<i>N</i>-(噻唑-2-基)-2-[4-(芳氧基)苯氧基]丙酰胺的合成、晶体结构与除草活性

引用本文: 杨子辉, 陈爱羽, 胡艾希, 叶姣. N-(噻唑-2-基)-2-[4-(芳氧基)苯氧基]丙酰胺的合成、晶体结构与除草活性[J]. 有机化学, 2017, 37(1): 149-156. doi: 10.6023/cjoc201607041 shu

Citation: Yang Zihui, Chen Aiyu, Hu Aixi, Ye Jiao. Synthesis, Crystal Structure and Herbicidal Activity of N-(Thiazol-2-yl)-2-(4-aryloxyphenoxy) propionamides[J]. Chinese Journal of Organic Chemistry, 2017, 37(1): 149-156. doi: 10.6023/cjoc201607041 shu

N-(噻唑-2-基)-2-[4-(芳氧基)苯氧基]丙酰胺的合成、晶体结构与除草活性

杨子辉 ,
陈爱羽 ,
胡艾希 ^{*,
,} ,
叶姣 ^{*,
,}

湖南大学化学化工学院长沙 410082

通讯作者: 胡艾希, E-mail: axhu@hnu.edu.cn; 叶姣, yejiao@hnu.edu.cn

基金项目:
十二五国家科技支撑计划 2011BAE06B01

摘要: 2-氨基噻唑衍生物与（R）-（+）-2-（4-羟基苯氧）丙酰氯反应合成18种N-（噻唑-2-基）-2-[4-（芳氧基）苯氧基]丙酰胺，其化学结构经¹H NMR、¹³C NMR、元素分析、EI-MS和旋光度确证.采用单晶X射线衍射仪测定了（R）-N-（4-三氟甲基-5-乙氧羰基噻唑-2-基）-2-[4-（3-氟-5-氯吡啶-2-氧基）苯氧基]丙酰胺的晶体结构，该晶体属于四方晶系，空间群为P41212，晶胞参数为：a=14.45502（18）Å，b=14.45502（18）Å，c=21.7813（5）Å；Z=8，V=4551.14（15）Å³，D_c=1.558 Mg/m³，F（000）=2176，μ=3.013 mm^-1，最终偏离因子R=0.0302，wR=0.0687.除草活性表明，在1500 g/hm²剂量下，大部分化合物对单子叶杂草马唐（Digitaria sanguinalis）和稗草（Echinochloa crusgalli）均具有较高的抑制活性，部分化合物对马唐和稗草的茎叶和土壤处理表现为100%的抑制活性.

关键词:

English

Synthesis, Crystal Structure and Herbicidal Activity of N-(Thiazol-2-yl)-2-(4-aryloxyphenoxy) propionamides

Yang Zihui ,
Chen Aiyu ,
Hu Aixi ^{*,
,} ,
Ye Jiao ^{*,
,}

Colleage of Chemistry and Chemical Engineering, Hunan University, Changsha 410082

Corresponding author: Hu Aixi, axhu@hnu.edu.cn; Ye Jiao, yejiao@hnu.edu.cn

Received Date: 27 July 2016
Revised Date: 26 August 2016
Fund Project:
the National Science and Technology Pillar Program of China During the Twelfth Five-year Plan Period

Abstract: Eighteen N-(thiazol-2-yl)-2-(4-aryloxyphenoxy) propionamides were synthesized by reaction of (R)-(+)-2-(4-hy-droxyphenoxy) propanoyl chlorides with 2-aminothiazole derivatives.Their structures were confirmed by ¹H NMR, ¹³C NMR, elemental analysis, EI-MS and optical rotation.The crystal structure of (R)-N-(4-trifluoromethyl-5-ethoxycarbonylthiazole-2-yl)-2-[4-(3-fluoro-5-chloropyridin-2-yl) oxy) phenoxy) propionamide was determined by X-ray diffraction analysis.The crystal belonged to the tetragonal system, space group P41212 with a=14.45502(18)Å, b=14.45502(18)Å, c=21.7813(5)Å;Z=8, V=4551.14(15)Å³, D_c=1.558 Mg/m³, F(000)=2176, μ=3.013 mm^-1, and the final R=0.0302, wR=0.0687.The bioassay results indicated that most of title compounds displayed moderate to excellent herbicidal activity against crabgrass (Digitaria sanguinalis) and barnyard grass (Echinochloa crusgalli) at the dose of 1500 g/hm².Some compounds showed 100% inhibition against the growth of the crabgrass and barnyard grass when applied at the pre-emergence and post-emergence treatment.

Key words:

噻唑类化合物具有广泛的医药活性^{[8, 9]}, 如抗癌^{[10, 11]}、抗菌等^[12].在农业领域, 特别是在除草剂研究中备受关注^[13], 相继开发出多个含噻唑环的品种, 如噻草胺和甲基苯噻隆等^[14].基于2-(4-芳氧苯氧基)丙酸衍生物的药效团和噻唑衍生物^[15]的结构特点, 采用拼合原理设计了N-(噻唑-2-基)-2-(4-芳氧基苯氧基)丙酰胺(1) (图 1).以具有α-H的羰基化合物为原料, 经α-卤代、环合和酰化制得化合物1, 对其除草活性进行筛选.化合物1的合成路线见Scheme 1.

图图式 1 化合物1的合成路线

Figure 图式 1. Synthetic routes of target compounds 1

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2-(4-芳氧苯氧基)羧酸衍生物是一类选择性抑制植物乙酰辅酶A羧化酶的除草剂.柳爱平等^[1]合成的N-吡啶芳氧苯氧羧酸衍生物(R, R)-N-(3-氯吡啶-2-基)-N-[2-(4-(3-氟-5-氯吡啶-2-氧基)苯氧基)]丙酰基-[2-(4-(3-氟-5-氯吡啶-2-基氧基)苯氧基)]丙酰胺在2250 g/hm²剂量下对马唐、稗草和狗尾草的茎叶处理的抑制率均为100%. Kim等^[2]合成的N-(2-氟苯基)-[2-(4-(芳乙烯氧基)苯氧基)]丙酰胺具有一定的除草活性. Yu等^[3]合成的[2-(4-嘧啶氧基苯氧基)]丙酰胺膦酸酯在100 g/L浓度下对双子叶植物油菜有较好的防效.关爱莹等^[4]报道的喹草烯(SYP-1924)在7.5 g/hm²剂量下对稗草的防效为90%.周银平等^[5]报道的含苯并噁唑的2-(4-芳氧苯氧基)丙酰胺在300 g/hm²剂量下对狗尾草和千金子的抑制率为100%.李为忠等^[6]报道的化合物在200 g/hm²剂量下对千金子的抑制率为95.0%, 且对水稻安全.刘祈星等^[7]以噁唑酰草胺(Metamifop)为先导制备的2-(4-杂芳氧苯氧基)丙酸衍生物中, 最好的化合物对马唐和稗草的IC₅₀值分别为15.4和22.8 g/hm², 均低于噁唑酰草胺的31.9和25.0 g/hm².

图1 化合物1的设计思路

Figure 1. Design strategy of compounds 1

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1 结果与讨论

1.1 化合物1f晶体结构解析

图2 1f的单晶结构图

Figure 2. Molecular crystal structure of compound 1f

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化合物1f单晶体, 其特征在于单晶体中丙酰胺氮上的氢原子作为氢键受体与另一分子噻唑环上的氮原子形成分子间的氢键N (2)-H…N (3)ⁱ; 分子间的氢键键长为2.28(4) Å, 氢键键角为164(3)°.其分子结构中C (12)构型为R构型.

图3 氢键图

Figure 3. Hydrogen bonds of compound 1f

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(R)-N-(4-三氟甲基-5-乙氧羰基噻唑-2-基)-2-[4-(3-氟-5-氯吡啶-2-氧基)苯氧基]丙酰胺(1f)的单晶结构如图 2所示, 氢键图如图 3所示.

化合物1f晶体数据存于英国剑桥数据中心, CCDC号为1500380, 分子式为C₂₁H₁₆ClF₄N₃O₅S, M_r=533.04, m.p. 59~62 ℃.属四方晶系, 空间群为P4₁2₁2, 晶胞参数为: a=14.45502(18) Å, b=14.45502(18) Å, c=21.7813(5) Å; Z=8, V=4551.14(15) Å³, D_c=1.558 Mg/m³, F(000)=2176, μ=3.013 mm^-1, 3700个可观测点[I＞2σ(I)], 可观测点精修最终偏离因子R=0.0302, wR=0.0687, 绝对结构参数为0.014(8), (Δ/σ)_max=0.019, S=1.03, (Δρ)_max=0.30 e/Å³, (Δρ)_min=-0.25 e/Å³.

1.2 除草活性评价

表1 化合物1a~1r的除草活性(抑制率/%, 1500 g/hm²)^a Table1. Herbicidal activities of compounds 1a~1r(inhibition rate/%, 1500 g/hm²)

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Compd.	Pre-emergence treatment				Post-emergence treatments
Compd.	B.C.	A.R.	E.C.	D.S.	B.C.	A.R.	E.C.	D.S.
1a	0	10.0	100	100	10.0	35.8	15.0	10.0
1b	0	5.0	100	100	12.3	44.5	100	100
1c	0	0	100	100	25.3	0	100	100
1d	0	0	100	100	21.7	5.0	100	100
1e	0	0	100	100	15.8	15.0	100	100
1f	0	0	100	100	2.4	0	100	100
1g	0	10.0	100	100	5.0	34.1	15.0	10.0
1h	0	0	100	100	5.0	75.7	100	100
1i	0	0	87.3	100	5.0	15.0	100	100
1j	0	0	71.1	73.7	7.9	15.0	100	100
1k	0	0	99.1	100	13.8	47.1	100	100
1l	0	0	100	100	0	15.0	100	100
1m	0	0	87.3	100	0	30.6	10.0	10.0
1n	0	0	95.5	100	0	42.8	100	100
1o	0	0	76.5	98.8	0	5.0	100	100
1p	0	0	87.3	84.0	0	10.0	100	100
1q	0	0	68.4	76.1	1.2	15.0	100	100
1r	0	0	100	100	2.8	10.0	100	100
Metamifop	0	0	100	100	0	0	100	100
^a试验材料为油菜(Brassica Campestris, B.C.)、苋菜(Amaranthus retroflexus, A.R.)、稗草(Echinochloa crusgalli, E.C.)、马唐(Digitaria sanguinalis, D.S.).阳性对照药:噁唑酰草胺(Metamifop).

表1 化合物1a~1r的除草活性(抑制率/%, 1500 g/hm²)^a
Table1. Herbicidal activities of compounds 1a~1r(inhibition rate/%, 1500 g/hm²)

化合物1对双子叶杂草油菜和苋菜的抑制作用不明显, 表现出对单子叶杂草的明显选择性, 其中1h在同剂量下对苋菜的茎叶处理的抑制率为75.7%.

除草活性表明, 化合物1对单子叶杂草具有很好的抑制活性, 使得植株叶片失绿, 发黄, 叶片皱缩, 逐渐枯萎, 植株生长受到强烈抑制.其中1b~1f、1k、1l和1r在1500 g/hm²剂量下对单子叶杂草马唐和稗草均表现为100%的抑制活性, 与噁唑酰草胺相当, 并且茎叶处理的效果略优于土壤处理, 属苗后除草剂, 说明叶片的渗透和传递可以影响药剂对植物的杀伤效果, 其他部分化合物如1i、1j、1o、1p和1q对单子叶杂草有一定抑制活性.

以噁唑酰草胺为阳性对照, 对化合物1a~1r进行除草活性筛选, 其活性结果列入表 1.

总体而言, 取代基R和Ar对化合物1的活性都具有较大的影响.当Ar为3-氟-5-氯吡啶环时, 对马唐和稗草的茎叶和土壤处理抑制活性略优于3-氯-5-三氟甲基吡啶和喹喔啉, 如1d对马唐和稗草的土壤处理抑制率优于1j.当Ar相同时, 当R为硝基, 2, 4-二氯苄基及4-甲氧基苄基时, 活性普遍要比R为H时好, 如化合物1b和1d在茎叶处理的条件下, 对马唐、稗草表现出100%抑制活性, 而化合物1a和1m在同样的条件茎叶处理时只表现出10%的抑制活性. Ar基团对除草活性影响大小顺序依次为: 3-氟-5-氯吡啶＞3-氯-5-三氟甲基吡啶＞喹喔啉; R基团影响顺序为: NO₂, 4-CH₃OC₆H₄CH₂, 2, 4-Cl₂C₆H₄CH₂＞H.

2 结论

设计合成了18个N-(噻唑-2-基)-2-[4-(芳氧基)苯氧基]丙酰胺类化合物1a~1r, 其化学结构经¹H NMR、¹³C NMR、EI-MS、元素分析和旋光度确证.经除草活性筛选试验发现, 以剂量1500 g/hm²分别进行茎叶处理和土壤处理时, 化合物1对单子叶杂草马唐和稗草均具有较好的除草活性, 其中1b~1f、1k、1l和1r对马唐和稗草表现为100%的抑制活性.降低浓度的除草活性实验在进一步研究中.

3 实验部分

3.1 仪器与试剂

ZF-2型三用紫外仪(上海安亭电子仪器厂); R-1002N型旋转蒸发仪、SHB-Ⅲ型循环水式多用真空泵(郑州长城科工贸有限公司); RY-1G型熔点仪(天津天光光学仪器有限公司); VARIAN INOVA-400核磁共振仪(美国Varian公司), ¹H NMR核磁共振频率为400 MHz, ¹³C NMR核磁共振频率为100 MHz, TMS为内标; Agilent 1100 Series型高效液相色谱-质谱联用系统(EI, 美国Agilent公司); VARIO EL Ⅲ元素分析仪(德国); Bruker AXS SMART 1000 CCDX射线单晶衍射仪(德国).

薄层层析硅胶板(烟台江友硅胶开发有限公司).溶剂和试剂均为市售分析纯或化学纯.

3.2 实验方法

3.3 化合物1f的单晶测定

0.1 g 1f溶入5 mL二氯甲烷和石油醚混合溶剂中, 室温静置10 d, 析出1f单晶体, 选取0.42 mm×0.37 mm×0.28 mm单晶体, 该晶体在BRUKER SMART APEX 1000 CCD衍射仪上收集衍射数据, 利用石墨单色器单色化了的Mo Kα射线(λ=1.54184 Å), 在150(2) K下以ω-φ扫描方式收集衍射数据, 在3.67°≤2θ≤66.86°范围收集9802个数据, 其中独立衍射点3960个, 可观测点3700个.然后运用Bruker的SAINTPLUS程序^[22]将数据还原, 同时运用SADABS程序^[23]进行经验吸收校正.应用SHELXS-97和SHELXL-97程序^[24]直接法解析和精修结构.所有的非氢原子采用全矩阵最小二乘法进行结构精修.所有非氢原子都做各向异性精修.理论加氢, 氢原子各向同性热参数修正.

3.4 目标化合物的除草活性测定

辅助材料(Supporting Information) 化合物1a~1r的¹H NMR、¹³C NMR谱图和1f晶体的结构数据.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

感谢南开大学元素有机化学研究所李永红老师在活性方面提供的帮助.

采用盆栽法测试化合物1的除草活性.

盆栽法(土壤处理):在直径8 cm的塑料小杯中放入一定量的土, 加入一定量的水, 播种后覆盖一定厚度的土壤, 于花房中培养, 幼苗出土前以塑料覆盖.每天加以定量的清水以保持正常生长.出苗前进行土壤处理, 处理剂量为1500 g/hm², 30 d后调查结果, 测定地上部鲜重, 以鲜重抑制百分数来表示药效^[24].

盆栽法(茎叶处理):在直径8 cm的塑料小杯中放入一定量的土, 加入一定量的水, 播种15颗发芽的种子于泥土下0.5 cm深, 播种后覆盖一定厚度的土壤, 于花房中培养, 幼苗出土前以塑料覆盖.出苗后, 每天加以定量的清水以保持正常生长.当幼苗长到一定时期进行茎叶喷洒待测化合物的溶液, 处理剂量为1500 g/hm², 30 d后调查结果, 测定地上部鲜重, 以鲜重抑制百分数来表示药效.

3.2.1 化合物2和3的合成

4-叔丁基-5-硝基-2-氨基噻唑(2b)的合成:冰浴下, 13.2 g (50 mmol) 4-叔丁基-2-氨基噻唑硝酸盐粉末分批加入到20 mL浓硫酸中, 控制温度低于10 ℃搅拌, 升至40 ℃反应10.0 h, 倒入碎冰中淬灭.冰浴下, NaOH溶液中和, 析出砖红色固体, 抽滤, 乙醇/水重结晶, 干燥得砖红色固体2b, m.p. 189~191 ℃(文献值^[17a]: m.p. 191~192 ℃), 收率50.1%.

4-三氟甲基-2-氨基噻唑-5-羧酸乙酯(2f)参照文献[20]合成, 得白色固体, 收率88.0%. m.p. 168~169 ℃(文献值^[20]: m.p. 168~171 ℃).

4-叔丁基-5-(4-甲氧基苄基)-2-氨基噻唑(2c)参照文献[17b]合成, 收率71.7%. m.p. 118~120 ℃(文献值^[17b]: m.p. 118.8~120.5 ℃).

中间体3参照文献[7]合成. (R)-2-[4-(3-氟-5-氯吡啶-2-氧基)苯氧基]丙酸(3a):白色固体, m.p. 209~211 ℃(文献值^[15]: m.p. 211~212 ℃), [α]_D²⁰+30.00 (c 1, CH₂Cl₂). (R)-2-[4-(3-氯-5-三氟甲基吡啶-2-氧基)苯氧基]丙酸(3g):棕色液体, [α]_D²⁰+25.06 (c 1, CH₂Cl₂); MS m/z: 361 [M⁺]. (R)-2-[2-[4-(6-氯喹喔啉-2-氧基)苯氧基]丙酸(3m): m.p. 210~212 ℃(文献值^[15]: m.p. 211~212 ℃), [α]_D²⁰+33.75 (c 1, CH₂Cl₂).

4-叔丁基-5-(2, 4-二氯苄基)-2-氨基噻唑(2d)参照文献[18]合成, 收率85.7%. m.p. 126~128 ℃(文献值^[18]: m.p. 125~127 ℃).

4-甲基-2-氨基噻唑-5-羧酸乙酯(2e)参照文献[19]合成, 得白色固体, 收率92.3%. m.p.176~178 ℃(文献值^[19]: m.p.174~176 ℃).

4-叔丁基-2-氨基噻唑(2a):参照文献[16]合成, 得淡黄色固体, 收率80.8%. m.p. 96~98 ℃(文献值^[16]: m.p. 98~99 ℃).

3.2.2 化合物1a~1r的合成

(R)-N-(4-甲基-5-乙氧羰基噻唑-2-基)-2-[4-(3-氯-5-三氟甲基吡啶-2-氧基)苯氧基]丙酰胺(1k):反应5.0 h, 黄色固体, 收率65.0%. m.p. 96~99 ℃; [α]_D²⁰+15.50 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.37 (t, J=7.0 Hz, 3H, CH₃), 1.69 (d, J=6.8 Hz, 3H, CH₃), 2.65 (s, 3H, CH₃), 4.33 (q, J=7.0 Hz, 2H, COOCH₂), 4.93 (q, J=6.8 Hz, 1H, CH), 7.00 (d, J=8.0 Hz, 2H, C₆H₄-2, 6-H), 7.14 (d, J=8.0 Hz, 2H, C₆H₄-3, 5-H), 7.98 (s, 1H, C₅H₂N-6-H), 8.26 (s, 1H, C₅H₂N-4-H), 9.80 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 14.39, 17.03, 18.47, 61.12, 75.06, 116.64, 120.63 (q, ¹J_C-F=250 Hz), 123.09, 127.61, 127.91, 128.82, 131.20, 133.74, 136.34 (q, ³J_C-F=3.3 Hz), 139.13, 142.52 (q, ³J_C-F=5.2 Hz), 147.68, 153.83, 156.30, 170.20; EI-MS m/z: 529.1 [M⁺]. Anal. calcd for C₂₂H₁₉ClF₃N₃O₅S: C 49.86, H 3.61, N 7.93; found 49.80, H 3.53, N 7.83.

(R)-N-[4-叔丁基-5-(4-甲氧基苄基)噻唑-2-基]-2-[4-(6-氯喹喔啉-2-基氧基)苯氧基]丙酰胺(1o):反应5.0 h, 淡黄色固体, 收率66.7%. m.p. 65~67 ℃; [α]_D²⁰+24.42 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.38 (s, 9H, 3×CH₃), 1.66 (d, J=6.7 Hz, 3H, CH₃), 3.79 (s, 3H, OCH₃), 4.19 (s, 2H, CH₂), 4.86 (q, J=6.7 Hz, 1H, CH), 6.84 (d, J=8.4 Hz, 2H, OC₆H₄), 7.02 (d, J=8.0 Hz, 2H, C₆H₄-2, 6-H), 7.11 (d, J=8.4 Hz, 2H, OC₆H₄), 7.23 (d, J=8.0 Hz, 2H, C₆H₄-3, 5-H), 7.60 (dd, J=8.9, 2.1 Hz, 1H, quinoxalin-H), 7.69 (d, J=8.9 Hz, 1H, quinoxalin-H), 8.05 (d, J=2.2 Hz, 1H, quinoxalin-H), 8.69 (s, 1H, quinoxalin-H); ¹³C NMR (100 MHz, CDCl₃) δ: 18.46, 30.92, 32.29, 35.59, 55.25, 75.40, 114.02, 116.81, 119.30, 121.44, 122.24, 122.64, 122.99, 124.26, 125.40, 129.29, 132.47, 132.96, 136.45, 142.56, 147.56, 152.24, 154.18, 158.27, 161.24, 169.57; EI-MS m/z: 602.2 [M⁺]. Anal. calcd for C₃₂H₃₁ClN₄O₄S: C 63.72, H 5.18, N 9.29; found C 63.62, H 5.08, N 9.19.

(R)-N-[4-叔丁基-5-(4-甲氧基苄基)噻唑-2-基]-2-[4-(3-氯-5-三氟甲基吡啶-2-氧基苯氧基]丙酰胺(1i):反应3.0 h, 淡黄色固体, 收率69.8%. m.p. 69~71 ℃; [α]_D²⁰+21.00 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.40 (s, 9H, 3×CH₃), 1.65 (d, J=6.7 Hz, 3H), 3.80 (s, 3H, OCH₃), 4.19 (s, 2H, CH₂), 4.83~4.88 (m, 1H, CH), 6.84 (d, J=8.0 Hz, 2H, CH₃OC₆H₄), 7.06 (s, 2H, C₆H₄-2, 6-H), 7.11~7.13 (m, 4H, C₆H₄, CH₃OC₆H₄, C₆H₄-3, 5-H), 7.97 (s, 1H, C₅H₂N-6-H), 8.26 (s, 1H, C₅H₂N-4-H); ¹³C NMR (100 MHz, CDCl₃) δ: 18.76, 30.93, 32.27, 35.83, 55.22, 75.15, 114.09, 116.69, 120.67 (q, ¹J_C-F=260 Hz), 122.60, 122.92, 127.38, 128.02, 128.81, 129.36, 130.90, 131.23, 133.20, 138.44 (q, ³J_C-F=4.0 Hz), 140.24, 142.59 (q, ³J_C-F=3.9 Hz), 147.52, 158.26, 169.36; EI-MS m/z: 619.2 [M⁺]. Anal. calcd for C₃₀H₂₉ClF₃N₃O₄S: C 58.11, H 4.71, N 6.78; found C 58.00, H 4.66, N 6.70.

(R)-N-[4-叔丁基-5-(2, 4-二氯苄基)噻唑-2-基]-2-[4-(3-氟-5-氯吡啶-2-氧基)苯氧基]丙酰胺(1d):反应3.0 h, 白色固体, 收率75.0%. m.p. 54~57 ℃; [α]_D²⁰+32.50 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.32 (s, 9H, 3×CH₃), 1.61 (d, J=6.7 Hz, 3H, CH₃), 4.19 (s, 2H, CH₂), 4.80 (q, J=6.7 Hz, 1H, CH), 6.97 (d, J=9.0 Hz, 2H, C₆H₄2, 6-H), 7.08~7.11 (m, 3H, C₆H₄, C₆H₄-3, 5-H, C₆H₃-6-H), 7.23~7.24 (m, 2H, C₆H₃), 7.46~7.49 (m, F-H, 1H, C₅H₂N-4-H), 7.84 (d, J=2.0 Hz, 1H, C₅H₂N-6-H), 9.54 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 18.74, 31.17, 32.44, 36.17, 75.15, 116.30, 116.89, 122.36, 122.63, 123.65, 125.00, 125.23, 128.73, 129.40, 129.69, 132.44, 138.92, 140.18 (d, ³J_C-F=6.1 Hz), 147.04 (d, ¹J_C-F=260 Hz), 147.77, 152.21, 153.89 (d, ²J_C-F=16.6 Hz), 159.27, 169.66; EI-MS m/z: 607.1 [M⁺]. Anal. calcd for C₂₈H₂₅Cl₃FN₃O₃S: C 55.23, H 4.14, N 6.90; found C 55.10, H 4.10, N 6.82.

(R)-N-(4-叔丁基噻唑-2-基)-2-[4-(6-氯喹喔啉-2-基氧基)苯氧基]丙酰胺(1m):反应2.0 h, 淡黄色固体, 收率74.3%. m.p. 56~59 ℃; [α]_D²⁰+11.50 (c1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.32(s, 9H, 3×CH₃), 1.70 (d, J=6.8 Hz, 3H, CH₃), 4.92 (q, J=6.7 Hz, 1H, CH), 6.60 (s, 1H, thiazole-5-H), 7.06 (d, J=9.0 Hz, 2H, C₆H₄-2, 6-H), 7.23 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.60 (dd, J=9.0, 2.0 Hz, 1H, quinoxalin-H), 7.69 (d, J=8.0 Hz, 1H, qui-noxalin-H), 8.05 (d, J=2.2 Hz, 1H, quinoxalin-H), 8.69 (s, 1H, quinoxalin-H), 9.68 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ; 18.40, 30.26, 34.62, 75.50, 105.88, 116.86, 122.96, 127.88, 128.90, 131.22, 132.95, 138.58, 140.19, 142.22, 147.43, 153.96, 157.46, 161.50, 162.40, 169.76; EI-MS m/z: 482.1 [M⁺]. Anal. calcd for C₂₄H₂₃ClN₄O₃S: C 59.68, H 4.80, N 11.60; found C 59.58, H 4.72, N 11.52.

(R)-N-(4-三氟甲基-5-乙氧羰基噻唑-2-基)-2-[4-(6-氯喹喔啉-2-基氧基)苯氧基]丙酰胺(1r):反应5.0 h, 白色固体, 收率72.8%. m.p. 92~95 ℃; [α]_D²⁰+26.25 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.29 (t, J=7.1 Hz, 3H, CH₃), 1.65 (d, J=6.8 Hz, 3H, CH₃), 4.19~4.34 (m, 2H, COOCH₂), 4.76 (q, J=6.8 Hz, 1H, CH), 6.96 (d, J=9.0 Hz, 2H, C₆H₄-2, 6-H), 7.18 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.60 (dd, J=8.9, 2.3 Hz, 1H, quinoxalin-H), 7.68 (d, J=8.9 Hz, 1H, quinoxalin-H), 8.05 (d, J=2.2 Hz, 1H, quinoxalin-H), 8.67 (s, 1H, quinoxalin-H); ¹³C NMR (100 MHz, CDCl₃) δ: 14.04, 18.37, 62.39, 74.68, 116.78, 118.50 (q, ¹J_C-F=230 Hz), 122.87, 122.94 (d, ³J_C-F=14.0 Hz), 123.07, 124.11, 128.02, 128.85, 131.27, 133.08, 138.43, 139.90, 140.12, 147.65, 153.42, 157.02, 158.41, 170.87; EI-MS m/z: 566.1 [M⁺]. Anal. calcd for C₂₄H₁₈ClF₃N₄O₅S: C 50.84, H, 3.20, N 9.88; found C 50.74, H 3.10, N 9.78.

(R)-N-(4-叔丁基-5-硝基噻唑-2-基)-2-[4-(3-氯-5-三氟甲基吡啶-2-氧基)苯氧基]丙酰胺(1h):反应3.5 h, 黄色固体, 收率68.0 %. m.p. 63~66 ℃; [α]_D²⁰+21.25 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.46 (s, 9H, 3×CH₃), 1.70 (d, J=6.8 Hz, 3H, CH₃), 4.95 (q, J=6.8 Hz, 1H, CH), 7.05 (d, J=9.0 Hz, 2H, C₆H₄-2, 6-H), 7.17 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.99 (s, 1H, C₅H₂N-6-H), 8.27 (s, 1H, C₅H₂N-4-H), 9.66 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 18.41, 28.44, 36.90, 75.16, 116.98, 120.47 (q, ¹J_C-F=240 Hz), 123.23, 127.51, 130.68, 136.45 (q, ³J_C-F=3.2 Hz), 142.54 (q, ³J_C-F=4.4 Hz), 145.82, 147.90, 150.64, 153.75, 155.15, 159.72, 170.65; EI-MS m/z: 544.1 [M⁺]. Anal. calcd for C₂₂H₂₀ClF₃N₄O₅S: C 48.49, H 3.70, N 10.28; found C 48.40, H 3.63, N 10.20.

(R)-N-(4-三氟甲基-5-乙氧羰基噻唑-2-基)-2-[4-(3-氯-5-三氟甲基吡啶-2-氧基)苯氧基]丙酰胺(1l):反应5.0 h, 淡黄色固体, 收率70.5%. m.p. 71~74 ℃; [α]_D²⁰+20.75 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.32 (t, J=7.0 Hz, 3H, CH₃), 1.62 (d, J=6.8 Hz, 3H, CH₃), 4.32 (q, J=7.0 Hz, 2H, OCH₂), 4.90 (q, J=6.8 Hz, 1H, CH), 6.92 (d, J=9.0 Hz, 2H, C₆H₄-2, 6-H), 7.07 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.90 (s, 1H, C₅H₂N-6-H), 8.18 (s, 1H, C₅H₂N-4-H), 9.98 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 14.00, 18.44, 62.71, 74.86, 116.64, 119.13, 120.30 (q, ¹J_C-F=230 Hz), 123.13 (d, ³J_C-F=9.4 Hz), 128.82, 136.39 (q, ³J_C-F=3.3 Hz), 142.52 (q, ³J_C-F=4.3 Hz), 144.54, 147.54, 147.78, 149.26, 153.64, 153.90, 158.42, 159.35, 161.22, 171.09; EI-MS m/z: 583.1 [M⁺]. Anal. calcd for C₂₂H₁₆ClF₆N₃O₅S: C 45.25, H 2.76, N 7.20; found C 45.20, H 2.63, N 7.10.

(R)-N-(4-叔丁基噻唑-2-基)-2-[4-(3-氟-5-氯吡啶-2-氧基)苯氧基]丙酰胺(1a):反应2.0 h, 橙色固体, 收率66.5%. m.p. 57~60 ℃; [α]_D²⁰+19.75 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.30 (s, 9H, 3×CH₃), 1.67 (d, J=7.0 Hz, 3H, CH₃), 4.87 (q, J=7.0 Hz, 1H, CH), 6.58 (s, 1H, thiazole 5-H), 7.01 (d, J=9.0 Hz, 2H, C₆H₄-2, 6-H), 7.13 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.51 (dd, J=9.0, 2.0 Hz, 1H, C₅H₂N-4-H), 7.87 (d, J=2.0 Hz, 1H, C₅H₂N-6-H), 9.63 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 18.40, 29.92, 34.34, 75.50, 105.43, 116.69, 122.57, 124.98, 125.16, 140.18 (d, ³J_C-F=6.0 Hz), 147.01 (d, ¹J_C-F=260 Hz), 147.79, 151.16 (d, ²J_C-F=14.1 Hz), 153.62, 155.74, 161.37, 169.92; EI-MS m/z: 449.1 [M⁺]. Anal. calcd for C₂₁H₂₁ClFN₃O₃S: C 56.06, H 4.70, N 9.34; found C 55.93, H 4.60, N 9.25.

(R)-N-(4-甲基-5-乙氧羰基噻唑-2-基)-2-[4-(6-氯喹喔啉-2-基氧基)苯氧基]丙酰胺(1q):反应3.0 h, 白色固体, 收率74.5%. m.p. 113~116 ℃; [α]_D²⁰+20.25 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.38 (t, J=7.1 Hz, 3H, CH₃), 1.72 (d, J=6.7 Hz, 3H, CH₃), 2.68 (s, 3H, CH₃), 4.33 (d, J=7.1 Hz, 2H, OCH₂), 4.98 (q, J=6.7 Hz, 1H, CH), 7.07 (d, J=9.0 Hz, 2H, C₆H₄-2, 6-H), 7.25 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.61 (dd, J=9.0, 2.3 Hz, 1H, quinoxalin-H), 7.69 (d, J=9.0 Hz, 1H, quinoxalin-H), 8.05 (d, J=2.2 Hz, 1H, quinoxalin-H), 8.69 (s, 1H, quinoxalin-H); ¹³C NMR (100 MHz, CDCl₃) δ: 14.32, 17.20, 18.39, 61.15, 75.06, 116.63, 123.17, 127.89, 128.75, 131.61, 132.82, 138.45, 139.80, 140.06, 147.35, 150.44, 153.54, 156.36, 156.98, 158.16, 162.51, 170.24; EI-MS m/z: 512.1 [M⁺]. Anal. calcd for C₂₄H₂₁ClN₄O₅S: C 56.19, H 4.13, N 10.92; found C 56.10, H 4.03, N 10.82.

(R)-N-(4-叔丁基噻唑-2-基)-2-[4-(3-氯-5-三氟甲基吡啶-2-氧基)苯氧基]丙酰胺(1g):反应1.0 h, 黄色固体, 收率70.1%. m.p. 52~55 ℃; [α]_D²⁰+16.33 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.30 (s, 9H, 3×CH₃), 1.68 (d, J=6.8 Hz, 3H, CH₃), 4.89 (q, J=6.8 Hz, 1H, CH), 6.59 (s, 1H, thiazole, 5-H), 7.04 (d, J=9.0 Hz, 2H, C₆H₄-2, 6-H), 7.14 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.97 (d, J=2.0 Hz, 1H, C₅H₂N-6-H), 8.26 (s, 1H, C₅H₂N-4-H), 9.60 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 18.40, 30.29, 34.64, 75.17, 105.44, 117.02, 120.91 (q, ¹J_C-F=280 Hz), 123.05, 125.89, 127.63, 136.38 (q, ³J_C-F=3.1 Hz), 142.59 (q, ³J_C-F=4.3 Hz), 145.27, 147.30, 154.05, 155.80, 161.34, 169.98; EI-MS m/z: 499.1 [M⁺]. Anal. calcd for C₂₂H₂₁ClF₃N₃O₃S: C 52.85, H 4.23, N 8.41; found C 52.78, H 4.20, N 8.36.

(R)-N-(4-甲基-5-乙氧羰基噻唑-2-基)-2-[4-(3-氟-5-氯吡啶-2-氧基)苯氧基]丙酰胺(1e):反应3.0 h, 淡黄色固体, 收率72.9%. m.p. 53~56 ℃; [α]_D²⁰+10.08 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.36 (t, J=7.1 Hz, 3H), 1.68 (d, J=6.8 Hz, 3H, CH₃), 2.64 (s, 3H, CH₃), 4.33 (q, J=7.1 Hz, 2H, OCH₂), 4.91 (q, J=6.8 Hz, 1H, CH), 6.98 (d, J=9.0 Hz, 2H, C₆H₄-2, 6-H), 7.13 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.51 (dd, J_F-H=9.0 Hz, J₂=2.0 Hz, 1H, C₅H₂N-4-H), 7.87(d, J=2.2 Hz, 1H, C₅H₂N-6-H), 9.70 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 14.34, 17.49, 18.76, 60.84, 75.17, 116.59, 122.32, 122.72, 125.09, 125.27, 140.16 (d, ³J_C-F=6.1 Hz), 146.95(d, ¹J_C-F=270 Hz), 147.94, 151.11 (d, ²J_C-F=9.6 Hz), 153.43, 156.39, 158.26, 162.73, 170.43; EI-MS m/z: 479.1 [M⁺]. Anal. calcd for C₂₁H₁₉ClFN₃O₅S: C 52.56, H 3.99, N 8.76; found C 52.50, H 3.80, N 8.67.

(R)-N-[4-叔丁基-5-(4-甲氧基苄基)噻唑-2-基]-2-[4-(3-氟-5-氯吡啶-2-氧基)苯氧基]丙酰胺(1c):反应2.0 h, 黄色固体, 收率77.8%. m.p. 58~60 ℃; [α]_D²⁰+15.25 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.34 (s, 9H, 3×CH₃), 1.61 (d, J=6.7 Hz, 3H, CH₃), 3.77 (s, 3H, OCH₃), 4.16 (s, 2H, CH₂), 4.79 (q, J=6.7 Hz, 1H, CH), 6.81 (d, J=8.4 Hz, 2H, CH₃OC₆H₄), 6.97 (d, J=8.4 Hz, 2H, CH₃O-C₆H₄), 7.08~7.10 (m, 4H, C₆H₄), 7.48 (d, J_F-H=8.9 Hz, 1H, C₅H₂N-4-H), 7.84 (s, 1H, C₅H₂N-6-H); ¹³C NMR (100 MHz, CDCl₃) δ: 18.60, 29.76, 31.15, 32.13, 55.08, 75.10, 114.00, 116.22, 116.50, 116.85, 118.59, 122.57, 124.09, 124.95, 125.14, 127.88, 129.33, 140.15 (d, ³J_C-F=6.0 Hz), 146.97 (d, ¹J_C-F=260 Hz), 147.69, 153.83 (d, ²J_C-F=9.8 Hz), 159.66, 169.73; EI-MS m/z: 569.2 [M⁺]. Anal. calcd for C₂₉H₂₉ClFN₃O₄S: C, 61.10, H 5.13, N 7.37; found C 60.88, H 5.04, N 7.27.

(R)-N-(4-叔丁基-5-硝基噻唑-2-基)-2-[4-(3-氟-5-氯吡啶-2-氧基)苯氧基]丙酰胺(1b):反应3.0 h, 橙红色固体, 收率71.2%. m.p. 58~61 ℃; [α]_D²⁰+25.33 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.46 (s, 9H, 3×CH₃), 1.69 (d, J=6.8 Hz, 3H, CH₃), 4.93 (q, J=6.8 Hz, 1H, CH), 7.02 (d, J=9.0 Hz, 2H, C₆H₄2, 6-H), 7.16 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.52 (dd, J=9.0, 2.0 Hz, 1H, C₅H₂N-4-H), 7.87 (d, J=2.0 Hz, 1H, C₅H₂N-6-H), 9.66 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 18.39, 28.39, 37.14, 75.15, 117.10, 122.76, 125.09, 125.37, 140.17 (d, ³J_C-F=6.0 Hz), 144.75, 147.10 (d, ¹J_C-F=260 Hz), 148.16, 151.06 (d, ²J_C-F=9.6 Hz), 153.32, 155.08, 162.18, 170.82; EI-MS m/z: 494.1 [M⁺]. Anal. calcd for C₂₁H₂₀ClFN₄O₅S: C 50.96, H 4.07, N11.32; found C 50.82, H 3.93, N 11.30.

(R)-N-[4-叔丁基-5-(2, 4-二氯苄基)噻唑-2-基]-2-[4-(3-氯-5-三氟甲基吡啶-2-氧基)苯氧基]丙酰胺(1j):反应5.0 h, 淡黄色固体, 收率67.5%. m.p. 61~64 ℃; [α]_D²⁰+24.90 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.34 (s, 9H, 3×CH₃), 1.65 (d, J=6.8 Hz, 3H, CH₃), 4.28 (s, 2H, CH₂), 4.85 (q, J=6.8 Hz, 1H, CH), 7.02~7.06 (m, 3H, C₆H₃ 6-H, C₆H₄-2, 6-H), 7.11~7.21 (m, 3H, C₆H₃-5-H, C₆H₄-3, 5-H), 7.40 (d, J=2.1 Hz, 1H, C₆H₃-3-H), 7.98 (d, J=2.0 Hz, 1H, C₅H₂N-6-H), 8.27 (s, 1H, C₅H₂N-4-H), 9.45 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 18.45, 30.08, 30.53, 35.66, 75.14, 116.73, 120.49 (q, ¹J_C-F=250 Hz), 122.84, 127.03, 127.13, 128.97, 129.15, 130.49, 130.71, 132.88, 133.03, 134.18, 136.20 (q, ³J_C-F=3.0 Hz), 136.45, 142.39 (q, ³J_C-F=4.4 Hz), 147.41, 152.18, 154.03, 154.18, 169.50; EI-MS m/z: 657.1 [M⁺]. Anal. calcd for C₂₉H₂₅Cl₃F₃N₃O₃S: C 52.86, H 3.82, N 6.38; found C 52.78, H 3.78, N 6.30.

(R)-N-(4-叔丁基-5-硝基噻唑-2-基)-2-[4-(6-氯喹喔啉-2-基氧基)苯氧基]丙酰胺(1n):反应2.0 h, 深黄色固体, 收率58.7%. m.p. 79~82 ℃; [α]_D²⁰+29.80 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.47 (s, 9H, 3×CH₃), 1.71 (d, J=6.8 Hz, 3H, CH₃), 4.97 (q, J=6.8 Hz, 1H, CH), 7.07 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.29 (s, 2H, C₆H₄-2, 6-H), 7.58~7.64 (m, 1H, quinoxalin-H), 7.68 (d, J=8.9 Hz, 1H, quinoxalin-H), 8.06 (d, J=2.1 Hz, 1H, quinoxalin-H), 8.70 (s, 1H, quinoxalin-H), 9.71 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 18.39, 28.27, 37.13, 75.09, 116.88, 123.06, 127.91, 128.62, 132.76, 132.96, 138.24, 139.75, 140.10, 147.65, 153.29, 154.95, 156.84, 157.06, 161.94, 170.99; EI-MS m/z: 527.1 [M⁺]. Anal. calcd for C₂₄H₂₂ClN₅O₅S: C 54.60, H 4.20, N 13.26; found C 54.52, H 4.10, N 13.20.

(R)-N-[4-叔丁基-5-(2, 4-二氯苄基)噻唑-2-基]-2-[4-(6-氯喹喔啉-2-基氧基)苯氧基]丙酰胺(1p):反应5.0 h, 淡黄色固体, 收率78.0%. m.p. 82~84 ℃; [α]_D²⁰+15.75 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.35 (s, 9H, 3×CH₃), 1.67 (d, J=6.7 Hz, 3H, CH₃), 4.28 (s, 2H, CH₂), 4.87 (q, J=6.7 Hz, 1H, CH), 7.05 (d, J=8.5 Hz, 3H, C₆H₄-2, 6-H, C₆H₃-6-H), 7.18 (d, J=7.7 Hz, 1H, C₆H₃-5-H), 7.23 (s, 2H, C₆H₄-3, 5-H), 7.41 (s, 1H, C₆H₃ 3-H), 7.61 (d, J=8.5 Hz, 1H, quinoxalin-H), 7.69 (d, J=8.9 Hz, 1H, quinoxalin-H), 8.06 (s, 1H, quinoxalin-H), 8.69 (s, 1H, quinoxalin-H), 9.47 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 18.53, 30.26, 30.79, 35.77, 75.32, 116.81, 122.03, 122.83, 127.29, 127.97, 128.77, 129.29, 130.77, 131.20, 132.90, 133.16, 134.28, 136.53, 137.23, 138.41, 139.89, 140.33, 147.29, 153.88, 154.36, 157.16, 169.65; EI-MS m/z: 640.1 [M⁺]. Anal. calcd for C₃₁H₂₇Cl₃N₄O₃S: C 58.00, H 4.24, N 8.73; found C 57.90, H 4.20, N 8.63.

将2.0 mmol化合物3a, 3g和3m溶于30 mL甲苯中, 分别加入0.71 g (6.0 mmol)二氯亚砜和2滴DMF, 回流5.0 h, 脱去甲苯和二氯亚砜得到酰氯.滴加该酰氯的二氯甲烷溶液到由1.0 mmol中间体2、25 mL二氯甲烷和0.1g (1.0 mmol)三乙胺组成的溶液中, 约15 min滴完, 室温反应1.0~5.0 h, 有机层经水洗, 饱和食盐水洗, 干燥, 脱溶, 粗品经柱层析[V(石油醚):V(乙酸乙酯)=7:1~5:1]得到化合物1a~1r.

(R)-N-(4-三氟甲基-5-乙氧羰基噻唑-2-基)-2-[4-(3-氟-5-氯吡啶-2-氧基)苯氧基]丙酰胺(1f):反应5.0 h, 白色晶体, 收率74.1%. m.p. 59~62 ℃; [α]_D²⁰+17.75 (c 1, CH₂Cl₂); ¹H NMR (400 MHz, CDCl₃) δ: 1.39 (t, J=7.0 Hz, 3H, CH₃), 1.68 (d, J=6.8 Hz, 3H, CH₃), 4.39 (q, J=7.0 Hz, 2H, OCH₂), 4.95 (q, J=6.8 Hz, 1H, CH), 6.98 (d, J=9.0 Hz, 2H, C₆H₄-2, 6-H), 7.14 (d, J=9.0 Hz, 2H, C₆H₄-3, 5-H), 7.51 (dd, J_F-H=9.0, 2.0 Hz, 1H, C₅H₂N-4-H), 7.87 (d, J=2.0 Hz, 1H, C₅H₂N-6-H), 9.91 (s, 1H, CONH); ¹³C NMR (100 MHz, CDCl₃) δ: 14.04, 18.14, 62.73, 74.87, 116.65, 118.58, 122.93, 124.06, 125.11, 125.29, 140.18 (d, ³J_C-F=7.0 Hz), 147.02 (d, ¹J_C-F=260 Hz), 148.17, 148.34, 151.07 (d, ²J_C-F=11.3 Hz), 153.23, 158.28, 159.20, 170.89; EI-MS m/z: 533.1 [M⁺]. Anal. calcd for C₂₁H₁₆ClF₄N₃O₅S: C 47.24, H 3.02, N 7.87; found C 47.20, H 2.92, N 7.69.

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图 1 化合物1的设计思路

Figure 1 Design strategy of compounds 1

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图式 1 化合物1的合成路线

Scheme 1 Synthetic routes of target compounds 1

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图 2 1f的单晶结构图

Figure 2 Molecular crystal structure of compound 1f

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图 3 氢键图

Figure 3 Hydrogen bonds of compound 1f

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表 1 化合物1a~1r的除草活性(抑制率/%, 1500 g/hm²)^a

Table 1. Herbicidal activities of compounds 1a~1r(inhibition rate/%, 1500 g/hm²)

Compd.	Pre-emergence treatment				Post-emergence treatments
Compd.	B.C.	A.R.	E.C.	D.S.	B.C.	A.R.	E.C.	D.S.
1a	0	10.0	100	100	10.0	35.8	15.0	10.0
1b	0	5.0	100	100	12.3	44.5	100	100
1c	0	0	100	100	25.3	0	100	100
1d	0	0	100	100	21.7	5.0	100	100
1e	0	0	100	100	15.8	15.0	100	100
1f	0	0	100	100	2.4	0	100	100
1g	0	10.0	100	100	5.0	34.1	15.0	10.0
1h	0	0	100	100	5.0	75.7	100	100
1i	0	0	87.3	100	5.0	15.0	100	100
1j	0	0	71.1	73.7	7.9	15.0	100	100
1k	0	0	99.1	100	13.8	47.1	100	100
1l	0	0	100	100	0	15.0	100	100
1m	0	0	87.3	100	0	30.6	10.0	10.0
1n	0	0	95.5	100	0	42.8	100	100
1o	0	0	76.5	98.8	0	5.0	100	100
1p	0	0	87.3	84.0	0	10.0	100	100
1q	0	0	68.4	76.1	1.2	15.0	100	100
1r	0	0	100	100	2.8	10.0	100	100
Metamifop	0	0	100	100	0	0	100	100
^a试验材料为油菜(Brassica Campestris, B.C.)、苋菜(Amaranthus retroflexus, A.R.)、稗草(Echinochloa crusgalli, E.C.)、马唐(Digitaria sanguinalis, D.S.).阳性对照药:噁唑酰草胺(Metamifop).

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