＊ 微波促進下苯并噻吩的傅-克酰基化反應

張變香,石高升,王瓊,楊祺,康婧玲

(山西大學化學化工學院,山西太原 030006)

＊微波促進下苯并噻吩的傅-克?；磻?/p>

張變香,石高升,王瓊,楊祺,康婧玲

(山西大學化學化工學院,山西太原 030006)

進行了苯并噻吩與酸酐、乙酰氯、苯甲酰氯和草酰氯的傅-克?；磻?探究了微波輻射對該反應的影響.通過1H NMR、13C NMR對產(chǎn)物的結構進行了表征,采用高效液相色譜法測定了產(chǎn)物的產(chǎn)率與產(chǎn)物異構體的比例.結果表明,在苯并噻吩與草酰氯的反應中選擇性地得到了3,3′-二苯并噻吩乙二酮,并且常溫下12 h進行的反應在微波輻射下反應時間縮短為25 min,產(chǎn)率比常溫反應提高了20%.

微波輻射;苯并噻吩衍生物;傅-克?；?/p>

苯并噻吩、噻吩衍生物是自然界中存在的含硫雜原子的環(huán)狀化合物之一,不僅是重要的有機合成中間體,而且作為醫(yī)藥、農(nóng)藥、機能性材料等的基本骨架近年來被廣泛利用[1-4].然而帶有功能性基團的小分子苯并噻吩,作為原料因其合成步驟多產(chǎn)率低而使得價格昂貴.有關合成此類化合物的報道較多,主要類型有苯衍生物和噻吩衍生物的關環(huán)反應[5-12];帶有鹵素或羧基取代基的苯并噻吩的偶聯(lián)反應[12-14].以無取代基的苯并噻吩為原料一步合成苯并噻吩衍生物的報道較少[15],尋找簡便有效的合成苯并噻吩衍生物的方法具有重要的意義.

微波作用下的有機反應具有反應時間短、收率高、副反應少、操作簡便及環(huán)境友好等優(yōu)點,近年來在有機合成尤其是雜環(huán)化合物的合成中得到了廣泛的應用[16-17].本文用微波催化和傳統(tǒng)的加熱回流兩種方法對苯并噻吩的傅-克?；磻M行了研究,討論了催化劑的種類和用量、反應溶劑、溫度、加樣方式對反應的影響.結果表明:微波催化與傳統(tǒng)的加熱回流方法相比,具有反應速度快、轉化率和選擇性好等優(yōu)點.

1 實驗部分

1.1 儀器與試劑

予華X-4數(shù)字顯示顯微熔點測定儀;島津UV-265型紫外可見光譜儀;Bruker DRX-300 M Hz核磁共振儀(5 mm樣品管,內標為 TM S,溶劑為CDCl3,測試溫度 25℃,1H NM R和13C NM R的工作頻率分別為300.40 M Hz和75.45 M Hz),P200II型高效液相色譜儀.本實驗所用試劑苯并噻吩(BT)、乙酰氯(AC)、苯甲酰氯(BC)、酸酐(AA)、草酰氯(OC)均為分析純.

1.2 常溫與微波輻射下苯并噻吩的傅-克?；磻?/h3>

在裝有恒壓滴液漏斗、冷凝管(帶有干燥管)的100 m L三口燒瓶中放入磁攪拌子,在冰浴中依次加入苯并噻吩、溶劑、催化劑,攪拌均勻后,在10～30 min內緩慢加入酰基化試劑,滴加完畢后,恢復至室溫反應,反應中通過薄層硅膠板(TLC)跟蹤.反應完全后,將混合物置入冰水中,滴加鹽酸酸解.反應終止后,用乙醚萃取,有機層用飽和碳酸氫鈉和氯化鈉溶液各洗兩次,用無水硫酸鎂干燥,減壓蒸去有機溶劑,所得粗產(chǎn)物用柱層析分離(CH2Cl2∶n-Hexane=1∶1),通過液相色譜法計算轉化率和2位、3位?；a(chǎn)物的比例(反應式如下式所示).

除了苯并噻吩與草酰氯的微波輻射反應,其它的微波反應的加藥品方式與常溫相同,加完藥品后,將長頸燒瓶轉入微波反應器中,設置恒定功率及反應時間,反應后處理與常溫反應的方法相同.草酰氯與苯并噻吩的微波反應的加藥品依次為溶劑、催化劑、草酰氯試劑,攪拌均勻后,在10～30 min內緩慢加入苯并噻吩.

1.3 產(chǎn)物的數(shù)據(jù)

2-乙酰基苯并噻吩:m.p.83～84 ℃(lit[18]83～84 ℃);1H NM R(CDCl3,300 M Hz)δ:2.94(s,M e,3H),7.37～7.93(m,A rH,5H);13C NMR(CDCl3,75 M Hz)δ:27.06,123.24,125.23,126.15,127.68,129.96,139.33,142.83,144.18,192.57.

3-乙?；讲⑧绶?m.p.63～65 ℃(lit[18]62～64℃);1H NM R(CDCl3,300 M Hz)δ:2.58(s,CH3,3H),7.80～7.66(m,A rH,2H),7.35～7.46(m,A rH,2H),8.19(s,A rH,1H);13C NMR(CDCl3,75 M Hz)δ:27.56,121.94,122.44,124.15,124.61,126.70,129.60,138.80,139.54,191.64.

2-苯甲?；讲⑧绶?m.p.45～48℃(lit[18]47～48℃);1H NM R(CDCl3,300 M Hz)δ:6.82～7.03(m,A rH,5H),32～7.40(m,A rH,4H);13C NM R(CDCl3,75 M Hz)δ:122.78,123.33,124.57,125.01,126.91,127.83,128.86,131.71,136.85,137.04,139.41,142.41,189.85.

3-苯甲酰基苯并噻吩:m.p.50～53 ℃(lit[18]52～53 ℃);1H NMR(CDCl3,300 M Hz)δ:8.48(s,A rH,1H),6.88～7.05(m,A rH,5H),7.27～7.40(m,A rH,4H);13C NMR(CDCl3,75 M Hz)δ:121.78,122.45,124.53,125.03,126.91,127.83,128.67,131.71,133.83,138.14,138.52,141.86,188.71.

3,3′-二苯并噻吩乙二酮:m.p.167～169 ℃(lit[19]166～168 ℃);1H NM R(CDCl3,300 M Hz)δ:7.45～7.51(m,A rH,2H);7.89～7.92(d,J=7.2 H,A rH,1H);8.07(s,A rH,1H);8.54～8.56(d,J=7.2 Hz,A rH,1H).13C NM R(CDCl3,75 M Hz)δ:120.21,122.36,124.91,125.60,136.36,136.62,137.19,140.09,184.96.

2 結果與討論

傅-克反應屬于碳正離子對芳烴的親電取代反應,在通常情況下,未取代的五員雜環(huán)芳烴比未取代的苯更容易進行傅-克反應,而且產(chǎn)物是異構體的混合物.以苯并噻吩為例,在凱庫勒共振體中2、3位都存在較強的活性,容易被碳正離子進攻[20].另外,Klasinc[21]根據(jù)MO法計算了苯并噻吩環(huán)上的π電子密度,結果表明環(huán)上的電子云分布不均,3位比2位稍大(Scheme 1),因此在反應中導致異構體產(chǎn)物含量不同.產(chǎn)物的比例與催化劑的種類及用量、反應物的加入順序、溫度和溶劑有關,一般以3位?；a(chǎn)物為主.

示意圖1 苯并噻吩的共振式結構Scheme 1 Resonance form of the benzothiophene

2.1 非微波條件下?；臈l件優(yōu)化

以苯并噻吩和乙酰氯為底物,無水三氯化鋁為催化劑,反應12 h,就反應溫度、溶劑和催化劑用量對酰基化產(chǎn)物的產(chǎn)率影響進行了討論(表1,P92).

表1 A lCl3作用下苯并噻吩(BT)和乙酰氯(AC)的?；磻猅able 1 AlCl3 catalyzed acylation of BT with AC

由表1可知,增加無水三氯化鋁的用量,?；a(chǎn)物的產(chǎn)率增大,但用量加到苯并噻吩的3倍時,產(chǎn)率有所降低.反應溫度從室溫15℃增加到35℃時,乙?；讲⑧绶缘漠a(chǎn)率變化不大.在反應溫度相同的條件下,以二氯甲烷為溶劑時乙酰基苯并噻吩的產(chǎn)率較好.

2.2 ?；噭┖痛呋瘎︴；磻挠绊?/h3>

在上述優(yōu)化的反應條件下,即苯并噻吩、酰化劑和催化劑的摩爾比為1∶1.2∶2、反應12 h、溶劑為二氯甲烷的條件下,研究了其它?；噭┖痛呋瘎Ψ磻挠绊?如表2).由表2可知,在苯并噻吩和乙酰氯的反應中,FeCl3、ZnCl2催化活性低于A lCl3,而FeCl3在催化苯并噻吩與苯甲酰氯的反應時,?；a(chǎn)物的產(chǎn)率有所提高.FeCl3和A lCl3催化乙酸酐的酰基化反應的效果與乙酰氯的相當.

表2 ?；噭┖痛呋瘎Ψ磻挠绊慣able 2 Effect of acylation reagentsand catalysts on the reaction

2.3 微波輻射下苯并噻吩的酰基化反應

2.3.1 苯并噻吩和乙酰氯的?；磻?/p>

首先進行了在微波作用下,苯并噻吩、酰化劑和催化劑的摩爾比為1∶1.2∶2,溶劑為二氯甲烷的乙?；磻?如表3).

表3 微波輻射下苯并噻吩(BT)和乙酰氯(AC)的?；磻猅able 3 Acylation of BT with AC under m icrowave irradiation

由表3可知,A lCl3催化下微波照射20 min、功率為196 W,產(chǎn)率達到最大值86%,比常規(guī)反應條件下提高了20%.微波照射15 min、功率為260 W時,出現(xiàn)了黑色副產(chǎn)物.微波對 FeCl3催化的反應有較大影響,5 min后原料轉化率為36%,產(chǎn)率為30%,隨著微波照射時間的增加,轉化率和產(chǎn)率都有所增大,微波照射15 m in后原料轉化率都達到最大值98%.微波照射FeCl3催化下,苯并噻吩2、3位?；a(chǎn)物的比例都在0.9左右,3位產(chǎn)物稍稍多于2位產(chǎn)物,選擇性上不如A lCl3催化的?；磻?比例在0.6左右).

圖1是在FeCl3催化下苯并噻吩與乙酰氯的反應體系在常規(guī)反應10 min與微波輻射10 min后,反應混合液的液相色譜對比圖,可以看出微波輻射下原料的轉化率、產(chǎn)物的收率都有了明顯提高.

圖1 微波輻射與常規(guī)條件下?；磻谋容^Fig.1 Relative analysis of the acylation under microwave radiation and no rm al condition by using HPLC

2.3.2 微波輻射下FeCl3的用量對酰基化反應的影響

由以上結果得知,FeCl3對苯并噻吩與苯甲酰氯的?；磻休^好的催化效果,因此討論了在二氯甲烷為溶劑,FeCl3的用量對?；磻挠绊?表4).

表4 微波輻射下FeCl3催化的苯并噻吩(BT)與苯甲酰氯(BC)的反應Table 4 FeCl3 catalyzed acylation of BT with BC under microwave-irradition

由表4可知,增加催化劑FeCl3的用量,苯并噻吩的轉化率和?；a(chǎn)物的產(chǎn)率都有所增大,當催化劑FeCl3的用量為2倍時,苯并噻吩的轉化率最好;再增加催化劑的用量,轉化率和產(chǎn)率下降,可能是過多的FeCl3包裹了FeCl3的絡合物,使FeCl3的絡合物不能和苯并噻吩充分反應.

2.3.3 苯并噻吩與草酰氯的?；磻?/p>

在以A lCl3為催化劑、微波的輸出功率為260 W時,草酰氯和苯并噻吩的反應選擇性地得到了3,3′-二苯并噻吩乙二酮,討論結果如表5所示.

表5 微波作用下苯并噻吩(BT)和草酰氯(OC)的?；姆磻猅able 5 Acylation of BT with OC under microwave-irraditiona

由表5可知,以CH2Cl2為溶劑,苯并噻吩和草酰氯在微波中進行反應,苯并噻吩的轉化率和3,3′-二苯并噻吩乙二酮的產(chǎn)率較高.因為CH2Cl2能溶解A lCl3復合物,有利于碳正離子的生成,選擇性地得到碳正離子親電取代產(chǎn)物;CH2ClCH2Cl雖然轉化率較高,但得到的副產(chǎn)物較多,無論苯并噻吩與草酰氯的摩爾比為1∶2.2或是2∶1,親電取代產(chǎn)物的產(chǎn)率大約都在40%;CS2對A lCl3復合物溶解性較差,碳正離子親電取代反應相對較緩慢,苯并噻吩的轉化率較低.以FeCl3為催化劑,CS2為溶劑時幾乎沒有發(fā)生反應;CH2Cl2為溶劑時,產(chǎn)率較低.

根據(jù)Friedel-Crafts反應機理,苯并噻吩與草酰氯在A lCl3作用下的反應符合碳正離子親電取代反應歷程,催化劑首先和草酰氯生成復合物,形成碳正離子進攻苯并噻吩環(huán)上電子云密度較高的3位,得到3,3′-二苯并噻吩乙二酮(Scheme 2).這一結果類似于[Emim]Cl-A lCl3離子液體催化草酰氯與蒽的反應[22],與A lCl3催化下草酰氯和萘的反應主要生成二萘甲酮有所不同[23].

示意圖2 3,3′-二苯并噻吩乙二酮的合成機理Scheme 2 Synthetic mechanism of 3,3′-dibenzothiophene enthyldione

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Microwave-Enhanced Friedel-Craftsacylation of Benzothiophene

ZHANGBian-xiang,SH IGao-sheng,WANG Qiong,YANG Qi,KANG Jing-ling
(School of Chemistry and Chemical Engineering,Shanxi University,Taiyuan030006,China)

The Friedel-Crafts acylation reactions of benzothiophene were investigatel,and the effect of microwave radiation on the reaction was discussed.The structures of products were characterized by1H NM R and13C NMR.The yield and C-2/C-3 isomer ratio of the products were determined by high performance liquid chromatography(HPLC).The effects of various conditions on the reaction were investigated by HPLC analysis.In the result,we obtained selectively 3,3′-dibenzothiophene ethyldione in the reaction of benzothiophene and oxalyl chlo ride,and found that compared with the normal temperature reaction for 12 hours,microwave radiation reaction needed 25 minutes,and yield could increased by 20%.

microwave radiation;benzothiophene derivatives;Friedel-Crafts acylation

O626

A

0253-2395(2011)01-0090-06＊

2010-09-13;

2010-11-13

留學回國人員科研啟動基金(2006);山西省自然科學基金(2007011022)

張變香(1968-),女,山西太谷人,博士,副教授,從事有機合成和雜原子化學研究.E-mail:zbxthh@sxu.edu.cn