CN109879771A - A method of using antifebrin as Material synthesis P-aminobenzene-sulfonamide - Google Patents
A method of using antifebrin as Material synthesis P-aminobenzene-sulfonamide Download PDFInfo
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- CN109879771A CN109879771A CN201910283515.XA CN201910283515A CN109879771A CN 109879771 A CN109879771 A CN 109879771A CN 201910283515 A CN201910283515 A CN 201910283515A CN 109879771 A CN109879771 A CN 109879771A
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- antifebrin
- aminobenzene
- sulfonamide
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Abstract
The invention discloses a kind of using antifebrin as the method for Material synthesis P-aminobenzene-sulfonamide, comprising the following steps: prepares antifebrin；Prepare N-acetylsulfanilyl chloride；It prepares acetylaminobenzene cyclic amides and hydrolyzes and obtain sulfanilamide (SN).Limited problem is promoted for ASC yield in chlorosulfonation, preparation process is improved from two antifebrin, ASC angles, antifebrin is synthesized by using aniline, toluenesulfonic acid, hexamethylene etc., greatly improve the yield of antifebrin, and process economics environmental protection is by being added phosphorus pentoxide as reactant, utilize its water suction and the characteristic for promoting reaction forward to carry out, greatly improve the yield of ASC, carbon tetrachloride is added as solvent simultaneously, reduce reaction mixture viscosity, chlorosulfonic acid solubility is improved, so that reaction is more abundant, further increases the yield of sulfanilamide (SN).
Description
Technical field
The present invention relates to the technology of preparing of aminobenzene sulfonamide, specifically a kind of using antifebrin is Material synthesis to amino
The method of benzsulfamide.
Background technique
P-aminobenzene-sulfonamide, abbreviation sulfanilamide (SN).Sulfonamides is one kind of four major class anti-infectious agents.Since sulfonamides presses down
Bacterium effect is good, and technology maturation, raw material is easy to get, cheap, the clinical use through decades, the certain share still kept so far.
China is the big producer of sulfonamides, and is the medicine using big country, and annual output is at ten thousand tons or so, and wherein significant portion is sold to
Overseas market.Using antifebrin as raw material, N-acetylsulfanilyl chloride is prepared through chlorosulphonic acid, then obtain through ammonolysis reaction
Acetamido benzsulfamide is hydrolyzed, and final products are recrystallized to obtain.
Chlorosulfonation is that the essential step of sulfanilamide (SN) is prepared using antifebrin as raw material, how to improve acetyl amino phenyl in the step
The purity and yield of sulfonic acid chloride (ASC), so that the yield for directly improving sulfanilamide (SN) is a problem to be solved, because of current chlorosulfonation
In reaction, is generated by reaction process compared with juicy, the content of by-product sulfuric acid is caused to reduce, so that the generation of ASC is influenced, and
Since reaction system viscosity is larger, the problem of reactant insufficient contact, the promotion of ASC yield is further limited.
Summary of the invention
The purpose of the present invention is to provide a kind of using antifebrin as the method for Material synthesis P-aminobenzene-sulfonamide, with solution
Certainly the problems mentioned above in the background art.
To achieve the above object, the invention provides the following technical scheme:
A method of using antifebrin as Material synthesis P-aminobenzene-sulfonamide, comprising the following steps:
S1, antifebrin is prepared, new steaming aniline, suitable glacial acetic acid, hexamethylene, p-methyl benzenesulfonic acid and zinc powder is added,
Heating is completely dissolved p-methyl benzenesulfonic acid on electric jacket, and adjusting fraction distillates speed 1~2 after heating temperature is raised to 75 DEG C
Drop/s；When temperature drops to 75 DEG C, reaction was completed, stirs while hot, and reaction solution is poured into the beaker for being placed with mixture of ice and water,
Ice-water bath crystallisation by cooling filters, and washs, dry, weighs, and recrystallization obtains antifebrin；
S2, N-acetylsulfanilyl chloride is prepared, is mixed with the phosphorus pentoxide of 1:4.2 mass ratio and chlorosulfonic acid,
And antifebrin obtained in step 1 is added in three times in 1.5h and stirs, 20 DEG C are then heated to, is disappeared substantially to bubble
After be heated to 50-60 DEG C, stop water-bath after reacting 2-3h, stand cooling, rubble ice, analysis is added to mixed liquor under stirring
Linen N-acetylsulfanilyl chloride out, filtering and washing air-dry；
S3 prepares acetylaminobenzene cyclic amides, and the product of N-acetylsulfanilyl chloride is put into 20% ammonium hydroxide
It is stirred to react 2-3h, heating stirring washs after suction filtration, obtains acetylaminobenzene cyclic amides finished product；
Acetylaminobenzene cyclic amides is added in industrial soda by S4, obtains P-aminobenzene-sulfonamide with ice-water bath cooling
Crystallization, filters to obtain P-aminobenzene-sulfonamide finished product.
As a further solution of the present invention: further including in step s 2, adding in three times while antifebrin is added
Enter carbon tetrachloride.
As a further solution of the present invention: the mass ratio of gross mass and chlorosulfonic acid that carbon tetrachloride is added is 1:1.24.
As a further solution of the present invention: in step S1, p-methyl benzenesulfonic acid is completely dissolved rear heating temperature and is raised to 75 DEG C,
And adjust fraction distillates speed in 1~2 drop/s.
As a further solution of the present invention: the vapo(u)rizing temperature that processing is distilled in step S1 is 110-125 DEG C, distillation time
For 30-45min.
As a further solution of the present invention: water-bath is carried out after phosphorus pentoxide and chlorosulfonic acid mixing in step S2, it is on the rocks
It is cooled to 10 DEG C.
As a further solution of the present invention: in water bath condition after acetamidobenzenesulfonyl chloride is mixed with ammonium hydroxide in step S3
Under with 60-70 DEG C of heating 10-15min and stir.
As a further solution of the present invention: in step S4, acetyl amino phenyl cyclic amides adjusts pH after mixing with industrial soda
To 7-8.
Compared with prior art, the beneficial effects of the present invention are: the present invention for ASC yield in chlorosulfonation promoted by
The problem of limit, improves preparation process from two antifebrin, ASC angles, closes by using aniline, toluenesulfonic acid, hexamethylene etc.
At antifebrin, the yield of antifebrin, and process economics environmental protection are greatly improved；By the way that phosphorus pentoxide is added as reaction
Object greatly improves the yield of ASC using its water suction and the characteristic for promoting reaction forward to carry out, while carbon tetrachloride work is added
For solvent, reaction mixture viscosity is reduced, improves chlorosulfonic acid solubility, so that reaction is more abundant, further increases sulfanilamide (SN)
Yield；
Specific embodiment
The following is a clear and complete description of the technical scheme in the embodiments of the invention, it is clear that described embodiment
Only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, the common skill in this field
Art personnel every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
Embodiment one,
A method of using antifebrin as Material synthesis P-aminobenzene-sulfonamide, comprising the following steps:
S1, antifebrin is prepared, 30mL is added in the round-bottomed flask of 100mL and newly steams aniline, suitable glacial acetic acid, hexamethylene
Alkane, p-methyl benzenesulfonic acid and zinc powder are a little, and heating is completely dissolved p-methyl benzenesulfonic acid on electric jacket, and temperature is raised to 75 DEG C or so
When, hexamethylene starts to be distilled out of, and temperature continues to rise after hexamethylene has been steamed, and control temperature is no more than 120 DEG C, adjusts fraction
Speed is distillated in 1~2 drop/s or so；When temperature drops to 75 DEG C, reaction was completed, stirs while hot, and reaction solution is poured into and is placed with
In the 100mL small beaker of 40mL mixture of ice and water, ice-water bath crystallisation by cooling is filtered, and washs, dry, is weighed, and recrystallization obtains
Antifebrin finished product about 28g rolls over hundred yields 91.3%；
S2, N-acetylsulfanilyl chloride being prepared, the phosphorus pentoxide of the chlorosulfonic acid and 25.7g that take 108g is mixed,
Antifebrin obtained in step 1 is added in 1.5h in three times and stirs to 10 DEG C for water-bath refrigerated with ice, is then heated to
20 DEG C, more bubble is generated, 50-60 DEG C is heated to after bubble disappears substantially, stops water-bath after reacting 2-3h, stands cold
But, rubble ice is added to mixed liquor under stirring, linen N-acetylsulfanilyl chloride, filtering and washing wind is precipitated
It is dry, obtain N-acetylsulfanilyl chloride finished product about 106g；
S3 prepares acetylaminobenzene cyclic amides, and the product of N-acetylsulfanilyl chloride is put into the ammonia of 180g 20%
It is stirred to react 2-3h in water, with 60-70 DEG C of heating 10-15min and is stirred under water bath condition, washs, obtained to second after suction filtration
Acylamino- phenyl ring amide finished product；
Acetylaminobenzene cyclic amides is added in 180g industrial soda by S4, adjusts pH to 7-8, cooling with ice-water bath
It is crystallized to P-aminobenzene-sulfonamide, filters to obtain P-aminobenzene-sulfonamide finished product 28.6g.
Embodiment two,
A method of using antifebrin as Material synthesis P-aminobenzene-sulfonamide, comprising the following steps:
S1, antifebrin is prepared, method is the same as example 1；
S2, N-acetylsulfanilyl chloride is prepared, the phosphorus pentoxide mixing of the chlorosulfonic acid and 27.7g of 116.3g is taken to stir
Mix, antifebrin obtained in step 1 is added in 1.5h in three times and stirs to 10 DEG C for water-bath refrigerated with ice, then plus
Heat generates more bubble to 20 DEG C, and 50-60 DEG C is heated to after bubble disappears substantially, stops water-bath after reacting 2-3h, stands
It is cooling, rubble ice is added to mixed liquor under stirring, linen N-acetylsulfanilyl chloride, filtering and washing wind is precipitated
It is dry, obtain N-acetylsulfanilyl chloride finished product about 106g；
The subsequent method for preparing P-aminobenzene-sulfonamide is the same as example 1, and obtains P-aminobenzene-sulfonamide finished product 33.7g.
Embodiment three,
A method of using antifebrin as Material synthesis P-aminobenzene-sulfonamide, comprising the following steps:
S1, antifebrin is prepared, which is the same as example 1；
S2, N-acetylsulfanilyl chloride being prepared, the phosphorus pentoxide of the chlorosulfonic acid and 25.7g that take 108g is mixed,
Antifebrin obtained in step 1 is added in 1.5h in three times and stirs to 10 DEG C for water-bath refrigerated with ice, in whipping process
Carbon tetrachloride 134.7g is added, is then heated to 20 DEG C, generates more bubble, be heated to 50-60 after bubble disappears substantially
DEG C, stop water-bath after reacting 2-3h, stand cooling, rubble ice is added to mixed liquor under stirring, it is linen right to be precipitated
Acetamidobenzenesulfonyl chloride, filtering and washing air-dry, and obtain N-acetylsulfanilyl chloride finished product about 133.3g；
The subsequent method for preparing P-aminobenzene-sulfonamide is the same as example 1, and obtains P-aminobenzene-sulfonamide finished product
42.5g。
Example IV,
A method of using antifebrin as Material synthesis P-aminobenzene-sulfonamide, comprising the following steps:
S1, antifebrin is prepared, which is the same as example 1；
S2, N-acetylsulfanilyl chloride is prepared, the phosphorus pentoxide mixing of the chlorosulfonic acid and 27.7g of 116.3g is taken to stir
It mixes, antifebrin obtained in step 1 is added in 1.5h in three times and stirs to 10 DEG C for water-bath refrigerated with ice, stirred
Carbon tetrachloride 145g is added in journey, is then heated to 20 DEG C, generates more bubble, be heated to 50- after bubble disappears substantially
60 DEG C, stops water-bath after reacting 2-3h, stand cooling, rubble ice is added to mixed liquor under stirring, be precipitated linen
N-acetylsulfanilyl chloride, filtering and washing air-dry, and obtain N-acetylsulfanilyl chloride finished product about 142.6g；
The subsequent method for preparing P-aminobenzene-sulfonamide is the same as example 1, and obtains P-aminobenzene-sulfonamide finished product
45.3g。
Comparative example one,
1, antifebrin is prepared, the glacial acetic acid of the aniline of 30ml and 45ml are mixed, 0.06g zinc powder is added and carries out at distillation
Reason, keeping vapo(u)rizing temperature is 110-125 DEG C, distillation time 30-45min, using the water and acetic acid of condenser recycling distillation, reaction
(temperature is begun to decline) is cooling after the completion, washs after suction filtration, then crude product is added in 100ml water, and temperature control heating is precipitated after cooling
Antifebrin crystal air-dries after cold water washing, obtains antifebrin finished product about 28g, rolls over hundred yields 74.7%,
2, Step 2: phosphorus pentoxide is added without in three and step 4, with the antifebrin and chlorosulfonic acid of same quality
P-aminobenzene-sulfonamide is prepared, finished product 21.4g is obtained.
Table 1, N-acetylsulfanilyl chloride (ASC) and P-aminobenzene-sulfonamide yield table.
| Project | Antifebrin yield (%) | ASC yield (%) | P-aminobenzene-sulfonamide yield (%) |
| Embodiment one | 91.3 | 81.1 | 72.4 |
| Embodiment two | 91.3 | 83.6 | 75.6 |
| Embodiment three | 91.3 | 88.2 | 82.6 |
| Example IV | 91.3 | 91.8 | 85.1 |
| Comparative example one | 74.7 | 62.5 | 56.9 |
As it can be seen that preparing antifebrin using improved method, it is greatly improved its yield；In chlorosulfonation, add
Enter phosphorus pentoxide, the moisture generated in chlorosulfonation is absorbed by phosphorus pentoxide, and sulfuric acid content is reduced, and side reaction is also corresponding
Reduction, phosphorus pentoxide generates very active influence to chlorosulfonation, improves the yield of P-aminobenzene-sulfonamide；
In addition, using carbon tetrachloride as solvent in chlorosulfonation, the advantages of reducing mixture viscosity using it, further
Improve the yield of ASC and P-aminobenzene-sulfonamide.
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case where without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Benefit requires rather than above description limits, it is intended that all by what is fallen within the meaning and scope of the equivalent elements of the claims
Variation is included within the present invention.
In addition, it should be understood that although this specification is described in terms of embodiments, but not each embodiment is only wrapped
Containing an independent technical solution, this description of the specification is merely for the sake of clarity, and those skilled in the art should
It considers the specification as a whole, the technical solutions in the various embodiments may also be suitably combined, forms those skilled in the art
The other embodiments being understood that.
Claims (8)
1. a kind of using antifebrin as the method for Material synthesis P-aminobenzene-sulfonamide, it is characterised in that: the following steps are included:
S1, antifebrin is prepared, new steaming aniline, suitable glacial acetic acid, hexamethylene, p-methyl benzenesulfonic acid and zinc powder is added, in electric heating
Putting on heating is completely dissolved p-methyl benzenesulfonic acid；When temperature drops to 75 DEG C, reaction was completed, stirs while hot, and reaction solution is poured into
It is placed in the beaker of mixture of ice and water, ice-water bath crystallisation by cooling, filters, wash, it is dry, it weighs, recrystallization obtains acetophenone
Amine；
S2, N-acetylsulfanilyl chloride is prepared, is mixed with the phosphorus pentoxide of 1:4.2 mass ratio and chlorosulfonic acid, and
Antifebrin obtained in step 1 is added in 1.5h in three times and stirs, is then heated to 20 DEG C, after bubble disappears substantially plus
Heat stops water-bath after reacting 2-3h, stands cooling, rubble ice is added to mixed liquor under stirring, ash is precipitated to 50-60 DEG C
The N-acetylsulfanilyl chloride of white, filtering and washing air-dry；
S3 prepares acetylaminobenzene cyclic amides, and the product of N-acetylsulfanilyl chloride is put into 20% ammonium hydroxide and is stirred
2-3h is reacted, heating stirring washs after suction filtration, obtains acetylaminobenzene cyclic amides finished product；
Acetylaminobenzene cyclic amides is added in industrial soda by S4, obtains P-aminobenzene-sulfonamide crystallization with ice-water bath is cooling,
Filter to obtain P-aminobenzene-sulfonamide finished product.
2. according to claim 1 a kind of using antifebrin as the method for Material synthesis P-aminobenzene-sulfonamide, feature
It is: further include: in step s 2, carbon tetrachloride is added in three times while antifebrin is added.
3. according to claim 2 a kind of using antifebrin as the method for Material synthesis P-aminobenzene-sulfonamide, feature
Be: the mass ratio of gross mass and chlorosulfonic acid that carbon tetrachloride is added is 1:1.24.
4. according to claim 1 a kind of using antifebrin as the method for Material synthesis P-aminobenzene-sulfonamide, feature
Be: in step S1, p-methyl benzenesulfonic acid is completely dissolved rear heating temperature and is raised to 75 DEG C, and adjust fraction distillates speed 1~2
Drop/s.
5. according to claim 4 a kind of using antifebrin as the method for Material synthesis P-aminobenzene-sulfonamide, feature
Be: the vapo(u)rizing temperature that processing is distilled in step S1 is 110-125 DEG C, distillation time 30-45min.
6. according to claim 1 a kind of using antifebrin as the method for Material synthesis P-aminobenzene-sulfonamide, feature
It is: carries out water-bath after phosphorus pentoxide and chlorosulfonic acid mixing in step S2, refrigerated with ice is to 10 DEG C.
7. according to claim 1 a kind of using antifebrin as the method for Material synthesis P-aminobenzene-sulfonamide, feature
Be: after acetamidobenzenesulfonyl chloride is mixed with ammonium hydroxide in step S3 under water bath condition with 60-70 DEG C of heating 10-15min simultaneously
Stirring.
8. according to claim 1 a kind of using antifebrin as the method for Material synthesis P-aminobenzene-sulfonamide, feature
Be: in step S4, acetyl amino phenyl cyclic amides adjusts pH to 7-8 after mixing with industrial soda.
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Cited By (1)
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| CN110724074A (en) * | 2019-10-28 | 2020-01-24 | 新乡市锦源化工有限公司 | Synthesis process of p-acetamido benzene sulfonamide |
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Application publication date: 20190614 |