Method for diazotization of 5-methyl-4,5,6, 7-tetrahydrothiazolo [5, 4-c] pyridine by use of micro reaction device

Abstract

The invention discloses a method for diazotization of 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c] pyridine by use of a micro reaction device, sulphate 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridine-2-amine is used as a raw material, and concentrated sulfuric acid, hypophosphorous acid and sodium nitrite are used for preparing the 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c] pyridine in the micro reaction device. Compared with the prior art, the diazotization of the 5-methyl-4,5,6, 7-tetrahydrothiazolo [5, 4-c] pyridine is realized by use of the micro reaction device, and the method has the advantages of simple process, continuous production, small reaction volume, short time, smaller equipment corrosion, higher operation safety and higher selectivity and the like. At the same time, through use of the high efficient heat transfer ability and easy direct amplification characteristic of a micro channel reactor, the method has high conversion rate, the conversion rate is above 75%, the product quality is good, energy consumption is low, and the method is a green, environmentally-friendly and efficient method for synthesis of the 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c] pyridine, and is suitable for industrial application.

Description

technical field

[0001] The invention belongs to the field of chemical synthesis, and in particular relates to a method for realizing diazotization of 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine by using a micro-reaction device. Background technique

[0002] The reaction of aromatic primary amine and nitrous acid to produce diazonium compound is called diazotization reaction, and diazotization reaction is an intermediate process of many organic reactions. As important reagents and intermediates in organic synthesis, diazo compounds are widely used in the fields of biomedicine, color reaction, quantitative analysis, material surface modification and microelectronics industry. The diazotization reaction is an exothermic reaction, and the reaction speed is fast; the chemical properties of the diazonium salt are very active, and various reactions can occur, so the focus of the diazotization reaction is to achieve precise temperature control. In the traditional process, in...

Examples

Embodiment 1

[0042] In the microchannel reaction device, the diameter of the connecting pipe is 2.1mm, the length of the inlet pipe is 15cm, the length of the connecting pipe between the T-shaped valve and the microchannel reactor is 25cm, and the length of the connecting pipe between the microreactor and the outlet is 20cm.

[0043] Take 3.84ml of concentrated sulfuric acid and 5.6ml of hypophosphorous acid dissolved in 30mL of distilled water, the temperature is controlled at 5°C. Take 4.77g of sulfuric acid 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-C]pyridin-2-amine, dissolve it in the above solution, and dilute to 50ml, the temperature is controlled at 0°C. Take 2.484g of sodium nitrite, dissolve it in 20ml of water, and set the volume to 25ml, and control the temperature at 0°C. After pre-cooling the above two volume-constant solutions to 0°C, pump them in at the same time, and enter the microchannel reactor through the T-shaped mixing valve. min, 0.15mL / min, reaction temperatur...

Embodiment 2

[0045]In the microchannel reaction device, the diameter of the connecting pipe is 2.1mm, the length of the inlet pipe is 15cm, the length of the connecting pipe between the T-shaped valve and the microchannel reactor is 25cm, and the length of the connecting pipe between the microreactor and the outlet is 20cm.

[0046] Take 3.84ml of concentrated sulfuric acid and 5.6ml of hypophosphorous acid dissolved in 30mL of distilled water, the temperature is controlled at 5°C. Take 4.77g of sulfuric acid 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-C]pyridin-2-amine, dissolve it in the above solution, and dilute to 50ml, the temperature is controlled at 0°C. Take 2.484g of sodium nitrite, dissolve it in 20ml of water, and set the volume to 25ml, and control the temperature at 0°C. The above two solutions after constant volume were pre-cooled to 0°C, pumped in at the same time, and entered into the microchannel reactor through the T-shaped mixing valve. The volume of the reactor was ...

Embodiment 3

[0048] In the microchannel reaction device, the diameter of the connecting pipe is 2.1mm, the length of the inlet pipe is 15cm, the length of the connecting pipe between the T-shaped valve and the microchannel reactor is 25cm, and the length of the connecting pipe between the microreactor and the outlet is 20cm.

[0049] Take 3.84ml of concentrated sulfuric acid and 5.6ml of hypophosphorous acid dissolved in 30mL of distilled water, the temperature is controlled at 5°C. Take 4.77g of sulfuric acid 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-C]pyridin-2-amine, dissolve it in the above solution, and dilute to 50ml, the temperature is controlled at 0°C. Take 2.484g of sodium nitrite, dissolve it in 20ml of water, and set the volume to 25ml, and control the temperature at 0°C. After pre-cooling the above two constant-volume solutions to 0°C, pump them in at the same time, and enter the microchannel reactor through the T-shaped mixing valve. The volume of the reactor is 10mL, an...

technical field

[0001] The invention belongs to the field of chemical synthesis, and in particular relates to a method for realizing diazotization of 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine by using a micro-reaction device. Background technique

[0002] The reaction of aromatic primary amine and nitrous acid to produce diazonium compound is called diazotization reaction, and diazotization reaction is an intermediate process of many organic reactions. As important reagents and intermediates in organic synthesis, diazo compounds are widely used in the fields of biomedicine, color reaction, quantitative analysis, material surface modification and microelectronics industry. The diazotization reaction is an exothermic reaction, and the reaction speed is fast; the chemical properties of the diazonium salt are very active, and various reactions can occur, so the focus of the diazotization reaction is to achieve precise temperature control. In the traditional process, in...

Examples

Embodiment 1

[0042] In the microchannel reaction device, the diameter of the connecting pipe is 2.1mm, the length of the inlet pipe is 15cm, the length of the connecting pipe between the T-shaped valve and the microchannel reactor is 25cm, and the length of the connecting pipe between the microreactor and the outlet is 20cm.

[0043] Take 3.84ml of concentrated sulfuric acid and 5.6ml of hypophosphorous acid dissolved in 30mL of distilled water, the temperature is controlled at 5°C. Take 4.77g of sulfuric acid 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-C]pyridin-2-amine, dissolve it in the above solution, and dilute to 50ml, the temperature is controlled at 0°C. Take 2.484g of sodium nitrite, dissolve it in 20ml of water, and set the volume to 25ml, and control the temperature at 0°C. After pre-cooling the above two volume-constant solutions to 0°C, pump them in at the same time, and enter the microchannel reactor through the T-shaped mixing valve. min, 0.15mL / min, reaction temperatur...

Embodiment 2

[0045]In the microchannel reaction device, the diameter of the connecting pipe is 2.1mm, the length of the inlet pipe is 15cm, the length of the connecting pipe between the T-shaped valve and the microchannel reactor is 25cm, and the length of the connecting pipe between the microreactor and the outlet is 20cm.

[0046] Take 3.84ml of concentrated sulfuric acid and 5.6ml of hypophosphorous acid dissolved in 30mL of distilled water, the temperature is controlled at 5°C. Take 4.77g of sulfuric acid 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-C]pyridin-2-amine, dissolve it in the above solution, and dilute to 50ml, the temperature is controlled at 0°C. Take 2.484g of sodium nitrite, dissolve it in 20ml of water, and set the volume to 25ml, and control the temperature at 0°C. The above two solutions after constant volume were pre-cooled to 0°C, pumped in at the same time, and entered into the microchannel reactor through the T-shaped mixing valve. The volume of the reactor was ...

Embodiment 3

[0048] In the microchannel reaction device, the diameter of the connecting pipe is 2.1mm, the length of the inlet pipe is 15cm, the length of the connecting pipe between the T-shaped valve and the microchannel reactor is 25cm, and the length of the connecting pipe between the microreactor and the outlet is 20cm.

[0049] Take 3.84ml of concentrated sulfuric acid and 5.6ml of hypophosphorous acid dissolved in 30mL of distilled water, the temperature is controlled at 5°C. Take 4.77g of sulfuric acid 5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-C]pyridin-2-amine, dissolve it in the above solution, and dilute to 50ml, the temperature is controlled at 0°C. Take 2.484g of sodium nitrite, dissolve it in 20ml of water, and set the volume to 25ml, and control the temperature at 0°C. After pre-cooling the above two constant-volume solutions to 0°C, pump them in at the same time, and enter the microchannel reactor through the T-shaped mixing valve. The volume of the reactor is 10mL, an...

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