CN110204522A - A kind of preparation method of 5,6- dihydro -2H- pyran-2-one - Google Patents
A kind of preparation method of 5,6- dihydro -2H- pyran-2-one Download PDFInfo
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- CN110204522A CN110204522A CN201910487383.2A CN201910487383A CN110204522A CN 110204522 A CN110204522 A CN 110204522A CN 201910487383 A CN201910487383 A CN 201910487383A CN 110204522 A CN110204522 A CN 110204522A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
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Abstract
The present invention relates to the new synthesis routes of one kind 5,6- dihydro -2H- pyran-2-one, using 3- (benzyloxy) propionic acid as raw material, synthesize 5,6- dihydro -2H- pyran-2-one through chlorination reaction, condensation reaction, cyclic reduction reaction, four step high yield of elimination reaction.5,6- dihydro -2H- pyran-2-one preparation method provided by the invention be a kind of high yield, low cost, environmental protection, it is easy to operate, be suitable for industrialized preparation method.
Description
Technical field
The present invention relates to pharmaceutical chemistry synthesis technical fields, and in particular to the preparation of one kind 5,6- dihydro -2H- pyran-2-one
Method.
Background technique
5,6- dihydro -2H- pyran-2-ones are important medicine intermediate, on the ground that field of medicinal chemistry has its important
Position.With the development of the society, the development of pharmaceutical synthesis field, to the development & production of 5,6- dihydro -2H- pyran-2-one also such as
The progress of the fire such as bitter edible plant, existing document report crosses synthetic route, as shown in Fig. 2, present in technical problem: 1. total recovery is non-
It is often low, only 10%.2. third step, which uses PCC (pyridine chlorochromate), can generate a large amount of chromic salts waste, pollute, improves
Cost is not easy to industrialize.
Summary of the invention
The technical problem to be solved by the present invention is to the shortcomings that overcoming the prior art, provide one kind 5,6- dihydro -2H- pyrrole
Mutter the preparation method of -2- ketone, should preparation method is simple, preparation cost is cheap, and is a kind of high yield, environmental protection, is suitable for work
The preparation method of industry.
One kind 5,6- dihydro -2H- pyran-2-one preparation method, comprising the following steps:
Step 1: under nitrogen protection, 3- (benzyloxy) propionic acid, solvent is added in reaction flask, acylated examination is added dropwise under ice bath
Agent, drop finish, room temperature reaction, after reaction, are evaporated under reduced pressure solvent, obtain intermediate 1；
Step 2: being added 2,2- dimethyl -1,3- dioxanes -4,6- diketone, solvent and pyridine in reaction flask, cooling,
The dichloromethane solution of intermediate 1 is added dropwise, drop finishes, and reacts at room temperature, washing, and salt water washing is dry, is evaporated under reduced pressure solvent, obtains
186g intermediate 2；
Step 3: being added intermediate 2, palladium-carbon catalyst, solvent in autoclave, and nitrogen displacement is passed through hydrogen to certain
Pressure, temperature reaction, after reaction, nitrogen displacement, filtering are evaporated under reduced pressure solvent, obtain intermediate 3；
Step 4: the addition intermediate 3, p-methyl benzenesulfonic acid, solvent in reaction flask, temperature reaction, after reaction, water
It washes, it is dry, it is evaporated under reduced pressure solvent, obtains product.
Preferably, solvent described in step 1 is methylene chloride, dichloroethanes, toluene.
Preferably, solvent described in step 2 is methylene chloride, chloroform, tetrahydrofuran.
Preferably, the quality of palladium-carbon catalyst described in step 3 is the 5~15% of material quality.
Preferably, solvent described in step 3 is tetrahydrofuran, ethyl acetate.
Preferably, pressure limit described in step 3 is 1~20atm.
Preferably, temperature reaction temperature described in step 3 is 30~60 DEG C.
Preferably, solvent described in step 4 is benzene, toluene.
Preferably, temperature reaction temperature described in step 4 is 80~120 DEG C.
The beneficial effects of the present invention are:
(1) at low cost；It the use of cheap and easily-available 3- (benzyloxy) propionic acid is that raw material greatly reduces synthesis cost；
(2) high income；The route total recovery 51% is much higher than traditional route 10%；
(3) it is convenient for industrialized production；The reaction route is mild, easy to operate, convenient for operation.
Detailed description of the invention
Fig. 1 is 5,6- of embodiment of the present invention dihydro -2H- pyran-2-one preparation method route map；
Fig. 2 is 5,6- dihydro -2H- pyran-2-one preparation method route map in the prior art.
Specific embodiment
With reference to embodiments, the technical solution in the present invention is clearly and completely described.Based in the present invention
Embodiment, every other embodiment obtained by those of ordinary skill in the art without making creative efforts, all
Belong to the scope of protection of the invention.
Embodiment 1
Step 1: under nitrogen protection, 180g 3- (benzyloxy) propionic acid, 1L methylene chloride are added in reaction flask, under ice bath
95g oxalyl chloride is added dropwise, drop finishes, and reacts at room temperature 3 hours, after reaction, is evaporated under reduced pressure solvent, obtains 180g intermediate 1, receives
Rate: 90%.
Step 2: 109g 2,2- dimethyl -1,3- dioxanes -4,6- diketone, 800ml dichloromethane are added in reaction flask
Alkane and 146ml pyridine are cooled to 5 DEG C, and the dichloromethane solution of 150g intermediate 1 is added dropwise, and drop finishes, and react at room temperature 4 hours, water
It washes, salt water washing, it is dry, it is evaporated under reduced pressure solvent, obtains 186g intermediate 2, yield: 80%.
Step 3: being added 180g intermediate 2,18g palladium-carbon catalyst, 700ml tetrahydrofuran in autoclave, and nitrogen is set
It changes, is passed through hydrogen to 20atm, 50 DEG C of 8 hours of reaction, after reaction, nitrogen displacement, filtering are evaporated under reduced pressure solvent, obtain
58g intermediate 3, yield: 85%.
Step 4: being added 40g intermediate 3,77g p-methyl benzenesulfonic acid, 200ml toluene in reaction flask, and 80 DEG C of reactions are 5 small
When, after reaction, wash, it is dry, it is evaporated under reduced pressure solvent, obtains 28g product 5, yield: 83%.
The above described is only a preferred embodiment of the present invention, be not intended to limit the scope of the present invention,
Therefore all technical solutions formed using equivalent substitution or equivalent transformation, it falls within the scope of protection required by the present invention.
Claims (9)
1. one kind 5,6- dihydro -2H- pyran-2-one preparation method, which comprises the following steps:
Step 1: under nitrogen protection, 3- (benzyloxy) propionic acid, solvent is added in reaction flask, acylating reagent is added dropwise under ice bath, drips
Finish, room temperature reaction, after reaction, is evaporated under reduced pressure solvent, obtains intermediate 1；
Step 2: being added 2,2- dimethyl -1,3- dioxanes -4,6- diketone, solvent and pyridine in reaction flask, cools down, and is added dropwise
The dichloromethane solution of intermediate 1, drop finish, and react at room temperature, washing, and salt water washing is dry, are evaporated under reduced pressure solvent, obtain in 186g
Mesosome 2；
Step 3: being added intermediate 2, palladium-carbon catalyst, solvent in autoclave, nitrogen displacement, is passed through hydrogen to certain pressure,
Temperature reaction, after reaction, nitrogen displacement, filtering are evaporated under reduced pressure solvent, obtain intermediate 3；
Step 4: being added intermediate 3, p-methyl benzenesulfonic acid, solvent in reaction flask, and temperature reaction is washed after reaction, done
It is dry, it is evaporated under reduced pressure solvent, obtains product.
2. a kind of 5,6- dihydro -2H- pyran-2-one preparation method according to claim 1, it is characterised in that: step 1
Described in solvent be methylene chloride, dichloroethanes, toluene.
3. a kind of 5,6- dihydro -2H- pyran-2-one preparation method according to claim 1, it is characterised in that: step 2
Described in solvent be methylene chloride, chloroform, tetrahydrofuran.
4. a kind of 5,6- dihydro -2H- pyran-2-one preparation method according to claim 1, it is characterised in that: step 3
Described in palladium-carbon catalyst quality be material quality 5~15%.
5. a kind of 5,6- dihydro -2H- pyran-2-one preparation method according to claim 1, it is characterised in that: step 3
Described in solvent be tetrahydrofuran, ethyl acetate.
6. a kind of 5,6- dihydro -2H- pyran-2-one preparation method according to claim 1, it is characterised in that: step 3
Described in pressure limit be 1~20atm.
7. a kind of 5,6- dihydro -2H- pyran-2-one preparation method according to claim 1, it is characterised in that: step 3
Described in temperature reaction temperature be 30~60 DEG C.
8. a kind of 5,6- dihydro -2H- pyran-2-one preparation method according to claim 1, it is characterised in that: step 4
Described in solvent be benzene, toluene.
9. a kind of 5,6- dihydro -2H- pyran-2-one preparation method according to claim 1, it is characterised in that: step 4
Described in temperature reaction temperature be 80~120 DEG C.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201910487383.2A CN110204522B (en) | 2019-06-05 | 2019-06-05 | Preparation method of 5, 6-dihydro-2H-pyran-2-one |
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| CN201910487383.2A CN110204522B (en) | 2019-06-05 | 2019-06-05 | Preparation method of 5, 6-dihydro-2H-pyran-2-one |
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| CN110204522A true CN110204522A (en) | 2019-09-06 |
| CN110204522B CN110204522B (en) | 2022-04-05 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018005806A2 (en) * | 2016-06-30 | 2018-01-04 | Ardra Bio Inc. | Methods and microorganisms for producing flavors and fragrance chemicals |
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2019
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018005806A2 (en) * | 2016-06-30 | 2018-01-04 | Ardra Bio Inc. | Methods and microorganisms for producing flavors and fragrance chemicals |
Non-Patent Citations (2)
| Title |
|---|
| LEONARD LERME等: "The synthesis of P-keto lactones via cyclization of P-keto ester dianions or the cyclization of Meldrum"s acid derivatives", 《CAN. J. CHEM.》 * |
| 黄宪 等: "4,5,6-三取代-2H-吡喃-2-酮的简便合成法", 《有机化学》 * |
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