CN107879927A - A kind of method for preparing α chlorinated carboxylic acids - Google Patents

Abstract

The invention discloses a method for preparing α-chlorocarboxylic acid, comprising dissolving amino acid in hydrochloric acid to form a homogeneous solution; then injecting the obtained homogeneous solution and sodium nitrite aqueous solution from a microchannel reaction device respectively Pump A and syringe pump B are pumped into the mixing valve at the same time. After being fully mixed, they are respectively pumped into the microreactor in the microchannel reaction device at a constant flow rate for reaction; the effluent liquid is collected, which is α-chlorocarboxylic acid. The method provided by the invention realizes the continuous production of α-chlorocarboxylic acid, has good product quality, simple operation, less material consumption, safe process, environmental protection, energy saving and high efficiency, and is suitable for industrial application.

Description

A kind of method for preparing α-chlorocarboxylic acid

technical field

The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for preparing α-chlorocarboxylic acid.

Background technique

The synthesis of halogenated compounds has attracted attention in the past few decades. In addition to being directly used as solvents and lubricants, organic halides are also important intermediates for the synthesis of dyes, pesticides, spices and medicines. The preparation of organic halides mainly includes three types: the addition reaction of halogen atoms and unsaturated hydrocarbons; the halogen substitution reaction of halogen atoms replacing other functional groups in molecules; the substitution reaction of halogen atoms replacing hydrogen atoms in organic molecules. In the substitution reaction, the halogen substitution reaction that occurs on the saturated aliphatic chain is generally a free radical substitution reaction, the reaction position selectivity is poor, and the product obtained is often a mixture; The strong electron-withdrawing effect of the carboxyl group weakens the α-carbon-hydrogen bond and reduces the energy of the carbon-hydrogen bond. The hydrogen atom is easy to leave with a proton, and it is easy to undergo an electrophilic substitution reaction by a halogen atom. Because the α-halogenation reaction of carboxylic acid has high activity and good reaction selectivity, the method is used to prepare α-halogenated carboxylic acid with fast reaction speed, high conversion rate and good product purity.

In 2015, there was a report on the synthesis of chlorocarboxylic acids on chirality. The amino acid is dissolved in the hydrochloric acid solution, and the temperature of the solution is kept below -5°C. Then dissolve the solid sodium nitrite in frozen water, add the aqueous solution of sodium nitrite dropwise to the mixed solution, control the temperature below 0°C, and stir in an ice bath for 5 hours. Afterwards, the ice bath was removed for an overnight reaction. The diazotization reaction occurs in this series of complex and difficult-to-control reactions, involving the action of primary amines and nitrous acid at low temperature to form diazonium salts. The diazotization reaction requires high temperature. At room temperature where the temperature is not too high, an explosion may occur; if the reaction temperature is too low, it will have a great adverse effect on the reaction conversion rate. The diazotization reaction temperature often depends on the stability of the diazonium salt. The principle that the diazotization reaction is generally carried out at a lower temperature is not absolute. The diazotization reaction takes a long time in the batch reaction pot, and it is often necessary to maintain a lower reaction temperature.

Contents of the invention

The technical problem to be solved by the present invention is to provide a method for the continuous production of amino acids to prepare α-chlorocarboxylic acids, so as to avoid the high risk of conventional operations and reduce the use of solvents and raw materials, reduce side reactions, and reduce raw materials and environmental cost.

In order to solve this technical problem, the technical scheme provided by the invention is as follows:

A method for preparing α-chlorocarboxylic acids, comprising the steps of:

(1) Amino acids are dissolved in hydrochloric acid to form a homogeneous solution;

(2) The homogeneous solution obtained in step (1) and the aqueous solution of sodium nitrite are pumped into the mixing valve from the syringe pump A and the syringe pump B in the microchannel reaction device respectively, and after fully mixing, they are respectively pumped into the microchannel at a constant flow rate The microreactor in the reaction device reacts; the liquid that flows out is collected, which is α-chlorocarboxylic acid.

The reaction solution entering the microchannel reaction device of the present invention is a homogeneous solution. If there are more particles in the solution, the reactor will be blocked, the pressure drop of the container will increase, and even the reaction cannot be carried out effectively. The present invention adopts a homogeneous solution Not only can the reaction be carried out effectively, the purity of the product is high, but also the burden of post-processing can be reduced.

The amino acids described in the present invention are alanine, arginine, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, glycine, aspartic acid, leucine amino acid, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, preferably L-threonine, phenylalanine, alanine acid, glutamic acid.

In step (1), the molar concentration of hydrochloric acid is 7-8mol/L, and the hydrochloric acid is cooled to -5-0°C and mixed with amino acid, and the molar ratio of amino acid to hydrogen chloride in hydrochloric acid is 1:4-6, preferably 1: 4.5～5.5; the temperature after mixing amino acid and hydrochloric acid is -3～5℃.

In step (2), the mass fraction of sodium nitrite in the sodium nitrite aqueous solution is 40%, and the molar ratio of sodium nitrite to hydrogen chloride in hydrochloric acid is 1:2-3, preferably 1:2.4-2.6.

In step (2), the reaction solution is stored in a glass syringe matched with a syringe pump, the flow rate of the syringe pump A is 0.011～2mL/min, preferably 0.125～1mL/min; the flow rate of the syringe pump B is 0.02-1 mL/min, preferably 0.063-0.5 mL/min.

In step (2), the reaction temperature of the microreactor is 10-50°C, preferably 20-25°C; the residence time of the reaction is 5-70min, preferably 25-55min.

In step (2), the microchannel reaction device comprises a syringe pump A, a syringe pump B, a mixing valve, a microreactor and a receiving device, and the syringe pump A and the syringe pump B are connected in parallel through a connecting pipe and a mixing valve, and the mixing Valves, microreactors and receiving devices are connected in series through connecting pipes.

The microreactor of the present invention is provided with a coil tube, and the volume of the microreactor is 5-20mL.

The diameter of the connecting pipe of the present invention is 0.5～4mm, including the connecting pipe between the liquid inlet pipe, the mixing valve and the microreactor, and the liquid outlet pipe between the microreactor and the receiving device, the length of each connecting pipe 10-70 cm; the pipe diameter of the microreactor is 0.5-4 mm, preferably 0.5-1 mm. Although a too small pipe diameter can effectively increase the specific surface area, it will lead to an increase in the liquid flow pressure, which may cause clogging, pipe bursting and other adverse conditions. The material connecting pipe used in the present invention must be controlled within the above preferred range.

The mixing valve in the microchannel reactor of the present invention can be a T-shaped mixing valve, a Y-shaped mixing valve, an inverted Y-shaped mixing valve, and the like.

Microreactors usually contain small channel size (equivalent diameter less than 10μm-1000μm) and channel diversity, such as zigzag, heart shape, etc., fluid flows in these channels, and requires the required reaction to occur in these channels . This leads to a very large surface area/volume ratio in the microstructured chemical equipment, resulting in a huge mass and heat transfer effect, which is thousands or even ten thousand times that of conventional reactions, which avoids local overheating, General defects such as uneven mixing. When diazotization is carried out in microchannels, favorable factors such as less material input, high heat and mass transfer efficiency, and greatly shortened reaction time determine that the diazotization reaction can be carried out at a slightly higher temperature.

Beneficial effects: the reaction utilizes micro-flow field technology to precisely control the reaction temperature, the whole process has short reaction time, little toxicity and pollution, and little side reaction. The α-chlorocarboxylic acid can be prepared under the conditions of shorter time, favorable temperature and less amount of raw materials. The invention realizes the continuous production of α-chlorocarboxylic acid, has good product quality, simple operation, less material consumption, environmental protection, energy saving and high efficiency, and is suitable for industrial application.

Description of drawings

Fig. 1 is the structural representation of microchannel reaction device of the present invention; Wherein 1 is syringe pump A, 2 is syringe pump B, 3 is mixing valve, 4 is microreactor, 5 is receiving device.

Fig. 2 is the reaction equation of the present invention.

Detailed ways

The present invention can be better understood from the following examples. However, those skilled in the art can easily understand that the content described in the embodiments is only for illustrating the present invention, and should not and will not limit the present invention described in the claims.

Example 1

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weigh L-threonine (4.4679 g, 0.0375 mol) and dissolve it in the hydrochloric acid to obtain a homogeneous mixed solution and transfer it to a syringe matched with syringe pump A at a flow rate of 0.125 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.063 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 20°C, and the reaction time is 54.4min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0034, and the yield was 90.8%.

Comparative example 1

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. L-threonine (4.4679 g, 0.0375 mol) was weighed and dissolved in the hydrochloric acid to obtain a mixed solution. Sodium nitrite (5.1735 g, 0.075 mol) solid was then dissolved in frozen water at -5-0°C. An aqueous solution of sodium nitrite (40%) was added dropwise to the mixed solution of hydrochloric acid and threonine, and the temperature was controlled at -5-0° C., and stirred in an ice bath for 5 hours. after. The ice bath was removed and the reaction was carried out overnight, and the α-chlorocarboxylic acid product was obtained after 12 hours. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0034, and the yield was 63%.

Example 2

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weighed L-threonine (4.4679 g, 0.0375 mol) and dissolved it in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 25°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0033, and the yield was 87.4%.

Example 3

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weighed L-threonine (4.4679 g, 0.0375 mol) and dissolved it in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 20°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0034, and the yield was 94.7%.

Example 4

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weigh L-threonine (4.4679 g, 0.0375 mol) and dissolve it in the hydrochloric acid to obtain a homogeneous mixed solution and transfer it to a syringe matched with syringe pump A at a flow rate of 0.125 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.063 mL/min. The two are mixed with a Y-type mixing valve and pumped together into the microreactor. The volume of the microreactor is 10mL, the reaction temperature is 25°C, and the reaction time is 54.4min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0035, and the yield was 88.9%.

Example 5

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weigh L-threonine (4.4679 g, 0.0375 mol) and dissolve it in the hydrochloric acid to obtain a homogeneous mixed solution and transfer it to a syringe matched with syringe pump A at a flow rate of 0.5 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.25 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 25°C, and the reaction time is 13.3min. The reaction liquid is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0036, and the yield was 90.5%.

Example 6

Add hydrochloric acid (25mL, 7mol/L) into the beaker and cool to -5~0°C. Weighed L-threonine (4.1671 g, 0.035 mol) and dissolved it in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (4.8286 g, 0.07 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 25°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0034, and the yield was 90.4%.

Example 7

Add hydrochloric acid (25mL, 7mol/L) into the beaker and cool to -5~0°C. Weighed L-threonine (4.1671 g, 0.035 mol) and dissolved it in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (4.8286 g, 0.07 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 20°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0040, and the yield was 91.2%.

Example 8

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weighed L-threonine (5.5809 g, 0.0469 mol) and dissolved it in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 25°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0038, and the yield was 90.3%.

Example 9

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weighed L-threonine (5.5809 g, 0.0469 mol) and dissolved it in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 20°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0041, and the yield was 91.2%.

Example 10

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weigh L-threonine (4.4679 g, 0.0375 mol) and dissolve it in the hydrochloric acid to obtain a homogeneous mixed solution and transfer it to a syringe matched with syringe pump A at a flow rate of 0.25 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.125 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 25°C, and the reaction time is 26.7min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0037, and the yield was 89.1%.

Example 11

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weigh L-threonine (4.4679 g, 0.0375 mol) and dissolve it in the hydrochloric acid to obtain a homogeneous mixed solution and transfer it to a syringe matched with syringe pump A at a flow rate of 0.25 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.125 mL/min. The two are mixed with a Y-type mixing valve and pumped into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 20°C, and the reaction time is 26.7min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0041, and the yield was 88.7%.

Example 12

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weighed L-threonine (4.4679 g, 0.0375 mol) and dissolved it in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. The two are mixed with a Y-type mixing valve and pumped into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 10°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0035, and the yield was 93.1%.

Example 13

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weighed L-threonine (4.4679 g, 0.0375 mol) and dissolved it in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. The two are mixed with a Y-type mixing valve and pumped together into the microreactor. The volume of the microreactor is 10mL, the reaction temperature is 50°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0034, and the yield was 92.2%.

Example 14

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weighed L-threonine (4.4679 g, 0.0375 mol) and dissolved it in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 5mL, the reaction temperature is 10°C, and the reaction time is 3.33min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0039, and the yield was 90.5%.

Example 15

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Weighed L-threonine (4.4679 g, 0.0375 mol) and dissolved it in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. The two are mixed with a Y-type mixing valve and pumped together into the microreactor. The volume of the microreactor is 20mL, the reaction temperature is 10°C, and the reaction time is 13.33min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 151.0038, and the yield was 93.1%.

Example 16

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Phenylalanine (6.7208 g, 0.0375 mol) was weighed and dissolved in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 25°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 211.0401, and the yield was 87.2%.

Example 17

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Glycine (2.8151 g, 0.0375 mol) was weighed and dissolved in the hydrochloric acid to obtain a homogeneous mixed solution, which was transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 25°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 106.9769, and the yield was 85.7%.

Example 18

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Alanine (3.3409 g, 0.0375 mol) was weighed and dissolved in the hydrochloric acid to obtain a homogeneous mixed solution, which was transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 25°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid mass spectrometry, HRMS (TOF) m/z [MH] ^- was 120.9933, and the yield was 93.4%.

Example 19

Add hydrochloric acid (25mL, 7.5mol/L) into the beaker and cool to -5~0°C. Glutamic acid (5.5174 g, 0.0375 mol) was weighed and dissolved in the hydrochloric acid to obtain a homogeneous mixed solution, which was then transferred to a syringe matched with syringe pump A at a flow rate of 1 mL/min. An aqueous solution (40%) of sodium nitrite (5.1735 g, 0.075 mol) was transferred to a syringe fitted with syringe pump B at a flow rate of 0.5 mL/min. Mix the two with a Y-type mixing valve and pump them into the microreactor together. The volume of the microreactor is 10mL, the reaction temperature is 25°C, and the reaction time is 6.67min. The reaction solution is the α-chlorocarboxylic acid product. The obtained product was detected by liquid chromatography-mass spectrometry, HRMS (TOF) m/z [MH] ^- was 178.9989, and the yield was 89.6%.

Claims (10)

1. A kind of 1. method for preparing alpha-chloro carboxylic acid, it is characterised in that comprise the following steps：

   (1) amino acid is dissolved in hydrochloric acid, forms homogeneous phase solution；

   (2) homogeneous phase solution and sodium nitrite in aqueous solution obtained step (1) is respectively from the syringe pump A in the reaction unit of microchannel Mixing valve is pumped into simultaneously with syringe pump B, after being sufficiently mixed, respectively with micro- anti-in constant flow pump in a subtle way pathway reaction device Device is answered to be reacted；Collect trickle, as alpha-chloro carboxylic acid.
2. 2. the method for preparing alpha-chloro carboxylic acid as claimed in claim 1, it is characterised in that described amino acid is alanine, essence Propylhomoserin, aspartic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, glycine, aspartic acid, bright ammonia Acid, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine.
3. 3. the method for preparing alpha-chloro carboxylic acid as claimed in claim 1, it is characterised in that in step (1), the molar concentration of hydrochloric acid For 7~8mol/L, hydrochloric acid is cooled to after -5~0 DEG C and mixed with amino acid, the mol ratio of amino acid and hydrogen chloride in hydrochloric acid is 1: 4 ~6, amino acid is -3~5 DEG C with the temperature after mixed in hydrochloric acid.
4. 4. the method for preparing alpha-chloro carboxylic acid as claimed in claim 1, it is characterised in that in step (2), sodium nitrite in aqueous solution The mass fraction of Sodium Nitrite is 40%, and the mol ratio of natrium nitrosum and hydrogen chloride in hydrochloric acid is 1: 2~3.
5. 5. as claimed in claim 1 prepare alpha-chloro carboxylic acid method, it is characterised in that in step (2), reaction solution be stored in In the glass syringe that syringe pump matches, the flow velocity of the syringe pump A is 0.011~2mL/min；The stream of the syringe pump B Speed is 0.02~1mL/min.
6. 6. the method for preparing alpha-chloro carboxylic acid as claimed in claim 1, it is characterised in that in step (2), the microreactor Reaction temperature is 10~50 DEG C, and the residence time of reaction is 5~70min.
7. 7. the method for preparing alpha-chloro carboxylic acid as claimed in claim 1, it is characterised in that in step (2), the microchannel plate should Device includes syringe pump A, syringe pump B, mixing valve, microreactor and reception device, and syringe pump A and syringe pump B are with parallel connection side Formula is connected by connecting tube with mixing valve, and mixing valve, microreactor and reception device are connected by connecting tube in a series arrangement Connect.
8. 8. the method for preparing alpha-chloro carboxylic acid as claimed in claim 7, it is characterised in that coil pipe is set in the microreactor, it is micro- Reactor volume is 5~20mL.
9. 9. the method for alpha-chloro carboxylic acid is prepared as described in claim 7 or 8, it is characterised in that the pipeline of the microreactor is straight Footpath is 0.5~4mm.
10. 10. the method for alpha-chloro carboxylic acid is prepared as described in claim 7 or 8, it is characterised in that the connecting tube it is a diameter of 0.5~4mm, length are 10~70cm.