CN105646209A - Synthesizing method of ethyl 2-oxocyclopentylacetate - Google Patents
Synthesizing method of ethyl 2-oxocyclopentylacetate Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C67/32—Decarboxylation
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Abstract
The invention discloses a synthesizing method of ethyl 2-oxocyclopentylacetate and belongs to the technical field of organic synthesizing. Diethyl adipate is used as raw material, and condensation, substitution, hydrolysis decarboxylation and esterification are performed to obtain ethyl 2-oxocyclopentylacetate. Sodium is dissolved into excessive anhydrous ethanol to form the ethanol liquid of sodium ethoxide, the ethanol liquid of the sodium ethoxide is allowed for standing to reach room temperature, then zirconium dioxide is added to catalyze the cyclization reaction of the diethyl adipate, and lithium chloride is added to catalyze the esterification reaction. The synthesizing method has the advantages that reaction conditions and reaction process are optimized, reaction time is shortened, use of toluene solvent and anhydrous ethanol is reduced, the reaction conditions are mild, yield is increased, process cost is lowered at the same time, and high economic benefits are achieved.
Description
Technical field:
The present invention relates to the synthetic method of a kind of 2-oxocyclopentyl ethyl acetate, belong to the field of chemical synthesis.
Background technology:
2-oxocyclopentyl ethyl acetate is to prepare DP receptor antagonist to draw the important intermediate of sieve logical sequence, mainly has following several at present both at home and abroad about its synthetic method:
Document Tetrahedron, 1981, vol.37, No.25,4503-4508 discloses a kind of method adopting Ketocyclopentane and nafoxidine generation enamine to react again with bromoacetate, and the method yield is relatively low, and uses the benzene that toxicity is bigger as solvent.
Adopting the method that Ketocyclopentane reacts with bromoacetate when lithium diisopropylamine exists, yield is higher however it is necessary that the cryogenic conditions adopting-78 DEG C, high for manufacturing technique requirent, is unfavorable for raising and the industrialization promotion of economic benefit.
Adopting Ketocyclopentane carboxylic acid, ethyl ester is raw material, 2-oxocyclopentyl ethyl acetate is obtained through replacement, hydrolysis decarboxylation, esterification three-step reaction, but the yield of the method is relatively low, the yield of each step respectively 27.5%, 75.2%, 96.4%, overall yield of reaction is 27.5%.
J.Chem.Soc et al. is prepared Ketocyclopentane carboxylic acid, ethyl ester by the own diester of adipic acid; 2-oxocyclopentyl ethyl acetate is obtained then through replacement, hydrolysis decarboxylation, esterification four-step reaction; the total recovery of the method is 47.7-54.0%; branch's yield respectively 86%, 85%, 87%, 90%, but the method reactions steps is more, it is necessary to repeatedly carry out post processing purification; the three wastes produced are more; and expend substantial amounts of manpower and materials, additionally react with hypertoxic benzene for solvent, be unfavorable for labor protection.
Chinese invention patent CN201310012765.2 discloses a kind of method preparing 2-oxocyclopentyl ethyl acetate: with diethylene adipate for initiation material, " treating different things alike " method of employing, obtain 2-oxocyclopentyl acetic acid through condensation, replacement, hydrolysis deacidification, obtain 2-oxocyclopentyl ethyl acetate then through esterification. this inventive method overcomes the shortcomings of existing synthetic method, there is raw material be easy to get, convenient post-treatment, with short production cycle, " three wastes " discharge is few, it is suitable for the advantages such as large-scale production, but the method is on the disclosed synthetic method basis of J.Chem.Soc et al., Simplified flowsheet step, adopt and diethylene adipate and sodium are merged at toluene medium ring and is directly added into ethyl chloroacetate, after hydrolysis decarboxylation, it is made directly esterification without purification simultaneously, by simplifying operating procedure thus reducing the production cycle, lifting for productivity does not have too many improvement and raising, economic benefit is still optimistic not.
Summary of the invention:
Technical problem solved by the invention:
The present invention is directed to the deficiencies in the prior art, with diethylene adipate for initiation material, by optimizing reaction condition, add catalysts preparation synthesis 2-oxocyclopentyl acetic acid, the productivity of reaction can be effectively improved, and reduce reaction temperature, improve industrial benefit, have simultaneously raw material be easy to get, convenient post-treatment, advantage with short production cycle, be beneficial to industrialization promotion.
The present invention provides following technical scheme:
The synthetic method of a kind of 2-oxocyclopentyl ethyl acetate, with diethylene adipate for raw material, obtains 2-oxocyclopentyl ethyl acetate through condensation, replacement, hydrolysis decarboxylation, esterification, including following operating procedure:
The first step: 1mol sodium is dissolved in the ethanol forming Sodium ethylate in excessive dehydrated alcohol, the alcoholic solution of Sodium ethylate is stood to room temperature and adds zirconium dioxide, Ketocyclopentane Ethyl formate is obtained after adding toluene 500ml and diethylene adipate 0.7mol, 40-55 DEG C of reaction 5-6h after stirring 10-15 minute;
Second step: drip ethyl chloroacetate 0.7mol in the Ketocyclopentane Ethyl formate obtained in the first step, control temperature and be 90-95 DEG C, time for adding is 30min, keeps 90-95 DEG C of thermotonus 2-3h, be cooled to room temperature treatment and obtain crude product ester after reaction after being added dropwise to complete;
3rd step: the hydrochloric acid solution 400ml stirring point adding 5mol/L in the crude product ester obtained by second step takes organic layer, water layer adopts methylbenzene extraction, adopt the concentration of saturated common salt solution washing to obtain brown liquid after merging organic layer, brown liquid is filtrated to get after drying crude brown oil;
4th step: is added in the crude brown oil that the 3rd step is obtained ethanol solution 400-500mL, the hydrochloric acid solution 1ml of 5mol/L, lithium chloride, back flow reaction 6h under 60-70 DEG C of temperature conditions, ethyl acetate 400ml dilution is added after concentration, dry, sucking filtration after adopting saturated sodium carbonate liquor to wash, concentrating under reduced pressure collects 115-120 DEG C of fraction, obtains 2-oxocyclopentyl ethyl acetate.
Preferably, adding zirconium dioxide in the described first step, the addition of zirconium dioxide is 2-5g;
Described zirconium dioxide is analytical pure, its active constituent content >=99%, dioxide-containing silica��0.01%, content of titanium dioxide��0.005%, iron oxide content��0.005%, calcium oxide content��0.05%, content of magnesia��0.05%.
Preferably, adding lithium chloride in described 4th step is analytically pure anhydrous Lithium chloride, and its addition is 0.05mol, and lithium chloride active constituent content is be more than or equal to 99%.
Preferably, the alcoholic solution of Sodium ethylate is stood to room temperature by the described first step and adds zirconium dioxide, after stirring 15 minutes, add toluene 500ml and diethylene adipate 0.7mol, after 50 DEG C of reaction 5-6h, obtain Ketocyclopentane Ethyl formate.
Preferably, keep 95 DEG C of thermotonus 2h after described second step is added dropwise to complete to ethyl chloroacetate, be cooled to room temperature treatment after reaction and obtain crude product ester.
Preferably, described 4th step is added the hydrochloric acid solution 1ml of ethanol solution 400mL, 5mol/L, lithium chloride, back flow reaction 6h under 60 DEG C of temperature conditions in the crude brown oil that the 3rd step obtains.
Zirconium dioxide is mainly used in piezoelectric ceramics goods, domestic ceramics, refractory material and the zirconia block of precious metal melting, zirconium pipe, crucible etc., is also used for producing steel and non-ferrous metal, optical glass and zirconia fiber; Zirconium dioxide can be used as the inert filler of plastics, rubber, latex etc., extender, suitable in sebific duct, adhesive tape, pressing, extruded product and footwear etc., also serve as the filler of epoxy adhesive and fluid sealant, also it is the conventional raw material manufacturing pottery, enamel and glass drying oven, for manufacturing function ceramics and structural ceramics, or make grinding-material.
Most of cyclization processes to come off a little molecule, in order to promote micromolecular coming off, is often required to use condensation accelerator. Such as: dehydration condensation, often carry out in concentrated sulfuric acid; Dehydrohalogenation cyclization is often required to acid binding agent, sometimes also with copper catalyst; Dehydrogenation cyclization is everlasting under aluminum trichloride (anhydrous), disulphur dichloride or potassium hydroxide exist and is carried out, and sometimes also to add mild oxidation agent; Dealcoholysis or deamination cyclization, carry out under the catalytic action of acid or alkali of being everlasting. Diethylene adipate and sodium vigorous reaction in benzene and dehydrated alcohol in prior art, response time is long, reaction yield is low, the present invention adopts zirconium dioxide as catalyst, metallic sodium is dissolved in the ethanol generating Sodium ethylate in excessive dehydrated alcohol is molten has a strong basicity, and zirconium dioxide produces zirconates, stable chemical nature with alkali congruent melting, this process has good promotion process for the ring-closure reaction of catalysis diethyl adipate, improves ring-closure reaction yield.
Lithium chloride is white crystal, soluble in water, the organic solvent such as ethanol, acetone, pyridine, is mainly used as scaling powder, desiccant, chemical reagent, and is used for the fields such as fireworks processed, aneroid battery and lithium metal.In conventional art, in final step, esterification carries out in the alcoholic solution containing sulphuric acid, hydrogen chloride or thionyl chloride, esterification side reaction is more, response time is long, and the present invention adds concentrated hydrochloric acid solution and a small amount of lithium chloride in ethanol solution, it is possible to be effectively improved reaction yield.
Beneficial effects of the present invention:
1. the present invention adopts zirconium dioxide as catalyst, metallic sodium is dissolved in that the ethanol generating Sodium ethylate in excessive dehydrated alcohol is molten has strong basicity, zirconium dioxide produces zirconates with alkali congruent melting, stable chemical nature, this process has good promotion process for the ring-closure reaction of catalysis diethyl adipate, improves ring-closure reaction yield.
2. the present invention adds concentrated hydrochloric acid solution and a small amount of lithium chloride in ethanol solution, it is possible to effectively catalytic esterification, improves reaction yield.
3. the present invention optimizes reaction condition and reaction process, shortens the response time, decreases the application of toluene solvant and dehydrated alcohol, and reaction condition is gentleer, improves yield, reduces process costs simultaneously, has higher economic benefit.
Detailed description of the invention:
Below embodiments of the invention being described in detail, the present embodiment is carried out under premised on inventive technique scheme, gives detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment. The experimental program of unreceipted actual conditions in embodiment, generally conventionally condition or manufacturer it is proposed that condition implement.
Catalyst experiment one:
Experiment purpose: zirconia catalyst ring-closure reaction
Experimental technique: 1mol sodium is dissolved in the ethanol forming Sodium ethylate in excessive dehydrated alcohol, stands the alcoholic solution of Sodium ethylate to room temperature and adds zirconium dioxide, add toluene 500ml and diethylene adipate after stirring 10 minutes
0.7mol, obtains Ketocyclopentane Ethyl formate after 50 DEG C of reaction 6h.
Table one: zirconium dioxide addition affects result for Ketocyclopentane Ethyl formate yield.
| Experiment number | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
| Zirconium dioxide (g) | 0 | 0.5 | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Productivity (%) | 83.2 | 86.7 | 87.1 | 91.3 | 92.5 | 94.6 | 91.8 | 87.3 | 87.8 |
Adding zirconium dioxide and can be effectively improved the productivity of Ketocyclopentane Ethyl formate, wherein when zirconium dioxide addition is when 2-5g, the productivity of Ketocyclopentane Ethyl formate can reach more than 90%, has higher economic benefit.
Experiment purpose: lithium chloride catalytic esterification
Experimental technique: the 2-oxocyclopentyl acetic acid of 0.5mol is added ethanol solution 400mL, the hydrochloric acid solution 1ml of 5mol/L, lithium chloride, back flow reaction 6h under 60 DEG C of temperature conditions, ethyl acetate 400ml dilution is added after concentration, dry, sucking filtration after adopting saturated sodium carbonate liquor to wash, concentrating under reduced pressure collects 115-120 DEG C of fraction, obtains 2-oxocyclopentyl ethyl acetate.
Table two: lithium chloride addition affects result for 2-oxocyclopentyl ethyl acetate yield.
| Experiment number | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Lithium chloride (mol) | 0 | 0.01 | 0.02 | 0.05 | 0.7 | 0.1 | 0.2 |
| Productivity (%) | 90.02 | 91.36 | 91.57 | 95.28 | 92.76 | 93.36 | 92.68 |
2-oxocyclopentyl acetic acid is esterified in generation 2-oxocyclopentyl ethyl acetate process in acid condition, add lithium chloride and can improve the yield of 2-oxocyclopentyl ethyl acetate, as Cl in the hydrochloric acid solution adding 5mol/L in the molal weight and this step of lithium chloride-Time the mass concentration 10 times i.e. molal weight of lithium chloride is 0.05mol, catalytic efficiency is the highest, it is possible to by the output increased of 2-oxocyclopentyl ethyl acetate to more than 95%, has higher economic benefit.
Specific embodiment
Embodiment one
A kind of synthetic method of 2-oxocyclopentyl ethyl acetate, including following operating procedure:
The first step: 1mol sodium is dissolved in the ethanol forming Sodium ethylate in excessive dehydrated alcohol, the alcoholic solution of Sodium ethylate is stood to room temperature interpolation zirconium dioxide 2g and makes catalyst, add toluene 500ml and diethylene adipate 0.7mol after stirring 10 minutes, after 40 DEG C of reaction 5h, obtain Ketocyclopentane Ethyl formate;
Second step: drip ethyl chloroacetate 0.7mol in the Ketocyclopentane Ethyl formate obtained in the first step, controlling temperature is 90 DEG C, and time for adding is 30min, keeps 90 DEG C of thermotonus 2h, be cooled to room temperature treatment and obtain crude product ester after reaction after being added dropwise to complete;
3rd step: the hydrochloric acid solution 400ml stirring point adding 5mol/L in the crude product ester obtained by second step takes organic layer, water layer adopts methylbenzene extraction, adopt the concentration of saturated common salt solution washing to obtain brown liquid after merging organic layer, brown liquid is filtrated to get after drying crude brown oil;
4th step: is added in the crude brown oil that the 3rd step is obtained ethanol solution 400mL, the hydrochloric acid solution 1ml of 5mol/L, lithium chloride 0.05mol, back flow reaction 6h under 60 DEG C of temperature conditions, ethyl acetate 400ml dilution is added after concentration, dry, sucking filtration after adopting saturated sodium carbonate liquor to wash, concentrating under reduced pressure collects 115-120 DEG C of fraction, obtains 2-oxocyclopentyl ethyl acetate.
Embodiment two
A kind of synthetic method of 2-oxocyclopentyl ethyl acetate, including following operating procedure:
The first step: 1mol sodium is dissolved in the ethanol forming Sodium ethylate in excessive dehydrated alcohol, the alcoholic solution of Sodium ethylate is stood to room temperature interpolation zirconium dioxide 5g and makes catalyst, add toluene 500ml and diethylene adipate 0.7mol after stirring 15 minutes, after 55 DEG C of reaction 6h, obtain Ketocyclopentane Ethyl formate;
Second step: drip ethyl chloroacetate 0.7mol in the Ketocyclopentane Ethyl formate obtained in the first step, controlling temperature is 95 DEG C, and time for adding is 30min, keeps 95 DEG C of thermotonus 3h, be cooled to room temperature treatment and obtain crude product ester after reaction after being added dropwise to complete;
3rd step: the hydrochloric acid solution 400ml stirring point adding 5mol/L in the crude product ester obtained by second step takes organic layer, water layer adopts methylbenzene extraction, adopt the concentration of saturated common salt solution washing to obtain brown liquid after merging organic layer, brown liquid is filtrated to get after drying crude brown oil;
4th step: is added in the crude brown oil that the 3rd step is obtained ethanol solution 500mL, the hydrochloric acid solution 1ml of 5mol/L, lithium chloride 0.05mol, back flow reaction 6h under 70 DEG C of temperature conditions, ethyl acetate 400ml dilution is added after concentration, dry, sucking filtration after adopting saturated sodium carbonate liquor to wash, concentrating under reduced pressure collects 115-120 DEG C of fraction, obtains 2-oxocyclopentyl ethyl acetate.
Embodiment three
A kind of synthetic method of 2-oxocyclopentyl ethyl acetate, including following operating procedure:
The first step: 1mol sodium is dissolved in the ethanol forming Sodium ethylate in excessive dehydrated alcohol, the alcoholic solution of Sodium ethylate is stood to room temperature interpolation zirconium dioxide 3g and makes catalyst, add toluene 500ml and diethylene adipate 0.7mol after stirring 10 minutes, after 55 DEG C of reaction 5h, obtain Ketocyclopentane Ethyl formate;
Second step: drip ethyl chloroacetate 0.7mol in the Ketocyclopentane Ethyl formate obtained in the first step, controlling temperature is 90 DEG C, and time for adding is 30min, keeps 90 DEG C of thermotonus 3h, be cooled to room temperature treatment and obtain crude product ester after reaction after being added dropwise to complete;
3rd step: the hydrochloric acid solution 400ml stirring point adding 5mol/L in the crude product ester obtained by second step takes organic layer, water layer adopts methylbenzene extraction, adopt the concentration of saturated common salt solution washing to obtain brown liquid after merging organic layer, brown liquid is filtrated to get after drying crude brown oil;
4th step: is added in the crude brown oil that the 3rd step is obtained ethanol solution 400mL, the hydrochloric acid solution 1ml of 5mol/L, lithium chloride 0.05mol, back flow reaction 6h under 70 DEG C of temperature conditions, ethyl acetate 400ml dilution is added after concentration, dry, sucking filtration after adopting saturated sodium carbonate liquor to wash, concentrating under reduced pressure collects 115-120 DEG C of fraction, obtains 2-oxocyclopentyl ethyl acetate.
Embodiment four
A kind of synthetic method of 2-oxocyclopentyl ethyl acetate, including following operating procedure:
The first step: 1mol sodium is dissolved in the ethanol forming Sodium ethylate in excessive dehydrated alcohol, the alcoholic solution of Sodium ethylate is stood to room temperature interpolation zirconium dioxide 4g and makes catalyst, add toluene 500ml and diethylene adipate 0.7mol after stirring 15 minutes, after 50 DEG C of reaction 6h, obtain Ketocyclopentane Ethyl formate;
Second step: drip ethyl chloroacetate 0.7mol in the Ketocyclopentane Ethyl formate obtained in the first step, controlling temperature is 90 DEG C, and time for adding is 30min, keeps 90 DEG C of thermotonus 2h, be cooled to room temperature treatment and obtain crude product ester after reaction after being added dropwise to complete;
3rd step: the hydrochloric acid solution 400ml stirring point adding 5mol/L in the crude product ester obtained by second step takes organic layer, water layer adopts methylbenzene extraction, adopt the concentration of saturated common salt solution washing to obtain brown liquid after merging organic layer, brown liquid is filtrated to get after drying crude brown oil;
4th step: is added in the crude brown oil that the 3rd step is obtained ethanol solution 500mL, the hydrochloric acid solution 1ml of 5mol/L, lithium chloride 0.05mol, back flow reaction 6h under 60 DEG C of temperature conditions, ethyl acetate 400ml dilution is added after concentration, dry, sucking filtration after adopting saturated sodium carbonate liquor to wash, concentrating under reduced pressure collects 115-120 DEG C of fraction, obtains 2-oxocyclopentyl ethyl acetate.
Embodiment five
A kind of synthetic method of 2-oxocyclopentyl ethyl acetate, including following operating procedure:
The first step: 1mol sodium is dissolved in the ethanol forming Sodium ethylate in excessive dehydrated alcohol, the alcoholic solution of Sodium ethylate is stood to room temperature interpolation zirconium dioxide 5g and makes catalyst, add toluene 500ml and diethylene adipate 0.7mol after stirring 15 minutes, after 50 DEG C of reaction 6h, obtain Ketocyclopentane Ethyl formate;
Second step: drip ethyl chloroacetate 0.7mol in the Ketocyclopentane Ethyl formate obtained in the first step, controlling temperature is 95 DEG C, and time for adding is 30min, keeps 95 DEG C of thermotonus 2h, be cooled to room temperature treatment and obtain crude product ester after reaction after being added dropwise to complete;
3rd step: the hydrochloric acid solution 400ml stirring point adding 5mol/L in the crude product ester obtained by second step takes organic layer, water layer adopts methylbenzene extraction, adopt the concentration of saturated common salt solution washing to obtain brown liquid after merging organic layer, brown liquid is filtrated to get after drying crude brown oil;
4th step: is added in the crude brown oil that the 3rd step is obtained ethanol solution 400mL, the hydrochloric acid solution 1ml of 5mol/L, lithium chloride 0.05mol, back flow reaction 6h under 60 DEG C of temperature conditions, ethyl acetate 400ml dilution is added after concentration, dry, sucking filtration after adopting saturated sodium carbonate liquor to wash, concentrating under reduced pressure collects 115-120 DEG C of fraction, obtains 2-oxocyclopentyl ethyl acetate.
Wherein, zirconium dioxide is analytical pure, its active constituent content >=99%, dioxide-containing silica��0.01%, content of titanium dioxide��0.005%, iron oxide content��0.005%, calcium oxide content��0.05%, content of magnesia��0.05%.
Lithium chloride is analytically pure anhydrous Lithium chloride, and lithium chloride active constituent content is be more than or equal to 99%.
Table three: according to embodiment method Ketocyclopentane Ethyl formate, 2-oxocyclopentyl ethyl acetate productivity and overall yield of reaction.
| Ketocyclopentane Ethyl formate | 2-oxocyclopentyl ethyl acetate | Total recovery | |
| Embodiment one | 94.72 | 96.71 | 76.19 |
| Embodiment two | 93.48 | 97.25 | 76.52 |
| Embodiment three | 94.23 | 95.81 | 75.30 |
| Embodiment four | 93.91 | 97.01 | 75.39 |
| Embodiment five | 94.62 | 97.59 | 76.57 |
Adopt the inventive method, it is possible to be effectively improved total recovery, be beneficial to industrialization promotion, there is higher economic benefit.
Above content is only the better embodiment of the present invention, for those of ordinary skill in the art, according to the thought of the present invention, all will change in specific embodiments and applications, and this specification content should not be construed as limitation of the present invention.
Claims (6)
1. a synthetic method for 2-oxocyclopentyl ethyl acetate, with diethylene adipate for raw material, obtains 2-oxocyclopentyl ethyl acetate through condensation, replacement, hydrolysis decarboxylation, esterification, it is characterised in that include following operating procedure:
The first step: 1mol sodium is dissolved in the ethanol forming Sodium ethylate in excessive dehydrated alcohol, the alcoholic solution of Sodium ethylate is stood to room temperature and adds zirconium dioxide, Ketocyclopentane Ethyl formate is obtained after adding toluene 500ml and diethylene adipate 0.7mol, 40-55 DEG C of reaction 5-6h after stirring 10-15 minute;
Second step: drip ethyl chloroacetate 0.7mol in the Ketocyclopentane Ethyl formate obtained in the first step, control temperature and be 90-95 DEG C, time for adding is 30min, keeps 90-95 DEG C of thermotonus 2-3h, be cooled to room temperature treatment and obtain crude product ester after reaction after being added dropwise to complete;
3rd step: the hydrochloric acid solution 400ml stirring point adding 5mol/L in the crude product ester obtained by second step takes organic layer, water layer adopts methylbenzene extraction, adopt the concentration of saturated common salt solution washing to obtain brown liquid after merging organic layer, brown liquid is filtrated to get after drying crude brown oil;
4th step: is added in the crude brown oil that the 3rd step is obtained ethanol solution 400-500mL, the hydrochloric acid solution 1ml of 5mol/L, lithium chloride, back flow reaction 6h under 60-70 DEG C of temperature conditions, ethyl acetate 400ml dilution is added after concentration, dry, sucking filtration after adopting saturated sodium carbonate liquor to wash, concentrating under reduced pressure collects 115-120 DEG C of fraction, obtains 2-oxocyclopentyl ethyl acetate.
2. the synthetic method of a kind of 2-oxocyclopentyl ethyl acetate according to claim 1, it is characterised in that:
Adding zirconium dioxide in the described first step, the addition of zirconium dioxide is 2-5g;
Described zirconium dioxide is analytical pure, its active constituent content >=99%, dioxide-containing silica��0.01%, content of titanium dioxide��0.005%, iron oxide content��0.005%, calcium oxide content��0.05%, content of magnesia��0.05%.
3. the synthetic method of a kind of 2-oxocyclopentyl ethyl acetate according to claim 1, it is characterized in that: adding lithium chloride in described 4th step is analytically pure anhydrous Lithium chloride, its addition is 0.05mol, and lithium chloride active constituent content is be more than or equal to 99%.
4. the synthetic method of a kind of 2-oxocyclopentyl ethyl acetate according to claim 1, it is characterized in that: the alcoholic solution of Sodium ethylate is stood to room temperature by the described first step and adds zirconium dioxide, add toluene 500ml and diethylene adipate 0.7mol after stirring 15 minutes, after 50 DEG C of reaction 5-6h, obtain Ketocyclopentane Ethyl formate.
5. the synthetic method of a kind of 2-oxocyclopentyl ethyl acetate according to claim 1, it is characterised in that: keep 95 DEG C of thermotonus 2h after described second step is added dropwise to complete to ethyl chloroacetate, be cooled to room temperature treatment after reaction and obtain crude product ester.
6. the synthetic method of a kind of 2-oxocyclopentyl ethyl acetate according to claim 1, it is characterized in that: described 4th step is added ethanol solution 400mL in the crude brown oil that the 3rd step obtains, the hydrochloric acid solution 1mol of 5mol/L, lithium chloride, back flow reaction 6h under 60 DEG C of temperature conditions.
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