CN116082224A - Preparation method of piroctone key intermediate - Google Patents
Preparation method of piroctone key intermediate Download PDFInfo
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- CN116082224A CN116082224A CN202211687887.7A CN202211687887A CN116082224A CN 116082224 A CN116082224 A CN 116082224A CN 202211687887 A CN202211687887 A CN 202211687887A CN 116082224 A CN116082224 A CN 116082224A
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- piroctone
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- key intermediate
- nonadiene
- tetramethyl
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- 229950001046 piroctone Drugs 0.000 title claims abstract description 28
- OIQJEQLSYJSNDS-UHFFFAOYSA-N piroctone Chemical compound CC(C)(C)CC(C)CC1=CC(C)=CC(=O)N1O OIQJEQLSYJSNDS-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- -1 2,6,8,8-tetramethyl-1, 3-nonadiene Chemical compound 0.000 claims abstract description 32
- 238000005698 Diels-Alder reaction Methods 0.000 claims abstract description 20
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims abstract description 16
- 239000011968 lewis acid catalyst Substances 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- 239000012298 atmosphere Substances 0.000 claims abstract description 6
- 230000001681 protective effect Effects 0.000 claims abstract description 6
- 238000004821 distillation Methods 0.000 claims description 15
- 239000012295 chemical reaction liquid Substances 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 229910052747 lanthanoid Inorganic materials 0.000 claims description 8
- 150000002602 lanthanoids Chemical class 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 6
- 238000005086 pumping Methods 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- 229940045803 cuprous chloride Drugs 0.000 claims description 3
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 claims description 3
- 235000005074 zinc chloride Nutrition 0.000 claims description 3
- 239000011592 zinc chloride Substances 0.000 claims description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract description 7
- 239000002253 acid Substances 0.000 abstract description 5
- 239000002699 waste material Substances 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000007864 aqueous solution Substances 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 238000003908 quality control method Methods 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 208000001840 Dandruff Diseases 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 6
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- ICAKDTKJOYSXGC-UHFFFAOYSA-K lanthanum(iii) chloride Chemical compound Cl[La](Cl)Cl ICAKDTKJOYSXGC-UHFFFAOYSA-K 0.000 description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- ICKYUJFKBKOPJT-UHFFFAOYSA-K samarium(3+);tribromide Chemical compound Br[Sm](Br)Br ICKYUJFKBKOPJT-UHFFFAOYSA-K 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 150000003842 bromide salts Chemical class 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 238000006077 hetero Diels-Alder cycloaddition reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000003780 keratinization Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- MCVVUJPXSBQTRZ-UHFFFAOYSA-N methyl but-2-enoate Chemical compound COC(=O)C=CC MCVVUJPXSBQTRZ-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- BTSZTGGZJQFALU-UHFFFAOYSA-N piroctone olamine Chemical compound NCCO.CC(C)(C)CC(C)CC1=CC(C)=CC(=O)N1O BTSZTGGZJQFALU-UHFFFAOYSA-N 0.000 description 1
- 229940081510 piroctone olamine Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
Abstract
The invention provides a preparation method of a piroctone key intermediate, and relates to the technical field of organic synthesis. Under the protective atmosphere, 2,6,8,8-tetramethyl-1, 3-nonadiene, n-cyanic acid and an anhydrous Lewis acid catalyst are mixed for Diels-Alder reaction to obtain the key intermediate (compound III) of piroctone. The key intermediate of the piroctone ketone can be prepared through one-step reaction, so that the synthesis steps are simplified; according to the invention, 2,6,8,8-tetramethyl-1, 3-nonadiene and n-cyanic acid are used as raw materials, wherein the corrosiveness of n-cyanic acid (non-n-cyanic acid aqueous solution) is smaller than that of aluminum trichloride and concentrated sulfuric acid, and the use of a large amount of aluminum trichloride and concentrated sulfuric acid is avoided, so that a large amount of waste acid is avoided, and the environment is protected; the preparation method provided by the invention has high product yield and good purity, and is beneficial to quality control of the subsequent OCT preparation reaction.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of a piroctone key intermediate.
Background
Along with the improvement of living standard, people pay more attention to their own external image. In known surveys, more than half of the people are found to have dandruff problems. Causes of dandruff include not only physiological scalp keratinization but also pathological causes such as fungal infection, various skin diseases. The piroctone olamine (OCT, compound I) is a novel anti-dandruff antipruritic agent developed by the company of West Terst (Hoechst), and the principle of removing dandruff and relieving itching is that the external mode caused by dandruff is blocked from the source according to the effects of sterilization and oxidation resistance, so that the dandruff and the itching are reasonably eradicated. Experimental research shows that OCT has obvious anti-dandruff effect, is nontoxic and non-irritating, and is widely used in washing and caring products such as anti-dandruff pet shampoo, hair growth and caring liquid, hair cream and the like (DE 3626210, WO 2021043628).
A more typical synthetic route for OCT is shown below:
wherein, the compound III is used as a key intermediate for preparing OCT, methyl butenoate (compound IV) is used as a raw material, friedel-crafts acylation reaction is carried out under the catalysis of aluminum trichloride to obtain an intermediate V, the intermediate is cyclized under the catalysis of concentrated sulfuric acid to obtain a compound II, and then the compound II reacts with ammonia to generate the compound III. The preparation of the compound III needs multi-step reaction, and aluminum trichloride and concentrated sulfuric acid are used, so that serious waste acid pollution is caused; meanwhile, as aluminum trichloride and concentrated sulfuric acid have strong corrosiveness, a plurality of inconveniences are brought to industrial safety.
Disclosure of Invention
In view of the above, the present invention aims to provide a preparation method of a piroctone key intermediate. The preparation method provided by the invention synthesizes the piroctone key intermediate (compound III) in one step, has small raw material corrosiveness, and can avoid the generation of a large amount of waste acid; and the yield is high.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a preparation method of a piroctone key intermediate, which is shown as a compound III and comprises the following steps:
under the protective atmosphere, mixing 2,6,8,8-tetramethyl-1, 3-nonadiene, n-cyanic acid and an anhydrous Lewis acid catalyst for Diels-Alder reaction to obtain the key intermediate of piroctone;
preferably, the molar ratio of the 2,6,8,8-tetramethyl-1, 3-nonadiene to the n-cyanic acid is 1:1-2.
Preferably, the anhydrous lewis acid catalyst comprises one or more of cuprous chloride, boron trichloride, zinc dichloride, a halogen salt of a lanthanide, and a sulfate of a lanthanide.
Preferably, the molar amount of the anhydrous Lewis acid catalyst is 1 to 10% of the molar amount of 2,6,8,8-tetramethyl-1, 3-nonadiene.
Preferably, the Diels-Alder reaction is carried out in a pipeline reactor; the prepared reaction liquid obtained by mixing 2,6,8,8-tetramethyl-1, 3-nonadiene, n-cyanic acid and anhydrous Lewis acid catalyst is pumped into a pipeline reactor through a high-pressure pump.
Preferably, the temperature of the Diels-Alder reaction is 200-300 ℃.
Preferably, the pumping pressure of the high-pressure pump is more than 30 kg, and the residence time of the prefabricated reaction liquid in the pipeline reactor is 1-3 h.
Preferably, after the Diels-Alder reaction, the method further comprises the steps of carrying out reduced pressure distillation on the obtained reaction liquid, and separating a front fraction to obtain a main fraction, wherein the main fraction is the key intermediate of the piroctone.
Preferably, the vacuum degree of the reduced pressure distillation is 100Pa or less, and the temperature of the reduced pressure distillation is 100-200 ℃.
Preferably, the main component of the front cut fraction is cyanic acid, and the front cut fraction is recycled to the Diels-Alder reaction.
The invention provides a preparation method of a key intermediate of piroctone, which comprises the steps of mixing 2,6,8,8-tetramethyl-1, 3-nonadiene, n-cyanic acid and an anhydrous Lewis acid catalyst for Diels-Alder reaction under a protective atmosphere to obtain the key intermediate of piroctone (compound III). The key intermediate of the piroctone ketone can be prepared through one-step reaction, so that the synthesis steps are simplified; according to the invention, 2,6,8,8-tetramethyl-1, 3-nonadiene and n-cyanic acid are used as raw materials, wherein the corrosiveness of n-cyanic acid (non-n-cyanic acid aqueous solution) is smaller than that of aluminum trichloride and concentrated sulfuric acid, and the use of a large amount of aluminum trichloride and concentrated sulfuric acid is avoided, so that a large amount of waste acid is avoided, and the environment is protected; the preparation method provided by the invention has high product yield and good purity, and is beneficial to quality control of the subsequent OCT preparation reaction. Furthermore, the invention adopts the pipeline reactor, so that the safety of the reaction can be increased.
The results of the examples show that the key intermediate (compound III) of piroctone prepared by the preparation method provided by the invention has the product yield of more than 84% and the purity of more than 95%.
Detailed Description
The invention provides a preparation method of a piroctone key intermediate, which is shown as a compound III and comprises the following steps:
under the protective atmosphere, mixing 2,6,8,8-tetramethyl-1, 3-nonadiene, n-cyanic acid and an anhydrous Lewis acid catalyst for Diels-Alder reaction to obtain the key intermediate of piroctone;
in the present invention, unless otherwise specified, the starting materials used are known compounds, which are commercially available or synthesized according to the methods of the related literature design.
In the present invention, the molar ratio of 2,6,8,8-tetramethyl-1, 3-nonadiene (compound VI) to n-cyanic acid is preferably 1:1 to 2, more preferably 1:1.1 to 1.5; the 2,6,8,8-tetramethyl-1, 3-nonadiene (compound VI) is synthesized in the reference "A Straightforward Hetero-Diels-Alder Approx to (2-ambo, 4'R,8' R) - α/β/γ/δ -4-Thiatocopherol" (Stefano Menichetti, et al., eur. J.Org. Chem.,2010,2218 ～ 2225.) and is also commercially available. In the present invention, the anhydrous lewis acid catalyst preferably includes one or more of cuprous chloride, boron trichloride, zinc dichloride, a halogen salt of a lanthanoid, and a sulfate of a lanthanoid, more preferably a halogen salt of a lanthanoid, which is preferably a chloride salt or a bromide salt of a lanthanoid, further preferably lanthanum chloride or samarium bromide; the molar amount of the anhydrous Lewis acid catalyst is 1 to 10%, more preferably 1.5 to 5% of the molar amount of 2,6,8,8-tetramethyl-1, 3-nonadiene. In the present invention, the protective atmosphere is preferably a nitrogen atmosphere. In the present invention, the method for mixing 2,6,8,8-tetramethyl-1, 3-nonadiene, n-cyanic acid and anhydrous Lewis acid catalyst is preferably as follows: 2,6,8,8-tetramethyl-1, 3-nonadiene is put into a preparation bottle, then n-cyanic acid and anhydrous Lewis acid catalyst are sequentially put into the preparation bottle, and the mixture is stirred and dissolved at room temperature to obtain a prefabricated reaction liquid.
In the present invention, the Diels-Alder reaction is preferably carried out in a pipeline reactor; the prepared reaction liquid obtained by mixing 2,6,8,8-tetramethyl-1, 3-nonadiene, n-cyanic acid and anhydrous Lewis acid catalyst is preferably pumped into a pipeline reactor through a high-pressure pump. The present invention is not particularly limited to the pipe reactor, and a pipe reactor well known to those skilled in the art may be used; the high pressure pump is preferably a syringe pump. In the present invention, the temperature of the Diels-Alder reaction is preferably 200 to 300 ℃, more preferably 260 to 280 ℃. In the present invention, the pumping pressure of the high-pressure pump is preferably 30 kg or more ， More preferably 30-50 kg, the residence time of the prefabricated reaction liquid in the pipeline reactor is preferably 1-3 h, and more preferably 1.5-2 h, so that the raw materials can complete the reaction; the flow rate of the high-pressure pump is determined according to the reaction temperature, the inner diameter of the pipeline reactor, the length and the like, so as to ensure that the residence time is within the range. In the present invention, the Diels-Alder reaction has the following reaction formula:
after the Diels-Alder reaction, the invention also preferably carries out reduced pressure distillation on the obtained reaction liquid, and separates a front fraction to obtain a main fraction, wherein the main fraction is the key intermediate of the piroctone. In the present invention, the specific operation of the reduced pressure distillation is preferably: the reaction liquid obtained after Diels-Alder reaction flows out of the pipeline reactor, and the flowing reaction liquid is collected into a collecting bottle under the protection of nitrogen; the collected reaction solution was transferred to a distillation flask and distilled under reduced pressure. In the present invention, the vacuum degree of the reduced pressure distillation is preferably 100Pa or less, and the temperature of the reduced pressure distillation is preferably 100 to 200 ℃. In the invention, the main component of the front fraction is cyanic acid, and the front fraction is preferably recycled to Diels-Alder reaction, namely cyanic acid can be repeatedly used; the residual liquid of the reduced pressure distillation is mainly catalyst and impurities generated by side reactions.
The preparation method provided by the invention synthesizes the piroctone key intermediate (compound III) in one step, has small raw material corrosiveness, and can avoid the generation of a large amount of waste acid; and the yield is high.
The following examples are provided to illustrate the preparation of key intermediates of piroctone in the present invention in detail, but they should not be construed as limiting the scope of the invention.
Example 1
The preparation method of the piroctone key intermediate (compound III) comprises the following steps:
under the protection of nitrogen, 180g of 2,6,8,8-tetramethyl-1, 3-nonadiene (compound VI) is added into a preparation bottle, then 56g of n-cyanic acid is added, and then 5g of anhydrous lanthanum chloride is added, and stirring and clearing are carried out at room temperature, so as to obtain a prefabricated reaction liquid; the mixture is kept under the protection of nitrogen for standby;
maintaining the temperature of the pipeline reactor at 280 ℃, pumping the prefabricated reaction liquid into the pipeline reactor by using a syringe pump, adjusting the flow of the syringe pump, and keeping the material stay in the pipeline reactor for 2 hours;
along with the continuous pumping of the reaction liquid, the materials with the finished reaction continuously flow out of the pipeline reactor; collecting the effluent materials in a collecting bottle under the protection of nitrogen until the reaction materials are completely treated;
transferring the collected materials into a distillation flask, performing high vacuum reduced pressure distillation (vacuum degree is less than or equal to 100Pa, distillation temperature is 120-150 ℃), and separating front fraction to obtain the final productThe obtained main fraction is the key intermediate of piroctone (compound III), and the quality of the obtained product is 201g, and the GC purity is more than 98%; the yield thereof was found to be 91%. Chemical Formula C 14 H 23 NO；Mass spectrum(70eV)m/z(relative intensity):221.1778(100.0％),222.1813(14.8％),223.1842(1.4％)；Elemental Analysis:C,75.98；H,10.45；N,6.35；O,7.22.
Example 2
To improve the conversion and selectivity of 2,6,8,8-tetramethyl-1, 3-nonadiene (compound VI) and improve the stirring condition, the addition amount of the feed is increased to 82g except for the n-cyanic acid, and the addition amount is kept unchanged compared with the addition amount of the feed in example 1;
the experimental operation process, the reaction conditions and the post-treatment process in the example 1 are the same, so that a key intermediate of piroctone ketone (compound III) is finally obtained, the quality of the obtained product is 212g, and the GC purity is more than 98%; the yield thereof was found to be 96%; the data are characterized in the same way as in example 1.
Example 3
Compared with example 1, the lanthanum chloride is replaced by 7g of samarium bromide, and other feeding amounts are kept unchanged;
in comparison with example 1, the residence time of the material in the pipeline reactor was increased to 3h, the rest of the experimental procedure remaining unchanged; by the same post-treatment process as in example 1, a key intermediate of piroctone (compound III) is finally obtained, the quality of the obtained product is 186g, and the gc purity is more than 95%; the yield thereof was found to be 84%; the data are characterized in the same way as in example 1.
From the above examples, it can be seen that the present invention uses 2,6,8,8-tetramethyl-1, 3-nonadiene as a raw material, and makes it possible to obtain a key intermediate of piroctone (compound III) in a single step by a classical Diels-Alder reaction with n-cyanic acid in a tubular reactor under the action of a catalyst.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
1. The preparation method of the piroctone key intermediate is shown as a compound III, and is characterized by comprising the following steps:
under the protective atmosphere, mixing 2,6,8,8-tetramethyl-1, 3-nonadiene, n-cyanic acid and an anhydrous Lewis acid catalyst for Diels-Alder reaction to obtain the key intermediate of piroctone;
2. the method according to claim 1, wherein the molar ratio of 2,6,8,8-tetramethyl-1, 3-nonadiene to n-cyanic acid is 1:1-2.
3. The preparation method according to claim 1, wherein the anhydrous lewis acid catalyst comprises one or more of cuprous chloride, boron trichloride, zinc dichloride, a halogen salt of a lanthanoid element, and a sulfate of a lanthanoid element.
4. A process according to claim 3, wherein the molar amount of the anhydrous lewis acid catalyst is from 1 to 10% of the molar amount of 2,6,8,8-tetramethyl-1, 3-nonadiene.
5. The method of claim 1, wherein the Diels-Alder reaction is carried out in a pipeline reactor; the prepared reaction liquid obtained by mixing 2,6,8,8-tetramethyl-1, 3-nonadiene, n-cyanic acid and anhydrous Lewis acid catalyst is pumped into a pipeline reactor through a high-pressure pump.
6. The process according to claim 5, wherein the Diels-Alder reaction is carried out at a temperature of 200 to 300 ℃.
7. The method according to claim 5 or 6, wherein the pumping pressure of the high-pressure pump is 30 kg or more, and the residence time of the preliminary reaction solution in the pipe reactor is 1 to 3 hours.
8. The preparation method according to claim 1, further comprising subjecting the obtained reaction solution to reduced pressure distillation after the Diels-Alder reaction, and separating a front cut to obtain a main cut, wherein the main cut is the key intermediate of piroctone.
9. The method according to claim 8, wherein the vacuum degree of the reduced pressure distillation is 100Pa or less, and the temperature of the reduced pressure distillation is 100 to 200 ℃.
10. The process of claim 8, wherein the primary component of the front-end fraction is n-cyanic acid and the front-end fraction is recycled to Diels-Alder reaction.
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| JP2012187473A (en) * | 2011-03-09 | 2012-10-04 | Osaka City Univ | Catalyst for aza diels alder reaction, and method for producing tetrahydropyridine compound using the same |
| WO2020229203A1 (en) * | 2019-05-14 | 2020-11-19 | Unilever N.V. | Hair care composition comprising a 2(1h)-pyridinone and piroctone olamine |
| CN114096230A (en) * | 2019-05-14 | 2022-02-25 | 联合利华知识产权控股有限公司 | 2(1H) -pyridones and their use to treat inflammatory conditions |
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2022
- 2022-12-28 CN CN202211687887.7A patent/CN116082224A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
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