祝顯虹, 周安西, 羅年華, 彭 亮, 曾顯柱, 鄭大貴

(上饒師范學(xué)院 江西省普通高校應(yīng)用有機(jī)化學(xué)重點(diǎn)實(shí)驗(yàn)室,江西 上饒 334001)

·研究論文·

N,N-二甲基乙酰胺促進(jìn)的羧酸肉桂酯的合成及其促進(jìn)機(jī)理

祝顯虹, 周安西, 羅年華, 彭 亮, 曾顯柱, 鄭大貴*

(上饒師范學(xué)院 江西省普通高校應(yīng)用有機(jī)化學(xué)重點(diǎn)實(shí)驗(yàn)室,江西 上饒 334001)

在N,N-二甲基乙酰胺(DMAc)促進(jìn)下,羧酸(1a～1v)依次與SOCl2和肉桂醇反應(yīng)合成了22個(gè)羧酸肉桂酯(2a～2v,其中2j, 2k, 2o, 2t和2v為新化合物),其結(jié)構(gòu)經(jīng)1H NMR,13C NMR, IR和MS(EI)表征。以巴豆酸肉桂酯(2i)的合成為例,研究了巴豆酸(1i)用量，肉桂醇用量，SOCl2用量，DMAc用量對(duì)2i產(chǎn)率的影響和醇的加入方式對(duì)產(chǎn)物組成的影響。結(jié)果表明：在最優(yōu)合成條件(1i 1.0 eq.,肉桂醇1.3 eq., SOCl21.3 eq., DMAc 2 mL, CH2Cl26 mL,酰氯化后加入芐醇)下，2i產(chǎn)率82.2%。采用1H NMR跟蹤反應(yīng)，確證了DMAc促進(jìn)反應(yīng)的機(jī)理。

N,N-二甲基乙酰胺; 肉桂醇; 肉桂酯; 合成; 促進(jìn)機(jī)理

羧酸酰氯化合成羧酸酯或酰胺是常用的有機(jī)合成方法。羧酸酰氯化常用的氯代試劑有：SOCl2、(COCl)2、PCl3、POCl3、PCl5和三聚氯乙腈等[1-3]。使用促進(jìn)劑促進(jìn)“氯代試劑”,可將羧基活化制得活性中間體AG, AG與Cl-反應(yīng)生成酰氯(Scheme 1)。相對(duì)于單獨(dú)使用氯代試劑的方法,用“促進(jìn)劑-氯代試劑”的方法反應(yīng)條件更溫和、反應(yīng)效果更好。

“PPh3-氯代試劑”是應(yīng)用最廣泛的“促進(jìn)劑-氯代試劑”組合。其中氯代試劑包括CCl4[4]、三聚氯乙腈[5]、四甲基-α-氯烯胺[6]、Cl3CCCl3[7]、CCl3CN[8-9]和Cl3CCONH2[10]等。這類組合與羧酸作用后均可制得活性中間體AG-1。通過“苯并三氮唑-SOCl2”能將羧酸高效轉(zhuǎn)化為酰氯[11],其原理為：苯并三氮唑先與SOCl2作用制得中間產(chǎn)物，再與羧酸反應(yīng)得到活性中間體AG-2;“取代環(huán)丙烯酮-草酰氯”[12]和“環(huán)庚三烯酮-草酰氯”[13]分別使羧基活化制得中間體AG-3和AG-4。以上方法均能較大地提高羧基碳的電正性,有利于Cl-的親核進(jìn)攻,加速酰氯形成。此外，還可采用“(N,N-二烷基取代酰胺)-氯代試劑”組合,先相互作用生成Vilsmeier鹽；羧酸與Vilsmeier鹽反應(yīng)制得類似于AG-5的活性中間體,如“DMAc-SOCl2”[14-18]、 “DMF-鄰苯二甲酰氯”[16]、“四甲基脲(或1,3-二甲基-2-咪唑烷酮)-鄰苯二甲酰氯”[16]等。

本文在DMAc促進(jìn)下,羧酸(1a～1v)依次與SOCl2和肉桂醇反應(yīng)合成了22個(gè)羧酸肉桂酯(2a～2v,其中2j, 2k, 2o, 2t和2v為新化合物),其結(jié)構(gòu)經(jīng)1H NMR,13C NMR, IR和MS(EI)表征。以巴豆酸肉桂酯(2i)的合成為例,研究了巴豆酸(1i)用量，肉桂醇用量，SOCl2用量，DMAc用量對(duì)2i產(chǎn)率的影響和醇的加入方式對(duì)產(chǎn)物組成的影響。結(jié)果表明：在最優(yōu)合成條件(1i 1.0 eq.,肉桂醇1.3 eq., DMAc 2 mL, CH2Cl26 mL,酰氯化后加入芐醇)下，2i產(chǎn)率82.2%。采用1H NMR跟蹤反應(yīng)，確證了DMAc促進(jìn)反應(yīng)的機(jī)理。

Scheme 1

Scheme 2

1 實(shí)驗(yàn)部分

1.1 儀器與試劑

X-6型顯微熔點(diǎn)儀(溫度未校正)；Bruker Avance 400型核磁共振儀(CDCl3為溶劑，TMS為內(nèi)標(biāo))；Bruker Tensor 27型紅外光譜儀(KBr壓片)；Agilent Techologies 5975C型質(zhì)譜儀；Bruker Daltonics APEX II 47e型高分辨質(zhì)譜儀。

1a～1v和肉桂醇(純度≥98%)，阿拉丁試劑公司;正己氧羰基丙烯酸按文獻(xiàn)[19]方法合成;SOCl2,工業(yè)品,用前重蒸;DMAc,分析純,用前經(jīng)預(yù)處理;其余所用試劑均為分析純。

1.2 2a～2i的合成(以2i為例)

在反應(yīng)瓶中依次加入1a 0.861 g(10 mmol, 1.0 eq.), DMAc 2 mL和CH2Cl26 mL,攪拌使其溶解；冷卻至0 ℃,緩慢滴加SOCl20.94 mL(13 mmol, 1.3 eq.),滴畢，反應(yīng)2 h。加入肉桂醇1.745 g(13 mmol, 1.3 eq.),于25 ℃反應(yīng)5 h。依次加入蒸餾水40 mL和乙酸乙酯40 mL,分液,水層用乙酸乙酯(2×40 mL)萃取,合并有機(jī)層,依次用飽和NaHCO3溶液(30 mL)和飽和食鹽水洗至無DMAc(TLC跟蹤),無水Na2SO4干燥,旋蒸除溶,殘余物經(jīng)硅膠柱層析[洗脫劑：石油醚,洗脫副產(chǎn)物肉桂基氯；洗脫劑：V(乙酸乙酯) ∶V(石油醚)=1 ∶50]純化,旋蒸除溶后真空干燥得2i。

用類似的方法合成2a～2h, 2j～2v。

辛酸肉桂醇酯(2a)[20]: 無色油狀液體,產(chǎn)率68.2%;1H NMRδ: 7.39～7.25(m, 5H), 6.65(d,J=16.0 Hz, 1H), 6.28(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.73(dd,J=6.4 Hz, 1.2 Hz, 2H), 2.34(t,J=7.6 Hz, 2H), 1.68～1.61(m, 2H), 1.31～1.25(m, 8H), 0.87(t,J=6.8 Hz, 3H);13C NMRδ: 173.6, 136.3, 134.1, 128.6, 128.0, 126.6, 123.4, 64.8, 34.4, 31.7, 29.1, 28.9, 25.0, 22.6, 14.1; IRν: 3 028, 2 957, 2 929, 2 857, 1 736, 1 499, 1 450, 1 380, 966, 745, 692 cm-1; MS(EI)m/z: 260.1[M+], 127.1[C7H15CO+]。

癸酸肉桂醇酯(2b)[21]: 無色油狀液體,產(chǎn)率91.7%;1H NMRδ: 7.40～7.25(m, 5H), 6.64(d,J=16.0 Hz, 1H), 6.28 (dt,J=16.0 Hz, 6.4 Hz, 1H), 4.73(dd,J=6.4 Hz, 1.2 Hz, 2H), 2.34(t,J=7.6 Hz, 2H), 1.68～1.61 (m, 2H), 1.30～1.25(m, 12H), 0.87(t,J=6.8 Hz, 3H);13C NMRδ: 173.6, 136.3, 134.0, 128.6, 128.0, 126.6, 123.4, 64.8, 34.4, 31.9, 29.4, 29.3, 29.3, 29.2, 25.0, 22.7, 14.1; IRν: 3 028, 2 949, 2 926, 2 855, 1 736, 1 496, 1 450, 1381, 965, 745, 692 cm-1; MS(EI)m/z: 288.2[M+], 155.1[C9H19CO+]。

2-甲基丙酸肉桂醇酯(2f)[26]: 無色油狀液體,產(chǎn)率82.4%;1H NMRδ: 7.40～7.25(m, 5H), 6.64(d,J=16.0 Hz, 1H), 6.28(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.72(dd,J=6.4 Hz, 1.2 Hz, 2H), 2.59(hept,J=6.8 Hz , 1H), 1.19(d,J=6.8 Hz, 6H);13C NMRδ: 176.9, 136.3, 133.9, 128.6, 128.0, 126.6, 123.5, 64.9, 34.1, 19.0; IRν: 3 028, 2 975, 2 937, 1 734, 1 493, 1 489, 1 468, 1 389, 965, 742, 691 cm-1; MS(EI)m/z: 204.1[M+], 71.1[C3H7CO+, 100]。

肉桂酸肉桂酯(2h)[23,27]: 白色固體,m.p.45.4～46.2 ℃(42～43 ℃[28]),產(chǎn)率86.9%;1H NMRδ: 7.73(d,J= 16.0 Hz, 1H), 7.54～7.52(m, 2H), 7.42～7.26(m, 8H), 6.71(d,J=16.0 Hz, 1H), 6.49(d,J=16.0 Hz, 1H), 6.36(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.87(dd,J=6.4 Hz, 1.2 Hz, 2H);13C NMRδ: 166.7, 145.1, 136.3, 134.4, 134.3, 130.3, 128.9, 128.6, 128.1, 128.1, 126.7, 123.4, 118.0, 65.1; IRν: 3 027, 2 934, 1 715, 1 637, 1 496, 1 449, 969, 768, 750, 708, 686 cm-1; MS(EI)m/z: 264.1[M+], 131.1[C8H7CO+]。

巴豆酸肉桂醇酯(2i)[27]: 無色油狀液體,產(chǎn)率82.2%;1H NMRδ: 7.40～7.25(m, 5H), 7.02(dq,J=16.0 Hz, 6.8 Hz, 1H), 6.65(d,J=16.0 Hz, 1H), 6.30(dt,J=16.0 Hz, 6.4 Hz, 1H), 5.89(dq,J=16.0 Hz, 1.6 Hz, 1H), 4.78(dd,J=6.4 Hz, 1.2 Hz, 2H), 1.89(dd,J=6.8 Hz, 1.6 Hz, 3H);13C NMRδ: 166.2, 145.0, 136.3, 134.0, 128.6, 128.0, 126.6, 123.5, 122.6, 64.7, 18.0; IRν: 3 022, 2 943, 2 915, 1 720, 1 658, 1 496, 1 446, 968, 749, 692 cm-1; MS(EI)m/z: 202.1[M+], 69.0[C3H5CO+]。

正己氧羰基丙烯酸肉桂醇酯(2j): 無色油狀液體,產(chǎn)率88.3%;1H NMRδ: 7.41～7.26(m, 5H), 6.89(s, 2H), 6.70(d,J=16.0 Hz, 1H), 6.31(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.86(dd,J=6.4 Hz, 1.2 Hz, 2H), 4.20(t,J=6.8 Hz, 2H), 1.71～1.64(m, 2H), 1.32～1.30(m, 6H), 0.89(t,J=6.8 Hz, 3H);13C NMRδ: 165.0, 164.8, 136.0, 134.9, 134.1, 133.3, 128.7, 128.6, 128.3, 126.7, 125.7, 122.4, 77.2, 31.4, 28.5, 25.5, 22.5, 14.0; IRν: 3 027, 2 957, 2 932, 2 859, 1 724, 1 650, 1 451, 980, 748, 689 cm-1; HR-MS(ESI)m/z: Calcd for C19H24O4{[M+NH4]+}334.201 3, found 334.201 5。

環(huán)戊基甲酸肉桂醇酯(2k): 無色油狀液體,產(chǎn)率80.7%;1H NMRδ: 7.39～7.24(m, 5H), 6.63(d,J=16.0 Hz, 1H), 6.28(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.72(dd,J=6.4 Hz, 1.2 Hz, 2H), 2.77(quint,J=8.0 Hz, 1H), 1.89～1.56(m, 8H);13C NMRδ: 176.5, 136.4, 133.9, 128.6, 128.0, 126.6, 123.6, 64.9, 43.9, 30.1, 25.9; IRν: 3 027, 2 958, 2 871, 1 731, 1 495, 1 449, 968, 745, 692 cm-1; HR-MS(ESI)m/z: Calcd for C15H18O2{[M+Na]+}253.119 9, found 253.119 8。

苯甲酸肉桂醇酯(2m)[21,27,30]: 白色固體, m.p.38.4～39.8 ℃(m.p.38～39 ℃[28]),產(chǎn)率69.7%;1H NMRδ: 8.14～8.07(m, 2H), 7.51～7.22(m, 8H), 6.70(d,J=16.0 Hz, 1H), 6.37(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.95(dd,J=6.4 Hz, 1.2 Hz, 2H);13C NMRδ: 166.4, 136.3, 134.3, 133.1, 130.6, 130.3, 129.7, 128.9, 128.7, 128.5, 128.2, 126.7, 123.4, 65.6; IRν: 3 058, 3 028, 2 943, 2 870, 1 717, 1 600, 1 491, 966, 748, 712, 692 cm-1; MS(EI)m/z: 238.1[M+], 105.1[C6H5CO+]。

2-甲基苯甲酸肉桂醇酯(2n)[28,30]: 無色油狀液體,產(chǎn)率68.2%;1H NMRδ: 7.97～7.95(m, 1H), 7.41～7.22(m, 8H), 6.72(d,J=16.0 Hz, 1H), 6.39(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.94(dd,J=6.4 Hz, 1.2 Hz, 2H);13C NMRδ: 167.4, 140.3, 136.4, 134.3, 132.1, 131.8, 130.7, 129.7, 128.7, 128.1, 126.7, 125.8, 123.5, 65.3, 21.8; IRν: 3 060, 3 026, 2 930, 2 870, 1 717, 1 602, 1 494, 966, 742, 692 cm-1; MS(EI)m/z: 252.1[M+], 119.1[C7H7CO+]。

3-甲基苯甲酸肉桂醇酯(2o): 無色油狀液體,產(chǎn)率60.7%;1H NMRδ: 7.95～7.87(m, 2H), 7.41～7.23(m, 7H), 6.73(d,J=16.0 Hz, 1H), 6.40(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.96(d,J=6.4 Hz, 2H), 2.39(s, 3H);13C NMRδ: 166.6, 138.2, 136.3, 134.3, 133.8, 130.2, 130.2, 128.6, 128.3, 128.1, 126.9, 126.7, 123.4, 65.5, 21.3; IRν: 3 082, 3 027, 2 946, 2 873, 1 720, 1 608, 1 495, 1 449, 964, 743, 692 cm-1; HR-MS(ESI)m/z: Calcd for C17H16O2{[M+K]+}291.078 2, found 291.078 3。

4-甲基苯甲酸肉桂醇酯(2p)[21,28]: 白色固體,m.p.24.3～26.0 ℃,產(chǎn)率57.0%;1H NMRδ: 7.98～7.96(m, 2H), 7.40～7.20(m, 7H), 6.70(d,J=16.0 Hz, 1H), 6.38(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.94(dd,J=6.4 Hz, 1.2 Hz, 2H), 2.37(s, 3H);13C NMRδ: 166.5, 143.7, 136.4, 134.2, 129.8, 129.2, 128.7, 128.1, 127.6, 126.7, 123.5, 65.4, 21.7; IRν: 3 082, 3 059, 2 946, 2 878, 1 716, 1 612, 1 509, 1 449, 966, 841, 753, 692 cm-1; MS(EI)m/z: 252.1[M+], 119.1[C7H7CO+]。

2-氯苯甲酸肉桂醇酯(2q)[27]: 無色油狀液體,產(chǎn)率72.1%;1H NMRδ: 7.86～7.84(m, 1H), 7.44～7.37(m, 4H), 7.33～7.24(m, 4H), 6.74(d,J=16.0 Hz, 1H), 6.38(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.97(dd,J=6.4 Hz, 1.2 Hz, 2H);13C NMRδ: 165.5, 136.2, 134.7, 133.8, 132.6, 131.5, 131.2, 130.2, 128.7, 128.2, 126.7, 126.6, 122.8, 66.1; IRν: 3 060, 3 027, 2 946, 2 879, 1 731, 1 592, 1 495, 1 436, 967, 747, 692 cm-1; MS(EI)m/z: 272.0[M+], 139.1[C7H4COCl+]。

3-氯苯甲酸肉桂醇酯(2r)[27]: 淡黃色油狀液體,產(chǎn)率79.0%;1H NMRδ: 8.05～8.04(m, 1H), 7.96～7.94(m, 1H), 7.52～7.50(m, 1H), 7.41～7.30(m, 6H), 6.72(d,J=16.0 Hz, 1H), 6.38(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.97(dd,J=6.4 Hz, 1.2 Hz, 2H);13C NMRδ: 165.2, 136.1, 134.8, 134.6, 133.0, 132.0, 129.8, 129.7, 128.7, 128.2, 127.8, 126.7, 122.9, 66.0; IRν: 3 060, 3 027, 2 946, 2 881, 1 720, 1 576, 1 496, 1 448, 965, 748, 692 cm-1; MS(EI)m/z: 272.0[M+], 139.1[C7H4COCl+]。

4-氯苯甲酸肉桂醇酯(2s)[21]: 白色固體,m.p.43.4～44.5 ℃(m.p. 44～46 ℃[27]),產(chǎn)率78.0%;1H NMRδ: 8.02～8.00(m, 2H), 7.42～7.25(m, 7H), 6.73(d,J=16.0 Hz, 1H), 6.39(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.97(dd,J=6.4 Hz, 1.2 Hz, 2H);13C NMRδ: 165.5, 139.5, 136.2, 134.6, 131.1, 128.8, 128.7, 128.7, 128.2, 126.7, 123.0, 65.8; IRν: 3 081, 3 027, 2 954, 2 875, 1 715, 1 593, 1 487, 1 448, 969, 760, 692 cm-1; MS(EI)m/z: 272.0[M+], 139.1[C7H4ClCO+]。

2-甲氧基苯甲酸肉桂醇酯(2t): 淡黃色固體,m.p.47.7～48.5 ℃,產(chǎn)率76.8%;1H NMRδ: 7.86～7.83(m, 1H), 7.46～7.24(m, 6H), 7.00～6.96(m, 2H), 6.75(d,J=16.0 Hz, 1H), 6.39(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.96(dd,J=6.4 Hz, 1.2 Hz, 2H), 3.90(s, 3H);13C NMRδ: 165.9, 159.3, 136.4, 134.0, 133.6, 131.7, 128.6, 128.0, 126.7, 123.5, 120.2, 120.1, 112.1, 65.3, 56.0; IRν: 3 055, 3 016, 2 976, 2 923, 2 830, 1 712, 1 594, 1 492, 1 434, 972, 745, 692 cm-1; HR-MS(ESI)m/z: Calcd for C17H16O3{[M+H]+}269.117 2, found 269.117 1。

2-硝基苯甲酸肉桂醇酯(2u)[31]: 白色固體,m.p.59.3～61.4 ℃(m.p.63 ℃[32]),產(chǎn)率59.5%;1H NMRδ: 7.91～7.90(m, 1H), 7.77～7.75(m, 1H), 7.68～7.59(m, 2H),7.42～7.26(m, 5H), 6.72(d,J=16.0 Hz,1H), 6.34(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.98(dd,J=6.4 Hz, 1.2 Hz, 2H);13C NMRδ: 165.2, 148.2, 136.1, 135.3, 132.9, 131.8, 129.9, 128.7, 128.3, 127.7, 126.8, 124.0, 122.0, 67.0; IRν: 3 100, 3 042, 2 952, 2 886, 1 725, 1 577, 1 530, 1 484, 967, 873, 691 cm-1; MS(EI)m/z: 283.0[M+], 151.0[C6H4NO2CO+]。

Scheme 3表1 2i的合成條件優(yōu)化Table 1 Optimization of the synthesis reaction conditions for 2i

a1: 條件同1.2; 2: 0 ℃下，1i和肉桂醇同時(shí)加入DMAc, SOCl2和CH2Cl2中，反應(yīng)2 h；于25 ℃反應(yīng)5 h;b分離產(chǎn)率。

2-乙酰基苯甲酸肉桂醇酯(2v): 無色油狀液體,產(chǎn)率46.3%;1H NMRδ: 7.91～7.90(m, 1H), 7.73～7.72(m, 1H), 7.60～7.54(m, 2H), 7.31～7.26(m, 5H), 6.47(d,J=16.0 Hz, 1H), 6.16(dt,J=16.0 Hz, 6.4 Hz, 1H), 4.08～4.03(m, 1H), 3.75～3.71(m, 1H), 1.90(s, 3H);13C NMRδ: 168.0, 147.9, 136.4, 134.6, 133.0, 130.7, 128.5, 127.9, 127.4, 126.5, 125.6, 124.5, 122.3, 108.5, 65.0, 25.7; IRν: 3 061, 3 026, 2 994, 2 936, 2 864, 1 771, 1 466, 1 284, 968, 890, 768, 695 cm-1; HR-MS(ESI)m/z: Calcd for C18H16O3{[M+NH4]+}298.143 8, found 298.143 7。

2 結(jié)果與討論

2.1 2的合成條件優(yōu)化

以2i的合成(Scheme 3)為例,研究了1i用量，肉桂醇用量，SOCl2用量，DMAc用量對(duì)2i產(chǎn)率的影響和醇的加入方式對(duì)產(chǎn)物組成的影響,結(jié)果見表1。

由表1可見，Entry 1和Entry 2～7為DMAc用量對(duì)產(chǎn)率的影響，當(dāng)DMAc用量為2 mL時(shí)(Entry 3),產(chǎn)率比完全不用DMAc(Entry 1)提高50%以上。繼續(xù)增大DMAc用量,產(chǎn)率基本穩(wěn)定,其可能原因?yàn)椋悍磻?yīng)溫度較低時(shí),油狀DMAc會(huì)影響反應(yīng)傳質(zhì)。這在另外的實(shí)驗(yàn)中得以證實(shí)(將CH2Cl2用量從6 mL減少至3 mL,其余反應(yīng)條件同Entry 11,產(chǎn)率僅70.3%)。此外,DMAc用過過多還會(huì)增加產(chǎn)物分離純化過程中水洗的次數(shù)。因此,DMAc的適宜用量為2 mL。

Scheme 4

Scheme 5

Entry 8～13為SOCl2用量對(duì)產(chǎn)率的影響。SOCl2用量從1.0 eq.增加到1.3 eq.,產(chǎn)率提高,副產(chǎn)物肉桂基氯(3)產(chǎn)率約10%。當(dāng)SOCl2用量增加到1.4 eq.(Entry 12),產(chǎn)率反而下降,3產(chǎn)率明顯提高。其可能原因?yàn)椋喝夤鸫技尤敕磻?yīng)體系后,過量SOCl2和過量DMAc仍在反應(yīng)生成Vilsmeier鹽,由于與Vilsmeier鹽反應(yīng)以及與SOCl2反應(yīng)的活性均是醇大于羧酸,醇更容易轉(zhuǎn)變?yōu)槁却鸁N。通過改變投料方式,即將肉桂醇和1i同時(shí)加入DMAc, SOCl2和CH2Cl2中(Entry 13和Entry 14), 3產(chǎn)率明顯提高,這一結(jié)果驗(yàn)證了上述分析。

綜上,合成2i的最佳條件為：1i 1.0 eq.,肉桂醇1.3 eq., DMAc 2 mL, SOCl21.3 eq., CH2Cl26 mL,酰氯化后加入芐醇。

2.2 DMAc促進(jìn)反應(yīng)機(jī)理

DMAc可能從三個(gè)方面協(xié)同促進(jìn)酯的合成(Scheme 4):(1)作催化劑,DMAc與SOCl2反應(yīng)生成Vilsmeier鹽(Ⅰ)[33]; Ⅰ與羧酸反應(yīng)生成中間產(chǎn)物(Ⅱ),由于Ⅱ的羰基碳比羧酸的羰基碳電正性更強(qiáng),容易接受Cl-的親核進(jìn)攻,加速了酰氯的生成(與此相似,Ⅰ與醇反應(yīng)生成Ⅲ,加速了氯代烴的生成);(2)作為堿,DMAc吸收副產(chǎn)物HCl，生成DMAc鹽酸鹽(Ⅳ),也促進(jìn)反應(yīng)朝生成酰氯(或氯代烴)的方向進(jìn)行。當(dāng)酰氯生成后加入醇成酯,Ⅳ釋放出的質(zhì)子又能起到催化作用[34]。

為驗(yàn)證上述機(jī)理,我們?cè)诒菊n題組前期工作[16]的基礎(chǔ)上,以1h為例，用1H NMR跟蹤反應(yīng),確證了Ⅱ的存在。實(shí)驗(yàn)方法為：冰水浴冷卻下,DMAc 1 mL(10.8 mmol), SOCl20.8 mL(11.0 mmol)在CDCl310 mL中反應(yīng)70 min(生成Ⅰ[16])。加入肉桂酸1.778 g(12 mmol),每隔10 min取樣，用1H NMR跟蹤反應(yīng)。加入1h 40 min后,反應(yīng)混合液中同時(shí)檢測(cè)到1h, Ⅱ和.3(Scheme 5)。

圖1為反應(yīng)混合液的1H NMR 譜圖。由圖1可見，1h, Ⅱ和3雙鍵碳上所連aH的δ分別為7.77(d,J=16.0 Hz), 7.86(d,J=16.0 Hz)和7.85(d,J=15.6 Hz)。bH的δ分別為6.47(d,J=16.0 Hz), 6.54(d,J=16.0 Hz)和6.66(d,J=15.6 Hz)。此外，還能觀察到Ⅳ的存在,其δ分別為12.35(s, 1H), 3.25(s, 6H), 2.64(s, 3H)。相關(guān)氫的積分比(0.99 ∶0.89=1.11 ∶1.00)與1h和DMAc的投料比(12 ∶11=1.09 ∶1.00)基本吻合。

δ圖1 DMAc-SOCl2-1h的1H NMR譜圖Figure 1 1H NMR spectrum of the DMAc-SOCl2-1h

報(bào)道了一種N,N-二甲基乙酰胺促進(jìn)的羧酸肉桂酯的合成方法。該方法具有反應(yīng)條件溫和、操作簡(jiǎn)單、底物適用范圍較廣等優(yōu)點(diǎn)。

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N,N-Dimethylacetamide-promoted Synthesis of Cinnamyl Carboxylate and The Co-promoted Mechanism

ZHU Xian-hong, ZHOU An-xi, LUO Nian-hua,PENG Liang, ZENG Xian-zhu, ZHENG Da-gui*

(Key Laboratory of Applied Organic Chemistry, Higher Institutions of Jiangxi Province,Shangrao Normal University, Shangrao 334001)

Twenty two cinnamyl carboxylates(2a～2v, among them 2j, 2k, 2o, 2t and 2v were novel compounds) were synthesized by theN,N-dimethylacetamide(DMAc)-promoted reaction of carboxylic(1a～1v) with SOCl2and cinnamyl alcohol, respectively. The structures were characterized by1H NMR,13C NMR, IR and MS(EI). Effects of the dosage of crotonic acid(1i), cinnamic alcohol, SOCl2and DMAc on yield of cinnamyl crotonate(2i) and the addition protocol of alcohol on products composition were investigated, using the synthsis of 2i as example. The results indicated that under the optimized reaction conditions(1i 1.0 eq., cinnamic alcohol 1.3 eq., SOCl21.3 eq., DMAc 2 mL, CH2Cl26 mL, adding benzyl alcohol after acylation), the yield of 2i was 82.2%. The co-promoted mechanism of DMAc was confirmed by1H NMR tracing results.

dimethylacetamide; cinnamyl alcohol; cinnamyl carboxylate; synthesis; co-promoted mechanism

2016-09-26

江西省教育廳科技項(xiàng)目(GJJ151062); 信江英才866工程領(lǐng)軍人才培養(yǎng)計(jì)劃項(xiàng)目(2013-37)

祝顯虹(1983-)，男，漢族，江西玉山人，碩士，實(shí)驗(yàn)師，主要從事有機(jī)合成的研究。 E-mail: xianhongzhu@163.com

鄭大貴，教授, E-mail: daguizheng@163.com

O625.52

A

10.15952/j.cnki.cjsc.1005-1511.2017.02.16229