CN107033038B - The preparation method of probenecid - Google Patents
The preparation method of probenecid Download PDFInfo
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- CN107033038B CN107033038B CN201710303396.0A CN201710303396A CN107033038B CN 107033038 B CN107033038 B CN 107033038B CN 201710303396 A CN201710303396 A CN 201710303396A CN 107033038 B CN107033038 B CN 107033038B
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- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 229960003081 probenecid Drugs 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 48
- UCAGLBKTLXCODC-UHFFFAOYSA-N carzenide Chemical compound NS(=O)(=O)C1=CC=C(C(O)=O)C=C1 UCAGLBKTLXCODC-UHFFFAOYSA-N 0.000 claims abstract description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 33
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 239000000706 filtrate Substances 0.000 claims abstract description 18
- 239000000463 material Substances 0.000 claims abstract description 18
- 238000001914 filtration Methods 0.000 claims abstract description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 13
- 238000002425 crystallisation Methods 0.000 claims abstract description 13
- 230000008025 crystallization Effects 0.000 claims abstract description 13
- 238000001035 drying Methods 0.000 claims abstract description 13
- 238000010438 heat treatment Methods 0.000 claims abstract description 11
- 239000012043 crude product Substances 0.000 claims abstract description 10
- 239000006052 feed supplement Substances 0.000 claims abstract description 8
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 7
- 238000005303 weighing Methods 0.000 claims abstract description 6
- 238000004064 recycling Methods 0.000 claims abstract description 5
- 238000003756 stirring Methods 0.000 claims description 20
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 5
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- JKQOBWVOAYFWKG-UHFFFAOYSA-N molybdenum trioxide Chemical compound O=[Mo](=O)=O JKQOBWVOAYFWKG-UHFFFAOYSA-N 0.000 claims 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 claims 1
- 229910001948 sodium oxide Inorganic materials 0.000 claims 1
- -1 that is Chemical compound 0.000 claims 1
- 230000035484 reaction time Effects 0.000 abstract description 9
- 239000000243 solution Substances 0.000 abstract description 9
- 238000011084 recovery Methods 0.000 abstract description 6
- 230000007613 environmental effect Effects 0.000 abstract description 5
- 238000005516 engineering process Methods 0.000 abstract description 4
- 239000002699 waste material Substances 0.000 abstract description 4
- 239000012670 alkaline solution Substances 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/42—Separation; Purification; Stabilisation; Use of additives
- C07C303/44—Separation; Purification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of preparations of probenecid, it is characterised in that specific synthesis step is as follows: weighing water, sodium hydroxide, P―Carboxybenzenesulfonamide is added in reaction kettle, until P―Carboxybenzenesulfonamide is entirely molten, load weighted n-Propyl Bromide is added；By heat temperature raising, feed supplement reheats heating, and active carbon is added in solution, filters carbon removal while hot, collects filtrate；Filtration drying obtains crude product probenecid, and 50% hydrochloric acid is added dropwise and stands crystallization, filtration drying, the recycling of reclaimed materials, crude product probenecid, is added in alkaline solution, dissolves by heating, heat filtering, 50% acetic acid is added to pH5.0~5.2 in filtrate, and crystallization 1 hour, filtering, crystallizing and drying obtained probenecid fine work.It obviously increases total recovery, reduces waste discharge, to mitigate the pressure of environmental protection disposition；Its synthesis technology reaction time is short, and high income further increases yield after recycling by reclaimed materials, total recovery reaches 83.5%.
Description
Technical field
The present invention relates to a kind of preparation methods of probenecid, belong to the manufacture field of probenecid.
Background technique
The synthesis technology of traditional probenecid is as follows:
P―Carboxybenzenesulfonamide+N-Propyl Bromide → p- [(dipropyl amido) sulfonyl] benzoic acid (probenecid)；
Reagent: 20.12 grams of P―Carboxybenzenesulfonamide, 30.75 grams of n-Propyl Bromide, 14 grams of sodium hydroxide, dimethyl sulfoxide 32ML,
Ethyl acetate 0.4L, hexane 0.2L；
Reaction condition: the reaction time is 24 hours, and reaction temperature is 15~20 DEG C, normal pressure.
Product: 10.13 grams, yield 35.5%；The synthetic route reaction time is long, and yield is very low, and only 35.5%, it returns
Rewinding can not recycle, and environmental protection disposition pressure is big.
Summary of the invention
The object of the invention is that a kind of preparation method of probenecid is provided, and the various conditions in synthesis process, such as high temperature,
High pressure, the reaction time totally 8 hours, before feed supplement and each 4 hours after feed supplement；The step for being recycled by reclaimed materials can obviously increase
Yield is added up, waste discharge is reduced, to mitigate the pressure of environmental protection disposition；Its synthesis technology reaction time is short, high income, leads to
It crosses after reclaimed materials recycles and further increases yield, total recovery reaches 83.5%.
The technical scheme of the present invention is realized as follows: a kind of preparation method of probenecid, it is characterised in that specific to close
At steps are as follows:
1, P―Carboxybenzenesulfonamide+n-Propyl Bromide → p- [(dipropyl amido) sulfonyl] benzoic acid (probenecid)
1. weighing 575.0 milliliters of water, 92.0 grams of sodium hydroxide, 125.0 grams of P―Carboxybenzenesulfonamide, it is added in reaction kettle,
Stirring is warming up to 40 ± 5 DEG C, until P―Carboxybenzenesulfonamide is entirely molten, 175.0 grams i.e. 130.0 millis of load weighted n-Propyl Bromide are added
It rises, since n-Propyl Bromide is liquid, 175.0 grams are equivalent to 130.0 milliliters；
2. heat temperature raising is kept for 100.0~108.0 DEG C of temperature, 0.18~0.35MPa of pressure, stirs 4 hours, be cooled to
90 DEG C hereinafter, pressure relief；
3. feed supplement weighs 20.0 grams of sodium hydroxide, add 50.0 milliliters of water, 90.2 grams (67.0 milliliters) are added after stirring and dissolving
N-Propyl Bromide is mixed, is poured into reaction kettle；
4. heat temperature raising is kept for 100.0~108.0 DEG C of temperature, 0.18~0.35MPa of pressure, stir 4 hours, cools down, solution
Except pressure；
5. solution is added 3.75 grams of active carbon, heating is kept for 60 ± 5 DEG C 30 minutes, filters carbon removal while hot, collects filtrate；
6. 50% acetic acid is added dropwise in filtrate at 60 DEG C, until PH5.0~5.2, cool down crystallization 1 hour, filtration drying obtains crude product third
Sulphur relaxes 133.1 grams, yield 75.0%；
7. collecting the above-mentioned filtrate 6. filtered out after probenecid, 50% hydrochloric acid (17%) is added dropwise to solution PH 2.0~2.2, stands
Crystallization, filtration drying obtain 34.0 grams of reclaimed materials；
8. the recycling of reclaimed materials: weighing 156.0 milliliters of water, 25.0 grams of sodium hydroxide, 34.0 grams of reclaimed materials, reaction is added
In kettle, stirring is warming up to 40 DEG C, until reclaimed materials is entirely molten, 48.0 grams of (35.0 milliliters) N-Propyl Bromides are added.Heat temperature raising keeps temperature
It 100~108 DEG C, 0.18~0.35MPa of pressure, stirs 4 hours, cooling, pressure relief.Then feed supplement weighs sodium hydroxide 5.5
Gram, add 13.0 milliliters of water, 13.0 grams of (10 milliliters) N-Propyl Bromides are added after stirring and dissolving, mixes, pour into reaction kettle.Heating rises
Temperature is kept for 100~108 DEG C of temperature, 0.18~0.35MPa of pressure, is stirred 4 hours, cooling, pressure relief.Activity is added in solution
1 gram of charcoal, heating is kept for 60 ± 5 DEG C 30 minutes, filters carbon removal while hot, collects filtrate.50% acetic acid is added dropwise in filtrate at 60 DEG C, until
PH5.0~5.2 cool down crystallization 1 hour, and filtration drying obtains 34.2 grams of crude product probenecid, yield 71.0%；
2, the purification of probenecid:, being added in alkaline solution by 167.3 grams of crude product probenecid, dissolves by heating, heat filtering, filter
50% acetic acid is added to PH5.0~5.2 in liquid, and crystallization 1 hour, filtering, crystallizing and drying obtained 148.0 grams of probenecid fine work, yield
88.4%, total recovery: 83.5%.
The positive effect of the present invention is that the synthesis technology reaction time is short, and high income recycles laggard one by reclaimed materials
Step improves yield, and total recovery reaches 83.5%；Waste discharge is efficiently reduced, to mitigate the pressure of environmental protection disposition；With production
For 1 ton of probenecid:
Conventional method:
Raw material: 1986.2 kilograms of P―Carboxybenzenesulfonamide
3035.5 kilograms of n-Propyl Bromide
1382.0 kilograms of sodium hydroxide
3160 liters of dimethyl sulfoxide
39486 liters of ethyl acetate
19743 liters of hexane
Reaction condition: reaction temperature is 15~20 DEG C, normal pressure.Reaction time is 24 hours.Yield 35.5%.
New method:
Raw material:
844.6 kilograms of P―Carboxybenzenesulfonamide
2204.0 kilograms of n-Propyl Bromide
962.8 kilograms of sodium hydroxide
304 liters of glacial acetic acid
473 liters of hydrochloric acid
Reaction condition: reaction temperature is 100.0~108.0 DEG C, 0.18~0.35MPa of pressure.Reaction time is 8 hours.
Yield 83.5%.
Two methods comparison:
1 method of the invention reduces inventory and is respectively as follows: 1141.6 kilograms of P―Carboxybenzenesulfonamide, n-Propyl Bromide 831.5
Kilogram, 419.2 kilograms of sodium hydroxide, cancels and use 3160 liters of dimethyl sulfoxide, 39486 liters of ethyl acetate, 19743 liters of hexane.
Greatly reduce the investment of Material Cost.
2, from the angle of environmental protection, greatly reduce the discharge of the three wastes.
3 method lists of the invention are reduced work hours 16 hours from the point of view of reaction time, be equivalent to conventional method three/
One, greatly reduce cost of human resources.Cancel simultaneously using dimethyl sulfoxide, ethyl acetate and hexane, avoids into one
The series of processes such as the separating-purifying of step effectively shorten the production cycle 24 hours.
4 avoid thus bring impurity due to eliminating the use of three kinds of organic solvents from the angle of product quality
Caused by product quality risk.
Specific embodiment
Below with reference to embodiment, the present invention will be further described:
Embodiment 1
P―Carboxybenzenesulfonamide+n-Propyl Bromide → p- [(dipropyl amido) sulfonyl] benzoic acid (probenecid)
Reagent: 125.0 grams~12.5 tons of P―Carboxybenzenesulfonamide；
326.2 grams~32.6 tons of n-Propyl Bromide；
142.5 grams~14.2 tons of sodium hydroxide；
50% 100 milliliters of acetic acid~10000 liters is to be diluted by glacial acetic acid and obtained: glacial acetic acid 50ml taken, water is added to mix, constant volume
To 100ml；
50% 140 milliliters of hydrochloric acid~14000 liters is obtained by hydrochloric acid: taking hydrochloric acid 50ml, water is added to mix, constant volume arrives
100ml；
1. weighing 575.0 milliliters of water, 92.0 grams of sodium hydroxide, 125.0 grams of P―Carboxybenzenesulfonamide, it is added in reaction kettle,
Stirring is warming up to 40 ± 5 DEG C, until P―Carboxybenzenesulfonamide is entirely molten, 175.0 grams of load weighted n-Propyl Bromide is added, n-Propyl Bromide is
Liquid, 175.0 grams are equivalent to 130.0 milliliters.
2. heat temperature raising is kept for 100.0~108.0 DEG C of temperature, 0.18~0.35MPa of pressure, stirs 4 hours, be cooled to
90 DEG C hereinafter, pressure relief.
2. expecting, 20.0 grams of sodium hydroxide are weighed, adds 50.0 milliliters of water, 90.2 grams i.e. 67.0 milliliters are added after stirring and dissolving
N-Propyl Bromide is mixed, is poured into reaction kettle.
4. heat temperature raising is kept for 100.0~108.0 DEG C of temperature, 0.18~0.35MPa of pressure, stir 4 hours, cools down, solution
Except pressure.
5. solution is added 3.75 grams of active carbon, heating is kept for 60 ± 5 DEG C 30 minutes, filters carbon removal while hot, collects filtrate.
6. 50% acetic acid is added dropwise in filtrate at 60 DEG C, pH5.0~5.2 are adjusted to, are cooled down crystallization 1 hour, filtration drying obtains crude product
133.1 grams of probenecid, yield 75.0%.
7. collecting the above-mentioned filtrate 6. filtered out after probenecid, 50% hydrochloric acid of dropwise addition to pH value of solution 2.0~2.2 stands crystallization,
Filtration drying obtains 34.0 grams of reclaimed materials.
8. the recycling of reclaimed materials: weighing 156.0 milliliters of water, 25.0 grams of sodium hydroxide, 34.0 grams of reclaimed materials, reaction is added
In kettle, stirring is warming up to 40 DEG C, until reclaimed materials is entirely molten, 48.0 grams i.e. 35.0 milliliters are added) n-Propyl Bromide.Heat temperature raising is kept
It 100~108 DEG C of temperature, 0.18~0.35MPa of pressure, stirs 4 hours, cooling, pressure relief.Then feed supplement weighs hydroxide
5.5 grams of sodium, add 13.0 milliliters of water, 13.0 grams i.e. 10 milliliters of n-Propyl Bromides are added after stirring and dissolving, mixes, pours into reaction kettle.
Heat temperature raising is kept for 100~108 DEG C of temperature, 0.18~0.35MPa of pressure, is stirred 4 hours, cooling, pressure relief.Solution adds
Enter 1 gram of active carbon, heating is kept for 60 ± 5 DEG C 30 minutes, filters carbon removal while hot, collects filtrate.50% vinegar is added dropwise in filtrate at 60 DEG C
Acid, until pH5.0~5.2, cool down crystallization 1 hour, filtration drying obtains 34.2 grams of crude product probenecid, yield 71.0%.
The purification of probenecid:, being added in alkaline solution by 167.3 grams of crude product probenecid, dissolves by heating, heat filtering, filtrate
50% acetic acid is added to pH5.0~5.2, crystallization 1 hour, filtering, crystallizing and drying obtained 148.0 grams of probenecid fine work, yield 88.4%.
Total recovery: 83.5%.
Claims (1)
1. a kind of preparation of probenecid, it is characterised in that specific synthesis step is as follows:
P―Carboxybenzenesulfonamide+N-Propyl Bromide → p- [(dipropyl amido) sulfonyl] benzoic acid, that is, probenecid
1. 575.0 milliliters of water intaking, 125.0 grams of P―Carboxybenzenesulfonamide, is added in reaction kettle, stirring rises by 92.0 grams of sodium hydroxide
Temperature is to 40 ± 5 DEG C, until P―Carboxybenzenesulfonamide is entirely molten, 175.0 grams of load weighted N-Propyl Bromide or liquid N-Propyl Bromide 130.0 is added
Milliliter;
2. heat temperature raising is kept for 100.0~108.0 DEG C of temperature, 0.18~0.35MPa of pressure, stirs 4 hours, be cooled to 90 DEG C
Hereinafter, pressure relief;
3. feed supplement weighs 20.0 grams of sodium hydroxide, add 50.0 milliliters of water, 90.2 grams of N-Propyl Bromides or 67.0 millis are added after stirring and dissolving
The liquid N-Propyl Bromide risen is mixed, is poured into reaction kettle;
4. heat temperature raising is kept for 100.0~108.0 DEG C of temperature, 0.18~0.35MPa of pressure, stir 4 hours, cooling releases pressure
Power;
5. solution is added 3.75 grams of active carbon, heating is kept for 60 ± 5 DEG C 30 minutes, filters carbon removal while hot, collects filtrate;
6. 50% acetic acid is added dropwise in filtrate at 60 DEG C, until PH5.0~5.2, cool down crystallization 1 hour, filtration drying obtains crude product probenecid
133.1 grams, yield 75.0%;
7. collecting the above-mentioned filtrate 6. filtered out after probenecid, 17% hydrochloric acid is added dropwise to solution PH 2.0~2.2, stands crystallization, filtering
It is dry, obtain 34.0 grams of reclaimed materials;
8. the recycling of reclaimed materials: weighing 156.0 milliliters of water, 25.0 grams of sodium hydroxide, 34.0 grams of reclaimed materials, reaction kettle is added
Interior, stirring is warming up to 40 DEG C, until reclaimed materials is entirely molten, 48.0 grams of N-Propyl Bromides or 35.0 milliliters of liquid N-Propyl Bromide are added;Heat temperature raising,
It is kept for 100~108 DEG C of temperature, 0.18~0.35MPa of pressure, stirred 4 hours, cooling, pressure relief;Then feed supplement weighs hydrogen
5.5 grams of sodium oxide molybdena, add 13.0 milliliters of water, 13.0 grams of N-Propyl Bromides or 10 milliliters of liquid N-Propyl Bromide are added after stirring and dissolving, mixes,
Enter in reaction kettle;Heat temperature raising is kept for 100~108 DEG C of temperature, 0.18~0.35MPa of pressure, is stirred 4 hours, is cooled down, and is released
Pressure;Solution is added 1 gram of active carbon, and heating is kept for 60 ± 5 DEG C 30 minutes, filters carbon removal while hot, collects filtrate;Filtrate is at 60 DEG C
50% acetic acid of lower dropwise addition, until PH5.0~5.2, cool down crystallization 1 hour, filtration drying obtains 34.2 grams of crude product probenecid, yield
71.0%。
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB674298A (en) * | 1949-08-20 | 1952-06-18 | Sharp & Dohme Inc | Improvements in or relating to sulphamylbenzoic acids |
| WO2001004087A1 (en) * | 1999-07-13 | 2001-01-18 | Eli Lilly And Company Limited | Sulfonamide substituted benzylamine derivatives and their use as medicaments |
| CN102976980A (en) * | 2012-12-07 | 2013-03-20 | 山东省化工研究院 | Probenecid purification method |
| CN103613521A (en) * | 2013-11-21 | 2014-03-05 | 山东省化工研究院 | Water-phase synthetic method of probenecid |
-
2017
- 2017-05-03 CN CN201710303396.0A patent/CN107033038B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB674298A (en) * | 1949-08-20 | 1952-06-18 | Sharp & Dohme Inc | Improvements in or relating to sulphamylbenzoic acids |
| WO2001004087A1 (en) * | 1999-07-13 | 2001-01-18 | Eli Lilly And Company Limited | Sulfonamide substituted benzylamine derivatives and their use as medicaments |
| CN102976980A (en) * | 2012-12-07 | 2013-03-20 | 山东省化工研究院 | Probenecid purification method |
| CN103613521A (en) * | 2013-11-21 | 2014-03-05 | 山东省化工研究院 | Water-phase synthetic method of probenecid |
Non-Patent Citations (1)
| Title |
|---|
| p-(N,N-Dialkylsulfamoyl)benzoic acids;Goldberg, A. A.和Wragg, A. H.;《Journal of the Chemical Society》;19601231;1408-1409页 * |
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