CN116217526A - 芳香杂环取代α-亚甲基-γ-丁内酯类化合物、制备方法及应用 - Google Patents

芳香杂环取代α-亚甲基-γ-丁内酯类化合物、制备方法及应用 Download PDF

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CN116217526A
CN116217526A CN202310172043.7A CN202310172043A CN116217526A CN 116217526 A CN116217526 A CN 116217526A CN 202310172043 A CN202310172043 A CN 202310172043A CN 116217526 A CN116217526 A CN 116217526A
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methylene
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butyrolactone
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冯俊涛
李路伟
王勇
陈光友
雷鹏
闫合
马志卿
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Northwest A&F University
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Abstract

本发明公开了一种芳香杂环取代α‑亚甲基‑γ‑丁内酯类化合物、制备方法及应用；本发明在α‑亚甲基‑γ‑丁内酯β、γ位引入不同的芳香杂环及直链羧酸酯；例如，萘、苯并噻吩、苯并呋喃、苯并噻唑等，得到了一类结构新颖的化合物；所述化合物的结构如式I所示：

Description

芳香杂环取代α-亚甲基-γ-丁内酯类化合物、制备方法及 应用
技术领域
本发明属于病原菌控制技术领域，具体涉及芳香杂环取代α-亚甲基-γ-丁内酯类化合物、制备方法及应用。
背景技术
由真菌和卵菌引起的病害造成粮食损失占总病害的80％以上。常见病害有水稻稻瘟病、小麦赤霉病、马铃薯晚疫病、苹果腐烂病菌等。针对病害主要的防治手段便是化学杀菌剂。寻找新的先导化合物是杀菌剂创制的关键问题。具有α-亚甲基-γ-丁内酯骨架片段的倍半萜内酯类化合物具有丰富的生物活性，例如抑菌、抗癌、抗病毒、消炎、降压、杀虫、除草、调节植物生长等生物活性。该类化合物还有高效、低毒、低残留等特点，作为一类活性物质在医药领域得到广泛的应用，但在农用领域研究较少。
为发现新型农用杀菌剂，发明人将不同芳香杂环或脂肪链取代的醛引入α-亚甲基-γ-丁内酯中，得到一系列新颖化合物，并发现它们对植物病原真菌有良好的防治的作用。目前尚没有本发明中芳香杂环取代α-亚甲基-γ-丁内酯化合物的报道，为此，本发明公开了一系列结构新颖的α-亚甲基-γ-丁内酯化合物作为农用杀菌剂的应用。
发明内容
本发明的目的是提供一种芳香杂环取代α-亚甲基-γ-丁内酯类化合物、制备方法及应用。本发明在α-亚甲基-γ-丁内酯β、γ位引入不同的芳香杂环及直链羧酸酯；例如，萘、苯并噻吩、苯并呋喃、苯并噻唑等，得到了一类结构新颖的化合物；本发明的化合物具有广谱的杀菌活性，尤其对苹果腐烂病菌、水稻纹枯病菌、小麦赤霉病菌、小麦全蚀病菌、番茄灰霉病菌具有明显的抑制效果，可以作为杀菌剂用于上述植物病害的防治。
具体方案包括：
芳香杂环取代α-亚甲基-γ-丁内酯类化合物，为式I所示的化合物；
Figure BDA0004099623610000021
R1选自氢，五元、六元芳香杂环，苯并五元、六元芳香杂环，苯基中的一种；R1的取代方式为单取代；R2选自C1-C4酯基，苯并五元、六元芳香杂环，苯基中的一种；R2的取代方式为单取代。
芳香杂环取代α-亚甲基-γ-丁内酯类化合物，为式I所示的化合物；
Figure BDA0004099623610000022
式I中各取代基具体见下表：
Figure BDA0004099623610000023
Figure BDA0004099623610000031
Figure BDA0004099623610000041
一种芳香杂环取代α-亚甲基-γ-丁内酯类化合物的制备方法，所述的该类化合物为本发明任一所述的芳香杂环取代α-亚甲基-γ-丁内酯类化合物；
化合物I-1到I-28的制备方法，包括：2-(溴甲基)丙烯酸甲酯、铟粉和氯化铵混合后甲醇溶解，再加入不同取代的芳香杂环醛；反应完成后旋出溶剂，得到粗产品；粗产品中加入二氯甲烷溶解，并加入催化量的对甲苯磺酸，室温反应完成后，经硅胶柱层析分离纯化得到α-亚甲基-γ-丁内酯衍生物I-1到I-28；
化合物I-29到I-68的制备方法，包括：三乙烯二胺作催化剂，R1CHO与丙烯酸甲酯室温反应后，水洗和二氯甲烷萃取，旋干得到中间体B，然后加入氢溴酸、浓硫酸和二氯甲烷，0℃反应完后经萃取、水洗、干燥和薄层柱层析(石油醚：乙酸乙酯＝18:1)得到中间体C；中间体C和R2CHO加入THF和水溶解后，将铟粉投入，氮气保护下反应；用乙酸乙酯萃取和干燥浓缩后经硅胶柱层析纯化得中间体D；中间体D溶解于二氯甲烷中，加入催化量的对甲苯磺酸，室温反应完成后，经硅胶柱层析分离纯化得到α-亚甲基-γ-丁内酯衍生物I-29到I-68。
可选的，化合物I-1到I-28的制备方法中，所述的2-(溴甲基)丙烯酸甲酯：铟粉：氯化铵：芳香杂环醛的摩尔比为1.5：2：1：1.2。
可选的，化合物I-29到I-68的制备方法中，三乙烯二胺：R1CHO：丙烯酸甲酯：氢溴酸：浓硫酸的摩尔比为10：67.5：100：59：306。中间体C：R2CHO：铟的摩尔比为1：1.3：1.3。
可选的，硅胶柱层析分离纯化的条件为石油醚：乙酸乙酯＝6:1～10:1。
本发明的芳香杂环取代α-亚甲基-γ-丁内酯类化合物用于制备植物杀菌剂的应用。
可选的，所述的植物杀菌剂用于防治苹果腐烂病菌、水稻纹枯病菌、小麦赤霉病菌、小麦全蚀病菌和/或番茄灰霉病菌。
本发明的有益效果为：
本发明将不同的芳香杂环引入到天然产物α-亚甲基-γ-丁内酯中，所得到的化合物结构新颖，且具有良好的杀菌活性，尤其对苹果腐烂病、水稻纹枯病、小麦赤霉病、小麦全蚀病和番茄灰霉病具有明显的抑制效果。
附图说明
附图是用来提供对本公开的进一步理解，并且构成说明书的一部分，与下面的具体实施方式一起用于解释本公开，但并不构成对本公开的限制。在附图中：
图1为本发明化合物I-01的氢谱图；
图2为本发明化合物I-38的氢谱图；
图3为本发明化合物I-44的氢谱图；
图4为本发明化合物I-45的氢谱图。
具体实施方式
以下结合具体实例对本发明作进一步说明，但本发明并不限于这些实施例。所述方法，如无特别说明，均为常规方法。所述材料，如无特别说明，均能从公开商业途径获得。
本发明公开的α-亚甲基-γ-丁内酯类化合物，具有式I的结构通式；
Figure BDA0004099623610000061
R1选自氢，五元、六元芳香杂环，苯并五元、六元芳香杂环，苯基中的一种；R1的取代方式为单取代；R2选自C1-C4酯基，苯并五元、六元芳香杂环，苯基中的一种；R2的取代方式为单取代。
更加详细的，见表1中所列数据：
表1
Figure BDA0004099623610000062
Figure BDA0004099623610000071
Figure BDA0004099623610000081
本发明的芳香杂环取代α-亚甲基-γ-丁内酯类化合物I-01到I-68按以下方案合成：
方案1：化合物I-01到I-28的制备方法，包括取2-(溴甲基)丙烯酸甲酯(1.5mmol)，铟粉(2mmol)，氯化铵(1mmol)，5mL甲醇加入到圆底烧瓶中，室温搅拌10分钟后，加入不同取代的芳香杂环醛(R2CHO,1.2mmol)，搅拌过夜。TLC检测完成后，减压旋出溶剂，无须进一步纯化直接加入无水二氯甲烷5mL，催化量的对甲苯磺酸(0.2mmol)，室温搅拌12小时，反应完成后，经硅胶柱层析分离纯化得到α-亚甲基-γ-丁内酯衍生物I-01到I-28。
Figure BDA0004099623610000091
反应条件：(a)2-(溴甲基)丙烯酸甲酯，甲醇，氯化铵，铟粉，室温；(b)：对甲苯磺酸，二氯甲烷，室温。
方案2：化合物I-29到I-68的制备方法，包括三乙烯二胺(10mmol)作催化剂，不同取代的醛(R1CHO,67.5mmol)与丙烯酸甲酯(100mmol)反应，室温反应6-7天后，水洗，二氯甲烷萃取，减压蒸馏，得到中间体B，然后加入18.7mL(48％)氢溴酸(59mmol)，浓硫酸17mL，二氯甲烷10mL，0℃搅拌过夜，粗产品经萃取，水洗，干燥，薄层硅胶柱层析(石油醚：乙酸乙酯＝18:1)得到中间体C。在圆底烧瓶中加入1mmol中间体C，醛(R2CHO)1.3mmol，5mL THF和5mL超纯水，最后将148mg铟粉(1.3mmol)迅速投入到烧瓶中，氮气保护，室温搅拌6～8小时。反应完后用乙酸乙酯萃取，无水硫酸钠干燥，减压浓缩，经硅胶柱层析(石油醚：乙酸乙酯＝8:1)纯化得中间体D。最后将中间体D溶解于5mL二氯甲烷中，加入催化量的对甲苯磺酸，室温搅拌过夜反应完成后，经硅胶柱层析分离纯化得到α-亚甲基-γ-丁内酯衍生物I-29到I-68。
Figure BDA0004099623610000092
反应条件：(a)不同取代的芳香醛(R1CHO)，丙烯酸甲酯，三乙烯二胺，室温搅拌；(b)氢溴酸，浓硫酸，二氯甲烷，0-25℃；(c)不同取代的醛(R2CHO)，铟粉，四氢呋喃，水，室温；(d)对甲苯磺酸，二氯甲烷，室温。
以下如无特殊说明，所用的试剂比值均为体积比。
实施例1：化合物I-01的制备
Figure BDA0004099623610000101
取2-(溴甲基)丙烯酸甲酯(1.5mmol)，铟粉(2mmol)，氯化铵(1mmol)，5mL甲醇加入到15mL圆底烧瓶中，室温搅拌10分钟后，加入2-萘甲醛(1.2mmol)，室温搅拌过夜。TLC检测完成后，减压旋出溶剂，无须进一步纯化直接加入无水二氯甲烷5mL，催化量的对甲苯磺酸(0.1mmol)，室温搅拌12小时，反应完成后，经硅胶柱层析(石油醚：乙酸乙酯＝10:1)分离纯化得到白色固体，收率93％。
熔点：65.5–68.3℃。1H NMR(400MHz,Chloroform-d)δ7.88(d,J＝8.6Hz,1H),7.86–7.81(m,2H),7.80(s,1H),7.56–7.47(m,2H),7.39(dd,J＝8.6,1.8Hz,1H),6.35(t,J＝2.8Hz,1H),5.75–5.66(m,2H),3.48(ddt,J＝17.0,8.1,2.6Hz,1H),2.99(ddt,J＝17.1,6.1,2.9Hz,1H).其氢谱图见图1.
方案1中的其他化合物(I-02到I-28)与实施例1中不同的是：R2CHO，例如：不同取代的1-萘甲醛、2-萘甲醛、苯并噻吩-2-甲醛、苯并噻吩-3-甲醛、苯并呋喃-2-甲醛、苯并呋喃-3-甲醛、喹啉甲醛、吲哚甲醛、肉桂醛等。
实施例2：化合物I-38的制备
Figure BDA0004099623610000102
向100mL的圆底烧瓶中，加入对甲基苯甲醛(67.5mmol)、丙烯酸甲酯(100mmol)、三乙烯二胺(10mmol)，室温搅拌反应6天后，水洗，二氯甲烷萃取，减压蒸馏得中间体B。在0℃下，向中间体B的二氯甲烷(10mL)溶液中，依次缓慢滴加(48％)氢溴酸(59mmol，18.7mL)，浓硫酸(17mL)，搅拌过夜，经萃取，水洗，干燥，硅胶柱层析(石油醚：乙酸乙酯＝18:1)得中间体C。在圆底烧瓶中加入中间体C(1mmol)，醛(R2CHO，1.3mmol)，加入5mL THF和5mL超纯水，将铟粉(1.3mmol)迅速投入到烧瓶中，氮气保护，搅拌6小时。乙酸乙酯萃取，水洗，干燥，减压浓缩，经硅胶柱层析(石油醚：乙酸乙酯＝6:1)纯化得中间体D。然后将中间体D溶解于5mL二氯甲烷中，加入催化量的对甲苯磺酸，室温搅拌过夜，反应完成后经硅胶柱层析(石油醚：乙酸乙酯＝8:1)分离纯化得到亮黄色固体，收率84％。
熔点：135.8–137.4℃.1H NMR(500MHz,Chloroform-d)δ7.91(dd,J＝17.1,8.2Hz,2H),7.61(d,J＝7.1Hz,1H),7.57–7.35(m,7H),7.34–7.26(m,2H),6.53(d,J＝2.8Hz,1H),6.24(d,J＝5.6Hz,1H),5.58(d,J＝2.5Hz,1H),4.27(dt,J＝5.5,2.7Hz,1H).其氢谱图见图2.
方案2中的其他化合物(I-29到I-68)与实施例2中不同的是R1CHO，例如：对甲苯甲醛、苯甲醛、1-萘甲醛、苯并噻吩-2-甲醛等；R2CHO，例如：不同单/双取代苯甲醛、脂肪醛等。
化合物的外观、熔点、收率及1H NMR数据如下所示。
3-methylene-5-(naphthalen-2-yl)dihydrofuran-2(3H)-one(1)
White solid,yield 93％.m.p.65.5–68.3℃.1H NMR(400MHz,Chloroform-d)δ7.88(d,J＝8.6Hz,1H),7.86–7.81(m,2H),7.80(s,1H),7.56–7.47(m,2H),7.39(dd,J＝8.6,1.8Hz,1H),6.35(t,J＝2.8Hz,1H),5.75–5.66(m,2H),3.48(ddt,J＝17.0,8.1,2.6Hz,1H),2.99(ddt,J＝17.1,6.1,2.9Hz,1H).
5-(1-bromonaphthalen-2-yl)-3-methylenedihydrofuran-2(3H)-one(2)
White solid,yield 90％.m.p.93.4–97.2℃.1H NMR(400MHz,Chloroform-d)δ8.31(d,J＝8.5Hz,1H),7.94–7.76(m,2H),7.71–7.42(m,3H),6.36(t,J＝2.9Hz,1H),6.13(dd,J＝8.3,6.2Hz,1H),5.71(t,J＝2.6Hz,1H),3.70(ddt,J＝17.4,8.3,2.6Hz,1H),2.82(ddt,J＝17.4,6.0,2.9Hz,1H).
3-methylene-5-(naphthalen-1-yl)dihydrofuran-2(3H)-one(3)
White solid,yield 94％.m.p.80.5–85.0℃.1H NMR(400MHz,Chloroform-d)δ7.95–7.72(m,3H),7.62–7.42(m,4H),6.35(t,J＝2.9Hz,1H),6.27(dd,J＝8.4,5.6Hz,1H),5.67(t,J＝2.5Hz,1H),3.64(ddt,J＝17.0,8.4,2.7Hz,1H),2.97(ddt,J＝17.0,5.5,2.8Hz,1H).
5-(4-bromonaphthalen-1-yl)-3-methylenedihydrofuran-2(3H)-one(4)
Yellow solid,yield 93％.m.p.70.4–74.9℃.1H NMR(400MHz,Chloroform-d)δ8.35(dd,J＝7.9,1.8Hz,1H),7.79(d,J＝7.8Hz,2H),7.71–7.52(m,2H),7.41(d,J＝7.8Hz,1H),6.36(t,J＝2.9Hz,1H),6.23(dd,J＝8.4,5.6Hz,1H),5.69(t,J＝2.5Hz,1H),3.66(ddt,J＝17.1,8.4,2.7Hz,1H),2.93(ddt,J＝17.0,5.5,2.7Hz,1H).
5-(2-hydroxynaphthalen-1-yl)-3-methylenedihydrofuran-2(3H)-one(5)
White solid,yield 63％.m.p.90.4–93.2℃.1H NMR(400MHz,Chloroform-d)δ7.50–7.19(m,5H),6.31(t,J＝2.9Hz,1H),5.69(t,J＝2.6Hz,1H),5.53(dd,J＝8.0,6.5Hz,1H),3.41(ddt,J＝17.1,8.1,2.5Hz,1H),2.91(ddt,J＝17.1,6.2,2.9Hz,1H).
5-(2-methoxynaphthalen-1-yl)-3-methylenedihydrofuran-2(3H)-one(6)
Yellow oily liquid,yield 91％.1H NMR(500 MHz,Chloroform-d)δ8.40(dd,J＝8.2,1.5 Hz,1H),7.80(d,J＝8.3 Hz,1H),7.59(dddd,J＝22.3,8.2,6.8,1.4 Hz,2H),7.49(d,J＝8.0 Hz,1H),6.82(d,J＝8.0 Hz,1H),6.38(t,J＝2.8 Hz,1H),6.22(dd,J＝8.2,5.7 Hz,1H),5.71(t,J＝2.5 Hz,1H),4.04(s,3H),3.61(ddt,J＝17.0,8.2,2.6 Hz,1H),3.03(ddt,J＝17.0,5.6,2.8 Hz,1H).
5-(4-methoxynaphthalen-1-yl)-3-methylenedihydrofuran-2(3H)-one(7)
Yellow oily liquid,yield 88％.1H NMR(400 MHz,Chloroform-d)δ8.39–8.32(m,1H),7.79–7.72(m,1H),7.55(dddd,J＝18.7,8.1,6.9,1.4 Hz,2H),7.45(dd,J＝8.0,0.9 Hz,1H),6.79(d,J＝8.0 Hz,1H),6.34(t,J＝2.8 Hz,1H),6.19(ddd,J＝8.2,5.6,0.9Hz,1H),5.68(t,J＝2.5 Hz,1H),4.01(s,3H),3.58(ddt,J＝17.0,8.3,2.6 Hz,1H),2.99(ddt,J＝17.0,5.6,2.7 Hz,1H).
3-(4-methylene-5-oxotetrahydrofuran-2-yl)-4H-chromen-4-one(8)
Light yellow solid,yield 88％.m.p.72.3–74.6℃.1H NMR(400 MHz,Chloroform-d)δ8.21(dd,J＝8.0,1.7 Hz,1H),8.00(d,J＝1.2 Hz,1H),7.72(ddd,J＝8.6,7.1,1.8 Hz,1H),7.56–7.37(m,2H),6.33(t,J＝2.9 Hz,1H),5.71(t,J＝2.6 Hz,1H),5.60(ddd,J＝8.4,5.9,1.2 Hz,1H),3.57(ddt,J＝17.5,8.4,2.6 Hz,1H),2.91(ddt,J＝17.5,5.8,2.8 Hz,1H).
3-methylene-5-(quinolin-8-yl)dihydrofuran-2(3H)-one(9)
White solid,yield 46％.m.p.80.0–82.9℃.1H NMR(400 MHz,Chloroform-d)δ8.89(dd,J＝4.2,1.8 Hz,1H),8.18(dd,J＝8.3,1.8 Hz,1H),7.83–7.72(m,2H),7.59–7.50(m,1H),7.45(dd,J＝8.3,4.2 Hz,1H),6.58(dd,J＝8.4,5.9 Hz,1H),6.32(t,J＝2.9 Hz,1H),5.64(t,J＝2.6 Hz,1H),3.84–3.68(m,2H),2.89(ddt,J＝17.4,5.8,2.8 Hz,1H).
5-(benzo[b]thiophen-2-yl)-3-methylenedihydrofuran-2(3H)-one(10)
Yellow solid,yield 88％.m.p.145.0–147.5℃.1H NMR(400 MHz,Chloroform-d)δ7.78(ddd,J＝26.6,6.7,2.6 Hz,2H),7.43–7.25(m,3H),6.34(t,J＝2.9 Hz,1H),5.88–5.67(m,2H),3.45(ddt,J＝17.1,8.1,2.6Hz,1H),3.14(ddt,J＝17.1,5.8,2.8 Hz,1H).
5-(benzo[b]thiophen-3-yl)-3-methylenedihydrofuran-2(3H)-one(11)
Yellow solid,yield 83％.m.p.147.0–149.2℃.1H NMR(400 MHz,Chloroform-d)δ7.96–7.77(m,1H),7.74–7.60(m,1H),7.51–7.33(m,3H),6.36(t,J＝2.9 Hz,1H),5.96–5.78(m,1H),5.73(t,J＝2.5 Hz,1H),3.49(ddt,J＝17.0,8.2,2.6 Hz,1H),3.12(ddt,J＝17.0,5.9,2.8 Hz,1H).
5-(benzofuran-2-yl)-3-methylenedihydrofuran-2(3H)-one(12)
Yellow solid,yield 82％.m.p.94.0–95.7℃.1H NMR(400 MHz,Chloroform-d)δ7.56(d,J＝7.7 Hz,1H),7.46(d,J＝8.2 Hz,1H),7.31(dd,J＝8.3,6.9 Hz,1H),6.78(s,1H),6.35(t,J＝2.9 Hz,1H),5.76(t,J＝2.6 Hz,1H),5.64(dd,J＝8.2,5.9 Hz,1H),3.41–3.22(m,2H).
5-(benzofuran-3-yl)-3-methylenedihydrofuran-2(3H)-one(13)
Yellow solid.m.p.94.0–95.9℃.1H NMR(400 MHz,Chloroform-d)δ7.62(d,J＝1.0 Hz,1H),7.57–7.42(m,2H),7.38–7.18(m,2H),6.34(t,J＝2.9 Hz,1H),5.82–5.66(m,2H),3.40(ddt,J＝17.1,8.2,2.5 Hz,1H),3.11(ddt,J＝17.1,6.0,2.8 Hz,1H).
5-(benzo[d]thiazol-2-yl)-3-methylenedihydrofuran-2(3H)-one(14)
Yellow solid,yield 81％.m.p.120.5–123.3℃.1H NMR(400 MHz,Chloroform-d)δ8.03(dt,J＝8.2,0.9 Hz,1H),7.98–7.87(m,1H),7.48(dddd,J＝34.2,8.2,7.2,1.2Hz,2H),6.38(t,J＝2.9 Hz,1H),5.90(dd,J＝8.6,5.2 Hz,1H),5.79(t,J＝2.6 Hz,1H),3.58(ddt,J＝17.4,8.6,2.8 Hz,1H),3.42(ddt,J＝17.4,5.4,2.7Hz,1H).
3-methylene-5-(quinolin-8-yl)dihydrofuran-2(3H)-one(15)
Yellow solid,yield 53％.m.p.143.0–145.2℃.1H NMR(400 MHz,Chloroform-d)δ8.89(dd,J＝4.2,1.8Hz,1H),8.18(dd,J＝8.3,1.8 Hz,1H),7.83–7.72(m,2H),7.59–7.50(m,1H),7.45(dd,J＝8.3,4.2 Hz,1H),6.58(dd,J＝8.4,5.9 Hz,1H),6.32(t,J＝2.9Hz,1H),5.64(t,J＝2.6 Hz,1H),3.84–3.68(m,2H),2.89(ddt,J＝17.4,5.8,2.8 Hz,1H).
5-(6-bromopyridin-2-yl)-3-methylenedihydrofuran-2(3H)-one(16)
Yellow oily liquid,yield 56％.1H NMR(500 MHz,Chloroform-d)δ7.63(t,J＝7.8 Hz,1H),7.47(dd,J＝17.4,7.7 Hz,2H),6.34(t,J＝2.9 Hz,1H),5.75(t,J＝2.6 Hz,1H),5.60(dd,J＝8.7,5.5 Hz,1H),3.51(ddt,J＝17.5,8.7,2.7 Hz,1H),3.18(ddt,J＝17.5,5.6,2.8 Hz,1H).
5-(5-bromopyridin-3-yl)-3-methylenedihydrofuran-2(3H)-one(17)
Yellow oily liquid,yield 61％.1H NMR(400 MHz,Chloroform-d)δ8.68(d,J＝2.2 Hz,1H),8.51(d,J＝2.0 Hz,1H),7.84(t,J＝2.2 Hz,1H),6.37(t,J＝2.9 Hz,1H),5.77(t,J＝2.6 Hz,1H),5.55(t,J＝7.4 Hz,1H),3.48(ddt,J＝17.0,8.1,2.5 Hz,1H),2.91(ddt,J＝17.0,6.3,3.0 Hz,1H).
5-(2-chloropyridin-3-yl)-3-methylenedihydrofuran-2(3H)-one(18)
Yellow oily liquid,yield 36％.1H NMR(400 MHz,Chloroform-d)δ8.38(dd,J＝4.8,1.9 Hz,2H),7.80(dd,J＝7.7,1.9 Hz,2H),7.34(dd,J＝7.7,4.8 Hz,2H),6.34(t,J＝2.9 Hz,2H),5.83–5.75(m,3H),5.75(s,1H),3.81–3.59(m,3H),2.82(ddt,J＝17.5,5.9,2.8 Hz,2H).
5-(5-bromothiophen-2-yl)-3-methylenedihydrofuran-2(3H)-one(19)
Yellow oily liquid,yield 67％.1H NMR(400 MHz,DMSO-d6)δ7.75(s,1H),7.28(s,1H),6.13(s,1H),5.88(dd,J＝8.0,5.9 Hz,1H),5.83(s,1H),3.46(ddt,J＝17.2,8.1,2.6 Hz,1H),3.07(ddt,J＝17.2,5.8,2.8 Hz,1H).
5-(5-bromothiophen-2-yl)-3-methylenedihydrofuran-2(3H)-one(20)
Red brown solid,yield 72％.m.p.104.0–106.3℃.1H NMR(400 MHz,Chloroform-d)δ6.88(d,J＝3.5 Hz,1H),6.64(dq,J＝3.5,1.2 Hz,1H),6.29(t,J＝2.8Hz,1H),5.77–5.59(m,2H),3.37(ddt,J＝17.1,7.9,2.5 Hz,1H),3.07(ddt,J＝17.1,6.0,2.8 Hz,1H),2.47(d,J＝1.1 Hz,3H).
5-(4-fluorophenyl)-3-methylenedihydrofuran-2(3H)-one(21)
Yellow oily liquid,yield 91％.1H NMR(400 MHz,Chloroform-d)δ7.30(dt,J＝9.0,6.2 Hz,2H),7.08(t,J＝8.6 Hz,2H),6.32(t,J＝2.9 Hz,1H),5.71(t,J＝2.5 Hz,1H),5.51(t,J＝7.3 Hz,1H),3.41(ddt,J＝17.0,8.0,2.5 Hz,1H),2.89(ddt,J＝17.1,6.2,3.0 Hz,1H).
5-(4-(tert-butyl)phenyl)-3-methylenedihydrofuran-2(3H)-one(22)
White solid,yield 93％.m.p.84.2–85.5℃.1H NMR(400 MHz,Chloroform-d)δ7.45–7.37(m,2H),7.26(d,J＝8.3 Hz,2H),6.30(t,J＝2.9 Hz,1H),5.69(t,J＝2.5 Hz,1H),5.51(dd,J＝8.0,6.5 Hz,1H),3.38(ddt,J＝17.1,8.0,2.5 Hz,1H),2.93(ddt,J＝17.1,6.2,2.9 Hz,1H),1.32(s,9H).
3-methylene-5-(4-nitrophenyl)dihydrofuran-2(3H)-one(23)
White solid,yield 72％.m.p.95.6–98.1℃.1H NMR(400 MHz,Chloroform-d)δ8.27(d,J＝8.4 Hz,2H),7.53(d,J＝8.4 Hz,2H),6.37(t,J＝2.8 Hz,1H),5.77(d,J＝2.7Hz,1H),5.65(t,J＝7.4 Hz,1H),3.62–3.35(m,1H),2.88(ddt,J＝17.1,6.3,3.0 Hz,1H).
5-(3-bromo-4-fluorophenyl)-3-methylenedihydrofuran-2(3H)-one(24)
White solid,yield 79％.m.p.95.6–98.0℃.1H NMR(400 MHz,Chloroform-d)δ7.47(dp,J＝4.4,2.0 Hz,2H),7.31–7.21(m,2H),6.33(t,J＝2.9 Hz,1H),5.72(t,J＝2.6Hz,1H),5.49(dd,J＝8.1,6.5 Hz,1H),3.42(ddt,J＝17.0,8.1,2.5 Hz,1H),2.88(ddt,J＝17.0,6.1,2.9 Hz,1H).
5-(4-hydroxy-3,5-dimethoxyphenyl)-3-methylenedihydrofuran-2(3H)-one(25)
Yellow solid,yield 61％.m.p.85.3-87.4℃.1H NMR(500 MHz,Chloroform-d)δ6.52(s,2H),6.29(t,J＝2.8 Hz,1H),5.68(t,J＝2.6 Hz,1H),5.59(s,1H),5.43(t,J＝7.3Hz,1H),3.87(s,6H),3.36(ddt,J＝17.1,7.9,2.5 Hz,1H),2.89(ddt,J＝17.0,6.3,3.0Hz,1H).
(E)-3-methylene-5-styryldihydrofuran-2(3H)-one(26)
White solid,yield 88％.m.p.58.1 -60.0℃.1H NMR(400 MHz,Chloroform-d)δ7.43–7.26(m,5H),6.69(d,J＝15.8 Hz,1H),6.34–6.09(m,2H),5.69(t,J＝2.6 Hz,1H),5.14(q,J＝6.5 Hz,1H),3.23(ddt,J＝17.0,7.9,2.5 Hz,1H),2.81(ddt,J＝17.1,6.0,2.9Hz,1H).
(E)-3-methylene-5-(1-phenylprop-1-en-2-yl)dihydrofuran-2(3H)-one(27)
White solid,yield 89％.m.p.57.1 -59.0℃.1H NMR(400 MHz,Chloroform-d)δ7.38–7.32(m,2H),7.30–7.25(m,3H),6.59(s,1H),6.30(t,J＝2.9 Hz,1H),5.69(t,J＝2.6Hz,1H),5.10–4.96(m,1H),3.19(ddt,J＝17.3,8.2,2.6 Hz,1H),2.85(ddt,J＝17.3,6.1,2.9 Hz,1H),1.85(d,J＝1.4 Hz,3H).
(Z)-5-(1-bromo-2-phenylvinyl)-3-methylenedihydrofuran-2(3H)-one(28)
White solid,yield 85％.m.p.68.8 -69.9℃.1H NMR(400 MHz,Chloroform-d)δ7.69–7.52(m,2H),7.45–7.28(m,3H),7.16(s,1H),6.33(t,J＝3.0 Hz,1H),5.72(t,J＝2.6Hz,1H),5.19(dd,J＝8.4,5.2 Hz,1H),3.25(ddt,J＝17.5,8.4,2.8 Hz,1H),3.06(ddt,J＝17.6,5.5,2.9 Hz,1H).
3-methylene-5-(naphthalen-1-yl)-4-(p-tolyl)dihydrofuran-2(3H)-one(29)
White solid,yield 89％.m.p.108.0 -110.0℃.1H NMR(400 MHz,Chloroform-d)δ7.95–7.75(m,2H),7.58–7.38(m,4H),7.38–7.28(m,1H),7.22–7.05(m,4H),6.45(d,J＝2.8 Hz,1H),6.16(d,J＝5.5 Hz,1H),5.51(d,J＝2.5 Hz,1H),4.18(dt,J＝5.5,2.7 Hz,1H),2.37(s,3H).
3-methylene-5-(naphthalen-2-yl)-4-(p-tolyl)dihydrofuran-2(3H)-one(30)
White solid,yield 88％.m.p.106.0 -109.7℃.1H NMR(400 MHz,Chloroform-d)δ7.86–7.81(m,2H),7.81–7.75(m,1H),7.69(d,J＝1.7 Hz,1H),7.53–7.44(m,2H),7.31–7.23(m,1H),7.19(s,1H),7.09–7.03(m,2H),6.46(d,J＝3.3 Hz,1H),5.51(d,J＝7.8 Hz,1H),5.47(d,J＝2.9 Hz,1H),4.09(dt,J＝7.7,3.2 Hz,1H),2.37(s,3H).
5-(1-bromonaphthalen-2-yl)-3-methylene-4-(p-tolyl)dihydrofuran-2(3H)-one(31)
White solid,yield 87％.m.p.113.3 -118.0℃.1H NMR(400 MHz,Chloroform-d)δ8.18(d,J＝8.5 Hz,1H),7.69(dd,J＝7.8,1.4 Hz,1H),7.62–7.39(m,3H),7.18(d,J＝8.6 Hz,1H),6.82–6.66(m,4H),6.56(d,J＝2.3 Hz,1H),6.38(d,J＝7.6 Hz,1H),5.69(d,J＝2.0 Hz,1H),4.89(dt,J＝7.5,2.2 Hz,1H),2.05(s,3H).
5-(2-methoxynaphthalen-1-yl)-3-methylene-4-(p-tolyl)dihydrofuran-2(3H)-one(32)
Yellow oily liquid,yield 73％.1H NMR(500 MHz,Chloroform-d)δ7.91(d,J＝9.0 Hz,1H),7.84(dd,J＝8.1,1.5 Hz,1H),7.71(d,J＝8.6 Hz,1H),7.46–7.30(m,3H),7.17(d,J＝7.8 Hz,2H),7.12–7.06(m,2H),6.57(d,J＝3.3 Hz,1H),6.37(d,J＝6.7 Hz,1H),5.57(d,J＝2.8 Hz,1H),4.60(dt,J＝6.5,3.1 Hz,1H),3.87(s,3H),2.38(s,3H).
3-(4-methylene-5-oxo-3-(p-tolyl)tetrahydrofuran-2-yl)-4H-chromen-4-one(33)
Yellow solid,yield 68％.m.p.128.7–136.1℃.1H NMR(500 MHz,Chloroform-d)δ8.26(dd,J＝8.0,1.7Hz,1H),8.13(dd,J＝7.9,1.7 Hz,2H),7.93(s,1H),7.79–7.71(m,3H),7.66(ddd,J＝8.6,7.2,1.7 Hz,2H),7.55–7.45(m,2H),7.40(ddd,J＝9.3,7.8,1.6Hz,4H),7.31(s,1H),6.91(q,J＝8.2 Hz,8H),6.54(dd,J＝14.4,2.5 Hz,3H),5.94(dd,J＝7.2,1.3 Hz,2H),5.78(d,J＝1.9 Hz,2H),5.61(d,J＝2.4 Hz,1H),5.37–5.32(m,2H),4.82(dt,J＝7.1,2.0 Hz,2H),4.49(dt,J＝5.0,2.6 Hz,1H),2.39(s,3H),2.18(s,6H).
5-(benzo[b]thiophen-2-yl)-3-methylene-4-(p-tolyl)dihydrofuran-2(3H)-one(34)
Yellow solid,yield 82％.m.p.111.7–116.0℃.1H NMR(400 MHz,Chloroform-d)δ7.93(dt,J＝8.1,1.0Hz,1H),7.50(ddd,J＝4.5,2.8,1.0 Hz,2H),7.46–7.34(m,2H),7.28(s,2H),7.23–7.16(m,2H),6.56(d,J＝3.2 Hz,1H),5.82(dd,J＝7.0,0.9 Hz,1H),5.60(d,J＝2.8 Hz,1H),4.41–4.35(m,1H),2.45(s,3H).
5-(benzo[b]thiophen-3-yl)-3-methylene-4-(p-tolyl)dihydrofuran-2(3H)-one(35)
Yellow solid,yield 84％.m.p.114.1–117.2℃.1H NMR(500 MHz,Chloroform-d)δ7.76–7.71(m,1H),7.36–7.14(m,4H),6.76(d,J＝7.9 Hz,2H),6.71–6.66(m,2H),6.58(d,J＝2.7 Hz,1H),6.23(dd,J＝7.9,1.2 Hz,1H),5.66(d,J＝2.4 Hz,1H),4.77(dt,J＝7.8,2.6 Hz,1H),2.13(s,3H).
5-(benzofuran-2-yl)-3-methylene-4-(p-tolyl)dihydrofuran-2(3H)-one(36)
Yellow oily liquid,yield 73％.1H NMR(500MHz,Chloroform-d)δ7.63–7.57(m,1H),7.55(d,J＝8.2Hz,1H),7.38(ddd,J＝8.4,7.2,1.4Hz,1H),7.33–7.26(m,2H),7.22(d,J＝7.8Hz,2H),7.16(s,2H),6.82(s,1H),6.55(d,J＝3.2Hz,1H),5.61(d,J＝2.9Hz,1H),5.49(d,J＝7.3Hz,1H),4.60(dd,J＝7.1,3.3Hz,1H),2.39(s,3H).
5-(benzofuran-3-yl)-3-methylene-4-(p-tolyl)dihydrofuran-2(3H)-one(37)
Yellow oily liquid,yield 79％.1H NMR(500MHz,Chloroform-d)δ7.64(s,1H),7.57–7.52(m,1H),7.41–7.33(m,2H),7.25(t,J＝7.7Hz,3H),7.16(d,J＝8.1Hz,2H),6.86(q,J＝8.2Hz,1H),6.54(d,J＝3.3Hz,1H),5.63(d,J＝7.6Hz,1H),5.57(d,J＝2.9Hz,1H),4.36(dt,J＝7.6,3.1Hz,1H),2.42(s,3H).
3-methylene-5-(naphthalen-1-yl)-4-phenyldihydrofuran-2(3H)-one(38)
Light yellow solid,yield 84％.m.p.135.8–137.4℃.1H NMR(500MHz,Chloroform-d)δ7.91(dd,J＝17.1,8.2Hz,2H),7.61(d,J＝7.1Hz,1H),7.57–7.35(m,7H),7.34–7.26(m,2H),6.53(d,J＝2.8Hz,1H),6.24(d,J＝5.6Hz,1H),5.58(d,J＝2.5Hz,1H),4.27(dt,J＝5.5,2.7Hz,1H).
3-methylene-5-(naphthalen-2-yl)-4-phenyldihydrofuran-2(3H)-one(39)
Light yellow solid,yield 68％.m.p.56.0–58.0℃.1H NMR(500MHz,Chloroform-d)δ7.89(dd,J＝6.9,4.0Hz,2H),7.86–7.81(m,1H),7.75(d,J＝1.7Hz,1H),7.59–7.51(m,2H),7.47–7.36(m,3H),7.36–7.29(m,1H),7.26–7.21(m,2H),6.54(d,J＝3.3Hz,1H),5.59(d,J＝7.7Hz,1H),5.54(d,J＝2.9Hz,1H),4.19(dt,J＝7.6,3.1Hz,1H).
5-(4-isopropylphenyl)-3-methylene-4-(naphthalen-1-yl)dihydrofuC21H16O2ran-2(3H)-one(40)
Yellow solid,yield 75％.m.p.95.3–97.6℃.1H NMR(400MHz,Chloroform-d)δ8.04(d,J＝8.7Hz,1H),7.95–7.76(m,2H),7.63(dd,J＝17.8,8.4Hz,1H),7.54(q,J＝8.8,8.1Hz,1H),7.50–7.36(m,2H),7.20–7.05(m,2H),6.79(d,J＝7.3Hz,1H),6.71(d,J＝7.9Hz,2H),6.67(d,J＝3.2Hz,1H),6.53(s,1H),6.51(s,1H),6.04(d,J＝8.4Hz,1H),5.69(d,J＝2.8Hz,1H),5.60–5.52(m,1H),3.72(q,J＝7.1Hz,1H),2.62(h,J＝6.9Hz,1H),1.24(t,J＝7.2Hz,3H),1.01(dd,J＝6.9,2.7Hz,6H).
5-(4-bromophenyl)-3-methylene-4-(naphthalen-1-yl)dihydrofuran-2(3H)-one(41)
Yellow solid,yield 78％.m.p.121.0–124.0℃.1H NMR(400MHz,Chloroform-d)δ8.03(d,J＝8.5Hz,1H),7.80(d,J＝8.1Hz,1H),7.62(d,J＝8.2Hz,1H),7.56(t,J＝7.4Hz,1H),7.49(t,J＝7.7Hz,1H),7.14(t,J＝7.8Hz,1H),7.01–6.94(m,2H),6.83(d,J＝7.3Hz,1H),6.67(d,J＝3.2Hz,1H),6.49(d,J＝8.2Hz,2H),6.01(d,J＝8.6Hz,1H),5.69(d,J＝2.8Hz,1H),5.57(dt,J＝8.6,3.1Hz,1H).
4-(benzo[b]thiophen-2-yl)-5-(4-fluorophenyl)-3-methylenedihydrofuran-2(3H)-one(42)
White solid,yield 84％.1H NMR(500MHz,Chloroform-d)δ7.70–7.62(m,2H),7.36–7.26(m,2H),7.09–7.02(m,2H),6.90(dd,J＝18.0,9.4Hz,3H),6.64(d,J＝3.0Hz,1H),5.90(d,J＝8.1Hz,1H),5.84(d,J＝2.6Hz,1H),5.03(dt,J＝8.2,2.8Hz,1H).
4-(benzo[b]thiophen-2-yl)-5-(3-fluorophenyl)-3-methylenedihydrofuran-2(3H)-one(43)
White solid,yield 80％.1H NMR(500MHz,Chloroform-d)δ7.64–7.56(m,2H),7.29–7.19(m,2H),7.08(td,J＝8.1,5.7Hz,1H),6.89–6.75(m,4H),6.57(d,J＝2.9Hz,1H),5.82(d,J＝8.2Hz,1H),5.78(d,J＝2.6Hz,1H),4.98(dt,J＝8.2,2.8Hz,1H).
4-(benzo[b]thiophen-2-yl)-5-(2-fluorophenyl)-3-methylenedihydrofuran-2(3H)-one(44)
White solid,yield 74％.1H NMR(500MHz,Chloroform-d)δ7.57(t,J＝7.4Hz,2H),7.27–7.14(m,3H),7.10(tdd,J＝7.6,5.4,1.8Hz,1H),6.99–6.94(m,1H),6.93(d,J＝5.8Hz,1H),6.84–6.75(m,1H),6.57(d,J＝2.7Hz,1H),6.11(d,J＝8.0Hz,1H),5.78(d,J＝2.4Hz,1H),5.04(dt,J＝8.1,2.6Hz,1H).其氢谱图见图3.
4-(benzo[b]thiophen-2-yl)-3-methylene-5-(4-(trifluoromethyl)phenyl)dihydrofuran-2(3H)-one(45)
White solid,yield 80％.1H NMR(500MHz,Chloroform-d)δ7.63–7.54(m,2H),7.39(s,2H),7.30–7.20(m,2H),7.15(d,J＝8.1Hz,2H),6.85(s,1H),6.59(d,J＝2.9Hz,1H),5.90(d,J＝8.2Hz,1H),5.81(d,J＝2.6Hz,1H),5.03(dt,J＝8.2,2.8Hz,1H).其氢谱图见图4.
4-(benzo[b]thiophen-2-yl)-3-methylene-5-(2-(trifluoromethyl)phenyl)dihydrofuran-2(3H)-one(47)
White solid,yield 86％.1H NMR(500 MHz,Chloroform-d)δ7.58–7.52(m,3H),7.31(dd,J＝6.4,2.7 Hz,1H),7.23(d,J＝7.1 Hz,1H),7.23–7.14(m,3H),6.85(s,1H),6.63(d,J＝2.2 Hz,1H),6.20(d,J＝7.4 Hz,1H),5.84(d,J＝2.0 Hz,1H),4.99–4.93(m,1H).
4-(benzo[b]thiophen-2-yl)-5-(4-chlorophenyl)-3-methylenedihydrofuran-2(3H)-one(48)
White solid,yield 88％.1H NMR(500 MHz,Chloroform-d)δ7.71–7.63(m,2H),7.37–7.26(m,2H),7.21–7.15(m,2H),7.05–6.99(m,2H),6.94(s,1H),6.63(d,J＝3.0 Hz,1H),5.88(d,J＝8.1 Hz,1H),5.84(d,J＝2.6 Hz,1H),5.04(dt,J＝8.1,2.8 Hz,1H).
4-(benzo[b]thiophen-2-yl)-5-(3-chlorophenyl)-3-methylenedihydrofuran-2(3H)-one(49)
White solid,yield 75％.1H NMR(500 MHz,Chloroform-d)δ7.64–7.56(m,2H),7.31–7.18(m,2H),7.14–7.09(m,1H),7.06(t,J＝1.9 Hz,1H),7.02(t,J＝7.8 Hz,1H),6.87(d,J＝6.4 Hz,2H),6.57(d,J＝2.9 Hz,1H),5.82–5.76(m,2H),4.97(dt,J＝8.2,2.8Hz,1H).
4-(benzo[b]thiophen-2-yl)-5-(2-chlorophenyl)-3-methylenedihydrofuran-2(3H)-one(50)
White solid,yield 89％.1H NMR(500 MHz,Chloroform-d)δ7.59–7.52(m,2H),7.29–7.23(m,1H),7.23–7.19(m,1H),7.17(ddd,J＝8.5,4.9,1.5 Hz,2H),7.09–7.00(m,2H),6.90(s,1H),6.58(d,J＝2.4 Hz,1H),6.16(d,J＝7.5 Hz,1H),5.80(d,J＝2.1 Hz,1H),5.13(dt,J＝7.4,2.2 Hz,1H).
4-(benzo[b]thiophen-2-yl)-5-(4-bromophenyl)-3-methylenedihydrofuran-2(3H)-one(51)
White solid,yield 92％.1H NMR(500 MHz,Chloroform-d)δ7.72–7.63(m,2H),7.37–7.30(m,4H),7.29(dd,J＝7.2,1.4 Hz,1H),6.99–6.92(m,3H),6.63(d,J＝3.0 Hz,1H),5.88–5.81(m,2H),5.04(dt,J＝8.1,2.8Hz,1H).
4-(benzo[b]thiophen-2-yl)-5-(3-bromophenyl)-3-methylenedihydrofuran-2(3H)-one(52)
White solid,yield 91％.1H NMR(500 MHz,Chloroform-d)δ7.64–7.56(m,2H),7.29–7.19(m,4H),6.96(t,J＝7.8 Hz,1H),6.93–6.89(m,1H),6.88(s,1H),6.57(d,J＝3.0Hz,1H),5.79(dd,J＝5.5,2.9 Hz,2H),4.97(dt,J＝8.2,2.8 Hz,1H).
4-(benzo[b]thiophen-2-yl)-5-(2-bromophenyl)-3-methylenedihydrofuran-2(3H)-one(53)
White solid,yield 81％.1H NMR(500 MHz,Chloroform-d)δ7.65–7.59(m,2H),7.43(dd,J＝7.9,1.3 Hz,1H),7.29(ddd,J＝9.3,7.8,1.6 Hz,2H),7.26–7.20(m,1H),7.13(td,J＝7.7,1.3 Hz,1H),7.04(td,J＝7.7,1.7Hz,1H),6.99(s,1H),6.65(d,J＝2.3 Hz,1H),6.18(d,J＝7.4 Hz,1H),5.87(d,J＝2.0 Hz,1H),5.24(dt,J＝7.5,2.3 Hz,1H).
4-(benzo[b]thiophen-2-yl)-5-(4-methoxyphenyl)-3-methylenedihydrofuran-2(3H)-one(54)
White solid,yield 87％.1H NMR(500 MHz,Chloroform-d)δ7.90–7.83(m,1H),7.79–7.72(m,1H),7.46–7.36(m,2H),7.32–7.25(m,2H),7.17(s,1H),6.97–6.91(m,2H),6.56(d,J＝3.4 Hz,1H),5.75(d,J＝2.9 Hz,1H),5.48(d,J＝8.0 Hz,1H),4.47(dt,J＝8.0,3.1 Hz,1H),3.85(s,3H).
4-(benzo[b]thiophen-2-yl)-5-(3-methoxyphenyl)-3-methylenedihydrofuran-2(3H)-one(55)
White solid,yield 80％.1H NMR(500 MHz,Chloroform-d)δ7.65(d,J＝7.9 Hz,1H),7.61(dd,J＝7.7,1.4 Hz,1H),7.44–7.14(m,5H),6.89–6.82(m,2H),6.69(d,J＝8.3Hz,1H),6.58(dd,J＝5.1,2.7 Hz,1H),6.17(d,J＝7.8 Hz,1H),5.79(dd,J＝12.9,2.4 Hz,1H),5.09(dt,J＝7.9,2.4 Hz,1H),3.70(s,3H).
4-(benzo[b]thiophen-2-yl)-5-(2-methoxyphenyl)-3-methylenedihydrofuran-2(3H)-one(56)
White solid,yield 86％.1H NMR(500 MHz,Chloroform-d)δ7.83(d,J＝7.8 Hz,1H),7.79–7.74(m,1H),7.45–7.36(m,2H),7.36–7.26(m,2H),7.25–7.14(m,2H),7.12–7.06(m,2H),6.63–6.58(m,2H),5.88(d,J＝2.6 Hz,1H),5.41–5.32(m,1H),4.95(dt,J＝8.2,2.8 Hz,1H).
4-(benzo[b]thiophen-2-yl)-5-(4-isopropylphenyl)-3-methylenedihydrofuran-2(3H)-one(57)
White solid,yield 87％.1H NMR(500 MHz,Chloroform-d)δ7.66(d,J＝7.8 Hz,1H),7.60(dd,J＝7.4,1.5 Hz,1H),7.35–7.29(m,1H),7.27(td,J＝7.5,1.5 Hz,1H),7.05(d,J＝8.2 Hz,2H),6.97(d,J＝8.2 Hz,2H),6.82(s,1H),6.61(d,J＝3.1Hz,1H),5.89(d,J＝8.1Hz,1H),5.79(d,J＝2.7Hz,1H),5.01(dt,J＝8.2,2.9Hz,1H),2.83(p,J＝6.9Hz,1H),1.17(dd,J＝6.9,1.7Hz,6H).
4-(benzo[b]thiophen-2-yl)-3-methylene-5-(p-tolyl)dihydrofuran-2(3H)-one(58)
White solid,yield 85％.1H NMR(500MHz,Chloroform-d)δ7.74–7.62(m,2H),7.37–7.24(m,2H),7.02(d,J＝8.1Hz,2H),6.97(d,J＝8.2Hz,2H),6.92(s,1H),6.61(d,J＝3.0Hz,1H),5.88(d,J＝8.1Hz,1H),5.80(d,J＝2.7Hz,1H),5.02(dt,J＝8.2,2.9Hz,1H),2.28(s,3H).
4-(benzo[b]thiophen-2-yl)-3-methylene-5-(o-tolyl)dihydrofuran-2(3H)-one(59)
White solid,yield 79％.1H NMR(500MHz,Chloroform-d)δ6.39–6.30(m,2H),5.98(dtd,J＝20.7,7.3,1.3Hz,2H),5.81(t,J＝8.0Hz,1H),5.62(s,1H),5.45(dd,J＝8.4,2.6Hz,1H),5.38(d,J＝7.6Hz,1H),5.32–5.26(m,2H),4.55(d,J＝8.1Hz,1H),4.51(d,J＝2.6Hz,1H),3.70(dt,J＝8.2,2.8Hz,1H),2.26(s,3H).
4-(benzo[b]thiophen-2-yl)-3-methylene-5-(m-tolyl)dihydrofuran-2(3H)-one(60)
White solid,yield 88％.1H NMR(500MHz,Chloroform-d)δ7.61–7.53(m,2H),7.21(dddd,J＝27.5,12.5,7.2,2.3Hz,3H),7.09(td,J＝7.2,6.3,3.6Hz,2H),6.98–6.92(m,1H),6.83(s,1H),6.54(d,J＝2.8Hz,1H),6.10(d,J＝8.0Hz,1H),5.67(d,J＝2.5Hz,1H),5.01(dt,J＝7.9,2.7Hz,1H),2.12(s,3H).
4-(benzo[b]thiophen-2-yl)-3-methylene-5-phenethyldihydrofuran-2(3H)-one(61)
White solid,yield 81％.1H NMR(500MHz,Chloroform-d)δ7.85(d,J＝7.8Hz,1H),7.79(dd,J＝7.3,1.6Hz,1H),7.46–7.36(m,2H),7.33–7.27(m,2H),7.26–7.21(m,1H),7.20(s,1H),7.18–7.13(m,2H),6.58(d,J＝2.7Hz,1H),5.88(d,J＝2.4Hz,1H),4.78(td,J＝7.5,4.0Hz,1H),4.76–4.70(m,1H),2.89(ddd,J＝13.9,9.0,4.8Hz,1H),2.73(dt,J＝13.8,8.2Hz,1H),1.92–1.81(m,1H),1.73(dtd,J＝14.4,8.5,3.2Hz,1H).
(E)-4-(benzo[b]thiophen-2-yl)-3-methylene-5-(1-phenylprop-1-en-2-yl)dihydrofuran-2(3H)-one(63)White solid,yield 89％.1H NMR(500MHz,Chloroform-d)δ7.69–7.58(m,2H),7.50–7.45(m,2H),7.38–7.25(m,2H),7.21(d,J＝8.2Hz,2H),6.93(s,1H),6.66(d,J＝2.9Hz,1H),5.94(d,J＝8.3Hz,1H),5.89(d,J＝2.6Hz,1H),5.09(dt,J＝8.3,2.7Hz,1H).
4-(benzo[b]thiophen-2-yl)-3-methylene-5-phenyldihydrofuran-2(3H)-one(64)
White solid,yield 83％.1H NMR(500MHz,Chloroform-d)δ7.65(ddd,J＝15.7,7.6,1.2Hz,2H),7.35–7.17(m,6H),7.11–7.05(m,2H),6.90(s,1H),6.63(d,J＝3.0Hz,1H),5.91(d,J＝8.2Hz,1H),5.82(d,J＝2.7Hz,1H),5.04(dt,J＝8.2,2.8Hz,1H),1.32(s,1H),0.93(ddd,J＝18.5,9.4,5.4Hz,0H).
ethyl 3-(benzo[b]thiophen-2-yl)-4-methylene-5-oxotetrahydrofuran-2-carboxylate(65)
White solid,yield 78％.1H NMR(500MHz,Chloroform-d)δ7.88–7.81(m,1H),7.78(dd,J＝7.1,1.5Hz,1H),7.46–7.33(m,2H),7.29(s,1H),6.60(d,J＝2.9Hz,1H),5.89(d,J＝2.5Hz,1H),5.00(d,J＝5.8Hz,1H),4.73(dt,J＝5.6,2.7Hz,1H),4.36(qd,J＝7.1,1.3Hz,2H),1.37(t,J＝7.1Hz,3H).
实施例3：式I化合物对5种植物病原菌的抑制活性
采用菌丝生长速率法对式I化合物抑菌活性进行测定。供试菌种为苹果腐烂病菌、水稻纹枯病菌、小麦赤霉病菌、小麦全蚀病菌、番茄灰霉病菌。
分别称式I化合物，用二甲基亚砜配制成浓度为10000g/mL的母液，用移枪吸取上述母液，加入到已灭菌、稍微冷却的马铃薯薯葡萄糖琼脂培养基(PDA)中，制成50g/mL含药培养基，倒入直径为90mm的培养皿中，每皿10mL，制成带药PDA平板。每个药剂3次重复。二甲基亚砜为空白对照。将培养好的供试病原菌平板用打孔器制备成直径6mm的菌饼，分别接种于上述倒好的含药PDA平板中，然后置于25℃培养箱中黑暗培养。等空白对照PDA平板中菌落充分生长后，以十字交叉法测量各处理的菌落直径，取其平均值。
用以下公式计算菌丝生长抑制率：
Figure BDA0004099623610000181
化合物离体杀菌活性数据见表2。
表2式I化合物的离体杀菌活性结果(抑制率％)
Figure BDA0004099623610000182
Figure BDA0004099623610000191
注：+表示化合物对病原菌的抑制率为0～40％，++表示化合物对病原菌的抑制率为41～79％，+++表示化合物对病原菌的抑制率为80％～100％。
从上表可以看出，本发明提供的式Ⅰ化合物在50g/mL对所测试的5种植物病原菌均具有一定的抑制活性。
化合物I-01、I-02、I-03、I-04、I-06、I-07、I-08、I-09、I-10、I-12、I-13、I-24、I-31、I-33、I-35、I-36、I-37、I-38、I-39、I-41、I-43、I-44、I-45、I-46、I-47、I-48、I-49、I-50、I-51、I-53、I-54、I-56、I-57、I-58、I-59、I-61和I-65对苹果腐烂病菌的抑制率在80％以上。
化合物I-01、I-03、I-04、I-06、I-07、I-09、I-10、I-12、I-13、I-16、I-18、I-25、I-30、I-41、I-42、I-43、I-44、I-45、I-46、I-47、I-48、I-49、I-53、I-54、I-55、I-56、I-57、I-58、I-59、I-60、I-61和I-62对水稻纹枯病菌的抑制率在80％以上。
化合物I-12、I-18、I-23、I-38、I-42、I-43、I-44、I-45、I-46、I-47、I-48、I-50、I-53、I-58、I-60、I-61和I-65对小麦赤霉病菌的抑制率在80％以上。
化合物I-01、I-02、I-05、I-06、I-09、I-10、I-12、I-14、I-17、I-22、I-24和I-27对小麦全蚀病菌的抑制率在80％以上。
化合物I-01、I-02、I-03、I-06、I-07、I-12、I-26、I-41和I-65对番茄灰霉病菌的抑制率在80％以上。
数据表明，式I化合物对苹果腐烂病菌、水稻纹枯病菌、小麦赤霉病菌、小麦全蚀病菌、番茄灰霉病菌具有较好的抑制作用，可以作为杀菌剂用于上述植物病原菌的防治。
部分化合物对上述病原真菌的EC50值如下：(本领域常用的生测方法)
化合物I-01、I-03、I-11、I-23、I-26、I-27对小麦全蚀病菌的EC50值分别为2.31、4.03、12.63、4.10、14.04、3.91μg/mL；化合物I-03、I-06、I-07、I-35、I-38对苹果腐烂病菌的EC50值分别为2.30、1.09、1.17、0.81、0.50μg/mL；化合物I-01、I-03、I-04、I-06、I-07、I-11、I-12、I-21对水稻纹枯病菌的EC50为3.74、2.80、0.81、4.35、6.83、4.05、1.43、6.50μg/mL。
以上详细描述了本公开的优选实施方式，但是，本公开并不限于上述实施方式中的具体细节，在本公开的技术构思范围内，可以对本公开的技术方案进行多种简单变型，这些简单变型均属于本公开的保护范围。
另外需要说明的是，在上述具体实施方式中所描述的各个具体技术特征，在不矛盾的情况下，可以通过任何合适的方式进行组合，为了避免不必要的重复，本公开对各种可能的组合方式不再另行说明。
此外，本公开的各种不同的实施方式之间也可以进行任意组合，只要其不违背本公开的思想，其同样应当视为本公开所公开的内容。

Claims (8)

1.一种芳香杂环取代α-亚甲基-γ-丁内酯类化合物，其特征在于，为式I所示的化合物；
Figure FDA0004099623600000011
R1选自氢、五元或六元芳香杂环、苯并五元或六元芳香杂环和苯基中的一种；R1的取代方式为单取代；
R2选自C1-C4酯基、苯并五元或六元芳香杂环和苯基中的一种；R2的取代方式为单取代。
2.一种芳香杂环取代α-亚甲基-γ-丁内酯类化合物，其特征在于，为式I所示的化合物；
Figure FDA0004099623600000012
式I中各取代基具体见下表：
Figure FDA0004099623600000013
Figure FDA0004099623600000021
Figure FDA0004099623600000031
3.一种芳香杂环取代α-亚甲基-γ-丁内酯类化合物的制备方法，其特征在于，所述的该类化合物为权利要求1或2所述的芳香杂环取代α-亚甲基-γ-丁内酯类化合物；
化合物I-1到I-28的制备方法，包括：2-(溴甲基)丙烯酸甲酯、铟粉和氯化铵混合后甲醇溶解，再加入不同取代的芳香杂环醛；反应完成后旋出溶剂，得到粗产品；粗产品中加入二氯甲烷溶解，并加入催化量的对甲苯磺酸，室温反应完成后，经硅胶柱层析分离纯化得到α-亚甲基-γ-丁内酯衍生物I-1到I-28；
化合物I-29到I-68的制备方法，包括：三乙烯二胺作催化剂，R1CHO与丙烯酸甲酯室温反应后，水洗和二氯甲烷萃取，旋干得到中间体B，然后加入氢溴酸、浓硫酸和二氯甲烷，0℃反应完后经萃取、水洗、干燥和薄层柱层析得到中间体C；中间体C和R2CHO加入THF和水溶解后，将铟粉投入，氮气保护下反应；用乙酸乙酯萃取和干燥浓缩后经硅胶柱层析纯化得中间体D；中间体D溶解于二氯甲烷中，加入催化量的对甲苯磺酸，室温反应完成后，经硅胶柱层析分离纯化得到α-亚甲基-γ-丁内酯衍生物I-29到I-68。
4.根据权利要求3所述的芳香杂环取代α-亚甲基-γ-丁内酯类化合物的制备方法，其特征在于，化合物I-1到I-28的制备方法中，所述的2-(溴甲基)丙烯酸甲酯：铟粉：氯化铵：芳香杂环醛的摩尔比为1.5：2：1：1.2。
5.根据权利要求3所述的芳香杂环取代α-亚甲基-γ-丁内酯类化合物的制备方法，其特征在于，化合物I-29到I-68的制备方法中，三乙烯二胺：R1CHO：丙烯酸甲酯：氢溴酸：浓硫酸的摩尔比为10：67.5：100：59：306。中间体C：R2CHO：铟粉的摩尔比为1：1.3：1.3。
6.根据权利要求3所述的芳香杂环取代α-亚甲基-γ-丁内酯类化合物的制备方法，其特征在于，硅胶柱层析分离纯化的条件为石油醚：乙酸乙酯＝6:1～10:1。
7.权利要求1-2任一所述的芳香杂环取代α-亚甲基-γ-丁内酯类化合物用于制备植物杀菌剂的应用。
8.根据权利要求7所述的应用，所述的植物杀菌剂用于防治苹果腐烂病菌、水稻纹枯病菌、小麦赤霉病菌、小麦全蚀病菌和/或番茄灰霉病菌。
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