WO2022141699A1 - 一种9-芴甲醛的制备方法 - Google Patents
一种9-芴甲醛的制备方法 Download PDFInfo
- Publication number
- WO2022141699A1 WO2022141699A1 PCT/CN2021/073307 CN2021073307W WO2022141699A1 WO 2022141699 A1 WO2022141699 A1 WO 2022141699A1 CN 2021073307 W CN2021073307 W CN 2021073307W WO 2022141699 A1 WO2022141699 A1 WO 2022141699A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- fluorene
- formaldehyde
- preparation
- reaction
- metal alkoxide
- Prior art date
Links
- RNDGADNGORZKGH-UHFFFAOYSA-N 9h-fluorene-9-carbaldehyde Chemical compound C1=CC=C2C(C=O)C3=CC=CC=C3C2=C1 RNDGADNGORZKGH-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims abstract description 7
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims abstract description 68
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims abstract description 18
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- 229910052751 metal Inorganic materials 0.000 claims abstract description 14
- 239000002184 metal Substances 0.000 claims abstract description 14
- 150000004703 alkoxides Chemical class 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 4
- 239000007787 solid Substances 0.000 claims abstract description 4
- 239000008346 aqueous phase Substances 0.000 claims abstract description 3
- 238000001816 cooling Methods 0.000 claims abstract description 3
- 238000010791 quenching Methods 0.000 claims abstract description 3
- 230000000171 quenching effect Effects 0.000 claims abstract description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 45
- 238000002360 preparation method Methods 0.000 claims description 13
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-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
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract description 3
- 230000001376 precipitating effect Effects 0.000 abstract description 2
- -1 Schiff base compounds Chemical class 0.000 description 7
- 239000002585 base Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 239000007789 gas Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- XXSCONYSQQLHTH-UHFFFAOYSA-N 9h-fluoren-9-ylmethanol Chemical compound C1=CC=C2C(CO)C3=CC=CC=C3C2=C1 XXSCONYSQQLHTH-UHFFFAOYSA-N 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 3
- OQKYEMHWZYHWBL-UHFFFAOYSA-N 9h-fluoren-1-ylmethanol Chemical compound C1C2=CC=CC=C2C2=C1C(CO)=CC=C2 OQKYEMHWZYHWBL-UHFFFAOYSA-N 0.000 description 2
- DNVJGJUGFFYUPT-UHFFFAOYSA-N 9h-fluorene-9-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)C3=CC=CC=C3C2=C1 DNVJGJUGFFYUPT-UHFFFAOYSA-N 0.000 description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
- 239000002262 Schiff base Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000011280 coal tar Substances 0.000 description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WMSUFWLPZLCIHP-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 9h-fluoren-9-ylmethyl carbonate Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)ON1C(=O)CCC1=O WMSUFWLPZLCIHP-UHFFFAOYSA-N 0.000 description 1
- XYVDWGHXJFGOEU-UHFFFAOYSA-N C1=CC=CC=2C3=CC=CC=C3CC12.[Na] Chemical compound C1=CC=CC=2C3=CC=CC=C3CC12.[Na] XYVDWGHXJFGOEU-UHFFFAOYSA-N 0.000 description 1
- 125000006414 CCl Chemical group ClC* 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229920002593 Polyethylene Glycol 800 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 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
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
Definitions
- the invention relates to the field of fine chemical intermediate synthesis, in particular to a preparation method of a chemical intermediate 9-fluorene carboxaldehyde.
- 9-Fluorene carboxaldehyde is an important chemical intermediate, which is a key intermediate in the synthesis of 9-fluorene methanol, 9-fluorene carboxylic acid and fluorene-containing Schiff base.
- 9-Fluorene methanol is the key raw material for the preparation of amino protecting agents chloroformic acid-9-fluorene methyl ester (Fm°C-Cl) and 9-fluorenylmethyl-N-succinimidyl carbonate (Fm°C-OSU).
- 9-Fluorenecarboxylic acid can be used in dyes, paints, medicines, resins, pesticides, etc.
- Fluorene-containing Schiff base compounds are important intermediates for the synthesis of organic electroluminescent materials.
- Industrial fluorene is extracted from coal tar, a relatively cheap and readily available basic raw material.
- the content of fluorene in coal tar reaches 1-2%, and the annual fluorene resource in my country can reach 14,000 tons, and now about 1,000 tons are separated every year, which provides raw material guarantee for the development of fluorene-derived products.
- the methylene group at the 9-position of fluorene is affected by two benzene rings and is an active methylene group.
- the hydrogen atom on it can be removed by a strong base to form a carbanion.
- the synthesis of 9-fluorene carboxaldehyde is obtained by removing a proton on the methylene group at the 9-position of fluorene by strong bases such as alkali metal alkoxide or sodium hydrogen to generate an anion of fluorene, and then nucleophilic substitution reaction with ethyl formate.
- Zheng Jihuang et al. used potassium ethoxide as the base, ethanol as the reaction medium, PEG800 as the phase transfer catalyst, and fluorene reacted with ethyl formate to generate 9-fluorene carboxaldehyde. (Zheng Jihuang, Zeng Longmei. Improvement of Fluorene Methanol Synthesis Method [J]. Chemical Reagents, 1992, 014(003): 189-189.).
- Potassium ethoxide is an unconventional alkali metal alkoxide, and the market supply is relatively small. Potassium ethoxide needs to be prepared on site with metal potassium, and the production process has high safety risks.
- Jiang Yechao et al used sodium ethoxide as alkali (Jiang Yechao.
- ethyl formate The boiling point of ethyl formate is also relatively low, and it is used as a solvent at 53 °C, which is volatile and has large solvent loss, which brings pressure on exhaust gas treatment and environmental protection.
- Chinese patent CN103351280A uses sodium ethoxide as the base and tetrahydrofuran as the reaction medium, and fluorene reacts with ethyl formate to generate 9-fluorene formaldehyde; tetrahydrofuran can be co-dissolved with water, it is difficult to remove water, and it is used as a solvent, which is difficult to recover and apply; in addition, the boiling point of tetrahydrofuran The lower temperature is 66°C.
- the existing 9-fluorene formaldehyde synthesis method has the defects of large production safety hazard, large solvent loss, and low conversion rate.
- the technical problem to be solved by the present invention is to provide a synthetic method of 9-fluorene formaldehyde which is suitable for industrial production, has high production safety, is environment-friendly and efficient.
- a preparation method of 9-fluorene formaldehyde comprising the following steps: adding industrial fluorene, metal alkoxide and ethyl formate in a solvent, reacting at 30-80 DEG C for 0.5-10 hours to obtain 9-fluorene formaldehyde; after the reaction, cooling down , after quenching the reaction with acid, extracting, adjusting the pH of the aqueous phase to pH less than 3, precipitating a solid, and recrystallizing to obtain the target product.
- the molar ratio of fluorene, metal alkoxide and ethyl formate is 1:1-3:1-6.
- the metal alkoxide is an alkali metal alkoxide with stable supply in the market, including conventional alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, and combinations thereof; in a preferred example of the present invention, sodium methoxide is selected. and potassium tert-butoxide or combined alkali metal alkoxides of sodium ethoxide and potassium tert-butoxide.
- the molar ratio of the fluorene to the metal alkoxide is 1:1.5-2.1; further, the molar ratio of the fluorene to the metal alkoxide is 1:2.0-2.1. If the metal alkoxide is a mixture, the above molar ratio refers to the ratio of the total molar amount of the fluorene to the metal alkoxide mixture.
- the molar ratio of fluorene to ethyl formate is 1:1.5-6; further, the molar ratio of fluorene to ethyl formate is 1:2-4.
- the solvent is selected from tetrahydrofuran, toluene, xylene (including ortho-xylene, meta-xylene, para-xylene) or a mixed solvent thereof.
- the usage amount of the solvent is 1 to 10 times the mass of fluorene; further, the usage amount of the solvent is 2 to 5 times the mass of fluorene; further, the usage amount of the solvent is 1 to 5 times the mass of fluorene 3 to 5 times.
- the reaction temperature is 35-75°C; further, the reaction temperature is 35-50°C.
- the preparation method of 9-fluorene formaldehyde provided by the invention has the characteristics of safety, environmental protection and easy operation, high conversion rate of fluorene and good product purity, and also provides a new way for improving the utilization rate of industrial fluorene.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
一种化学中间体9-芴甲醛的制备方法，包括如下步骤：在溶剂中加入工业芴、金属醇盐及甲酸乙酯，在30～80℃反应0.5～10小时得到9-芴甲醛；反应结束后，降温，用酸淬灭反应后进行萃取，水相调酸至pH小于3，析出固体，重结晶得到目标产物。
Description
本发明涉及及精细化学中间体合成领域，尤其涉及一种化学中间体9-芴甲醛的制备方法。
9-芴甲醛是一种重要化学中间体，是合成9-芴甲醇、9-芴甲酸以及含芴Schiff碱的关键中间体。9-芴甲醇是制备氨基保护剂氯代甲酸-9-芴甲酯(Fm℃-Cl)、9-芴甲基-N-琥珀酰亚胺基碳酸酯(Fm℃-OSU)的关键原料。9-芴甲酸可以用于染料、油漆、医药、树脂、杀虫剂等。含芴Schiff碱化合物是合成有机电致发光材料的重要中间体。
工业芴是煤焦油中提取出来的，相对价廉、易得的基础原料。芴在煤焦油中含量达到1～2％，我国每年的芴资源可达1.4万吨，现在每年分离的约1000吨，为开发芴衍生产品的生产提供了原料保障。芴-9位的亚甲基受2个苯环的影响，是活泼亚甲基，它上面的氢原子可以通过强碱脱去，生成碳负离子。9-芴甲醛的合成是通过碱金属醇盐或钠氢等强碱脱去芴-9位亚甲基上的一个质子生成芴负离子，再与甲酸乙酯发生亲核取代反应得到。
目前9-芴甲醛作为分离产物被报道，只有在合成9-芴甲醇的过程中作为一个非分离中间体被报道。周祖新等以钠氢做碱，甲酸乙酯既是反应物也是反应介质，与芴反应生成9-芴甲醛(周祖新,顾建生.氢化钠催化法合成芴甲醇[J].化学试剂，2003,25(006):373-374.)。由于钠氢来源较困难，使用条件较苛刻，而且反应过程中会释放可燃气体氢气，生产过程中存在较大的安全隐患。郑基煌等人以乙醇钾做碱，以乙醇做反应介质，PEG800做相转移催化剂，芴与甲酸乙酯反应生成9-芴甲醛。(郑基煌，曾陇梅.芴甲醇合成方法的改进[J].化学试剂,1992,014(003):189-189.)。乙醇钾为非常规碱金属醇盐，市场供应比较少，需用金属钾现场制备乙醇钾，生产工艺具有较高的安全风险。姜业朝等人以乙醇钠作碱(姜业朝.宝鸡文理学院学报[J],2002,22(3):193-216)，中国专利CN104649866A以甲醇钠作碱，均以甲酸乙酯作为原料和反应介质，与芴反应生成9-芴甲醛；但用甲酸乙酯做溶剂，由于甲酸乙酯在醇钠等强碱作用下会剧烈分解，产生大量的一氧化碳气体，甲酸乙酯消耗量大，而且大量释放的一氧化碳也存在安全隐患。甲酸乙酯的沸点也比较低，为53℃作溶剂使用，易挥发，溶剂损失大，带来尾气处理和环保压力。中国专利CN103351280A以乙醇钠作碱，以四氢呋喃为反应介质，芴与甲酸乙酯反应生成9-芴甲醛；四氢呋喃能够与水共溶，难以除水，作溶剂使用，难以回收套用；另外四氢呋喃的沸点较低，为66℃，作溶剂使用，易挥发，溶剂损失大，还会带来尾气处理和环保压力。同时四氢呋喃的运输、储存过程也存在安全隐患。另外甲醇钠、乙醇钠及其生成的芴钠在甲苯等非极性溶剂里溶解度比较低，反应速度慢，芴的转化率也比较低。
综上，现有的9-芴甲醛合成方法，具有生产安全隐患较大、溶剂损耗大、转化率较低的缺陷，目前亟需一种能够适用于工业化生产的、生产安全度较高、环保、高效的9-芴甲醛的制备方法。
发明内容
本发明要解决的技术问题是：提供一种能够适用于工业化生产的、生产安全度较高、环保、高效的9-芴甲醛的合成方法。
本发明解决上述技术问题的技术方案如下：
一种9-芴甲醛的制备方法，包括如下步骤：在溶剂中加入工业芴、金属醇盐及甲酸乙酯，在30～80℃反应0.5～10小时得到9-芴甲醛；反应结束后，降温，用酸淬灭反应后进行萃取，水相调酸至pH小于3，析出固体，重结晶得到目标产物。
所述芴、金属醇盐及甲酸乙酯的投料摩尔比为1：1～3：1～6。
优选的，金属醇盐为有市场稳定供应的碱金属醇盐，包括甲醇钠、乙醇钠、叔丁醇钾等常规碱金属醇盐及其组合；在本发明的优选例中，选用了甲醇钠和叔丁醇钾或乙醇钠和叔丁醇钾的组合碱金属醇盐。
优选的，所述芴与金属醇盐的投料摩尔比为1：1.5～2.1；更进一步的，所述芴与金属醇盐的投料摩尔比为1：2.0～2.1。如金属醇盐为混合物，上述投料摩尔比是指芴与金属醇盐混合物的总摩尔量的比值。
优选的，所述芴与甲酸乙酯的投料摩尔比为1：1.5～6；进一步的，所述芴与甲酸乙酯的投料摩尔比为1：2～4。
优选的，所述溶剂选自四氢呋喃、甲苯、二甲苯(包括邻二甲苯、间二甲苯、对二甲苯)或者它们的混合溶剂。
优选的，所述溶剂的使用量为芴质量的1～10倍；进一步的，所述溶剂的使用量为芴质量的2～5倍；更进一步的，所述溶剂的使用量为芴质量的3～5倍。
优选的，所述反应温度为35～75℃；进一步的，所述反应温度为35～50℃。
本发明中化合物的中文命名与结构式有冲突的，以结构式为准；结构式有明显错误的除外。
本发明提供的9-芴甲醛的制备方法具有安全、环保、易操作的特性，芴的转化率高，产物纯度好，也为提高工业芴的利用率提供了新的出路。
以下结合实例说明本发明，但不限制本发明。在本领域内，技术人员对本发明所做的简单替换或改进均属于本发明所保护的技术方案内。
实施例：
在带机械搅拌，恒压滴液漏斗和回流冷凝管的四口烧瓶中，加入化学计量的甲苯，开启搅拌，加入化学计量工业芴，化学计量甲醇钠，反应体系由白色变换浅棕色，并出现大量悬浮物，控制物料温度，滴加化学计量的甲酸乙酯，滴加完毕，继续保温反应到指定时间，取样，稀酸淬灭后气相中控。试验结果如下表1所示。
以上所述的仅是本发明的优选实施方式，应当指出，对于本领域的普通技术人员来说，在不脱离本发明创造构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。
Claims (10)
- 一种9-芴甲醛的制备方法，包括如下步骤：在溶剂中加入工业芴、金属醇盐及甲酸乙酯，在30～80℃反应0.5～10小时得到9-芴甲醛；反应结束后，降温，用酸淬灭反应后进行萃取，水相调酸至pH小于3，析出固体，重结晶得到目标产物；所述芴、金属醇盐及甲酸乙酯的投料摩尔比为1：1～3：1～6。
- 如权利要求1所述的9-芴甲醛的制备方法，其特征在于，所述金属醇盐为甲醇钠、乙醇钠、叔丁醇钾及其组合。
- 如权利要求1所述的9-芴甲醛的制备方法，其特征在于，所述芴与金属醇盐的投料摩尔比为1：1.5～2.1。
- 如权利要求3所述的9-芴甲醛的制备方法，其特征在于，所述芴与金属醇盐的投料摩尔比为1：2.0～2.1。
- 如权利要求1所述的9-芴甲醛的制备方法，其特征在于，所述芴与甲酸乙酯的投料摩尔比为1：1.5～6。
- 如权利要求1所述的9-芴甲醛的制备方法，其特征在于，所述溶剂选自四氢呋喃、甲苯、二甲苯或者它们的混合溶剂。
- 如权利要求1所述的9-芴甲醛的制备方法，其特征在于，所述溶剂的使用量为芴质量的1～10倍。
- 如权利要求7所述的9-芴甲醛的制备方法，其特征在于，所述溶剂的使用量为芴质量的2～5倍。
- 如权利要求1所述的9-芴甲醛的制备方法，其特征在于，所述反应的温度为35～75℃。
- 如权利要求9所述的9-芴甲醛的制备方法，其特征在于，所述反应的温度为35～50℃。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011597221.3A CN112724003B (zh) | 2020-12-29 | 2020-12-29 | 一种9-芴甲醛的制备方法 |
| CN202011597221.3 | 2020-12-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022141699A1 true WO2022141699A1 (zh) | 2022-07-07 |
Family
ID=75611342
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2021/073307 WO2022141699A1 (zh) | 2020-12-29 | 2021-01-22 | 一种9-芴甲醛的制备方法 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN112724003B (zh) |
| WO (1) | WO2022141699A1 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112724003B (zh) * | 2020-12-29 | 2022-12-27 | 常州吉恩药业有限公司 | 一种9-芴甲醛的制备方法 |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08268950A (ja) * | 1995-03-30 | 1996-10-15 | Nippon Steel Chem Co Ltd | フルオレン−９−カルバアルデヒド類の製造方法 |
| JPH11255686A (ja) * | 1998-03-11 | 1999-09-21 | Sumikin Chem Co Ltd | ９−フルオレニルメタノールの製造方法 |
| CN1884242A (zh) * | 2005-06-22 | 2006-12-27 | 上海宝钢化工有限公司 | 一种制取9－芴甲醇的方法 |
| CN102108049A (zh) * | 2010-12-17 | 2011-06-29 | 上海博康精细化工有限公司 | 9-芴甲酸的制备方法 |
| CN102850187A (zh) * | 2011-06-29 | 2013-01-02 | 鞍钢股份有限公司 | 一种9-芴甲醇的制取方法 |
| CN103351280A (zh) * | 2013-06-17 | 2013-10-16 | 张家港威胜生物医药有限公司 | 一种关于9-芴甲醇的简易制备工艺 |
| CN104649866A (zh) * | 2013-11-21 | 2015-05-27 | 天津广顺化学科技有限公司 | 基于低成本安全可靠的9-芴甲醇制备方法 |
| CN112724003A (zh) * | 2020-12-29 | 2021-04-30 | 常州吉恩药业有限公司 | 一种9-芴甲醛的制备方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9682060B2 (en) * | 2015-10-16 | 2017-06-20 | The Board Of Trustees Of The University Of Illinois | Small molecules that induce intrinsic pathway apoptosis |
-
2020
- 2020-12-29 CN CN202011597221.3A patent/CN112724003B/zh active Active
-
2021
- 2021-01-22 WO PCT/CN2021/073307 patent/WO2022141699A1/zh active Application Filing
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08268950A (ja) * | 1995-03-30 | 1996-10-15 | Nippon Steel Chem Co Ltd | フルオレン−９−カルバアルデヒド類の製造方法 |
| JPH11255686A (ja) * | 1998-03-11 | 1999-09-21 | Sumikin Chem Co Ltd | ９−フルオレニルメタノールの製造方法 |
| CN1884242A (zh) * | 2005-06-22 | 2006-12-27 | 上海宝钢化工有限公司 | 一种制取9－芴甲醇的方法 |
| CN102108049A (zh) * | 2010-12-17 | 2011-06-29 | 上海博康精细化工有限公司 | 9-芴甲酸的制备方法 |
| CN102850187A (zh) * | 2011-06-29 | 2013-01-02 | 鞍钢股份有限公司 | 一种9-芴甲醇的制取方法 |
| CN103351280A (zh) * | 2013-06-17 | 2013-10-16 | 张家港威胜生物医药有限公司 | 一种关于9-芴甲醇的简易制备工艺 |
| CN104649866A (zh) * | 2013-11-21 | 2015-05-27 | 天津广顺化学科技有限公司 | 基于低成本安全可靠的9-芴甲醇制备方法 |
| CN112724003A (zh) * | 2020-12-29 | 2021-04-30 | 常州吉恩药业有限公司 | 一种9-芴甲醛的制备方法 |
Non-Patent Citations (1)
| Title |
|---|
| JIANG YECHAO: "Improved Method of Synthesizing 9-Fluorenemethanol", BAOJI WEN-LI XUEYUAN XUEBAO. ZIRAN KEXUE BAN - JOURNAL OF BAOJICOLLEGE OF ARTS AND SCIENCE. NATURAL SCIENCE ED., BAOJI WEN-LI XUEYUAN ZAZHIHE, BAOJI, CN, vol. 22, no. 3, 15 September 2002 (2002-09-15), CN , XP055948608, ISSN: 1007-1261, DOI: 10.13467/j.cnki.jbuns.2002.03.013 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112724003B (zh) | 2022-12-27 |
| CN112724003A (zh) | 2021-04-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Qiu et al. | Direct conversion of phenols into primary anilines with hydrazine catalyzed by palladium | |
| CN106938976B (zh) | 一种以醇和胺为原料催化氧化制备亚胺类化合物的方法 | |
| CN112979498A (zh) | 一种3-氟-4-三氟甲基苯氰的制备方法 | |
| WO2022141699A1 (zh) | 一种9-芴甲醛的制备方法 | |
| WO2022073343A1 (zh) | 一种9,9-二[4-(2-羟基乙氧基)苯基]芴的合成方法 | |
| CN114349674B (zh) | 一种硫脲类化合物及其制备方法 | |
| CN113831318A (zh) | 一种胡椒乙胺的合成方法 | |
| CN103992294B (zh) | 一种丙烯酰胺类活性稀释剂的合成方法 | |
| CN101831662B (zh) | 制备丁二酸单甲酯的方法 | |
| CN112028748A (zh) | 一种2，5-二甲氧基氯苯的制备方法 | |
| CN105032473B (zh) | 一种采用硫酸改性处理纳米级hzsm‑5催化剂制备二烷氧基甲烷的方法 | |
| CN101781199B (zh) | 一种o-酰基杯[4]芳烃的化学合成方法 | |
| CN101591238B (zh) | 丙烯海松酸的制备方法 | |
| CN107216244B (zh) | 一种制备3,5,5-三甲基-3-环己烯-1-酮的方法 | |
| Sheppard | Fluoroalkyl quinonemethides | |
| CN108658803B (zh) | 一种n,n-二烷基二苯基丙酰胺的合成方法 | |
| CN111253358A (zh) | 一种异香豆素芳香醚类化合物的合成方法 | |
| CN110172041B (zh) | 合成环嗪酮的新方法 | |
| CN111423319B (zh) | 一种洛索洛芬的制备方法 | |
| CN108774155A (zh) | 一种3-氟-4-氰基苯酚的制备方法 | |
| EP4036189A1 (en) | Process for synthesis of polyhydrocarbons as heat transfer agents | |
| CN113980686B (zh) | 一种含环己基的侧向邻二氟苯类液晶化合物的制备方法 | |
| JP4157361B2 (ja) | ９−スピロフルオレン化合物の製造方法 | |
| CN113698355B (zh) | 一种4,5-二羟基哒嗪的合成方法 | |
| CN112409186B (zh) | 一种在水中合成n-甲基苯胺的方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21912479 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 21912479 Country of ref document: EP Kind code of ref document: A1 |