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Isophthalic acid (1.130 g, 6.8 mmol) and 1,2-diaminobenzene (1.417 g, 13.1 mmol) were dissolved in 20 mL of polyphosphoric acid. The stirred mixture was maintained at 190 °C for 24 h. The solution was allowed to cool at room temperature (20 – 25 °C) and slowly stirred in 50 mL of ice. The reaction mixture was neutralized with NaOH and the precipitate was filtered out and washed with cold water. The solid was recrystallized from methanol to yield a white-off solid (1.06 g, yield 57percent, mp 183-186 °C). 1H NMR (DMSO-d6, 400 MHz): 13.16 (s, 2H, Hc), 9.06 (t, 4Jf-d = 1.6 Hz, 1H, Hf), 8.26 (dd, 4Jd-f = 1.6 Hz, 3Jd-e = 7.8 Hz, 2H, Hd), 7.74 (t, 3Je-d = 7.8 Hz, 1H, He), 7.69 (bs, 2H, Hb’), 7.58 (bs, 2H, Hb), 7.24 (d, 3Ja-b = 4.3 Hz, 4H, HaHa’). 13C NMR (DMSO-d6, 100 MHz): 125.3 (Cf), 128.0 (Cd), 130.2 (Ce), 119.5-112.1 (Cb), 123.3-122.4 (Ca). HRMS-ESI (m/z): calcd for [BBB+H]+ C20H15N4, 311.1291; found, 311.1294 (error: 1 ppm).
Reference:
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With sulfuric acid; bromine; silver sulfate; at 55℃; for 25h;
33.23 g (0.2 mol) of isophthalic acid and 37.42 g (0.12 mol) of silver sulphate are dissolved in 330 ml of sulphuric acid. 13.3 ml (0.26 mol) of bromine are then added over 1 h. The solution is heated at 55 C. for 24 h. The medium is then poured into ice, the insoluble material is filtered and taken up in ethyl acetate. The remaining solid is taken up in water and basified with a saturated aqueous sodium hydrogen carbonate solution. The insoluble material is filtered and the filtrate is acidified and then extracted with ethyl acetate. The organic phase is washed with water and then dried over magnesium sulphate and concentrated. [00640] White powder. m=42.1 g. Y=86%. m.p.=285-7 C. 1H NMR (DMSO): 8.40 (2H, s), 8.57 (1H, t), 13.76 (2H, COOH, s).
86.7%
With silver(II) sulfate; sulfuric acid; bromine; In water; at 60℃; for 32h;
A mixture of A (12.2 g, 73.5 mmol), Ag2SO4 (13.3 g, 43 mmol) and Br2 (5ml, 97 mmol) in conc. sulphuric acidwas stirred at 60C for 32 h. The excess of Br2 was removed by addition of saturated Na2S2O3 solution very slowly. Theresidue was poured into ice-water. The solids were isolated by filtration and given into a NaHCO3 solution. The AgBrwas then removed by filtration. The solution was acidified with concentrated hydrochloric acid to give white precipitates.The solid was filtered and washed with water several times to give the product as white solid 20.5g (Yield. 86.7%). 1HNMR(DMSO-d6): delta = 8.23 (d, 2H), 8.40 (t, 1H).
86.7%
With silver(II) sulfate; sulfuric acid; bromine; at 60℃; for 32h;
A mixture ofA (12.2 g, 73.5 mmol), Ag2SO4 (13.3g, 43 mmol) and Br2 (5 ml, 97 mmol) in conc. sulphuric acid was stirred at 60 C. for 32 h. The excess of Br2 was removed by addition of saturated Na2S2O3 solution very slowly. The residue was poured into ice-watet The solids were isolated by filtration and given into a NaHCO3 solution. The AgBr was then removed by filtration. The solution was acidified with concentrated hydrochloric acid to give white precipitates. The solid was filtered and washed with water several times to give the product as white solid 20.5 g (Yield. 86.7%). 1H-NMR (DMSO-d5): oe=8.23 (d, 2H), 8.40 (t, 1H).
20%
With N-Bromosuccinimide; sulfuric acid; at 60℃;
Into a 100-mL round-bottom flask, was placed a solution of isophthalic acid (10 g, 60 24 mmol, 1 00 equiv) in 980ZoH2SO4 (60 mL) This was followed by the addition of N-bromosuccimmide (12 80 g, 72 32 mmol, 1 20 equiv), in portions at 6O0C in 10 mm The resulting solution was stirred overnight at 6O0C in an oil bath The reaction was cooled to room temperature and then quenched by the addition of water/ice The solids were collected by filtration, and washed with 2x60 mL of hexane The solid was dried in an oven under reduced pressure The crude product was purified by re-crystallization from ethyl acetate to give 3 g (20%) of 5-bromoisophthalic acid as a white solid.
With N-Bromosuccinimide; sulfuric acid; water; at 59.84℃; for 20h;Sealed tube;
5-Bromoisophthalic acid was prepared under the hydrothermal conditions. A mixture of isophthalic acid (16.6 mg, 0.1 mmol), H2SO4 (9.8 mg, 0.2mmol) and N-bromosuccinimide (NBS) (14.13 mg, 0.1 mmol), H2O (12 mL) was sealed into a 25 mL stainless steel reactor with a Teflon liner and heated at 333 K for 20 h. The reactor was then cooled slowly to room temperature and the solution filtered. Yellow block-shaped crystals were obtained from the filtrate after several days at room temperature.
13.2 g
With N-Bromosuccinimide; sulfuric acid; at 60℃; for 6h;
Isophthalic acid (II) (5 g, 60 mmol) was dissolved in concentrated sulfuric acid (30 mL) at room temperature and raised to 60 C. NBS (10.6 g, 60 mmol) was then added to the solution in three batches and 3 g was added every half hour. TLC followed the reaction. After the reaction was completed, the reaction solution was poured into ice (200 g) and precipitated as a white solid. Filtered, filtered with water (100 mL) and petroleum ether (50 mL). The solvent was evaporated to dryness using a rotary evaporator to give 13.2 g of 5-bromoisophthalic acid as a white solid in a yield of 90% and used directly in the next step.
12 g
With N-Bromosuccinimide; sulfuric acid; at 60℃; for 2h;
A (14.0 g, 0.084 mol) was dissolved in 40 mL cone. H2SO4 at 60 C under stirring. N-Bromosuccinimide (NBS, 16 g, 0.090 mol) was added to the reaction in portions over 1 hour and the mixture was stirred at 60 C for an additional hour. After the reaction was completed, the mixture was poured into 200 g crushed ice and stirred at room temperature for 1 hour. Light yellow solid was obtained by filtration and washed with DI water (100 mL). The crude product was recrystallized from ethyl acetate to give pure B (12 g, 59 % yield).
With sulfuric acid; sulfur trioxide; bromine; at 110 - 150℃; for 7 - 22h;
Into a 50 ml pressure and sealable glass tube, 1.66 g (10 mmol) of isophthalic acid, 6.00 g of 10 wt percent fuming sulfuric acid and 1.6 g (10 mmol) of bromine were charged, and the content was stirred at 130° C. for 22 hours. After the conclusion of the reaction, the content was cooled to room temperature, and placed in a beaker containing ice water to give a solid. The resulting solid was filtered off, washed with cooling, and further dried under reduced pressure to give 2.41 g (purity: 83.5percent) of a crude crystal of the aimed product (yield: 81.9percent). Then, the crystals were solved in 10 g of methanol at 60° C., cooled to room temperature, and thereafter filtered off to give 1.61 g (purity: 100percent) of a white crystal (yield of recrystallization: 80.1percent). This crystal was identified as 5-bromopisophthalic acid by MASS, 1H-NMR and melting point. EXAMPLES 2 TO 7 [0033] Procedures were carried out similarly to that of Example 1 except that the reaction temperature, the concentration of fuming sulfuric acid and the amount of bromine were changed. The results on the resulting monobromo products were shown in Table 1. [TABLE-US-00001] TABLE 1 Concentration of Fuming Quantitative Yield (percent) Ex. Sulfuric Acid Bromine Tempera- Time 4,5- 2,5- No. (wt percent)-(g) g(mmol) ture(° C.) (h.) 5BIP IP DBIP DBIP 2 10-6 1.6(10) 110 22 34.5 58.0 trace - 3 20-6 1.6(10) 110 22 48.6 43.2 trace - 4 30-6 1.6(10) 110 22 62.8 24.6 2.3 - 5 10-6 1.6(10) 150 22 77.0 4.1 8.0 - 6 20-6 1.6(10) 150 7 53.8 46.5 0.7 - 7 10-6 3.2(20) 150 7 79.1 6.4 5.8 trace IP: Isophthalic Acid, 5BIP:5-Bromoisophthalic Acid, 4,5-DBIP: 4,5-Dibromoisophthalic Acid 2,5-DBIP: 2,5-Dibromoisophthalic Acid EXAMPLE 8 [0034] Into a 50 ml pressure and sealable glass tube, 1.66 g (10 mmol) of isopthalic acid, 6.00 g of 30 wt percent fuming sulfuric acid and 1.6 g (10 mmol) of bromine were charged, and the content was stirred at 150° C. for 22 hours. After the conclusion of the reaction, the content was cooled to room temperature, and placed in a beaker containing ice water to give a solid. Then, the resulting solid was filtered off, washed with cooling, and further purified by column chromatography on silica gel (chloroform/methanol=6/1, v/v) to give 0.51 g (yield: 20.7percent) of 5-bromoisophthalic acid, 0.76 g (yield: 23.5percent) of 4,5-dibromoisophthalic acid and 0.07 g (yield: 2.1percent) of 2,5-dibromoisophthalic acid. These crystals were identified by MASS, 1H-NMR and melting point. EXAMPLES 9 TO 16 [0035] Procedures were carried out similarly to that of Example 8 except that the reaction temperature, the concentration of fuming sulfuric acid and the amount of bromine were changed. The results on the resulting monobromo and dibromo products were shown in Table 2. [TABLE-US-00002] TABLE 2 Concentration of Fuming Quantitative Yield (percent) Ex. Sulfuric Acid Bromine Tempera- Time 4,5- 2,5- No. (wt percent)-(g) g(mmol) ture(° C.) (h.) 5BIP IP DBIP DBIP 9 60-6 1.6(10) 110 22 45.0 1.4 18.7 1.0 10 20-6 1.6(10) 130 22 49.2 0.0 15.3 trace 11 30-6 1.6(10) 130 22 53.1 0.8 13.6 1.0 12 20-6 1.6(10) 150 22 43.1 0.0 20.0 0.8 13 20-6 3.2(20) 150 7 37.5 0.0 23.3 1.5 14 10-12 1.6(10) 150 7 47.0 0.6 18.1 1.2 15 20-12 1.6(10) 150 7 49.8 0.7 20.3 1.4 16 20-12 3.2(10) 150 7 11.9 0.0 26.2 4.9 IP: Isophthalic Acid, 5BIP:5-Bromoisophthalic Acid, 4,5-DBIP: 4,5-Dibromoisophthalic Acid 2,5-DBIP: 2,5-Dibromoisophthalic Acid
With sulfuric acid; sulfur trioxide; bromine; at 120℃; for 7h;
Into a 100 ml pressure and sealable glass tube, 9.70 g (50 mmol) of dimethyl isophthalate, 30.00 g of 10 wt percent fuming sulfuric acid and 10.40 g (100 mmol) of bromine were charged, and the content was stirred at 120° C. for 7 hours. After the conclusion of the reaction, the content was cooled to room temperature, and placed in a beaker containing ice water to give a solid. The resulting solid was filtered off, washed with cooling, and further dried under reduced pressure to give 11.95 g of a crude crystal of the aimed product (reaction yield: 50.4percent 5-bromoisophthalic acid, 19.6percent isophthalic acid, 4.9percent 2,5-dibromoisophthalic acid, 7.2percent 4,5-dibromoisophthalic acid, 7.0percent dimethyl 5-bromoisophthalate, 1.5percent dimethyl isophthalate, 0.9percent dimethyl 2,5-dibromoisophthalate and 0.2percent dimethyl 4,5-dibromoisophthalate). Then, dimethyl esters were derived from the crystal by heating and stirring it with 65.50 g (2.04 mol) of methanol and 1.75 g (30 mol percent) of sulfuric acid in an autoclave at 120° C. [0038] In succession, the esters were subjected to rectification to give 6.73 g (yield: 49.3percent, vacuum boiling point: 159° C./4.8mmHg) of aimed dimethyl 5-bromoisophthalate and 1.67 g (yield: 17.2percent, vacuum boiling point: 133° C./4.8mmHg) of dimethyl isophthalate corresponding to a raw material. The resulting crystals were identified as dimethyl 5-bromoisophthalate and 5-bromoisophthalic acid by MASS, 1H-NMR and melting point.