* 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.
With 1,1'-carbonyldiimidazole In acetonitrile at 20 - 30℃; Inert atmosphere
Example 2: Synthesis of 2-(2,6-dioxopiperidin-3-yl)-isoindole-1 -dione(Thalidomide) 1,1-carbonyldiimidazole (21.5 g or 0.13 mole) was added to a stirred mixture of phthalic acid (10.0 g. or 0.06 mole) in acetonitrile (100 ml) maintained under nitrogen at ambient temperature. To this mixture, 3-aminopiperidine 2,6-dione hydrochloride (9.9 g or 0.06 mole) was added, and the reaction mixture was stirred at 25 to 30 °C until the reaction was completed as monitored by TLC. After completion of the reaction, the solvent was distilled out under reduced pressure. Water (100 ml) was added to the reaction mass and the reaction mass was slowly cooled at 0 to 5 °C while stirring. The isolated solid was filtered, washed with water, then by methanol, and suck dried. Finally the isolated sold was dried at 55 to 60 °C under vacuum until constant weight to get thalidomide. Yield: 1 1.6 g, 75.2percent (molar). Purity by HPLC 99.13percent
Reference：
[1] Journal of Pharmacy and Pharmacology, 2011, vol. 63, # 9, p. 1156 - 1160
6
[ 88-99-3 ]
[ 118-45-6 ]
Reference：
[1] Journal of the Chemical Society, 1929, p. 255
7
[ 88-99-3 ]
[ 4752-10-7 ]
Reference：
[1] Journal of the Indian Chemical Society, 1990, vol. 67, # 9, p. 779 - 780
8
[ 220819-28-3 ]
[ 83-73-8 ]
[ 88-99-3 ]
[ 443-48-1 ]
[ 126613-32-9 ]
Reference：
[1] Scientia Pharmaceutica, 1998, vol. 66, # 4, p. 309 - 324
9
[ 88-99-3 ]
[ 156-87-6 ]
[ 883-44-3 ]
Reference：
[1] Chemistry - A European Journal, 2014, vol. 20, # 44, p. 14256 - 14260
10
[ 88-99-3 ]
[ 5466-84-2 ]
Reference：
[1] European Journal of Medicinal Chemistry, 1987, vol. 22, p. 229 - 238
[2] Chemische Berichte, 1878, vol. 11, p. 393[3] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1878, vol. 10, p. 196
[4] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 230
11
[ 88-99-3 ]
[ 641-70-3 ]
Reference：
[1] European Journal of Medicinal Chemistry, 1987, vol. 22, p. 229 - 238
[2] Journal of the American Chemical Society, 1920, vol. 42, p. 1876
[3] Journal of the American Chemical Society, 1901, vol. 23, p. 751
[4] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1878, vol. 10, p. 192[5] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 225
12
[ 88-99-3 ]
[ 108-95-2 ]
[ 77-09-8 ]
Reference：
[1] Z. chim. Promysl., 1924, vol. 1, # 4, p. 26[2] Chem. Zentralbl., 1926, vol. 97, # II, p. 753
[3] Journal of the Chemical Society, 1920, vol. 117, p. 215
13
[ 67-56-1 ]
[ 88-99-3 ]
[ 36978-41-3 ]
[ 3711-04-4 ]
[ 2420-87-3 ]
Reference：
[1] Patent: CN105330633, 2016, A, . Location in patent: Paragraph 0030; 0031
14
[ 206362-19-8 ]
[ 88-99-3 ]
[ 443-48-1 ]
[ 126613-32-9 ]
Reference：
[1] European Journal of Medicinal Chemistry, 1998, vol. 33, # 9, p. 675 - 683
15
[ 220819-25-0 ]
[ 130-26-7 ]
[ 88-99-3 ]
[ 443-48-1 ]
[ 126613-32-9 ]
Reference：
[1] Scientia Pharmaceutica, 1998, vol. 66, # 4, p. 309 - 324
16
[ 220819-28-3 ]
[ 83-73-8 ]
[ 88-99-3 ]
[ 443-48-1 ]
[ 126613-32-9 ]
Reference：
[1] Scientia Pharmaceutica, 1998, vol. 66, # 4, p. 309 - 324
17
[ 7647-01-0 ]
[ 73825-95-3 ]
[ 88-99-3 ]
[ 616-29-5 ]
Reference：
[1] Chemische Berichte, 1889, vol. 22, p. 225
[2] Chemische Berichte, 1888, vol. 21, p. 2690
18
[ 10035-10-6 ]
[ 73825-95-3 ]
[ 88-99-3 ]
[ 616-29-5 ]
Reference：
[1] Chemische Berichte, 1889, vol. 22, p. 225
19
[ 7647-01-0 ]
[ 88-99-3 ]
[ 616-29-5 ]
Reference：
[1] Chemische Berichte, 1888, vol. 21, p. 2690
20
[ 88-99-3 ]
[ 583-53-9 ]
Reference：
[1] Organic and Biomolecular Chemistry, 2011, vol. 9, # 15, p. 5431 - 5435
Reference：
[1] Patent: CN105330633, 2016, A, . Location in patent: Paragraph 0030; 0031
26
[ 88-99-3 ]
[ 89-20-3 ]
Reference：
[1] Monatshefte fuer Chemie, 1913, vol. 34, p. 69
[2] Chemiker-Zeitung, Chemische Apparatur, 1880, vol. 4, p. 407[3] Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1880, p. 862
[4] Journal of the Chemical Society, 1921, vol. 119, p. 1790
[5] Journal of the Chemical Society, 1929, p. 253
[6] Monatshefte fuer Chemie, 1913, vol. 34, p. 69
27
[ 88-99-3 ]
[ 89-20-3 ]
[ 56962-08-4 ]
Reference：
[1] Journal of the Chemical Society, 1929, p. 255
Reference：
[1] Justus Liebigs Annalen der Chemie, 1871, vol. 160, p. 64
[2] Chemische Berichte, 1878, vol. 11, p. 393[3] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1878, vol. 10, p. 196
[4] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 230
[5] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1878, vol. 10, p. 192[6] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 225
[7] Recueil des Travaux Chimiques des Pays-Bas, 1908, vol. 27, p. 277
[8] Journal of the American Chemical Society, 1901, vol. 23, p. 751
[9] Chemische Berichte, 1901, vol. 34, p. 3744
[10] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1878, vol. 10, p. 192[11] Justus Liebigs Annalen der Chemie, 1881, vol. 208, p. 225
31
[ 7697-37-2 ]
[ 88-99-3 ]
[ 610-27-5 ]
[ 603-11-2 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1908, vol. 27, p. 277
32
[ 104-76-7 ]
[ 88-99-3 ]
[ 117-81-7 ]
Reference：
[1] RSC Advances, 2018, vol. 8, # 66, p. 37835 - 37840
[2] Asian Journal of Chemistry, 2014, vol. 26, # 17, p. 5769 - 5772
[3] Kogyo Kagaku Zasshi, 1956, vol. 59, p. 895,897[4] Technology Reports of the Osaka University, 1957, vol. 7, p. 199,203
33
[ 18908-66-2 ]
[ 88-99-3 ]
[ 117-81-7 ]
Reference：
[1] Synthesis, 1985, # 1, p. 40 - 45
34
[ 111-83-1 ]
[ 88-99-3 ]
[ 117-84-0 ]
Reference：
[1] Patent: US3959347, 1976, A,
35
[ 111-83-1 ]
[ 88-99-3 ]
[ 117-84-0 ]
Reference：
[1] Synthesis, 1985, # 1, p. 40 - 45
36
[ 111-87-5 ]
[ 88-99-3 ]
[ 117-84-0 ]
Reference：
[1] Journal of the American Chemical Society, 1949, vol. 71, p. 3730
[2] Indian Journal of Chemistry - Section A Inorganic, Physical, Theoretical and Analytical Chemistry, 2017, vol. 56A, # 7, p. 747 - 755
37
[ 88-99-3 ]
[ 105-53-3 ]
[ 25177-85-9 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 14, p. 4216 - 4220
38
[ 88-99-3 ]
[ 6301-60-6 ]
Reference：
[1] Synthetic Communications, 2003, vol. 33, # 8, p. 1319 - 1323
[2] Journal of the American Chemical Society, 1919, vol. 41, p. 294
39
[ 71-41-0 ]
[ 88-99-3 ]
[ 131-18-0 ]
Reference：
[1] Patent: US2130014, 1935, ,
40
[ 123-51-3 ]
[ 88-99-3 ]
[ 605-50-5 ]
Reference：
[1] Organic Preparations and Procedures International, 2001, vol. 33, # 4, p. 395 - 400
With acidic cation exchange resin Amberlyst 70; at 55 - 145℃;Flow reactor; Green chemistry;
General procedure: Phthalic acid and various alcohols at a respective ratio of 1:7 were respectively mixed at 55 C., and introduced in to the vertical reactor at a liquid hourly space velocity (LHSV) of 3 hour-1. The respective reaction temperature was shown Table 2. The analysis results of the products were shown in Table 2.
EXAMPLE 8 Preparation of dioctyltin phthalate from phthalic acid Phthalic acid and dioctyltin oxide are introduced into a screw drier in accordance with Example 4b. At the exit, dioctyltin phthalate (compound 5) is obtained as a white free-flowing powder.
sodium [1,1'-biphenyl]-3,3',4,4'-tetracarboxylate[ No CAS ]
[ 88-99-3 ]
[ 22803-05-0 ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; In water;
(1) Preparation of biphenyltetracarboxylic acid In a reactor equipped with a stirrer and a heating apparatus, 69 parts of aqueous solution of sodium 3,3',4,4'-biphenyltetracarboxylate (containing 5.4% of BPTA and 4.2% of phthalic acid) obtained by dimerization of sodium 4-chlorophthalate was placed. Then, 14 parts of concentrated hydrochloric acid was added thereto with stirring to deposit crude BPTA with heating, followed by filtration while hot. The resulting white cake in an amount of 7.2 parts together with 36 parts of water was placed again in the reactor and heated with stirring, followed by hot filtration. The thus obtained white cake in an amount of 4.7 parts was dried with hot air at 120 C. for 5 hours to give 2.6 parts of crude 3,3',4,4'-biphenyltetracarboxylic acid (BPTA) in white particles having a purity of 95% and containing 2% of phthalic acid.
With sodium acetate; acetic anhydride;palladium/charcoal; In 1,4-dioxane; benzene;
EXAMPLE 1 SPC10 84.5 g (0.4 mol) of <strong>[603-11-2]3-nitrophthalic acid</strong> are hydrogenated in 250 ml of dioxane in the presence of 4 g of a palladium/charcoal catalyst containing 5% by weight of palladium, at 25C. The reaction solution is filtered and 47.02 g (0.48 mol) of maleic anhydride are then added. The reaction mixture is kept at room temperature for 12 hours (approx. 20-25C). After this time, 105 g (94% of theory) of 3-(maleinamidyl)-phthalic acid crystallise out. This acid is filtered off, washed with 20 ml of dioxane, suction-drained, pressed and sucked dry. 111.68 g (0.4 mol) of the above 3-(maleinamidyl)-phthalic acid are mixed with 26 g of anhydrous sodium acetate, 165 ml of acetic anhydride and 800 ml of benzene and the mixture is heated to 80C for 3 hours, whilst stirring. The resulting solution is freed from the sodium acetate by filtration, and freed from the benzene in vacuo. After drying the crystalline residue at 60C/0.05 mm Hg, 82.7 g (85% of theory) of 3-(maleinimidyl)-phthalic anhydride are obtained; melting point 167 - 169C. NMR spectrum (CDCl3): delta = 7.27 ppm (methine protons). 3-(Maleinamidyl)-phthalic acid, manufactured in accordance with the above example, can also be converted into 2-(maleinimidyl)-phthalic anhydride by the following method: the solid 3-(maleinamidyl)-phthalic acid is first heated for approx. 12 hours at approx. 110C/100 mm Hg, whereby it is converted into 3-(maleinimidyl)-phthalic acid (melting point: 130 - 132C). The latter can be converted by means of acetic anhydride into 3-(maleinimidyl)-phthalic anhydride in about 90% yield, melting point 167-169C.
EXAMPLE III To the glass liner of a rotating autoclave was added 37 grams (0.37 mole) of allyl acetate, 48 grams (0.29 mole) of phthalic acid and 9 grams (0.03 mole) of anhydrous stannic chloride. The autoclave was sealed and nitrogen pressed in until an initial operating pressure of 30 atmospheres was reached. Thereafter the autoclave was heated to a temperature of 100 C. and maintained in a range of from 99-102 C. for a period of 4 hours, the maximum pressure at this temperature reaching 45 atmospheres. At the end of the 4-hour period, heating was discontinued and the autoclave was allowed to return to room temperature. After standing at room temperature for a period of 16 hours the excess pressure was discharged and the autoclave was opened. The desired product comprising allyl phthalate was recovered therefrom.
Reference Example VII: Cleavage of Phthalic acid bisallylester with Me2AI-CI246 mg (1 mmol) of <strong>[131-17-9]diallyl phthalate</strong> are dissolved in 10 ml of dry toluene under nitrogen. The solution is heated to reflux (1 10 C) and 2.1 ml of a 1 molar solution of dimethyl aluminium chloride (2.1 equiv.) are added via a syringe under nitrogen. The reaction mixture is stirred over night at 1 10 C. The reaction mixture is cooled to roomtemperature, quenched with 15 ml of 2 molar HCI and extracted with 7 x 15 ml of ethyl acetate. The combined organic phases are extracted with 2 x 12 ml of saturated sodium bicarbonate solution. The combined basic, aqueous phase is adjusted to pH 1 with 10 ml of diluted (2 Molar) sulfuric acid. The acidic aqueous phase is again extracted with 7 x 15 ml of ethyl acetate and the combined organic phase are washed with brine, dried over sodium sulfate, filtered and evaporated in vacuum to phthalic acid. H-NMR and LC-MS confirm the structure of phthalic acid (identical to a commercial sample from Fluka).
Reference Example V: Cleavage of Phthalic acid bisallylester with Me2A1-C1 246 mg (1mmol) of <strong>[131-17-9]diallyl phthalate</strong> are dissolved in 10 ml of dry toluene under nitrogen. The solution is heated to reflux (110 C) and 2.1 ml of a 1 molar solution of dimethyl aluminium chloride (2.1 equiv.) are added via a syringe under nitrogen. The reaction mixture is stirred over night at 110 C. The reaction mixture is cooled to room temperature, quenched with 15 ml of 2 molar HCI and extracted with 7 x 15 ml of ethyl acetate. The combined organic phases are extracted with 2 x 12 ml of saturated sodium bicarbonate solution. The combined basic, aqueous phase is adjusted to pH 1 with 10 ml of diluted sulfuric acid. The acidic aqueous is again extracted with 7 * 15 ml of ethyl acetate and the combined organic phase are washed with brine, dried over sodium sulfate, filtered and in vacuum to phthalic acid. 1H-NMR and LC-MS confirm the structure of phthalic acid.
[Ag2(phthalic acid(-2H))(2,4-diamine-6-phenyl-1,3,5-triazine)]n[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
50.61%
In water; at 180℃; for 120h;Autoclave; High pressure;
A mixture of AgNO3 (340 mg, 2 mmol), 1,2-H2bdc (166 mg, 1 mmol), phdat (187 mg, 1 mmol), and H2O (10 mL) was stirred for 20 min. The mixture was transferred to a Teflon-lined stainless steel autoclave and kept at 180 C for 5 days. After the autoclave had been cooled to room temperature over 6-7 h, colorless strip crystalline solids of complex 1 (287 mg) were isolated from the mother liquid, washed with water. Yield: 50.61% (based on 1,2-H2bdc). Anal. Calcd: C17H13Ag2N5O4(%): C 36.01, H 2.31, N 12.35, Found: C 36.08, H 2.39, N 12.45. IR (KBr pellet, cm-1): 3408, 3305, 3190, 1621, 1555, 1489, 1451, 1401, 1259, 1085, 1035, 904, 857, 824, 695, 651.
General procedure: A mixture of 0.1mol carboxylate(mass=0.1M), 2.0g TC-1~6, 0.75g NaI, 0.05g Cu and 20mL H2O was put into a flask equipped with stirring device, reflux condenser, thermometer and dropping funnel. The mixture was heated up to 35~40 for 1h. Then quantitative allyl chloride according to n(Cl): n(COONa)=2:1 was added dropwise during 2h. After refluxing for 2~4h, the excess of allyl chloride was distilled off. The reaction mixture was cooled to room temperature and filtered out quaternary ammonium salts and Cu powder. Then, organic layer was separated, washed with water, and dried overnight with MgSO4. The crude product was purified by vacuum distillation in presence of high boiling point solvent or by a silica-gel column chlomatography with petroleum ether and EtOAc. Products were obtained in excellent yield.
With 3,3'-(2,2'-(hexane-1,6-diylbis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(1-propyl-1H-benzo[d]imidazol-3-ium) chloride; triethylamine; at 55℃; for 0.416667h;
General procedure: The carboxylic acids (1.1 mmol), the alkyl/allyl/aryl halides(1.00 mmol), dicationic IL catalyst DBimIL-3b (0.05 mmol) and tri-ethylamine (1.25 mmol) were loaded in a two necked flask andthe mixture was stirred at 60 C for particular time. Progress ofthe reactions was monitored by TLC as well as the developmentof a white solid (Et3NHX) in the reaction mixture was a useful indication of the reaction progress. After completion of reaction,the mixture was allowed to cool at RT. The reaction mass was extracted in ethyl acetate (2 × 10 mL). The extract was washed with distilled water (2 × 10 mL) and 10% NaHCO3(2 × 10 mL), dried(anhydrous Na2SO4) and then concentrated in a rotary evaporator. The obtained products were pure as characterized by NMR and mass spectrometry. The obtained yields varied from 55-91%(Table 2). After the reaction, white solid of IL along with Et3NHX (X = Cl/Br)was dissolved in THF and filtered to remove Et3NHX. THF wasremoved using rotavapour and finally IL was washed thoroughly with EtOAc (2 × 10 mL) and recycled after drying in a vacuum at 60 C for 2 h.
With 1,1'-carbonyldiimidazole; In acetonitrile; at 20 - 30℃;Inert atmosphere;
Example 2: Synthesis of 2-(2,6-dioxopiperidin-3-yl)-isoindole-1 -dione(Thalidomide) 1,1-carbonyldiimidazole (21.5 g or 0.13 mole) was added to a stirred mixture of phthalic acid (10.0 g. or 0.06 mole) in acetonitrile (100 ml) maintained under nitrogen at ambient temperature. To this mixture, 3-aminopiperidine 2,6-dione hydrochloride (9.9 g or 0.06 mole) was added, and the reaction mixture was stirred at 25 to 30 C until the reaction was completed as monitored by TLC. After completion of the reaction, the solvent was distilled out under reduced pressure. Water (100 ml) was added to the reaction mass and the reaction mass was slowly cooled at 0 to 5 C while stirring. The isolated solid was filtered, washed with water, then by methanol, and suck dried. Finally the isolated sold was dried at 55 to 60 C under vacuum until constant weight to get thalidomide. Yield: 1 1.6 g, 75.2% (molar). Purity by HPLC 99.13%
With sodium hypochlorite; ruthenium(III) chloride trihydrate; sulfuric acid; tetrabutylammomium bromide; In water; 1,2-dichloro-ethane; at 23℃; for 0.5h;pH 9;Green chemistry;
General procedure: In a 250-mL three necked flask equipped with pH and temperature sensor were placed 40 mL of aq. NaOCI (10 % Assay) at room temperature. The pH at the aqueous phase was brought to pH 9 ± 0.1 by addition of 20 % (v/v) H2SO4. To this aqueous NaOCl solution; mixture of naphthalene (0.81 g, 5 mmol), RuCl3*3H2O (0.0065 g,0.5 mol%), tetrabutyl ammonium bromide (0.040 g, 2.5 mol%) and 10 mL of 1,2-dichloroethane were added. Stirring was commenced with a mechanical stirrer and reaction continued at room temperature (23 ± 2 C) duringthe period of 10-30 min. The pH was controlled during the reaction by using manual addition of 20 % of NaOH to keep the pH at 9 ± 0.1. After the hypochlorite solution was used up (reaction shows colour change from yellow to white cloudy) a few drops of hypochlorite solution were added to reoxidize the ruthenium catalyst. The phases were separated and an aqueous phase is acidified with dilute 20 % aq. H2SO4 to brought pH at 2.5-3. The acidic solution containing organic products was extracted with diethylether (30 x 3 = 90 mL); solvent evaporation resulted into crude 3-chlorophthalic acid (0.842 g, 4.2 mmol). Derivatization of phthalic acids using N, O-bis(trimethylsilyl)trifluoroacetamide with 1 % trimethylchlorosilane (BSTFA) was performed for gc analysis.
The phthalic acid (1mmol) dissolved in 20 ml of acid in the aqueous solution, the stirring 1.5 hours later, into the chlorine gas, reaction 3 hours, all the solvent is pumped, by adding ethyl acetate 50 ml, the resulting solution with saturated salt water washing 3 times, the organic phase after separation, the aqueous phase is extracted with twice ethyl acetate (50 ml). The combined organic phase, drying agent, filtration of the drying agent, the solvent evaporation to dryness, to obtain the corresponding ortho and meta-substituted phthalic acid chloride (yield 100%, GC purity (two isomers) 99%).
The phthalic acid (1mmol) dissolved in 20 ml of acid in the aqueous solution, the stirring 1.5 hours later, into the chlorine gas, reaction 3 hours, all the solvent is pumped, by adding ethyl acetate 50 ml, the resulting solution with saturated salt water washing 3 times, the organic phase after separation, the aqueous phase is extracted with twice ethyl acetate (50 ml). The combined organic phase, drying agent, filtration of the drying agent, the solvent evaporation to dryness, to obtain the corresponding ortho and meta-substituted phthalic acid chloride (yield 100percent, GC purity (two isomers) 99percent). The phthalic acid chloride (1mmol) dissolved in 20 ml of methanol, add alkaline solution, stirring 1.5 hours, all the solvent is pumped, by adding ethyl acetate 50 ml, the resulting solution with saturated salt water washing 3 times, the organic phase after separation, the aqueous phase is extracted with twice ethyl acetate (50 ml). The combined organic phase, drying agent, filtration of the drying agent, the solvent evaporation to dryness, to obtain the corresponding ortho and meta-substituted phthalic acid methyl ester mixture (the yield is 100percent, GC purity (two isomers) 99percent). The respectively 50mLDMF, 10mmol the above-mentioned phthalic acid methyl ester mixture, 10mmol metal nickel powder and 10mL1mol/L dilute hydrochloric acid solution is added with a condensation device 250 ml stirring at room temperature in three-necked flask 0.5h to the 60 °C to continue stirring 5h, tracking detection reaction by TLC, until the reaction is stopped when the substrate is no longer reduce the reaction, the reaction cooling, filtering to remove the metallic catalyst, solvent evaporation to dryness. Adding ethyl acetate 50 ml, the resulting solution with saturated salt water washing 3 times, the organic phase after separation, the aqueous phase is extracted with twice ethyl acetate (50 ml). The combined organic phase, drying agent, filtration of the drying agent, to evaporate the solvent, to the corresponding of the biphenyl tetracarboxylic acid ester mixture (yield 90percent, GC purity (three isomers) 95percent). The biphenyltetracarboxylic acid methyl ester mixture (1mmol) dissolved in 20 ml of aqueous solution of alkali, stirring 1.5 hours, neutralizing solution instillment acid, instillment to PH value is less than 2 is stopped when the dropping, stirring 3 hours, all the solvent is pumped, by adding ethyl acetate 50 ml, the resulting solution with saturated salt water washing 3 times, the organic phase after separation, the aqueous phase is extracted with twice ethyl acetate (50 ml). The combined organic phase, drying agent, filtration of the drying agent, to evaporate the solvent, to the corresponding ortho and meta substituted neighbouring benzene two bitter wine mixture (yield 90percent, GC purity (three isomers) 90percent).
With ammonium hydroxide; In N,N-dimethyl-formamide; at 20℃;Darkness;
A mixture of Ag2O (23.2 mg, 0.1 mmol), pza (24.6 mg,0.2 mmol) and H2pca (33.3 mg, 0.2 mmol) was stirred in water-DMF (DMF = N,N0-dimethylformamide) mixed solvent (6 mL, v/v:1/1). Then aqueous NH3 solution (25%, 0.5 mL) was dropped intothe mixture to give a clear solution under ultrasonic treatment.The resultant solution was allowed to evaporate slowly in darknessat room temperature for several days to afford the product aslamellar clear yellow crystals of 1. (Yield: 75%, based on silver).Anal. Calc. (found) for Ag6C29H17N3O14: C, 27.24 (27.95); H, 1.34(1.42); N, 3.29 (3.52)%. IR (KBr): m (cm1) = 3409 (m), 3313 (m),1689 (m), 1562 (s), 1441 (m), 1403 (s), 1378 (s), 1257 (w), 1154(m), 1084 (m), 1027 (m), 849 (m), 823 (m), 766 (m), 696 (m),645 (m), 575 (w), 416 (w).
A 100 mL three-necked flask equipped with a mechanical stirrer, thermometer, reflux condenser was charged with 20 mL (3-aminopropyl) trimethoxysilane, 5 mL of phthalic acid, 10 mL of anhydrous methanol, and stirred at 60 C for 30 minutes. Then add 5mL of concentrated sulfuric acid, 90 C reaction for 3 hours, and then refined to high temperature silane coupling agent. The yield of the silane coupling agent was 45. 3%.
2-(2-(2,4-dimethylphenylthio)phenylcarbamoyl)benzoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
With 1,1'-carbonyldiimidazole; In N,N-dimethyl-formamide; for 1h;
General procedure: To a mixture of <strong>[1019453-85-0]2-(2,4-dimethylphenylthio)benzenamine</strong> (5, 8.7 mmol) and acid derivative (10 mmol) inDMF (10 mL) at 0-5 C, was added dropwise coupling agentsolution CDI (17.5 mmol in 5 mL DMF) The reaction mass,allowed to warm at room temperature and stirred for an 1 h(TLC check with hexane/ethyl acetate 9:1). Quenched reaction mass with water (15 mL) and filtered to afford desiredproduct (6i-o).
At room temperature, accurately weighed etanercept raw material (359mg, 1mmol)Was added to a 50 ml beaker, and phthalic acid (166 mg, 1 mmol)Under the ultrasound state anhydrous methanol was added dropwise until just completely dissolved, continue ultrasound 5min, filter paper filtration.The filtrate was transferred to a 50ml beaker. The 50ml beaker was placed in a large beaker containing purified water and the crystals were evaporated in vacuo (-0.05MP) at room temperature. About 72-96h after a large number of transparent crystal precipitation, filtration, cold methanol washing cake, that is, the desired salt.
A solution of <strong>[22059-21-8]1-aminocyclopropanecarboxylic acid</strong> (500 mg, 4.95 mmol) in toluene (15 ml) was treated with phtalic acid (732 mg, 4.95 mmol) and triethylamine (45 mu, 320 muiotaetaomicron). The resulting solution was stirred 48 h at reflux temperature and evaporated. The residue was retaken in a water (20 ml) and aqueous hydrogen chloride solution (2 ml, 1M) mixture and stirred 20 min. The solid was filtered off, washed with water and dried at the high vaccum pump affording 993 mg (87% of th.) of the title compound.LC-MS (Method 1): Rt = 0.61 min; MS (ESIpos): m/z = 232 [M+H]+-NMR (500 MHz, DMSO-d6) delta [ppm]: 13.01 (br s, 1H), 8.30-7.47 (m, 4H), 1.70-1.35 (m, 4H)
(2R)-3-tert-butoxy-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With triethylamine; In dichloromethane;Reflux;
A solution of <strong>[18783-53-4]O-tert-butyl-D-serine</strong> (500 mg, 3.10 mmol) in toluene (20 ml) was treated with phtalic acid (459 mg, 3.10 mmol) and triethylamine (28 mu, 200 muiotaetaomicron). The resulting solution was stirred overnight at reflux temperature and evaporated. The residue was retaken in ethyl acetate and extracted twice with an aqueous hydrogen chloride solution (2 ml, 1M) followed by a saturated sodium chloride solution. The organic phase was dried over sodium sulfate and evaporated affording 830 mg (90% of th.) of the title compound.LC-MS (Method 2): Rt = 1.52 min; MS (ESIneg): m/z = 290 [M+H]"-NMR (400 MHz, DMSO-d6) delta [ppm]: 13.37 (br s, 1H), 8.06-7.61 (m, 4H), 4.90 (dd, 1H), 4.02- 3.82 (m, 2H), 1.01 (s, 9H).
(2S)-3-tert-butoxy-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With triethylamine; In dichloromethane; for 4h;Reflux;
A solution of O-tert-butyl-1-serine (500 mg, 3.10 mmol) in toluene (20 ml) was treated with phtalic acid (459 mg, 3.10 mmol) and triethylamine (28 mu, 200 muiotaetaomicron). The resulting solution was stirred 4 h at reflux temperature and evaporated. The residue was retaken in N,N- dimethylformamide (10 ml), water (150 ml) and aqueous hydrogen chloride solution (5 ml, 1M). The solution was extracted twice with ethyl acetate. The organic phase was washed with a saturated sodium chloride solution, dried over sodium sulfate and evaporated affording 987 mg (89% of th.) of the title compound.LC-MS (Method 1): Rt = 0.84 min; MS (ESIpos): m/z = 292 [M+H]+-NMR (400 MHz, DMSO-d6) delta [ppm]: 13.37 (br s, 1H), 8.16-7.56 (m, 4H), 4.90 (dd, 1H), 4.01- 3.83 (m, 2H), 1.01 (s, 9H).
Add 2.0g to 50mL DMF solventPhthalic acid (0.012 mol) and 4.8 g potassium hydrogencarbonate (0.048 mol),Stir at room temperature to form a potassium salt.6.64 g of n-bromodecane (0.03 mol) was added to the mixed solution,The reaction was stirred at 90 C for 12 hours.Stop the reaction and allow the solution to cool to room temperature.It was poured into 300 mL of water and extracted with ethyl acetate.Dry over anhydrous sodium sulfate, filter and spin dry solvent.The crude product was subjected to column chromatography using petroleum ether/ethyl acetate (24/1) as eluent.
Chemistry
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Inhibitors/Agonists
Material Science
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