CN113150008B - Synthesis method of polysubstituted 2-oxabicyclo [2, 2] octane-3-imine derivative under catalysis of DBU - Google Patents

Synthesis method of polysubstituted 2-oxabicyclo [2, 2] octane-3-imine derivative under catalysis of DBU Download PDF

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CN113150008B
CN113150008B CN202110234601.9A CN202110234601A CN113150008B CN 113150008 B CN113150008 B CN 113150008B CN 202110234601 A CN202110234601 A CN 202110234601A CN 113150008 B CN113150008 B CN 113150008B
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octane
oxabicyclo
dbu
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imine
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CN113150008A (en
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黄晓红
付晓晴
贾艳艳
王悦
李团结
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Jiangsu Normal University
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Abstract

The synthesis method of polysubstituted 2-oxabicyclo [2, 2] octane-3-imine derivatives under the catalysis of DBU comprises the following steps: 3-aryl-1- (pyridine-2-yl) -2-propylene-1-ketone or 3-aryl-1- (pyrazine-2-yl) -2-propylene-1-ketone or malononitrile or cyanoacetamide is used as a raw material, and the molar ratio of the two is 2:1, DBU (1, 8-Diazabicyclo [5.4.0 ]) undec-7-ene) as an alkali, reacting in an ethanol solvent, and stirring at 25 ℃ to react to generate a target product. The synthesis process route is simple and convenient, and the highest yield reaches 90 percent.

Description

Synthesis method of polysubstituted 2-oxabicyclo [2, 2] octane-3-imine derivative under catalysis of DBU
Technical Field
The invention belongs to the technical field of organic synthesis, and relates to a method for synthesizing polysubstituted 2-oxabicyclo [2.2.2] octane-3-imine derivatives at room temperature by taking azachalcone and malononitrile or cyanoacetamide as raw materials under the catalysis of DBU.
Background
2-oxabicyclo [2.2.2]The octane-3-one skeleton is common in a variety of natural products and drug molecules, and these compounds having a bicyclolactone structure have received extensive attention from synthetic chemists and pharmacologists due to their structural uniqueness and exhibit a variety of important biological activities, for example, scholarine a, isolated from the glycopyrrolate tree, has a potential therapeutic effect on respiratory diseases [ Cai, x. -h; tan, q. -g.; liu, y. -p.; feng, t.; du, z. -z.; li, W. -Q.; luo, x. — d.org.lett.2008,10,577.]Basilioides has a certain therapeutic effect on neurodegenerative diseases [ Navarrete, c.; sancho, r.; caballero, f.j.; polastro, f.; fiebech, b.l.; sterner, O.; appendix, g.;
Figure BDA0002960164420000011
E.J.Pharmacol.Exp.Ther.2006,319,422.]harringtonide and cephalolide showed strong cytotoxic activity [ Evanno, l.; jossang, a.; nguyen-poublin, j.; delaroche, d.; seuleiman, m.; bodo, B.; nay, B.planta Med.2008,870]Therefore, the development of highly efficient synthesis of 2-oxabicyclo [2.2.2]The method for preparing octane-3-ketone derivative is 2-oxabicyclo [2.2.2]2-oxabicyclo [2.2.2] as one of the key technologies for discovering octane-3-ketone drugs]Acidic hydrolysis of octane-3-imine for the preparation of 2-oxaBicyclo [2.2.2]An efficient method for the construction of 2-oxabicyclo [2.2.2] n-2-ones from octane-3-one derivatives]Methods for octane-3-imine building blocks have been reported, polysubstituted 2-oxabicyclo [2.2.2]The variety of octane-3-imine derivatives is also very limited. The present invention therefore aims to develop a highly efficient synthesis of polysubstituted 2-oxabicyclo [2.2.2]]The octane-3-imine derivative has potential industrial application prospect in products from cheap and easily-obtained raw materials.
Disclosure of Invention
The invention aims to provide a method for efficiently synthesizing polysubstituted 2-oxabicyclo [2.2.2] octane-3-imine derivatives, which comprises the following steps: the aza chalcone is used as a raw material, DBU is used as alkali, the raw material and the DBU react in an ethanol solution, and the target product is generated by stirring and reacting at 25 ℃.
The invention is realized by the following method: adding 2mmol of 3-aryl-1- (pyridine-2-yl) -2-propylene-1-ketone or 3-aryl-1- (pyrazine-2-yl) -2-propylene-1-ketone, 1mmol of malononitrile or cyanoacetamide and 1.2 mmol of DBU into a 50mL round bottom flask with a magnetic stirring bar, stirring and reacting at 25 ℃, carrying out Thin Layer Chromatography (TLC), after the reaction is finished, carrying out vacuum suction filtration to obtain a crude product, reserving a mother solution for separating and collecting the crude product, and recrystallizing the crude product by using an ethanol/acetone (V/V = 1) mixed solution to obtain a target product, namely the 2-oxabicyclo [2.2.2] octane-3-imine derivative.
The 3-aryl-1- (pyridine-2-yl) -2-propylene-1-ketone or 3-aryl-1- (pyrazine-2-yl) -2-propylene-1-ketone is used as an initial raw material, the catalytic system is organic base DBU, reaction solvent ethanol is used, and the reaction temperature is 25 ℃.
The invention has the following advantages:
when the 2-oxabicyclo [2.2.2] octane-3-imine derivative is synthesized, 3-aryl-1- (pyridine-2-yl) -2-propylene-1-ketone or 3-aryl-1- (pyrazine-2-yl) -2-propylene-1-ketone which is relatively low in price and easy to prepare is adopted as a raw material, ethanol which is low in toxicity and relatively green is used as a solvent, and the reaction temperature is room temperature.
Detailed Description
Example 1:
Figure BDA0002960164420000021
5, 8-bis- (4-chlorophenyl) -3-imine-6- (pyridine-2-acyl) -1-pyridin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-cyano preparation: adding 3- (4-chlorophenyl) -1- (pyridine-2-yl) -2-propylene-1-ketone (2 mmol), malononitrile (1 mmol) and 1.2 mmol of DBU into a 50mL round-bottom flask with a magnetic stirrer, adding 5mL of ethanol solution, stirring and reacting at 25 ℃ for 24 hours, carrying out vacuum filtration on reaction mixed solution to obtain a solid crude product, and recrystallizing the crude product in the mixed solution of ethanol and acetone to obtain the target product.
Example 2:
3-imine-6- (pyridine-2-formyl) -1-pyridin-2-yl-5, 8-di-p-methylphenyl-2-oxa-bicyclo [2.2.2] octane-4-carboxamide preparation: adding 3- (4-methylphenyl) -1- (pyridine-2-yl) -2-propylene-1-ketone (2 mmol), cyanoacetamide (1 mmol) and 1.2 mmol of DBU into a 50mL round-bottom flask with a magnetic stirrer, adding 5mL of ethanol solution, stirring and reacting at 25 ℃ for 24 hours, decompressing and filtering reaction mixed solution to obtain a solid crude product, and recrystallizing the crude product in the ethanol/acetone mixed solution to obtain the target product.
The reaction materials, reaction conditions and yields of examples 1 to 16 are shown in Table 1.
TABLE 1 starting materials, reaction conditions and yields for the reactions of examples 1-16
Figure BDA0002960164420000031
As can be seen from Table 1, the method of the invention has the advantages of easily obtained raw materials, simple and safe operation, high yield and convenient post-treatment, thereby having great implementation value and potential social and economic benefits.
The characterization data of the obtained compounds are as follows.
5, 8-bis- (4-chlorophenyl) -3-imine-6- (pyridine-2-acyl) -1-pyridin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-cyano (3 a)
IR(KBr)(v,cm -1 )3479,3414,3243,1702,1680,1617,1592,1581,1494,1434,1344,1320, 1213,1098,1059,1012,996,890,787,746,619. 1 H NMR(400MHz,CDCl 3 )δ8.36–8.34(m, 1H),8.29(d,J＝4.4Hz,1H),7.66(d,J＝8.4Hz,2H),7.63–7.52(m,4H),7.46(d,J＝8.4Hz, 2H),7.27–7.21(m,3H),7.13(d,J＝8.6Hz,2H),7.00–6.97(m,1H),5.93(d,J＝6.4Hz,1H), 4.17(d,J＝6.4Hz,1H),3.76(dd,J＝11.1,6.0Hz,1H),3.62(dd,J＝14.9,11.2Hz,1H),2.38 (dd,J＝15.0,6.0Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ199.2,156.7,152.3,148.4,137.2, 136.8,136.5,135.0,134.2,133.0,131.1,130.0,129.1,129.0,127.0,123.1,122.0,120.4,115.8, 84.2,48.8,47.4,40.1,39.0；HRMS(APCI)m/z:Calcd.for C 31 H 23 Cl 2 N 4 O 2 [M+H] + :553.1193, found:553.1192.
5, 8-bis- (2-chlorophenyl) -3-imine-6- (pyridine-2-acyl) -1-pyridin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-cyano (3 b)
IR(KBr)(v,cm -1 ):3477,3413,1690,1616,1594,1581,1475,1435,1400,1364,1350,1321, 1290,1273,1212,1085,1036,994,978,774,746,737,709,616； 1 H NMR(400MHz,CDCl 3 ):δ 8.54(d,J＝4.8Hz,1H),8.30(d,J＝4.0Hz,1H),7.85(dd,J＝6.8,2.4Hz,1H),7.81(dd,J＝7.6, 1.6Hz,1H),7.63(d,J＝7.6Hz,1H),7.54-7.49(m,3H),7.38-7.27(m,5H),7.12-7.07(m,2H), 6.97(t,J＝6.0Hz,1H),7.00–6.94(m,1H),6.56(s,1H),5.65(d,J＝12.4Hz,1H),5.34(d,J＝ 12.8Hz,1H),5.15(dd,J＝12.8,2.8Hz,1H),3.11(t,J＝13.6Hz,1H),2.16(dd,J＝14.4,3.2Hz, 1H)； 13 C NMR(100MHz,CDCl 3 ):δ199.2,160.5,152.5,148.0,147.7,136.82,136.6,139.0, 135.2,134.4,132.1,130.3,129.9,128.6,127.4,127.0,122.6,122.1,120.0,113.4,112.6,74.8, 52.6,46.1,43.4,40.9,40.6.；HRMS(APCI)m/z:Calcd.for C 31 H 23 Cl 2 N 4 O 2 [M+H] + :553.1193, found:553.1189.
5, 8-bis- (3-bromophenyl) -3-imine-6- (pyridine-2-acyl) -1-pyridin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-cyano (3 c)
IR(KBr)(v,cm -1 ):3474,3423,1761,1702,1684,1590,1569,1475,1434,1358,1330,1281, 1259,1217,1164,1125,1103,1075,1054,996,909,827,780,740,693,621； 1 H NMR(400 MHz,CDCl 3 ):δ8.39-8.37(m,1H),8.29-8.26(m,1H),7.87(s,1H),7.63-7.50(m,6H),7.42- 7.33(m,3H),7.25-7.21(m,1H),7.17(d,J＝5.2Hz,2H),6.98-6.95(m,1H),5.90(d,J＝6.8 Hz,1H),4.15(d,J＝6.8Hz,1H),3.77(dd,J＝11.0Hz,6.2Hz,1H),3.56(dd,J＝15.0Hz,11.0 Hz,1H),2.38(dd,J＝15.0Hz,6.2Hz,1H)； 13 C NMR(100MHz,CDCl 3 ):δ199.9,160.0,152.6, 148.3,147.5,138.7,136.7,136.6,132.3,132.2,131.8,130.5,130.0,127.7,127.0,122.9,122.7, 122.5,121.9,120.3,113.7,112.6,74.6,48.7,47.8,45.5,39.8；HRMS(ESI)m/z:Calcd.for C 31 H 23 Br 2 N 4 O 2 [M+H] + :643.0162,found:643.0149.
3-imine-6- (pyridine-2-formyl) -1-pyridin-2-yl-5, 8-di-p-tolyl-2-oxa-bicyclo [2.2.2] octane-4-cyano (3 d)
IR(KBr)(v,cm -1 ):3342,3055,3025,2247,1766,1737,1699,1638,1616,1591,1514,1468, 1415,1344,1306,1291,1275,1261,1190,1137,1086,1058,1020,995,952,921,846,817； 1 H NMR(400MHz,CDCl 3 ):δ8.37(d,J＝4.8Hz,1H),8.32(d,J＝4.8Hz,1H),7.64-7.48(m,6H), 7.29(d,J＝8.0Hz,2H),7.22-7.19(m,1H),7.09(d,J＝8.0Hz,2H),7.02(d,J＝8.0Hz, 2H),6.96(dd,J＝7.2Hz,5.6Hz,1H),5.97(d,J＝6.0Hz,1H),4.22(d,J＝6.4Hz,1H),3.85(dd, J＝10.8Hz,5.6Hz,1H),3.70(dd,J＝15.2Hz,11.2Hz,1H),2.47(dd,J＝14.8Hz,5.6Hz,1H), 2.39(s,3H),2.28(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ199.3,166.8,156.3,152.3,148.4, 148.3,138.9,138.2,137.0,136.5,135.7,130.6,129.7,128.1,126.8,123.2,122.0,120.7,115.1, 86.5,54.1,48.7,46.9,40.0,39.5,21.2,21.1；HRMS(APCI)m/z:Calcd.for C 33 H 29 N 4 O 2 [M+H] + : 513.2286,found:513.2294.
5, 8-bis- (2, 3-dimethoxyphenyl) -3-imine-6- (pyridine-2-formyl) -1-pyridin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-cyano (3 e)
IR(KBr)(v,cm -1 ):3057,3004,2928,2838,1979,1678,1585,1481,1357,1293,1216,1151, 1092,1001,969,902,871,805,785； 1 H NMR(400MHz,CDCl 3 ):δ8.47(d,J＝4.4Hz,1H), 8.20(d,J＝4.4Hz,1H),7.62(d,J＝8.0Hz,1H),7.51-7.43(m,2H),7.37-7.32(m,3H),7.20 (dd,J＝7.2Hz,5.6Hz,1H),7.09(t,J＝8.2Hz,1H),6.91-6.88(m,2H),6.76-6.67(m,2H), 5.76(d,J＝12.4Hz,1H),5.17(d,J＝12.8Hz,1H),4.97(dd,J＝13.2Hz,2.8Hz,1H),4.03(s, 3H)4.02(s,3H),3.85(s,3H),3.74(s,3H),3.02(t,J＝13.6Hz,1H),2.06(dd,J＝14.0Hz,2.0 Hz,1H)； 13 C NMR(100MHz,CDCl 3 ):δ200.2,160.6,152.8,152.5,152.1,148.0,147.9,147.6, 147.2,136.6,136.2,130.9,128.5,126.5,123.8,123.1,122.4,121.7,120.45,120.40,119.4, 114.41,114.35,112.95,112.77,74.9,61.6,61.1,55.7,55.5,50.4,47.0,41.1,40.4,37.5；HRMS (APCI)m/z:Calcd.for C 35 H 33 N 4 O 6 [M+H] + :605.2395,found:605.2407.
5, 8-bis- (3, 4-dichlorophenyl) -3-imine-6- (pyridine-2-formyl) -1-pyridin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-cyano (3 f)
IR(KBr)(v,cm -1 ):3240,1694,1617,1516,1471,1406.1354,1286,1265,1237,1150,1099, 1082,1053,1017,1000,848,818,619,596； 1 H NMR(400MHz,CDCl 3 ):δ8.38(d,J＝4.4Hz, 1H),8.26(d,J＝4.8Hz,1H),7.82(d,J＝1.6Hz,1H),7.62-7.51(m,6H),7.36(d,J＝8.4Hz, 1H),7.28(d,J＝2.0Hz,1H),7.25-7.23(m,1H),7.09(dd,J＝8.4Hz,2.0Hz,1H),6.97(t,J＝ 5.8Hz,1H),5.88(d,J＝6.4Hz,1H),4.15(d,J＝6.0Hz,1H),3.72(dd,J＝11.0Hz,6.2Hz,1H), 3.56(dd,J＝15.2Hz,11.2Hz,1H),2.34(dd,J＝14.8Hz,6.0Hz,1H)； 13 C NMR(100MHz, DMSO-d 6 ):δ199.4,159.1,156.8,152.2,148.4,148.1,140.6,137.3,137.0,136.0,132.6,131.5, 131.2,131.0,130.8,130.7,130.5,129.3,127.5,123.3,121.5,120.6,116.0,84.5,49.8,47.8,47.1, 40.8,38.2；HRMS(APCI)m/z:Calcd.for C 31 H 21 Cl 4 N 4 O 2 [M+H] + :623.0384,found:623.0389.
3-imine-5, 8-diphenyl-6- (pyridine-2-formyl) -1-pyridin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-cyano (3 g)
IR(KBr)(v,cm -1 ):3230,1776,1696,1672,1683,1616,1591,1582,1365,1335,1243,1216, 1106,1079,1049,994,781,767,701,618； 1 H NMR(400MHz,CDCl 3 ):δ8.50(d,J＝4.4Hz, 1H),8.24(d,J＝4.4Hz,1H),7.66-7.60(m,3H),7.54-7.51(m,3H),7.49-7.33(m,5H),7.25- 7.22(m,1H),7.17-7.15(m,3H),6.94(dd,J＝6.8Hz,4.2Hz,1H),6.07(s,1H),5.78(d,J＝ 12.4Hz,1H),4.41(d,J＝12.8Hz,1H),4.22(dd,J＝12.8Hz,2.8Hz,1H),3.15(t,J＝13.6Hz, 1H),2.22(dd,J＝14.4Hz,3.0Hz,1H)； 13 C NMR(100MHz,CDCl 3 ):δ199.8,160.5,152.8, 148.0,147.5,136.8,136.6,136.5,134.7,129.6,129.0,128.9,128.8,128.4,126.7,122.5,121.9, 120.3,114.2,113.2,74.6,50.4,49.1,48.5,45.9,39.9；HRMS(APCI)m/z:Calcd.for C 31 H 25 N 4 O 2 [M+H] + :485.1973,found:485.1977.
3-imine-6- (pyridine-2-formyl) -1-pyridin-2-yl-5, 8-dithien-2-yl-2-oxa-bicyclo [2.2.2] octane-4-cyano (3 h)
IR(KBr)(v,cm -1 ):3474,3416,1689,1638,1617,1593,1581,1434,1399,1313,1279,1249, 1233,1085,1045,1036,779,703； 1 H NMR(400MHz,CDCl 3 ):δ8.50(d,J＝4.4Hz,1H),8.30 (s,1H),7.71-7.64(m,2H),7.54(t,J＝7.8Hz,1H),7.42(d,J＝7.6Hz,1H),7.35-7.32(m,2H), 7.29-7.26(m,1H),7.10-7.05(m,3H),6.79(t,J＝4.2Hz,2H),5.56(s,1H),4.68(d,J＝12.0 Hz,1H),4.52(dd,J＝12.6Hz,2.6Hz,1H),3.02(t,J＝13.4Hz,1H),2.40(d,J＝13.6Hz,1H)； 13 C NMR(100MHz,CDCl 3 ):δ 13 C NMR(101MHz,CDCl 3 )δ159.7,152.6,148.0,147.4,139.1, 136.8,136.6,128.6,127.5,127.1,127.0,126.7,126.1,125.8,122.7,122.0,120.4,114.4,113.2, 74.3,50.0,44.1,41.8,41.6；HRMS(APCI)m/z:Calcd.for C 27 H 21 N 4 O 2 S 2 [M+H] + :497.1101, found:497.1104.
3-imine-6- (pyridine-2-formyl) -1-pyrazin-2-yl-5, 8-di-p-methylphenyl-2-oxa-bicyclo [2.2.2] octane-4-cyano (3 i)
IR(KBr)(v,cm -1 ):2975,1737,1655,1495,1353,1176,1037,802,762,590； 1 H NMR(400 MHz,CDCl 3 ):δ9.23(s,1H),9.18(d,J＝1.2Hz,1H),8.47(d,J＝2.8Hz,1H),8.26(d,J＝2.4 Hz,1H),8.06(t,J＝1.6Hz,1H),7.91(d,J＝8.0Hz,2H),7.81(t,J＝1.6Hz,1H),7.38(d,J＝8.0Hz,2H),7.10(d,J＝8.4Hz,2H),7.03(d,J＝8.0Hz,2H),5.38(dd,J＝9.4Hz,1.2Hz,1H), 4.48(d,J＝9.6Hz,1H),3.75(dd,J＝10.8Hz,8.4Hz,1H),3.36(dd,J＝14.8Hz,8.0Hz,1H), 2.54-2.47(m,1H),2.44(s,3H),2.21(s,3H)； 13 C NMR(100MHz,DMSO-d 6 ):δ197.5,160.2, 152.7,148.7,146.7,145.0,143.9,143.8,142.8,142.7,138.4,138.1,135.6,133.8,130.5,129.9, 129.8,128.5,116.3,82.9,55.6,50.0,44.7,41.8,31.7,21.3,21.0；HRMS(APCI)m/z:Calcd.for C 31 H 27 N 6 O 2 [M+H] + :515.2190,found:515.2182.、
5, 8-bis- (4-bromophenyl) -3-imine-6- (pyridine-2-formyl) -1-pyrazin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-cyano (3 j)
IR(KBr)(v,cm -1 ):3413,1696,1672,1637,1616,1489,1408,1354,1345,1283,1263,1128, 1112,1083,1059,1017,1008,984,887,869,847,829,798； 1 H NMR(400MHz,CDCl 3 ):δ 9.19(d,J＝1.2Hz,2H),8.52(d,J＝2.4Hz,1H),8.28(d,J＝2.4Hz,1H),8.08-8.07(m,1H), 7.92(d,J＝8.8Hz,2H),7.82-7.81(m,1H),7.72(d,J＝8.4Hz,2H),7.37(d,J＝8.8Hz,2H), 7.10(d,J＝8.8Hz,2H),5.33(d,J＝8.0Hz,1H),4.37(d,J＝9.6Hz,1H),3.77(dd,J＝10.6Hz, 8.2Hz,1H),3.32(dd,J＝15.2Hz,8.0Hz,1H),2.58-2.51(m,1H)； 13 C NMR(100MHz, CDCl 3 ):δ 13 C NMR(101MHz,DMSO)δ196.9,159.0,152.0,148.4,146.2,144.7,143.6,143.4, 142.4,137.1,135.7,132.3,131.9,131.8,130.5,122.2,121.8,115.6,82.5,79.2,54.5,49.1,43.7, 41.4,31.0；HRMS(APCI)m/z:Calcd.for C 29 H 21 Br 2 N 6 O 2 [M+H] + :645.0067,found:645.0048.
3-imine-6- (pyridine-2-formyl) -1-pyridin-2-yl-5, 8-di-p-methylphenyl-2-oxa-bicyclo [2.2.2] octane-4-carboxamide (3 k)
IR(KBr)(v,cm -1 ):3315,3191,2360,1699,1685,1616,1594,1514,1435,1396,1334,1322, 1288,1154,1085,994,817,788,618； 1 H NMR(400MHz,CDCl 3 ):δ8.45(d,J＝3.6Hz,1H), 8.20(s,1H),7.80(d,J＝7.6Hz,1H),7.53(s,1H),7.44-7.38(m,3H),7.32(t,J＝6.0Hz,3H), 7.18-7.14(m,3H),6.88(d,J＝8.0Hz,3H),6.32(d,J＝10.8Hz,1H),5.56(s,1H),5.18(s,1H), 4.38(d,J＝12.4Hz,1H),4.13(dd,J＝13.0Hz,3.4Hz,1H),3.69(t,J＝13.2Hz,1H),2.32(s, 3H),2.14(s,3H),1.95(d,J＝10.8Hz,1H)； 13 C NMR(100MHz,CDCl 3 ):δ201.3,167.8,161.3, 153.5,147.9,146.6,137.6,137.4,136.1,135.5,133.4,129.6,129.2,129.0,128.8,126.1,122.2, 121.9,121.4,120.9,77.2,74.7,55.4,48.2,45.5,39.2,21.1,21.0.；HRMS(APCI)m/z:Calcd.for C 33 H 31 N 4 O 3 [M+H] + :531.2391,found:531.2396.
5, 8-bis- (4-bromophenyl) -3-imine-6- (pyridine-2-formyl) -1-pyrazin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-carboxamide (3 l)
IR(KBr)(v,cm -1 ):3552,3367,3310,3184,1695,1616,1594,1569,1488,1435,1398, 1330,1290,1217,1086,1074,1011,995,831,820,787,740,706,651； 1 H NMR(400MHz, CDCl 3 ):δ8.(d,J＝3.6Hz,1H),8.19(s,1H),7.77(d,J＝7.2Hz,1H),7.52-7.34(m,7H),7.26- 7.17(m,4H),6.92(s,1H),6.32(d,J＝9.6Hz,1H),5.56(s,1H),5.14(s,1H),4.40(d,J＝12.4 Hz,1H),4.13(dd,J＝13.0Hz,3.0HZ,1H),3.65(t,J＝13.4Hz,1H),1.95(d,J＝11.6Hz,1H)； 13 C NMR(100MHz,DMSO-d 6 ):δ 13 C NMR(101MHz,DMSO)δ200.5,166.5,162.3,153.6, 148.2,147.4,138.5,137.2,136.7,136.2,131.4,131.9,130.9,126.5,122.1,121.2,121.10 121.0, 120.4,75.0,53.8,48.7,47.7,44.9,38.4；HRMS(APCI)m/z:Calcd.for C 31 H 25 Br 2 N 4 O 3 [M+H] + : 661.0268,found:661.0263.
5, 8-bis- (3-chlorophenyl) -3-imine-6- (pyridine-2-formyl) -1-pyrazin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-carboxamide (3 m)
IR(KBr)(v,cm -1 ):3553,3361,3314,3185,3063,2922,1693,1617,1595,1571,1475, 1437,1397,1369,1324,1301,1288,1214,1202,1079,1049,996,987,852,787,713,705； 1 H NMR(400MHz,CDCl 3 ):δ8.49(d,J＝4.4Hz,1H),8.19(d,J＝4.0Hz,1H),7.77(d,J＝8.0Hz, 1H),7.54-7.45(m,4H),7.44-7.3(m,3H),7.31-7.29(m,2H),7.21-7.17(m,1H),7.07-7.06(m, 2H),6.91(s,1H),6.38(d,J＝12.0Hz,1H),5.60(s,1H),5.22(s,1H),4.38(d,J＝12.4Hz,1H), 4.14(dd,J＝12.8Hz,3.6Hz,1H),3.65(t,J＝13.0Hz,1H),1.96(dd,J＝13.4Hz,3.0Hz,1H)； 13 C NMR(100MHz,DMSO-d 6 ):200.5,166.4,162.2,153.6,148.2,147.4,141.6,140.0,136.7, 136.2,133.0,132.6,130.4,129.7,128.8,128.0,127.7,126.5,122.1,121.1,120.4,120.3,75.0, 53.6,48.5,47.9,45.1,38.5；HRMS(APCI)m/z:Calcd.for C 31 H 25 Cl 2 N 4 O 3 [M+H] + :571.1299, found:571.1293.
3-imine-6- (pyridine-2-formyl) -1-pyridin-2-yl-5, 8-dithien-2-yl-2-oxa-bicyclo [2.2.2] octane-4-carboxamide (3 n)
IR(KBr)(v,cm -1 ):3482,3195,3087,1701,1669,1616,1585,1434,1399,1374,1350,1332, 1313,1291,1218,1041,995,779,704,617； 1 H NMR(400MHz,CDCl 3 ):δ8.65-8.64(m,1H), 8.52-8.50(m,1H),7.90-7.86(m,2H),7.73(td,J＝8.0Hz,2.0Hz,1H),7.68(d,J＝8.0Hz,1H), 7.40(ddd,J＝6.0Hz,4.8Hz,1.2Hz,1H),7.37-7.31(m,3H),7.24(dd,J＝4.2Hz,0.8Hz,1H), 7.18(dd,J＝3.6Hz,1.2Hz,1H),7.08(dd,J＝5.2Hz,3.6Hz,1H),6.96(dd,J＝5.2Hz,3.6Hz, 1H),6.70(s,1H),5.72(s,1H),4.79(dd,J＝19.2Hz,10.6Hz,1H),4.57(dd,J＝10.4Hz,2.4Hz, 1H),4.30(dd,J＝13.0Hz,2.6Hz,1H),4.13(dd,J＝19.0Hz,2.6Hz,1H),2.80(t,J＝13.4Hz, 1H),2.26(dt,J＝13.2Hz,1.8Hz,1H)； 13 C NMR(100MHz,CDCl 3 ):δ198.9,166.2,158.5, 153.0,149.0,147.8,139.7,139.6,138.4,136.6,129.4,127.5,127.0,126.5,125.9,125.4,124.3, 121.7,120.0,118.2,81.5,77.2,54.8,44.6,43.1,39.5,36.7；HRMS(APCI)m/z:Calcd.for C 27 H 23 N 4 O 3 S 2 [M+H] + :515.1207,found:515.1194.
3-imine-6- (pyrazine-2-formyl) -1-pyrazin-2-yl-5, 8-di-p-methylphenyl-2-oxa-bicyclo [2.2.2] octane-4-carboxamide (3 o)
IR(KBr)(v,cm -1 ):3316,3188,3026,2922,1688.68,1603,1514,1397,1333,1308,1285, 1159,1090,1053,1019,981,858,818； 1 H NMR(400MHz,CDCl 3 ):δ9.09(s,1H),8.57(s, 1H),8.47(s,1H),8.40(s,1H),8.24(s,1H),8.15(s,1H),7.37(d,J＝6.8Hz,2H),7.27(s,1H), 7.16(d,J＝7.2Hz,2H),6.86(d,J＝6.8Hz,2H),6.38(d,J＝12.4Hz,1H),5.62(s,1H),5.30(s, 1H),4.28(d,J＝12.4Hz,1H),4.10(d,J＝12.8Hz,1H),3.69(t,J＝13.2Hz,1H),2.32(s,3H), 2.13(s,3H),2.04(d,J＝12.8Hz,1H)； 13 C NMR(100MHz,CDCl 3 ):δ202.4,167.7,157.6,147.4, 147.1,143.5,143.25,143.0,142.9,141.8,138.0,137.96,134.8,132.5,129.3,129.0,128.9,120.4, 77.2,74.9,55.2,48.3,48.0,45.1,38.5,21.1,20.9；HRMS(APCI)m/z:Calcd.for C 31 H 29 N 6 O 3 [M+H] + :533.2296,found:533.2296.
5, 8-bis- (4-bromophenyl) -3-imine-6- (pyrazine-2-formyl) -1-pyrazin-2-yl-2-oxa-bicyclo [2.2.2] octane-4-carboxamide (3 p)
IR(KBr)(v,cm -1 ):3466,3319,3195,3044,1705,1687,1610,1568,1488,1405,1385,1369, 1326,1286,1228,1166,1093,1073,1046,1016,1009,982,833,821； 1 H NMR(400MHz, DMSO-d 6 )δ8.57(d,J＝2.8Hz,1H),8.53(dd,J＝5.2Hz,1.6Hz,2H),8.40(q,J＝2.4Hz,1.6 Hz,2H),8.19(d,J＝2.4Hz,1H),7.58(d,J＝8.4Hz,2H),7.39(d,J＝8.4Hz,4H),7.33(d,J＝ 8.8Hz,2H),6.63(s,1H),6.12(d,J＝12.4Hz,1H),6.04(s,1H),4.30(d,J＝12.4Hz,1H),4.05- 3.94(m,2H,CH),1.78(d,J＝10.4Hz,1H)； 13 C NMR(100MHz,DMSO-d 6 ):δ199.5,166.4, 158.5,148.0,147.4,143.4,143.2,143.0,142.6,142.1,138.3,137.1,131.4,131.2,131.1,121.3, 121.2,120.2,74.9,53.7,49.3,46.9,44.3,37.9.；HRMS(APCI)m/z:Calcd.for C 29 H 23 Br 2 N 6 O 3 [M+H] + :663.0173,found:663.0168。

Claims (1)

  1. A method for synthesizing polysubstituted 2-oxabicyclo [2, 2] octane-3-imine derivatives under the catalysis of DBU is characterized by comprising the following steps: the method comprises the following steps of (1) reacting azachalcone and malononitrile or cyanoacetamide serving as raw materials and DBU serving as alkali in an organic solvent to generate a target product;
    the organic solvent is ethanol;
    the reaction condition is that the stirring reaction is carried out at 25 ℃;
    the molar ratio of the azachalcone to the malononitrile is 2: 1;
    the molar ratio of the azachalcone to the cyanoacetamide is 2: 1;
    the structural formula of the azachalcone is shown as the following formula 1, and the structural formula of the polysubstituted 2-oxabicyclo [2, 2] octane-3-imine derivative is shown as the following formula 3;
    Figure FDA0003701785800000011
    wherein Z is CH or N, R is CN or CONH 2 Ar is one of the formulae
    4-ClC 6 H 4
    2-ClC 6 H 4
    3-BrC 6 H 4
    4-CH 3 C 6 H 4
    2，3-(CH 3 O) 2 C 6 H 3
    3，4-Cl 2 C 6 H 3
    C 6 H 5
    Figure FDA0003701785800000012
    4-BrC 6 H 4
    3-ClC 6 H 4 。
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1982001650A1 (en) * 1980-11-10 1982-05-27 Shamrock Corp Diamond Biologically active heterobicyclic hydroximidates and thiolhydroximidates and carbamate ester derivatives thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1982001650A1 (en) * 1980-11-10 1982-05-27 Shamrock Corp Diamond Biologically active heterobicyclic hydroximidates and thiolhydroximidates and carbamate ester derivatives thereof

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* Cited by examiner, † Cited by third party
Title
Phosphine-catalyzed [4 + 2] annulation and vinylogous addition reactions between 1,4-dien-3-ones and 1,1-dicyanoalkenes;Rong Zhou，等;《Org. Biomol. Chem.》;20121231;第10卷;第773-781页 *
The Structures of Marvel"s δ-Lactone and "Polymer";Alex T. Rowland，等;《J. Org. Chem.》;19881231;第53卷(第2期);第434-437页 *

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