CN105152956A - Process and device for acylation reaction of acetaminophen - Google Patents
Process and device for acylation reaction of acetaminophen Download PDFInfo
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- CN105152956A CN105152956A CN201510472206.9A CN201510472206A CN105152956A CN 105152956 A CN105152956 A CN 105152956A CN 201510472206 A CN201510472206 A CN 201510472206A CN 105152956 A CN105152956 A CN 105152956A
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- paracetamol
- acylation reaction
- acetic acid
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Abstract
The invention belongs to field of medicine preparation, and particularly relates to an acylation reaction of acetaminophen. A process for the acylation reaction of acetaminophen comprises the following steps: material preparation, acylation reaction, rectification with acetic acid; recovery of olefine acid, spin-filtering, recovery of a mother solution of acetaminophen, washing and drying. A device for the acylation reaction of acetaminophen is characterized by arranging a rectifying tower between a reaction vessel and a condenser. According to the process, the reaction temperature is reduced, so that the reaction can be carried out below 108 DEG C; the reaction time is shortened to 8.5h; the steam amount of waste acid is reduced by 25%; and the cost of secondary treatment is reduced. The concentration of acetic acid in the waste diluted acid is reduced, and the concentration of waste diluted acid is 50%. The use ratio of raw materials is improved; the cost is saved; and the yield is increased.
Description
Technical field
The invention belongs to field of medicine preparations, particularly a kind of paracetamol acylation reaction.
Background technology
Paracetamol (paracetamol or acetaminophen), molecular formula C
8h
9nO
2, be generally white crystalline powder, also referred to as acetanilide, acetaminophen or Paracetamol, be a kind of conventional bringing down a fever and analgesic drug product, be usually used in cat fever, arthrodynia, neurodynia, migraine, pain caused by cancer and postoperative analgesia etc.It is the main component of many Tamiflus and anodyne.Obtained through acetic acid acidylate by p-aminophenol.
Conventional acylation process temperature of reaction is higher, and the useless diluted acid of generation is more, and in diluted acid, acetic acid concentration is comparatively large, and cause wastage of material, long reaction time, productive rate is low.
Summary of the invention
The object of this invention is to provide a kind of low temperature, useless diluted acid steams less, conservation, the reaction times is short and the paracetamol acylation reaction technique that productive rate is high, provides its reaction unit simultaneously.
For solving above technical problem, the technical solution used in the present invention is:
Paracetamol acylation reaction technique of the present invention, comprises the following steps: get the raw materials ready, acylation reaction, acetic acid rectifying, olefin(e) acid recovery, rejection filter, paracetamol disposing mother liquor, washing and drying.
In described acetic acid rectification step, tower bottom of rectifying tower temperature is 108 ± 2 DEG C, and tower top temperature is 90 ± 2 DEG C.
In described acetic acid rectification step, rectifier column reflux ratio is 1: 9.
The acetic acid solution obtained in described acetic acid rectification step refluxes back in reactor and carries out acylation reaction.
Described material preparation step is: add p-aminophenol 1200Kg in a kettle., paracetamol mother liquor 2400L and Glacial acetic acid 1000Kg.
The paracetamol mother liquor reclaimed in described paracetamol disposing mother liquor is in batching step.
Described paracetamol mother liquor comprises the component of following parts by weight:
Paracetamol 9 ~ 11 parts
P-aminophenol≤0.02 part
Acetic acid 53 ~ 54 parts
35 ~ 37 parts, water.
The temperature of reaction of described acylation reaction is 108 DEG C ~ 132 DEG C, and the reaction times is 8.5h.
The diluted acid amount that described dilute acid recycle obtains is 1400 ~ 2300L, and massfraction is 50wt%.
The device that paracetamol acylation reaction technique of the present invention adopts, is provided with rectifying tower between reactor and condenser.
Compared with prior art, the present invention has following beneficial effect:
1, reduce temperature of reaction, can react at 108 DEG C;
2, the reaction times has shortened to 8.5h;
3, the spent acid amount of steaming reduces 25%, reduces secondary treatment expense;
4, in useless diluted acid, the concentration of acetic acid reduces, and useless dilute acid concentration is 50%, improves raw material availability, cost-saving;
5, improve productive rate.
Accompanying drawing explanation
Fig. 1 is the structural representation of apparatus of the present invention.
In figure: 1, reactor; 2, condenser; 3, rectifying tower.
Embodiment
Below in conjunction with embodiment, the present invention is described further.
Embodiment 1
Paracetamol acylation reaction technique of the present invention is as follows:
(1) get the raw materials ready: in reactor 1, add p-aminophenol 1200Kg, paracetamol mother liquor 2400L and Glacial acetic acid 1000Kg;
Paracetamol mother liquor comprises the component of following parts by weight:
Paracetamol 9 ~ 11 parts
P-aminophenol≤0.02 part
Acetic acid 53 ~ 54 parts
35 ~ 37 parts, water.
(2) acylation reaction: the temperature of reactor 1 is brought up to 108 DEG C, reacts;
(3) acetic acid rectifying: the acid steamed in reactor 1 enters in rectifying tower 2, rectifying tower 2 bottom temperature is 108 DEG C, and tower top temperature is 90 DEG C, and reflux ratio is 1: 9;
(4) dilute acid recycle: the diluted acid that rectifying tower 2 steams enters condensation in condenser 3 becomes useless diluted acid; Rectifying tower 2 rectifying acetic acid out refluxes back in reactor 1 and continues to participate in acylation reaction;
Stop after reaction 8.5h, drop to normal temperature;
Through measuring and analyzing:
Dilute acid recycle amount is: 1400L, and quality of acetic acid mark is 50%;
(5) rejection filter, washing, drying:
Carry out rejection filter by the product in reactor 1, washing, drying, obtain 1400Kg acetparaminosalol phenolic product;
(6) paracetamol disposing mother liquor: by the disposing mother liquor process obtained after rejection filter, for later product acylation reaction.
Embodiment 2
Paracetamol acylation reaction technique of the present invention is as follows:
(1) get the raw materials ready:
P-aminophenol 1200Kg is added, paracetamol mother liquor 2400L and Glacial acetic acid 1000Kg in reactor 1
Paracetamol mother liquor comprises the component of following parts by weight:
Paracetamol 9 ~ 11 parts
P-aminophenol≤0.02 part
Acetic acid 53 ~ 54 parts
35 ~ 37 parts, water.
(2) acylation reaction: the temperature of reactor 1 is brought up to 132 DEG C, reacts;
(3) acetic acid rectifying: the acid steamed in reactor 1 enters in rectifying tower 2, rectifying tower 2 bottom temperature is 108 DEG C, and tower top temperature is 90 DEG C, and reflux ratio is 1: 9;
(4) dilute acid recycle: the diluted acid that rectifying tower 2 steams enters condensation in condenser 3 becomes useless diluted acid; Rectifying tower 2 rectifying acetic acid out refluxes back in reactor 1 and continues to participate in acylation reaction;
Stop after reaction 8.5h, drop to normal temperature;
Through measuring and analyzing:
Dilute acid recycle amount is: 2000L, and quality of acetic acid mark is 52%;
(5) rejection filter, washing, drying:
Carry out rejection filter by the product in reactor 1, washing, drying, obtain 1500Kg acetparaminosalol phenolic product;
(6) the disposing mother liquor process that will obtain after rejection filter of paracetamol disposing mother liquor, for later product acylation reaction.
Embodiment 3
A kind of embodiment 1 that realizes is made up of the reactor 1 be connected successively, rectifying tower 2 and condenser 3 with the device of technique described in embodiment 2.
Claims (10)
1. a paracetamol acylation reaction technique, is characterized in that: comprise the following steps: get the raw materials ready, acylation reaction, acetic acid rectifying, olefin(e) acid recovery, rejection filter, paracetamol disposing mother liquor, washing and drying.
2. paracetamol acylation reaction technique according to claim 1, is characterized in that:
In described acetic acid rectification step, rectifying tower (2) bottom temperature is 108 ± 2 DEG C, and tower top temperature is 90 ± 2 DEG C.
3. paracetamol acylation reaction technique according to claim 1, is characterized in that:
In described acetic acid rectification step, rectifying tower (2) reflux ratio is 1: 9.
4. paracetamol acylation reaction technique according to claim 1, is characterized in that:
The acetic acid solution obtained in described acetic acid rectification step refluxes back in reactor (1) and carries out acylation reaction.
5. paracetamol acylation reaction technique according to claim 1, is characterized in that:
Described material preparation step is: in reactor (1), add p-aminophenol 1200Kg, paracetamol mother liquor 2400L and Glacial acetic acid 1000Kg.
6. paracetamol acylation reaction technique according to claim 1, is characterized in that:
The paracetamol mother liquor reclaimed in described paracetamol disposing mother liquor is in batching step.
7. paracetamol acylation reaction technique according to claim 1, is characterized in that:
Described paracetamol mother liquor comprises the component of following parts by weight:
Paracetamol 9 ~ 11 parts
P-aminophenol≤0.02 part
Acetic acid 53 ~ 54 parts
35 ~ 37 parts, water.
8. paracetamol acylation reaction technique according to claim 1, is characterized in that:
The temperature of reaction of described acylation reaction is 108 DEG C ~ 132 DEG C, and the reaction times is 8.5h.
9. paracetamol acylation reaction technique according to claim 1, is characterized in that:
The diluted acid amount that described dilute acid recycle obtains is 1400 ~ 2300L, and massfraction is 50wt%.
10. a device for paracetamol acylation reaction technique employing, is characterized in that: be provided with rectifying tower (2) between reactor (1) and condenser (3).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201510472206.9A CN105152956A (en) | 2015-08-05 | 2015-08-05 | Process and device for acylation reaction of acetaminophen |
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|---|---|---|---|
| CN201510472206.9A CN105152956A (en) | 2015-08-05 | 2015-08-05 | Process and device for acylation reaction of acetaminophen |
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| CN201510472206.9A Pending CN105152956A (en) | 2015-08-05 | 2015-08-05 | Process and device for acylation reaction of acetaminophen |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107790078A (en) * | 2017-12-08 | 2018-03-13 | 南京大学 | A kind of device and technique for producing paracetamol |
| CN111170880A (en) * | 2020-01-06 | 2020-05-19 | 河北冀衡（集团）药业有限公司 | Production system and method of acetaminophen |
| CN112479914A (en) * | 2020-11-24 | 2021-03-12 | 蚌埠丰原医药科技发展有限公司 | Device and method for continuously producing acetaminophen |
| CN115894271A (en) * | 2022-11-25 | 2023-04-04 | 河北冀衡药业股份有限公司 | Preparation method of acetaminophen by controlling content of acetaminophen impurity H |
| RU2820549C1 (en) * | 2023-10-20 | 2024-06-05 | Общество с ограниченной ответственностью "ДЖИЭСЭМ КЕМИКЭЛ" | METHOD OF PRODUCING PARACETAMOL BY ACYLATION OF p-AMINOPHENOL WITH ACETIC ACID AND DEVICE FOR PRODUCING PARACETAMOL USING SAID METHOD |
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| CN101250131A (en) * | 2008-03-15 | 2008-08-27 | 西北师范大学 | Preparation technique of p-acetyl aminophenol |
| US20120065423A1 (en) * | 2010-07-30 | 2012-03-15 | Granules India Limited | Reactive distillation process for preparation of acetaminophen |
| CN102432453A (en) * | 2011-10-31 | 2012-05-02 | 安丘市鲁安药业有限责任公司 | Process and equipment for purifying dilute acetic acid solution |
| CN104557593A (en) * | 2014-12-13 | 2015-04-29 | 常熟华港制药有限公司 | Preparation process of paracetamol |
-
2015
- 2015-08-05 CN CN201510472206.9A patent/CN105152956A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101250131A (en) * | 2008-03-15 | 2008-08-27 | 西北师范大学 | Preparation technique of p-acetyl aminophenol |
| US20120065423A1 (en) * | 2010-07-30 | 2012-03-15 | Granules India Limited | Reactive distillation process for preparation of acetaminophen |
| CN102432453A (en) * | 2011-10-31 | 2012-05-02 | 安丘市鲁安药业有限责任公司 | Process and equipment for purifying dilute acetic acid solution |
| CN104557593A (en) * | 2014-12-13 | 2015-04-29 | 常熟华港制药有限公司 | Preparation process of paracetamol |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107790078A (en) * | 2017-12-08 | 2018-03-13 | 南京大学 | A kind of device and technique for producing paracetamol |
| CN107790078B (en) * | 2017-12-08 | 2024-03-19 | 南京大学 | Device and process for producing acetaminophen |
| CN111170880A (en) * | 2020-01-06 | 2020-05-19 | 河北冀衡（集团）药业有限公司 | Production system and method of acetaminophen |
| CN112479914A (en) * | 2020-11-24 | 2021-03-12 | 蚌埠丰原医药科技发展有限公司 | Device and method for continuously producing acetaminophen |
| CN112479914B (en) * | 2020-11-24 | 2023-05-09 | 蚌埠丰原医药科技发展有限公司 | Device and method for continuously producing acetaminophen |
| CN115894271A (en) * | 2022-11-25 | 2023-04-04 | 河北冀衡药业股份有限公司 | Preparation method of acetaminophen by controlling content of acetaminophen impurity H |
| RU2820549C1 (en) * | 2023-10-20 | 2024-06-05 | Общество с ограниченной ответственностью "ДЖИЭСЭМ КЕМИКЭЛ" | METHOD OF PRODUCING PARACETAMOL BY ACYLATION OF p-AMINOPHENOL WITH ACETIC ACID AND DEVICE FOR PRODUCING PARACETAMOL USING SAID METHOD |
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