IES20180283A2 - O-toluene formamide organic intermediates synthesis method - Google Patents
O-toluene formamide organic intermediates synthesis method Download PDFInfo
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- IES20180283A2 IES20180283A2 IES2018/0283A IES20180283A IES20180283A2 IE S20180283 A2 IES20180283 A2 IE S20180283A2 IE S20180283 A IES20180283 A IE S20180283A IE S20180283 A2 IES20180283 A2 IE S20180283A2
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- Prior art keywords
- solution
- toluene
- mass fraction
- added
- formamide
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- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 title claims abstract description 46
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 238000001308 synthesis method Methods 0.000 title claims abstract description 18
- 239000000543 intermediate Substances 0.000 title claims abstract description 17
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims abstract description 15
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- 238000003756 stirring Methods 0.000 claims abstract description 12
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims abstract description 8
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 claims abstract description 8
- 229910052939 potassium sulfate Inorganic materials 0.000 claims abstract description 8
- 235000011151 potassium sulphates Nutrition 0.000 claims abstract description 8
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims abstract description 7
- WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000004914 cyclooctane Substances 0.000 claims abstract description 7
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 claims abstract description 7
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 230000018044 dehydration Effects 0.000 claims abstract description 6
- 238000006297 dehydration reaction Methods 0.000 claims abstract description 6
- QQBWQAURZPGDOG-UHFFFAOYSA-N ethyl hexanoate;zinc Chemical compound [Zn].CCCCCC(=O)OCC QQBWQAURZPGDOG-UHFFFAOYSA-N 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 abstract description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 8
- NWPNXBQSRGKSJB-UHFFFAOYSA-N 2-methylbenzonitrile Chemical compound CC1=CC=CC=C1C#N NWPNXBQSRGKSJB-UHFFFAOYSA-N 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000007797 corrosion Effects 0.000 description 3
- 238000005260 corrosion Methods 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000004880 explosion Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000779 smoke Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000000492 nasalseptum Anatomy 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000002341 toxic gas Substances 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
Abstract
The present invention discloses drug intermediates o-toluene formamide organic intermediates synthesis method, comprises the following steps: 6-(1-bromide carbonyl)-toluene, cyclooctane solution was added to the reaction vessel, controlled the stirring speed, controlled the temperature of the solution, added the dimethylamine solution with a mass fraction, added 6 mol aluminum isopropoxide, continued to react; then added potassium sulfate solution with a mass fraction, added2-ethyl hexanoate zinc powder, raised the temperature of the solution, controlled the stirring speed, continued to react, adjusted the pH with oxalate solution with a mass fraction, reduced the temperature, standed, washed with sodium bromide solution, washed with propargyl alcohol solutionwith a mass fraction, recrystallized in methyl ether solution with a mass fraction, dehydrated with anhydrous calcium chloride dehydration, got the finished product o-toluene formamide.
Description
O~toluene formamide organic intermediates synthesis method FIELD OF THE INVENTION The present invention relates to a method for preparing an organic synthesis intermediate, relates to o-toluene formamide organic intermediates synthesis method.
GENERAL BACKGROUND O—toluene formamide is mainly used for organic and pharmaceutical synthesis, the existing methods mostly adopt o-tolunitrile, ethanol, sodium hydroxide, hydrogen peroxide as the reaction raw materials; the raw material o-toluonitrile is toxic, its vapor or smoke can irritate the eyes, mucous membranes and upper respiratory tract; in case of high heat, oxidants can burn, and emit toxic gases, factors above will do harm to the health of the operating personnel, The raw material sodium hydroxide is strongly irritating and corrosive, dust or smoke can irritate the eyes and respiratory tract, corrodes the nasal septum, skin and eye contact with N a0I-I can cause burns, factors above will have an adverse effect on the health of the production operator; and the strong corrosivity of sodium oxide will lead to the production equipment corrosion requirements increase, equipment manufacturing cost rise, is not conducive to cost control. The raw material hydrogen peroxide has strong corrosion, inhalation of the product vapor or fog has a strong irritation to the respiratory tract, eye Contact with liquid can cause irreversible damage or even blindness. In a sealed container with an appropriate ignition source or temperature, a gas phase explosion occurs. Factors above will increase the risk coefficient of the synthesis process, which is not conducive to safe production. Therefore, the above synthesis method has many shortcomings, it is necessary to propose a new synthesis method.
SUMMARY OF TH EINVENTION Based on the technical problems existing in the general background technology, the invention proposed 0-toluene formamide organic intermediates synthesis method, including the following steps: A:6—(l -bromide carbonyl)~toluene, cyclooctane solution was added to the reaction vessel, controlled the stirring speed at 310-330 rpm, controlled the temperature of the solution to 30—36°C, added the dimethylamine solution, added aluminum isopropoxide in batches within 40-60 min, continued to react for 90-1 20 min; Bzthen added potassium sulfate solution, added 2—ethyl hexanoate zinc powder, raised the temperature of the solution to 40-47°C,controlled the stirring speed at 210-230 rpm, continued to react for 160-190 min, adjusted the pH to 8.5-9 with oxalate solution, reduced the temperature to S-10"C, standed for 30-50 min, washed with sodium bromide solution for 30-40 min, washed with propargyl alcohol solution for 50-70 min, recrystallized in methyl ether solution, dehydrated with dehydration, got the finished product o-toluene formamide.
Preferably, the cyclooctane solution has a mass fraction of 20-26%.
Preferably, the dimethylamine solution has a mass fraction of 10-15%.
Preferably, the potassium sulfate solution has a mass fraction of 15-22%.
Preferably, the oxalate solution has a mass fraction of 10-16%.
Preferably, the sodium bromide solution has a mass fraction of 5-11%.
Preferably, the propargyl alcohol solution has a mass fraction of 40-46%.
Preferably, the methyl ether solution has a mass fraction of 60-65%.
Throughout the reaction process can be the following reaction formula: ‘M rm tégvté 5:2 it /‘ VNM 2,.’/‘ "* g rt ‘*1 K. ~. W 4 {'sf"§~?*xi wt - -;» . M" ii 3%? €»r::3fai ii»-it <:2,§»i:,.é.§i..s_i »---«--sun» gt wt)’ E .2 M Compared with the synthesis method disclosed in the background art, the invention provides o-toluene formamide organic intermediates synthesis method, it is unnecessary to use o-tolunitrile, sodium hydroxide, hydrogen peroxide as the reaction raw materials, avoiding o—tolunitrile as raw materials harm to the health of the operation personnel; also avoiding sodium hydroxide as raw materials with the strong stimulation and corrosive, increasing the corrosion resistance requirements of the production equipment, resulting in the adverse impact of equipment manufacturing costs rising.
Moreover, avoiding hydrogen peroxide with strong corrosive harm to the health of production personnel and the risk of hydrogen peroxide by gas explosion, thereby reducing the risk of the synthesis process coefficient, is conducive to safe production, reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, while providing a new synthesis method of the invention, laying a good foundation to further improve the reaction yield.
‘DESCRIPTION OF THE DRAWINGS Figure l is the infrared analysis spectrum of finished product o-toluene formamide.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS The following examples with reference to specific embodiments of the present invention are further illustrated: Embodiment 1: O—toluene formamide intermediates synthesis method, comprises the following steps: A: 2 mol 6—(l-bromide carbonyl)—toluene, 900ml cyclooctanel solution with a mass fraction of % was added to the reaction Vessel, controlled the stirring speed at 310 rpm. controlled the temperature of the solution to 30°C, added 4mol the dimethylamine solution with a mass fraction of l0%, added 4 mol aluminum isopropoxide twice within 40 min, continued to react for 90 min; B: then added 700ml potassium sulfate solution with a mass fraction of 15%, added Zmol 2-ethyl hexanoate zinc powder, raised the temperature of the solution to 40 °C, controlled the stirring speed at 210 rpm, continued to react for 160 min, adjusted the pH to 8.5 with oxalate solution with a mass fraction of 10%, reduced the temperature to 5°C, standed for 30 min, washed with sodium bromide solution with a mass fraction of 5% for 30 min, washed with propargyl alcohol solutionwith a mass fraction of 40% for 50 min, recrystallized in methyl ether solution with a mass fraction of 60%, dehydrated with anhydrous calcium chloride dehydration, got the finished product o—t0luene formamide 265.41g, yield of98.3%.
Embodiment 2: 0—toluene formamide intermediates synthesis method, comprises the following steps: A: 2 mol 6—(l—bromide carbonyl)-toluene, 900ml cyclooctane solution with a mass fraction of 23% was added to the reaction vessel, controlled the stirring speed at 320 rpm, controlled the temperature of the solution to 33 "C, added 5mol the dimethylarnine solution with a mass fraction of l3%, added 5 mol aluminum isopropoxide 3 times within 50 min, continued to react for 100 min; B: then added 700ml potassium sulfate solution with a mass fraction of 18%, added 3mol 2-ethyl hexanoate zinc powder, raised the temperature of the solution to 43 °C, controlled the stirring speed at 220 rpm, continued to react for 170 min, adjusted the pH to 8.7 with oxalate solution with a mass fraction of 13%, reduced the temperature to 8°C, standed for 40 min, washed with sodium bromide solution with a mass fraction of 8% for 35 min, washed with propargyl alcohol solutionwith a mass fraction of 43% for 60 min, recrystallized in methyl ether solution with amass fraction of 63%, dehydrated with anhydrous calcium chloride dehydration, got the finished product o—toluene formamide 265.95g, yield of 98.5%.
Embodiment 3: O—toluene formamide intermediates synthesis method, comprises the following steps: A: 2 mol 6—(l—bromide carbonyl)-toluene, 900ml cyclooctane solution with a mass fraction of 26% was added to the reaction vessel, controlled the stirring speed at 330 rpm, controlled the temperature of the solution to 36°C , added 6mol the dimethylamine solution with a mass fraction of l5%, added 6 mol aluminum isopropoxide 4 times within 60 min, continued to react for 120 min; B: then added 700ml potassium sulfate solution with a mass fraction of 22%, added 4mol 2—ethyl hexanoate zinc powder, raised the temperature of the solution to 47°C, controlled the stirring speed at 230 rpm, continued to react for l90 min, adjusted the pH to 9 with oxalate solution with a mass fraction of l6%, reduced the temperature to lO“C, standed for 50 min, washed with sodium bromide solution with a mass fraction of 11% for 40 min, washed with propargyl alcohol solutionwith a mass fraction of 46% for 70 min, recrystallized in methyl ether solution with a mass fraction of 65%, dehydrated with anhydrous calcium chloride dehydration, got the finished product o—toluene formamide 266.76g, yield of 98.8%.
Figure I is the infrared analysis spectrum of finished product o-toluene formamide.
Table l is the infrared analysis data.
Table l infrared analysis data Serial Peak position Transmittance Width of Half peak Peak difference number (cm'1) (%) (cm'1) (%) 1 640 55 9 3 l 2 68 '1 51 44 34 3 748 49 13 3 3 4 776 69 27 l 6 l 139 58 l 2 3 7 6 1395 3 8 28 45 7 l 597 63 l 5 14 8 1622 29 25 29 9 l 658 9 40 42 l 0 3 l 97 36 66 42 l l 33 83 17 60 63 The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of the present invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the range of the invention.
Claims (4)
1. Claims ’1V O-toluene formamide organic intermediates synthesis method, comprises the following steps: A:6-(‘l~bromide carbonyl)—toluene, cyclooctane solution was added to the reaction vessel, controlled the stirring speed at 310-330 rpm, controlled the temperature of the solution to 30-36°C, added the dimethylamine solution, added aluminum isopropoxide in batches within 40-60 min, continued to react for 90-l20 min; B:then added potassium sulfate solution, added 2-ethyl hexanoate zinc powder, raised the temperature of the solution to 40-47°C,controlled the stirring speed at 210-230 rpm, continued to react for 160-190 min, adjusted the pH to 8.5-9 with oxalate solution, reduced the temperature to 5-10°C, standed for 30-50 min, washed with sodium bromide solution for 30-40 min, washed with propargyl alcohol solution for 50-70 min, recrystallized in methyl ether solution, dehydrated with dehydration, got the finished product o—toluene formamide.
2. O-toluene formamide organic intermediates synthesis method according to claim 1 wherein the cyclooctane solution has a mass fraction of 20-26%.
3. 0-toluene formamide organic intermediates synthesis method according to claim ll wherein the dimethylamine solution has a mass fraction of 10-15%.
4. O—toluene formamide organic intermediates synthesis method according to claim 1 wherein the potassium sulfate solution has a mass fraction of 15-22%. 5‘ 0—toluene formamide organic intermediates synthesis method according to claim '1 wherein the oxalate solution has a mass fraction of ‘l0-16%.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNCHINA17/09/20172017108217354 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IES20180283A2 true IES20180283A2 (en) | 2020-10-14 |
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