74% |
Stage #1: at -30 - 5℃; Stage #2: With hydrogenchloride In tetrahydrofuran |
(Example 2) Example 2 was carried out in a reaction apparatus 50 shown in Figure 2. Here, each length of branch introduction flow channels 16a to 16e was set at 0.5 m, and a portion from a main flow channel 12 to 5 cm of branch introduction flow channels 16a to 16e was arranged in a thermostatic liquid tank 28. The length of an adjusting flow channel 18 was set at 1 m. Each of the flow channel lengths of a flow channel 12a between introduction points 12o and 12p in the main flow channel 12 and a flow channel 12b between introduction points 12p and 12q was set at 3 m, and each of the flow channel lengths of a flow channel 12c between introduction points 12q and 12r, a flow channel 12d between introduction points 12r and 12s and a flow channel 12e from an introduction point 12s to an edge of the thermostatic liquid tank 28 was set at 1 m. The other conditions were set at the same condition as in Example 1. A Grignard reagent: 1-bromomagnesium-5-chloropentane (0.45 mol/L) was diluted by a tetrahydrofuran solvent and the diluted solution was used as a raw material M2. Diethyl oxalate (7.4 mol/L) which had not been diluted by the solvent was used as a raw material M1. The raw material M2 and the raw material M1 were supplied to a flowing-type fine reaction flow channel 32, at 110 mL/min and 5.1 mL/min, respectively. From the above described conditions, a mixed solution of these materials stays in the flowing-type fine reaction flow channel 32 for approximately 42 seconds. The Grignard reagent and diethyl oxalate were accommodated in a supply container and controlled at 10°C and room temperature respectively, and the thermostatic liquid tank 28 accommodated methanol as a refrigerant 30 and was controlled at -15°C. The produced liquid was collected and quenched with a dilute hydrochloric acid. The target substance of ethyl-7-chloro-2-oxalic pentane was obtained in the yield of 90percent.; (Example 2') Example 2' was carried out while controlling the temperature of a thermostatic liquid tank 28 to -5°C, and setting other conditions at the same conditions as in Example 2. As a result, the yield of ethyl-7-chloro-2oxalic pentane was 86percent.; (Example 3) Example 3 was carried out in a reaction apparatus 50 shown in Figure 2. Here, a circular pipe having an inner diameter 3 mm and an outer diameter 4 mm was used for the pipe which constitutes a main flow channel 12, an introduction flow channel 14 and each of branch introduction flow channels 16a to 16e. The lengths of the respective branch introduction flow channels 16a to 16e were set at 0.5 m. The length of an adjusting flow channel 18 was set at 1 m. The flow channel lengths of a flow channel 12a between introduction points 12o and 12p in the main flow channel 12 and a flow channel 12b between introduction points 12p and 12q were each set at 3 m, and the flow channel lengths of a flow channel 12c between introduction points 12q and 12r, a flow channel 12d between introduction points 12r and 12s and a flow channel 12e from an introduction point 12s to an edge of a thermostatic liquid tank 28 were set at 1 m respectively. The other conditions were the same as in Example 1. A Grignard reagent: 1-bromomagnesium-5-chloropentane (0.45 mol/L) was diluted by a tetrahydrofuran solvent and the diluted solution was used as a raw material M2. Diethyl oxalate (7.4 mol/L) which had not been diluted by the solvent was used as a raw material M1. The raw material M2 and the raw material M1 were supplied to a flowing-type fine reaction flow channel 32, at 965 mL/min and 47 mL/min, respectively. From the above described conditions, a mixed solution of these materials stays in a flowing-type fine reaction flow channel 32 for approximately 4.9 seconds. The Grignard reagent and diethyl oxalate were accommodated in a supply container and controlled at 10°C and room temperature respectively, and the thermostatic liquid tank 28 accommodated methanol as a refrigerant 30 and was controlled at -30°C. The produced liquid was collected and quenched with a dilute hydrochloric acid. The target substance of ethyl-7-chloro-2-oxalic pentane was obtained in the yield of 88percent.; (Example 4) Example 4 was carried out in a reaction apparatus 50 shown in Figure 2. Here, a circular pipe having an inner diameter 1 mm and an outer diameter 3 mm was used for the pipe which constitutes a main flow channel 12. A circular pipe having an inner diameter 3 mm and an outer diameter 4 mm was used for the pipe which constitutes an introduction flow channel 14. A circular pipe having an inner diameter 1 mm and an outer diameter 3 mm was used for the pipe which constitutes each of branch introduction flow channels 16a to 16e. Lengths of branch introduction flow channels 16a to 16e were set at 0.5 m, 1.5 m, 2.0 m, 2.5 m and 3.0 m respectively, and portions from the main flow channel 12 to 5 cm of all branch introduction flow channels were arranged in a thermostatic liquid tank 28. The length of an adjusting flow channel 18 was set at 1 m. The flow channel length of a flow channel 12a between introduction points 12o and 12p in the main flow channel 12 was set at 1.0 m, and the flow channel lengths of a flow channel 12b between introduction points 12p and 12q, a flow channel 12c between introduction points 12q and 12r, a flow channel 12d between introduction points 12r and 12s, and a flow channel 12e from an introduction point 12s to an edge of the thermostatic liquid tank 28 were set at 0.5 m respectively. The other conditions were the same as in the above described reaction apparatus 10. A Grignard reagent: 1-bromomagnesium-5-chloropentane (0.45 mol/L) was diluted by a tetrahydrofuran solvent and the diluted solution was used as a raw material M2. Diethyl oxalate (7.4 mol/L) which had not been diluted by the solvent was used as a raw material M1. The raw material M2 and the raw material M1 were supplied to a flowing-type fine reaction flow channel 32, at 109 mL/min and 5.1 mL/min, respectively. From the above described conditions, a mixed solution of these materials stays in the flowing-type fine reaction flow channel 32 for approximately 1.6 seconds. The Grignard reagent and diethyl oxalate were accommodated in a supply container and controlled at 10°C and room temperature respectively, and the thermostatic liquid tank 28 accommodated methanol as a refrigerant 30 and was controlled at -15°C. The produced liquid was collected and quenched with a dilute hydrochloric acid. The target substance of ethyl-7-chloro-2-oxalic pentane was obtained in the yield of 90percent.; (Example 4') Example 4' was carried out while controlling the temperature of a thermostatic liquid tank 28 to 5°C, and setting other conditions at the same conditions as in Example 4. As a result, the yield of ethyl-7-chloro-2oxalic pentane was 89percent.; (Example 5) Example 5 was carried out in a reaction apparatus 50 shown in Figure 2. Here, a circular pipe having an inner diameter 1 mm and an outer diameter 3 mm was used for the pipe which constitutes a main flow channel 12. A circular pipe having an inner diameter 3 mm and an outer diameter 4 mm was used for the pipe which constitutes an introduction flow channel 14. A circular pipe having an inner diameter 1 mm and an outer diameter 3 mm was used for the pipe which constitutes each of branch introduction flow channels 16a to 16e. Each length of branch introduction flow channels 16a to 16e was set at 0.5 m, and portions from the main flow channel 12 to 5 cm of all the branch introduction flow channels 16a to 16e were arranged in a thermostatic liquid tank 28. The length of an adjusting flow channel 18 was set at 1 m. The flow channel length of a flow channel 12a between introduction points 12o and 12p in the main flow channel 12 was set at 1.0 m, and the flow channel lengths of a flow channel 12b, a flow channel 12c, a flow channel 12d, and a flow channel 12e respectively between introduction points 12p and 12q, between introduction points 12q and 12r, between introduction points 12r and 12s, and from an introduction point 12s to an edge of the thermostatic liquid tank 28 were set at 0.5 m. The other conditions were the same as in the above described reaction apparatus 10. A Grignard reagent: 1-bromomagnesium-5-chloropentane (0.45 mol/L) was diluted by a tetrahydrofuran solvent and the diluted solution was used as a raw material M2. Diethyl oxalate (2.0 mol/L) which had been diluted by the same solvent was used as a raw material M1. The raw material M2 and the raw material M1 were supplied to a flowing-type fine reaction flow channel 32, at 100 mL/min and 17 mL/min, respectively. From the above described conditions, a mixed solution of these materials stays in the flowing-type fine reaction flow channel 32 for approximately 1.4 seconds. The Grignard reagent and diethyl oxalate were accommodated in a supply container and controlled at 10°C and room temperature respectively, and the thermostatic liquid tank 28 accommodated methanol as a refrigerant 30 and was controlled at -15°C. The produced liquid was collected and quenched with a dilute hydrochloric acid. The target substance of ethyl-7-chloro-2-oxalic pentane was obtained in the yield of 84percent.; (Comparative example 1) The above described reaction was carried out by using a microreactor system made by Cellular Process Chemistry GmbH. The Grignard reagent: 1-bromomagnesium-5-chloropentane (0.45 mol/L) was diluted by a tetrahydrofuran solvent and the diluted solution was used as a raw material M2. Diethyl oxalate (5.5 mol/L) which had been diluted by the same solvent was used as a raw material M1. The raw material M2 and the raw material M1 were supplied to a flowing-type fine reaction flow channel, at 16 mL/min and 1 mL/min, respectively. The reaction apparatus was kept at -5°C by an attached temperature controller. The yield of a target substance was 84percent, but plug-up occurred and the raw materials could not be supplied on the way.; (Comparative example 2) In comparison with Example 3, branch introduction flow channels 16a to 16e to be connected to the main flow channel 12 were made to be one channel instead of 5 channels. Comparative example 2 was carried out under the same conditions as in Example 3, except the above described condition. The yield of a target substance was 74percent.(Result) The result of the above described examples will now be described together in the following Table. |