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With dihydrogen peroxide; iodine; In water; acetic acid; at 20 - 50℃; for 1 - 5h;Product distribution / selectivity; |
Example 1 To a mixture of 5.00 g (36.4 mmole) of 2-aminobenzoic acid, 100 ml of acetic acid and 4.63 g (18.2 mmole) of molecular iodine, 2.06 ml (18.2 mmole) of a 30% by weight aqueous solution of hydrogen peroxide was added dropwise. After the reaction mixture was stirred at the room temperature (20C) for 5 hours, 360 ml of water was added, and 6.03 g of crystals were obtained by filtration. The results of the reaction (the conversion of 2-aminobenzoic acid, the selectivities of 2-amino-5-iodobenzoic acid and 2-amino-3-iodobenzoic acid, the purity of 2-amino-5-iodobenzoic acid and the yields of isolated 2-amino-5-iodobenzoic acid) are shown in Table 1. Example 2 To a mixture of 5.00 g (36.4 mmole) of 2-aminobenzoic acid, 100 ml of acetic acid and 4.63 g (18.2 mmole) of molecular iodine, 4.12 ml (36.4 mmole) of a 30% by weight aqueous solution of hydrogen peroxide was added dropwise. After the reaction mixture was stirred at the room temperature (20 C) for 5 hours, the reaction mixture was added to 260 ml of water, and 7.57 g of crystals were obtained by filtration. The results of the reaction are shown in Table 1. The conversion increased by increasing the amount of hydrogen peroxide of the oxidizing agent.Example 3 To a mixture of 5.00 g (36.4 mmole) of 2-aminobenzoic acid, 100 ml of acetic acid and 4.63 g (18.2 mmole) of molecular iodine, 4.12 ml (36.4 mmole) of a 30% by weight aqueous solution of hydrogen peroxide was added dropwise. After the reaction mixture was stirred at 50 C for 3 hours, the reaction mixture was added to 400 ml of water, and 8.34 g of crystals were obtained by filtration. The results of the reaction are shown in Table 1.Example 4 To a mixture of 20.00 g (145.6 mmole) of 2-aminobenzoic acid, 150 ml of acetic acid and 18.51 g (72.8 mmole) of molecular iodine, 16.53 ml (145.6 mmole) of a 30% by weight aqueous solution of hydrogen peroxide was added dropwise. After the reaction mixture was stirred at 50 C for 1 hour, the reaction mixture was added to 200 ml of water, and 36.92 g of crystals were obtained by filtration. The results of the reaction are shown in Table 1.Example 5 To a mixture of 5.00 g (36.4 mmole) of 2-aminobenzoic acid, 100 ml of acetic acid and 4.63 g (18.2 mmole) of molecular iodine, 8.24 ml (72.8 mmole) of a 30% by weight aqueous solution of hydrogen peroxide was added dropwise. After the reaction mixture was stirred at 50 C for 1 hour, the reaction mixture was added to 400 ml of water, and 5.57 g of crystals were obtained by filtration. The results of the reaction are shown in Table 1. As described above, the yield of the isolated product decreased when the ratio of the amounts by mole ([C]/[B]) of hydrogen peroxide (C) to the molecular iodine (B) exceeded 4.Example 6 To a mixture of 5.00 g (36.4 mmole) of 2-aminobenzoic acid, 100 ml of acetic acid and 4.63 g (18.2 mmole) of molecular iodine, 10.3 ml (91.0 mmole) of a 30% by weight aqueous solution of hydrogen peroxide was added dropwise. After the reaction mixture was stirred at the room temperature for 5 hour, the reaction mixture was analyzed in accordance with the high performance liquid chromatography. The results of the reaction are shown in Table 1. The selectivities of the object product decreased even at the low temperature when the ratio of the amounts by mole ([C]/[B]) of hydrogen peroxide (C) to the molecular iodine (B) was 5.0.Example 7 To a mixture of 5.00 g (36.4 mmole) of 2-aminobenzoic acid, 100 ml of acetic acid and 4.63 g (18.2 mmole) of molecular iodine, 1.03 ml (9.1 mmole) of a 30% by weight aqueous solution of hydrogen peroxide was added dropwise. After the reaction mixture was stirred at the room temperature for 5 hour, the reaction mixture was analyzed in accordance with the high performance liquid chromatography. The results of the reaction are shown in Table 1. The conversion of 2-aminobenzoic acid markedly decreased when the ratio of the amounts by mole ([C]/[B]) of hydrogen peroxide (C) to the molecular iodine (B) was 0.5. |
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With potassium hydroxide; iodine; In water; acetic acid; at 20℃; for 1h;Product distribution / selectivity; |
Comparative Example 1 Into 63 ml of water containing 2.15 g (38.3 mmole) of KOH, 3.13 g (22.8 mmole) of 2-aminobenzoic acid was dissolved, and an alkaline solution prepared by dissolving 5.79 g (22.8 mmole) of molecular iodine in 32 ml of water containing 3.11 g (55.4 mmole) of KOH was added dropwise over 10 minutes. To the reaction mixture, 12.5 ml of acetic acid and 63 ml of water were added. The obtained mixture was stirred at the room temperature for 1 hour, and 4.78 g of crystals were obtained by filtration. The results are shown in Table 1. When KOH was used as the iodinating obtained. However, as described in BACKGROUND ART, a half of iodine added into the reaction system was not used for the iodination but recovered as KI, and the step for recovering and recycling iodine was necessary. Therefore, the process was complicated, and the cost increased. |
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With iodine; iodic acid; In water; acetic acid; at 20℃; for 3h;Product distribution / selectivity; |
Example 8 To a mixture of 5.00 g (36.4 mmole) of 2-aminobenzoic acid, 100 ml of acetic acid and 3.56 g (14.0 mmole) of molecular iodine, 2.12 g (8.4 mmole) of a 70% by weight aqueous solution of iodic acid was added dropwise. After the reaction mixture was stirred at the room temperature for 3 hour, the reaction mixture was analyzed in accordance with the high performance liquid chromatography. The results of the reaction are shown in Table 1. It was shown by the values obtained by the analysis of the reaction mixture that the yield of 2-amino-5-iodobenzoic acid was 60% as calculated based on the amount of iodine atom (this result is shown in the parenthesis since this result is different from the yield of the isolated product). A relatively great conversion was obtained when iodic acid of the oxidizing agent was used as the iodinating agent. However, it was difficult that the selectivity of the object product as great as that obtained by using hydrogen peroxide was obtained. |
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