Continuous reaction research process for low-bis-phenylamine impurity-o-methoxy-bis-acetanilide
By employing a low-temperature continuous flow reaction process and centrifugal washing technology, the problem of high bis(2-methoxyphenyl)amine impurities in o-methoxy-N-acetylacetanilide was solved, resulting in improved product yield and quality, prevention of impurity accumulation, and optimization of crystal size and distribution.
Patent Information
- Application Number
- CN202511702229.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-19
- Publication Date
- 2026-01-02
AI Technical Summary
The existing o-methoxy-N-acetylacetanilide process has high levels of bis(2-methoxyphenyl)amine impurities, which affect product quality and stability. Furthermore, the traditional batch reactor leads to the accumulation of impurities, resulting in a decrease in product color and purity.
A low-temperature continuous flow reaction process is adopted, in which the reaction is carried out at high temperature and then quenched at low temperature in the reactor. The mixture is continuously overflowed into the crystallization vessel and centrifuged and washed. The solid-liquid transfer pump is used to transport the mixture to a centrifuge for centrifugal washing. The mother liquor is quantitatively discarded to avoid the accumulation of impurities and optimize the crystal growth time.
It effectively reduced bis(2-methoxyphenyl)amine impurities, improved product yield and quality stability, prevented the accumulation of impurities in the product, optimized crystal size and distribution, and enhanced product concentration and stability.
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Figure CN121248431A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of chemical synthesis, in particular to a continuous reaction research process of low diphenylamine impurity-ortho-methoxy diethylphenylamine. BACKGROUND
[0002] Ortho-methoxy-N-acetoacetyl aniline (also named as ortho-methoxy diethylphenylamine) structural formula: .
[0003] Appearance: white to off-white crystals or powder; Molecular weight: 207.226; Boiling point: 372.9±22.0 °C at 760 mmHg; Density: 1.2±0.1 g / cm3; Flash point: 179.3±22.3 °C; CAS No.: 92-15-9; Melting point: 85-87 °C (lit.).
[0004] Use: ortho-methoxy-N-acetoacetyl aniline is an important dye, organic pigment intermediate, which can produce C.I. Pigment Yellow 17, C.I. Pigment Yellow 65 and C.I. Pigment Yellow 74.
[0005] Prior art: the traditional process of ortho-methoxy-N-acetoacetyl aniline is to add ortho-methoxy aniline and ethanol solvent to the reaction kettle to lay the bottom, drop bisvinyl ketone for condensation reaction, control the reaction temperature by cold medium, keep warm for a certain time after the drop of bisvinyl ketone is completed, and finally cool and crystallize to obtain ortho-methoxy acetoacetyl aniline product. Because the residence time and reaction time of the traditional process are too long, the ortho-methoxy aniline raw material is self-polymerized into bis (2-methoxyphenyl) amine impurity at high temperature, which seriously affects the quality and color of the downstream product. At the same time, the traditional process uses batch kettle reactor, with the increase of the number of mother liquor reuse, the pigment accumulates in the product, affecting the appearance of the product, and the purity of the product decreases with the increase of the number of reuse, and the stability of the product cannot be guaranteed.
[0006]
[0007] Ortho-methoxy aniline bis (2-methoxyphenyl) amine. SUMMARY
[0008] The purpose of the present application is to provide a continuous reaction research process of low diphenylamine impurity-ortho-methoxy diethylphenylamine, which solves the problems of high bis (2-methoxyphenyl) amine impurity and batch stability in ortho-methoxy-N-acetoacetyl aniline.
[0009] The present application relates to a kind of low biphenyl amine type impurity-continuous reaction research process of o-methoxy bisethylphenylamine, in the condensation kettle preparation certain concentration ethanol bottom, control o-methoxy aniline and bisethylenone molar ratio is added to kettle and carries out fast condensation reaction, condensation kettle liquid is continuously overflowed into crystallization kettle and is further reacted under low temperature condition, guarantee raw material fully reacts, improve product yield, then it is transported to centrifuge using solid-liquid delivery pump and is washed, centrifugal washing liquid returns condensation kettle, and the product is filtered and dried to obtain finished product.The specific content is as follows: 1.reaction kettle bottom 0.5t ethanol concentration is 20~40% saturated mother liquor, o-methoxy aniline and bisethylenone feeding pipe end is located at liquid level 1 / 2, control reaction kettle temperature is 50~60℃ throughout the process; 2.control o-methoxy aniline and bisethylenone are added in proportion, o-methoxy aniline drop rate is 1000~2000kg / h, bisethylenone drop rate is 720~1440 kg / h, residence time is 20~40min;Overflow into crystal growing kettle; 3 control residence time 30~60min, temperature 35~40℃, so that crystal uniformly grows 4.3t ethanol concentration is 20~40% saturated mother liquor is laid in crystallization kettle, control crystallization kettle reaction temperature is 5~10℃, residence time is 60~100min, column kettle is transported to centrifuge using solid-liquid delivery pump and is washed, 95% centrifugal mother liquor and 5% fresh washing liquid are combined into reaction kettle, and the product is dried to obtain finished product.
[0010] The present application provides a kind of low biphenyl amine type impurity-continuous reaction research process of o-methoxy-N-acetyl acetylphenylamine, including the following steps: (1) in reaction kettle bottom ethanol concentration is 20~40% o-methoxy-N-acetyl acetylphenylamine saturated mother liquor, o-methoxy aniline and bisethylenone feeding pipe end is located below liquid level; (2) control o-methoxy aniline and bisethylenone are added in proportion to the system obtained in step (1), after drop completion, residence time is 20~40 min, control reaction kettle temperature is 50~60℃ throughout the process;Wherein, the total mass of o-methoxy aniline drop is: 333~1333kg, and the total mass of bisethylenone drop is: 240~960kg; (3) overflow into crystal growing kettle: the liquid after reaction of step (2) is continuously introduced into crystal growing kettle through overflow port, residence time is 30~60min, temperature is 35~40℃ (4) overflow into crystallization kettle: The material liquid after step (3) is continuously introduced into the crystallization kettle through the overflow port, and before being introduced, a saturated mother liquor of o-methoxy-N-acetylacetanilide is laid on the bottom of the crystallization kettle, the reaction temperature of the crystallization kettle is controlled at 5-10 DEG C, and the residence time is 60-100 min; (5) centrifugation, wet product, finished product: The mixed liquid in the column kettle after the reaction of step (3) is transported to a centrifuge for centrifugal washing by using a solid-liquid conveying pump. The method for centrifugal washing is that the pump outlet pipe is directly connected to the centrifuge, and the centrifuge is centrifuged while being sprayed with washing liquid to wash away the impurities in the mixed liquid in the column kettle after the reaction of step (3). The solid obtained after centrifugation, i.e. the wet product, is dried to obtain the finished product.
[0011] The 95% centrifugal mother liquor obtained after centrifugation and 5% fresh washing liquid are mixed and introduced into the reaction kettle as the next batch of mother liquor for reuse.
[0012] In an embodiment of the present application, in step (1), the saturated mother liquor is prepared as follows: excess 50-100 g of o-methoxy-N-acetylacetanilide product is dissolved in 100 g of an ethanol solution with an ethanol concentration of 20-40% at room temperature, and the filtrate after filtration is the saturated mother liquor of o-methoxy-N-acetylacetanilide.
[0013] In an embodiment of the present application, in step (2), the dropping speed of o-methoxyaniline is 1000-2000 kg / h, and the dropping speed of divinyl ketone is 720-1440 kg / h.
[0014] In an embodiment of the present application, in step (4), the saturated mother liquor is an o-methoxy-N-acetylacetanilide saturated mother liquor with an ethanol concentration of 20-40%.
[0015] In an embodiment of the present application, in step (5), the centrifuge is centrifuged at 5000 / rpm.
[0016] In an embodiment of the present application, in step (5), the washing liquid is an ethanol aqueous solution with an ethanol concentration of 20-40%.
[0017] In an embodiment of the present application, in step (5), the drying condition is steam drying at 110 DEG C for 5 s.
[0018] In an embodiment of the present application, in step (1), the ends of the feeding pipes of o-methoxyaniline and divinyl ketone are located at 1 / 2 of the liquid level.
[0019] In an embodiment of the present application, in step (1), the saturated mother liquor is an o-methoxy-N-acetylacetanilide saturated mother liquor with an ethanol concentration of 20-40%.
[0020] In one embodiment of the present application, in step (1), the saturated mother liquor is added in an amount of 0.5t-1.0t.
[0021] In one embodiment of the present application, in step (2), the temperature in the reaction kettle is controlled at 50-60°C.
[0022] Advantages The present application provides a continuous reaction research process for low diphenylamine impurity-ortho-methoxy bis-ethylphenylamine, which has the following advantages: 1) By rapidly reacting at high temperature and quenching at low temperature in the reaction kettle, the residence time of ortho-methoxy aniline raw material is shortened, the bis(2-methoxyphenyl)amine impurity is reduced, and the self-polymerization of bis-vinyl ketone is reduced, thereby reducing the consumption of ortho-methoxy aniline; 2) By continuous flow reaction, the product yield is improved, and the product quality is stable and controllable; 3) The mother liquor is quantitatively eliminated, which avoids the accumulation of impurities in the product and improves the product quality; 4) The double-drop process avoids the accumulation of ortho-methoxy aniline in the mother liquor, thereby improving the product alkali turbidity.
[0023] 5) By crystal growth, the crystal nucleus growth time is prolonged, the product is prevented from being precipitated explosively, the product particle size is optimized, the product is concentrated in 20-50 meshes, and the crystal is in block shape. BRIEF DESCRIPTION OF DRAWINGS
[0024] Figure 1 The process flow chart of the present application. DETAILED DESCRIPTION
[0025] The detection method / formula involved in the following examples is as follows: Ortho-methoxy-N-acetyl acetoanilide purity detection: Purity (%) = ((sample peak area / external standard peak area) x purity (%) of compound in sample) / sample mass Wherein, the sample peak area is the compound peak area on the HPLC chromatogram, the external standard peak area is the external standard peak area on the HPLC chromatogram, the purity of the compound in the external standard sample is the known purity of the compound in the external standard sample, and the sample mass is the mass of the sample to be tested.
[0026] Ortho-methoxy-N-acetyl acetoanilide yield calculation formula: Yield = actual output product amount / theoretical output product amount.
[0027] The preparation method of the saturated mother liquor involved in the following examples is as follows: 100 g of excess o-methoxy-N-acetoacetanilide product was dissolved in 100 g of an ethanol solution with an ethanol concentration of 20-60% at room temperature. The filtrate after filtration was the saturated mother liquor. The specific preparation method was as follows: 100 g of o-methoxy-N-acetoacetanilide product was added to 100 g of an ethanol solution with an ethanol concentration of 20% (v / v) to prepare a saturated mother liquor with an ethanol concentration of 20% (v / v). 100 g of o-methoxy-N-acetoacetanilide product was added to 100 g of an ethanol solution with an ethanol concentration of 40% (v / v) to prepare a saturated mother liquor with an ethanol concentration of 40% (v / v). 100 g of o-methoxy-N-acetoacetanilide product was added to 100 g of an ethanol solution with an ethanol concentration of 35% (v / v) to prepare a saturated mother liquor with an ethanol concentration of 35% (v / v). 100 g of o-methoxy-N-acetoacetanilide product was added to 100 g of an ethanol solution with an ethanol concentration of 60% (v / v) to prepare a saturated mother liquor with an ethanol concentration of 60% (v / v). 100 g of o-methoxy-N-acetoacetanilide product was added to 100 g of an ethanol solution with an ethanol concentration of 10% (v / v) to prepare a saturated mother liquor with an ethanol concentration of 10% (v / v). 100 g of o-methoxy-N-acetoacetanilide product was added to 100 g of an ethanol solution with an ethanol concentration of 50% (v / v) to prepare a saturated mother liquor with an ethanol concentration of 50% (v / v). The saturated mother liquor with an ethanol concentration of 20% (v / v), the saturated mother liquor with an ethanol concentration of 40% (v / v), the saturated mother liquor with an ethanol concentration of 35% (v / v), the saturated mother liquor with an ethanol concentration of 60% (v / v), the saturated mother liquor with an ethanol concentration of 10% (v / v), and the saturated mother liquor with an ethanol concentration of 50% (v / v) were prepared, respectively.
[0028] The CAS number of o-methoxyaniline involved in the following examples is 90-04-0, and the structural formula is: .
[0029] The CAS number of divinylketone involved is 674-82-8, and the structural formula is: .
[0030] Example 1: Preparation of o-methoxy-N-acetoacetanilide A continuous reaction research process for a low-biphenylamine impurity, o-methoxydivinylaniline (o-methoxy-N-acetoacetanilide), includes the following steps: (1) In the reactor, lay the bottom 0.5 t of ethanol concentration of 20% saturated mother liquor, o-methoxy aniline and divinyl ketone feeding pipe end located at the liquid surface 1 / 2.
[0031] (2) Control o-methoxy aniline and divinyl ketone drop into the system obtained in step (1) in proportion (equimolar ratio), the drop rate of o-methoxy aniline is 1000 kg / h, the drop rate of divinyl ketone is 720 kg / h, the residence time is 20 min (the residence time in the reactor from the beginning of drop to overflow), the temperature in the reactor is controlled at 50℃ throughout the process; wherein the total mass of o-methoxy aniline drop is: 333 kg, the total mass of divinyl ketone drop is: 240 kg; (3) Overflow into the crystal growing reactor.
[0032] The liquid in step (2) is naturally flowed out through the overflow port and continuously introduced into the crystal growing reactor, the residence time is controlled at 30 min, and the temperature is controlled at 35℃; (4) Overflow into the crystallization reactor.
[0033] The liquid in step (3) is naturally flowed out through the overflow port and continuously introduced into the crystallization reactor, before introduction, 3 t of ethanol concentration of 20% saturated mother liquor is laid on the bottom of the crystallization reactor, the reaction temperature of the crystallization reactor is controlled at 8℃, and the reaction time is 100 min; (5) Centrifugation, wet product, finished product: The mixed liquid in the crystallization reactor after the reaction in step (4) is pumped to the centrifuge for centrifugal washing by using a solid-liquid pump, the pumping treatment capacity is 1720 kg / h, the centrifugal washing method is: the pump outlet pipe is directly connected to the centrifuge, the centrifuge is centrifuged (the centrifugal condition is: speed 5000 rpm), and the washing liquid (the washing liquid is: ethanol aqueous solution with an ethanol concentration of 20% (v / v)) is sprayed at the same time to remove the impurities in the mixed liquid; the solid (wet product) obtained after centrifugation is dried (110℃ steam drying, residence time 5 s) to obtain the finished product.
[0034] During the centrifugation process, 5% of the mother liquor (100 kg / h of mother liquor from the centrifuge is taken as an example, 95 kg / h is returned to the reactor, and 5 kg / h is discarded) is discarded, the washing liquid just makes up for the loss, this process also means that the mother liquor is always discarded and replaced at a certain proportion (about 5%), which ensures the stability of the mother liquor quality and prevents the continuous accumulation of impurities. The 95% (w / w) centrifugal mother liquor obtained after centrifugation and 5% (w / w, to make up for the loss of mother liquor) fresh washing liquid (the washing liquid is: ethanol aqueous solution with an ethanol concentration of 20% (v / v)) are mixed and used as the next batch of mother liquor; and introduced into the reactor.
[0035] The results show: The product yield was 98.5% and the purity was 99.85%, and the thin layer result did not detect the impurity of bis (2-methoxyphenyl) amine.
[0036] Example 2: Preparation of o-methoxy-N-acetylacetanilide A continuous reaction process for studying a low bisphenylamine impurity, o-methoxy bisethylphenylamine, includes the following steps: (1) A reaction kettle is laid with 0.5 t of saturated mother liquor with an ethanol concentration of 40%, and the end of the feeding pipe of o-methoxyaniline and divinyl ketone is located at 1 / 2 of the liquid level.
[0037] (2) Control the proportional addition of o-methoxyaniline and divinyl ketone to the system obtained in step (1), the addition rate of o-methoxyaniline is 2000 kg / h, the addition rate of divinyl ketone is 1440 kg / h, the residence time is 30 min (the residence time in the kettle from the start of dropping to overflowing), and the temperature in the reaction kettle is controlled at 50°C throughout; wherein the total mass of o-methoxyaniline added is: 1000 kg, and the total mass of divinyl ketone added is: 720 kg; (3) Overflow into the crystal growing kettle.
[0038] The liquid in step (2) is naturally flowed out through the overflow port and continuously introduced into the crystal growing kettle, the residence time is controlled at 30 min, and the temperature is controlled at 35°C; (4) Overflow into the crystallization kettle: The liquid after reaction in step (3) is naturally flowed out through the overflow port and continuously introduced into the crystallization kettle, before introduction, 3 t of saturated mother liquor with an ethanol concentration of 40% is laid on the bottom of the crystallization kettle, the reaction temperature of the crystallization kettle is controlled at 10°C, and the reaction time is 80 min; (5) Centrifugation, wet product, finished product: The mixed liquid in the crystallization kettle after the reaction in step (4) is pumped to the centrifuge for centrifugal washing using a solid-liquid pump, the pumping treatment capacity is 3440 kg / h, and the centrifugal washing method is: the pump outlet pipe is directly connected to the centrifuge, the centrifuge is centrifuged (centrifugal condition: speed 5000 rpm) while being sprayed with washing liquid (washing liquid: ethanol aqueous solution with an ethanol concentration of 40% (v / v)), to remove impurities in the mixed liquid; the solid (wet product) obtained after centrifugation is dried (110°C steam drying, residence time 5 s) to obtain the finished product.
[0039] During centrifugation, 5% of the mother liquor is discarded (for example, 100 kg / h of mother liquor is discharged from the centrifuge, 95 kg / h is returned to the reaction kettle, and 5 kg / h is discarded. During centrifugation, the mother liquor will be lost (about 5% of the mother liquor), and the washing liquid will just make up for this loss. This process is equivalent to the mother liquor being continuously discarded and replaced at a certain proportion (about 5%) to ensure the stability of the mother liquor quality and prevent the accumulation of impurities.
[0040] The results show that: The product yield is 98.6%, the purity is 99.89%, and the thin-layer result does not detect the presence of bis(2-methoxyphenyl)amine impurities.
[0041] Example 3: Preparation of o-methoxy-N-acetylacetanilide A continuous reaction process for preparing a low bisphenylamine impurity, o-methoxybisacetophenone, includes the following steps: (1) Place 0.5 t of saturated mother liquor with an ethanol concentration of 40% in the reaction kettle, and place the end of the o-methoxyaniline and bisacetylketone feeding pipe at 1 / 2 of the liquid level.
[0042] (2) Control the equal proportion of o-methoxyaniline and bisacetylketone to be added to the system obtained in step (1), with an o-methoxyaniline drop rate of 1500 kg / h and a bisacetylketone drop rate of 1080 kg / h. The residence time is 35 min (the residence time of each drop in the kettle from the start of drop addition to overflow), and the temperature in the reaction kettle is controlled at 55°C throughout the process. The total mass of o-methoxyaniline added is 875 kg, and the total mass of bisacetylketone added is 630 kg. (3) Overflow into the crystal growth kettle.
[0043] The liquid from step (2) is naturally discharged through the overflow port and continuously introduced into the crystal growth kettle, with a residence time of 30 min and a temperature of 35°C. (4) Overflow into the crystallization kettle.
[0044] The liquid from step (3) is naturally discharged through the overflow port and continuously introduced into the crystallization kettle. Before introduction, 3 t of saturated mother liquor with an ethanol concentration of 40% is placed in the crystallization kettle. The reaction temperature in the crystallization kettle is controlled at 5°C, and the reaction time is 80 min. (5) Centrifugation, wet product, and finished product: After the reaction in step (4) is completed, the mixed liquid in the crystallization vessel is transported to a centrifuge for centrifugal washing using a solid-liquid transfer pump. The pumping capacity is 2580 kg / h. The centrifugal washing method is as follows: the pump outlet pipe is directly connected to the centrifuge. While centrifuging (centrifugation conditions: speed 5000 rpm), the centrifuge sprays washing liquid (washing liquid is: ethanol aqueous solution with ethanol concentration of 40% (v / v)) to remove impurities in the mixed liquid. The solid obtained after centrifugation (moist product) is dried (steam dried at 110℃, residence time 5s) to obtain the finished product.
[0045] During centrifugation, 5% of the mother liquor is discarded (taking a centrifuge capacity of 100 kg / h as an example, 95 kg / h is returned to the reactor, and 5 kg / h is discarded; during centrifugation, there will be a loss of mother liquor (approximately 5% of the mother liquor volume). The washing liquid replenishes this loss. This process is equivalent to the mother liquor being continuously discarded and replaced at a certain ratio (approximately 5%), ensuring the stability of the mother liquor quality and preventing the continuous accumulation of impurities). The 95% (w / w) centrifuged mother liquor obtained after centrifugation is mixed with 5% (w / w, to replenish the missing portion of the mother liquor) fresh washing liquid (the washing liquid is an ethanol aqueous solution with a concentration of 40% (v / v) ethanol) as the next batch of reused mother liquor; this mixture is then added to the reactor.
[0046] The results show: The product yield was 98.1%, the purity was 99.91%, and no bis(2-methoxyphenyl)amine impurity was detected in the thin-layer chromatography results.
[0047] Example 4: Preparation of o-methoxy-N-acetoacetanilide A research process for the continuous reaction of o-methoxybisethylaniline with low diphenylamine impurities includes the following steps: (1) Place 0.5t of saturated mother liquor with an ethanol concentration of 35% at the bottom of the reactor, and place the end of the feed pipe for o-methoxyaniline and diketene at 1 / 2 of the liquid surface.
[0048] (2) Add o-methoxyaniline and diketene in equal proportions to the system obtained in step (1). The dropping rate of o-methoxyaniline is 1000 g / h, the dropping rate of diketene is 720 kg / h, and the residence time is 25 min (the residence time of each drop from the start of the dropping to the overflow in the reactor). The temperature inside the reactor is controlled at 55℃ throughout the process. The total mass of o-methoxyaniline added is 416 kg, and the total mass of diketene added is 300 kg. (3) Overflow into the crystal growth vessel.
[0049] The liquid from step (2) is allowed to flow out naturally through the overflow port and continuously introduced into the crystal growth vessel, with a residence time of 30 minutes and a temperature of 35°C. (4) Overflow into the crystallization kettle.
[0050] After the reaction in step (3), the liquid is allowed to flow out naturally through the overflow port and continuously introduced into the crystallization vessel. Before introducing, 3t of saturated mother liquor with an ethanol concentration of 35% is placed at the bottom of the crystallization vessel. The reaction temperature of the crystallization vessel is controlled at 10℃ and the reaction time is 80min. (5) Centrifuged, damp, and finished products: After the reaction in step (4) is completed, the mixed liquid in the crystallization vessel is transported to a centrifuge for centrifugal washing using a solid-liquid transfer pump. The pumping capacity is 1720 kg / h. The centrifugal washing method is as follows: the pump outlet pipe is directly connected to the centrifuge. While centrifuging (centrifugation conditions: speed 5000 rpm), the centrifuge sprays washing liquid (washing liquid is: ethanol aqueous solution with ethanol concentration of 35% (v / v)) to remove impurities in the mixed liquid. The solid (moist product) obtained after centrifugation is dried (steam dried at 110℃, residence time 5s) to obtain the finished product.
[0051] During centrifugation, 5% of the mother liquor is discarded (taking a centrifuge capacity of 100 kg / h as an example, 95 kg / h of the mother liquor is returned to the reactor, and 5 kg / h is discarded; during centrifugation, there will be a loss of mother liquor (approximately 5% of the mother liquor volume). The washing liquid replenishes this loss. This process is equivalent to the mother liquor being constantly discarded and replaced at a certain ratio (approximately 5%), ensuring the stability of the mother liquor quality and preventing the continuous accumulation of impurities). The 95% (w / w) centrifuged mother liquor obtained after centrifugation is mixed with 5% (w / w, to replenish the missing portion of the mother liquor) fresh washing liquid (the washing liquid is an ethanol aqueous solution with a concentration of 35% (v / v) ethanol) as the next batch of reused mother liquor; this mixture is then added to the reactor.
[0052] The results show: The product yield was 98.4%, the purity was 99.89%, and no bis(2-methoxyphenyl)amine impurity was detected in the thin-layer chromatography results.
[0053] Example 5: Effect of saturated mother liquor with different ethanol concentrations on the preparation of o-methoxy-N-acetylacetanilide Includes the following steps: The ethanol concentration is adjusted to 60%, 10%, and 50%, respectively. That is, the saturated mother liquor with an ethanol concentration of 20% in steps (1) and (4) is replaced with a saturated mother liquor with an ethanol concentration of 60%, a saturated mother liquor with an ethanol concentration of 10%, and a saturated mother liquor with an ethanol concentration of 50%, respectively. At the same time, the washing solution in step (4) is adjusted to a 60% (v / v) ethanol aqueous solution, a 10% (v / v) ethanol aqueous solution, and a 50% (v / v) ethanol aqueous solution, respectively. The remaining conditions were the same as in Example 1. The product was prepared according to the method of Example 1.
[0054] The product yield was 98.5% and the purity was 99.84% when using saturated mother liquor with an ethanol concentration of 60%. The thin-layer chromatography results showed that bis(2-methoxyphenyl)amine was an impurity.
[0055] The product yield was 97.3% and the purity was 99.23% when using 10% ethanol saturated mother liquor. The thin-layer chromatography results showed that bis(2-methoxyphenyl)amine was an impurity.
[0056] The product yield was 98.1% and the purity was 99.55% when using saturated mother liquor with an ethanol concentration of 50%. The thin-layer chromatography results showed that bis(2-methoxyphenyl)amine was an impurity.
[0057] Example 6: Effect of different residence times on the preparation of o-methoxy-N-acetylacetanilide Includes the following steps: The residence time in the reactor was adjusted to 50 min and 15 min, that is, the residence time in step (2) was adjusted to 50 min and 15 min; the other conditions were the same as in Example 1, and the product was prepared according to the method of Example 1.
[0058] The residence time was adjusted to 50 min, and the product yield was 97.1% with a purity of 99.52%. Bis(2-methoxyphenyl)amine impurity was detected in the thin-layer chromatography results. The residence time was adjusted to 15 min, and the product yield was 94.3% with a purity of 98.35%. Bis(2-methoxyphenyl)amine impurity was detected in the thin-layer chromatography results.
[0059] Example 7: Effect of different reactor temperatures on the preparation of o-methoxy-N-acetoacetanilide Includes the following steps: The reactor temperature was adjusted to 35℃, 40℃, and 60℃, that is, the temperature inside the reactor was controlled at 50℃ throughout the process in step (2) was adjusted to 35℃, 40℃, and 60℃ throughout the process in step (2); the other conditions were the same as in Example 1, and the product was prepared according to the method of Example 1.
[0060] The temperature inside the reactor was controlled at 35℃ throughout the process. The product yield was 93.1% and the purity was 99.53%. Bis(2-methoxyphenyl)amine impurity was detected in the thin-layer chromatography results.
[0061] The temperature inside the reactor was controlled at 40℃ throughout the process. The product yield was 94.3% and the purity was 99.58%. Bis(2-methoxyphenyl)amine impurity was detected in the thin-layer chromatography results. The temperature inside the reactor was controlled at 60℃ throughout the process, and the product yield was 98.3% with a purity of 99.85%. No bis(2-methoxyphenyl)amine impurities were detected in the thin-layer chromatography results.
[0062] Example 8: Effect of different cooling vessel temperatures on the preparation of o-methoxy-N-acetoacetanilide Includes the following steps: The temperature of the cooling vessel was adjusted to 2℃, 4℃, and 6℃, that is, the temperature of the crystallization vessel in step (3) was adjusted to 8℃ to 2℃, 4℃, and 6℃. The other conditions were the same as in Example 1, and the product was prepared according to the method of Example 1.
[0063] The cooling vessel temperature was adjusted to 2℃, and the product yield was 98.8% with a purity of 99.76%. Thin-layer chromatography detected bis(2-methoxyphenyl)amine as an impurity. The temperature of the cooling vessel was adjusted to 4℃, and the product yield was 98.3% with a purity of 99.81%. Bis(2-methoxyphenyl)amine impurity was detected in the thin-layer chromatography results. The temperature of the cooling vessel was adjusted to 6℃, and the product yield was 98.3% with a purity of 99.89%. No bis(2-methoxyphenyl)amine impurity was detected in the thin-layer chromatography results.
[0064] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.
Claims
1. A continuous reaction research process for o-methoxy-N-acetoacetanilide with low diphenylamine impurities, characterized in that, Includes the following steps: (1) Spread a saturated mother liquor of o-methoxy-N-acetylacetanilide with an ethanol concentration of 20-40% at the bottom of the reactor, and place the end of the o-methoxyaniline and diketene feed pipe below the liquid surface; (2) Add o-methoxyaniline and diketene in equal proportions to the system obtained in step (1). After the addition is completed, the residence time is 20-40 min, and the temperature inside the reactor is controlled at 50-60℃ throughout the process. The total mass of o-methoxyaniline added is 333-1333 kg, and the total mass of diketene added is 240-960 kg. (3) Overflow into the crystal growth reactor: The reaction solution after step (2) is continuously introduced into the crystal growth vessel through the overflow port, and the residence time is 30~60 min, and the temperature is 35~40℃. (4) Overflow into the crystallization kettle: After step (3) is completed, the liquid is allowed to flow out naturally through the overflow port and continuously introduced into the crystallization vessel. Before introducing, a saturated mother liquor of o-methoxy-N-acetylacetanilide is laid at the bottom of the crystallization vessel. The reaction temperature of the crystallization vessel is controlled at 5~10℃ and the residence time is 60~100 min. (5) Centrifuged, damp, and finished products: After the reaction in step (3) is completed, the mixed liquid in the tower is transported to a centrifuge for centrifugal washing using a solid-liquid transfer pump. The centrifugal washing method is as follows: the pump outlet pipe is directly connected to the centrifuge, and the centrifuge sprays washing liquid while centrifuging to wash away the impurities in the mixed liquid in the tower after the reaction in step (3). The solid obtained after centrifugation is the wet product, which is then dried to obtain the finished product.
2. The continuous reaction research process according to claim 1, characterized in that, In step (1), the saturated mother liquor is prepared by dissolving an excess of 50-100g of o-methoxy-N-acetylaniline product in 100g of ethanol solution with a concentration of 20-40% at room temperature, and the filtrate after filtration is the o-methoxy-N-acetylaniline saturated mother liquor.
3. The continuous reaction research process according to claim 1 or 2, characterized in that, In step (2), the dropping acceleration rate of o-methoxyaniline is 1000~2000 kg / h, and the dropping acceleration rate of diketene is 720~1440 kg / h.
4. The continuous reaction research process according to any one of claims 1 to 3, characterized in that, In step (4), the saturated mother liquor is a saturated mother liquor of o-methoxy-N-acetylacetanilide with an ethanol concentration of 20-40%.
5. The continuous reaction research process according to any one of claims 1 to 4, characterized in that, In step (5), the centrifugation conditions are: 5000 rpm.
6. The continuous reaction research process according to any one of claims 1 to 5, characterized in that, In step (5), the washing solution is an aqueous solution of ethanol with a concentration of 20-40%.
7. The continuous reaction research process according to any one of claims 1 to 6, characterized in that, In step (5), the drying conditions are: steam drying at 110℃ and residence time of 5s.
8. The continuous reaction research process according to any one of claims 1 to 7, characterized in that, In step (1), the ends of the feed tubes for o-methoxyaniline and diketene are located at 1 / 2 of the liquid surface.
9. The continuous reaction research process according to any one of claims 1 to 8, characterized in that, In step (1), the saturated mother liquor is a saturated mother liquor of o-methoxy-N-acetylacetanilide with an ethanol concentration of 20-40%; Preferably, in step (1), the amount of saturated mother liquor added is 0.5t~1.0t.
10. The continuous reaction research process according to any one of claims 1 to 9, characterized in that, In step (2), the temperature inside the reactor is controlled at 50~60℃ throughout the process.