室溫下碘催化一鍋合成4-噻唑啉酮類化合物

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(淮陰師范學院 化學化工學院,江蘇 淮安 223300)

0 引言

近年來,雜環(huán)化合物顯示出越來越重要的作用,其中4-噻唑啉酮類雜環(huán)化合物在農藥和醫(yī)藥領域都表現(xiàn)出較好的生物活性,如:殺菌[1,2]、殺蟲[3]、除草[4]、抗HIV[5,6]、抗癌[7]、抗黃熱病病毒[8]等活性．合成4-噻唑啉酮類化合物的傳統(tǒng)方法是:席夫堿和巰基乙酸反應[9],或醛、胺和巰基乙酸反應,用苯作溶劑,回流10～12h[10];以四氫呋喃(tetrahydrofuran,THF)為溶劑,N,N′-二環(huán)己基碳化二亞胺(dicyclohexylcarbodiimide,DCC)作為脫水劑,室溫下一鍋反應合環(huán)[11];也有通過苯作溶劑微波輻射合成4-噻唑啉酮類化合物[12]．顯然,這些方法反應時間長,且使用有毒的溶劑或催化劑．

自從Cromwell等[13]把I2用于催化合成氮雜環(huán)丙烷以來,I2作為催化劑在有機合成中的重要作用,已引起人們的極大關注．I2除被用作氧化劑外[14,15],研究表明,它作為一種催化劑具有易得、高效、操作簡單等優(yōu)點,因此已被廣泛用于有機合成,具有很好的應用前景．本文報道在室溫下,以冰醋酸為介質,碘單質為催化劑,使醛、胺與巰基乙酸發(fā)生縮合反應,生成4-噻唑啉酮類化合物(圖1),與傳統(tǒng)方法比該法具有反應時間短、操作簡便和環(huán)境友好等優(yōu)點．所得化合物的結構均經(jīng)元素分析和1H NMR確證,采用X射線單晶衍射分析方法測定了化合物3f的結構．

a: R=4-Cl,Ar=4-CH3C6H4;b: R=3,4-(OCH2O),Ar=4-CH3C6H4;c: R=4-benzoxazolyl,Ar=4-CH3C6H4;
d: R=3,4-(OCH2O),Ar=4-ClC6H4;e: R=4-benzoxazolyl,Ar=4-ClC6H4;f: R=4-CH3,Ar=4-ClC6H4;g: R=2-Cl,Ar=3-Cl-4-CH3C6H3;h: R=4-CH3O,Ar=3-Cl-4-CH3C6H3;i: R=4-Cl,Ar=C6H5

圖1 4-噻唑啉酮類化合物的合成

1 實驗部分

1.1 儀器與試劑

X-24型數(shù)字顯示顯微熔點儀(北京泰克儀器有限公司),溫度計未經(jīng)校正;Bruker DPX 400MHz核磁共振儀(溶劑為CDCl3);Yanaco MT-3CHN 元素分析儀;BRUCKER SMART 1000 X射線衍射儀．

4-苯并惡唑基苯甲醛自制,其他試劑均為市售化學純或分析純．

1.2 4-噻唑啉酮類化合物的合成

將1mmol醛,1mmol胺,1mmol巰基乙酸和0.064g (0.25mmol)碘單質加入到盛有2 mL冰醋酸的圓底燒瓶中,室溫下攪拌反應2～4h(TLC檢測),反應完成后,將反應液倒入50mL冰水中并攪拌5min,抽濾,固體物用無水乙醇重結晶得產(chǎn)物．

2 結果與討論

圖2 化合物3f的分子結構圖

該反應在冰醋酸中進行,I2的用量為25%(mol)室溫攪拌2～4h即可完成,操作方便、產(chǎn)率高、環(huán)境友好,但在相似條件下,反應物中含有強吸電子基團時如-NO2等,幾乎得不到預期產(chǎn)物．表1給出了4-噻唑啉酮3a～3i合成的時間、產(chǎn)率和熔點．所有產(chǎn)物結構經(jīng)核磁共振氫譜和元素分析表征,噻唑烷環(huán)中的CH由于與吸電子原子N及S相連,導致其質子化學位移向低場移動,一般在δ6.10附近;目標化合物噻唑烷環(huán)中潛手性碳原子C(2)上的兩個質子HA和HB出現(xiàn)在δ 3.79～4.02附近,相互偶合裂分為雙重峰屬于典型的AB體系;把目標化合物3f溶于無水乙醇中,靜置,兩周后逐漸長成淺灰色晶體.該晶體屬于三斜晶系,空間群為P-1,晶胞參數(shù)：a=0.81506(12)nm,b=0.96414(14)nm,c=0.99470(15)nm,α=87.777°(2),β=74.946°(2),γ=72.030°(2),V=0.71729(18)nm3,Z=2,Dc=1.407g/cm3,μ=0.406mm-1,F(000)=316,R=0.0503,wR=0.1106.圖2是化合物3f的分子結構圖,部分鍵長、鍵角見表2．

表1 4-噻唑啉酮(3a～3i)合成的反應時間、產(chǎn)物熔點和產(chǎn)率

3a: 白色晶體,1H NMR(CDCl3,400 MHz)δ: 7.01～7.29 (m,8H,ArH),6.05 (s,1H,CH),4.01 (d,1H,CH2S),3.89 (d,1H,CH2S),2.28 (s,3H,CH3).Anal.calcd for C16H14ClNOS: C 63.25,H 4.64,N 4.61;found C 63.47,H 4.71,N 4.34.

3b: 淺黃色晶體,1H NMR(CDCl3,400 MHz)δ: 6.67～7.27 (m,7H,ArH),6.00 (s,1H,CH),5.95 (s,2H,OCH2O),3.98 (d,1H,CH2S),3.87 (d,1H,CH2S),2.28 (s,3H,CH3).Anal.calcd for C17H15NO3S: C 65.16,H 4.82,N 4.47;found C 65.37,H 4.58,N 4.61.

3c: 淺黃色晶體,1H NMR(CDCl3,400 MHz)δ: 7.05～8.10 (m,12H,ArH),6.13 (s,1H,CH),4.06 (d,1H,CH2S),4.02 (d,1H,CH2S),2.26 (s,3H,CH3).Anal.calcd for C23H18N2O2S: C 71.48,H 4.69,N 7.25;found C 71.37,H 4.48,N 7.51.

3d: 淺黃色晶體,1H NMR(CDCl3,400 MHz)δ: 6.68～7.29 (m,7H,ArH),6.02 (s,1H,CH),5.96 (s,2H,OCH2O),3.98 (d,1H,CH2S),3.87 (d,1H,CH2S).Anal.calcd for C16H12ClNO3S: C 57.57,H 3.62,N 4.20;found C 57.37,H 3.38,N 4.03.

3e: 淺黃色晶體,1H NMR(CDCl3,400 MHz)δ: 7.15～8.46 (m,12H,ArH),6.14 (s,1H,CH),4.02 (d,1H,CH2S),3.98 (d,1H,CH2S).Anal.calcd for C22H15ClN2O2S: C 64.94,H 3.72,N 6.88;found C 65.17,H 3.57,N 7.03.

3f: 白色晶體,1H NMR(CDCl3,400 MHz)δ: 7.11～7.34 (m,8H,ArH),6.06 (s,1H,CH),3.98 (d,1H,CH2S),3.87 (d,1H,CH2S),2.32 (s,3H,CH3).Anal.calcd for C16H14ClNOS: C 63.25,H 4.64,N 4.61;found C 63.17,H 4.85,N 4.77.

3g: 淺灰色晶體,1H NMR(CDCl3,300 MHz)δ: 7.03 7.41 (m,7H,ArH),6.50 (s,1H,CH),3.92 (d,1H,CH2S),3.79 (d,1H,CH2S),2.28 (s,3H,CH3).Anal.calcd for C16H13Cl2NOS: C 56.81,H 3.87,N 4.14;found C 56.67,H 3.71,N 4.01.

3h: 棕色晶體,1H NMR(CDCl3,300 MHz)δ: 6.79 7.26 (m,7H,ArH),6.02 (s,1H,CH),3.95 (d,1H,CH2S),3.85 (d,1H,CH2S),3.76 (s,3H,OCH3),2.26 (s,3H,CH3).Anal.calcd for C17H16ClNO2S: C 61.16,H 4.83,N 4.20;found C 60.93,H 4.62,N 4.29.

3i: 白色固體,1H NMR(CDCl3,400 MHz)δ: 7.12～7.34 (m,9H,ArH),6.07 (s,1H,CH),3.98 (d,1H,CH2S),3.87 (d,1H,CH2S),2.32 (s,3H,CH3).Anal.calcd for C15H12ClNOS: C 62.17,H 4.17,N 4.83;found C 61.99,H 4.32,N 4.91.

表2 化合物3f的部分鍵長(10-1 nm)和鍵角(°)

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