CN107325042A - One kind catalyzes and synthesizes the dihydropyridine 2 of 5 methyl 3,4（1H）The method of ketone chemical intermediate - Google Patents
One kind catalyzes and synthesizes the dihydropyridine 2 of 5 methyl 3,4（1H）The method of ketone chemical intermediate Download PDFInfo
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- CN107325042A CN107325042A CN201710671635.8A CN201710671635A CN107325042A CN 107325042 A CN107325042 A CN 107325042A CN 201710671635 A CN201710671635 A CN 201710671635A CN 107325042 A CN107325042 A CN 107325042A
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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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Abstract
The invention belongs to the technical field of organic chemical industry, it is related to 5 methyl 3, the method of (1H) the ketone chemical intermediate of 4 dihydropyridine 2 synthesis, more specifically, it is related to one kind using 3 methyl 2 (4 morpholinyl) ring methyl butyrates as raw material, through being catalyzed ammonolysis synthesis pyridone, yield is not less than 80%.The ring fourth thing that patent of the present invention is provided is catalyzed the preparation method of ammonolysis synthesis pyridone, high slat-containing wastewater is not produced, morpholine reclaims simple, have the advantages that process route is simple, product yield is high, catalyst is simple easy to recovery of applied, it is adapted to industrialized production, has broad application prospects.
Description
Technical field
The invention belongs to the technical field of organic chemical industry, it is related to 5- methyl -3,4 dihydropyridine -2 (1H) -one (referred to as：Pyrrole
Pyridine ketone, No. CAS：91936-25-3) the method for chemical intermediate synthesis, more particularly, to one kind with 3- methyl -2- (4-
Quinoline base) ring methyl butyrate is (referred to as：Ring fourth thing, No. CAS：91936-24-2) it is raw material, through being catalyzed ammonolysis synthesis pyridone, yield
It is not less than 80%.The features of the present invention has that process route is simple, catalyst is inexpensively easily reclaimed, amount of industrial wastewater is few, product is received
The advantages of rate is high.
Background technology
Pyridone, is a kind of important chemical intermediate, it can generate the chloro- 5- of 2- through chlorination shown in structure such as formula (1)
Picoline and the chloro-5-methypyridine of 2,3- bis-, both highly important agricultural chemicals and medicine intermediate.Wherein, the chloro- 5- of 2-
Picoline can be with synthetic pesticide imidacloprid, Acetamiprid, thiacloprid, Nitenpyram etc..The chloro-5-methypyridines of 2,3- bis- can be closed
Into highly effective pesticide haloxyfop, UC 62644, fluazinam etc..
At present, the document of open report pyridine synthesis ketone is less, and US4473696 is described first carries out acidolysis conjunction by ring fourth thing
Into 4- carboxaldehyde radicals methyl valerates, 4- carboxaldehyde radicals methyl valerate obtains pyridone with ammonium acetate reaction again.It is main that this technique is present
During problem is ring fourth thing acidolysis, morpholine recovery difficult in substantial amounts of high slat-containing wastewater, industrial production is generated big, it is difficult to full
The requirement that toe ring is protected.
Therefore, patent of the present invention provides the preparation method that a kind of ring fourth thing is catalyzed ammonolysis synthesis pyridone, height is not produced
Brine waste, morpholine reclaims simple, should be with process route is simple, product yield is high, catalyst is simply easy to recovery of applied etc. excellent
Point, is adapted to industrialized production, has broad application prospects.
The content of the invention
The invention belongs to the technical field of organic chemical industry, it is related to the synthetic method of pyridone chemical intermediate, more specifically,
It is related to one kind using ring fourth thing as raw material, through being catalyzed ammonolysis one-step synthesis method pyridone, yield is not less than 80%.The features of the present invention
With process route is simple, inexpensively easily recovery, few, the high and suitable industrialized production of product yield of amount of industrial wastewater etc. are excellent for catalyst
Point.Wherein, the chemical equation of pyridine synthesis ketone is expressed as follows：
One kind catalyzes and synthesizes the new method of 5- methyl -3,4 dihydropyridine -2 (1H) -one, specifically includes following steps：
(1) ring fourth thing, ammoniacal liquor and recovery catalyst are added in autoclave, and are heated to design temperature, insulation reaction
A few hours.
(2) after ammonolysis reaction terminates, reaction solution is filtered, after filter cake is repeatedly washed with water, catalyst circulation is reclaimed
It is applied to step (1).
(3) filtrate after filtering carries out distillation recovery morpholine, finally carries out high vacuum distillation, obtains pyridone crude product.
(4) pyridone crude product is recrystallized, you can obtain the pyridone product of high-purity.
In above-mentioned steps (1), described ammonia concn is 1%~100%, and consumption is 1~20 times of ring fourth thing molal quantity.
In above-mentioned steps (1), described catalyst is iron, zinc, copper, ferroso-ferric oxide, di-iron trioxide, ferrous oxide,
One or more in zinc oxide, cupric oxide, cuprous oxide, iron chloride, frerrous chloride, zinc chloride, copper chloride and stannous chloride
Mixture, consumption is the 0.01%~20% of ring fourth amount of substance.
In above-mentioned steps (1), described 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, ethanol, chloroform, ethyl acetate, hexamethylene, one or more mixtures of butanone and acetone.
The present invention solves asking more than high slat-containing wastewater in the two-step method pyridine synthesis ketone technique that patent US4473696 is reported
The novel synthesis of topic, it is proposed that a kind of process route is simple, environmental protection, yield and high income, it possesses advantages below：
(1) process route is simple：Ring fourth thing catalysis ammonolysis synthesis pyridone is one kettle way, 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 thing catalysis ammonolysis synthesis pyridone wastewater flow rate is few, can efficiently solve two
The problem of wastewater flow rate is big in footwork acidolysis process, process route environmental protection, it is easy to industrialized production；
(3) product yield is high：Ring fourth thing 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：The catalyst being related in the present invention is common metal inorganic compound, valency
Lattice are cheap, excellent catalytic effect, and react end rear catalyst insoluble in reaction kettle liquid, easy to recovery of applied.
Embodiment
Those skilled in the art are better understood from the present invention for convenience, this patent are done into one with reference to specific example
The detailed description of step.But, it should be noted that technical staff realizes the purpose of the present invention by suitably changing correlated condition, 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 is referred both to " mass percent ".
Embodiment 1
By 340.41g ring fourth things (content 80.37%), 15% ammoniacal liquor 872.85g, (mol ratio of ammoniacal liquor and ring fourth thing is
6:1) it is added to iron powder 10.21g (catalyst amount is the 3% of ring fourth amount of substance) in 2L autoclave, controls mixing speed
400r/min, 60 DEG C of insulation reaction 3h.Then, obtained reaction kettle liquid is subjected to suction filtration, and repeatedly washed on a small quantity with 155.47g water
Filter cake is washed, moist catalyst 25.38g, filtrate 1365.15g is obtained.Then air-distillation filtrate, reclaims ammoniacal liquor 1031.85g, dense
Degree 9.78%, vacuum distillation reclaims morpholine 192.43g, concentration 49.16%.It is thick that last kettle material obtains pyridone through high vacuum distillation
Product 134.51g, content is 74.24%.Pyridone crude product obtains White crystal pyridone after recrystallizing and dry through chlorobenzene again
94.85g, purity 98.95%, yield is 65.83%.
Embodiment 2-5
On the basis of embodiment 1, using the ammoniacal liquor (molal quantity is constant) of various concentrations, 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 is numbered | 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.The acquired results such as institute of table 2
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, 3 are the results are shown in Table.
Influence of the catalyst amount of table 3 to product yield
| Embodiment is numbered | 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 is numbered | 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 is numbered | 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, investigate catalyst and apply mechanically influence of the number of times to product yield, other conditions are constant.Institute
Obtain result as shown in table 6.
The catalyst of table 6 applies mechanically influence of the number of times to product yield
| Embodiment is numbered | Apply mechanically number of times | 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, refining effect of the recrystallization solvent to pyridone crude product (content 80.31%) is investigated,
Other conditions are constant, and acquired results are shown in Table 7.
Refining effect of the recrystallization solvent of table 7 to pyridone crude product
Claims (5)
1. the method that one kind catalyzes and synthesizes 5- methyl -3,4 dihydropyridine -2 (1H) -one, it is characterised in that comprise the following steps：
(1) 3- methyl -2- (4- morpholinyls) ring methyl butyrate, ammoniacal liquor and catalyst is added in autoclave, and is heated to set
Constant temperature degree, insulation reaction a few hours；
(2) after ammonolysis reaction terminates, reaction solution is filtered, after filter cake is repeatedly washed with water, catalyst recycled is reclaimed
To step (1)；
(3) filtrate after filtering carries out distillation recovery morpholine, finally carries out high vacuum distillation, obtains 5- methyl -3,4 dihydro pyrroles
Pyridine -2 (1H) -one crude product；
(4) 5- methyl -3,4 dihydropyridine -2 (1H) -one crude product is recrystallized, you can obtain 5- methyl -3,4 of high-purity
Dihydropyridine -2 (1H) -one product.
2. the method according to claim 1 for catalyzing and synthesizing 5- methyl -3,4 dihydropyridine -2 (1H) -one, its feature exists
In in above-mentioned steps (1), described ammonia concn is 1%~100%, and consumption is 1~20 times of ring fourth thing molal quantity.
3. the method according to claim 1 for catalyzing and synthesizing 5- methyl -3,4 dihydropyridine -2 (1H) -one, its feature exists
In in above-mentioned steps (1), described catalyst is iron, zinc, copper, ferroso-ferric oxide, di-iron trioxide, ferrous oxide, oxidation
One or more mixing in zinc, cupric oxide, cuprous oxide, iron chloride, frerrous chloride, zinc chloride, copper chloride and stannous chloride
Thing, consumption is the 0.01%~20% of 3- methyl -2- (4- morpholinyls) ring methyl butyrate quality.
4. the method according to claim 1 for catalyzing and synthesizing 5- methyl -3,4 dihydropyridine -2 (1H) -one, its feature exists
In in above-mentioned steps (1), described 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, its feature exists
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, one or more mixtures of butanone and acetone.
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| CN201710671635.8A CN107325042B (en) | 2017-08-08 | 2017-08-08 | A method of catalyzing and synthesizing -3,4 dihydropyridine -2(1H of 5- methyl) -one chemical intermediate |
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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 |
|---|
| IWAO OJIMA等: "New routes to nitrogen heterocycles through intramolecular amidocarbonylation of alkenamides catalyzed by rhodium complexes", 《TETRAHEDRON LETTERS》 * |
| IWAO OJIMA等: "New synthesis of nitrogen heterocycles through amide-directed hydrocarbonylation of alkenamides catalyzed by rhodium complexes", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
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