CN103664682B - A kind of method of synthesizing 2-methane amide pimelinketone - Google Patents
A kind of method of synthesizing 2-methane amide pimelinketone Download PDFInfo
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- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 150000001408 amides Chemical class 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 38
- 230000002194 synthesizing effect Effects 0.000 title description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 230000007062 hydrolysis Effects 0.000 claims abstract description 16
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 16
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000004202 carbamide Substances 0.000 claims abstract description 14
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 14
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 12
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 239000008346 aqueous phase Substances 0.000 claims abstract description 4
- 239000012452 mother liquor Substances 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 230000001590 oxidative effect Effects 0.000 claims abstract description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 22
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 235000006408 oxalic acid Nutrition 0.000 claims description 7
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- 235000011149 sulphuric acid Nutrition 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 239000001117 sulphuric acid Substances 0.000 claims description 5
- 150000003863 ammonium salts Chemical class 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- 238000005265 energy consumption Methods 0.000 abstract description 6
- 238000005516 engineering process Methods 0.000 abstract description 4
- 238000009833 condensation Methods 0.000 abstract description 3
- 230000005494 condensation Effects 0.000 abstract description 3
- 239000010865 sewage Substances 0.000 abstract description 3
- 238000005406 washing Methods 0.000 abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- WZWSOGGTVQXXSN-UHFFFAOYSA-N cyclohexanone;toluene Chemical compound CC1=CC=CC=C1.O=C1CCCCC1 WZWSOGGTVQXXSN-UHFFFAOYSA-N 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- DRZZAQBCCAFIED-UHFFFAOYSA-N cyclohexanone;1,2-xylene Chemical compound O=C1CCCCC1.CC1=CC=CC=C1C DRZZAQBCCAFIED-UHFFFAOYSA-N 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
- 239000002351 wastewater Substances 0.000 description 3
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229960000346 gliclazide Drugs 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- -1 Pimelinketone ion Chemical class 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- CSKROPPOPPCYRH-UHFFFAOYSA-N cyclohexanone;hydrate Chemical compound O.O=C1CCCCC1 CSKROPPOPPCYRH-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses the method for a kind of low emission less energy-consumption synthesis 2-methane amide pimelinketone, belong to pharmaceutical chemistry and technical field of organic synthesis.The present invention with non-oxidizing proton acid or its salt for catalyzer, aromatic hydrocarbons does solvent and water entrainer, with pimelinketone, urea is raw material, one kettle way prepares 2-methane amide pimelinketone, the volution of present invention process synthesis is without refrigerated separation, save a large amount of washing water, and invented technology also will be generated water by the condensation that pimelinketone is saturated, aqueous phase mother liquor after volution hydrolysis steams water and separates product is for preparing the recycle of hydrolysis diluted acid, eliminate the loss that pimelinketone causes because dissolving in water, not only improve pimelinketone utilization ratio but also achieve sewage zero-discharge, applicable industrial applications easy and simple to handle.
Description
Technical field
The present invention relates to a kind of method of synthesizing 2-methane amide pimelinketone, belong to pharmaceutical chemistry and technical field of organic synthesis.
Background technology
2-methane amide pimelinketone is the important source material of hypoglycemic drug gliclazide and weedicide, existing synthetic method is as follows: method one [Journalfprakt.Chemie, Band318, Heft5,1976, S, 773 ~ 778] with pimelinketone, urea for raw material, tosic acid makees catalyzer, toluene band water synthesizing spiro (yield 91.0%).Because catalyzer tosic acid is oxidisability organic acid, in reaction process, especially pyroreaction, oxidized portion pimelinketone generates red-brown syrupy shape impurity, make the intermediate volution color of generation comparatively dark, just can be hydrolyzed after water and organic solvent purifying after must cooling.But adopt separate operations both to increase Equipment Foundations input and turn increase energy consumption.Separate purifying rear center body volution dilute sulphuric acid and be hydrolyzed to obtain product 2-methane amide pimelinketone (yield 80.0%).Chemical equation is as follows:
Although this method substep yield is higher, due to pimelinketone solubleness comparatively large (3 ~ 5%) in water, separate operations had both been produced utilization ratio (pimelinketone overall utilization≤60%) that a large amount of waste water again reduces pimelinketone.(a kind of preparation method of gliclazide intermediate pimelinketone-2-methane amide, still there is the method drawback of separate operations in application number: 201110423685.7) only improve the hydrolysis process of aforesaid method to patent.
United States Patent (USP) [UnitedStatesPatent, Appl.No.:777,322] and [Li Guofang, application chemical industry [J], 2010,39 (5), 641-644] all advocate one kettle way operate continuously reduction energy consumption, but the method adopts heavy dose of (urea volatile salt quality feed ratio 2:1) volatile salt as urea high temperature polymerization inhibitor, add the consumption of hydrolysis sulfuric acid, and the method does not mention the recovery technology of waste water cyclohexanone yet.Therefore, still there is the defect of the not high and contaminate environment of pimelinketone utilization ratio in this technique.
Summary of the invention
For solving the method drawback of above-mentioned existing 2-methane amide pimelinketone synthesis technique, the present invention adopts new catalyst, one kettle way operate continuously synthesis 2-methane amide pimelinketone, in conjunction with the simple and effective method extracting pimelinketone from waste water, there is provided a kind of novel process of high yield less energy-consumption low emission synthesis 2-methane amide pimelinketone, present invention process is applicable to industrial applications.
The present invention realizes with following technical scheme: a kind of method of synthesizing 2-methane amide pimelinketone, with pimelinketone, urea, aromatic hydrocarbons for raw material, it is characterized in that one kettle way prepares 2-methane amide pimelinketone with non-oxidizing proton acid or its salt for catalyzer;
Described catalyzer be oxalic acid, phosphoric acid, polyphosphoric acid, tetra-sodium any one;
Further, described catalyzer is phosphoric acid, polyphosphoric acid or oxalic acid;
Described catalyzer is arbitrary ammonium salt of oxalic acid, phosphoric acid, polyphosphoric acid or tetra-sodium, sodium salt or sylvite;
Further, described catalyzer is arbitrary ammonium salt of oxalic acid, phosphoric acid, polyphosphoric acid or tetra-sodium;
The consumption of described catalyzer is 0.001 ~ 0.005 times of pimelinketone quality;
Described aromatic hydrocarbons is benzene, toluene or dimethylbenzene, and its consumption is 0.1 ~ 1 times of pimelinketone quality.
A kind of method of synthesizing 2-methane amide pimelinketone, be that 1:0.1 ~ 1:0.3 ~ 0.6:0.001 ~ 0.005 pimelinketone, urea, aromatic hydrocarbons and catalyzer adds reactor by mass ratio, 100 ~ 150 DEG C of reactions to anhydrous generation, then the 1M dilute sulphuric acid of 2.5 ~ 3.5 times of pimelinketone quality is directly added, hydrolysis volution obtains wet product 2-methane amide pimelinketone, by its dry obtained sterling at 70 ~ 100 DEG C, complete one kettle way and produce;
The generation water of above-mentioned reaction process, volution hydrolytic process steam water, separate wet product 2-methane amide pimelinketone after aqueous phase mother liquor collect respectively, all for preparing the 1M dilute sulphuric acid of present method hydrolysis, carry out recycle, not only improve pimelinketone utilization ratio but also achieve sewage zero-discharge;
The optimal reaction temperature of above-mentioned reaction is 120 ~ 140 DEG C, and optimum reacting time is 2 ~ 5 hours.
The invention has the beneficial effects as follows: by adopting new catalyst condensation process, reduce the oxidation of condensation reaction cyclohexanone, the separate operations of former technique is formed one kettle way successive reaction, and total reaction time shortens, and energy consumption declines to a great extent; In addition, synthesizing spiro of the present invention does not need refrigerated separation to save a large amount of washing water, and by being generated water by the saturated condensation of pimelinketone, volution hydrolysis steams water and the aqueous phase mother liquor after separating out product is used for preparing the recycle of hydrolysis diluted acid, not only improve the utilization ratio of pimelinketone but also achieve sewage zero-discharge.Therefore, invented technology less energy-consumption, low emission, environmental friendliness, industrial applications promotion prospect is good.
Accompanying drawing and explanation thereof:
Fig. 1 is the infrared spectrum of the 2-methane amide pimelinketone that present invention process obtains;
Fig. 2 is MS spectrogram and 2-methane amide pimelinketone standard MS spectrogram (SATURN gas chromatograph-mass spectrometer the carries database spectrogram) comparison diagram of the 2-methane amide pimelinketone that present invention process obtains.
Product infrared spectrum test result (Japanese JASCO company FTIR2430 type Fourier infrared spectrograph, KBr sheet) according to Fig. 1, the degree of unsaturation of 2-methane amide pimelinketone is 3, containing two carbonyls and a six-ring in molecule; 3426.8cm
-1and 3199.5cm (A)
-1(B) bands of a spectrum at place are the flexible and anti-stretching vibration Absorption Characteristics peaks of the N-H key of primary amide; 2946.4cm
-1(C), 2914.8cm
-1(D), 2868.3cm
-1and 2841.8cm
-1(E) absorption peak at place is produced by the c h bond absorption of vibrations of six-ring methylene radical; Carbonyl absorption of vibrations on six-ring produces 1708.1cm
-1(F) absorption peak at place, due to NH
2push away electronic effect, the carbonyl vibration absorption peak of acid amides drops to 1635.9cm
-1(G).
Fig. 2 (on) be the MS spectrogram detected with acetone solution product SATURN gas chromatograph-mass spectrometer (VARIANWS company of the U.S.), because experiment adopts FAB ion source and ion strap mass analyzer, with standard spectrogram Fig. 2 of 2-methane amide pimelinketone (under: BP141.090440, SATURN gas chromatograph-mass spectrometer database spectrogram) slightly difference.Fig. 2 (on) display, 2-methane amide pimelinketone has obvious molecular ion peak m/z141M
+, quasi-molecular ion peak m/z142 (M+H)
+intensity is maximum, meets FAB ion source feature.The dehydration of 2-methane amide pimelinketone forms m/z123 (M-H
2o)
+quasi-molecular ions, loses NH
3or OH forms m/z124 (M-NH
3)
+or (M-OH)
+quasi-molecular ions, de-CO forms m/z113 (M-CO)
+peak.The fracture of 2-methane amide pimelinketone branch chain place loses CONH
2and de-H-shaped becomes m/z96 (M-CONH
2-H)
+peak.Pimelinketone ion breaks ring and produces m/z69 and m/z55 quasi-molecular ions, and McLafferty rearrangement produces C
nh
2no
+ion (m/z58,72,86).
Embodiment
Embodiment 1
Comparative example [reference literature Journalfprakt.Chemie, Band318, Heft5,1976, S, 773 ~ 778]
190g pimelinketone, 120g urea, 1g tosic acid and 200ml toluene are joined 2000ml three-necked bottle, back flow reaction adds 300ml water and stirs cooling blowing after 10 hours, volution obtains 200g, mp:185.1 ~ 188.3 DEG C, single step yield 91% after washing drying again with water.The rare H of dry volution 200g, 470ml1M
2sO
4join 2000ml three-necked bottle heating hydrolysis complete, obtain 2-methane amide pimelinketone 102g, mp:127.3 ~ 129.6 DEG C (X-5 micro melting point apparatus mensuration, Tyke, Beijing Instrument Ltd., following example same measured method), (single step yield 80.0%), reclaims pimelinketone 71g.2-methane amide pimelinketone (102g) is calculated, total recovery 59.6% to consume pimelinketone (119g).
Embodiment 2 ~ 6 is present invention process operational instances.
Embodiment 2
124g pimelinketone, 42g urea, 0.6g85.0% phosphoric acid and 15g dimethylbenzene are joined 1000ml three-necked bottle, and 138 DEG C of back flow reaction add the rare H of 320g1M after 2.5 hours
2sO
4heating hydrolysis volution, reacts complete, collects dimethylbenzene cyclohexanone mixture 77g, obtains 2-methane amide pimelinketone 58g, mp:127.1 ~ 129.0 DEG C, to consume pimelinketone (62g), total recovery 65.3%.
Embodiment 3
The dimethylbenzene cyclohexanone mixture 77g collected by example 2 and the new pimelinketone of 62g, 42g urea, 0.6g85.0% phosphoric acid join 1000ml three-necked bottle, 135 DEG C of back flow reaction add 1M rare H2SO4 heating hydrolysis volution that 322g is prepared by example 2 recycle-water after 3 hours, react complete, collect dimethylbenzene cyclohexanone mixture 89g, obtain 2-methane amide pimelinketone 56.2g, mp:127.0 ~ 129.3 DEG C, to consume pimelinketone (50g), total recovery 78.1%.
Embodiment 4
124g pimelinketone, 42g urea, 0.6g85.0% phosphoric acid and 15g toluene are joined 1000ml three-necked bottle, and 136 DEG C of back flow reaction add the rare H of 320g1M after 3 hours
2sO
4heating hydrolysis volution, reacts complete, collects toluene cyclohexanone mixture 78.4g, obtains 2-methane amide pimelinketone 57.8g, mp:127.2 ~ 129.5 DEG C, to consume 60.6g pimelinketone, and total recovery 66.3%.
Embodiment 5
The toluene cyclohexanone mixture 78.4g collected by example 4 and the new pimelinketone of 60.6g, 42g urea, 0.6g85.0% phosphoric acid join 1000ml three-necked bottle, and 135 DEG C of back flow reaction add the rare H of 1M that 322g is prepared by example 4 recycle-water after 3 hours
2sO
4heating hydrolysis volution, reacts complete, collects toluene cyclohexanone mixture 87.5g, obtains 2-methane amide pimelinketone 57.7g, mp:126.7 ~ 129.1 DEG C, to consume pimelinketone (51.5g), total recovery 77.9%.
Embodiment 6
36g pimelinketone, 13g urea, 0.36g ammonium phosphate and 28g toluene are joined 500ml three-necked bottle, and 128 DEG C of back flow reaction add the rare H of 99g1M after 3 hours
2sO
4heating hydrolysis volution, reacts complete, collects toluene cyclohexanone mixture 50.3g, obtains 2-methane amide pimelinketone 12.5g, mp:126.4 ~ 128.1 DEG C, to consume 13.7g pimelinketone, and total recovery 63.4%.
Claims (8)
1. synthesize a method for 2-methane amide pimelinketone, with pimelinketone, urea, aromatic hydrocarbons for raw material, it is characterized in that one kettle way prepares 2-methane amide pimelinketone with non-oxidizing proton acid or its salt for catalyzer;
Described catalyzer is any one of oxalic acid, phosphoric acid, polyphosphoric acid or tetra-sodium, or arbitrary ammonium salt of above-mentioned acid, sodium salt or sylvite.
2. the method for synthesis 2-methane amide pimelinketone according to claim 1, is characterized in that described catalyzer is phosphoric acid, polyphosphoric acid or oxalic acid.
3. the method for synthesis 2-methane amide pimelinketone according to claim 1, is characterized in that described catalyzer is arbitrary ammonium salt of oxalic acid, phosphoric acid, polyphosphoric acid or tetra-sodium.
4. the method for synthesis 2-methane amide pimelinketone according to claim 1, is characterized in that the consumption of described catalyzer is 0.001 ~ 0.005 times of pimelinketone quality.
5. the method for synthesis 2-methane amide pimelinketone according to claim 1, it is characterized in that described aromatic hydrocarbons is benzene, toluene or dimethylbenzene, its consumption is 0.1 ~ 1 times of pimelinketone quality.
6. the method for synthesis 2-methane amide pimelinketone according to claim 1, it is characterized in that being that 1:0.1 ~ 1:0.3 ~ 0.6:0.001 ~ 0.005 pimelinketone, urea, aromatic hydrocarbons and catalyzer adds reactor by mass ratio, 100 ~ 150 DEG C of reactions to anhydrous generation, then the 1M dilute sulphuric acid of 2.5 ~ 3.5 times of pimelinketone quality is directly added, hydrolysis volution obtains wet product 2-methane amide pimelinketone, by its dry obtained sterling at 70 ~ 100 DEG C, complete one kettle way and produce.
7. the method for synthesis 2-methane amide pimelinketone according to claim 6, it is characterized in that described reaction process to generate water, volution hydrolytic process steam water, separate wet product 2-methane amide pimelinketone after aqueous phase mother liquor collect respectively, all for preparing the 1M dilute sulphuric acid of present method hydrolysis, carry out recycle.
8. the method for synthesis 2-methane amide pimelinketone according to claim 6, it is characterized in that the temperature of reaction of described reaction is 110 ~ 140 DEG C, the reaction times is 2 ~ 5 hours.
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| CN104529913B (en) * | 2014-12-23 | 2018-11-30 | 菏泽市方明制药有限公司 | The preparation method of 6- cyclohexyl -3,4- and cyclohexyl -5- nitrogen caprolactam -4- alkene |
| CN105218394B (en) * | 2015-08-31 | 2017-03-15 | 江苏瑞科医药科技有限公司 | A kind of synthesis technique for improving 2 Methanamide Ketohexamethylene yield of Gliclazide intermediate |
| CN112661664A (en) * | 2020-12-30 | 2021-04-16 | 安徽金鼎医药股份有限公司 | Synthesis process of gliclazide intermediate 2-formamide cyclohexanone |
| CN114534644B (en) * | 2022-02-15 | 2023-01-03 | 浙江博朗新材料有限公司 | Device and method for preparing 2-formamide cyclohexanone by catalyzing spiro hydrolysis with solid acid |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4169952A (en) * | 1977-03-14 | 1979-10-02 | E. I. Du Pont De Nemours And Company | Process for the preparation of cyclohexanone-2-carboxamide |
| CN103159642A (en) * | 2011-12-17 | 2013-06-19 | 山东方明药业集团股份有限公司 | Preparation method of gliclazide intermediate cyclohexanone-2-methanmide |
-
2013
- 2013-11-22 CN CN201310594636.9A patent/CN103664682B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4169952A (en) * | 1977-03-14 | 1979-10-02 | E. I. Du Pont De Nemours And Company | Process for the preparation of cyclohexanone-2-carboxamide |
| CN103159642A (en) * | 2011-12-17 | 2013-06-19 | 山东方明药业集团股份有限公司 | Preparation method of gliclazide intermediate cyclohexanone-2-methanmide |
Non-Patent Citations (3)
| Title |
|---|
| 2-甲酰胺环己酮的简便合成;李国防;《应用化工》;20100531;第39卷(第5期);第641-644页 * |
| A simple synthesis of cyclohexanone-2-carboxamide and its reactions;Bischoff Christian，Herma Hannelore;《J.Prakt.Chem.》;19761231;第318卷(第5期);第775页 * |
| Ureas in organic synthesis. II. Synthesis of hydrogenated acridine-1,8-diones and 1,4-dihydropyridines by reaction of ureas with 1,3-dicarbonyl compounds;Bakibaev A.A.，Filimonov V.D.;《Zhurnal Organicheskoi Khimii》;19911231;第27卷(第4期);第858页 * |
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| CN103664682A (en) | 2014-03-26 |
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