新型α-萜品烯马来酰亚胺基双磺酰胺化合物的合成及其除草活性
2012-11-23马献力黄建新段文贵莫启进林桂汕
马献力, 黄建新, 段文贵, 莫启进, 林桂汕, 岑 波, 黄 翊
(1. 广西大学 化学化工学院,广西 南宁 530004; 2. 桂林医学院 药学院,广西 桂林 541004)
近年来,通过α-蒎烯(1)分子的结构修饰合成具有生物活性的衍生物已成为有机合成化学和松脂化学的研究热点。磺酰胺类化合物含S, N, O杂原子,一般都具有杀菌[1,2]、抗病毒[3~8]及除草[9,10]等生物活性,目前磺酰胺类化合物已经在医药、生命科学、超分子等领域中有着非常广泛的应用。
近年来,本课题组对松香松节油基生物活性化合物作了许多研究工作,取得了一系列研究成果[11~16]。本文在此基础上,进一步开展1的改性研究。先将1转化为N-氨基-α-萜品烯马来酰亚胺(4),通过其氨基的改性反应,将磺酰胺活性基团引入到4的骨架中,设计并合成了8个新型的具有潜在生物活性的取代苯基-α-萜品烯马来酰亚胺基双磺酰胺化合物(5a~5h, Scheme 1),其结构经1H NMR,13C NMR, IR和ESI-MS表征。并测试了其除草活性,为松节油的深度开发利用提供新的途径。
1 实验部分
1.1 仪器与试剂
X-4型数字显示显微熔点仪(温度计未校正);Bruker AV 600 MHz型核磁共振仪(CDCl3为溶剂,TMS为内标); Nicolet Nexus 470 FT-IR型红外光谱仪(KBr压片);Agilent 1100 LC/MSD Trap SL型高效液相色谱-质谱联用仪(LC-MS)。
1(97%),广西梧州松脂股份有限公司;α-萜品烯马来酸酐(3)按文献[17,18]方法合成;其余所用试剂均为分析纯。
1.2 合成
(1)N-氨基-α-萜品烯马来酰亚胺(4)的合成
在反应瓶中加入353.20 g(227.4 mmol),无水乙醇122.4 mL,搅拌下于84 ℃滴加水合肼13.24 mL(272.8 mmol)(10 min内),回流反应2 h。加入蒸馏水90 mL,回流至溶液变澄清,于60 ℃加入石油醚50 mL,搅拌10 min后倾入大烧杯中静置冷却至室温。抽滤,滤饼用石油醚洗涤4次~5次,用乙醇重结晶得白色固体4,产率72%, m.p.146 ℃~147 ℃;1H NMRδ: 5.95(d,J=8.5 Hz, 1H, 8-H), 5.87(d,J=8.5 Hz, 1H, 7-H), 4.22(s, 2H, NH2), 2.93(d,J=7.7 Hz, 1H, 2-H), 2.66~2.49(m, 2H, 5,11-H), 1.55~1.38(m, 5H, 6-CH3, 9-Ha, 10-Ha), 1.38~1.21(m, 2H, 9-Hb, 10-Hb), 1.10(d,J=6.8 Hz, 3H, 11-CH3), 0.97(d,J=7.0 Hz, 3H, 11-CH3);13C NMRδ: 174.21, 173.81, 136.26, 135.52, 48.77, 45.0, 43.61, 36.85, 34.21, 29.63, 22.87, 22.59, 18.35, 16.83; IRν: 3 302, 3 144, 3 035, 2 964, 2 869, 1 764, 1 709, 1 453, 1 355 cm-1; ESI-MSm/z: 248(M+)。
(2) 5的合成(以5a为例)
在反应瓶中加入43.724 8 g(15 mmol), 二甲氨基吡啶(DMAP)58.7 mg, 三乙胺6.8 mL及二氯甲烷30 mL,搅拌使其溶解;升温至回流,滴加苯磺酰氯(Ⅰa)2.119 2 g(12 mmol)(30 min内),回流反应至终点(TLC检测)。蒸出溶剂,残余物经硅胶柱层析[洗脱剂:V(二氯甲烷) ∶V(石油醚)=3 ∶1]纯化后再用二氯甲烷重结晶得白色晶体5a1.568 4 g。
用类似的方法合成白色固体5b~5h。
1.3 除草活性测试
油菜平皿法[10]: 在6 cm的培养皿中铺好一张直径为5.6 cm的滤纸,加入一定浓度的供试药液2 mL(以等体积的蒸馏水作为空白对照)。播种浸种4 h的油菜种子10粒,于(28±1) ℃黑暗培养72 h后测定胚根长度,计算抑制率。
稗草小杯法[10]: 在50 mL小烧杯中铺好玻璃珠和滤纸后,加入一定浓度的供试药液6 mL(以等体积的蒸馏水作为空白对照液)。播种刚刚露白的稗草种子10粒,于(28±1) ℃光照培养72 h后测定小苗的高度(每个处理重复两次),计算抑制率。
2 结果与讨论
2.1 合成与实验结果
在5a的合成中,尝试在不加催化剂的条件下,将磺酰氯在室温下缓慢滴加到过量的4的二氯甲烷中。反应较慢,10 h后分析发现两个反应物都未反应完。其原因可能是4的氨基连在环状酰亚胺的氮原子上,而此氮原子受到与它相连的两个羰基强拉电子作用,电子云密度很低,这种吸电子诱导效应通过N—N键传递给氨基,从而使得氨基上电子云密度降低,亲核性减弱,从而影响化学反应速率。而加入催化剂DMAP反应4 h后作TLC分析,发现反应已经基本结束,说明DMAP有很好的催化效果。
5a~5h的实验结果,IR和MS数据见表1;1H NMR和13C NMR数据见表2。
表1 5的实验结果,IR和MS数据Table 1 Experimental results, IR and MS data of 5
表2 5的NMR数据Table 2 NMR data of 5
续表2
Comp1H NMR δ(J/Hz)13C NMR δ5b7.99(d, J=8.4, 2H, ArH), 7.80(d, J=8.3, 2H, ArH), 7.35(d, J=8.1, 2H, ArH), 7.30(d, J=8.1, 2H, ArH), 6.05(d, J=8.4, 1H, 8-H), 5.98(d, J=8.4, 1H, 7-H), 3.06(d, J=8.3, 1H, 2-H), 2.68(d, J=8.3, 1H, 5-H), 2.46(d, J=2.9, 6H, ArCH3), 2.38~ 2.30(m, 1H, 11-H), 1.53~1.48(m, 1H, 9-Ha), 1.47~1.41(m, 1H, 10-Ha), 1.39(s, 3H, 6-CH3), 1.37~1.31(m, 1H, 9-Hb), 1.31~1.25(m, 1H, 10-Hb), 1.05(d, J=6.8, 3H, 11-CH3), 0.97(d, J=6.9, 3H, 11-CH3)172.31, 171.78, 145.88, 145.70, 136.65, 136.19, 135.78, 135.08, 129.54, 129.54, 129.46, 129.46, 129.32, 129.32, 129.28, 129.28, 48.79, 45.10, 43.75, 36.93, 34.14, 29.58, 22.94, 22.38, 21.81, 21.81, 18.32, 16.795c7.96(d, J=8.8, 2H, ArH), 7.81(d, J=8.8, 2H, ArH), 7.71(d, J=8.8, 2H, ArH), 7.68(d, J=8.8, 2H, ArH), 6.04(d, J=8.4, 1H, 8-H), 5.97(d, J=8.4, 1H, 7-H), 3.08(d, J=8.3, 1H, 2-H), 2.70(d, J=8.3, 1H, 5-H), 2.32(hept, J=6.8, 1H, 11-H), 1.54~1.49(m, 1H, 9-Ha), 1.48~1.42(m, 1H, 10-Hb), 1.40(s, 3H, 6-CH3), 1.38~1.33(m, 1H, 9-Hb), 1.32~1.27(m, 1H, 10-Hb), 1.06(d, J=6.8, 3H, 11-CH3), 0.99(d, J=6.9, 3H, 11-CH3)172.22, 171.72, 137.94, 136.84, 136.66, 135.81, 132.33, 132.33, 132.11, 132.11, 130.84, 130.84, 130.69, 130.69, 130.43, 130.27, 48.82, 45.14, 43.84, 36.99, 34.07, 29.66, 22.96, 22.36, 18.31, 16.775d8.25(t, J=1.8, 1H, ArH), 8.08(d, J=8.0, 1H, ArH), 7.99(d, J=8.0, 1H, ArH), 7.92(t, J=1.8, 1H, ArH), 7.83~7.82(m, 1H, ArH), 7.82~7.80(m, 1H, ArH), 7.47(td, J=8.0, 1.7, 2H, ArH), 6.19(d, J=8.4, 1H, 7-H), 6.10(d, J=8.4, 1H, 8-H), 3.09(d, J=8.4, 1H, 5-H), 2.72(d, J=8.4, 1H, 2-H), 2.34(dt, J=13.8, 6.9, 1H, 11-H), 1.53~1.50(m, 1H, 9-Ha), 1.49~1.44(m, 1H, 10-Ha), 1.43(s, 3H, 6-CH3), 1.40~1.34(m, 1H, 9-Ha), 1.34~1.28(m, 1H, 10-Hb), 1.05(d, J=6.8, 3H, 11-CH3), 1.01(d, J=6.9, 3H, 11-CH3)172.30, 171.76, 140.79, 139.53, 137.91, 137.91, 136.88, 135.90, 132.32, 132.01, 130.81, 130.65, 128.01, 128.01, 122.76, 122.38, 49.00, 45.30, 44.06, 37.24, 34.31, 29.77, 23.11, 22.49, 18.60, 16.895e8.04(d, J=8.7, 2H, ArH), 7.89(d, J=8.7, 2H, ArH), 7.54(d, J=8.7, 2H, ArH), 7.51(d, J=8.7, 2H, ArH), 5.95(d, J=8.5, 1H, 8-H), 5.87(d, J=8.4, 1H, 7-H), 2.93(d, J=7.8, 1H, 2-H), 2.63~2.54(m, 2H, 5,11-H), 1.52~1.47(m, 4H, 6-CH3, 9-Ha), 1.46~1.41(m, 1H, 10-Ha), 1.35~1.30(m, 1H, 9-Hb), 1.29~1.23(m, 1H, 10-Hb), 1.10(d, J=6.8, 3H, 11-CH3), 0.97(d, J=7.0, 3H, 11-CH3)174.42, 174.02, 141.65, 137.51, 136.40, 135.67, 130.97, 130.97, 130.81, 130.81, 129.46, 129.46, 192.43, 129.24, 129.24, 128.55, 48.89, 45.13, 43.75, 37.01, 34.34, 29.78, 22.99, 22.75, 18.52, 16.985f8.11(t, J=1.9, 1H, ArH), 8.05~8.02(m, 1H, ArH), 7.95~7.92(m, 1H, ArH), 7.80(t, J=1.9, 1H, ArH), 7.68~7.65(m, 2H, ArH), 7.56~7.51(m, 2H, ArH), 6.17(d, J=8.4, 1H, 7-H), 6.09(d, J=8.4, 1H, 8-H), 3.09(d, J=8.4, 1H, 5-H), 2.72(d, J=8.3, 1H, 2-H), 2.37~2.29(m, 1H, 11-H), 1.54~1.50(m, 1H, 9-Ha), 1.49~1.44(m, 1H, 10-Ha), 1.42(s, 3H, 6-CH3), 1.40~1.34(m, 1H, 9-Hb), 1.34~1.29(m, 1H, 10-Hb), 1.05(d, J=6.8, 3H, 11-CH3), 1.00(d, J=6.9, 3H, 11-CH3)172.30, 171.76, 140.69, 139.36, 136.88, 135.91, 135.20, 135.07, 134.96, 134.79, 130.57, 130.42, 129.54, 129.30, 127.61, 127.54, 49.01, 45.29, 44.05, 37.22, 34.30, 29.77, 23.11, 22.47, 18.53, 16.90
续表2
Comp1H NMR δ(J/Hz)13C NMR δ5g8.16~8.12(m, 2H, ArH), 8.01~7.97(m, 2H, ArH), 7.26~7.19(m, 4H,ArH), 6.05(d, J=8.4, 1H, 8-H), 5.97(d, J=8.4, 1H, 7-H), 3.08(d, J=8.3, 1H, 2-H), 2.70(d, J=8.3, 1H, 5-H), 2.32(hept, J=6.8, 1H, 11-H), 1.54~1.49(m, 1H, 9-Ha), 1.47~1.42(m, 1H, 10-Ha), 1.39(s,3H, 6-CH3), 1.35(m, 1H, 9-Hb), 1.32~1.27(m, 1H, 10-Hb), 1.05(d, J=6.8, 3H, 11-CH3), 0.98(d, J=7.0, 3H, 11-CH3)172.34, 171.92, 167.44, 167.27, 165.73, 165.56, 136.79, 135.92, 135.04, 134.00, 132.62, 132.62, 132.42, 132.42, 116.55, 116.39, 116.35, 116.19, 48.93, 45.27, 43.95, 37.12, 34.20), 29.79, 23.07, 22.49, 18.45, 16.895h8.03(d, J=9.0, 2H, ArH), 7.85(d, J=9.0, 2H, ArH), 7.01(d, J=9.0, 2H, ArH), 6.95(d, J=9.0, 2H, ArH), 6.05(d, J=8.4, 1H, 8-H), 5.98(d, J=8.4, 1H, 7-H), 3.89(s, 6H, OCH3), 3.06(d, J=8.3, 1H, 2-H), 2.68(d, J=8.3, 1H, 5-H), 2.39~2.31(m, 1H, 11-H), 1.54~1.48(m, 1H, 9-Ha), 1.47~1.42(m, 1H, 10-Ha), 1.39(s, 3H, 6-CH3), 1.36~1.31(m, 1H, 9-Hb), 1.31~1.25(m, 1H, 10-Hb), 1.05(d, J=6.8, 3H, 11-CH3), 0.97(d, J=7.0, 3H, 11-CH3)172.57, 172.03, 164.62, 164.46, 136.78, 135.90, 131.98 , 131.98, 131.77, 131.77, 130.54, 129.53, 114.21, 114.21, 113.97, 113.97, 55.88, 48.93, 45.23, 43.88, 37.07, 34.28, 29.72, 23.08, 22.55, 18.48, 16.93
表3 4和5的除草活性Table 3 Herbicidal activities of and 5
*测定方法见1.3;c=10(100) μg·mL-1
从表1可见,1 743 cm-1和1 795 cm-1峰为酰亚胺五元环上两个羰基C=O的伸缩振动特征吸收峰;1 500 cm-1~1 600 cm-1峰为苯环骨架伸缩振动吸收峰;5中-SO2-的对称和不对称伸缩振动吸收峰在1 341 cm-1和1 176 cm-1左右。从表1还可见5有分子离子峰或者准分子离子峰。
从表2可见,两个苯环的化学环境不等价,因此在氢谱和碳谱中在相邻区域会出现两组较为相似的峰,苯环上氢的化学位移在7.0~8.2,苯环上碳的化学位移在114~167。
2.2 除草活性
4和5的除草活性见表3。由表3可知,在100 μg·mL-1浓度下,4对油菜胚根生长显示强的抑制作用,抑制率达到84.6%,活性级别为A级,但对稗草的幼苗生长只有弱的抑制作用,抑制率为35%,活性级别为D级。大部分5对油菜的胚根生长显示一定的抑制作用,其中5f对油菜胚根生长抑制作用最好,抑制率为52.5%,活性级别均为C级。在浓度为100 μg·mL-1时,5对稗草的幼苗生长只有弱的抑制活性。从表3可以看出,R为氯时除草活性最好。
3 结论
合成了8个新型的α-萜品烯马来酰亚胺基双磺酰胺化合物。初步的除草活性测试表明,N-氨基-α-萜品烯马来酰亚胺具有良好的除草活性,值得进一步研究。
致谢:除草活性测试由南开大学元素所生测室完成,谨表谢意!
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