含有单取代嘧啶的新型磺酰脲类化合物的设计、合成及除草活性

2013年6月

摇

摇摇摇摇摇CHEMICALJOURNALOFCHINESEUNIVERSITIES摇摇摇摇摇

高等学校化学学报

摇1416~1422

No.6

摇摇

doi:10.7503/cjcu20120972

含有单取代嘧啶的新型磺酰脲类化合物的

设计、合成及除草活性

潘摇里,刘摇卓,陈有为,李永红,李正名

(南开大学元素有机化学研究所,元素有机化学国家重点实验室,天津300071)

摘要摇为了寻找高效的磺酰脲类除草剂,以商品化磺酰脲类除草剂为基础,将单取代嘧啶结构引入到分子中,合成了一系列新型磺酰脲类化合物,并通过1HNMR和高分辨质谱确定了其结构.采用盆栽法和平皿法测试了所有化合物的除草活性以及部分化合物对油菜的IC50值.结果表明,一些化合物具有一定的除草活性,其中化合物7b和7d对油菜和反枝苋具有较好的抑制活性.关键词摇磺酰脲;单取代嘧啶;除草活性

中图分类号摇O626.41摇摇摇摇文献标志码摇A摇摇摇摇

脱羧并与另一分子丙酮酸缩合成一分子乙酰乳酸.由于动物体内不存在AHAS酶,因此靶向AHAS酶的磺酰脲类除草剂[8~11]具有对哺乳动物低毒的特点,使其得到了广泛应用,同时具有杀菌[12~15]及抗结核病[16]等生物活性.本课题组研究发现,某些单取代嘧啶环的磺酰脲类化合物具有良好的除草活性[17,18]和抗结核病活性[19],已发展了单嘧磺隆和单嘧磺酯2个商品化药剂.为了系统研究其构效关系,本文合成了14个单取代嘧啶环的磺酰脲类化合物,并测试了其除草活性.目标化合物的合成路线见Scheme1.

乙酰羟基酸合成酶[1](AHAS)是支链氨基酸生物合成[2~7]第一步的催化剂,能催化一分子丙酮酸

Scheme1摇Syntheticroutesofthetitlecompounds

1摇实验部分

1.1摇仪器与试剂

X鄄4型数字显示显微熔点测定仪(北京泰克仪器有限公司);FTICR鄄MS(Varian7郾0T)高分辨率质

收稿日期:2012鄄10鄄26.

基金项目:国家自然科学基金(批准号:21272129)、国家“九七三冶计划项目(批准号:2010CB126106)和国家科技攻关计划项目(批准号:2011BAE06B05)资助.

联系人简介:李正名,男,教授,博士生导师,中国工程院院士,主要从事有机化学和农药化学研究.E鄄mail:nkzml@vip.163.com

摇No.6

摇潘摇里等:含有单取代嘧啶的新型磺酰脲类化合物的设计、合成及除草活性1417

谱仪;BrukerAvance鄄300MHz和BrukerAvance鄄400MHz核磁共振仪,以CDCl3或DMSO鄄d6为溶剂,1.2摇实验过程

TMS为内标.所用试剂均为市售分析纯或化学纯.

1.2.1摇中间体的合成摇2鄄氨基鄄4鄄三氟甲基嘧啶(3a)参照文献[11]方法合成,2鄄氨基鄄4鄄氯嘧啶(3b)和2鄄氨基鄄4鄄甲氧基嘧啶(6b)参照文献[20]方法合成.2鄄氨基鄄4鄄三氟甲基嘧啶(3a),m.p.171~172益值[19]:117~119益),ESI鄄MS:125郾9[M+H]+.

(文献值[11]:173~174益),ESI鄄MS:162郾1[M-H]-;2鄄氨基鄄4鄄氯嘧啶(3b),m.p.166~167益(文献值[19]:166~167益),ESI鄄MS:130郾0[M+H]+;2鄄氨基鄄4鄄甲氧基嘧啶(6b),m.p.117~118益(文献1.2.2摇目标化合物的合成及表征摇化合物4的合成:将6mmol磺胺1、12mL无水甲苯和30mmol(3郾82g)草酰氯加入装有回流冷凝管、温度计和尾气吸收装置的50mL三口烧瓶中,充分搅拌下加入温至90~100益反应12h,直到几乎无气体放出时停止反应.冷却后过滤除去不溶物,滤液减压蒸除溶剂,得到呈褐色油状物的粗品异氰酸酯2.不经提纯直接用于下一步反应.

在50mL圆底烧瓶中加入5郾8mmol嘧啶胺中间体3和20mL无水乙腈,再加入上述粗品异氰酸酯2,室温下搅拌过夜.生成大量沉淀,过滤,并用少量乙腈洗涤,固体烘干,得目标化合物4.若无沉淀生成,则将反应液减压蒸除溶剂,残余物经柱层析分离[V(石油醚)颐V(乙酸乙酯)=5颐1]得目标化合物4.

6郾6mmol氯甲酸乙酯,加热回流10h.冷却后滤除固体,减压蒸除溶剂.向残余物中加入15mL水,滤去不溶物,滤液用20%(体积分数)盐酸酸化至pH=6,有白色或淡黄色固体析出.经过滤、干燥得磺酰胺基甲酸乙酯5.

1鄄甲基鄄3鄄氯鄄4鄄甲氧基甲酰基鄄5鄄吡唑磺酰胺基甲酸乙酯(5a):m.p.130益;1HNMR(400MHz,CDCl3),啄:1郾248(t,3H,J12=7郾2Hz,COOCH2CH3),3郾917(s,3H,pyrazole—CH3),4郾173(q,2H,J12=7郾2Hz,J13=14郾4Hz,COOCH2CH3),4郾228(s,3H,COOCH3);ESI鄄FTICR鄄MS(C9H12ClN3O6S计算值),m/z:324郾0067(324郾0063)[M-H]-.

3鄄(2,2,2鄄三氟乙氧基)鄄2鄄吡啶磺酰胺基甲酸乙酯(5b):m.p.140~141益;1HNMR(400MHz,DMSO鄄d6),啄:1郾127(t,3H,J12=6郾8Hz,COOCH2CH3),4郾066(q,2H,J12=6郾8Hz,J13=14郾0Hz,COOCH2CH3),5郾035(q,2H,J12=8郾4Hz,J13=17郾2Hz,OCH2CF3),7郾734~7郾767(m,1H,Py—H5),7郾935(d,1H,JH=8郾4Hz,Py—H4),8郾304(d,1H,JH=4郾0Hz,Py—H6),11郾907(s,1H,SO2NH);ESI鄄FTICR鄄MS(C10H11F3N2O5S计算值),m/z:327郾02(327郾0268)[M-H]-.

MHz,CDCl3),啄:1郾214(t,3H,J12=7郾2Hz,COOCH2CH3),1郾452(t,3H,J12=7郾6Hz,SO2CH2CH3),COOCH2CH3),7郾285(t,1H,J12=6郾8Hz,Py—H),7郾1(t,1H,J12=7郾6Hz,Py—H),7郾9(d,值),m/z:360郾0335(360郾0330)[M-H]-.

2鄄(2鄄甲氧基乙氧基)苯基磺酰胺基甲酸乙酯(5d):m.p.97~98益;1HNMR(400MHz,DMSO鄄2鄄(乙基磺酰)咪唑并[1,2鄄a]吡啶鄄3鄄磺酰胺基甲酸乙酯(5c):m.p.143~144益;1HNMR(400化合物7的合成:向10mL丙酮中加入6mmol磺胺1和12mmol碳酸钾,搅拌下在10min内滴加

0郾1g1,4鄄二氮杂二环[2.2.2]辛烷(DABCO),然后在电磁搅拌下油浴缓慢升温至60益反应6h,再升

3郾596(q,2H,J12=7郾6Hz,J13=14郾8Hz,SO2CH2CH3),4郾114(q,2H,J12=7郾2Hz,J13=14郾0Hz,1H,JH=9郾2Hz,Py—H),9郾310(d,1H,JH=6郾8Hz,Py—H);ESI鄄FTICR鄄MS(C12H15N3O6S2计算d6),啄:1郾059(t,3H,J12=7郾2Hz,COOCH2CH3),3郾305(s,3H,CH2OCH3),3郾726(t,2H,J12=4郾8

Hz,CH2OCH3),3郾975(q,2H,J12=6郾8Hz,J13=14郾0Hz,COOCH2CH3),4郾277(t,2H,J12=4郾8Hz,Ar—OCH2),7郾111(t,1H,J12=7郾6Hz,Ar—H),7郾287(d,1H,JH=8郾4Hz,Ar—H),7郾636(t,1H,J12=8郾0Hz,Ar—H),7郾816(d,1H,JH=7郾6Hz,Ar—H),11郾672(s,1H,SO2NH);ESI鄄FTICR鄄MS(C12H17NO6S计算值),m/z:302郾0704(302郾0704)[M-H]-.

将磺酰胺基甲酸乙酯5和5郾6mmol嘧啶胺中间体6加入20mL甲苯中,加热回流8h.蒸出10mL

甲苯,再补加10mL甲苯,继续回流3h.冷却析出固体,过滤,用丙酮鄄石油醚混合物洗涤,得到目标

1418

高等学校化学学报摇摇摇摇摇摇摇摇摇摇摇摇摇摇摇摇Vol.34摇

化合物7.

72%,m.p.173益.

1鄄(1鄄甲基鄄3鄄氯鄄4鄄甲氧基甲酰基鄄5鄄吡唑磺酰基)鄄3鄄(4鄄氯嘧啶鄄2鄄基)鄄脲(4a):白色固体,产率

1

COOCH3),7郾141(d,1H,JH=5郾2Hz,pyrim—H5),8郾540(s,1H,CONH—pyrim),8郾546(d,1H,JH=5郾2Hz,pyrim—H6),12郾495(br,1H,SO2NH);ESI鄄FTICR鄄MS(C11H10Cl2N6O5S计算值),m/z:

1鄄[2鄄(乙基磺酰)咪唑并[1,2鄄a]吡啶鄄3鄄磺酰基]鄄3鄄(4鄄氯嘧啶鄄2鄄基)鄄脲(4b):淡黄色固体,产率

1

HNMR(400MHz,CDCl3),啄:3郾871(s,3H,pyrazole—CH3),4郾335(s,3H,

406郾9735(406郾9738)[M-H]-.56%,m.p.178~179益.

SO2CH2CH3),3郾613(q,2H,J12=7郾2Hz,J13=14郾4Hz,SO2CH2CH3),7郾369(d,1H,JH=5郾2Hz,pyrim—H5),7郾469(t,1H,J12=6郾8Hz,Py—H),7郾779(t,1H,J12=7郾6Hz,Py—H),7郾980(d,1H,JH=8郾8Hz,Py—H),8郾650(d,1H,JH=4郾8Hz,pyrim—H6),9郾177(d,1H,JH=7郾2Hz,Py—H),[M-H]-.

1鄄[2鄄(2鄄甲氧基乙氧基)苯基磺酰基]鄄3鄄(4鄄氯嘧啶鄄2鄄基)鄄脲(4c):白色固体,产率66%,m.p.

HNMR(400MHz,DMSO鄄d6),啄:1郾169(t,3H,J12=7郾2Hz,

10郾845(s,1H,CONH—pyrim);ESI鄄FTICR鄄MS(C14H13ClN6O5S2计算值),m/z:443郾0002(443郾0005)

130~131益.1HNMR(300MHz,DMSO鄄d6),啄:3郾098(s,3H,CH2OCH3),3郾538(t,2H,J12=4郾5Hz,1H,JH=8郾4Hz,Ar—H),7郾411(d,1H,JH=5郾4Hz,pyrim—H5),7郾672(t,1H,J12=7郾2Hz,Ar—H),7郾2(dd,1H,J12=1郾2Hz,J13=7郾8Hz,J34=1郾2Hz,Ar—H),8郾714(d,1H,JH=5郾4Hz,pyrim—H6),10郾858(s,1H,CONH—pyrim),12郾055(br,1H,SO2NH);ESI鄄FTICR鄄MS(C14H15ClN4O5S计算值),m/z:409郾0335(409郾0344)[M+Na]+.

1鄄(1鄄甲基鄄3鄄氯鄄4鄄甲氧基甲酰基鄄5鄄吡唑磺酰基)鄄3鄄(4鄄三氟甲基嘧啶鄄2鄄基)鄄脲(4d):白色固体,产CH2OCH3),4郾229(t,2H,J12=4郾5Hz,Ar—OCH2),7郾154(t,1H,J12=7郾5Hz,Ar—H),7郾277(d,

3H,COOCH3),7郾433(d,1H,JH=4郾8Hz,pyrim—H5),8郾038(s,1H,CONH—pyrim),8郾927(d,1H,JH=5郾2Hz,pyrim—H6),12郾310(br,1H,SO2NH);ESI鄄FTICR鄄MS(C12H10ClF3N6O5S计算值),m/z:441郾0003(441郾0001)[M-H]-.

165~166益.1HNMR(400MHz,DMSO鄄d6),啄:3郾824(t,2H,J12=4郾8Hz,CH2Cl),4郾400(t,2H,7郾695(t,1H,J12=7郾6Hz,Ar—H),7郾715(d,1H,JH=4郾8Hz,pyrim—H5),7郾928(d,1H,JH=8郾01H,SO2NH);ESI鄄FTICR鄄MS(C14H12ClF3N4O4S计算值),m/z:423郾0144(423郾0147)[M-H]-.

1鄄[2鄄(2鄄甲氧基乙氧基)苯基磺酰基]鄄3鄄(4鄄氯嘧啶鄄2鄄基)鄄脲(4f):白色固体,产率60%,m.p.J12=4郾8Hz,Ar—OCH2),7郾195(t,1H,J12=7郾6Hz,Ar—H),7郾294(d,1H,JH=8郾4Hz,Ar—H),Hz,Ar—H),9郾075(d,1H,JH=4郾8Hz,pyrim—H6),11郾037(s,1H,CONH—pyrim),11郾8(br,

1鄄[2鄄(2鄄氯乙氧基)苯基磺酰基]鄄3鄄(4鄄三氟甲基嘧啶鄄2鄄基)鄄脲(4e):白色固体,产率52%,m.p.

率46%,m.p.159~160益.1HNMR(400MHz,CDCl3),啄:3郾855(s,3H,pyrazole—CH3),4郾316(s,

123~124益.1HNMR(400MHz,CDCl3),啄:3郾219(s,3H,CH2OCH3),3郾687(t,2H,J12=5郾2Hz,1H,J12=7郾6Hz,Ar—H),7郾357(d,1H,JH=4郾8Hz,pyrim—H5),7郾573(t,1H,J12=8郾0Hz,Ar—H),8郾115(d,1H,JH=8郾0Hz,Ar—H),8郾357(s,1H,CONH—pyrim),8郾0(d,1H,JH=5郾2Hz,pyrim—H6),11郾494(br,1H,SO2NH);ESI鄄FTICR鄄MS(C15H15F3N4O5S计算值),m/z:419郾05(419郾02)[M-H]-.

70%.m.p.188益.1HNMR(400MHz,DMSO鄄d6),啄:2郾524(s,3H,pyrim—CH3),3郾754(s,3H,pyrazole—CH3),4郾142(s,3H,COOCH3),7郾221(d,1H,JH=5郾6Hz,pyrim—H5),8郾543(d,1H,JH=5郾6Hz,pyrim—H6),11郾272(s,1H,CONH—pyrim);ESI鄄FTICR鄄MS(C12H13ClN6O5S计算值),m/z:387郾0280(387郾0284)[M-H]-.

1鄄(1鄄甲基鄄3鄄氯鄄4鄄甲氧基甲酰基鄄5鄄吡唑磺酰基)鄄3鄄(4鄄甲基嘧啶鄄2鄄基)鄄脲(7a):白色固体,产率CH2OCH3),4郾239(t,2H,J12=5郾2Hz,Ar—OCH2),7郾026(d,1H,JH=8郾4Hz,Ar—H),7郾125(t,

摇No.6

摇潘摇里等:含有单取代嘧啶的新型磺酰脲类化合物的设计、合成及除草活性1419

56%,m.p.180~181益.1HNMR(400MHz,DMSO鄄d6),啄:2郾458(s,3H,pyrim—CH3),5郾016(q,2H,J12=8郾4Hz,J13=16郾8Hz,OCH2CF3),7郾135(d,1H,JH=5郾2Hz,pyrim—H5),7郾768~7郾800(m,1H,Py—H5),7郾921(d,1H,JH=8郾8Hz,Py—H4),8郾352(d,1H,JH=4郾4Hz,Py—H6),8郾554FTICR鄄MS(C13H12F3N5O4S计算值),m/z:390郾0492(390郾04)[M-H]-.77%.m.p.195~196益.

1

1鄄[3鄄(2,2,2鄄三氟乙氧基)鄄2鄄吡啶磺酰基]鄄3鄄(4鄄甲基嘧啶鄄2鄄基)鄄脲(7b):淡黄色固体,产率

(d,1H,JH=5郾2Hz,pyrim—H6),10郾694(s,1H,CONH—pyrim),13郾028(br,1H,SO2NH);ESI鄄

1鄄[2鄄(乙基磺酰)咪唑并[1,2鄄a]吡啶鄄3鄄磺酰基]鄄3鄄(4鄄甲基嘧啶鄄2鄄基)鄄脲(7c):白色固体,产率

HNMR(400MHz,DMSO鄄d6),啄:1郾156(t,3H,J12=7郾2Hz,

7郾161(d,1H,JH=5郾6Hz,pyrim—H5),7郾449(t,1H,J12=7郾2Hz,Py—H),7郾757(t,1H,J12=8郾0(C15H16N6O5S2计算值),m/z:423郾0559(423郾0551)[M-H]-.

SO2CH2CH3),2郾484(s,3H,pyrim—CH3),3郾615(q,2H,J12=7郾2Hz,J13=14郾4Hz,SO2CH2CH3),Hz,Py—H),7郾961(d,1H,JH=8郾8Hz,Py—H),8郾531(d,1H,JH=5郾2Hz,pyrim—H6),9郾193(d,

1鄄[2鄄(2鄄甲氧基乙氧基)苯基磺酰基]鄄3鄄(4鄄甲基嘧啶鄄2鄄基)鄄脲(7d):白色固体,产率61%,m.p.

1H,JH=7郾2Hz,Py—H),10郾972(s,1H,CONH—pyrim),13郾546(br,1H,SO2NH);ESI鄄FTICR鄄MS

169益.1HNMR(400MHz,DMSO鄄d6),啄:2郾471(s,3H,pyrim鄄CH3),3郾062(s,3H,CH2OCH3),3郾473~3郾497(m,2H,CH2OCH3),4郾194~4郾218(m,2H,Ar—OCH2),7郾139(d,1H,JH=5郾2Hz,pyrim—H5),7郾154(t,1H,J12=7郾2Hz,Ar—H),7郾265(d,1H,JH=8郾0Hz,Ar—H),7郾663(t,1H,J12=7郾6Hz,Ar—H),7郾6(d,1H,JH=7郾6Hz,Ar—H),8郾577(d,1H,JH=5郾2Hz,pyrim—H6),m/z:3郾0883(3郾00)[M+Na]+.

1鄄(1鄄甲基鄄3鄄氯鄄4鄄甲氧基甲酰基鄄5鄄吡唑磺酰基)鄄3鄄(4鄄甲氧基嘧啶鄄2鄄基)鄄脲(7e):白色固体,产率10郾566(s,1H,CONH—pyrim),12郾799(br,1H,SO2NH);ESI鄄FTICR鄄MS(C15H18N4O5S计算值),75%,m.p.183~184益.1HNMR(300MHz,DMSO鄄d6),啄:3郾741(s,3H,pyrazole—CH3),4郾005(s,3H,pyrim—OCH3),4郾091(s,3H,COOCH3),6郾756(d,1H,JH=6郾9Hz,pyrim—H5),8郾263(d,1H,JH=6郾9Hz,pyrim—H6),11郾518(s,1H,CONH—pyrim),13郾855(br,1H,SO2NH);ESI鄄FTICR鄄MS(C12H13ClN6O6S计算值),m/z:403郾0230(403郾0233)[M-H]-.

1鄄[3鄄(2,2,2鄄三氟乙氧基)鄄2鄄吡啶磺酰基]鄄3鄄(4鄄甲氧基嘧啶鄄2鄄基)鄄脲(7f):白色固体,产率74%,

m.p.173~174益.1HNMR(400MHz,DMSO鄄d6),啄:3郾937(s,3H,pyrim—OCH3),5郾023(q,2H,1H,Py—H5),7郾919(d,1H,JH=8郾4Hz,Py—H4),8郾350(d,1H,JH=4郾0Hz,Py—H6),8郾398(d,MS(C13H12F3N5O5S计算值),m/z:406郾0433(406郾0438)[M-H]-.

1

J12=7郾2Hz,J13=15郾6Hz,OCH2CF3),6郾678(d,1H,JH=4郾0Hz,pyrim—H5),7郾759~7郾803(m,

1H,JH=4郾0Hz,pyrim—H6),10郾710(s,1H,CONH—pyrim),13郾042(br,1H,SO2NH);ESI鄄FTICR鄄82%,m.p.191~192益.

1鄄[2鄄(乙基磺酰)咪唑并[1,2鄄a]吡啶鄄3鄄磺酰基]鄄3鄄(4鄄甲氧基嘧啶鄄2鄄基)鄄脲(7g):白色固体,产率

HNMR(400MHz,DMSO鄄d6),啄:1郾167(t,3H,J12=7郾2Hz,

6郾710(d,1H,JH=6郾8Hz,pyrim—H5),7郾347(t,1H,J12=7郾2Hz,Py—H),7郾654(t,1H,J12=8郾0(C15H16N6O6S2计算值),m/z:439郾0502(439郾0500)[M-H]-.

SO2CH2CH3),3郾667(q,2H,J12=7郾2Hz,J13=14郾8Hz,SO2CH2CH3),3郾987(s,3H,pyrim—OCH3),Hz,Py—H),7郾876(d,1H,JH=8郾8Hz,Py—H),8郾253(d,1H,JH=6郾8Hz,pyrim—H6),9郾146(d,

1鄄[2鄄(2鄄甲氧基乙氧基)苯基磺酰基]鄄3鄄(4鄄甲氧基嘧啶鄄2鄄基)鄄脲(7h):白色固体,产率77%,

1H,JH=7郾2Hz,Py—H),11郾323(s,1H,CONH—pyrim),13郾609(br,1H,SO2NH);ESI鄄FTICR鄄MS

2H,CH2OCH3),3郾952(s,3H,pyrim—OCH3),4郾192~4郾218(m,2H,Ar—OCH2),6郾681(d,1H,7郾666(t,1H,J12=7郾2Hz,Ar—H),7郾1(d,1H,JH=7郾6Hz,Ar—H),8郾434(d,1H,JH=5郾6Hz,JH=6郾0Hz,pyrim—H5),7郾151(t,1H,J12=7郾6Hz,Ar—H),7郾267(d,1H,JH=8郾4Hz,Ar—H),

m.p.141~142益.1HNMR(400MHz,DMSO鄄d6),啄:3郾075(s,3H,CH2OCH3),3郾466~3郾493(m,

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pyrim—H6),10郾566(s,1H,CONH—pyrim),12郾794(br,1H,SO2NH);ESI鄄FTICR鄄MS(C15H18N4O6S1.3摇除草活性测试

计算值),m/z:381郾0872(381郾0874)[M-H]-.

采用油菜平皿法和盆栽法[21~25]对14个化合物进行了除草活性测试,并以商品除草剂醚磺隆、醚苯磺隆和单嘧磺酯作为对照药剂.

盆栽法:在直径为8cm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,幼苗出土前以塑料布覆盖.每天加以定量的清水以保持正常生长.测试植物为油菜(Brassicanapus)、反枝苋(Amaranthusretroflexus)、稗草(Echinochloacrusgalli)和马唐(Digitariaadscendens).施药方法为喷施,处理21d后调查结果,测定地上部分鲜重,以鲜重抑制百分数来表示药效.

平皿法:实验靶标为油菜.在直径为6cm的培养皿中铺好一张直径为5郾6cm的滤纸,加入2mL一定浓度的供试化合物溶液,待测药剂至少配制4至5个浓度,每个浓度重复4次,以清水为对照.播种浸种4~6h的油菜种子15粒,于(30依1)益下,黑暗培养48h后测定胚胎长度.与空白对照比较,计算抑制百分率.采用DPS数据处理系统(8郾01版)数量型数据机值分析法计算得到IC50值.

2摇结果与讨论

2.1摇合摇成

由于氯原子和三氟甲基的吸电子作用可使嘧啶环2位上的氨基严重钝化,导致反应活性降低,无法与胺基甲酸乙酯发生氨解反应,但可与异氰酸酯发生亲核反应.因此,在合成目标化合物4时采用了异氰酸酯法.由于2鄄(乙基磺酰)咪唑并[1,2鄄a]吡啶鄄3鄄磺酰胺和3鄄(2,2,2鄄三氟乙氧基)鄄2鄄吡啶磺酰胺不能与光气或三光气反应生成相应的磺酰异氰酸酯,所以在制备目标化合物7时,采用氨基甲酸乙酯的方法进行脲桥的合成.2.2摇生物活性

目标化合物4和7对双子叶杂草油菜和反枝苋及单子叶杂草稗草和马唐的生物活性测定结果列于表1~3.

Table1摇Inhibitionsofcompounds4and7byPotPlantTestagainstweedsat375gai/ha*

Compd.4a4b4c4d4e4f7a7b7c7d7e7f7g7h

Monosulfuron鄄esterCinosulfuronTriasulfuron

Brassicanapus000088.684.372.995.111.197.846.380.58.491.9100100100

0010.016.820.69.242.010017.490.217.859.79.266.0100100100

Amaranthusretroflexus10.000020.0057.197.6095.315.057.1061.4100100100

15.015.060.810.060.820.045.595.565.310044.374.420.073.3100100100

Inhibition(%)

Echinochloacrusgalli000000029.4074.50000100100100

0010.015.020.00047.220.071.1010.010.00100100100

Digitariaadscendens0015.000010.05.080.020.0010.00100100100

0010.00015.000054.310.0000100100100

SoiltreatmentFoliagespraySoiltreatmentFoliagespraySoiltreatmentFoliagespraySoiltreatmentFoliagespray

15.0

摇摇*gai/ha:Gramsofactiveingredinetoftheusedherbicideperhectare.

摇No.6

摇潘摇里等:含有单取代嘧啶的新型磺酰脲类化合物的设计、合成及除草活性1421

Table2摇Inhibitionsofcompounds7band7dbyPotPlantTestagainstweedsat15,7.5and3.75gai/ha*

Compd.7b

Dosage/(gai·ha)

-1

7d

3.753.753.753.753.757.57.57.57.515

7.5

15

Soiltreatment

30.0

Brassicanapus

Inhibition(%)80.029.219.34.70.092.610010056.852.8100100

FoliagespraySoiltreatment

30.9

Amaranthusretroflexus

Foliagespray

30.2

85.00.0a96.381.298.288.279.71005.2

a

10.90

Monosulfuron鄄esterTriasulfuronCinosulfuron

86.127.694.499.475.5100

53.426.583.629.448.027.0

摇摇*Thedruginjuryoccurredwhenthestemsandleavesbecamebigger,sothetitlecompoundshadlittleactiononthefreshweight.

Table3摇IC50valuesofcompounds7band7dbyPetriDishTestagainstBrassicanapus

0.44757b

0.45987d

Monosulfuron鄄ester

0.0078

Triasulfuron0.0102

Compd.

摇摇从表1的375gai/ha剂量的初筛结果可见,大部分化合物对双子叶作物的除草活性明显高于单子叶作物.化合物4e,4f,7b,7d,7f和7h对油菜具有较好的抑制活性.化合物7b和7d对反枝苋具有较好的除草活性,同时化合物7d还对两种单子叶杂草具有较好的抑制活性.从表1中的活性规律可以看出,嘧啶4位取代基为给电子基团(甲基、甲氧基)时,除草活性要优于吸电子基团(氯原子、三氟甲基).表2的降低浓度复筛结果表明,化合物7b和7d在降低浓度后,活性有所下降,虽然化合物7d对油菜的土壤处理表现出明显的磺酰脲药害症状,但是抑制活性仍然不好.对化合物7b和7d进行了IC50值测定(表3),这两个化合物的IC50值与对照药醚苯磺隆以及醚磺隆相差一个数量级,说明这两个具有一定除草活性的结构还需要进一步优化,以寻找活性更佳的磺酰脲类除草剂.

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Design,SynthesisandHerbicidalActivityofNovelSulfonylureas

ContainingMonosubstitutedPyrimidineMoiety

(StateKeyLaboratoryofElemento鄄organicChemistry,ResearchInstituteofElemento鄄organicChemistry,

NankaiUniversity,Tianjin300071,China)

PANLi,LIUZhuo,CHENYou鄄Wei,LIYong鄄Hong,LIZheng鄄Ming*

Abstract摇Sulfonylureas,auniquegroupofherbicides,wereextensivelyappliedtocontrollingarangeofweedsinavarietyofcropsandvegetables.Inordertofindefficientsulfonylureaherbicides,thetitlecom鄄skeletons.Aseriesofsulfonylureacompoundsweresynthesizedandcharacterizedby1HNMRandHRMS.poundsweredesignedbyintroducingmonosubstitutedpyrimidinaminesintosomewell鄄knownsulfonylureaHerbicidalactivitiesandIC50valuesofthetitlecompoundsweredeterminedbyPotplanttestandPetridishtestagainstBrassicanapus,Amaranthusretroflexus,EchinochloacrusgalliandDigitariaadscendens.SomeagainstBrassicanapusandAmaranthusretroflexus.Furtherstructuralmodificationofnovelsulfonylureascon鄄tainingmonosubstitutedpyrimidinemoietywillberequiredforimprovingefficacyagainstweedsinourlab.Keywords摇Sulfonylurea;Monosubstitutedpyrimidine;Herbicidalactivity

(Ed.:P,H,N,K)

compoundsexhibitedherbicidalactivities.Compounds7band7dpossessedsignificantinhibitioneffects