新型含噻唑和吡唑環(huán)的醛腙類化合物的合成

呂 警, 王吉德, 解正峰

(新疆大學(xué) 化學(xué)化工學(xué)院,新疆 烏魯木齊 830046)

噻唑類化合物具有廣泛的生理活性，在過去的幾十年里，研究者通過各種的方法已合成不同噻唑環(huán)衍生物[1～12]。腙類化合物因具有特殊的生物活性和強(qiáng)配位能力, 在農(nóng)藥、醫(yī)藥、材料和分析試劑等方面而備受關(guān)注[13], 所以將噻唑環(huán)和吡唑環(huán)引入到腙類化合物分子中, 很可能由于拼合作用產(chǎn)生更強(qiáng)的生物活性。

本文報(bào)道1-苯基-3-甲基-5-取代吡唑-4-甲醛(Ⅰf～Ⅰh)與氨基硫脲縮合制得1-苯基-3-甲基-5-取代吡唑-4-甲醛縮氨基硫脲(Ⅱf～Ⅱh); Ⅱ與α-溴代芳基乙酮(1a～1e)反應(yīng)合成了15個(gè)新型含噻唑和吡唑環(huán)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-對(duì)甲苯氧基吡唑-4-基)-N′-(4-芳基噻唑-2-基)醛腙(4a～4e, Scheme 1),其結(jié)構(gòu)經(jīng)1H NMR, IR和元素分析表征。2c作X-射線單晶衍射測試。

Scheme1

1 實(shí)驗(yàn)部分

1．1 儀器與試劑

FP52型顯微熔點(diǎn)儀(溫度計(jì)未校正);VARIAN INOVA-400 MHz型核磁共振譜儀(CDCl3為溶劑,TMS為內(nèi)標(biāo)); BRUKER EQUINOX 55型傅里葉變換紅外光譜儀(KBr壓片);Thermo Flash EA-1112型元素分析儀；R-AXIS SPIDER型X-射線單晶衍射儀。

Ⅱf～Ⅱh[14，16]和1a～1e[15]按文獻(xiàn)方法制備；其余所用試劑均為分析純。

1．2 2a～5e的合成(以2a為例)

在三頸燒瓶中加入Ⅱf1 mmol的無水乙醇(25 mL)溶液和1a1 mmol,攪拌下回流反應(yīng)1 h。冷卻至室溫，滴加氨水至不再析出沉淀，過濾，濾餅用混合溶劑[V(DMF) ∶V(EtOH)=3 ∶2]重結(jié)晶得2a。

用類似方法合成2b～2e,3a～3e和4a～4e。2～4的實(shí)驗(yàn)結(jié)果見表1,表征數(shù)據(jù)見表2。

2 結(jié)果與討論

2.1 表征

由表2可見，2～4的IR譜圖具有共同特征:3 178 cm-1～3 071 cm-1出現(xiàn)υN-H特征吸收峰，1 640 cm-1～1 547 cm-1出現(xiàn)υC=N吸收峰，1 300 cm-1～1 210 cm-1出現(xiàn)υN-N-C吸收峰,695 cm-1～660 cm-1的強(qiáng)峰指派為υC-S-C特征吸收峰，另外芳?xì)湮辗宄霈F(xiàn)在3 100 cm-1～3 000 cm-1，芳環(huán)骨架吸收峰出現(xiàn)1 600 cm-1～1 460 cm-1。

2.2 2c的結(jié)體結(jié)構(gòu)

將2c用乙醇溶解，于室溫自然揮發(fā)，數(shù)天后得棕黃色柱狀單晶。將2c單晶(0.57 mm×0.52 mm×0.45 mm)置衍射儀上,用MoKα射線(λ=0.071 073 nm)以ω～2θ掃描方式在3.02°≤θ≤27.49°收集9 055個(gè)強(qiáng)反射數(shù)據(jù),其中獨(dú)立衍射點(diǎn)71 089個(gè)(Rint=0.066 0)。全部強(qiáng)度數(shù)據(jù)均經(jīng)Lp因子校正,并做經(jīng)驗(yàn)吸收校正. 晶體結(jié)構(gòu)用直接法解出,全部非氫原子的坐標(biāo)及各向異性參數(shù)經(jīng)最小二乘修正,用SHELXL-97程序?qū)2進(jìn)行精修獲得非氫原子坐標(biāo)及各向異性參數(shù),氫原子由差值Fourier合成。和理論計(jì)算得到,他們的坐標(biāo)和各向同性溫度因子參與結(jié)構(gòu)計(jì)算,但不參與修正。最后得到R1=0.054 5,ωR2=0.148 9,Rsigma=0.027,Rint=0.066 0,GOF=1.049,最后殘余電子密度峰最大最小值為0.647 e·nm-3～0.941 e·nm-3。2c的非氫原子坐標(biāo)和等效溫度因子見表3，晶體學(xué)參數(shù)見表4，部分鍵長和鍵角見表5;分子結(jié)構(gòu)及其在晶胞中的二維堆積分別見圖1和圖2。由圖1和圖2可看出,在2c晶體中, 噻唑環(huán)氮與另一分子上的NH相互作用分別形成分子間的N-H┈N氫鍵,N(5)-H(9A)為2.941 ?, N(10)-H(4A)為2.983 ?。由于2c具有較強(qiáng)分子間氫鍵,使其分子堆積緊密。

表 1 合成2～4的實(shí)驗(yàn)結(jié)果Table 1 Experamental results of synthesizing 2～4

表 2 2～4的表征數(shù)據(jù)Table 2 Characteristic data of 2～4

續(xù)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的原子坐標(biāo)(×104)和各向同性熱參數(shù)(×103)Table 3 Atomic coordinates(×104) and equivalent isotropic displacement parameters(×103) of 2c

表 4 2c的晶體學(xué)參數(shù)Table 4 Crystal data and refinement details of 2c

表 5 2c的部分鍵長和鍵角Table 5 Selection bond lengths and angles of 2c

圖 1 2c的分子結(jié)構(gòu)圖Figure 1 Molecular structures of 2c

圖 2 2c的晶胞堆積圖Figure 2 Packing drawing of 2c

[1] Holla B S, Malini K V, Rao B S,etal. Synthesis of some new 2,4-disubstituted thiazoles as possible antibacterial and anti-inflammatory agents[J].Eur J Med Chem,2003,38:313-318.

[2] Karegoudar P, Karthikeyan M S, Prasad D J,etal. Synthesis of some novel 2,4-disubstituted thiazoles as possible antimicrobial agents[J].Eur J Med Chem,2008,43:261-267.

[3] Cukurovali A, Yilmaz I, Gur S,etal. Synthesis,antibacterial and antifungal activity of some new thiazolylhydrazone derivatives containing 3-substituted cyclobutane ring[J].Eur J Med Chem,2006,41:201-207.

[4] Siddiqui H L, Iqbal A, Ahmad S,etal. Synthesis and spectroscopic studies of new schiff bases[J].Molecules,2006,11:206-211.

[5] Potewar T M, Ingale S A, Srinivasan K V, Efficient synthesis of 2,4-disubstituted thiazoles using ionic liquid under ambient conditions:A practical approach towards the synthesis of Fanetizole[J].Tetrahedron,2007,63:11066-11069.

[6] Karade H, Sathe M, Kaushik M P. An efficient method for the synthesis of 2-aminothiazoles using silica chloride as a heterogeneous catalyst[J].Catal Commun,2007,8:741-746.

[7] Narender M, Reddy M S, Sridhar R,etal. Aqueous phase synthesis of thiazoles and aminothiazoles in the presence ofb-cyclodextrin[J].Tetrahedron Lett,2005,46:5953-5955.

[8] Das B, Reddy V S, Ramu R. A rapid and high-yielding synthesis of thiazoles and aminothiazoles using ammonium-12-molybdophosphate[J].J Mol Catal A:Chem,2006,252:235-237.

[9] Kazzouli S E, Berteina-Raboin S, Mouaddib A. Solid support synthesis of 2,4-disubstituted thiazoles and aminothiazoles[J].Tetrahedron Lett,2002,43:3193-3196.

[10] Kabalka G W, Mereddy A R. Microwave promoted synthesis of functionalized 2-aminothiazoles[J].Tetrahedron Lett,2006,47:5171-5172.

[11] El-Subbagh H I, Al-Obaid A M. 2,4-Disubstituted thiazolesⅡ.A novel class of antitumor agents,synthesis and biological evaluation[J].Eur J Med Chem,1996,31:1017-1021.

[12] Easmon J, Heinisch G, Hofmann J,etal. Thiazolyl and benzothiazolyl hydrazones derived froma-(N)-acetylpyridines and diazines:Synthesis,antiproliferative activity and CoMFA studies[J].Eur J Med Chem,1997,32:397-408.

[13] Sayed L E, Iskander M F. Coordination compounds of hydrazine derivatives with transition metals——Ⅲ:The reaction of aroyl hydrazones with Ni(Ⅱ) and Cu(Ⅱ) salts[J].J Inorg Nucl Chem,1971,33(2):435-443.

[14] 李在國. 有機(jī)中間體制備[M].北京:化學(xué)工業(yè)出版社,2000.

[15] 史延年,盧彥昌,方建新，等。ω-芳氧乙酸氧基-ω-(1H-1,2,4-三唑-1-基)苯乙酮衍生物的研究[J].高等學(xué)?；瘜W(xué)學(xué)報(bào),1995,16(11):1710-1713.

[15] 黃泰山. 呋喃醛縮氨基硫腙的合成和結(jié)構(gòu)測定[J]廈門大學(xué)學(xué)報(bào)(自然科學(xué)版),1994,33(6):827-831.