CN106083554B - Method for preparing 2-acetyl cyclohexanone by one-pot method - Google Patents
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- OEKATORRSPXJHE-UHFFFAOYSA-N 2-acetylcyclohexan-1-one Chemical compound CC(=O)C1CCCCC1=O OEKATORRSPXJHE-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 title claims abstract description 31
- 238000005580 one pot reaction Methods 0.000 title abstract 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims abstract description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 28
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- 239000005457 ice water Substances 0.000 claims abstract description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000001816 cooling Methods 0.000 claims abstract 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 claims description 12
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 claims description 9
- 238000005292 vacuum distillation Methods 0.000 claims description 5
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 4
- DCAYPVUWAIABOU-UHFFFAOYSA-N hexadecane Chemical compound CCCCCCCCCCCCCCCC DCAYPVUWAIABOU-UHFFFAOYSA-N 0.000 claims description 4
- 238000001802 infusion Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- NRUBUZBAZRTHHX-UHFFFAOYSA-N lithium;propan-2-ylazanide Chemical compound [Li+].CC(C)[NH-] NRUBUZBAZRTHHX-UHFFFAOYSA-N 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 10
- 239000007788 liquid Substances 0.000 abstract description 8
- 238000004821 distillation Methods 0.000 abstract description 6
- 238000000926 separation method Methods 0.000 abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- 230000035484 reaction time Effects 0.000 abstract description 3
- 238000007670 refining Methods 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 2
- 239000013067 intermediate product Substances 0.000 abstract description 2
- 238000005406 washing Methods 0.000 abstract description 2
- 229960001701 chloroform Drugs 0.000 abstract 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 abstract 2
- 238000003756 stirring Methods 0.000 abstract 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 abstract 1
- 239000012346 acetyl chloride Substances 0.000 abstract 1
- 239000012295 chemical reaction liquid Substances 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 150000002081 enamines Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229940122783 Endothelin converting-enzyme inhibitor Drugs 0.000 description 3
- -1 chloroacetic chloride 2- acetyl cyclohexanone Chemical compound 0.000 description 3
- 239000002857 endothelin converting enzyme inhibitor Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000005935 nucleophilic addition reaction Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 1
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- WRLRISOTNFYPMU-UHFFFAOYSA-N [S].CC1=CC=CC=C1 Chemical compound [S].CC1=CC=CC=C1 WRLRISOTNFYPMU-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical compound O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000201 insect hormone Substances 0.000 description 1
- 239000010977 jade Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing 2-acetyl cyclohexanone by a one-pot method, which comprises the following steps: (1) adding cyclohexanone into tetrahydrofuran, dropwise adding lithium diisopropylamide under the condition of cooling in an ice water bath, and then stirring and reacting for 1h at room temperature; (2) under the condition of ice-water bath, dripping a trichloromethane solution of acetyl chloride into the reaction system in the step (1), removing the ice-water bath, and stirring at room temperature for reaction for 1 h; (3) and (3) washing the reaction liquid obtained in the step (2) twice with water for liquid separation, spin-drying trichloromethane, and then carrying out reduced pressure distillation to collect 118-136 ℃ fractions to obtain 2-acetyl cyclohexanone. According to the method, the intermediate product in the whole reaction process does not need to be purified and directly subjected to the next reaction, the finally obtained product is directly refined by reduced pressure distillation, the yield of the whole process is high, the reaction time is short, the energy consumption is low, the concentration of the 2-acetyl cyclohexanone obtained by direct reduced pressure distillation refining exceeds 96.0 wt%, and the yield exceeds 94%.
Description
Technical field
The present invention relates to a kind of preparation methods of organic compound, and in particular to a kind of one kettle way preparation 2- acetyl group hexamethylene
The method of ketone.
Background technique
The clinical application of endothelin-converting enzyme inhibitor, the healing for a large amount of cardiovascular patients provide possibility.By
Domestic and international present Research is it is found that research synthesizes the significance of endothelin-converting enzyme inhibitor intermediate.2- acetyl cyclohexanone
It is exactly a kind of important intermediate as endothelin-converting enzyme inhibitor, is also used as the intermediate of insect hormone, has non-
Often important research significance.
Generally have about the preparation method of 2- acetyl cyclohexanone at present following several:
First method:, can be with since the C=O bond on cyclohexanone has stronger electrophilicity using cyclohexanone as raw material
Nucleophilic addition occurs, produces enamine using secondary amine and hexamethylene reactive ketone, enamine hydrolyzes after reaction, so that carbonyl regenerates, therefore
And such method can also actually regard the indirect method that ketone is acylated as.Zhang Zhaogui etc. (Minute Organic Synthesis with set
Meter, Chemical Industry Press, version in 2016, the 113-116 pages) describe a kind of direct acyl group chemical combination of 2- acetyl cyclohexanone
Cheng Fa, by cyclohexanone and chloroacetic chloride or acetic anhydride.First with cyclohexanone and tetrahydropyridine or morpholine etc. in carbonic acid
Under the effect of the Catalyzed by p-Toluenesulfonic Acid of the dehydrating agents such as potassium or catalytic amount, heating removes water in benzole soln, and reaction generates α, β-
Unsaturated amine (Sichiff alkali);Then with α obtained, β-unsaturated amine carries out acyl as a kind of reactive intermediate and chloroacetic chloride
2- acetyl cyclohexanone is made in glycosylation reaction, final synthesize, and yield is about 70% or so.The disadvantage of this method is that final
Products collection efficiency is low, by-product is too many, be difficult to purify, post-process trouble, reaction process needs are carried out in two steps, and amplification is caused to produce
Shi Chengben is high.
Second method: for the improved method of above-mentioned first method.(Han Feng, Xu Chongfu, Li Zhenqi, the Zhou Liu such as Han Feng
It is happy, the synthesis and characterization of 2- acetyl cyclohexanone, Agriculture of Anhui science, 2009,37 (17), 7816-7817.) have studied 2- second
The synthetic method of acyl group cyclohexanone, the results showed that, cyclohexanone and morpholine are using organic solvent toluene as entrainer, to toluene sulphur
Acid is catalyst, carries out condensation reaction and generates enamine, acid binding agent triethylamine is then added, and the mixed of chloroacetic chloride and organic solvent is added dropwise
Close object, nucleophilic addition occurs for enamine and chloroacetic chloride, generates cationic imide, be eventually adding concentrated hydrochloric acid to cationic imide into
Row hydrolysis produces research product 2- acetyl cyclohexanone.The disadvantage of this method is that the reaction time is long, reaction step
It is more, product postprocessing trouble.
Summary of the invention
It is an object of the invention to make up the deficiencies in the prior art, a kind of one kettle way is provided and prepares 2- acetyl cyclohexanone
Method.The synthetic method is simple, convenient, directly reacts under normal pressure, rapid reaction and yield height is more than 95%, finally
Product is easy to purify, and product purity height can reach 96.0wt% or more, is suitble to large-scale production.
To achieve the goals above, the present invention adopts the following technical scheme:
A kind of method that one kettle way prepares 2- acetyl cyclohexanone, which is characterized in that described method includes following steps:
(1) cyclohexanone is added in tetrahydrofuran, is cooled to 0-5 DEG C with ice-water bath, lithium diisopropylamine solution is added dropwise,
Then ice-water bath is removed, is stirred to react 1h-2h at room temperature;
(2) under the conditions of ice-water bath, the chloroform soln of chloroacetic chloride is instilled in the reaction system of step (1), then
Ice-water bath is removed, is stirred to react 1h-2h at room temperature;
(3) first the chloroform in reaction solution obtained in step (2) is spin-dried for, then vacuum degree be -0.0960MPa item
It is evaporated under reduced pressure under part, collects 118-136 DEG C of fraction, obtain 2- acetyl cyclohexanone.
The molar ratio of cyclohexanone and lithium diisopropylamine is 1:1.2-1:1.5 in the step (1).
The solvent of the lithium diisopropylamine solution is tetrahydrofuran, hexadecane or ethylbenzene, and concentration is preferably 2mol/L.
The volume ratio of the tetrahydrofuran and lithium diisopropylamine solution is 1.2:1-1.5:1.
In the step (1) tetrahydrofuran attach most importance to steam after tetrahydrofuran.
The concentration of the chloroform soln of chloroacetic chloride is 7.5mol/L-8.5mol/L in the step (2).
The molar ratio of the infusion volume of chloroacetic chloride and the additional amount of cyclohexanone in step (1) is 2.4:1- in the step (2)
3:1。
Beneficial effects of the present invention:
The method of the invention prepares 2- acetyl cyclohexanone using " one kettle way ", and intermediate product is not in entire reaction process
Separately purification process is needed, directly progress next step reaction finally obtains product and directly passes through vacuum distillation purification, whole process
Yield is high, and the concentration for the 2- acetyl cyclohexanone that the reaction time is short, energy consumption is small, direct rectification under vacuum is refining to obtain is more than
96.0wt%, ultimate yield is 94% or more.In addition preparation method of the present invention it is raw materials used it is cheap and easy to get, easy to operate,
Reaction condition is mild, environmental pollution is small, is suitable for large-scale industrial production, provides for the amplification production of 2- acetyl cyclohexanone
New thinking.
The present invention will be described in detail combined with specific embodiments below.Protection scope of the present invention is not with specific implementation
Mode is limited, but is defined in the claims.
Detailed description of the invention
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of 2- acetyl cyclohexanone.
Fig. 2 is the liquid chromatogram of 2- acetyl cyclohexanone.
Specific embodiment
Embodiment 1
(1) it by cyclohexanone 3.4mL, is added in tetrahydrofuran 25mL steams again after, is cooled to 0-5 DEG C with ice-water bath, is added dropwise
Concentration is the lithium diisopropylamine 20mL of 2mol/L, then removes ice-water bath, is stirred to react 1.5h at room temperature;
(2) under the conditions of ice-water bath, the chloroform soln 9.8mL of 8mol/L chloroacetic chloride is instilled to the reaction of step (1)
In system, ice-water bath is then removed, is stirred to react 2h at room temperature;
(3) product in step (2) is first washed into twice of progress liquid separation, then uses Rotary Evaporators by the oil after liquid separation
Chloroform in phase is spin-dried for, then is evaporated under reduced pressure, and when the vacuum degree of vacuum distillation is -0.0960MPa, collects 118-136 DEG C
Fraction 3.2mL, gained fraction are 2- acetyl cyclohexanone, yield 95%.
The nuclear magnetic resonance spectroscopy of the 2- acetyl cyclohexanone being refining to obtain in the present embodiment is as shown in Figure 1, wherein chemical potential
It moves and the number of the corresponding H in each peak is consistent with standard spectrogram.High-efficient liquid phase chromatogram is as shown in Figure 2, it is known that the present embodiment
In the purity of 2- acetyl cyclohexanone that is prepared can reach 96.8wt%, testing result is as shown in table 1, and wherein peak 7 is 2-
Acetyl cyclohexanone.
1 2- acetyl cyclohexanone liquid chromatographic detection result of table
Peak # | Retention time | Area | Highly | Area % | Height % |
1 | 2.385 | 1077 | 103 | 0.002 | 0.004 |
2 | 3.184 | 36341 | 1598 | 0.063 | 0.056 |
3 | 3.952 | 520823 | 34078 | 0.897 | 1.195 |
4 | 4.528 | 1092862 | 84704 | 1.881 | 2.971 |
5 | 5.001 | 122836 | 8232 | 0.211 | 0.289 |
6 | 5.596 | 20273 | 1379 | 0.035 | 0.048 |
7 | 16.559 | 56254033 | 2718876 | 96.837 | 95.365 |
8 | 12.770 | 27882 | 1337 | 0.048 | 0.047 |
9 | 13.680 | 15299 | 720 | 0.026 | 0.025 |
It amounts to | 58091426 | 2851028 | 100.000 | 100.000 |
Embodiment 2
(1) it by cyclohexanone 2.2mL, is added in tetrahydrofuran 24mL steams again after, is cooled to 0-5 DEG C with ice-water bath, is added dropwise
Concentration is the lithium diisopropylamine solution 16mL of 2mol/L, then removes ice-water bath, is stirred to react 1.5h at room temperature;
(2) under the conditions of ice-water bath, the chloroform soln 8mL of 8mol/L chloroacetic chloride is instilled to the reactant of step (1)
In system, ice-water bath is then removed, is stirred to react 2h at room temperature:
(3) product in step (2) is first washed into twice of progress liquid separation, then uses Rotary Evaporators by the oil after liquid separation
Chloroform in phase is spin-dried for, then is evaporated under reduced pressure, and when the vacuum degree of vacuum distillation is -0.0960MPa, collects 118-136 DEG C
Fraction 2.0mL, gained fraction are 2- acetyl cyclohexanone, yield 94.2%.
Comparative example 3
(1) it by cyclohexanone 6mL, is added in tetrahydrofuran 40mL steams again after, under the conditions of 40 DEG C, is slowly added to sodium methoxide
Then 4.7g is stirred to react 2h at room temperature;
(2) under the conditions of ice-water bath, acetic anhydride 9.2mL is slowly dropped into the reaction system of step (1), then removes ice
Water-bath is stirred to react 1h at room temperature, obtains reaction solution;
(3) reaction solution 55mL obtained in step (2) is dissolved in 50mL water, is then extracted, is mentioned with 100mL methylene chloride
It takes, merge methylene chloride phase;The methylene chloride in methylene chloride phase is spin-dried for using Rotary Evaporators, then is evaporated under reduced pressure, is depressurized
When the vacuum degree of distillation is -0.0960MPa, 118-136 DEG C of fraction 10mL is collected, gained fraction is 2- acetyl group hexamethylene
Ketone, yield are about 20%, and purity is lower than 30wt%.
Comparative example 4
(1) cyclohexanone 7.8512g, morphine beautiful jade 8.3635g, toluene 20mL are added to 50mL round-bottomed flask the inside, addition
P-methyl benzenesulfonic acid 0.1g is as catalyst, and reaction temperature is 125 DEG C, and flow back 4h at this temperature, and then air-distillation removes
Toluene;
(2) product in step (1) is transferred in 100mL round-bottomed flask, in 0 DEG C of ice-water bath, triethylamine is added
8.091g is then slowly added into the chloroform soln 25mL of the chloroacetic chloride of 8mol/L, after dripping, removes ice-water bath, often
Temperature is lower to react 1h;
(3) concentrated hydrochloric acid and each 10mL of water are added after mixing in the round-bottomed flask in step (2), in 70 DEG C of reflux 1h
Liquid separation is carried out later, and the chloroform in oily phase twice, is spin-dried for, then subtract by the washing that 30mL is then added using Rotary Evaporators
Pressure distillation when the vacuum degree of vacuum distillation is -0.0960MPa, collects 118-136 DEG C of fraction 3mL, gained fraction is 2- second
Acyl group cyclohexanone, yield 48%, purity are lower than 90wt%.
Claims (7)
1. a kind of method that one kettle way prepares 2- acetyl cyclohexanone, which is characterized in that described method includes following steps:
(1) cyclohexanone is added in tetrahydrofuran, it is cooling with ice-water bath, lithium diisopropylamine solution is added dropwise, then removes ice
Water-bath is stirred to react 1h-2h at room temperature;
(2) under the conditions of ice-water bath, the chloroform soln of chloroacetic chloride is instilled in the reaction system of step (1), is then removed
Ice-water bath is stirred to react 1h-2h at room temperature;
(3) first the chloroform in reaction solution obtained in step (2) is spin-dried for, then under the conditions of vacuum degree is -0.0960MPa
Vacuum distillation collects 118-136 DEG C of fraction, obtains 2- acetyl cyclohexanone.
2. the method that a kind of one kettle way according to claim 1 prepares 2- acetyl cyclohexanone, which is characterized in that the step
Suddenly the molar ratio of cyclohexanone and lithium diisopropylamine is 1:1.2-1.5 in (1).
3. the method that a kind of one kettle way according to claim 1 prepares 2- acetyl cyclohexanone, which is characterized in that described two
The solvent of isopropylamino lithium solution is tetrahydrofuran, hexadecane or ethylbenzene, concentration 2mol/L.
4. the method that a kind of one kettle way according to claim 1 prepares 2- acetyl cyclohexanone, which is characterized in that tetrahydro furan
Muttering with the volume ratio of lithium diisopropylamine solution is 1.2-1.5:1.
5. the method that a kind of one kettle way according to claim 1 prepares 2- acetyl cyclohexanone, which is characterized in that the step
Suddenly in (1) tetrahydrofuran attach most importance to steam after tetrahydrofuran.
6. the method that a kind of one kettle way according to claim 1 prepares 2- acetyl cyclohexanone, which is characterized in that the step
Suddenly the concentration of the chloroform soln of chloroacetic chloride is 7.5mol/L-8.5mol/L in (2).
7. the method that a kind of one kettle way according to claim 1 prepares 2- acetyl cyclohexanone, which is characterized in that the step
Suddenly the molar ratio of the infusion volume of chloroacetic chloride and the additional amount of cyclohexanone in step (1) is 2.4-3:1 in (2).
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