* 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] Journal of Medicinal Chemistry, 2016, vol. 59, # 23, p. 10577 - 10585
2
[ 120-61-6 ]
[ 5292-45-5 ]
Yield
Reaction Conditions
Operation in experiment
95%
at 10 - 20℃; for 1 h;
In a 1000 ml four-necked flask, 926.97 g of 98percent sulfuric acid was introduced, Stirring down to 10~15°C ,Slowly add 97.7percent nitric acid 200.72g; Plus complete, keep 10~15 °C by adding dimethyl terephthalate 300.0g, about 30min plus, The reaction temperature was controlled at 15~20°C , After incubation for 30 minutes, The end point of the reaction was confirmed by TLC.After stirring for 15 minutes, the filter cake was rinsed with 900 ml of 5percent aqueous solution of sodium hydroxide and then rinsed with 500 ml of water to neutral. The filter cake was put into 3000 ml of water, and the mixture was stirred at room temperature for 30 minutes. Four bottles, add 1500g of ethanol for recrystallization: first heated to 50 ~ 55 , so that all the dissolved solids, and then cooled to 5 ° C below the full precipitation of the material; filtration, filter drying, the influx of goods 382.5g, 60°C dried in vacuo to obtain 351.2 g of white crystals in 95percent yield (as dimethyl dimethyl terephthalate), a gas chromatographic content of> 99percent, a melting point of 73.8 to 75.5 ° C (reported melting point: 73 to 76 ° C) .
82.9%
at 20℃; for 1 h; Cooling
nitration reaction: electromagnetic stirring dimethyl terephthalic acid (compound I) 10g is dissolved in 50 ml concentrated sulfuric acid, ice-bath cooling, will 5 ml fuming nitric acid slowly dropping to the reaction flask, does not exceed the temperature is maintained during 20 °C; of after-reaction of adding 1h, TLC (thin layer chromatography) monitoring the consumption of raw materials, the reaction liquid stirring slowly poured into 100 ml ice water, separating white solid, filtering, the filter cake is washed with saturated NaHCO3pH8 to, drying shall 10.2g white solid, that is, 2-nitro-terephthalic acid dimethyl ester (compound II), as shown in Figure 1, the yield 82.9percent
Reference：
[1] Journal of Organic Chemistry, 2001, vol. 66, # 12, p. 4356 - 4360
[2] Patent: CN103524386, 2016, B, . Location in patent: Paragraph 0029; 0030; 0031
[3] Patent: CN104072403, 2016, B, . Location in patent: Paragraph 0031-0033
[4] Liebigs Annalen der Chemie, 1987, p. 833 - 838
[5] Justus Liebigs Annalen der Chemie, 1912, vol. 393, p. 25
[6] Monatshefte fuer Chemie, 1912, vol. 33, p. 152,156, 166
[7] Proceedings of the National Academy of Sciences of the United States of America, vol. 10, p. 430[8] Chem. Zentralbl., 1925, vol. 96, # I, p. 62
3
[ 67-56-1 ]
[ 610-29-7 ]
[ 5292-45-5 ]
Reference：
[1] Tetrahedron Letters, 2008, vol. 49, # 38, p. 5544 - 5547
[2] Journal of the American Chemical Society, 2003, vol. 125, # 37, p. 11241 - 11248
[3] Inorganic Chemistry, 2018, vol. 57, # 3, p. 1040 - 1047
[4] Monatshefte fuer Chemie, 1900, vol. 21, p. 627[5] Monatshefte fuer Chemie, 1902, vol. 23, p. 410
[6] Monatshefte fuer Chemie, 1900, vol. 21, p. 627[7] Monatshefte fuer Chemie, 1902, vol. 23, p. 410
[8] Monatshefte fuer Chemie, 1900, vol. 21, p. 627[9] Monatshefte fuer Chemie, 1902, vol. 23, p. 410
[10] Monatshefte fuer Chemie, 1902, vol. 23, p. 406,410, 412
4
[ 610-29-7 ]
[ 5292-45-5 ]
Reference：
[1] Monatshefte fuer Chemie, 1901, vol. 22, p. 785[2] Monatshefte fuer Chemie, 1904, vol. 25, p. 478
[3] Patent: US4051148, 1977, A,
5
[ 610-29-7 ]
[ 10026-13-8 ]
[ 5292-45-5 ]
Reference：
[1] Patent: US4302241, 1981, A,
6
[ 100-21-0 ]
[ 5292-45-5 ]
Reference：
[1] Monatshefte fuer Chemie, 1900, vol. 21, p. 627[2] Monatshefte fuer Chemie, 1902, vol. 23, p. 410
a 5-carboxy-2-methoxycarbonyl-nitrobenzene 1N NaOH (50 mL) was slowly added dropwise at room temperature over 30 min to a stirred solution of di-methyl nitroterephthalate (12 g, 0.05 mmol) in dioxane (100 mL). After stirring overnight at room temperature the reaction was diluted with water, washed with ether, acidified with 1N HCl (50 mL) and extracted with ethyl acetate. After drying the ethyl acetate phase (MgSO4) and evaporation, the resulting residue was purified by flash chromatography (silica gel, 98:2:0.1 CHCl3:MeOH:HOAc) to yield the title compound (8.07 g, 72%).
53%
The acid chloride (48) was prepared by first converting dimethyl-nitro-terephthalate (48) to the mono-acid ester (52) according to literature procedures (Keenan, et al. "Conformational Preferences in a Benzodiazepine Series of Potent Nonpeptide Fibrinogen Receptor Antagonists" J. Med. Chem. 1999, 42, 545-559), and then refluxing compound 52 in excess thionyl chloride (Scheme 7).
51%
With sodium hydroxide; In 1,4-dioxane; water; at 20℃;
To a stirred solution of <strong>[5292-45-5]dimethyl-2-nitroterephthalate</strong> (24.0 g, 100.4 mmol) in dioxane (200 mL) was added 1N NaOH aqueous solution (100 mL) dropwise. The reaction mixture was stirred at RT overnight, water (200 mL) was added and the yellow solution was washed with diethyl ether (200 mL) twice. The aqueous layer was acidified with 1N HCl aqueous solution (120mL) until pH ?1, it was extracted with EtOAc. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was recrystallized in water to afford 3 as a white solid (11.6g, 51%), mp 177-179C (lit.2 177-179C). 1H NMR (DMSO-d6): delta 13.9 (br s, 1H), 8.46 (d, J=1.5Hz, 1H), 8.34 (dd, J=8.0, 1.5Hz, 1H), 7.99 (d, J=7.5Hz, 1H), 3.89 (s, 3H).
51%
With water; sodium hydroxide; In 1,4-dioxane; at 20℃;
(d) 4-(Methoxycarbonyl)-3-nitrobenzoic acid (3): To a stirred solution of<strong>[5292-45-5]dimethyl-2-nitroterephthalate</strong> (24.0 g, 100.4 mmol) in dioxane (200 mL) wasadded 1 N NaOH aqueous solution (100 mL) dropwise. The reaction mixturewas stirred at RT overnight, water (200 mL) was added and the yellow solutionwas washed with diethyl ether (200 mL) twice. The aqueous layer was acidifiedwith 1 N HCl aqueous solution (120 mL) until pH 1, it was extracted withEtOAc. The combined organic layers were dried over anhydrous Na2SO4,filtered and concentrated in vacuo. The crude product was recrystallized inwater to afford 3 as a white solid (11.6 g, 51%), mp 177-179 C (lit.2 177-179 C). 1H NMR (DMSO-d6): d 13.9 (br s, 1H), 8.46 (d, J = 1.5 Hz, 1H), 8.34 (dd,J = 8.0, 1.5 Hz, 1H), 7.99 (d, J = 7.5 Hz, 1H), 3.89 (s, 3H).
42%
With water; sodium hydroxide; In 1,4-dioxane; for 0.5h;Cooling with ice;
Synthesis of compound b: 4-(methoxycarbonyl)-3-nitrobenzoic acid [00151] Compound b (4-(methoxycarbonyl)-3-nitrobenzoic acid) was synthesized according to the method of CW Wagner et al. (/ Med Chem (2009) 52(19) 5950-5966). To a 500 mL round bottom flask charged with dimethylnitroterephthalate (25g, 104.5 mmol) and dioxane (232 mL) was added 1M NaOH solution dropwise over 30min over ice bath. Water (100 mL) was added to dilute and the aqueous solution was washed with EtOAc (50 mL x 2). The aqueous layer was acidified with 1M HCl (104 mL) to pH 3-4, extracted with EtOAc (150 mL x 3). The combined organic layers were dried with Na2S04 and then filtered. The filtrate was concentrated and the residue was recrystallized in water to give pure compound b as white crystalline solid (lOg, 42% yield). The NMR is consistent to the literature report. lH NMR (400MHz, CDC13) delta 8.66 (s, 1H), 8.39 (d, J = 8.0 Hz, 1H), 7.85 (d, J =8.0 Hz, 1H), 3.98 (s, 3H); MS 226 (M+l).
36%
With sodium hydroxide; In 1,4-dioxane; methanol; water;
EXAMPLE 72A Methyl 2-nitro-4-carboxybenzoate A solution of <strong>[5292-45-5]dimethyl nitroterephthalate</strong> (5.98 g, 25.0 mmol) and aqueous 1M NaOH. (25 mL) in dioxane (50 mL) was stirred at ambient temperature for 2 hours, then concentrated under reduced pressure. The remaining solution was diluted with water (50 mL) and extracted with diethyl ether (3*25 mL). The aqueous layer was acidified to a pH<3 with 1M HCl, then extracted with diethyl ether (3*25 mL). The second set of ether layers was washed with brine (1*10 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was precipitated from methanol (25 mL) and water (25 mL) to provide the titled compound (2.0 g, 36%). 1H NMR (300 MHz, d6-DMSO) delta8.46 (d, 1H, J=135), 8.33 (dd, 1H, J=1.7, 7.8), 7.99 (d, 1H, J=8.1), 3.89 (s,3); MS (ESI) m/z=224 (M-H).
With hydrogenchloride;Reflux;
A mixture of 100 grams of 1-nitrobenzene-2, 5-dicarboxylic acid dimethyl ester and 600-800 grams of concentrated hydrochloric acid was heated for 6 to 8 hours in a flask. The mixture was then quenched with cold water. The precipitate formed was filtered off with suction and washed with water. The yield of the 1 -nitrobenzene-2- methyloxycarbonyl-5-carboxylic acid product was about 90%. The melting point was recorded and was found to be 174 - 176 C for the product having a purity of 96 %.
With iron; ammonium chloride; In ethanol; water; for 0.5h;Reflux;
Nitro Reduction: To 50ml volume ratio of 1: 1 ethanol / water solution of ammonium chloride was added 2.3g, iron 2.3g, stirred heated to reflux for 30min; 2-nitro-dimethyl terephthalate (ie, compound II ) 10.0 g was dissolved in 25ml of ethanol, was added dropwise to the reaction flask slowly (to prevent the red material), after the addition was complete the reaction was continued at this temperature for 30min, TLC monitored the reaction was complete; cooled to room temperature, filtered through celite pad, the cake washed with until no product was adsorbed was washed with ethanol, and concentrated under reduced pressure to remove ethanol; aqueous layer was washed with saturated Na2CO3Solution was adjusted pH10, 50mlEA aqueous phase was extracted twice, the combined organic phase was washed by saturated sodium chloride, dried over anhydrous sodium sulfate, and evaporated to dryness to give 8.7g solid, i.e., 2-amino dimethyl terephthalate (i.e. compound III ), shown in Figure 2, a yield of 99.1percent,
98.9%
With hydrogen; In isopropyl alcohol; at 80℃; under 2250.23 Torr;pH 7 - 8;Large scale;
In the case of 200 kg of 2-nitro-terephthalic acid dimethyl ester, the catalyst used was a self-made catalyst. The total amount of catalyst used in the production was 0.1_3percent (0.2-6 kg) and the total amount of isopropyl alcohol was 8 times the raw material (1600 kg), in the hydrogenationThe order of the 2-nitro terephthalate, isopropanol and catalyst into the kettle is as follows:1, 2 - nitro - terephthalic acid dimethyl ester 200 kg, isopropyl alcohol 1600 kg added to the reactor, gas replacement.2, the introduction of hydrogen, hydrogenation reaction began to control the reaction temperature of 80 ± 5 ° C, the control reaction pressure of 0.3-1.0Mpa.3,The reaction ends the filtration catalyst,The filtrate cools down to below 20 degrees Celsius,Filter dry,To obtain the finished 2-amino terephthalate.4. The product obtained according to the above method was analyzed, and the conversion rate of dimethyl 2-nitro terephthalate was100percent, the selectivity of dimethyl 2-aminoterephthalate was 99.6percent, the content of dimethyl 2-aminoterephthalate was 99.9percentThe yield was 96.5percent.
In tetrahydrofuran; methanol;
a) Dimethyl 2-aminoterephthalate 23.9 g (0.1 mol) of <strong>[5292-45-5]dimethyl 2-nitroterephthalate</strong> are hydrogenated in a mixture of 100 ml of methanol and 200 ml of tetrahydrofuran with palladium/charcoal at 5 bar and 20° C. After the catalyst has been removed by suction filtering the solvent is evaporated off and the residue is recrystallized from methanol. Yield 18-19 g, yellowish crystals m.p. 130-131° C.
[8-(4-carbamimidoyl-phenylcarbamoyl)-5-oxo-4-phenethyl-2,3,4,5-tetrahydro-1<i>H</i>-benzo[<i>e</i>][1,4]diazepin-2-yl]-acetic acid methyl ester[ No CAS ]
A. 1.0 Kg. of fuming sulfuric acid is added dropwise to 500 g of nitroterephthalic acid in 2.5 liters of methanol and the so lution is refluxed for 4 hours. The reaction mixture is cooled to room temperature and cautiously diluted up to 10 liters with water. The solid is filtered, washed to neutrality with water and dried in vacuo at 40°-45° C to yield 550 g of nitroterephthalic acid dimethyl ester having a melting point of 72.5°-74.5° C.
[4-(pyridin-3-yloxymethylene)-2-phenoxybenzoyl]methionine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; potassium tert-butylate; In methoxybenzene; N,N-dimethyl-formamide;
EXAMPLE 157A dimethy phenoxyterephthalate To a solution of phenol (10.8 g) in anisole (40 mL) and DMF (90 mL) was added potassium tert-butoxide (12.1 g). The mixture was heated for 40 minutes while continuously passing a nitrogen stream through the reaction flask (~20 mL of solvent distilled over). The mixture was cooled to ambient temperature and <strong>[5292-45-5]dimethyl nitroterephthalate</strong> (23.9 g) was added. The resulting black mixture was stirred for 1 hour at ambient temperature and two hours at 100-105° C. The reaction mixture was poured into ice containing 2 mL of concentrated HCl. The mixture was extracted with ether. The ether layer was washed with water (3*) and saturated aqueous NaHCO3 (2*). The organic phase was dried over MgSO4, filtered, and concentrated in vacuo to give 24.1 g of an oil. Chromatography on silica gel (10percent ethyl acetate-hexanes) gave dimethy phenoxyterephthalate (15.9 g).
With sodium hydroxide; In methanol; ethanol; water; dimethyl sulfoxide;
A. 2-(4-Methoxyphenoxy)terephthalic acid Sodium metal (11.5 g) was dissolved in methanol (250 ml) and to this solution was added 4-methoxyphenol (62.1 g). The methanol was thoroughly removed by rotary evaporation and the residual sodium salt dissolved in dimethylsulphoxide. Dimethyl 2-nitroterephthalate (107.6 g) was added and the mixture stirred and heated at 120 for 2.5 h. The dark resulting solution was hydrolyzed by boiling under reflux with a solution of sodium hydroxide pellets (70 g) in water (500 ml) and ethanol (800 ml) for 2.5 h. The solution was acidified by pouring into excess iced hydrochloric acid and the precipitated 2-(4-methoxyphenoxy)terephthalic acid was filtered off, washed with water and dried at 90 in a vacuo to give 125.0 g, m.p. 280-283.
With potassium hydroxide; sodium hydroxide; In methanol; water; N,N-dimethyl-formamide;
EXAMPLE 3 90.2 g (0.726 mol) of p-thiocresol are dissolved in 600 ml of N,N-dimethylformamide, after which 31.7 g (0.792 mol) of finely powdered sodium hydroxide are added. After stirring for half an hour at 20°-25° C., 158.0 g (0.660 mol) of <strong>[5292-45-5]dimethyl nitroterephthalate</strong> are added to the homogeneous solution, and the reaction mixture is stirred for 1.5 hours at 70° C. After cooling to 20°-25° C., 1,000 ml of water are added and the precipitate which has separated out is filtered off. 275 g of moist product are obtained. This is heated in a solution of 89.5 g of KOH in 1,200 ml of methanol for one hour under reflux. The mixture is cooled to 20°-25° C., 1,000 ml of water and a little active charcoal are added and the resulting mixture is filtered after stirring for half an hour. The filtrate is freed from methanol in a rotary evaporator and the residual aqueous phase is extracted with three times 200 ml of methylene chloride. The precipitate formed after acidifying the aqueous phase with sulfuric acid is filtered off and washed with water. After drying in vacuo at 80° C., 140 g (74percent of theory) of 2-(4-methylphenylthio)-terephthalic acid remain; melting point >250° C.; IR spectrum (KBr): 1690 cm-1.
With potassium hydroxide; sodium hydroxide; In methanol; water; N,N-dimethyl-formamide;
2-(4-Methylphenylthio)-terephthalic acid can also be prepared as follows: 90.2 g (0.726 mol) of p-thiocresol are dissolved in 600 ml of N,N-dimethylformamide, after which 31.7 g (0.792 mol) of finely powdered sodium hydroxide are added. After stirring for half an hour at 20°-25° C., 158.0 g (0.660 mol) of <strong>[5292-45-5]dimethyl nitroterephthalate</strong> are added to the homogeneous solution and the reaction mixture is stirred for 1.5 hours at 70° C. After cooling to 20°-25° C., 1000 ml of water are added and the precipitate which has separated out is filtered off. 275 g of moist product are obtained. This is refluxed in a solution of 89.5 g of KOH in 1200 ml of methanol for one hour. The reaction mixture is cooled to 20°-25° C., 1000 ml of water and a little active charcoal are added and the resulting mixture is filtered after stirring for half an hour. The filtrate is freed from methanol in a rotary evaporator and the residual aqueous phase is extracted with three times 200 ml of methylene chloride. The precipitate formed on acidifying the aqueous phase with sulfuric acid is filtered off and washed with water. After drying in vacuo at 80° C., 140 g (74percent of theory) of 2-(4-methylphenylthio)-terephthalic acid remain.
EXAMPLE 4 Dimethyl 2-Nitro-1,4-benzenedicarboxylate To 150 ml of phosphorous oxychloride was added, with stirring, 211 g of 2-nitro-1,4-benzenedicarboxylic acid. To this mixture was added 425 g of phosphorous pentachloride in portions so that foaming was controlled. The mixture was heated to reflux (108°) until gas evolution ceased, then the phosphorous oxychloride was removed in-vacuo to give 268 g of residue. The residue was added over 0.75 hours to 200 ml of methanol. The solution temperature was allowed to rise to reflux during the addition and refluxing was continued for 1.75 hours longer. The mixture was then stripped and the residue recrystallized from acetonitrile and 1-chlorobutane (1:6) to give 137 g off white solid; m.p. 72.5°-74°, dimethyl 2-nitro-1,4-benzenedicarboxylate.
With potassium hydroxide; In methanol; water; N,N-dimethyl-formamide; paraffin;
(a) 10.0 g (0.23 mol) of a sodium hydride dispersion (55percent by weight in paraffin) are added in portions to 24.24 g (0.22 mol) of thiophenol in 150 ml of N,N-dimethylformamide. After the exothermic reaction has subsided (30 minutes), 47.84 g (0.20 mol) of methyl nitroterephthalate are added and the mixture is heated at 65°-70° C. for 1.5 hours. After cooling to room temperature (20°-25° C.), 300 ml of water are poured in and the product (diester) which has precipitated is filtered off. This diester is refluxed in a solution of 28.0 g (0.5 mol) of potassium hydroxide in 500 ml of methanol for 1.5 hours, the reaction mixture is concentrated and 250 ml of water are added. The heterogeneous reaction mixture is washed with methylene chloride (3* with 150 ml in each case), the aqueous phase is treated with active charcoal and filtered and the filtrate is concentrated. The filtrate is then acidified with concentrated sulfuric acid and the precipitate which has separated out is filtered off. After drying in vacuo at 80° C., 37.9 g (69percent of theory) of 2-phenylthio-terephthalic acid remain; melting point >250° C.
10 g (80.65 mmoles) of 4-methylbenzenethiol are added to a three-neck flask equipped with a thermometer and a condenser and dissolved in 50 cc of dimethyl formamide. 3.39 g (84.75 mmoles) of finely ground sodium hydroxide are added and the solution is left to rest at room temperature under constant stirring for half hour. Then, 18.89 g (79.04 mmoles) of dimethyl 2-nitrobenzene- l,4-dicarboxylate are added maintaining the temperature at 75 °C for 1.5 hours. Once the reaction is terminated, the mixture is cooled down and 100 ml of water are added . The precipitate formed is filtered and stirred for 1 hour under refluxing with a solution of 9.33 g ( 16.67 mmoles) of potassium hydroxide in 120 ml of methanol.The mixture is cooled and poured in water containing activated carbon for decoloration, after one hour of stirring the mixture is filtered on celite. The organic solvent is distilled on a rotary evaporator and the residue is washed with methylene chloride (twice ). The aqueous phase is then acidified with hydrochloric acid 37percent. The precipitate obtained is filtered on a buckner, washed with water and dried in a vacuum oven to a final yield of 2 1.72 g (yield : 95percent) of 2-(p- tolylthio) benzene- 1,4-dicarboxylic acid as a white solid
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
100K+ Compounds
Competitive Price
1-2 Day Shipping
