClPA Drying in 10-Gallon Glass-lined Reactor: A reactor was charged with about 6 kg of ODCB and 5.75 kg chlorophthalic anhydride (ClPA) obtained from Clariant Chemicals. The agitation was set at moderate level and the reactor was heated until the ODCB began to reflux (180 C.). The circulating oil temperature was set to 205 C. The ODCB/water azeotrope was distilled overhead through a condenser. The ClPA slurry was concentrated to a concentration of 61 wt % by distilling about 2.2 kg of ODCB. (It should be noted that a small amount of ClPA co-distilled with the ODCB, but the amount was negligible). A sample of distillate overhead was collected and its moisture content was determined using Karl Fischer titrator. The distillation was continued until the moisture content in overheads is less than 10 ppm, and preferably less than 5 ppm. HEGCl/ODCB addition and drying: An addition funnel was filled with 0.992 kg of dry hexaethylguanidinium chloride (HEGCl) solution (17.1 wt % HEGCl in ODCB as measured by HPLC) and sealed. The addition funnel was attached to reactor port. The HEGCl solution was added to ClPA solution over several minutes. K2CO3 Addition to 10-gallon Glass-Lined Reactor: The reactor and ClPA solution was maintained at about 170-175 C. (oil bypass to cool reactor slightly). A nitrogen blanket or slight positive nitrogen pressure was also maintained to protect the contents from moisture. The addition port on reactor was opened to allow the contents to be added into the reactor. The starting time for reaction was taken to be the moment when K2CO3 addition began. The K2CO3 slurry was added to the reactor under low agitation through the addition port in four approximately equal portions every 30 minutes over 2 hours. After each addition, pre-dried ODCB was used to rinse any residual slurry into reactor. The reaction port was closed, and oil flow to jacket was restarted to achieve reflux. The agitation was increased to ensure that reactor contents were thoroughly mixed. After a total of 8 hours following the initial K2CO3 addition, the conversion of ClPA to oxydiphthalic anhydride (ODPA) was complete. The reaction mixture was cooled to room temperature with stirring under nitrogen. ODPA (Oxydiphthalic Anhydride) Purification via conversion to Oxydiphthalic tetraacid (ODTA): About 1 gram (g) of water was added to 567 g of an ODPA reaction product mixture (23 wt % ODPA by HPLC analysis; contains 133.9 grams ODPA) contained in a quart bottle at room temperature in order to coagulate the finely divided potassium chloride (potassium chloride) while minimizing hydrolysis of the anhydride. This mixture was stirred at 460 rpm for 3 minutes. Within 1 minute, the mixture appeared to form a gel. The contents of the bottle were rinsed out of the bottle with 200 grams of ODCB and the solid ODPA suction filtered using a Buchner funnel and Whatman No.2 qualitative filter paper. The filter cake was then washed with ODCB (3×325 g) and suction dried to yield 299.88 grams of a solid mixture comprising an organic solvent (orthodichlorobenzene), a dianhydride (oxydianhydride, ODPA) and a metal halide salt (potassium chloride) as a flesh colored, chunky solid which upon analysis was shown to be 44 wt % ODPA (HPLC) (corresponds to about 98% ODPA recovery). The amount of potassium chloride present (approximately 88 grams) was well in excess of 10,000 ppm based on the weight of the dianhydride present in the mixture. The first mixture comprising ODPA-KCl-ODCB (299.88 g) was charged to a 2 liter (...
With potassium carbonate;1,1,2,2,3,3-Hexaethylguanidiniumchlorid; In dichlorobenzene, 1,2-; at 210℃;Molecular sieve; Inert atmosphere;Product distribution / selectivity;
Examples 1 to 8; Chlorophthalide Impurity Level; The following examples demonstrate the deleterious effect of chlorophthalide impurity on the reaction yield of oxydiphthalic anhydride, obtained from the reaction of <strong>[118-45-6]4-chlorophthalic anhydride</strong> (4-CIPA), understood to be a mixture of the 3-chloro and 4-chloro isomers, and K2CO3 in the presence of a phase transfer catalyst, hexaethylguanidinium chloride (HEGCl). Surprisingly, the data further show that for starting material containing an increased level of chlorophthalide impurity, the yield of oxydiphthalic anhydride increases when the level of catalyst is increased.Reagent grade o-dichlorobenzene (oDCB) was used as received from Fisher Scientific. Material used in the glove-box had been stored over 4 A molecular sieves and checked for water levels of less than 10 ppm via Karl-Fischer (KF) titrations (described below). Two samples of solid <strong>[118-45-6]4-chlorophthalic anhydride</strong> (4-CIPA) were obtained: One sample contained a low level of chlorophthalide impurity that was less than 250 ppm and a second sample had a chlorophthalide impurity that was more than 250 ppm. 4-CIPA can be obtained from vendors such as Aldrich, Jiangsu Tianyin Chemical Industry Co., Ltd., Dynamic International Enterprises Limited, Harbin Times, Wisechem International Co., Ltd., TCI Europe NV, Infine Chemicals Co., Limited, Shanghai Sunwise Chemical Co., Clariant, Ltd., Connect Marketing GmbH, NSTU Chemicals Hangzhou Co. and AK Scientific, Inc.An oDCB solution of phase transfer catalyst hexaethylguanidinium chloride (HEGCl) was prepared from a HEGCl-brine mixture which had a composition of about 35% HEGCL in the brine solution. (obtained from Vandermark Corporation) in the pilot facility on a >350 liter. Additional 4 A molecular sieves were added to the solution to ensure low moisture levels of less than 10 ppm, and the material was stored in a glove box. Commercially available K2CO3, obtained from Armand Corporation (Oxychem), was dried at 220 C. in a Kugelrohr oven overnight and stored in the glove-box. Extra fine particle size was used, identical to material used on a greater than 100 gal (379 liter) scale.The following methods/techniques were used in Examples 1 to 8.Karl-Fischer Titrations (KF). A sample of approximately 5 mL of solvent was obtained (from an oDCB distillate) taking care to ensure that the sample was dry. A 1 ml syringe was carefully filled with the solvent and care was taken to avoid the formation of air bubbles. This sample was then injected into the KF titrator. The titration was carried out automatically by the analyzer, and results are recorded in ppm water.One Pot ODPA reaction using pure 4-CIPA with <250 ppm chlorophthalide): All glassware was thoroughly dried in an oven at 120 C. prior to use. Flaked 4-CIPA (31.6 g; 0.173 mol, stored in glove box) and 12.0 g K2CO3 (0.087 mol; Kugelrohr dried; stored in glove box) was weighed out into a 250 ml three-neck round-bottom flask, which was equipped with a Dean-Stark trap with a condenser, a mechanical stirrer, and a nitrogen inlet. o-Dichlorobenzene (109 g) was added, which had been dried over 4 A molecular sieves (<5 ppm of water via KF titration). 4-CIPA completely dissolved in oDCB upon heating. The mixture was heated at reflux (210 C. oil bath temperature) for half an hour under a nitrogen atmosphere and 20 g of oDCB was distilled off. Reaction dryness was determined by sampling the distillate as <10 ppm water via KF. The nitrogen inlet was switched to a septum and nitrogen was allowed through the apparatus via the condenser opening. HEGCl/oDCB solution (6.4 mL, 11.45 wt %, 0.0038 mol) was slowly syringed into the reaction mixture. Vigorous CO2 evolution occurred and the reaction turned yellow in color immediately. An additional 30 g of oDCB was distilled off. The reaction was allowed to stir at 210 C. oil bath temperature for 6 hours. The reaction mixture was sampled periodically and the normalized yield was analyzed using an 1-HPLC method to monitor reaction yield. The normalized yield presented in the results is defined as follows: Normalized Yield %=100*2*(moles ODPA formed+moles ODDA formed+moles ODTA formed)/((2*(moles ODPA formed+moles ODDA formed+moles ODTA formed)+moles CIPA remaining+moles OHPA formed), in a sample of the reaction mixture, where ?*? means the factors are multiplied. Moles for each component were calculated from the HPLC determined wt % of that component divided by component MW.
With potassium carbonate;1,1,2,2,3,3-Hexaethylguanidiniumchlorid; In dichlorobenzene, 1,2-; at 210℃;Molecular sieve; Inert atmosphere;Product distribution / selectivity;
Examples 1 to 8. Chlorophthalide Impurity Level.[0038] The following examples demonstrate the deleterious effect of chlorophthalide impurity on the reaction yield of oxydiphthalic anhydride, obtained from the reaction of <strong>[118-45-6]4-chlorophthalic anhydride</strong> (4-ClPA), understood to be a mixture of the 3-chloro and 4-chloro isomers, and K2CO3 in the presence of a phase transfer catalyst, hexaethylguanidinium chloride (HEGCl). Surprisingly, the data further show that for starting material containing an increased level of chlorophthalide impurity, the yield of oxydiphthalic anhydride increases when the level of catalyst is increased.[0039] Reagent grade o-dichlorobenzene (oDCB) was used as received from Fisher Scientific. Material used in the glove-box had been stored over 4A molecular sieves and checked for water levels of less than 10 ppm via Karl-Fischer (KF) titrations (described below). Two samples of solid <strong>[118-45-6]4-chlorophthalic anhydride</strong> (4- ClPA) were obtained: One sample contained a low level of chlorophthalide impurity that was less than 250 ppm and a second sample had a chlorophthalide impurity that <n="16"/>was more than 250 ppm. 4-ClPA can be obtained from vendors such as Aldrich, Jiangsu Tianyin Chemical Industry Co., Ltd., Dynamic International Enterprises Limited, Harbin Times, Wisechem International Co., Ltd., TCI Europe NV, Infine Chemicals Co., Limited, Shanghai Sunwise Chemical Co., Clariant, Ltd., Connect Marketing GmbH, NSTU Chemicals Hangzhou Co. and AK Scientific, Inc.[0040] An oDCB solution of phase transfer catalyst hexaethylguanidiniurn chloride (HEGCl) was prepared from a HEGCl-brine mixture which had a composition of about 35 % HEGCL in the brine solution. (obtained from Vandermark Corporation) in the pilot facility on a > 350 liter. Additional 4A molecular sieves were added to the solution to ensure low moisture levels of less than 10 ppm, and the material was stored in a glove box. Commercially available K2CO3, obtained from Armand Corporation (Oxychem), was dried at 220 C in a Kugelrohr oven overnight and stored in the glove-box. Extra fine particle size was used, identical to material used on a greater than 100 gal (379 liter) scale.[0041] The following methods/techniques were used in Examples 1 to 8.[0042] Karl-Fischer Titrations (KF). A sample of approximately 5 mL of solvent was obtained (from an oDCB distillate) taking care to ensure that the sample was dry. A 1 mL syringe was carefully filled with the solvent and care was taken to avoid the formation of air bubbles. This sample was then injected into the KF titrator. The titration was carried out automatically by the analyzer, and results are recorded in ppm water.One Pot ODPA reaction using pure 4-C1PA with < 250 ppm chlorophthalide):All glassware was thoroughly dried in an oven at 120 C prior to use. Flaked 4-C1PA (31.6 g; 0.173 mol, stored in glove box) and 12.0 g K2CO3 (0.087 mol; Kugelrohr dried; stored in glove box) was weighed out into a 250 ml three-neck round-bottom flask, which was equipped with a Dean-Stark trap with a condenser, a mechanical stirrer, and a nitrogen inlet. o-Dichlorobenzene (109 g) was added, which had been dried over 4 A molecular sieves (<5 ppm of water via KF titration). 4-C1PA completely dissolved in oDCB upon heating. The mixture was heated at reflux (210 <n="17"/>C oil bath temperature) for half an hour under a nitrogen atmosphere and 20 g of oDCB was distilled off. Reaction dryness was determined by sampling the distillate as <10 ppm water via KF. The nitrogen inlet was switched to a septum and nitrogen was allowed through the apparatus via the condenser opening. HEGCl/oDCB solution (6.4 mL, 11.45 wt %, 0.0038 mol) was slowly syringed into the reaction mixture. Vigorous CO2 evolution occurred and the reaction turned yellow in color immediately. An additional 30 g of oDCB was distilled off. The reaction was allowed to stir at 210 C oil bath temperature for 6 hours. The reaction mixture was sampled periodically and the normalized yield was analyzed using an HPLC method to monitor reaction yield. The normalized yield presented in the results is defined as follows: Normalized Yield %= 100*2 *(moles ODPA formed + moles ODDA formed + moles ODTA formed)/((2* (moles ODPA formed + moles ODDA formed + moles ODTA formed) + moles ClPA remaining + moles OHPA formed), in a sample of the reaction mixture, where "*" means the factors are multiplied. Moles for each component were calculated from the HPLC determined wt % of that component divided by component MW.
With potassium carbonate;1,1,2,2,3,3-Hexaethylguanidiniumchlorid; In 1,2-dichloro-benzene; at 210℃; for 4h;Inert atmosphere;
Example 1; Preparation of 4,4'-oxydiphthalic anhydride (4,4'-ODPA or ODPA). The synthesis of 4,4'-ODPA from <strong>[118-45-6]4-chlorophthalic anhydride</strong>, K2CO3 and catalysts, such as HEGCl, produce various side products which need to be removed before the monomer 4,4'-ODPA can be used in a polymerization. After dilution of the reaction mixture with oDCB, the subsequent filtration step was conducted to simulate a DrM filtration unit, which required large amounts of solvent to dilute the feed to the filter unit and to pre-fill the filter unit. To minimize the oDCB utilization, the filtrate from the first filtration, termed mother liquor (ML), or the filtrate from the wash step termed wash liquor (WL), or the combination of the two was recycled for dilution of subsequent batches of the 4,4'-ODPA reaction mixture. The filtered solid is referred to as the wet cake (WC). This example describes the effectiveness of recycling the combined ML and WL for the purpose of reducing solvent usage.Reagent grade ortho-dichlorobenzene (oDCB) was used as received from Fisher Scientific. Material used in the glove box had been stored over 4 A molecular sieves and checked for water levels of less than 10 ppm via KF (described below). Solid 4-CIPA was obtained and was further purified by distillation. HEGCl in brine solution was used. K2CO3 was obtained and dried at 220 C. in a Kugelrohr overnight, then stored in the glove box. Extra fine particle size was used, identical to material used on a greater than 100 gal (379 liter) scale. The 85% H3PO4 was used as received from Fisher Scientific.Karl-Fischer Titration (KF) was used to measure water content in the 4,4'-ODPA prepared above. A sample of about 5 milliliter of solvent was obtained (normally from an oDCB distillate) taking care to ensure that the sample was dry. The plastic 1 milliliter gas-tight syringe was rinsed at least 3 times with the solvent to be checked, discarding each rinse. The syringe was carefully filled with the solvent and was then injected into the KF titrator. The analyzer carried out the titration automatically and results are recorded in ppm water.The following lab procedure was used for the 4,4'-ODPA reaction. All glassware was thoroughly dried in an oven at 120 C. prior to use. The HEGCl brine solution, 5.2 milliliter, (1.86 grams HEGCl) and about 260 grams of oDCB was charged to a 250 milliliter three-neck round-bottom flask, which was equipped with a Dean-Stark trap with a condenser, a mechanical stirrer, and a nitrogen inlet. The mixture was azeotropically dried to remove water and 120 grams solvent. The dryness was confirmed by KF titration. The reaction apparatus was transferred to a dry box with inert conditions to transfer flaked 4-CIPA (32.85 grams; 0.180 mol, stored in glove box) and 12.10 grains K2CO3 (0.088 mol; Kugelrohr dried; stored in glove box). The mixture was heated at reflux (210 C. oil bath temperature) for 4 hours under nitrogen atmosphere with 50 grams of oDCB being distilled off. Reaction dryness was determined by sampling distillate as <10 ppm via KF. Several batches of ODPA were prepared using the starting materials and amounts listed in Table 1. All batches were combined as one standard 4,4'-ODPA reaction mixture.
Sodium phenylphosphinate; In methoxybenzene; at 200℃; under 760.051 - 1824.12 Torr; for 2 - 7h;Conversion of starting material;
EXAMPLES 1-3 In each example, a 250 milliliter (ml) three-necked round-bottomed flask fitted with a stirrer and Dean-Stark trap was charged with 1,980.6 milligrams (mg) (18.315 millimoles [mmol]) of m-phenylenediamine, 6,687.2 mg (36.63 mmol) of <strong>[118-45-6]4-chlorophthalic anhydride</strong> and 14.67 mg of sodium phenylphosphinate. Anisole was added to afford the desired solids percentage and the flask was heated for 0.5 hour with stirring in a 198C oil bath, a temperature effective to produce gentle refluxing without distillation. The temperature was then raised to a specified temperature and water was collected in the trap until water evolution was complete. The remaining material in the flask was the desired C1PAMI slurry in anisole. Finally, the trap was replaced with a distillation head and the anisole was stripped to leave a paste that was analyzed by high pressure liquid chromatography. The results are given in Table 1. The yield of ClPAMI and corresponding amic acids was quantitative in each example, but conversion to C1PAMI varied and is given in the table. In Example 3, after a first stage, the reaction mixture was transferred to a pressure vessel with addition of anisole and a second stage was performed at about 200C reaction temperature and 2.4 atmospheres pressure (atm.). Comparison was made with a control employing a lower solids proportion. As shown in Table I, the method of the invention affords ClPAMI in a conversion of at least 99.75% after 7 hours or less. By contrast, the control afforded ClPAMI at a lower conversion level after a much greater reaction time.
55.3%
In glycerol; at 150℃; for 15h;
237.3 g (1.3 mol) of chlorophthalic anhydride prepared not enable the vacuum device,Stirring according to the method described in the step (1) of Example 1, and 59.4 g (0.5 mol) of m-phenylenediamine were put into 1300 g of glycerin.Stir and evenly disperse and mixHeat the reaction system to 150 C,Do reaction under normal pressure for 15 hours, followed by suction filtration.The filtrate is recycled and recycled.The filter cake is 196.2 g of crude bis(chlorophthalimide).The crude product yield is only 70.4%.Put the crude product into boiling water and stir it.After boiling,Removal of impurities on the surface of the product and inside the particles,After suction filtration,154.1 g of a bis(chlorophthalimide) product having an aromatic sulfone structure,The product yield is only 55.3%;By high performance liquid chromatography,The purity is 99.2%.
In 1,2-dichloro-benzene; at 20 - 180℃; for 32h;
EXAMPLE 4 This example illustrates an imidization reaction run with an initial excess of one reactant. A 50 gallon glass-lined reactor was charged with o-dichlorobenzene (ODCB; This example illustrates an imidization reaction run with an initial excess of one reactant. A 50 gallon glass-lined reactor was charged with o-dichlorobenzene (ODCB; 108.9 kilograms [Kg]), <strong>[118-45-6]4-chlorophthalic anhydride</strong> (CIPA) (9.990 Kg, 54.7217 moles) and m-phenylenediamine (2.9411 Kg, 27.2247 moles) to give a 0.50 mole % excess of CIPA based on 100% pure 4-CIPA. The CIPA contained from 0.5 to 1 mole % impurities. The reaction was slowly heated to about 180C over 4 hours and kept in this temperature range for 28 hours, during which time distillate was collected. Samples of the reaction slurry were obtained using a 1/4 inch diameter glass tube at 4, 5, 6 and 21 hours after charging the reactor, and analyzed using High Performance Liquid Chromatography (HPLC). At 24 hours additional 4-CIPA (40 g, 0.219 moles) was added to consume residual monoamine that persisted in the reaction. A sample taken at 28 hrs showed that monoamine was consumed. The slurry was suitable for polymerization to polyetherimide.
To a solution of <strong>[118-45-6]4-chlorophthalic anhydride</strong> (25 g) in benzene (200 ml) was added aluminum chloride (36.5 g), and the mixture was stirred at room temperature for 1 hr. and subsequently refluxed for 30 min. After cooling the reaction mixture, it was diluted with ethyl acetate (200 ml) and poured into ice water. Conc. hydrochloric acid (20 ml) was added and the mixture was stirred at room temperature for 30 min. After separating the organic layer, the layer was washed successively with 4N hydrochloric acid, water and brine, dried over sodium sulfate and concentrated until the crystals precipitated. The crystals were collected by filtration and washed with isopropyl ether to give 4-chloro-2-benzoylbenzoic acid (16 g) as colorless crystals.1H-NMR (CDCl3) delta: 7.35 (1H, d, J=2.2Hz), 7.37-7.47 (2H, m), 7.50-7.58 (2H, m), 7.66-7.73 (2H, m), 8.02 (1H, d, J=8.4Hz). To a solution of 4-chloro-2-benzoylbenzoic acid (13 g) in acetone (200 ml) was added potassium carbonate (6.9 g), and the mixture was stirred at room temperature for 10 min. to allow precipitation of potassium salt. Then diethyl bromomalonate (13.15 g) and DMF (10 ml) were added, and the mixture was stirred at room temperature for 20 hrs. The reaction mixture was concentrated, and ethyl acetate (100 ml) and water (100 ml) were added to the residue. The mixture was stirred at room temperature for 30 min. After separating the organic layer, the layer was washed with water and brine, dried over sodium sulfate and concentrated. A mixed solution of acetic acid (100 ml) and conc. hydrochloric acid (100 ml) was added to the obtained residue, and the mixture was stirred for 20 hrs at 120C. After cooling, the reaction mixture was concentrated, and the residue was dissolved in ethyl acetate, washed with water and brine, dried over sodium sulfate and concentrated. The obtained residue was crystallized from isopropyl ether and collected by filtration to give the title compound (9.78 g) as colorless crystals.1H-NMR (CDCl3) delta: 7.07 (1H, d, J=1.8Hz), 7.20-7.28 (2H, m), 7.45-7.54 (3H, m), 7.60 (1H, dd, J=1.8, 8.4Hz), 8.34 (1H, d, J=8.4Hz)
4-chloro-2-(methoxycarbonyl)benzoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium methylate; at 20℃; for 12h;
To a solution (50 ml) of 4-chloro phthalic anhydride (12.1 g) in methanol was added sodium methoxide (3.6 g) and the mixture was stirred at room temperature for 12 hrs. The solvent was under reduced pressure, and the residue was partitioned between ethyl acetate and 1N hydrochloric acid. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to give 4-chlorophthalic acid 1- and 2-methyl ester mixture. In addition, to a mixture of methyl bromoacetate (10.1 g), triethylamine (9.7 ml) and THF (70 ml) was added dropwise a solution (35 ml) of benzylamine (7.1 g) in THF at 0C with stirring and the mixture was stirred for 1 hr. The mixture was further stirred at room temperature for 1 hr. and the solvent was evaporated under reduced pressure. The residue was partitioned between ethyl acetate and water, and the organic layer was dried over magnesium sulfate and concentrated under reduced pressure to dryness. Then, to a mixture of this product, 4-chlorophthalic acid 1- and 2-methyl ester mixture (mentioned above) and acetonitrile (70 ml) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (16.5 g) and 4-hydroxybenzotriazole·monohydrate (11.2 g), and the mixture was stirred at room temperature for 12 hrs. The solvent was removed under reduced pressure, and the residue was partitioned between ethyl acetate and 1N hydrochloric acid. The organic layer was dried and concentrated to dryness. This product was dissolved in methanol (100 ml) and 28% sodium methoxide·methanol solution (26 g) was added at room temperature with stirring. The mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated, and the residue was partitioned between ethyl acetate and 1N hydrochloric acid. The organic layer was dried and concentrated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1) and recrystallized from hexane/ethyl acetate to give the title compound (4.5 g) as yellow crystals.1H-NMR (CDCl3) delta: 3.81 (3H, s), 5.61 (2H, s), 7.00-7.10 (2H, m), 7.16-7.32 (3H, m), 7.66 (1H, dd, J= 1.8, 8.4 Hz), 8.14 (1H, d, J= 1.8 Hz), 8.44 (1H, dd, J= 0.3, 8.4 Hz), 11.02 (1H, s).
A resealable 50-ml stainless steel tube was charged with 1.5 g 4- chlorotetrahydrophthalic anhydride, 0.262 G N-METHYL-4-CHLOROPHTHALIMIDE, 0. 841 g triethylamine, and 20 ML of water. The tube was sealed and heated in an oil bath at 170 C for 3 hours, and then cooled to room temperature. A small sample of the aqueous phase was analyzed by GCMS. The analysis showed that 83.2% exchange had occurred. Analysis further showed that the reaction mixture was composed of 2.4 mol% of N-METHYL-4-CHLOROPHTHALIMIDE, 11.9 mol% of N-METHYL-4-CHLORO tetrahydrophthalimide, 11.9 mol% of 4- CHLOROPHTHALIC anhydride (as the triethylamine salt of the corresponding diacid), and 73.8 mol% of 4-chlorotetrahydrophthalic anhydride (as the triethylamine salt of the corresponding diacid). The aqueous phase was extracted with 20 ml of toluene containing 3 wt% triethylamine in a separatory funnel at room temperature. The toluene extraction effectively removed the N-methyl-4-chlorotetrahydrophthalimide and the unreacted N-METHYL-4-CHLOROPHTHALIMIDE from the aqueous phase. The aqueous phase still contained the 4-chlorophthalic anhydride (as the triethylamine salt of the corresponding diacid), and the 4-CHLOROTETRAHYDROPHTHALIC anhydride (as the triethylamine salt of the corresponding diacid). The aqueous phase was distilled, during which the triethylamine salts cracked to liberate water and triethylamine, with the formation of 4-chlorophthalic anhydride and 4-CHLOROTETRAHYDROPHTHALIC anhydride. The water and triethylamine were taken overhead, and the still bottoms were collected. The still bottoms were then distilled to separate the 4- CHLOROTETRAHYDROPHTHALIC anhydride from the 4-CHLOROPHTHALIC anhydride A. The 4-CHLOROTETRAHYDROPHTHALIC anhydride was recombined with the water and TEA previously collected, and reused.
5-chloro-2-{4-[1-(3,4-dimethoxybenzyl)piperidin-4-yl]benzyl}-1H-isoindole-1,3(2H)-dione hydrochloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
To a solution of the compound prepared in reference example 3 (318 mg) in toluene (20 ml) was added <strong>[118-45-6]5-chloro-2-benzofuran-1,3-dione</strong> (186 mg). The reaction mixture was stirred for 6 days at 120C. To the reaction mixture was added IN hydrochloric acid and the resulting mixture was extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified by column chromatography on silica gel (dichloromethane: methanol = 9: 1) to give the compound of the present invention (12 mg) having the following physical data. TLC:Rf 0.48 (dichloromethane: methanol = 10: 1); NMR(CD3OD): delta 7.86-7.81 (m, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 7.14 (s, 1H), 7.06-7.01 (m, 3H), 4.78 (s, 2H), 4.26 (s, 2H), 3.88 (s, 3H), 3.85 (s, 3H), 3.58-3.54 (m, 2H), 3.10-3.00 (m, 2H), 2.90 (m, 1H), 2.10-1.90 (m, 4H).
1,1,2,2,3,3-Hexaethylguanidiniumchlorid; In 1,2-dichloro-benzene; at 180℃; for 5.0h;Product distribution / selectivity;
A dry 100 mL flask was charged with 2.0 g (7.3 mmol) of the disodium salt of bisphenol A, 2.67 g (14.6 mmol) of <strong>[118-45-6]4-chlorophthalic anhydride</strong>, 4 mL (14 mmol) of hexaethylguanidinium chloride as a 15 weight percent solution in o-dichlorobenzene, 48 g of dry o-dichlorobenzene, and 100 mg of o-terphenyl (internal standard). The flask was immersed in an oil bath maintained at 180° C. and the mixture was stirred magnetically. The reaction was followed as in Example 1. The yield of biphenol dianhydride had reached 25percent after 5 hours.
EXAMPLE 1 In a 50 milliliter (ml) three-neck flask were placed 14.1 grams (g) of 4chloro-o-xylene and 0.249 g (1.00 millimole) of cobalt (II) acetate tetrahydrate. The mixture was magnetically stirred at 170 C. and oxygen gas was continuously bubbled through the mixture using a capillary inlet tube at a rate of 0.02 SCFH. In 112 hours of reaction the yield of 4-chlorophthalic anhydride was 8.3% and the yield of 4-chlorotoluic acid was 38.7%, both based on starting material.
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