CN103483253A - Synthesis method of 8-hydroxyquinaldine - Google Patents
Synthesis method of 8-hydroxyquinaldine Download PDFInfo
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- CN103483253A CN103483253A CN201310489012.0A CN201310489012A CN103483253A CN 103483253 A CN103483253 A CN 103483253A CN 201310489012 A CN201310489012 A CN 201310489012A CN 103483253 A CN103483253 A CN 103483253A
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- Prior art keywords
- synthetic method
- paraldehyde
- quinaldine red
- temperature
- hydroxyl quinaldine
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- NBYLBWHHTUWMER-UHFFFAOYSA-N 2-Methylquinolin-8-ol Chemical compound C1=CC=C(O)C2=NC(C)=CC=C21 NBYLBWHHTUWMER-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000001308 synthesis method Methods 0.000 title abstract 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 20
- SQYNKIJPMDEDEG-UHFFFAOYSA-N paraldehyde Chemical compound CC1OC(C)OC(C)O1 SQYNKIJPMDEDEG-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229960003868 paraldehyde Drugs 0.000 claims abstract description 14
- 239000012043 crude product Substances 0.000 claims abstract description 12
- 239000000243 solution Substances 0.000 claims abstract description 12
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000001953 recrystallisation Methods 0.000 claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 239000007787 solid Substances 0.000 claims abstract description 9
- 238000004821 distillation Methods 0.000 claims abstract description 8
- 238000001256 steam distillation Methods 0.000 claims abstract description 6
- 238000001816 cooling Methods 0.000 claims abstract description 5
- 239000000047 product Substances 0.000 claims abstract description 5
- 238000001914 filtration Methods 0.000 claims abstract description 3
- 239000011259 mixed solution Substances 0.000 claims abstract description 3
- 238000010189 synthetic method Methods 0.000 claims description 12
- 238000009413 insulation Methods 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- -1 o-NP Chemical compound 0.000 claims description 2
- 239000012047 saturated solution Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 8
- MLUCVPSAIODCQM-NSCUHMNNSA-N crotonaldehyde Chemical compound C\C=C\C=O MLUCVPSAIODCQM-NSCUHMNNSA-N 0.000 abstract description 7
- MLUCVPSAIODCQM-UHFFFAOYSA-N crotonaldehyde Natural products CC=CC=O MLUCVPSAIODCQM-UHFFFAOYSA-N 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 5
- 231100000053 low toxicity Toxicity 0.000 abstract description 3
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 abstract 2
- 239000012670 alkaline solution Substances 0.000 abstract 1
- 239000013078 crystal Substances 0.000 abstract 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 abstract 1
- 230000003472 neutralizing effect Effects 0.000 abstract 1
- 238000004321 preservation Methods 0.000 abstract 1
- 231100000004 severe toxicity Toxicity 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000007795 chemical reaction product Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical compound NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 1
- DJHGAFSJWGLOIV-UHFFFAOYSA-N Arsenic acid Chemical compound O[As](O)(O)=O DJHGAFSJWGLOIV-UHFFFAOYSA-N 0.000 description 1
- 238000006890 Doebner-Miller synthesis reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940000488 arsenic acid Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 229960000443 hydrochloric acid Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical group NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- WQEVDHBJGNOKKO-UHFFFAOYSA-K vanadic acid Chemical compound O[V](O)(O)=O WQEVDHBJGNOKKO-UHFFFAOYSA-K 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of 8-hydroxyquinaldine. The synthesis method is characterized by comprising the steps of (1) fully dissolving o-aminophenol and o-nitrophenol in a mixed solution of hydrochloric acid and acetic acid at the temperature of 30-100 DEG C, slowly dropping paraldehyde at the temperature, and performing heat preservation reaction for 1-8h after the end of dropping; (2) removing unreacted o-nitrophenol by steam distillation, cooling the remaining solution to room temperature, neutralizing with an alkaline solution, and then filtering to obtain a solid crude product; (3) performing reduced pressure distillation and re-crystallization with an ethanol water solution to obtain a high-purity crystal product. According to the method disclosed by the invention, low-toxicity paraldehyde is used for replacing crotonaldehyde with severe toxicity, and the method has the advantages of simple process and low raw material cost, and is suitable for large-scale production.
Description
Technical field
The present invention relates to a kind of synthetic method of quinoline chemical intermediate, be specifically related to the synthetic method of 8-hydroxyl quinaldine red.
Background technology
8-hydroxyl quinaldine red (2-methyl-oxine) is a kind of important fine-chemical intermediate, mainly as the mensuration of metal ion extraction agent and metal ion, also for the preparation of the synthetic and medicine intermediate of dyestuff and pigment.
At present, the technique of preparation 8-hydroxyl quinaldine red mainly be take crotonic aldehyde as raw material, under oxygenant (as o-NP, ferric oxide, vanadic acid and arsenic acid etc.) effect, with Ortho-Aminophenol, reacts and forms.Most typical is Doebner-Miller quinoline synthesis method, take o-NP as oxygenant, under mineral acid exists, and crotonic aldehyde and Ortho-Aminophenol cyclization preparation.
This class methods disadvantage is the use of highly toxic product crotonic aldehyde.Crotonic aldehyde is national control class pharmacy product, and its toxicity is very large, has extremely strong tearing property, and this is very harmful to operator and production environment, has greatly limited plant-scale production.
Summary of the invention
Goal of the invention: the object of the invention is to for the deficiencies in the prior art, provide a kind of and substitute with the low toxicity paraldehyde method that hypertoxic crotonic aldehyde prepares 8-hydroxyl quinaldine red.
Technical scheme: the synthetic method of 8-hydroxyl quinaldine red of the present invention, its reaction formula is as follows:
Synthetic method comprises the steps:
(1) synthetic: as under 30～100 ℃, Ortho-Aminophenol, o-NP fully to be dissolved in hydrochloric acid and acetic acid mixed solution, and slowly to drip paraldehyde under this temperature, finish rear insulation reaction 1～8h;
(2) the thick purification: pass into steam distillation and remove unreacted o-NP, remaining liquid cooling, to room temperature, with rear filtration, obtains solid crude product in alkali lye, and purity is 60～95%;
(3) essence is purified: filter cake, again by underpressure distillation and aqueous ethanolic solution recrystallization, obtains white high-purity crystalline product, and purity reaches more than 96%.
Preferably, the amount of substance ratio of Ortho-Aminophenol, o-NP, paraldehyde, hydrochloric acid and acetic acid is (5～1): (3～1): (3～1): (10～1): 1.
Preferably, the mass percent concentration of described hydrochloric acid is 10%～37%.
Temperature while in step (1), dripping paraldehyde is preferably 60～90 ℃.
In step (3), the optimum condition of underpressure distillation is for collecting 180～195 ℃/25～30kPa cut.
In step (3), recrystallization aqueous ethanolic solution mass percent concentration used is preferably 30～60%, during recrystallization, at aqueous ethanolic solution, adds gac or diatomite and is made into the saturated solution under high temperature, and 0.5～1h refluxes, after filtered while hot, by the filtrate crystallisation by cooling, filter, drying.
Compared with prior art, its beneficial effect is in the present invention: synthetic method of the present invention substitutes hypertoxic crotonic aldehyde with the low toxicity paraldehyde and prepares 8-hydroxyl quinaldine red, and technique is simple, raw materials cost is low, is applicable to large-scale production.
The accompanying drawing explanation
The gas chromatogram of the adjacent amino aniline of Fig. 1 reaction raw materials;
The gas chromatogram of Fig. 2 reaction raw materials o-Nitraniline;
The gas chromatogram of Fig. 3 anhydrous acetic acid;
The gas chromatogram of Fig. 4 paraldehyde;
The gas chromatogram of Fig. 5 embodiment 1 reaction product 8-hydroxyl quinaldine red crude product;
The gas chromatogram of Fig. 6 embodiment 1 reaction product 8-hydroxyl quinaldine red sterling;
The gas chromatogram of Fig. 7 embodiment 2 reaction product 8-hydroxyl quinaldine red crude products;
The gas chromatogram of Fig. 8 embodiment 2 reaction product 8-hydroxyl quinaldine red sterlings;
The gas chromatogram of Fig. 9 embodiment 3 reaction product 8-hydroxyl quinaldine red crude products;
The gas chromatogram of Figure 10 embodiment 3 reaction product 8-hydroxyl quinaldine red sterlings.
Embodiment
Below technical solution of the present invention is elaborated, but protection scope of the present invention is not limited to described embodiment.
Embodiment 1: in 2L glass reaction still, add successively 109g Ortho-Aminophenol, 30g o-NP, 500mL30% hydrochloric acid and 30g Glacial acetic acid, after making it fully dissolve under 60 ℃, slowly drip paraldehyde 90g in 0.5～5h, finish, pass into the 0.5MPa water vapor after insulation 6h and carry out steam distillation 3h, reclaim o-NP, residual solution in reactor is chilled to room temperature, add 30%NaOH and be neutralized to pH=6.8, filter, dry after hot wash, obtain tawny solid crude product 100g, productive rate 63%, purity is that 90.0%(GC detects, and sees Fig. 5).
Above crude product is carried out respectively to underpressure distillation (collecting 185～190 ℃/25kPa cut) and 20% ethanol aqueous solution recrystallization, obtain white solid 65g, productive rate 65%, purity 98.7%(GC detects, and sees Fig. 6).
Embodiment 2: in 2L glass reaction still, add successively the 109g Ortho-Aminophenol, the 40g o-NP, 500mL37% hydrochloric acid and 45g Glacial acetic acid, after making it fully dissolve under 80 ℃, slowly drip paraldehyde 105g in 0.5～5h, finish, pass into the 0.5MPa water vapor after insulation 4h and carry out steam distillation 3h, reclaim o-NP in distillate, in reactor, residual solution is chilled to room temperature, after liquid caustic soda is neutralized to pH=6, sodium carbonate is neutralized to without Bubble formation again, filter, hot wash, the dry brown solid crude product 109g that obtains, productive rate 69%, purity 86.0%(GC detects, see Fig. 7).
Above crude product is carried out respectively to underpressure distillation (collecting 185-190 ℃/25kPa cut) and 30% ethanol aqueous solution recrystallization, obtain white solid 66.5g, productive rate 61%, purity 97.6%(GC detects, and sees Fig. 8).
Embodiment 3: in 2L glass reaction still, add successively 109g Ortho-Aminophenol, 50g o-NP, 500mL19% hydrochloric acid and 45g Glacial acetic acid, after making it fully dissolve under reflux temperature, slowly drip paraldehyde 120g in 0.5～5h, finish, pass into the 0.5MPa water vapor after insulation 2h and carry out steam distillation 3h, reclaim o-NP in distillate, in reactor, residual solution is chilled to room temperature, and ammonia neutralization is to pH=6.8, filter, hot wash, obtain brown solid crude product 116g, productive rate 73%, purity is that 82.1%(GC detects, and sees Fig. 9).
Above crude product is carried out respectively to underpressure distillation (collecting 185-190 ℃/25kPa cut) and 30% ethanol aqueous solution recrystallization, obtain white solid 71.5g, productive rate 62%, purity 99.7%(GC detects, and sees Figure 10).
As mentioned above, although meaned and explained the present invention with reference to specific preferred embodiment, it shall not be construed as the restriction to the present invention self.Under the spirit and scope of the present invention prerequisite that does not break away from the claims definition, can make in the form and details various variations to it.
Claims (6)
1. the synthetic method of a 8-hydroxyl quinaldine red, is characterized in that comprising the steps:
Under (1) 30 ~ 100 ℃, Ortho-Aminophenol, o-NP fully are dissolved in hydrochloric acid and acetic acid mixed solution, and slowly drip paraldehyde under this temperature, finish rear insulation reaction 1 ~ 8h;
(2) pass into steam distillation and remove unreacted o-NP, remaining liquid cooling, to room temperature, with rear filtration, obtains solid crude product in alkali lye;
(3) again by underpressure distillation and aqueous ethanolic solution recrystallization, obtain high-purity crystalline product.
2. the synthetic method of 8-hydroxyl quinaldine red according to claim 1 is characterized in that: the amount of substance ratio of Ortho-Aminophenol, o-NP, paraldehyde, hydrochloric acid and acetic acid is (5 ~ 1): (3 ~ 1): (3 ~ 1): (10 ~ 1): 1.
3. the synthetic method of 8-hydroxyl quinaldine red according to claim 1, it is characterized in that: the mass percent concentration of described hydrochloric acid is 10% ~ 37%.
4. the synthetic method of 8-hydroxyl quinaldine red according to claim 1 is characterized in that: the temperature while in step (1), dripping paraldehyde is 60 ~ 90 ℃.
5. the synthetic method of 8-hydroxyl quinaldine red according to claim 1 is characterized in that: in step (3), the condition of underpressure distillation is for collecting 180 ~ 195 ℃/25 ~ 30kPa cut.
6. the synthetic method of 8-hydroxyl quinaldine red according to claim 1, it is characterized in that: in step (3), recrystallization aqueous ethanolic solution mass percent concentration used is 30 ~ 60%, add gac or diatomite and be made into the saturated solution under high temperature at aqueous ethanolic solution during recrystallization, 0.5 ~ 1h refluxes, after filtered while hot, by the filtrate crystallisation by cooling, filter, drying.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310489012.0A CN103483253A (en) | 2013-10-17 | 2013-10-17 | Synthesis method of 8-hydroxyquinaldine |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310489012.0A CN103483253A (en) | 2013-10-17 | 2013-10-17 | Synthesis method of 8-hydroxyquinaldine |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102134219A (en) * | 2010-12-31 | 2011-07-27 | 华东理工大学 | Preparation method of quinoline derivative |
| WO2011158189A1 (en) * | 2010-06-15 | 2011-12-22 | Centre National De La Recherche Scientifique | X-ray and gamma-photon activable organic compounds, their preparation and their uses |
-
2013
- 2013-10-17 CN CN201310489012.0A patent/CN103483253A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011158189A1 (en) * | 2010-06-15 | 2011-12-22 | Centre National De La Recherche Scientifique | X-ray and gamma-photon activable organic compounds, their preparation and their uses |
| CN102134219A (en) * | 2010-12-31 | 2011-07-27 | 华东理工大学 | Preparation method of quinoline derivative |
Non-Patent Citations (3)
| Title |
|---|
| MORGANE PETIT等: "Substitution Effect on the One- and Two-photon Sensitivity of DMAQ "Caging" Groups", 《ORG. LETT.》, vol. 14, no. 24, 6 December 2012 (2012-12-06), pages 6366 - 6369 * |
| 刘约权等: "《实验化学（上册）》", 31 October 1999, 高等教育出版社, article "实验五十二 邻硝基苯酚和对硝基苯酚的合成", pages: 242-244 * |
| 李树安等: "Doebner-Miller法合成8-羟基喹哪啶的工艺研究", 《精细石油化工》, vol. 30, no. 4, 31 July 2013 (2013-07-31), pages 22 - 24 * |
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Application publication date: 20140101 |