CN112279753A - 一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法 - Google Patents
一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法 Download PDFInfo
- Publication number
- CN112279753A CN112279753A CN202011178976.XA CN202011178976A CN112279753A CN 112279753 A CN112279753 A CN 112279753A CN 202011178976 A CN202011178976 A CN 202011178976A CN 112279753 A CN112279753 A CN 112279753A
- Authority
- CN
- China
- Prior art keywords
- gamma
- bromo
- alkenyl
- fluoroketone
- formula
- 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
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
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/69—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to carbon-to-carbon double or triple bonds
-
- 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
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
-
- 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
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
-
- 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
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
-
- 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
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/79—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- 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
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/80—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及一种γ‑溴‑β,γ‑烯基氟代酮类衍生物的制备方法,该方法为:将式(IV)所示的化合物和对应的炔烃溶解在丙酮中,加入双三苯基膦二氯化钴、1,2‑双(二苯基膦基)苯、锌粉和水在N2保护下进行反应,得到的反应液经过滤、浓缩、分离后得到式(V)所示化合物,即γ‑溴‑β,γ‑烯基氟代酮衍生物;其中,R1为苯基,取代苯基,杂环,取代苯基中的取代基选自氢,氟,溴,三氟甲基,甲基或甲氧基中的一种或几种;R2为苯基或取代苯基,取代苯基中的取代基选自氢,溴,氯,甲基或乙基中的一种或几种。与现有技术相比,本发明产率高,经济适用性强,制备方法简便,易于操作,反应条件温和,且适用于工业生产,可应用于药物的设计合成。
Description
技术领域
本发明涉及有机合成领域,具体涉及一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法。
背景技术
在化合物分子结构中引入氟原子通常会引起其物理、化学性能以及药理生理活性的改变,基于氟原子的特殊性质,在化合物中引入氟原子一直是药物合成的研究热点。炔烃的加成来获取含氟烯烃化合物是常见的方法,且研究发现多取代含氟烯烃类化合物都具备一定的生物活性。因此发现新的和更有效的引发剂体系及其在有机合成中的应用是很有必要的。
发明内容
本发明的目的就是为了克服上述现有技术存在的缺陷而提供一种钴催化的由炔烃制备γ-溴-β,γ-烯基氟代酮类衍生物的简单方法。
本发明的目的可以通过以下技术方案来实现:
一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法,该方法为:将式(IV)所示的化合物和对应的炔烃溶解在丙酮中,加入双三苯基膦二氯化钴、1,2-双(二苯基膦基)苯、锌粉和水在N2保护下进行反应,得到的反应液经过滤、浓缩、分离后得到式(V)所示化合物,即γ-溴-β,γ-烯基氟代酮衍生物;
其中,R1为苯基,取代苯基,杂环,取代苯基中的取代基选自氢,氟,溴,三氟甲基,甲基或甲氧基中的一种或几种;R2为苯基或取代苯基,取代苯基中的取代基选自氢,溴,氯,甲基或乙基中的一种或几种。
进一步地,所述的化合物(IV)、炔烃、双三苯基膦二氯化钴、1,2-双(二苯基膦基)苯的摩尔比为1:(1.2-1.5):0.05:0.05。
进一步地,所述的反应温度为室温,反应时间为1-2h。
进一步地,浓缩后,将所得的浓缩物以体积比石油醚/乙酸乙酯=(300-100): 1为洗脱剂,进行柱层析分离。
进一步地,所述的化合物(IV)采用以下方法制备:将式(III)所示的化合物置于反应容器中,加入LiBr、Selectfluor和Et3N的THF溶液,进行反应,将所得的反应液经萃取,浓缩,分离,得到式(IV)所示的化合物;
其中,R1为苯基,取代苯基,杂环,取代苯基中的取代基选自氢,氟,溴,三氟甲基,甲基或甲氧基中的一种或几种。
进一步地,所述的反应温度为室温,反应时间为0.5-1h。
进一步地,所述的浓缩后,将浓缩物以体积比石油醚/乙酸乙酯=(300-200): 1为洗脱剂,进行柱层析分离。
进一步地,所述的化合物(III)、LiBr、Selectfluor和Et3N的摩尔比为1: (6.0-6.4):2.0:2.0。
进一步地,所述的式(III)所示的化合物的制备方法包括以下步骤:
(1)以式(I)所示的含甲基酮类化合物和三氟乙酸乙酯为原料,以无水THF 为溶剂,NaH为引发剂,在室温下进行反应,将得到的反应液经萃取,干燥,浓缩得到式(II)所示的化合物;
(2)以式(II)所示的化合物为原料加入三水合硝酸铜,以乙腈为溶剂,反应后,再在-20℃环境下加入Selectfluor,将得到的反应液经萃取,干燥,浓缩,提纯得到式(III)所示的化合物;
其中:R1为苯基,取代苯基,杂环,取代苯基中的取代基选自氢,氟,溴,三氟甲基,甲基或甲氧基中的一种或几种。
进一步地,步骤(2)中所述的反应时间为2h。
与现有技术相比,本发明产率高,经济适用性强,制备方法简便,易于操作,反应条件温和,且适用于工业生产,可应用于药物的设计合成。
具体实施方式
下面对本发明的实施例作详细说明,本实施例在以本发明技术方案为前提下进行实施,给出了详细的实施方式和具体的操作过程,但本发明的保护范围不限于下述的实施例。
化合物(IV):2-氟-2-溴-1-苯基乙烷-1-酮的制备
(1)重要中间体化合物(II)的合成
在干燥的250mL圆底烧瓶中,加入60%的NaH 4.0g(0.1mol),加入干燥适量的无水乙醚,并且均匀搅拌,之后称取苯乙4.8g(40mmol)和7.1g (50mmol)三氟乙酸乙酯,用适量的无水乙醚进行稀释,稀释完毕后,用恒压滴液漏斗,逐滴加入上述溶液,滴加完毕后,在室温下反应2h,用层析板跟踪检测,直到反应完全。反应完之后经过冷却,淬灭,萃取,洗涤、干燥和过滤等后处理,用旋转蒸发仪旋干滤液得到产品粗品。
(2)重要中间体化合物(III)的合成
将上述粗品化合物(II)加入干燥的250mL圆底烧瓶中,加入三水合硝酸铜 1.9g(8mmol),加入适量的乙腈并溶解,在室温下搅拌2h,将烧瓶放入冷井中搅拌,称取选择性氟化试剂selectfluor(48mmol,17g)溶解在50mL乙腈和4mL水的溶剂中,用恒压滴液漏斗加入上述烧瓶内,加料完毕后,在-20℃下反应6h,用层析板跟踪检测,直到反应完全,反应完之后温热至室温,经过滤,萃取,洗涤、干燥等后处理,用旋转蒸发仪旋干滤液得到产品粗品。
(3)化合物(IV)的合成
将上述粗品(III)加入干燥的250mL圆底烧瓶中,再加入干燥的四氢呋喃,搅拌至充分溶解,后加入无水溴化锂(256mmol,22.2g,6equiv),搅拌均匀后,接着加入selectfluor(80mmol,28.3g,2equiv),加料完毕后继续搅拌10min后,逐滴滴加三乙胺(80mmol,8g,2equiv),加料完毕后,室温下搅拌反应30min,用层析板跟踪检测,直到反应完全,反应完之后经过过滤,萃取,洗涤、干燥等后处理,用旋转蒸发仪旋干滤液得到产品粗品,旋干滤液得粗品,用体积比 PE:EA=100:1的洗脱液经柱层析进行分离,最终得到白色固体,即化合物(IV) (收率60%)。
1H NMR(500MHz,CDCl3):δ7.96(d,J=8.0Hz,2H),7.31(d,J=7.9Hz, 2H),7.18(d,J=51.1Hz,1H),2.44(s,3H)ppm,19F NMR(376MHz,CDCl3):δ -152.0(d,J=48.9Hz,1F)ppm.
实施例1
2-氟-4-溴-1,4-二苯基丁-3-烯-1-酮的制备
称取2-氟-2-溴-1-苯基乙烷-1-酮(2.17g,0.01mol)置于250mL圆底烧瓶中,加入苯乙炔(1.23g,0.012mol),双二苯基膦二氯化钴(33mg,0.1mmol), 1,2-双(二苯基膦基)苯(22mg,0.1mmol),锌粉(0.65g,0.01mol)以及30ml 丙酮1mL水,抽真空氮气回填三次后,在常温搅拌1小时后,TLC监测反应完全。抽滤,所得混合物分别用50mL,40mL,40mL的乙酸乙酯萃取三次,收集合并有机相,用无水硫酸钠干燥30分钟。过滤,减压蒸馏浓缩后的有机相用石油醚:乙酸乙酯=(200-100):1的洗脱剂进行柱层析分离,最后得到淡黄色油状液体(收率81%,Z/E=0.6:1)。
1H NMR(500MHz,CDCl3):(E):δ7.80(d,J=7.80Hz,2H),7.56–7.63(m, 1H),7.5–7.53(m,2H),7.24–7.46(m,3H),7.35–7.36(m,2H),6.48–6.52(m, 1H),5.81(dd,J=10,45Hz,1H);(Z):δ8.07(d,J=8.07Hz,2H),7.56–7.63(m,3 H),7.5–7.53(m,2H),7.24–7.46(m,3H),6.57(dd,J=10,50Hz,1H),6.48– 6.52(m,1H);
13C NMR(100MHz,CDCl3):(E):δ193.30(d,J=22Hz),137.09(d,J=3 Hz),134.23(d,J=12Hz),133.78,133.34(d,J=15Hz),130.05,129.03(d,J=3 Hz),129.03(d,J=3Hz),128.92,128.92,128.75(d,J=4Hz),128.75(d,J=4Hz), 127.91(d,J=2Hz),127.91(d,J=2Hz),126.09(d,J=20Hz),89.32(d,J=180 Hz);(Z):δ193.22(d,J=21Hz),138.23(d,J=2Hz),134.72(d,J=13Hz),134.29, 133.95,130.05,129.03(d,J=3Hz),129.03(d,J=3Hz),128.75(d,J=4Hz), 128.75(d,J=4Hz),128.53,128.53,127.91(d,J=2Hz),127.91(d,J=2Hz), 123.23(d,J=21Hz),91.57(d,J=178Hz);
19F NMR(376MHz,CDCl3):(E):δ-170.55(dd,J=48.1,6.1Hz);(Z):δ -178.37(dd,J=46.9,9.2Hz).
实施例2
2-氟-4-溴-1-对甲苯基-4-苯基丁-3-烯-1-酮的制备
称取2-氟-2-溴-1-对甲苯基乙烷-1-酮(2.31g,0.01mol)置于250mL圆底烧瓶中,加入苯乙炔(1.23g,0.012mol),双二苯基膦二氯化钴(33mg, 0.1mmol),1,2-双(二苯基膦基)苯(22mg,0.1mmol),锌粉(0.65g,0.01mol) 以及30ml丙酮1mL水,抽真空氮气回填三次后,在常温搅拌1小时后,TLC 监测反应完全。抽滤,所得混合物分别用50mL,40mL,40mL的乙酸乙酯萃取三次,收集合并有机相,用无水硫酸钠干燥30分钟。过滤,减压蒸馏浓缩后的有机相用石油醚:乙酸乙酯=(200-100):1的洗脱剂进行柱层析分离,最后得到淡黄色油状液体(收率72%,Z/E=0.65:1)。
1H NMR(500MHz,CDCl3):(E):δ7.69(d,J=5Hz,2H),7.51–7.52(m, 2H),7.44–7.48(m,3H),7.23(d,J=5Hz,2H),6.45–6.49(m,1H),5.79(dd,J= 10,50Hz,1H),2.40(s,3H);(Z):δ7.98(d,J=10Hz,2H),7.55–7.57(m,2H),7.33 –7.36(m,3H),7.23(d,J=5Hz,2H),6.55(dd,J=5,45Hz,1H),6.45–6.49(m, 1H),2.42(s,3H);
13C NMR(125MHz,CDCl3):(E):δ192.87(d,J=21.25Hz),145.32, 137.13(d,J=2.5Hz),133.13(d,J=15Hz),131.26,130.03,129.49,129.49, 129.14(d,J=2.5Hz),129.14(d,J=2.5Hz),128.92(d,J=2.5Hz),128.92(d,J =2.5Hz),128.73,128.73,126.35(d,J=21.25Hz),89.24(d,J=180Hz),21.80;(Z): δ192.77(d,J=21.25Hz),145.42,138.26(d,J=2.5Hz),134.51(d,J=12.5Hz), 131.48,130.06,129.63,129.63,129.04(d,J=2.5Hz),129.04(d,J=2.5Hz), 128.53,128.53,127.91(d,J=2.5Hz),127.91(d,J=2.5Hz),123.47(d,J=21.25 Hz),91.49(d,J=102.5Hz),21.80;
19F NMR(376MHz,CDCl3):(E):δ-178.43(dd,J=48.88,7.52Hz);(Z):δ -170.69(dd,J=48.88,7.52Hz);
实施例3
2-氟-4-溴-1-(4-(甲氧基)苯基)-4-苯基丁-3-烯-1-酮的制备
称取2-氟-2-溴-1-(4-(甲氧基)苯基)乙烷-1-酮(2.47g,0.01mol)置于250mL 圆底烧瓶中,加入苯乙炔(1.23g,0.012mol),双二苯基膦二氯化钴(33mg, 0.1mmol),1,2-双(二苯基膦基)苯(22mg,0.1mmol),锌粉(0.65g,0.01mol) 以及30ml丙酮1mL水,抽真空氮气回填三次后,在常温搅拌1小时后,TLC 监测反应完全。抽滤,所得混合物分别用50mL,40mL,40mL的乙酸乙酯萃取三次,收集合并有机相,用无水硫酸钠干燥30分钟。过滤,减压蒸馏浓缩后的有机相用石油醚:乙酸乙酯=(200-100):1的洗脱剂进行柱层析分离,最后得到淡黄色油状液体(收率78%,Z/E=1:1)。
1H NMR(400MHz,CDCl3):(E):δ7.77–7.81(m,2H),7.50–7.53(m, 2H),7.34–7.36(m,3H),6.87–6.91(m,2H),6.46–6.50(m,1H),5.75(dd,J= 10,50Hz,1H),3.86(s,3H);(Z):δ8.05–8.07(m,2H),7.55–7.59(m,2H),7.44 –7.47(m,3H),6.96–6.99(m,2H),6.55(dd,J=8,28Hz,1H),6.46–6.50(m, 1H),3.88(s,3H);
13C NMR(100MHz,CDCl3):(E):δ191.59(d,J=22Hz),145.30,137.10(d,J =3Hz),132.93(d,J=14Hz),132.93(d,J=14Hz),131.32(d,J=2Hz),128.92(d, J=2Hz),128.49,128.49,127.88(d,J=1Hz),126.68,126.68,123.61(d,J=20 Hz),113.99,113.99,89.22(d,J=179Hz),55.56;(Z):δ191.54(d,J=20Hz), 145.42,138.24(d,J=3Hz),134.30(d,J=13Hz),134.30(d,J=13Hz),131.45(d, J=4Hz),129.99(d,J=3Hz),128.68,128.68,127.88(d,J=1Hz),126.67,126.67, 126.47(d,J=19Hz),114.14,114.14,91.36(d,J=177Hz),55.56;
19F NMR(376MHz,CDCl3):(E):δ-169.90(dd,J=48.88,7.52Hz);(Z):δ -177.88–-178.03(m);
实施例4
2-氟-4-溴-1-苯基-4-(对甲苯基)丁-3-烯-1-酮的制备
称取2-氟-2-溴-1-苯基乙烷-1-酮(2.17g,0.01mol)置于250mL圆底烧瓶中,加入4-甲基苯乙炔(1.39g,0.012mol),双二苯基膦二氯化钴(33mg, 0.1mmol),1,2-双(二苯基膦基)苯(22mg,0.1mmol),锌粉(0.65g,0.01mol) 以及30ml丙酮1mL水,抽真空氮气回填三次后,在常温搅拌1小时后,TLC 监测反应完全。抽滤,所得混合物分别用50mL,40mL,40mL的乙酸乙酯萃取三次,收集合并有机相,用无水硫酸钠干燥30分钟。过滤,减压蒸馏浓缩后的有机相用石油醚:乙酸乙酯=(200-100):1的洗脱剂进行柱层析分离,最后得到淡黄色油状液体(收率66%,Z/E=0.72:1)
1H NMR(500MHz,CDCl3):(E):δ7.83(d,J=10Hz,2H),7.60–7.66(m, 2H),7.43–7.46(m,3H),7.28–7.29(m,2H),6.45–6.51(m,1H),5.85(dd,J= 10,50Hz,1H),2.44(S,3H);(Z):δ8.09(d,J=5Hz,2H),7.51–7.55(m,2H), 7.47–7.49(m,3H),7.18(d,J=10Hz),6.60(dd,J=10,45Hz,1H),6.45–6.51 (m,1H),2.38(S,3H);
13C NMR(125MHz,CDCl3):(E):δ193.34(d,J=22.5Hz),140.37,134.15, 133.93(d,J=16.25Hz),133.77(d,J=6.25Hz),129.41,129.04(d,J=3.75Hz), 129.04(d,J=3.75Hz),128.90(d,J=2.5Hz),128.90(d,J=2.5Hz),128.77, 128.77,127.84(d,J=2.5Hz),127.84(d,J=2.5Hz),125.68(d,J=18.75Hz), 91.66(d,J=177.5Hz),21.41;(Z):δ193.31(d,J=20Hz),140.46,135.41(d,J= 2.5Hz),135.02(d,J=12.5Hz),134.26,129.21,129.04(d,J=3.75Hz),129.04(d, J=3.75Hz),128.93(d,J=3.75Hz),128.93(d,J=3.75Hz),128.87,128.87, 127.84(d,J=2.5Hz),127.84(d,J=2.5Hz),122.26(d,J=20Hz),89.40(d,J= 178.75Hz),21.23;
19F NMR(376MHz,CDCl3):(E):δ-169.90(dd,J=48.88,7.52Hz);(Z):δ -178.03–-177.88(m);
实施例5
2-氟-4-溴-1-苯基-4-(4-氯苯基)丁-3-烯-1-酮的制备
称取2-氟-2-溴-1-苯基乙烷-1-酮(2.17g,0.01mol)置于250mL圆底烧瓶中,加入4-氯苯乙炔(1.64g,0.012mol),双二苯基膦二氯化钴(33mg, 0.1mmol),1,2-双(二苯基膦基)苯(22mg,0.1mmol),锌粉(0.65g,0.01mol) 以及30ml丙酮1mL水,抽真空氮气回填三次后,在常温搅拌1小时后,TLC 监测反应完全。抽滤,所得混合物分别用50mL,40mL,40mL的乙酸乙酯萃取三次,收集合并有机相,用无水硫酸钠干燥30分钟。过滤,减压蒸馏浓缩后的有机相用石油醚:乙酸乙酯=(200-100):1的洗脱剂进行柱层析分离,最后得到淡黄色油状液体(收率62%,Z/E=1.2:1)。
1H NMR(400MHz,CDCl3):(E):δ7.82(d,J=8Hz,2H),7.26–7.66(m, 7H),6.46–6.55(m,1H),5.73(dd,J=12,48Hz,1H);(Z):δ8.06(d,J=8Hz,2H), 7.26–7.66(m,7H),6.52(dd,J=8,44Hz,1H),6.46–6.55(m,1H);
13C NMR(100MHz,CDCl3):(E):δ193.23(d,J=22Hz),136.18,135.48(d, J=3Hz),134.28,133.73(d,J=2Hz),131.80(d,J=14Hz),130.31(d,J=2Hz), 130.31(d,J=2Hz),129.10,129.10,128.99(d,J=1Hz),128.99(d,J=1Hz), 128.83,128.83,126.69(d,J=20Hz),89.27(d,J=181Hz);(Z):δ193.06(d,J=21 Hz),136.67(d,J=3Hz),136.18,134.37,133.92(d,J=1Hz),133.13(d,J=13 Hz),129.16(d,J=2Hz),129.16(d,J=2Hz),129.06,129.06,128.95(d,J=2Hz), 128.95(d,J=2Hz),128.73,128.73,123.75(d,J=21Hz),91.42(d,J=178Hz);
19F NMR(376MHz,CDCl3):(E):δ-169.60(dd,J=48.88,7.52Hz);(Z):δ -178.13–-177.98(m)。
Claims (10)
2.根据权利要求1所述的一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法,其特征在于,所述的化合物(IV)、炔烃、双三苯基膦二氯化钴、1,2-双(二苯基膦基)苯的摩尔比为1:(1.2-1.5):0.05:0.05。
3.根据权利要求1所述的一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法,其特征在于,所述的反应温度为室温,反应时间为1-2h。
4.根据权利要求1所述的一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法,其特征在于,浓缩后,将所得的浓缩物以体积比石油醚/乙酸乙酯=(300-100):1为洗脱剂,进行柱层析分离。
6.根据权利要求5所述的一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法,其特征在于,所述的反应温度为室温,反应时间为0.5-1h。
7.根据权利要求5所述的一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法,其特征在于,所述的浓缩后,将浓缩物以体积比石油醚/乙酸乙酯=(300-200):1为洗脱剂,进行柱层析分离。
8.根据权利要求5所述的一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法,其特征在于,所述的化合物(III)、LiBr、Selectfluor和Et3N的摩尔比为1:(6.0-6.4):2.0:2.0。
9.根据权利要求5所述的一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法,其特征在于,所述的式(III)所示的化合物的制备方法包括以下步骤:
(1)以式(I)所示的含甲基酮类化合物和三氟乙酸乙酯为原料,以无水THF为溶剂,NaH为引发剂,在室温下进行反应,将得到的反应液经萃取,干燥,浓缩得到式(II)所示的化合物;
(2)以式(II)所示的化合物为原料加入三水合硝酸铜,以乙腈为溶剂,反应后,再在-20℃环境下加入Selectfluor,将得到的反应液经萃取,干燥,浓缩,提纯得到式(III)所示的化合物;
其中:R1为苯基,取代苯基,杂环,取代苯基中的取代基选自氢,氟,溴,三氟甲基,甲基或甲氧基中的一种或几种。
10.根据权利要求9所述的一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法,其特征在于,步骤(2)中所述的反应时间为2h。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011178976.XA CN112279753A (zh) | 2020-10-29 | 2020-10-29 | 一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011178976.XA CN112279753A (zh) | 2020-10-29 | 2020-10-29 | 一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN112279753A true CN112279753A (zh) | 2021-01-29 |
Family
ID=74374042
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202011178976.XA Pending CN112279753A (zh) | 2020-10-29 | 2020-10-29 | 一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112279753A (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113603595A (zh) * | 2021-07-09 | 2021-11-05 | 上海应用技术大学 | 一种γ-溴-β,γ-四取代烯基氟代乙酸乙酯衍生物及其制备方法 |
CN114573438A (zh) * | 2022-03-31 | 2022-06-03 | 上海应用技术大学 | 一种单氟氯/溴代丙酮类化合物及其制备方法 |
CN115231995A (zh) * | 2022-06-14 | 2022-10-25 | 上海应用技术大学 | 一种单氟二溴代丙酮衍生物及其制备与应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110156550A (zh) * | 2019-06-17 | 2019-08-23 | 遵义医科大学 | 一种使用苯酚及其衍生物为光催化剂进行氟烷基化的方法 |
CN110759836A (zh) * | 2019-11-01 | 2020-02-07 | 遵义医科大学 | 一种在丙酮诱导下对烯烃或者炔烃进行氟烷基化的方法 |
-
2020
- 2020-10-29 CN CN202011178976.XA patent/CN112279753A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110156550A (zh) * | 2019-06-17 | 2019-08-23 | 遵义医科大学 | 一种使用苯酚及其衍生物为光催化剂进行氟烷基化的方法 |
CN110759836A (zh) * | 2019-11-01 | 2020-02-07 | 遵义医科大学 | 一种在丙酮诱导下对烯烃或者炔烃进行氟烷基化的方法 |
Non-Patent Citations (7)
Title |
---|
DANFENG WANG 等: "Stereoselective synthesis ofa,a-difluoro-b,g-alkenyl ketones by free-radical reaction of iododifluoromethyl ketones with alkynes", 《TETRAHEDRON》 * |
GUOJIAO WU 等: "ACarbene-Extended ATRA Reaction", 《ANGEW.CHEM. INT.ED. 》 * |
GUOJIAO WU 等: "Stereoselective cobalt-catalyzed halofluoroalkylation of alkynes", 《CHEM. SCI.》 * |
JING-JING MA 等: "Copper-catalyzedfluoroalkylation of alkynes, and alkynyl & vinyl carboxylic acids withfluoroalkyl halides", 《ORG. BIOMOL. CHEM.》 * |
JUNQING LIANG 等: "Nickel-Catalyzed Coupling Reaction of α-Bromo-α-fluoroketones with Arylboronic Acids toward the Synthesis of α-Fluoroketones", 《ORG. LETT》 * |
MICHAEL P. JENNINGS 等: "A Facile Synthesis of Perfluoroalkyl Vinyl Iodides and Their Palladium-Mediated Cross-Coupling Reactions", 《J. ORG. CHEM.》 * |
XIAORUI FENG 等: "Copper-mediated regioselective hydrodifluoroalkylation of alkynes", 《ORG. BIOMOL. CHEM》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113603595A (zh) * | 2021-07-09 | 2021-11-05 | 上海应用技术大学 | 一种γ-溴-β,γ-四取代烯基氟代乙酸乙酯衍生物及其制备方法 |
CN114573438A (zh) * | 2022-03-31 | 2022-06-03 | 上海应用技术大学 | 一种单氟氯/溴代丙酮类化合物及其制备方法 |
CN115231995A (zh) * | 2022-06-14 | 2022-10-25 | 上海应用技术大学 | 一种单氟二溴代丙酮衍生物及其制备与应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN112279753A (zh) | 一种γ-溴-β,γ-烯基氟代酮类衍生物的制备方法 | |
CN109879733B (zh) | 一种单氟溴代丙酮衍生物的合成方法 | |
CN106588804A (zh) | 一种作为类法尼醇 x 受体(fxr)的化合物的制备方法 | |
Mojumdar et al. | [1] Benzofuro [3, 2-c] pyridine synthesis and coordination reactions | |
CN107188840B (zh) | 一种不对称二芳基硒醚化合物的合成方法 | |
CN111592533B (zh) | 1,2,4-噁二唑联吡啶取代苯甲酰胺类化合物及其制备方法和应用 | |
CN111454286A (zh) | 一种二氟烯基硼化合物的合成方法 | |
CN105924450B (zh) | 一种氮杂芴螺环芳烃的合成方法 | |
CN102746224A (zh) | 2-芳基-3,4-二取代异喹啉-1(2h)-酮类衍生物的制备方法 | |
CN106831397B (zh) | 一种蒽醌类化合物及其制备方法和医用用途 | |
CN112299981B (zh) | 一种α,α-二氟酮类衍生物的制备方法 | |
CN103421050A (zh) | 二茂铁二羧酸酯类化合物及其合成方法 | |
CN110078766A (zh) | 膦酰化苯并咪唑并异喹啉酮类化合物及其制备方法 | |
CN114213424A (zh) | 一种呋喃[3,2-b]并吡啶衍生物的合成方法 | |
CN102659512B (zh) | 一种卤代苯并[a]芴醇的制备方法 | |
CN102584709B (zh) | 一种改进的依普罗沙坦中间体芳基咪唑醛的制备工艺 | |
CN104860880A (zh) | 一种合成8-(硝基甲基)喹啉类化合物的方法 | |
CN104860881A (zh) | 8-(硝基甲基)喹啉类化合物和8-甲氨基四氢喹啉类化合物的合成方法 | |
CN109400431A (zh) | 一种苯乙炔类化合物双溴化合物的合成方法 | |
CN111747879A (zh) | 一种大工艺合成艾瑞昔布的方法 | |
CN110698422A (zh) | 一种芳巯基二唑类衍生物的合成方法 | |
CN103265479B (zh) | 一种6‑氯甲基烟酸叔丁酯的合成方法 | |
CN104529922A (zh) | 一种1,4,7-三氮杂环壬烷盐酸盐的制备方法 | |
CN109879815B (zh) | 2-溴-6-醛基吡啶及其制备方法 | |
CN111875534B (zh) | 1,8-二甲酰基咔唑的安全高效制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210129 |
|
RJ01 | Rejection of invention patent application after publication |