CN1446802A - Chemosynthesis method of 1-chloroformyl-3-acetyl-2-imidazolidinone - Google Patents
Chemosynthesis method of 1-chloroformyl-3-acetyl-2-imidazolidinone Download PDFInfo
- Publication number
- CN1446802A CN1446802A CN 02107658 CN02107658A CN1446802A CN 1446802 A CN1446802 A CN 1446802A CN 02107658 CN02107658 CN 02107658 CN 02107658 A CN02107658 A CN 02107658A CN 1446802 A CN1446802 A CN 1446802A
- Authority
- CN
- China
- Prior art keywords
- imidazolidone
- chloroformyl
- ethanoyl
- trichloromethyl
- chemical synthesis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- CCRQBNJTBJRTJD-UHFFFAOYSA-N 3-acetyl-2-oxoimidazolidine-1-carbonyl chloride Chemical compound CC(=O)N1CCN(C(Cl)=O)C1=O CCRQBNJTBJRTJD-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims abstract description 18
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000012346 acetyl chloride Substances 0.000 claims abstract description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 10
- 150000007530 organic bases Chemical class 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 34
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 17
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-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 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229960001701 chloroform Drugs 0.000 claims description 2
- 229940117389 dichlorobenzene Drugs 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- LAYPMCGIWDGYKX-UHFFFAOYSA-N trichloromethyl hydrogen carbonate Chemical compound OC(=O)OC(Cl)(Cl)Cl LAYPMCGIWDGYKX-UHFFFAOYSA-N 0.000 claims description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 230000003115 biocidal effect Effects 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 1
- 150000002148 esters Chemical class 0.000 abstract 1
- 239000002516 radical scavenger Substances 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 abstract 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- JJWACYUTERPMBM-UHFFFAOYSA-N 1-acetylimidazolidin-2-one Chemical compound CC(=O)N1CCNC1=O JJWACYUTERPMBM-UHFFFAOYSA-N 0.000 description 9
- 238000010992 reflux Methods 0.000 description 7
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 238000010907 mechanical stirring Methods 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000001291 vacuum drying Methods 0.000 description 5
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 2
- 239000005051 trimethylchlorosilane Substances 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- -1 1-ethanoyl Chemical group 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- PFADHNZAIFSXCK-UHFFFAOYSA-N benzene;1,2-dichloroethane Chemical compound ClCCCl.C1=CC=CC=C1 PFADHNZAIFSXCK-UHFFFAOYSA-N 0.000 description 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
1－氯甲酰基－3－乙酰基－2－咪唑烷酮的化学合成方法，以有机碱为捕酸剂，以2－咪唑烷酮、乙酰氯或乙酸酐、双(三氯甲基)碳酸酯为原料在有机溶剂中反应制得，该产品是新型半合成抗菌素的重要中间体。该合成方法是一种工艺先进合理、生产安全可靠、反应收率高、生产成本低、基本无三废的1－氯甲酰基－3－乙酰基－2－咪唑烷酮化学合成方法。The chemical synthesis method of 1-chloroformyl-3-acetyl-2-imidazolidinone uses an organic base as an acid scavenger, and 2-imidazolidinone, acetyl chloride or acetic anhydride, bis(trichloromethyl)carbonic acid The ester is prepared by reacting in an organic solvent as a raw material, and the product is an important intermediate of a new type of semi-synthetic antibiotic. The synthesis method is a chemical synthesis method of 1-chloroformyl-3-acetyl-2-imidazolidinone with advanced and reasonable technology, safe and reliable production, high reaction yield, low production cost and basically no three wastes.
Description
The present invention relates to a kind of is the earlier synthetic 1-ethanoyl of raw material-2-imidazolidone with Acetyl Chloride 98Min. or diacetyl oxide and 2-imidazolidone; use two (trichloromethyl) carbonic ethers to substitute phosgene directly and the chemical synthesis process of 1-ethanoyl-2-imidazolidone prepared in reaction 1-chloroformyl-3-ethanoyl-2-imidazolidone then, 1-chloroformyl-3-ethanoyl-2-imidazolidone is the important intermediate of new semi-synthetic antibiotic.
Before the present invention made, the chemical synthesis process of prior art 1-chloroformyl-3-ethanoyl-2-imidazolidone was to be that raw material reaction makes with phosgene or trichloromethylchloroformate and 1-ethanoyl-2-imidazolidone.Propose as Germany Beyer Co., Ltd (Brit, 1392850), 1-ethanoyl-2-imidazolidone in anhydrous benzene with trimethylchlorosilane and triethylamine back flow reaction 18 hours, then with phosgene at 5 ℃ of reactions and getting down, product M.P.104 ℃, productive rate 81%.Its shortcoming is to use hypertoxic raw material phosgene and source of goods difficulty and the expensive trimethylchlorosilane that restriction is in the world used, and reaction time is long, and potential safety hazard is big, and reaction yield is low, the production cost height, and quantity of three wastes is big, difficult, the industrialization difficulty.
Task of the present invention is the shortcoming that overcomes prior art, provides that a kind of technology is reasonable, production safety is reliable, reaction yield is high, production cost is low, does not have the 1-chloroformyl-3-ethanoyl-2-imidazolidone chemical synthesis process of the three wastes substantially.
The chemical synthesis process of 1-chloroformyl-3-ethanoyl-2-imidazolidone, it is characterized in that with the organic bases being acid-capture agent, with Acetyl Chloride 98Min. or diacetyl oxide and 2-imidazolidone is that raw material reacts in organic solvent, and then make with two (trichloromethyl) carbonate reaction, its molar ratio is the 2-imidazolidone: Acetyl Chloride 98Min. or diacetyl oxide: organic bases: two (trichloromethyl) carbonic ether=1: 1.0-1.5: 1.0-1.5: 0.27-0.50; The mass ratio of 2-imidazolidone and solvent is 1: 8-15, and its temperature of reaction is 0～70 ℃, and the reaction times is 5～10 hours, and its reaction equation is:
Organic solvent can be tetrahydrofuran (THF) or benzene or toluene or dimethylbenzene or chlorobenzene or dichlorobenzene or methylene dichloride or trichloromethane or tetracol phenixin or ethylene dichloride benzene.
Organic bases can be pyridine or triethylamine or N, dinethylformamide.
The present invention compared with prior art, the operational path advanced person, processing condition are reasonable, used raw material has been avoided hypertoxic phosgene, production safety is reliable, the reaction yield height, production cost is lower, does not have the three wastes substantially, has bigger implementary value and economic results in society.
Embodiment 1
Molar ratio is the 2-imidazolidone: Acetyl Chloride 98Min.: pyridine: two (trichloromethyl) carbonic ether=1: 1.1: 1.1: 0.293
In the 500mL four-hole boiling flask of mechanical stirring, constant pressure funnel, reflux condensing tube and thermometer is housed, add 0.5mol 2-imidazolidone and 150mL anhydrous tetrahydro furan, open and stir, under vigorous stirring, be cooled to 0 ℃, slowly drip the 0.55mol Acetyl Chloride 98Min. then, drip 70min approximately, finish and be warming up to 25 ℃, stirred 3 hours down, after reaction finishes at 20-30 ℃, tetrahydrofuran (THF) is reclaimed in vacuum distilling, resistates acetone recrystallization, vacuum-drying get elaboration 51.2g, yield 80%, fusing point 187.2-188.3 ℃, HPLC content 99.3%.
Mechanical stirring is being housed; constant pressure funnel; in the 500mL four-hole boiling flask of reflux condensing tube and thermometer; add 51.2gN-ethanoyl-2-imidazolidone; 39.2g pyridine and 250mL anhydrous tetrahydro furan; open and stir; under vigorous stirring, slowly drip solution and the organic bases (pyridine) prepared by two (trichloromethyl) carbonic ethers of 43.7g and 100mL anhydrous tetrahydro furan in advance; finish temperature rising reflux 3～5h; reaction finishes the final vacuum distillation and reclaims methylene dichloride; the resistates acetone recrystallization; vacuum-drying gets elaboration 68.6g; yield 90%; fusing point 104.0-104.5 ℃, HPLC content 99.7%.
Embodiment 2
Molar ratio is the 2-imidazolidone: Acetyl Chloride 98Min.: pyridine: two (trichloromethyl) carbonic ether=1: 1.3: 1.3: 0.293
In the 500mL four-hole boiling flask of mechanical stirring, constant pressure funnel, reflux condensing tube and thermometer is housed, add 0.5mol 2-imidazolidone and 150mL anhydrous tetrahydro furan, open and stir, under vigorous stirring, be cooled to 0 ℃, slowly drip the 0.65mol Acetyl Chloride 98Min. then, drip 80min approximately, finish and be warming up to 25 ℃, stirred 4 hours down at 20-30 ℃, after reaction finished, tetrahydrofuran (THF) was reclaimed in vacuum distilling, the resistates acetone recrystallization, vacuum-drying gets elaboration 52.5g, and yield 82% fusing point 187.0-188.2 ℃, HPLC content 99.2%.
Mechanical stirring is being housed; constant pressure funnel; in the 500mL four-hole boiling flask of reflux condensing tube and thermometer; add 52.5g N-ethanoyl-2-imidazolidone; 51.3g pyridine and 250mL anhydrous tetrahydro furan; open and stir; under vigorous stirring, slowly drip solution and the organic bases (pyridine) prepared by two (trichloromethyl) carbonic ethers of 44.8g and 100mL anhydrous tetrahydro furan in advance; finish temperature rising reflux 3～5h; reaction finishes the final vacuum distillation and reclaims methylene dichloride; the resistates acetone recrystallization; vacuum-drying gets elaboration 71.1g; yield 91% fusing point 103.5-104.0 ℃, HPLC content 99.3%.
Embodiment 3
Molar ratio is the 2-imidazolidone: Acetyl Chloride 98Min.: pyridine: two (trichloromethyl) carbonic ether=1: 1.5: 1.5: 0.293
Operating process is with embodiment 2.The yield 84% of N-ethanoyl-2-imidazolidone, fusing point 186.5-188.0 ℃, HPLC content 98.6%.The yield 92% of 1-chloroformyl-3-ethanoyl-2-imidazolidone, fusing point 103.8-104.2 ℃, HPLC content 99.5%.
Embodiment 4
Molar ratio is the 2-imidazolidone: Acetyl Chloride 98Min.: pyridine: two (trichloromethyl) carbonic ether=1: 1.3: 1.3: 0.35
Operating process is with embodiment 2.The yield 82% of N-ethanoyl-2-imidazolidone, fusing point 187.0-188.2 ℃, HPLC content 99.2%.The yield 93% fusing point 104.1-104.8 of 1-chloroformyl-3-ethanoyl-2-imidazolidone ℃, HPLC content 99.7%.
Embodiment 5
Molar ratio is the 2-imidazolidone: Acetyl Chloride 98Min.: pyridine: two (trichloromethyl) carbonic ether=1: 1.3: 1.3: 0.45
Operating process is with embodiment 2.The yield 82% of N-ethanoyl-2-imidazolidone, fusing point 187.0-188.2 ℃, HPLC content 99.2%.The yield 90% of 1-chloroformyl-3-ethanoyl-2-imidazolidone, fusing point 103.3-104.6 ℃, HPLC content 99.1%.
Embodiment 6
Molar ratio is the 2-imidazolidone: Acetyl Chloride 98Min.: pyridine: two (trichloromethyl) carbonic ether=1: 1.3: 1.5: 0.45
Operating process is with embodiment 2.The yield 82% of N-ethanoyl-2-imidazolidone, fusing point 187.0-188.2 ℃, HPLC content 99.2%.The yield 92.5% of 1-chloroformyl-3-ethanoyl-2-imidazolidone, fusing point 103.6-104.6 ℃, HPLC content 99.5%.
Embodiment 7
Molar ratio is the 2-imidazolidone: diacetyl oxide: pyridine: two (trichloromethyl) carbonic ether=1: 1.3: 1.3: 0.35
Mechanical stirring is being housed; constant pressure funnel; in the 500mL four-hole boiling flask of reflux condensing tube and thermometer; add 0.5mol 2-imidazolidone and 150mL anhydrous tetrahydro furan; open and stir; under vigorous stirring, be cooled to 0 ℃; slowly drip the 0.65mol diacetyl oxide then; drip 80min approximately; finish and be warming up to 25 ℃, stirred 4 hours down, after reaction finishes at 20-30 ℃; tetrahydrofuran (THF) and acetate are reclaimed in vacuum distilling; resistates acetone recrystallization, vacuum-drying get N-ethanoyl-2-imidazolidone, yield 80%; fusing point 187.1-188.7 ℃, HPLC content 99.0%.
The synthetic operation of 1-chloroformyl-3-ethanoyl-2-imidazolidone is identical with embodiment 2, yield 92.5%, fusing point 103.8-104.5 ℃, HPLC content 99.6%.
The patent of the present invention and Beyer Co., Ltd (Brit.1392850) relatively has production safety, and is easy to operate, and reaction time is short, and raw material is cheap and easy to get, the reaction yield height, and advantages such as good product quality are one and are suitable for industrialized method.
Claims (3)
1, the chemical synthesis process of 1-chloroformyl-3-ethanoyl-2-imidazolidone, it is characterized in that with the organic bases being acid-capture agent, with Acetyl Chloride 98Min. or diacetyl oxide and 2-imidazolidone is that raw material reacts in organic solvent, and then make with two (trichloromethyl) carbonate reaction, its molar ratio is the 2-imidazolidone: Acetyl Chloride 98Min. or diacetyl oxide: organic bases: two (trichloromethyl) carbonic ether=1: 1.0-1.5: 1.0-1.5: 0.27-0.50; The mass ratio of 2-imidazolidone and solvent is 1: 8-15, and its temperature of reaction is 0～70 ℃, the reaction times is 5～10 hours.
2, chemical synthesis process as claimed in claim 1 is characterized in that organic solvent can be tetrahydrofuran (THF) or benzene or toluene or dimethylbenzene or chlorobenzene or dichlorobenzene or methylene dichloride or trichloromethane or tetracol phenixin or ethylene dichloride.
3, chemical synthesis process as claimed in claim 1 is characterized in that organic bases can be pyridine or triethylamine or N, dinethylformamide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02107658 CN1446802A (en) | 2002-03-22 | 2002-03-22 | Chemosynthesis method of 1-chloroformyl-3-acetyl-2-imidazolidinone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02107658 CN1446802A (en) | 2002-03-22 | 2002-03-22 | Chemosynthesis method of 1-chloroformyl-3-acetyl-2-imidazolidinone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1446802A true CN1446802A (en) | 2003-10-08 |
Family
ID=28048415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02107658 Pending CN1446802A (en) | 2002-03-22 | 2002-03-22 | Chemosynthesis method of 1-chloroformyl-3-acetyl-2-imidazolidinone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1446802A (en) |
-
2002
- 2002-03-22 CN CN 02107658 patent/CN1446802A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1589249A (en) | Process for producing dihalogenoadamantane | |
| CN1133632C (en) | Process for preparation of taxanes from 10-deacetylbeccatin III | |
| CN1446802A (en) | Chemosynthesis method of 1-chloroformyl-3-acetyl-2-imidazolidinone | |
| CN1243005C (en) | Process for preparation of taxan derivatives | |
| Najdi et al. | Use of metal complexation in the synthesis of medium-ring acetylenic lactones | |
| CN1394852A (en) | Preparation method of tetrabutyl urea | |
| JP2005104964A (en) | Method for purifying adamantyl esters | |
| CN115385850B (en) | A kind of preparation method of 1,4-dihydropyridine compound | |
| JP4163400B2 (en) | Method for producing (meth) acrylic acid ester | |
| CN1199952C (en) | Chemosynthesis method of 1-choroformyl-2-imidazolidinone | |
| CN112374976A (en) | Novel method for synthesizing curcumin analogue | |
| CN108047191B (en) | Preparation method of cyclic polybutylene terephthalate | |
| CN1235873C (en) | Chemical synthesis method of isopropyl isocyanate | |
| JP6627653B2 (en) | Method for producing carboxylic acid thioester | |
| CN1271061C (en) | Process for the preparation of the 14beta-hydroxy-baccatin III -1,14-carbonate | |
| CN100522899C (en) | A kind of preparation method of symmetrical benzocyclobutene compound | |
| CN109761947A (en) | A kind of synthetic method of functionalized benzochromene compounds | |
| CN1388116A (en) | One kind of 4-cyano phenyl isocyanate and its chemical synthesis | |
| CN1313426C (en) | Synthesis of 2-methoxyl-5-iodophenol | |
| CN109369678A (en) | A new synthetic method of natural product isomer (-)-6-epi-Porantheridine | |
| JPH06321836A (en) | Method for purifying 9,9-bis(4-hydroxyphenyl)fluorene | |
| AU2003268683B2 (en) | Process for production of an acetylenic compound | |
| CN115785036B (en) | A kind of furan structure-containing diene compound and preparation method thereof | |
| CN113336717B (en) | Process for preparing oxazolecarboxylic acid esters | |
| JP4050915B2 (en) | 2-Adamantanone production method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |