CN107325042B - A method of catalyzing and synthesizing -3,4 dihydropyridine -2(1H of 5- methyl) -one chemical intermediate - Google Patents
A method of catalyzing and synthesizing -3,4 dihydropyridine -2(1H of 5- methyl) -one chemical intermediate Download PDFInfo
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- CN107325042B CN107325042B CN201710671635.8A CN201710671635A CN107325042B CN 107325042 B CN107325042 B CN 107325042B CN 201710671635 A CN201710671635 A CN 201710671635A CN 107325042 B CN107325042 B CN 107325042B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/86—Oxygen atoms
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention belongs to the technical fields of organic chemical industry, it is related to 5- methyl -3,4 dihydropyridine -2 (1H) -one chemical intermediate synthetic methods, more specifically, it is related to one kind using 3- methyl -2- (4- morpholinyl) ring methyl butyrate as raw material, it is catalyzed ammonolysis synthesis pyridone, yield is not less than 80%.The preparation method for the ring fourth object catalysis ammonolysis synthesis pyridone that the invention patent provides, high slat-containing wastewater is not generated, morpholine recycling is simple, has many advantages, such as that process route is simple, product yield is high, catalyst is simply easy to recovery of applied, it is suitble to industrialized production, has broad application prospects.
Description
Technical field
The invention belongs to the technical fields of organic chemical industry, are related to 5- methyl -3,4 dihydropyridine -2 (1H) -one (referred to as: pyrrole
Pyridine ketone, No. CAS: 91936-25-3) chemical intermediate synthetic method, more particularly, to one kind with 3- methyl -2- (4-
Quinoline base) and ring methyl butyrate (referred to as: ring fourth object, No. CAS: 91936-24-2) it is raw material, through being catalyzed ammonolysis synthesis pyridone, yield
Not less than 80%.With process route, simple, catalyst inexpensively easily recycles the features of the present invention, amount of industrial wastewater is few, product is received
The advantages that rate is high.
Background technique
Pyridone shown in structure such as formula (1), is a kind of important chemical intermediate, produces the chloro- 5- of 2- through chlorination
Picoline and 2, bis- chloro-5-methypyridine of 3-, both highly important pesticide and medicine intermediate.Wherein, the chloro- 5- of 2-
Picoline can be with synthetic pesticide imidacloprid, Acetamiprid, thiacloprid, Nitenpyram etc..Bis- chloro-5-methypyridine of 2,3- can close
At highly effective pesticide haloxyfop, UC 62644, fluazinam etc..
Currently, the document of open report pyridine synthesis ketone is less, US4473696, which is described, first carries out acidolysis conjunction for ring fourth object
At 4- carboxaldehyde radicals methyl valerate, 4- carboxaldehyde radicals methyl valerate reacts to obtain pyridone again with ammonium acetate.It is main existing for this technique
During problem is ring fourth object acidolysis, a large amount of high slat-containing wastewater is generated, morpholine recovery difficult is big in industrial production, it is difficult to full
The requirement that toe ring is protected.
For this purpose, the invention patent provides a kind of preparation method of ring fourth object catalysis ammonolysis synthesis pyridone, height is not generated
Brine waste, morpholine recycling is simple, this has, and process route is simple, product yield is high, catalyst is simply easy to recovery of applied etc. excellent
Point is suitble to industrialized production, has broad application prospects.
Summary of the invention
The invention belongs to the technical fields of organic chemical industry, are related to the synthetic method of pyridone chemical intermediate, more specifically,
It is related to one kind using ring fourth object as raw material, is catalyzed ammonolysis one-step synthesis method pyridone, yield is not less than 80%.The features of the present invention
, catalyst simple with process route inexpensively easily recycling, amount of industrial wastewater is few, product yield is high and suitable industrialized production etc. is excellent
Point.Wherein, the chemical equation of pyridine synthesis ketone is expressed as follows:
One kind catalyzing and synthesizing the new method of 5- methyl -3,4 dihydropyridine -2 (1H) -one, specifically includes the following steps:
(1) ring fourth object, ammonium hydroxide and recycling catalyst are added in autoclave, and are heated to set temperature, insulation reaction
A few hours.
(2) after ammonolysis reaction, reaction solution is filtered, after filter cake is repeatedly washed with water, recycles catalyst circulation
It is applied to step (1).
(3) filtered filtrate carries out distillation recovery morpholine, finally carries out high vacuum distillation, obtains pyridone crude product.
(4) pyridone crude product is recrystallized, the pyridone product of high-purity can be obtained.
In above-mentioned steps (1), the ammonia concn is 1%~100%, and dosage is 1~20 times of ring fourth object molal quantity.
In above-mentioned steps (1), the catalyst be iron, zinc, copper, ferroso-ferric oxide, di-iron trioxide, ferrous oxide,
One of zinc oxide, copper oxide, cuprous oxide, iron chloride, frerrous chloride, zinc chloride, copper chloride and stannous chloride are a variety of
Mixture, dosage are the 0.01%~20% of ring fourth amount of substance.
In above-mentioned steps (1), the reaction temperature is 50 DEG C~140 DEG C, and the reaction time is 1~10h.
In above-mentioned steps (4), the recrystallization solvent used is benzene,toluene,xylene, chlorobenzene, o-dichlorohenzene, acetonitrile, first
Alcohol, ethyl alcohol, chloroform, ethyl acetate, hexamethylene, butanone and acetone one or more mixtures.
The present invention solves asking more than high slat-containing wastewater in the two-step method pyridine synthesis ketone technique of patent US4473696 report
Topic, it is simple to propose a kind of process route, and environmental protection, the novel synthesis of yield and high income has following advantages:
(1) process route is simple: it is one kettle way that ring fourth object, which is catalyzed ammonolysis synthesis pyridone, is reported with patent US4473696
Two-step method compare, the process route is simple, has the advantages that production cost is low, equipment investment is few；
(2) wastewater flow rate is few, environmental friendly: ring fourth object catalysis ammonolysis synthesis pyridone wastewater flow rate is few, can efficiently solve two
The big problem of wastewater flow rate in footwork acidolysis process, process route environmental protection are easy to industrialized production；
(3) product yield is high: ring fourth object is catalyzed ammonolysis synthesis pyridone, and feed stock conversion is high, and product yield is not less than
80%；
(4) catalyst is inexpensively easy to recovery of applied: catalyst involved in the present invention is common metal inorganic compound, valence
Lattice are cheap, excellent catalytic effect, and catalyst is easy to recovery of applied insoluble in reaction kettle liquid after reaction.
Specific embodiment
The present invention is better understood in order to facilitate those skilled in the art, this patent is done into one below with reference to specific example
Walk detailed description.But it should be noted that technical staff by suitably change correlated condition and achieve the object of the present invention, and
Its change it will become apparent to those skilled in the art that be regarded as being included in scope of the presently claimed invention it
It is interior.
In addition, in embodiment unless otherwise indicated, " % " therein refers both to " mass percent ".
Embodiment 1
By the ammonium hydroxide 872.85g of 340.41g ring fourth object (content 80.37%), 15%, (molar ratio of ammonium hydroxide and ring fourth object is
It 6:1) is added in the autoclave of 2L with iron powder 10.21g (catalyst amount is the 3% of ring fourth amount of substance), controls mixing speed
400r/min, 60 DEG C of insulation reaction 3h.Then, obtained reaction kettle liquid is filtered, and is repeatedly washed on a small quantity with 155.47g water
Filter cake is washed, moist catalyst 25.38g, filtrate 1365.15g are obtained.Then air-distillation filtrate recycles ammonium hydroxide 1031.85g, dense
Degree 9.78%, vacuum distillation recycle morpholine 192.43g, concentration 49.16%.It is thick that last kettle material through high vacuum distillation obtains pyridone
Product 134.51g, content 74.24%.Pyridone crude product obtains White crystal pyridone after chlorobenzene recrystallization and drying again
94.85g, purity 98.95%, yield 65.83%.
Embodiment 2-5
On the basis of embodiment 1, using the ammonium hydroxide of various concentration (molal quantity is constant), other conditions are constant.Gained knot
Fruit is as shown in table 1.
Influence of the different ammonia concn of table 1 to product yield
| Embodiment number | Ammonia concn/% | Pyridone yield/% |
| Embodiment 2 | 5 | 60.14 |
| Embodiment 3 | 10 | 63.87 |
| Embodiment 4 | 20 | 64.51 |
| Embodiment 5 | 25 | 62.95 |
Embodiment 6-10
On the basis of embodiment 1, using different catalyst systems, other conditions are constant.Acquired results such as 2 institute of table
Show.
Influence of the different catalyst system of table 2 to product yield
Embodiment 10-13
On the basis of embodiment 9, influence of the catalyst amount to product yield is investigated, the results are shown in Table 3.
Influence of 3 catalyst amount of table to product yield
| Embodiment number | Catalyst quality/ring fourth amount of substance (%) | Yield/% |
| Embodiment 10 | 1 | 70.82 |
| Embodiment 11 | 5 | 73.36 |
| Embodiment 12 | 7 | 73.68 |
| Embodiment 13 | 9 | 72.96 |
Embodiment 14-17
On the basis of embodiment 9, using different reaction temperatures, other conditions are constant.Acquired results are as shown in table 4.
Influence of the different reaction temperature of table 4 to product yield
| Embodiment number | Reaction temperature/DEG C | Yield/% |
| Embodiment 14 | 65 | 75.32 |
| Embodiment 15 | 75 | 77.28 |
| Embodiment 16 | 85 | 80.63 |
| Embodiment 17 | 95 | 78.56 |
Embodiment 18-21
On the basis of embodiment 16, using the different reaction time, other conditions are constant.Acquired results are as shown in table 5.
Influence of the different reaction time of table 5 to product yield
| Embodiment number | Reaction time/h | Pyridone yield/% |
| Embodiment 18 | 2 | 70.66 |
| Embodiment 19 | 4 | 80.21 |
| Embodiment 20 | 5 | 80.32 |
| Embodiment 21 | 6 | 80.66 |
Embodiment 22-27
On the basis of embodiment 16, investigates catalyst and apply influence of the number to product yield, other conditions are constant.Institute
The results are shown in Table 6.
6 catalyst of table applies influence of the number to product yield
| Embodiment number | Apply number | Pyridone yield/% |
| Embodiment 22 | 0 | 80.63 |
| Embodiment 23 | 1 | 80.46 |
| Embodiment 24 | 2 | 80.51 |
| Embodiment 25 | 3 | 80.36 |
| Embodiment 26 | 4 | 80.33 |
| Embodiment 27 | 5 | 80.28 |
Embodiment 28-31
On the basis of embodiment 16, recrystallization solvent is investigated to the refining effect of pyridone crude product (content 80.31%),
Other conditions are constant, and acquired results are shown in Table 7.
Refining effect of 7 recrystallization solvent of table to pyridone crude product
Claims (5)
1. the method that one kind catalyzes and synthesizes 5- methyl -3,4 dihydropyridine -2 (1H) -one, which comprises the following steps:
(1) 3- methyl -2- (4- morpholinyl) ring methyl butyrate, ammonium hydroxide and catalyst is added in autoclave, and is heated to set
Determine temperature, insulation reaction a few hours；
(2) after ammonolysis reaction, reaction solution is filtered, after filter cake is repeatedly washed with water, recycling catalyst circulation is applied
To step (1)；
(3) filtered filtrate carries out distillation recovery morpholine, finally carries out high vacuum distillation, obtains 5- methyl -3,4 dihydro pyrrole
Pyridine -2 (1H) -one crude product；
(4) 5- methyl -3,4 dihydropyridine -2 (1H) -one crude product is recrystallized, 5- methyl -3,4 dihydro pyrrole can be obtained
Pyridine -2 (1H) -one product,
The catalyst is iron, zinc, copper, ferroso-ferric oxide, di-iron trioxide, ferrous oxide, zinc oxide, copper oxide, oxidation
One of cuprous, iron chloride, frerrous chloride, zinc chloride, copper chloride and stannous chloride or a variety of mixtures.
2. the method according to claim 1 for catalyzing and synthesizing 5- methyl -3,4 dihydropyridine -2 (1H) -one, feature exist
In in above-mentioned steps (1), the ammonia concn is 1%~100%, and dosage is 1~20 times of ring fourth object molal quantity.
3. the method according to claim 1 for catalyzing and synthesizing 5- methyl -3,4 dihydropyridine -2 (1H) -one, feature exist
In in above-mentioned steps (1), the catalyst amount is the 0.01% of 3- methyl -2- (4- morpholinyl) ring methyl butyrate quality
~20%.
4. the method according to claim 1 for catalyzing and synthesizing 5- methyl -3,4 dihydropyridine -2 (1H) -one, feature exist
In in above-mentioned steps (1), the reaction temperature is 50 DEG C~140 DEG C, and the reaction time is 1~10h.
5. the method according to claim 1 for catalyzing and synthesizing 5- methyl -3,4 dihydropyridine -2 (1H) -one, feature exist
In in above-mentioned steps (4), the recrystallization solvent used is benzene,toluene,xylene, chlorobenzene, o-dichlorohenzene, acetonitrile, methanol, second
Alcohol, chloroform, ethyl acetate, hexamethylene, butanone and acetone one or more mixtures.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4473696A (en) * | 1982-10-07 | 1984-09-25 | Ici Americas Inc. | Synthesis of 2-substituted-5-methyl-pyridines |
| US4612377A (en) * | 1983-03-30 | 1986-09-16 | Imperial Chemical Industries Plc | Preparation of 2-chloro-5-methylpyridine |
| US4645839A (en) * | 1982-12-17 | 1987-02-24 | Ici Americas Inc. | Sulphur dehydrogenation process to yield 5-methyl-2-pyridone |
| DE3630613A1 (en) * | 1986-09-09 | 1988-03-17 | Basf Ag | Substituted 3,4-dihydro-2-pyridones and a process for the preparation of 3,4-dihydro-2-pyridones and 3-pyrroline-2-ones |
| CN106117128A (en) * | 2016-06-26 | 2016-11-16 | 江苏扬农化工集团有限公司 | A kind of micro passage reaction prepares the method for pyridone chlorine addition product continuously |
-
2017
- 2017-08-08 CN CN201710671635.8A patent/CN107325042B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4473696A (en) * | 1982-10-07 | 1984-09-25 | Ici Americas Inc. | Synthesis of 2-substituted-5-methyl-pyridines |
| US4645839A (en) * | 1982-12-17 | 1987-02-24 | Ici Americas Inc. | Sulphur dehydrogenation process to yield 5-methyl-2-pyridone |
| US4612377A (en) * | 1983-03-30 | 1986-09-16 | Imperial Chemical Industries Plc | Preparation of 2-chloro-5-methylpyridine |
| DE3630613A1 (en) * | 1986-09-09 | 1988-03-17 | Basf Ag | Substituted 3,4-dihydro-2-pyridones and a process for the preparation of 3,4-dihydro-2-pyridones and 3-pyrroline-2-ones |
| CN106117128A (en) * | 2016-06-26 | 2016-11-16 | 江苏扬农化工集团有限公司 | A kind of micro passage reaction prepares the method for pyridone chlorine addition product continuously |
Non-Patent Citations (2)
| Title |
|---|
| New routes to nitrogen heterocycles through intramolecular amidocarbonylation of alkenamides catalyzed by rhodium complexes;Iwao Ojima等;《Tetrahedron Letters》;19891231;第30卷(第46期);第6283-6286页 * |
| New synthesis of nitrogen heterocycles through amide-directed hydrocarbonylation of alkenamides catalyzed by rhodium complexes;Iwao Ojima等;《Journal of Organic Chemistry》;19911231;第56卷(第6期);第2024-2030页 * |
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