新型含噻唑和吡唑环的醛腙类化合物的合成

吕 警, 王吉德, 解正峰

(新疆大学 化学化工学院,新疆 乌鲁木齐 830046)

噻唑类化合物具有广泛的生理活性，在过去的几十年里，研究者通过各种的方法已合成不同噻唑环衍生物[1～12]。腙类化合物因具有特殊的生物活性和强配位能力, 在农药、医药、材料和分析试剂等方面而备受关注[13], 所以将噻唑环和吡唑环引入到腙类化合物分子中, 很可能由于拼合作用产生更强的生物活性。

本文报道1-苯基-3-甲基-5-取代吡唑-4-甲醛(Ⅰf～Ⅰh)与氨基硫脲缩合制得1-苯基-3-甲基-5-取代吡唑-4-甲醛缩氨基硫脲(Ⅱf～Ⅱh); Ⅱ与α-溴代芳基乙酮(1a～1e)反应合成了15个新型含噻唑和吡唑环的醛腙——N-(1-苯基-3-甲基-5-氯吡唑-4-基)-N′-(4-芳基-噻唑-2-基)醛腙(2a～2e),N-(1-苯基-3-甲基-5-苯氧基吡唑-4-基)-N′-(4-芳基噻唑-2-基)醛腙(3a～3e)和N-(1-苯基-3-甲基-5-对甲苯氧基吡唑-4-基)-N′-(4-芳基噻唑-2-基)醛腙(4a～4e, Scheme 1),其结构经1H NMR, IR和元素分析表征。2c作X-射线单晶衍射测试。

Scheme1

1 实验部分

1．1 仪器与试剂

FP52型显微熔点仪(温度计未校正);VARIAN INOVA-400 MHz型核磁共振谱仪(CDCl3为溶剂,TMS为内标); BRUKER EQUINOX 55型傅里叶变换红外光谱仪(KBr压片);Thermo Flash EA-1112型元素分析仪；R-AXIS SPIDER型X-射线单晶衍射仪。

Ⅱf～Ⅱh[14，16]和1a～1e[15]按文献方法制备；其余所用试剂均为分析纯。

1．2 2a～5e的合成(以2a为例)

在三颈烧瓶中加入Ⅱf1 mmol的无水乙醇(25 mL)溶液和1a1 mmol,搅拌下回流反应1 h。冷却至室温，滴加氨水至不再析出沉淀，过滤，滤饼用混合溶剂[V(DMF) ∶V(EtOH)=3 ∶2]重结晶得2a。

用类似方法合成2b～2e,3a～3e和4a～4e。2～4的实验结果见表1,表征数据见表2。

2 结果与讨论

2.1 表征

由表2可见，2～4的IR谱图具有共同特征:3 178 cm-1～3 071 cm-1出现υN-H特征吸收峰，1 640 cm-1～1 547 cm-1出现υC=N吸收峰，1 300 cm-1～1 210 cm-1出现υN-N-C吸收峰,695 cm-1～660 cm-1的强峰指派为υC-S-C特征吸收峰，另外芳氢吸收峰出现在3 100 cm-1～3 000 cm-1，芳环骨架吸收峰出现1 600 cm-1～1 460 cm-1。

2.2 2c的结体结构

将2c用乙醇溶解，于室温自然挥发，数天后得棕黄色柱状单晶。将2c单晶(0.57 mm×0.52 mm×0.45 mm)置衍射仪上,用MoKα射线(λ=0.071 073 nm)以ω～2θ扫描方式在3.02°≤θ≤27.49°收集9 055个强反射数据,其中独立衍射点71 089个(Rint=0.066 0)。全部强度数据均经Lp因子校正,并做经验吸收校正. 晶体结构用直接法解出,全部非氢原子的坐标及各向异性参数经最小二乘修正,用SHELXL-97程序对F2进行精修获得非氢原子坐标及各向异性参数,氢原子由差值Fourier合成。和理论计算得到,他们的坐标和各向同性温度因子参与结构计算,但不参与修正。最后得到R1=0.054 5,ωR2=0.148 9,Rsigma=0.027,Rint=0.066 0,GOF=1.049,最后残余电子密度峰最大最小值为0.647 e·nm-3～0.941 e·nm-3。2c的非氢原子坐标和等效温度因子见表3，晶体学参数见表4，部分键长和键角见表5;分子结构及其在晶胞中的二维堆积分别见图1和图2。由图1和图2可看出,在2c晶体中, 噻唑环氮与另一分子上的NH相互作用分别形成分子间的N-H┈N氢键,N(5)-H(9A)为2.941 Å, N(10)-H(4A)为2.983 Å。由于2c具有较强分子间氢键,使其分子堆积紧密。

表 1 合成2～4的实验结果Table 1 Experamental results of synthesizing 2～4

表 2 2～4的表征数据Table 2 Characteristic data of 2～4

续表2

Comp1 H NMR δIR ν/cm-13c7.66(s, 1H, NH), 7.60(s, 1H, N=CH),7.53^6.77(m, 15H, ArH), 2.54(s, 3H, CH3)3 073, 3 007, 3 005, 1 567, 1 463, 1 227, 6903d7.70(s, 1H, NH), 7.62(s, 1H, N=CH), 7.52^6.79(m, 18H, ArH), 2.56(s, 3H, CH3), 2.44(s, 3H, CH3)3 077, 3 007, 2 998, 1 568, 1 478, 1 226, 6913e7.70(s, 1H, NH), 7.62(s, 1H, N=CH), 7.52^6.79(m, 18H, ArH), 2.56(s, 3H, CH3), 2.44(s, 3H, CH3)3 075, 3 008, 2 997, 1 569, 1 488, 1 248, 6924a7.70(s, 1H, NH), 7.66(s, 1H, N=CH), 7.53^6.87(m, 18H, ArH), 2.52(s, 3H, CH3), 2.32(s, 3H, ArCH3)3 078, 3 007, 2 996, 1 568, 1 478, 1 227, 6914b7.67(s, 1H, NH) 7.63(s, 1H, N=CH), 7.51^6.84(m, 17H, ArH), 2.50(s, 3H, CH3), 2.29 (s, 3H, ArCH3)3 072, 3 003, 2 997, 1 565, 1 482, 1 217, 6904c7.66(s, 1H, NH), 7.61(s, 1H, N=CH), 7.52^6.82(m, 17H, ArH), 2.48(s, 3H, CH3), 2.28 (s, 3H, ArCH3)3 073, 3 004, 2 995, 1 567, 1 483, 1 223, 6904d7.69(s, 1H, NH), 7.64(s, 1H, N=CH), 7.52^6.85(m, 20H, ArH), 2.51(s, 3H, CH3), 2.30(s, 3H, ArCH3), 2.45(s, 3H, ArCH3)3 078, 3 009, 2 999, 1 567, 1 498, 1 223, 6914e7.64(s, 1H, NH), 7.61(s, 1H, N=CH), 7.50^6.83(m, 20H, ArH), 3.73(s, 3H, ArOCH3), 2.49(s, 3H, CH3), 2.27(s, 3H, ArCH3)3 079, 3 010, 2 998, 1 568, 1 498, 1 211, 692

表 3 2c的原子坐标(×104)和各向同性热参数(×103)Table 3 Atomic coordinates(×104) and equivalent isotropic displacement parameters(×103) of 2c

表 4 2c的晶体学参数Table 4 Crystal data and refinement details of 2c

表 5 2c的部分键长和键角Table 5 Selection bond lengths and angles of 2c

图 1 2c的分子结构图Figure 1 Molecular structures of 2c

图 2 2c的晶胞堆积图Figure 2 Packing drawing of 2c

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