CN117924112A - Dark blue esterified liquid and preparation method thereof - Google Patents

Abstract

The invention provides a deep blue esterified liquid and a preparation method thereof. The preparation method comprises the following steps: pretreatment: dissolving 2-amino-4-acetamido anisole in a solvent to obtain a pretreatment liquid; hydroxylation reaction step: carrying out hydroxylation reaction on the pretreatment liquid and liquid ethylene oxide in a microchannel reactor to obtain a hydroxylation liquid; and (3) heat preservation reaction step: conveying the hydroxylation liquid from the micro-channel reactor to a reaction device for continuous heat preservation reaction to obtain a hydroxylation product; and (3) dehydration: carrying out vacuum dehydration on the hydroxylation product to obtain a dehydrated product; esterification reaction step: and (3) carrying out esterification reaction on the dehydrated product and acetic anhydride to obtain deep blue esterified liquid. The preparation method omits the gasification step of ethylene oxide, and simplifies the reaction device. In the preparation method, the instant storage of the ethylene oxide in the reactor is greatly reduced, the unsafe risk in the hydroxylation reaction process in the preparation process is reduced, and the intrinsic safety level of the reaction process is improved.

Description

Dark blue esterified liquid and preparation method thereof

Technical Field

The invention relates to a deep blue esterified liquid and a preparation method thereof, belonging to the technical field of dye intermediate synthesis.

Background

The dark blue esterified liquid is used as an intermediate of disperse dye and is generally used for synthesizing C.I. disperse violet 58 and C.I. disperse blue 79.

The existing production method of the deep blue esterified liquid mainly uses 2-amino-4-acetamido anisole as a raw material, and the raw material reacts with gaseous ethylene oxide in a water phase to prepare a hydroxy compound (2-methoxy-5-acetamido-N, N-dihydroxyethyl aniline), and then the hydroxy compound is dehydrated and esterified with acetic anhydride or acetic acid to obtain the deep blue esterified liquid (2-methoxy-5-acetamido-N, N-diacetoxyethyl aniline).

However, in the above method, the reaction of 2-amino-4-acetaminophen ether with ethylene oxide is a typical hydroxylation reaction, and thus, not only is the risk of the reaction itself high, but also the gasification process of ethylene oxide is at a high risk.

Therefore, research on a synthesis process capable of reducing reaction risk and improving intrinsic safety level in the hydroxylation reaction process becomes a technical problem to be solved in product research and development improvement.

Disclosure of Invention

Problems to be solved by the invention

In view of the technical problems in the prior art, the invention provides a preparation method of a deep blue esterification liquid. According to the preparation method of the deep blue esterified liquid, on the premise that the purity and the yield of the prepared deep blue esterified liquid reach the standards and the coupling value is qualified, the unsafe risk in the hydroxylation reaction process in the preparation process is greatly reduced, and the aim of realizing the intrinsic safety in the hydroxylation reaction process is fulfilled.

Furthermore, the preparation method of the deep blue esterified liquid has more reasonable process, lower production cost and production safety risk and is suitable for mass production.

Solution for solving the problem

The invention provides a preparation method of a deep blue esterified liquid, which comprises the following steps:

pretreatment: dissolving 2-amino-4-acetamido anisole in a solvent to obtain a pretreatment liquid;

Hydroxylation reaction step: carrying out hydroxylation reaction on the pretreatment liquid and liquid ethylene oxide in a micro-channel reactor to obtain a hydroxylation liquid;

And (3) heat preservation reaction step: conveying the hydroxylation liquid from the microchannel reactor to a reaction device for continuous heat preservation reaction to obtain a hydroxylation product;

And (3) dehydration: carrying out vacuum dehydration on the hydroxylation product to obtain a dehydrated product;

esterification reaction step: and carrying out esterification reaction on the dehydrated product and acetic anhydride to obtain deep blue esterified liquid.

The preparation method of the invention, wherein in the pretreatment step, the mass ratio of the 2-amino-4-acetamido anisole to the solvent is 1:0.8-1:1.2; and/or the number of the groups of groups,

In the hydroxylation reaction step, the molar ratio of the 2-amino-4-acetamido anisole to the liquid ethylene oxide is 1:2-1:2.5; and/or the number of the groups of groups,

In the esterification reaction step, the molar ratio of the dehydration product to the acetic anhydride is 1:2-1:2.7, preferably 1:2.1-2.5.

The preparation method of the invention, wherein in the pretreatment step, the dissolution temperature is 80-100 ℃, and the dissolution time is 0.5-1 h; preferably, the pretreatment step further includes a step of subjecting the pretreatment liquid to solid-liquid separation, and more preferably, the solid-liquid separation temperature is 80 to 100 ℃.

The preparation method of the invention, wherein in the hydroxylation reaction step, the hydroxylation reaction time is 4-6 min, the hydroxylation reaction temperature is 80-100 ℃, and the hydroxylation reaction pressure is 0.1-0.3 MPa.

The preparation method of the invention, wherein in the heat preservation step, the temperature of the heat preservation reaction is 80-100 ℃, and the time of the heat preservation reaction is 2-3 h.

The preparation method of the invention, wherein in the dehydration step, the temperature of the vacuum dehydration is 120-130 ℃, and the vacuum degree of the vacuum dehydration is-0.7 MPa to-0.9 MPa.

The preparation method comprises the steps of adding acetic anhydride into the dehydrated product in a dropwise manner, and carrying out esterification reaction after the completion of the dropwise addition to obtain a deep blue esterified liquid.

The preparation method provided by the invention is characterized in that the dripping time is 2-4 hours; and/or the number of the groups of groups,

The time of the esterification reaction is 1-2 h, and the temperature of the esterification reaction is 80-100 ℃.

The preparation method of the invention, wherein the amino value of the 2-amino-4-acetamido anisole is 98-99%; and/or the number of the groups of groups,

The mass concentration of the ethylene oxide is 98-99%; and/or the number of the groups of groups,

The mass concentration of the acetic anhydride is 98-99%.

The invention also provides a deep blue esterified liquid, which is prepared by the preparation method.

ADVANTAGEOUS EFFECTS OF INVENTION

The preparation method omits the step of gasifying the ethylene oxide, and simplifies the reaction device.

Furthermore, in the preparation method, the instant storage of the ethylene oxide in the reactor can be greatly reduced, so that the unsafe risk in the hydroxylation reaction process in the preparation process is greatly reduced, and the intrinsic safety level of the reaction process is improved.

Furthermore, the preparation method disclosed by the invention is more reasonable in process, lower in production cost and lower in production risk, and is suitable for mass production.

Detailed Description

Various exemplary embodiments, features and aspects of the invention are described in detail below. The word "exemplary" is used herein to mean "serving as an example, embodiment, or illustration. Any embodiment described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments.

Furthermore, in the following detailed description, numerous specific details are set forth in order to provide a better illustration of the invention. It will be understood by those skilled in the art that the present invention may be practiced without some of these specific details. In other instances, well known methods, procedures, means, equipment and steps have not been described in detail so as not to obscure the present invention.

Unless otherwise indicated, all units used in this specification are units of international standard, and numerical values, ranges of values, etc. appearing in the present invention are understood to include systematic errors unavoidable in industrial production.

In the present specification, the meaning of "can" includes both the meaning of performing a certain process and the meaning of not performing a certain process.

Reference throughout this specification to "some specific/preferred embodiments," "other specific/preferred embodiments," "an embodiment," and so forth, means that a particular element (e.g., feature, structure, property, and/or characteristic) described in connection with the embodiment is included in at least one embodiment described herein, and may or may not be present in other embodiments. In addition, it is to be understood that the elements may be combined in any suitable manner in the various embodiments.

In the present specification, the numerical range indicated by the term "numerical value a to numerical value B" means a range including the end point numerical value A, B.

In the present specification, when "normal temperature" and "room temperature" are used, the temperature may be 15 to 25 ℃.

In the present specification, the use of "monoester" means a compound represented by the following formula a or the following formula B:

in the present specification, "monohydroxy" is used to represent a compound represented by the following formula C:

The invention firstly provides a preparation method of a deep blue esterified liquid, which is characterized by comprising the following steps:

pretreatment: dissolving 2-amino-4-acetamido anisole in a solvent to obtain a pretreatment liquid;

Hydroxylation reaction step: carrying out hydroxylation reaction on the pretreatment liquid and liquid ethylene oxide in a micro-channel reactor to obtain a hydroxylation liquid;

And (3) heat preservation reaction step: conveying the hydroxylation liquid from the microchannel reactor to a reaction device for continuous heat preservation reaction to obtain a hydroxylation product;

And (3) dehydration: carrying out vacuum dehydration on the hydroxylation product to obtain a dehydrated product;

esterification reaction step: and carrying out esterification reaction on the dehydrated product and acetic anhydride to obtain deep blue esterified liquid.

Pretreatment step

In the pretreatment step, 2-amino-4-acetaminophen ether is dissolved in a solvent to obtain a pretreatment liquid.

Preferably, 2-amino-4-acetaminophen can be dissolved by heating. Specifically, in the pretreatment step of the present invention, the temperature of the dissolution is 80 to 100 ℃, for example 82 ℃, 85 ℃, 88 ℃, 90 ℃, 92 ℃, 95 ℃, 98 ℃, etc.; the dissolution time is 0.5 to 1h, for example 0.6h, 0.7h, 0.8h, 0.9h, etc.; when the dissolution temperature is 80-100 ℃ and the dissolution time is 0.5-1 h, the 2-amino-4-acetamido anisole is thoroughly dissolved, and the solid waste in the pretreatment liquid is less.

The type of the solvent is not particularly limited, and may be selected as required. Preferably, water or other common solvents may be included.

For the amount of the solvent used, in the present invention, the mass ratio of the 2-amino-4-acetamidoanisole to the solvent is 1:0.8 to 1:1.2, for example, 1:0.85, 1:0.9, 1:0.95, 1:1, 1:1.15, etc. When the mass ratio of the 2-amino-4-acetaminophen to the solvent is 1:0.8-1:1.2, the 2-amino-4-acetaminophen is thoroughly dissolved, and the solid waste in the pretreatment liquid is less.

Further, the pretreatment step further comprises a step of solid-liquid separation of the pretreatment liquid. The present invention is not particularly limited, and solid-liquid separation methods commonly used in the art, for example, may be used: filtration, centrifugation, and the like. Preferably, the temperature of the solid-liquid separation is 80 to 100 ℃, for example 82 ℃, 85 ℃, 88 ℃, 90 ℃, 92 ℃, 95 ℃, 98 ℃, etc.

The inventor of the invention discovers that the problem of blockage of the microchannel reactor in the subsequent step can be solved through solid-liquid separation, if the solid-liquid separation is not carried out, the pressure of the reactor can be increased in the feeding process, the discharging condition at the outlet is avoided, and after the solid-liquid separation is increased, the raw materials are pumped smoothly, and the reaction is stable and controlled.

Hydroxylation reaction step

In the hydroxylation reaction step, the pretreatment liquid and the liquid ethylene oxide are subjected to hydroxylation reaction in a microchannel reactor to obtain a hydroxylation liquid. In the invention, when the liquid chromatography detects that the 2-methoxy-5-acetamido-N, N-dihydroxyethyl aniline is more than 93 percent and the raw material 2-amino-4-acetamido anisole is less than 2 percent, the material can be discharged for subsequent thermal insulation reaction. The invention uses liquid ethylene oxide to carry out hydroxylation reaction, omits the step of gasifying the ethylene oxide, simplifies the reaction device, simultaneously avoids the risk existing in the process of gasifying the ethylene oxide, and improves the safety level of the production process.

Specifically, in the hydroxylation reaction step of the present invention, the time of the hydroxylation reaction is 4 to 6 minutes, for example, 4.5 minutes, 5 minutes, 5.5 minutes, etc.; the temperature of the hydroxylation reaction is 80-100 ℃, such as 82 ℃, 85 ℃, 88 ℃, 90 ℃, 92 ℃, 95 ℃, 98 ℃ and the like; the hydroxylation reaction pressure is 0.1 to 0.3MPa, for example, 0.12MPa, 0.15MPa, 0.18MPa, 0.2MPa, 0.22MPa, 0.25MPa, etc. When the hydroxylation reaction time is 4-6 min, the temperature is 80-100 ℃ and the pressure is 0.1-0.3 MPa, the pretreatment liquid and the liquid ethylene oxide can complete most hydroxylation reaction in the microchannel reactor.

For the amount of liquid ethylene oxide, in the present invention, the molar ratio of the 2-amino-4-acetamidoanisole to the liquid ethylene oxide is 1:2 to 1:2.5, for example 1:2.05, 1:2.1, 1:2.15, 1:2.2, 1:2.25, 1:2.3, 1:2.35, 1:2.4, 1:2.45, etc. When the molar ratio of the 2-amino-4-acetamido anisole to the liquid ethylene oxide entering the microchannel reactor is 1:2-1:2.5, fewer reaction byproducts are produced, and the subsequent reaction is facilitated.

Thermal insulation reaction step

The thermal insulation reaction comprises the steps of conveying the hydroxylation liquid from the micro-channel reactor to a reaction device for continuous thermal insulation reaction, and obtaining a hydroxylation product. In the present invention, when 2-methoxy-5-acetamido-N, N-dihydroxyethyl aniline is detected to be 95% or more and the by-product is detected to be 3.5% or less, preferably 2% or less by liquid chromatography, the incubation reaction is completed and the subsequent reaction may be performed. By carrying out the incubation reaction, unreacted raw materials can be allowed to continue to react, thereby making the purity of the product higher.

Specifically, in the step of the incubation reaction of the present invention, the temperature of the incubation reaction is 80 to 100 ℃, for example 82 ℃, 85 ℃, 88 ℃,90 ℃, 92 ℃, 95 ℃, 98 ℃, etc.; the reaction time for the heat preservation is 2 to 3 hours, for example, 2.1 hours, 2.2 hours, 2.3 hours, 2.4 hours, 2.5 hours, 2.6 hours, 2.7 hours, 2.8 hours, 2.9 hours and the like.

Further, in order to simplify the reaction procedure, the incubation reaction of the present invention may be carried out in an esterification reactor.

Dehydration step

In the dehydration step, the hydroxylation product may be subjected to vacuum dehydration to obtain a dehydrated product. Specifically, the hydroxylation product can be subjected to temperature-rising vacuum dehydration, so that a dehydrated product is obtained. By vacuum dehydration, the unsafe risk of the reaction can be further reduced.

Specifically, in the dehydration step of the present invention, the temperature of the vacuum dehydration is 120 to 130 ℃, for example, 121 ℃, 122 ℃, 123 ℃, 124 ℃, 125 ℃, 126 ℃, 127 ℃, 128 ℃, 129 ℃, etc.; the vacuum degree of the vacuum dehydration is-0.7 MPa to-0.9 MPa, such as-0.72 MPa, -0.75MPa, -0.78MPa, -0.8MPa, -0.82MPa, -0.85MPa, -0.88MPa and the like. When the vacuum dehydration temperature is 120-130 ℃ and the vacuum degree is-0.7 MPa to-0.9 MPa, the moisture in the hydroxylation product is thoroughly removed.

Esterification reaction step

The esterification reaction step comprises the step of carrying out esterification reaction on the dehydration product and acetic anhydride to obtain deep blue esterified liquid. In the invention, when liquid chromatography is used for detecting that the 2-methoxy-5-acetamido-N, N-diacetoxyethylaniline is more than 94%, the monoester is less than 2% and the byproducts are less than 4%, the esterification reaction reaches the end point, and the dark blue esterified liquid is obtained by cooling and discharging.

Concretely, the esterification reaction step comprises the steps of dropwise adding acetic anhydride into the dehydration product, and carrying out esterification reaction after the dropwise adding is completed to obtain deep blue esterified liquid. The dripping time is 2-4 h, such as 2.2h, 2.5h, 2.8h, 3h, 3.2h, 3.4h, 3.8h, etc.; the esterification reaction time is 1 to 2 hours, for example, 1.1 hours, 1.2 hours, 1.3 hours, 1.4 hours, 1.5 hours, 1.6 hours, 1.7 hours, 1.8 hours, 1.9 hours, etc. When the dripping time is 2-4 h and the esterification reaction time is 1-2 h, the reaction can be completely carried out to the end point of the reaction.

In the present invention, the temperature of the esterification reaction is 80 to 100 ℃, for example, 82 ℃, 85 ℃, 88 ℃, 90 ℃, 92 ℃, 95 ℃, 98 ℃, etc. When the temperature is too high, the reaction is too fast, heat is not removed, so that the temperature is crossed, and the product quality is affected; when the temperature is too low, the fluidity of the material is too poor, which is unfavorable for the reaction. Therefore, when the temperature of the esterification reaction is 80-100 ℃, the reaction speed and the material fluidity are reasonable, and the reaction is facilitated.

For the amount of acetic anhydride, in the present invention, the molar ratio of the dehydrated product to the acetic anhydride is 1:2 to 1:2.7, preferably 1:2.1 to 2.5; such as 1:2.05, 1:2.15, 1:2.2, 1:2.25, 1:2.3, 1:2.35, 1:2.4, 1:2.45, 1:2.5, 1:2.55, 1:2.6, 1:2.65, etc. When the molar ratio of the dehydration product to the acetic anhydride is 1:2-1:2.7, the imbalance of the material proportion caused by misoperation can be avoided, the stability of the reaction is improved, and the safety level of the production process is improved.

Further, the esterification reaction reaches the reaction end point and then further comprises the step of cooling and discharging. Specifically, the temperature of the cooling is 40 to 60 ℃, for example, 42 ℃, 45 ℃, 48 ℃,50 ℃, 52 ℃, 55 ℃, 58 ℃, and the like. When the temperature after the temperature is lowered is too low, the production efficiency is reduced; when the temperature after cooling is too high, the discharging smell is heavy, and the requirements on the esterification liquid container are also high.

The invention also provides a deep blue esterified liquid, which is prepared by the preparation method.

Examples

Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only for illustrating the present invention and should not be construed as limiting the scope of the present invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.

Microchannel reactor: and 5 reaction plates with total reaction volume of 41mL are arranged, cold source and heat source are arranged outside, two metering feed pumps are arranged in front, and the outlet of the reactor is connected with a back pressure valve.

Example 1

Pretreatment: 200g of water (11.11 mol) was added to a 500mL flask equipped with a stirrer and a thermometer, stirring was started, the temperature was raised to 70℃and 250g (purity: 99%) of 2-amino-4-acetaminophen (1.39 mol) was added thereto, the temperature was further raised to 80℃and kept at 80℃for 0.5 hour, and the pretreatment liquid was obtained by filtration at 80 ℃.

Hydroxylation reaction step: the micro-channel reactor is connected with a discharging back pressure valve, after the temperature of the reactor is raised to 80 ℃ and is stable, a feed pump is started, the volume ratio of the pretreatment liquid to the liquid ethylene oxide is 1:0.34 (the density of the pretreatment liquid is 1.1g/mL, the density of the ethylene oxide is 0.882g/mL, the mol ratio of the 2-amino-4-acetamido anisole to the ethylene oxide is calculated to be about 1:2.01), the back pressure is stable at 0.2+/-0.1 MPa, and the residence time is set for 4 minutes, so that the hydroxylation liquid is obtained. The purity of the product is 94.1% by HPLC high performance liquid chromatograph, the content of monohydroxy is 2.4%, the content of by-product is 1.3%, and the raw material 2-amino-4-acetamidoanisole is not detected.

And (3) heat preservation reaction step: and (3) discharging the hydroxylation liquid, continuously carrying out heat preservation reaction for 2 hours at 80 ℃ in a 500mL flask with a stirrer and a thermometer to obtain a hydroxylation product, and detecting the purity of the product to be 95.6% and the content of other byproducts to be 1.8% by using an HPLC high performance liquid chromatograph.

And (3) dehydration: placing the hydroxylation product into a 1000mL flask with a stirrer, a thermometer and a condenser, starting stirring and vacuum, slowly heating to 125+/-5 ℃ for dehydration at the vacuum degree of-0.8 MPa+/-0.1 MPa, and removing vacuum after dehydration to obtain a dehydrated product.

Esterification reaction step: cooling to 80 ℃, dropwise adding 312g (purity 99%) of acetic anhydride (3.06 mol) into the dehydrated product, keeping the temperature for 2 hours after 2 hours, detecting the purity of the product to be 94.1%, the monoester content to be 1.2% and the byproduct content to be 2.1% by using an HPLC high performance liquid chromatograph, cooling to 40 ℃ and discharging to obtain 702.3g of esterified liquid, wherein the solid content is 69.3%, and detecting the coupling value of the product to be 64.5% by using a titration method.

Example 2

Pretreatment: 200g of water (11.11 mol) was added to a 500mL flask equipped with a stirrer and a thermometer, stirring was started, the temperature was raised to 70℃and 250g (purity: 99%) of 2-amino-4-acetaminophen (1.39 mol) was added thereto, the temperature was further raised to 90℃and kept at that temperature for 0.5 hour, and the pretreatment liquid was obtained by filtration at 80 ℃.

Hydroxylation reaction step: the micro-channel reactor is connected with a discharging back pressure valve, after the temperature of the reactor is raised to 90 ℃ and is stable, a feed pump is started, the volume ratio of the pretreatment liquid to the liquid ethylene oxide is 1:0.34 (the density of the pretreatment liquid is 1.1g/mL, the density of the ethylene oxide is 0.882g/mL, the mol ratio of the 2-amino-4-acetamido anisole to the ethylene oxide is calculated to be about 1:2.01), the back pressure is stable at 0.2+/-0.1 MPa, and the residence time is set for 4 minutes, so that the hydroxylation liquid is obtained. The purity of the product is 94.0% by HPLC high performance liquid chromatograph, the content of monohydroxy is 2.6%, the content of other byproducts is 1.5%, and the raw material 2-amino-4-acetamidoanisole is not detected.

And (3) heat preservation reaction step: and (3) discharging the hydroxylation liquid, continuously carrying out heat preservation reaction for 2 hours at 90 ℃ in a 500mL flask with a stirrer and a thermometer to obtain a hydroxylation product, and detecting the purity of the product to be 95.5% and the content of byproducts to be 1.9% by using an HPLC high performance liquid chromatograph.

And (3) dehydration: placing the hydroxylation product into a 1000mL flask with a stirrer, a thermometer and a condenser, starting stirring and vacuum, slowly heating to 125+/-5 ℃ for dehydration at the vacuum degree of-0.8 MPa+/-0.1 MPa, and removing vacuum after dehydration to obtain a dehydrated product.

Esterification reaction step: cooling to 80 ℃, dropwise adding 369g (99% pure) acetic anhydride (3.62 mol) into the dehydrated product, keeping the temperature for 2 hours at 80 ℃ after 3 hours, detecting the purity of the product to be 94.3%, the content of monoester to be 0.8% and the content of other byproducts to be 3.5% by using an HPLC high performance liquid chromatograph, cooling to 50 ℃ and discharging to obtain 760.6g of esterified liquid, the solid content to be 64.5%, and detecting the coupling value of the product to be 60.8% by using a titration method.

Example 3

Pretreatment: 200g of water (11.11 mol) was added to a 500mL flask equipped with a stirrer and a thermometer, stirring was started, the temperature was raised to 70℃and 250g (purity: 99%) of 2-amino-4-acetaminophen (1.39 mol) was added thereto, the temperature was further raised to 80℃and kept at that temperature for 0.5 hour, and the pretreatment liquid was obtained by filtration at 80 ℃.

Hydroxylation reaction step: the micro-channel reactor is connected with a discharging back pressure valve, after the temperature of the reactor is raised to 100 ℃ and is stable, a feed pump is started, the volume ratio of the pretreatment liquid to the liquid ethylene oxide is 1:0.34 (the density of the pretreatment liquid is 1.1g/mL, the density of the ethylene oxide is 0.882g/mL, the mol ratio of the 2-amino-4-acetamido anisole to the ethylene oxide is calculated to be about 1:2.01), the back pressure is stable at 0.2+/-0.1 MPa, and the residence time is set for 4 minutes, so that the hydroxylation liquid is obtained. The purity of the product is 93.9% by HPLC high performance liquid chromatograph, the content of monohydroxy is 2.4%, the content of other byproducts is 1.1%, and the raw material 2-amino-4-acetamidoanisole is not detected.

And (3) heat preservation reaction step: and (3) discharging the hydroxylation liquid, continuously carrying out heat preservation reaction for 2 hours at 100 ℃ in a 500mL flask with a stirrer and a thermometer to obtain a hydroxylation product, and detecting the purity of the product to be 95.6% by using an HPLC high performance liquid chromatograph, wherein the content of a byproduct is 1.8%.

And (3) dehydration: placing the hydroxylation product into a 1000mL flask with a stirrer, a thermometer and a condenser, starting stirring and vacuum, slowly heating to 125+/-5 ℃ for dehydration at the vacuum degree of-0.8 MPa+/-0.1 MPa, and removing vacuum after dehydration to obtain a dehydrated product.

Esterification reaction step: cooling to 90 ℃, dropwise adding 312g (purity 99%) of acetic anhydride (3.06 mol) into the dehydrated product, keeping the temperature for 2 hours after the completion of the dropwise adding, continuing to keep the temperature at 90 ℃ for 2 hours, detecting that the purity of the product is 93.9%, the content of monoester is 1.3% and the content of other byproducts is 2.3% by using an HPLC (high performance liquid chromatography), cooling to 50 ℃ and discharging to obtain 706.1g of esterified liquid, wherein the solid content is 69.1%, and detecting the coupling value of the product by using a titration method.

Example 4

Pretreatment: 200g of water (11.11 mol) was added to a 500mL flask equipped with a stirrer and a thermometer, stirring was started, the temperature was raised to 70℃and 250g (purity: 99%) of 2-amino-4-acetaminophen (1.39 mol) was added thereto, the temperature was further raised to 80℃and kept at that temperature for 0.5 hour, and the pretreatment liquid was obtained by filtration at 80 ℃.

Hydroxylation reaction step: the micro-channel reactor is connected with a discharging back pressure valve, the reactor is heated to 80 ℃ and is stable, a feed pump is started, the volume ratio of the pretreatment liquid to the liquid ethylene oxide is 1:0.41 (the density of the pretreatment liquid is 1.1g/mL, the density of the ethylene oxide is 0.882g/mL, the mol ratio of the 2-amino-4-acetamido anisole to the ethylene oxide is calculated to be about 1:2.42), the back pressure is stabilized at 0.2+/-0.1 MPa, and the residence time is set for 4 minutes, so that the hydroxylation liquid is obtained. The purity of the product is 94.5% by HPLC high performance liquid chromatograph, the content of monohydroxy is 1.5%, the content of other byproducts is 2.3%, and the raw material 2-amino-4-acetamidoanisole is not detected.

And (3) heat preservation reaction step: and (3) discharging the hydroxylation liquid, continuously carrying out heat preservation reaction for 2 hours at 80 ℃ in a 500mL flask with a stirrer and a thermometer to obtain a hydroxylation product, and detecting the purity of the product to be 95.0% by using an HPLC high performance liquid chromatograph, wherein the content of byproducts is 3.2%.

And (3) dehydration: placing the hydroxylation product into a 1000mL flask with a stirrer, a thermometer and a condenser, starting stirring and vacuum, slowly heating to 125+/-5 ℃ for dehydration at the vacuum degree of-0.8 MPa+/-0.1 MPa, and removing vacuum after dehydration to obtain a dehydrated product.

Esterification reaction step: cooling to 80 ℃, dropwise adding 312g (purity 99%) of acetic anhydride (3.06 mol) into the dehydrated product, keeping the temperature for 2 hours at 80 ℃ after 3 hours, detecting the purity of the product to be 94.1%, the content of monoester to be 0.7% and the content of other byproducts to be 2.1% by using an HPLC high performance liquid chromatograph, cooling to 40 ℃ and discharging to obtain 704.3g of esterified liquid, wherein the solid content is 69.6%, and detecting the coupling value of the product to be 62.5% by using a titration method.

Example 5

Pretreatment: 200g of water (11.11 mol) was added to a 500mL flask equipped with a stirrer and a thermometer, stirring was started, the temperature was raised to 70℃and 250g (purity: 99%) of 2-amino-4-acetaminophen (1.39 mol) was added thereto, the temperature was further raised to 80℃and kept at that temperature for 0.5 hour, and the pretreatment liquid was obtained by filtration at 80 ℃.

Hydroxylation reaction step: the micro-channel reactor is connected with a discharging back pressure valve, the reactor is heated to 90 ℃ and is stable, a feed pump is started, the volume ratio of the pretreatment liquid to the liquid ethylene oxide is 1:0.37 (the density of the pretreatment liquid is 1.1g/mL, the density of the ethylene oxide is 0.882g/mL, the mol ratio of the 2-amino-4-acetamido anisole to the ethylene oxide is calculated to be about 1:2.18), the back pressure is stabilized at 0.2+/-0.1 MPa, and the residence time is set to 5 minutes, so that the hydroxylation liquid is obtained. The purity of the product is 94.4% by HPLC, the content of monohydroxy is 1.7%, the content of other byproducts is 2.3%, and the raw material 2-amino-4-acetamidoanisole is not detected.

And (3) heat preservation reaction step: and (3) discharging the hydroxylation liquid, continuously carrying out heat preservation reaction for 2 hours at 90 ℃ in a 500mL flask with a stirrer and a thermometer to obtain a hydroxylation product, and detecting the purity of the product to be 95.3% by using an HPLC high performance liquid chromatograph, wherein the content of byproducts is 2.8%.

And (3) dehydration: placing the hydroxylation product into a 1000mL flask with a stirrer, a thermometer and a condenser, starting stirring and vacuum, slowly heating to 125+/-5 ℃ for dehydration at the vacuum degree of-0.8 MPa+/-0.1 MPa, and removing vacuum after dehydration to obtain a dehydrated product.

Esterification reaction step: cooling to 100 ℃, dropwise adding 312g (purity 99%) of acetic anhydride (3.06 mol) into the dehydrated product, keeping the temperature for 2 hours after the completion of the dropwise adding, continuing to keep the temperature at 100 ℃ for 2 hours, detecting that the purity of the product is 94.3%, the content of monoester is 0.9%, the content of other byproducts is 2.2% by using an HPLC (high performance liquid chromatography), cooling to 60 ℃ and discharging to obtain 704.6g of esterified liquid, wherein the solid content is 68.7%, and detecting the coupling value of the product by using a titration method to be 63.6%.

Example 6

Pretreatment: 200g of water (11.11 mol) was added to a 500mL flask equipped with a stirrer and a thermometer, stirring was started, the temperature was raised to 70℃and 250g (purity: 99%) of 2-amino-4-acetaminophen (1.39 mol) was added thereto, the temperature was further raised to 80℃and kept at that temperature for 0.5 hour, and the pretreatment liquid was obtained by filtration at 80 ℃.

Hydroxylation reaction step: the micro-channel reactor is connected with a discharging back pressure valve, the reactor is heated to 90 ℃ and is stable, a feed pump is started, the volume ratio of the pretreatment liquid to the liquid ethylene oxide is 1:0.37 (the density of the pretreatment liquid is 1.1g/mL, the density of the ethylene oxide is 0.882g/mL, the mol ratio of the 2-amino-4-acetamido anisole to the ethylene oxide is calculated to be about 1:2.18), the back pressure is stabilized at 0.2+/-0.1 MPa, and the residence time is set for 6 minutes, so that the hydroxylation liquid is obtained. The purity of the product is 94.2% by HPLC high performance liquid chromatograph, the content of monohydroxy is 1.8%, the content of other byproducts is 2.5%, and the raw material 2-amino-4-acetamidoanisole is not detected.

And (3) heat preservation reaction step: and (3) discharging the hydroxylation liquid, continuously carrying out heat preservation reaction for 2 hours at 90 ℃ in a 500mL flask with a stirrer and a thermometer to obtain a hydroxylation product, and detecting the purity of the product to be 94.9% by using an HPLC high performance liquid chromatograph, wherein the content of byproducts is 3.0%.

And (3) dehydration: placing the hydroxylation product into a 1000mL flask with a stirrer, a thermometer and a condenser, starting stirring and vacuum, slowly heating to 125+/-5 ℃ for dehydration at the vacuum degree of-0.8 MPa+/-0.1 MPa, and removing vacuum after dehydration to obtain a dehydrated product.

Esterification reaction step: cooling to 90 ℃, dropwise adding 312g (purity 99%) of acetic anhydride (3.06 mol) into the dehydrated product, keeping the temperature for 2 hours after 2 hours, detecting the purity of the product to be 94.1%, the content of monoester to be 0.9% and the content of other byproducts to be 1.9% by using an HPLC high performance liquid chromatograph, cooling to 50 ℃ and discharging to obtain 702.9g of esterified liquid, the solid content to be 68.9%, and detecting the coupling value of the product to be 62.3% by adopting a titration method.

Comparative example 1

Hydroxylation reaction step: 200g of water (11.11 mol) and 250g (purity: 99%) of 2-amino-4-acetamidoanisole (1.39 mol) were charged into a 1000mL autoclave, the lid was closed, stirring was turned on, the temperature was raised to 80℃and 134.4g (99%) of vaporized ethylene oxide (about 3.05 mol) was introduced, and the time of aeration was 4 hours to obtain a hydroxylation liquid.

And (3) heat preservation reaction step: and (3) preserving the temperature of the hydroxylation liquid for 2 hours to obtain a hydroxylation product, detecting the purity of the product to be 92.6 percent by using an HPLC (high performance liquid chromatography), detecting the content of monohydroxy to be 4.6 percent, adding 10g of ethylene oxide, preserving the temperature for 1 hour, detecting the purity of the product to be 94.6 percent by using the HPLC, detecting the content of byproducts to be 2.6 percent, and discharging.

And (3) dehydration: placing the hydroxylation product into a 1000mL flask with a stirrer, a thermometer and a condenser, starting stirring and vacuum, slowly heating to 125+/-5 ℃ for dehydration at the vacuum degree of-0.8 MPa+/-0.1 MPa, and removing vacuum after dehydration to obtain a dehydrated product.

Esterification reaction step: cooling to 90 ℃, dropwise adding 312g (purity 99%) of acetic anhydride (3.06 mol) into the dehydrated product, keeping the temperature for 2 hours after the completion of the dropwise adding, continuing to keep the temperature for 2 hours at 90 ℃, detecting that the purity of the product is 94.0%, the content of monoester is 1.1%, the content of byproducts is 2.4% by using an HPLC (high performance liquid chromatography), cooling to 50 ℃, discharging to obtain 702.6g of esterified liquid, and detecting that the coupling value of the product is 63.5% by using a titration method.

Comparative example 2

Hydroxylation reaction step: 200g of water (11.11 mol) and 250g (purity: 99%) of 2-amino-4-acetamidoanisole (1.39 mol) were charged into a 1000mL autoclave, the lid was closed, stirring was turned on, the temperature was raised to 80℃and 146.7g (99%) of vaporized ethylene oxide (about 3.33 mol) was introduced, and the time of aeration was 4 hours to obtain a hydroxylation liquid.

And (3) heat preservation reaction step: and (3) preserving the temperature of the hydroxylation liquid for 2 hours to obtain a hydroxylation product, detecting the purity of the product to be 95.3% by using an HPLC high performance liquid chromatograph, and discharging.

And (3) dehydration: placing the hydroxylation product into a 1000mL flask with a stirrer, a thermometer and a condenser, starting stirring and vacuum, slowly heating to 125+/-5 ℃ for dehydration at the vacuum degree of-0.8 MPa+/-0.1 MPa, and removing vacuum after dehydration to obtain a dehydrated product.

Esterification reaction step: cooling to 90 ℃, dropwise adding 312g (purity 99%) of acetic anhydride (3.06 mol) into the dehydrated product, keeping the temperature for 2 hours after the completion of the dropwise adding, continuing to keep the temperature at 90 ℃ for 2 hours, detecting that the purity of the product is 94.3%, the content of monoester is 1.3%, the content of byproducts is 2.0% by using an HPLC (high performance liquid chromatography), cooling to 50 ℃ and discharging to obtain 704.1g of esterified liquid, wherein the solid content is 68.1%, and detecting the coupling value of the product by using a titration method is 64.2%.

Comparative example 3

Hydroxylation reaction step: 200g of water (11.11 mol) and 250g (99%) of 2-amino-4-acetamidoanisole (1.39 mol) were charged into a 1000mL autoclave, the lid was closed, stirring was turned on, the temperature was raised to 80℃and 171.1g (purity: 99%) of vaporized ethylene oxide (about 3.89 mol) was introduced, and the time of aeration was 4 hours to obtain a hydroxylation liquid.

And (3) heat preservation reaction step: and (3) preserving the temperature of the hydroxylation liquid for 2 hours to obtain a hydroxylation product, detecting the purity of the product to be 92.3% by using an HPLC high performance liquid chromatograph, detecting the content of byproducts to be 4.8%, and discharging.

And (3) dehydration: placing the hydroxylation product into a 1000mL flask with a stirrer, a thermometer and a condenser, starting stirring and vacuum, slowly heating to 125+/-5 ℃ for dehydration at the vacuum degree of-0.8 MPa+/-0.1 MPa, and removing vacuum after dehydration to obtain a dehydrated product.

Esterification reaction step: cooling to 90 ℃, dropwise adding 312g (purity 99%) of acetic anhydride (3.06 mol) into the dehydrated product, keeping the temperature for 2 hours after the completion of the dropwise adding, continuing to keep the temperature at 90 ℃ for 2 hours, detecting that the purity of the product is 93.7%, the monoester content is 1.3%, the byproduct content is 2.3% by using an HPLC (high performance liquid chromatography), cooling to 50 ℃ and discharging to obtain 703.6g of esterified liquid, wherein the solid content is 68.2%, and detecting the coupling value of the product by using a titration method to be 60.3%.

Performance testing

The purity detection method comprises the following steps: purity was measured by HPLC according to the method described in Q/RTR J02225-2021, and the results are shown in Table 1.

The coupling value detection method comprises the following steps: coupling value measurements were performed as described in standard Q/ZHX 002-2018 and the results are shown in Table 1.

TABLE 1 detection of raw material ratios and product Properties of examples 1 to 6 and comparative examples 1 to 3

As can be seen from Table 1, the purity of the hydroxylation product in the examples is not significantly different from that in comparative example 2, which shows that the hydroxylation reaction performed by using the microchannel reactor instead of the conventional autoclave has no significant influence on the reaction selectivity, and the hydroxylation product has no additional side reaction.

In examples 4, 5 and 6, different increases of ethylene oxide (all greater than the theoretical value) were used for the hydroxylation reaction, but no very large difference was observed in the hydroxylation result (no obvious difference in the content of the main product, slightly increased side reaction), which means that when the reaction is carried out in a microchannel reactor, a large number of side reactions are not generated under the condition of excess ethylene oxide in a certain range, the process stability is high, and the possibility of actual production between the transfer vehicles is high.

In comparative example 1, however, the amount of ethylene oxide used in the hydroxylation reaction step was significantly insufficient, and only marginally increased, and as the amount of ethylene oxide was increased, the amount of the main product of the hydroxylation reaction in comparative example 3 was decreased, which shows the effect of the excess ethylene oxide on the hydroxylation reaction in the autoclave environment, presumably due to the increase in side reactions caused by the long-term excess ethylene oxide, and the shorter time of the hydroxylation reaction in the microchannel route, the higher selectivity, the amount of ethylene oxide used was closer to the theoretical amount and the side reactions were less likely to occur.

A longer hydroxylation reaction time is required to obtain superior performance compared to comparative example 2, but its reaction equivalent is large, the reaction risk is high, and the production risk caused by heat accumulation is caused. In the hydroxylation reaction, the smaller the equivalent weight of the raw materials is, the safer the raw materials are, the adiabatic temperature rise can be controlled, and the production risk caused by heat accumulation is prevented.

In terms of reaction conversion, the amount of ethylene oxide used in the examples can be significantly less than that used in the comparative examples, and higher purity products can also be obtained.

Further, the detection value of the finished product of the esterified liquid obtained in the subsequent esterification reaction also shows that the hydroxylation product is normal and accords with the process condition. This shows that the invention reduces the risk in the reaction process and achieves the aim of safe production on the premise that the obtained product meets the requirements.

It should be noted that, although the technical solution of the present invention is described in specific examples, those skilled in the art can understand that the present invention should not be limited thereto.

The foregoing description of embodiments of the invention has been presented for purposes of illustration and description, and is not intended to be exhaustive or limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the various embodiments described. The terminology used herein was chosen in order to best explain the principles of the embodiments, the practical application, or the technical improvements in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.

Claims (10)

1. The preparation method of the deep blue esterified liquid is characterized by comprising the following steps of:

pretreatment: dissolving 2-amino-4-acetamido anisole in a solvent to obtain a pretreatment liquid;

Hydroxylation reaction step: carrying out hydroxylation reaction on the pretreatment liquid and liquid ethylene oxide in a micro-channel reactor to obtain a hydroxylation liquid;

And (3) heat preservation reaction step: conveying the hydroxylation liquid from the microchannel reactor to a reaction device for continuous heat preservation reaction to obtain a hydroxylation product;

And (3) dehydration: carrying out vacuum dehydration on the hydroxylation product to obtain a dehydrated product;

esterification reaction step: and carrying out esterification reaction on the dehydrated product and acetic anhydride to obtain deep blue esterified liquid.

2. The preparation method according to claim 1, wherein in the pretreatment step, the mass ratio of the 2-amino-4-acetamidoanisole to the solvent is 1:0.8 to 1:1.2; and/or the number of the groups of groups,

In the hydroxylation reaction step, the molar ratio of the 2-amino-4-acetamido anisole to the liquid ethylene oxide is 1:2-1:2.5; and/or the number of the groups of groups,

In the esterification reaction step, the molar ratio of the dehydration product to the acetic anhydride is 1:2-1:2.7, preferably 1:2.1-2.5.

3. The preparation method according to claim 1 or 2, wherein in the pretreatment step, the dissolution temperature is 80 to 100 ℃, and the dissolution time is 0.5 to 1h; preferably, the pretreatment step further includes a step of subjecting the pretreatment liquid to solid-liquid separation, and more preferably, the solid-liquid separation temperature is 80 to 100 ℃.

4. A production method according to any one of claims 1 to 3, wherein in the hydroxylation reaction step, the time of the hydroxylation reaction is 4 to 6 minutes, the temperature of the hydroxylation reaction is 80 to 100 ℃, and the pressure of the hydroxylation reaction is 0.1 to 0.3MPa.

5. The method according to any one of claims 1 to 4, wherein in the step of incubating, the temperature of the incubation is 80 to 100 ℃, and the time of the incubation is 2 to 3 hours.

6. The method according to any one of claims 1 to 5, wherein in the dehydration step, the temperature of the vacuum dehydration is 120 to 130 ℃, and the vacuum degree of the vacuum dehydration is-0.7 MPa to-0.9 MPa.

7. The method according to any one of claims 1 to 6, wherein the esterification step comprises adding acetic anhydride dropwise to the dehydrated product, and performing an esterification reaction after the completion of the addition to obtain a dark blue esterified liquid.

8. The method according to claim 7, wherein the time for dropping is 2 to 4 hours; and/or the number of the groups of groups,

The time of the esterification reaction is 1-2 h, and the temperature of the esterification reaction is 80-100 ℃.

9. The process according to any one of claims 1 to 8, wherein the 2-amino-4-acetamidoanisole has an amino value of 98 to 99%; and/or the number of the groups of groups,

The mass concentration of the ethylene oxide is 98-99%; and/or the number of the groups of groups,

The mass concentration of the acetic anhydride is 98-99%.

10. A deep blue esterified liquid prepared by the preparation method of any one of claims 1 to 9.