CN105198843A - One-pot synthesizing method of 2-(furan-2-yl)-2-glyoxalic acid - Google Patents
One-pot synthesizing method of 2-(furan-2-yl)-2-glyoxalic acid Download PDFInfo
- Publication number
- CN105198843A CN105198843A CN201510616708.4A CN201510616708A CN105198843A CN 105198843 A CN105198843 A CN 105198843A CN 201510616708 A CN201510616708 A CN 201510616708A CN 105198843 A CN105198843 A CN 105198843A
- Authority
- CN
- China
- Prior art keywords
- furan
- reaction
- furfural
- methanol
- acid
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 17
- 238000005580 one pot reaction Methods 0.000 title claims abstract description 7
- 230000002194 synthesizing effect Effects 0.000 title abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 claims abstract description 26
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 57
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- IXVPCJUAKDVYKX-UHFFFAOYSA-N 2-(furan-2-yl)-2-oxoacetic acid Chemical compound OC(=O)C(=O)C1=CC=CO1 IXVPCJUAKDVYKX-UHFFFAOYSA-N 0.000 claims description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 5
- 150000001879 copper Chemical class 0.000 claims description 5
- 239000003444 phase transfer catalyst Substances 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 4
- DDXLVDQZPFLQMZ-UHFFFAOYSA-M dodecyl(trimethyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)C DDXLVDQZPFLQMZ-UHFFFAOYSA-M 0.000 claims description 3
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- 239000003513 alkali Substances 0.000 claims 3
- KWOKMZBSAZNOBW-UHFFFAOYSA-N 1-(furan-2-yl)-2-nitroethanol Chemical compound [O-][N+](=O)CC(O)C1=CC=CO1 KWOKMZBSAZNOBW-UHFFFAOYSA-N 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 2
- 239000002585 base Substances 0.000 claims 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- 230000035484 reaction time Effects 0.000 claims 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims 1
- 238000006842 Henry reaction Methods 0.000 claims 1
- 239000008346 aqueous phase Substances 0.000 claims 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims 1
- 229910000024 caesium carbonate Inorganic materials 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 claims 1
- 229910000365 copper sulfate Inorganic materials 0.000 claims 1
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 claims 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims 1
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 claims 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 1
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims 1
- CEYYIKYYFSTQRU-UHFFFAOYSA-M trimethyl(tetradecyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)C CEYYIKYYFSTQRU-UHFFFAOYSA-M 0.000 claims 1
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 19
- 239000002253 acid Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 5
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 4
- 239000007791 liquid phase Substances 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000006146 oximation reaction Methods 0.000 description 3
- 239000012450 pharmaceutical intermediate Substances 0.000 description 3
- IEMMBWWQXVXBEU-UHFFFAOYSA-N 2-acetylfuran Chemical compound CC(=O)C1=CC=CO1 IEMMBWWQXVXBEU-UHFFFAOYSA-N 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 2
- 229960001668 cefuroxime Drugs 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- JHMIHJYIJSMCQH-UHFFFAOYSA-N azane;furan Chemical compound N.C=1C=COC=1 JHMIHJYIJSMCQH-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- RHDGNLCLDBVESU-UHFFFAOYSA-N but-3-en-4-olide Chemical compound O=C1CC=CO1 RHDGNLCLDBVESU-UHFFFAOYSA-N 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 210000003298 dental enamel Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Furan Compounds (AREA)
Abstract
Description
技术领域：Technical field:
本发明属于化学合成技术领域，涉及一种重要的医药中间体2-(呋喃-2-基)-2-氧代乙酸的一锅法合成。 The invention belongs to the technical field of chemical synthesis and relates to a one-pot synthesis of an important pharmaceutical intermediate 2-(furan-2-yl)-2-oxoacetic acid.
背景技术：Background technique:
2-(呋喃-2-基)-2-氧代乙酸，又名呋喃酮酸是生产抗生素头孢呋辛的重要中间体之一，它具有如下结构： 2-(furan-2-yl)-2-oxoacetic acid, also known as furanonic acid, is one of the important intermediates in the production of the antibiotic cefuroxime. It has the following structure:
头孢呋辛是一种非经胃肠给药的广谱头孢素菌类抗生素，在生产中该药需经半合成来得到，而呋喃酮酸是其重要中间体之一。 Cefuroxime is a broad-spectrum cephalosporin antibiotic for parenteral administration, which needs to be obtained by semi-synthesis in production, and furanonic acid is one of its important intermediates.
专利201010584693涉及了由2-呋喃甲酸合成呋喃酮酸的方法。该方法首先将2-呋喃甲酸与三氯化磷在搪瓷反应釜中进行氯代反应，得到呋喃甲酰氯。后者再在反应釜中与氰化钠进行氰化反应，最后进行水解可得到呋喃酮酸。该发明方法条件较为苛刻，而且用到了剧毒化合物氰化钠，具有较大的危险性。 Patent 201010584693 relates to a method for synthesizing furanonic acid from 2-furancarboxylic acid. In the method, 2-furancarboxylic acid and phosphorus trichloride are first chlorinated in an enamel reaction kettle to obtain furoyl chloride. The latter is then cyanided with sodium cyanide in the reactor, and finally hydrolyzed to obtain furanone acid. The conditions of the inventive method are relatively harsh, and the highly toxic compound sodium cyanide is used, which has great danger.
专利200910097425涉及了呋喃酮酸的合成方法。该方法是由亚硝酸钠和乙酰呋喃反应，经过肟化、重排、水解来得到呋喃酮酸。本发明采用了58~60oC的肟化反应温度，糠酸的生成率小于1%，提高了产率。专利201210334531进一步改进了上述方法，加入金属盐催化这一肟化反应，使得最终呋喃酮酸的产率得到进一步提高。该方法同时提及可以在氧化完成之后，直接对所得溶液进行酸化，并用于下一步反应的新方法，具有较高的借鉴价值。 Patent 200910097425 relates to the synthesis method of furanonic acid. In the method, sodium nitrite and acetylfuran are reacted to obtain furanonic acid through oximation, rearrangement and hydrolysis. The present invention adopts the oximation reaction temperature of 58-60oC, the formation rate of furoic acid is less than 1%, and the yield is improved. Patent 201210334531 further improved the above method, adding metal salts to catalyze the oximation reaction, so that the final yield of furanonic acid was further improved. The method also mentions a new method that can directly acidify the obtained solution after the oxidation is completed, and use it for the next reaction, which has a high reference value.
然而上述方法用到的主要原料乙酰呋喃价格较高，成为生产呋喃酮酸的主要成本来源。因此寻求重新设计的合成路线，以价格更加便宜的糠醛作为原料来生产呋喃酮酸就成为非常有意义的事情。 However, the price of acetylfuran, the main raw material used in the above method, is relatively high, which becomes the main source of cost for the production of furanonic acid. Therefore, it is very meaningful to seek a redesigned synthetic route and use cheaper furfural as a raw material to produce furanonic acid.
发明内容：Invention content:
本发明提供了一种医药中间体2-(呋喃-2-基)-2-氧代乙酸的一锅法合成方法（如下式所示）。 The invention provides a one-pot method for synthesizing a pharmaceutical intermediate 2-(furan-2-yl)-2-oxoacetic acid (shown in the following formula).
具体步骤为：The specific steps are:
步骤1） step 1)
将糠醛（0.96~96.1g,10.0~1000mmol）溶于甲醇与水的混合溶液（甲醇与水，体积比1:4，20~2000mL）中，加入硝基甲烷（0.64~640mL,12.0~1200mmol,1.2eq）、碱（1.0~100mmol,0.1eq）和相转移催化剂（1.0~100mmol,0.1eq），室温进行反应5h。TLC检测反应完成之后，将反应液直接用于下一步反应。 Dissolve furfural (0.96~96.1g, 10.0~1000mmol) in a mixed solution of methanol and water (methanol and water, volume ratio 1:4, 20~2000mL), add nitromethane (0.64~640mL, 12.0~1200mmol, 1.2eq), base (1.0~100mmol, 0.1eq) and phase transfer catalyst (1.0~100mmol, 0.1eq), react at room temperature for 5h. After the completion of the reaction detected by TLC, the reaction solution was directly used for the next reaction.
步骤2） Step 2)
向步骤1）中的反应液中加入乙酸（4~400mL），调节体系中乙酸：甲醇：水的比例为1：1：4，之后向体系中加入铜盐（1.0~100mmol,0.1eq），升温至90oC，并向体系中鼓入空气进行反应3h。待反应完成，冷却到室温将体系中的乙酸和甲醇通过旋转蒸发仪脱除得到含有产品的悬浊液，之后使用盐酸调节溶液的pH值为3，得到2-(呋喃-2-基)-2-氧代乙酸的溶液，液相检测转化率为85~90%，该溶液可直接用于下一步反应，制备呋喃铵盐产品。 Add acetic acid (4~400mL) to the reaction solution in step 1), adjust the ratio of acetic acid:methanol:water in the system to 1:1:4, then add copper salt (1.0~100mmol, 0.1eq) to the system, The temperature was raised to 90oC, and air was blown into the system to react for 3h. After the reaction is completed, cool to room temperature and remove the acetic acid and methanol in the system by a rotary evaporator to obtain a suspension containing the product, then use hydrochloric acid to adjust the pH value of the solution to 3 to obtain 2-(furan-2-yl)- The solution of 2-oxoacetic acid has a liquid phase detection conversion rate of 85-90%, and the solution can be directly used in the next reaction to prepare furan ammonium salt products.
本发明的有益效果为：The beneficial effects of the present invention are:
使用廉价易得的糠醛为主要原料，在温和的条件下经过两步一锅的反应，合成重要的医药中间体2-(呋喃-2-基)-2-氧代乙酸。本发明避开了之前工业上合成2-(呋喃-2-基)-2-氧代乙酸的常用方法，使得该产品的生产成本大大降低，并适合工业化规模的生产。 Using cheap and easily available furfural as the main raw material, the important pharmaceutical intermediate 2-(furan-2-yl)-2-oxoacetic acid was synthesized through a two-step one-pot reaction under mild conditions. The present invention avoids the previous common method for industrially synthesizing 2-(furan-2-yl)-2-oxoacetic acid, greatly reduces the production cost of the product, and is suitable for industrial scale production.
具体实施方式：Detailed ways:
实施例1：Example 1:
步骤1） step 1)
将糠醛（0.96g,10.0mmol）溶于甲醇与水的混合溶液（甲醇与水，体积比1:4，20mL）中，加入硝基甲烷（0.64mL,12.0mmol,1.2eq）、氢氧化钾（0.06g,1.0mmol,0.1eq）和苄基三乙基氯化铵（0.23g,1.0mmol,0.1eq），室温进行反应5h。TLC检测反应完成之后，将反应液直接用于下一步反应。 Dissolve furfural (0.96g, 10.0mmol) in a mixed solution of methanol and water (methanol and water, volume ratio 1:4, 20mL), add nitromethane (0.64mL, 12.0mmol, 1.2eq), potassium hydroxide (0.06g, 1.0mmol, 0.1eq) and benzyltriethylammonium chloride (0.23g, 1.0mmol, 0.1eq), react at room temperature for 5h. After the completion of the reaction detected by TLC, the reaction solution was directly used for the next reaction.
步骤2） step 2)
向步骤1）中的反应液中加入乙酸（4mL），调节体系中乙酸：甲醇：水的比例为1：1：4，之后向体系中加入一水合醋酸铜（0.20g,1.0mmol,0.1eq），升温至90oC，并向体系中鼓入空气进行反应3h。待反应完成，冷却到室温将体系中的乙酸和甲醇通过旋转蒸发仪脱除得到含有产品的悬浊液，之后使用盐酸调节溶液的pH值为3，得到2-(呋喃-2-基)-2-氧代乙酸的溶液，液相检测转化率为88%。 Add acetic acid (4mL) to the reaction solution in step 1), adjust the ratio of acetic acid:methanol:water in the system to 1:1:4, and then add copper acetate monohydrate (0.20g, 1.0mmol, 0.1eq ), the temperature was raised to 90oC, and air was blown into the system to react for 3h. After the reaction is completed, cool to room temperature and remove the acetic acid and methanol in the system by a rotary evaporator to obtain a suspension containing the product, then use hydrochloric acid to adjust the pH value of the solution to 3 to obtain 2-(furan-2-yl)- The solution of 2-oxoacetic acid has a liquid phase detection conversion rate of 88%.
实施例2：Example 2:
步骤1） step 1)
将糠醛（9.6g,100.0mmol）溶于甲醇与水的混合溶液（甲醇与水，体积比1:4，200mL）中，加入硝基甲烷（6.4mL,120.0mmol,1.2eq）、氢氧化钠（0.40g,10.0mmol,0.1eq）和十二烷基三甲基氯化铵（2.63g,10.0mmol,0.1eq），室温进行反应5h。TLC检测反应完成之后，将反应液直接用于下一步反应。 Dissolve furfural (9.6g, 100.0mmol) in a mixed solution of methanol and water (methanol and water, volume ratio 1:4, 200mL), add nitromethane (6.4mL, 120.0mmol, 1.2eq), sodium hydroxide (0.40g, 10.0mmol, 0.1eq) and dodecyltrimethylammonium chloride (2.63g, 10.0mmol, 0.1eq), react at room temperature for 5h. After the completion of the reaction detected by TLC, the reaction solution was directly used for the next reaction.
步骤2） step 2)
向步骤1）中的反应液中加入乙酸（40mL），调节体系中乙酸：甲醇：水的比例为1：1：4，之后向体系中加入氯化铜（1.3g,1.0mmol,0.1eq），升温至90oC，并向体系中鼓入空气进行反应3h。待反应完成，冷却到室温将体系中的乙酸和甲醇通过旋转蒸发仪脱除得到含有产品的悬浊液，之后使用盐酸调节溶液的pH值为3，得到2-(呋喃-2-基)-2-氧代乙酸的溶液，液相检测转化率为89%。 Add acetic acid (40mL) to the reaction solution in step 1), adjust the ratio of acetic acid:methanol:water in the system to 1:1:4, then add copper chloride (1.3g, 1.0mmol, 0.1eq) to the system , the temperature was raised to 90oC, and air was blown into the system to react for 3h. After the reaction is completed, cool to room temperature and remove the acetic acid and methanol in the system by a rotary evaporator to obtain a suspension containing the product, then use hydrochloric acid to adjust the pH value of the solution to 3 to obtain 2-(furan-2-yl)- The solution of 2-oxoacetic acid has a liquid phase detection conversion rate of 89%.
实施例3：Example 3:
步骤1） step 1)
将糠醛（96.1g,1000mmol）溶于甲醇与水的混合溶液（甲醇与水，体积比1:4,2000mL）中，加入硝基甲烷（640mL,1200mmol,1.2eq）、氢氧化钠（4.0g,100mmol,0.1eq）和四丁基氯化铵（27.8g,100mmol,0.1eq），室温进行反应5h。TLC检测反应完成之后，将反应液直接用于下一步反应。 Dissolve furfural (96.1g, 1000mmol) in a mixed solution of methanol and water (methanol and water, volume ratio 1:4, 2000mL), add nitromethane (640mL, 1200mmol, 1.2eq), sodium hydroxide (4.0g , 100mmol, 0.1eq) and tetrabutylammonium chloride (27.8g, 100mmol, 0.1eq), react at room temperature for 5h. After the completion of the reaction detected by TLC, the reaction solution was directly used for the next reaction.
步骤2） step 2)
向步骤1）中的反应液中加入乙酸（400mL），调节体系中乙酸：甲醇：水的比例为1：1：4，之后向体系中加入一水合醋酸铜（20.0g,1.0mmol,0.1eq），升温至90oC，并向体系中鼓入空气进行反应3h。待反应完成，冷却到室温将体系中的乙酸和甲醇通过旋转蒸发仪脱除得到含有产品的悬浊液，之后使用盐酸调节溶液的pH值为3，得到2-(呋喃-2-基)-2-氧代乙酸的溶液，液相检测转化率为89%。 Add acetic acid (400mL) to the reaction solution in step 1), adjust the ratio of acetic acid:methanol:water in the system to 1:1:4, then add copper acetate monohydrate (20.0g, 1.0mmol, 0.1eq ), the temperature was raised to 90oC, and air was blown into the system to react for 3h. After the reaction is completed, cool to room temperature and remove the acetic acid and methanol in the system by a rotary evaporator to obtain a suspension containing the product, then use hydrochloric acid to adjust the pH value of the solution to 3 to obtain 2-(furan-2-yl)- The solution of 2-oxoacetic acid has a liquid phase detection conversion rate of 89%.
上述虽然结合实施例对本发明的具体实施方式进行了描述，但并非对本发明保护范围的限制，所属领域技术人员应该明白，在本发明的技术方案的基础上，本领域技术人员不需要付出创造性劳动即可做出的各种修改或变形仍在本发明的保护范围以内。 Although the specific implementation of the present invention has been described above in conjunction with the examples, it is not intended to limit the protection scope of the present invention. Those skilled in the art should understand that on the basis of the technical solution of the present invention, those skilled in the art do not need to pay creative work Various modifications or variations that can be made are still within the protection scope of the present invention.
Claims (7)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510616708.4A CN105198843B (en) | 2015-09-25 | 2015-09-25 | The One-step Synthesis method of 2 (base of furans 2) 2 Oxoacetic Acids |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510616708.4A CN105198843B (en) | 2015-09-25 | 2015-09-25 | The One-step Synthesis method of 2 (base of furans 2) 2 Oxoacetic Acids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105198843A true CN105198843A (en) | 2015-12-30 |
| CN105198843B CN105198843B (en) | 2018-01-23 |
Family
ID=54946841
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510616708.4A Expired - Fee Related CN105198843B (en) | 2015-09-25 | 2015-09-25 | The One-step Synthesis method of 2 (base of furans 2) 2 Oxoacetic Acids |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105198843B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115504947A (en) * | 2022-08-23 | 2022-12-23 | 山东和源制药有限公司 | Preparation method of furanone acid |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5227745A (en) * | 1975-08-26 | 1977-03-02 | Mitsubishi Petrochem Co Ltd | Method for carbonating aldehydes |
| CN1571780A (en) * | 2001-09-28 | 2005-01-26 | 化学生物活动中心 | Synthetic method of 2-(2-nitroethylenyl)-furan and its purpose as anti-coccidium agent |
| CN101830783A (en) * | 2010-05-28 | 2010-09-15 | 济南大学 | Method for preparing aldehyde by oxidizing alcohol with oxygen in presence of Schiff-base complex catalyst |
| CN104193600A (en) * | 2014-08-11 | 2014-12-10 | 济南大学 | Method for preparing aldehyde or ketone from air oxidized alcohol by using aluminum oxide as co-catalyst |
-
2015
- 2015-09-25 CN CN201510616708.4A patent/CN105198843B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5227745A (en) * | 1975-08-26 | 1977-03-02 | Mitsubishi Petrochem Co Ltd | Method for carbonating aldehydes |
| CN1571780A (en) * | 2001-09-28 | 2005-01-26 | 化学生物活动中心 | Synthetic method of 2-(2-nitroethylenyl)-furan and its purpose as anti-coccidium agent |
| CN101830783A (en) * | 2010-05-28 | 2010-09-15 | 济南大学 | Method for preparing aldehyde by oxidizing alcohol with oxygen in presence of Schiff-base complex catalyst |
| CN104193600A (en) * | 2014-08-11 | 2014-12-10 | 济南大学 | Method for preparing aldehyde or ketone from air oxidized alcohol by using aluminum oxide as co-catalyst |
Non-Patent Citations (4)
| Title |
|---|
| ANJOY MAJHI ET AL: "TMEDA Catalyzed Henry (Nitroaldol) Reaction under Metal and Solvent-free Conditions", 《BULL. KOREAN CHEM. SOC.》 * |
| MILIND D.NIKALJE ET AL: "Synthesis of aryl α-keto-acids via the Cu-catalyzed conversion of aryl nitroaldol products", 《TETRAHEDRON LETTERS》 * |
| ROBERTO BALLINI ET AL: "Nitroaldol Reaction in Aqueous Media: An Important Improvement of the Henry Reaction", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
| XIAO ZHANG ET AL: "Total Synthesis of (-)-Isatisine A", 《ANGEW.CHEM.INT.ED.》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115504947A (en) * | 2022-08-23 | 2022-12-23 | 山东和源制药有限公司 | Preparation method of furanone acid |
| CN115504947B (en) * | 2022-08-23 | 2024-04-26 | 山东和源制药有限公司 | Preparation method of furanone acid |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105198843B (en) | 2018-01-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105820126B (en) | A kind of preparation method of olaparib | |
| CN106699774A (en) | Sulbactam sodium preparation method | |
| ES2507492T3 (en) | Process to prepare zanamivir and intermediates for use in the process | |
| CN107235967B (en) | Synthetic Technology of Antineoplastic Drug Tegafur | |
| CN103373916B (en) | Environment-friendly preparation method for lipid-lowering drug ciprofibrate | |
| CN101952246B (en) | A one-pot process for preparing 3-(2,2,2-trimethylhydrazinium)propionate dihydrate | |
| CN108440409B (en) | Green and efficient preparation method of rebamipide | |
| CN105198843A (en) | One-pot synthesizing method of 2-(furan-2-yl)-2-glyoxalic acid | |
| CN112694445A (en) | Purification method of oxalaggrin sodium intermediate | |
| CN107118215B (en) | A kind of preparation method for treating breast cancer medicines Rui Boxini intermediate | |
| CN104003934A (en) | 6-chlorine-3-fluorine-2-picolinic acid synthesis process | |
| CN104262242A (en) | method for synthesizing 3,5-diiodo-4-aminopyridine by employing in-situ iodized reagent production method | |
| CN106946880A (en) | A kind of method for preparing Rui Boxini intermediates | |
| CN104672179B (en) | Preparation method of [(1S)-3-methyl-1-[[(2R)-2-methylepoxyethyl]carbonyl]butyl]tert-butyl carbamate | |
| CN112390749B (en) | A method for synthesizing cabozantinib and its intermediates | |
| CN106928040A (en) | The preparation method of SGLT2 inhibitor intermediate | |
| CN110655507B (en) | Preparation method of anti-tumor medicine tegafur | |
| CN112624921A (en) | Synthesis method and application of 1-hydroxymethyl cyclopropyl acetic acid | |
| CN101747343B (en) | A kind of preparation method of sulbactam pivoxil | |
| CN112851508A (en) | Preparation method of Barosavir intermediate | |
| CN109970784A (en) | A method for preparing carbapenem antibiotic intermediate 4-BMA | |
| CN105294501A (en) | Method for preparing carfilzomib intermediate compound | |
| CN108033972A (en) | A kind of synthetic method of Cefprozil | |
| CN102603570B (en) | Preparation method for 2,3,4-trimethoxy benzonitrile | |
| CN110615734A (en) | Industrialized synthesis method of o-aldehyde phenyl fatty acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180123 Termination date: 20180925 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |