現(xiàn)代有機合成

1、近 代 有 機 合 成主講：主講： 翁玲玲翁玲玲comtemporary organic synthesis 有機合成化學(xué)既是一門基礎(chǔ)理論學(xué)科，又是一門與實踐密切有關(guān)的應(yīng)用性科學(xué)，并且與其它相關(guān)學(xué)科也不著緊密的聯(lián)系。有機合成的迅速發(fā)展與新理論、新反應(yīng)、新試劑和新技術(shù)有密切關(guān)系。 “近代有機合成”課程，是反映當(dāng)代有機合成進展的一門專業(yè)課程。通過學(xué)習(xí)了解近代有機合成的思路和手段、新型反應(yīng)的發(fā)展、新試劑的特點及其應(yīng)用等方面知識。 增強有機合成知識，開闊思路，提高有機合成的技巧，培養(yǎng)他們在從事新化合物的設(shè)計和合成、天然化合物的結(jié)構(gòu)改造、合成工藝路線的選擇和改進等工作中具有分析問題、解決問題的獨立工作能

2、力，為進一步從事科研和教學(xué)工作奠定較為扎實的基礎(chǔ)。 cooch3oc2h5cooooch3h3coooocoohohohohooohoh綠綠原原酸酸rcocl+c(cooc2h5)2rhrcoc(cooc2h5)2rrcoclc(cooch2ph)2rh+rcoc(cooch2ph)2rrcoch2rh2 / pd-c（除除r r = =h h) )( (甲甲酯酯衍衍生生物物）( (乙乙酯酯衍衍生生物物叔叔丁丁酯酯）rch(co2ch2ph)2oh-oh-_ocoohch2phocooc2h5ch2phocooch2phch2phohh2/pdcoohcoohphch2ocoohch2phcc

3、l3ch2o2cch(ch2)3conhnhco2ch2ccl3hnoshch2ococh3co2ch2ccl30 c , znph3cnhchco2c(ch3)3nhsco2ch2phch3ch3hcl/ch2cl2/c。0 ph3cnhchcoohnhsco2chphch3ch3dccph3cnhchcnhsco2chphch3ch3oh2/pdchnscoohch3ch3oph3cnhh3o+chnscoohch3ch3oh2nhccccchcch(chch)2ch2cooh菌菌霉霉素素(chch)4cooch3ncccchccccchcch(chch)2ch2cooc(ch3)3潛在功

4、能基latent functional group消毒防腐藥消毒防腐藥利凡諾利凡諾(ch3co)2o/ch3cooc2h5o2nchcnhcoch3ohhch2oho2nchcnh2hohch2ohh2nchcnhcoch3ohhch2ohh2,pd(caco3)重氮化h2noc2h5,cuso4ch3no2ch3no2clno2clcoohcl2,fecl3kmno4 , oh-cooho2nnhoc2h5pocl3no2noc2h5clnh4ohno2noc2h5nh2noc2h5nh2h2nfe,hclnoc2h5nh2h2nh3chohcoohch3ch(oh)cooh胃胺胃胺ch2c

5、nchcnbrchcnbr2alcl3,c6h6ccnch2chch3nch3ch3ccoohch2chch3nch3ch3nh3 h2so4cconh2ch2chch3nch3ch3cconh2ch2chch3nch3ch3ororooorch3ohoch ch2oorch3ooorch3orooorch3ooch3oohooh一、末端雙鍵成單羰基化合物（或二醇）zzch2zoohoooclch2ohooocro3/pyooooch2brmgccoc2h5oooohccoc2h5ch2dil.h2so4oooccoc2h5och2ooochcoohch2nabh4oochcoohhoch2o

6、och2coohhoch21、甲代丙烯基作為潛在的丙酮基可的松可的松18,19-雙去甲孕甾酮雙去甲孕甾酮lialh4ooch2ch2ohhoch2tsohooch2ch2otshoch2oso4/hio4ooch2ch2otsooch3onaooooch3ooch2ch3och2otsch3oootsch3oooooacmgbrooacomgbrh2oooacohoacoooch3ioh_oo3oooh_ooacoacoho去氧羅漢松酸（去氧羅漢松酸（deoxypodocarpic acid）c6h5oclc6h5och3ioc6h5ooc6h5och3ic6h5och3clc6h5och2c

7、h31. m-clc6h5co3h2. hio4c6h5och3ot-buokt-buokch3c6h5oseo2hoacch3c6h5ooh2o2ch3ohoch3c6h5ooc6h5coohch3hch2coohppacoohch3ho2、丙烯基作為潛在的乙酸基刺酮生物堿刺酮生物堿nch3och3o 1. kmno42. ch2n2nch3och3oco2ch3h3cco2onch3och3ooohonanh3et2och3och3ooch3och3oolahch3och3oohac2opych3och3ooacch3och3ooacchoag2o,ohch3och3oohcoohoso4

8、hio4ch3och3oohhnch3ch3och3onch31.?；?.胺化3.還原3、丙烯基作為潛在的醛基橋狀天然產(chǎn)物生物堿生物堿veatchine和和garryine合成的中間體合成的中間體1.b2. xon buschon buschohooso4hio4ochob or hohoon-buschacnx2.1.bon buschacnohoacnoso4hio4oacnchooh or hohoacnaconitine中間體中間體貝殼松貝殼松-16-烯烯-19-酸中間體酸中間體atisine全合成全合成rooch3oohroch3r=ch3r=(ch3)3chchoch3obzchs

9、bu noch3ch3o2coch3ch3o2cohch3hoch3ohoch3hoch3oohcch3hoch3oho二萜生物堿類合成二萜生物堿類合成ooch3brooch3och3holi nh3och3hoo3 jonesoch3ohchohclhoch3ohom.p. 233。cohoch3oohoch3ohookohohm.p. 205。coch3hoochoochoch3hooso4 pyochoch3hohohopb(oac)4kohochohchoochhohoochhoaco1.nabh42.ac2oochhacoacoo3ohacoacoca nh3ohacowolff k

10、ishnerhhocro3 pyhooch3och3hoocoroocohoh2coohcohchcoacoo3ohcowolff kishneroch3ch3oho2c1.2. h2omgbrho2choohooso4 hio4choohoohhooooooo赤霉酸中間體赤霉酸中間體h2cco2ch3cho1.2. oso4nhnh2nhnoohohhio4nhnohoh2c dmso dccnhnohoch2onnoohhoh2cnhnoohcnnoho洪達木（洪達木（hunteria）、白堅木（）、白堅木（aspidospermia）生物堿合成）生物堿合成bzoco2c2h5bzoco2

11、ch3ch2bzoco2ch3onhnh2nhnobzo(ch2)3二、內(nèi)部雙鍵成雙羰基化合物r2r1r3r4r1r2r3r4r1r2r3r4oo1、環(huán)己烯到環(huán)戊烯醛（羥基醛）斑蝥素（斑蝥素（cantharidin）的全合成）的全合成r2r1r2r1ohohchochor2r1r1r2choco2ch3co2ch3ooco2ch3co2ch3och2ohch2ohch3so2cloch2oso2ch3ch2oso2ch3c2h5sk/t buohoch2sc2h5ch2sc2h5oso4och2sc2h5ch2sc2h5ohohraney nic2h5ohrefluxoch3ch3ohohpr

12、oxyl acidor hio4och3chochoch3dioxaneheatingoch3ch3cho藜蘆生物堿藜蘆生物堿oorohoh3c1.oso42.me2cohoh3coohohohohohochoacooch3hooch3choho可的松全合成可的松全合成赤霉酸類赤霉酸類acoroacacorohchooacr=h or oac2、甲基環(huán)己烯到乙酰環(huán)戊烯18，19-雙去甲孕甾酮雙去甲孕甾酮choochooooooch3oohh重重排排ch3ohch3ohooohch3ohohch3och3mgbrh2ohch3oohch3h2ohch3och3oho16-去氫孕甾酮去氫孕甾酮康絲

13、堿（康絲堿（conessine）全合成）全合成ch3ooch3oocch3och3oochhacohhacooohhacoohhhchohhhooohoohh3、環(huán)合成雜環(huán)利血平中間體利血平中間體五環(huán)吲哚衍生物五環(huán)吲哚衍生物oco2rchonronhrchochonhrnrchohhooacch3o2cchohhoacch3o2coch3ch3o2cnhhoacch3o2coch3nhonhhoacch3o2coch3nh育亨賓育亨賓hhco2ronhnhhhoonhohcnohho士的寧士的寧nhohnnhohnchochonhonchooh阿嗎靈的四環(huán)中間體阿嗎靈的四環(huán)中間體nhnh2ch

14、2ohnhnhch2ohchohonhnhch2ohcho4、苯酚醚及二氫苯酚醚裂解成酯士的寧全合成士的寧全合成nhoch3och3nhoch3och3ntsco2ch3nco2ch3co2ch3ntsco2ch3acnco2ch3ntsco2ch3onco2ch3ntsco2ch3ononacoco2ch3nonacco2ch3ohnrh3coch3nco2ch3ach3conh3coo石松子堿石松子堿三、酮的裂解1、環(huán)己酮轉(zhuǎn)變?yōu)榄h(huán)戊酮oc6h5choochc6h5ch3iko bu tochc6h5kmno4 適量oocoohcoohkmno4過量 baodistoch3ooch3ooch

15、ohcoohcoohch3och3oohhh花側(cè)柏烯花側(cè)柏烯(cuparene)ch3ooch3oocooch3cooch3ch3odieckman水解脫羧ch3ooch3oh3coalcl3ch3oo甲基化ch3oooch3oocho3coohcoohch3o2、a-羥基酮裂解為醛酸cnoomichealoocnnabh4ocnohocnoo1.o2.水解 ocnohnaio4chocncoohchooo假荊芥內(nèi)酯（假荊芥內(nèi)酯（dl-nepetalactone）oochc6h5chc6h5ohoohcoohchocoohcohhooc6h5oo84%nabh4c6h5ohoh2, pd -c

16、hoacc6h5ohocro3 haccooh coohc6h5hppahhooco羅漢松酸（羅漢松酸（podocarpic acid）3 3、二酮類裂解成二羧酸、二酮類裂解成二羧酸酸甾酮酸甾酮hohhooonaomehohhoocnohohhocoohcoohcoohhohhooocnhohcoohcoohoohohotsooohohooocnooocoohcoohseo2hio41.ch2n22.lialh4ch2ohch2ohch2otsch2ots四、酚醚作為潛在功能基1、酚醚還原成環(huán)己烯酮甾體合成：還原芳香甾體合成：還原芳香a環(huán)合成環(huán)合成19-去甲甾體去甲甾體ororooorohro

17、ohroohoohooroo1.炔化2.水解ohocchoo孕孕甾甾酮酮甾體全合成甾體全合成b、c、d三環(huán)中間體三環(huán)中間體ch3ooch3ooohhoohhoch2orch3oorch3ochohrch3oonchocnnh2oh.hclorch3ocnrch3ocooch3och3ikobu tstobberch3ocooch3ohrch3ocoohohnabh4 co2rch3oohrch3oohrohoh2,pd c甾體甾體a、b、c三環(huán)化合物三環(huán)化合物rch3oohohrooohoooch3ooch3ooch3hooch3hooch3hhohhopd ch2制備制備18-去甲高甾體去甲

18、高甾體2、酚醚還原用于三環(huán)萜合成a a-芒柄花萜醇（芒柄花萜醇（ a a- onocerin）ohhoch2ch2rabcooch3ooch3ooch3h2,pd cooocooho咖咖薩薩因因酸酸( (cassaic acid) )瑞瑞牧牧烯烯(rimuene)非非洛洛克克烯烯(phyllocladene)hoooohhhho貝克松烯（貝克松烯（kaurene）全合成萜類生物堿：加山萸堿及維特欽全合成萜類生物堿：加山萸堿及維特欽och3co2meooch3co2meco2meooch3ooco2meoch3co2meoch3onacnacoch3onacnaco3、酚制得螺環(huán)化合物33，2

19、2，1-1-二環(huán)辛烷中間體二環(huán)辛烷中間體x=br,otsxohxooohotsohohcloooooohhoohbrbroothpoothp松香烯全合成松香烯全合成ohohch3mgbrorch3lianhydrousformic aciaohcooch3brcooch3ocooch3okobu thobu th2,pd cohcooch3ocooch3oocooch3obro/hch2cl2och3cooch3ohcoohh2,10%pd c48%hbrhoacch3oh/hcloch3ch3cobrch2chchcooch3och3cchchchcooch31.zn2.h3o3. h2o(

20、h )五、雜環(huán)作為潛在雙功能基1、呋喃環(huán)作為潛在的雙羰基化合物氫化漆酚（氫化漆酚（hydrourshiol）全合成）全合成ooooch3och3hohoooohohor2r1or2och3r1ch3oor2och3r1ch3or2r1ooohohn c15h31ocooch3ooch3och3cooch3ooch3och3coc16h33 nn c16h33mgbr順式茉莉酮（順式茉莉酮（cis-jasmone）全合成）全合成oh3ccho(c6h5)3pchc2h5oh3clibroh3ch3cohohh3coovtb6的合成的合成nohonhacnh2hooonhacch3ooch3oac

21、och2ch2oacnhacoacoch2ch2oacnhacch3ohoch3nhoch2ch2ohohch3oeto2cccco2etoco2etco2etoeto2cco2etorooc(ch2)6ohal2o3異構(gòu)化(ch2)6coobu toohooh(ch2)6coobu tch(ch2)6coot buoohhohoho(ch2)6coobu t多聚磷酸重排oliohc(ch2)6coot buch(ch2)6coot buooh利用呋喃開環(huán)反應(yīng)，方便地合成了前列腺素利用呋喃開環(huán)反應(yīng)，方便地合成了前列腺素e1的前體的前體2、吖內(nèi)酯作為潛在酰胺oco2rro2crohnhcoc6h

22、5nooc6h5nooc6h5rnooc6h5rco2roro2c(ch3)3climicheal丙酮二羧酸ooclch3och3ch3o2cocooch3ohnhcc6h5sclch3och3ocorohnhcc6h5sohoooclch3och3chonsc6h5oooclch3och3nxc6h5obasicpb(oac)4thfhclhydrolysis(ch3)2so4thfch3i/thfrtn(ch3)2nhcc6h5scsch3hnc6h5inh3 clohoohohoh3chhohohn(ch3)2conh2ohsnoc6h5och2och3oooh3cchohch3o2cc

23、onh2oooch3ch3oooohohoconh2nhcc6h5soooch3och3oooch3och3chochooooch3och3cooho3chooooch3och3choooch3ch3ooosodiumcarbonatensc6h5oooch3ch3ooonsc6h5och3o2cconh2ocyclopenine全合成全合成nh2hnoco2rcharhnnhoocharnono2onono2ocharno2hnoco2rcharchonaoch33、噻唑作為潛在四碳單元 srr srr3s2omemesmemessmememememememephmemephmeshomep

24、hmesmephmemephmeraney ninischch2ch2rrch3raney nirch2ch2ch2ch2rnis70%h2so4raney ni70%h2so4乙基丙基丁基己基甲烷乙基丙基丁基己基甲烷scoc2h5c3h7scc2h5c3h7sscc2h5c3h7sch3coscc2h5c3h7sc2h5scc2h5c3h7sc2h5chocc2h5c3h7c2h572%h2so4ac2ohclo4h2nnh2kohdmf pocl3raney ni巴拿馬蟻重要組分巴拿馬蟻重要組分3，7，11-三甲基三十一烷制備三甲基三十一烷制備(ch2)15ch3s(ch2)15ch3oh

25、coclcoohooocooho h2oraney nimemgis(ch2)15ch3amdt eisten反應(yīng)還原烷基化開環(huán)s(ch2)15ch3o大環(huán)烴的合成大環(huán)烴的合成s(ch2)4meoco(ch2)4comeos(ch2)4(ch2)4hoo(ch2)4(ch2)4hoonasssssscoch3coch3(ch2)12ch3cocch3o(ch2)12cocohooh1.naocl2.ni多酮衍生物多酮衍生物4、異噁烷為潛在環(huán)己烯酮孕甾酮的合成孕甾酮的合成noch2clr2r1oonr2r1ohohnr2r1ooor2r1ooor2r1or1naoetpd c h2ohoonoc

26、loooonooooonoohoooohoooohoohoohh甾族化合物的合成甾族化合物的合成noclnoonooohnooonoohonooonooooonopph3clph3pch2soch32-甲酰基二氫吡喃h3o(a)cro3(b)h2 pdmgcl(a)h(b)h(c)oh(d)hooch3(a)h2 pd(b)oh對異噁唑進行適當(dāng)?shù)母脑?，可制得多酮對異噁唑進行適當(dāng)?shù)母脑欤芍频枚嗤猲och2rrch2rch2ch2roo(a)h2/pd(b)h3omeomeooooonoch2lich3noch2cch2ch3oonoch3noch3oco2me異噁唑的環(huán)化性能可構(gòu)成芳環(huán)異噁唑的

27、環(huán)化性能可構(gòu)成芳環(huán)onoetoonclonoonoetonetohohonetohohohnetohohoho etnh22h2o用這個方法類似的制備了二氫菲和八氫菲的衍生物用這個方法類似的制備了二氫菲和八氫菲的衍生物nooohoa.meib.naohnoohhohoa.et3n,bf4b.naoh異噁唑環(huán)轉(zhuǎn)化為吡啶環(huán)異噁唑環(huán)轉(zhuǎn)化為吡啶環(huán)nhooonoonhooohh2,pd cet3nohoohnhoonh2nhohoooncloonh2,pd cet3nnooh5、二氫噁唑為潛在羧基onch3onararhooc97%archoh rcoohh2nhonor h2oh3oonch2ch3a

28、rchoh onarch3arhoocch392%ph cl ohoocch3(99%)o cl phchophn(ch3)2 phoocch3(80%)p (me2n) phbrcoohonbrmget2oh2nohonmgbrbronhooconhoohooch3o h3o rcoohh2nohonri onrmert buyield86%78%95%phonrrchonabh4h mei格氏試劑grignard reagents一、reactions：制備烴、醇、醚、酸及其它有機金屬化合物1、與含活潑氫化合物反應(yīng)生成烴類hoc2h5rhmg(oc2h5)xc6h5ohrhmg(oc6h5

29、)xc2h5shrhmg(sc2h5)xch3coohrhmg(ococh3)xhcchrhmgxcchch3conh2rhmgxnhcoch3hnh2(hnhch3、hn(ch3)2)rhmg(nh2)xhohrhmg(oh)xhxrhmgx22、與有機鹵代物反應(yīng)生成碳原子數(shù)較多的烷、烯烴等rxrrmgx2ch2chch2xrch2chch2mgx2ch3cohocohrrh3cmg(oh)xrcoonaconaomgxrrcorrmg(oh)xnaohh2orchoochohochomgxrchomgxomgx rhrmgxh2o 2mg(oh)x h2o3、與羧酸（無水）及羧酸鹽反應(yīng)生成

30、叔醇、醛、酮等4、與環(huán)氧乙烷類反應(yīng)生成伯醇5、與亞硝基或硝基化合物反應(yīng)生成胲ch2och2ch2ch2omgrx rch2ch2omgxrch2ch2ohh2o mg(oh)xrch2no2rrchnr(oh)rnorrnomgxrrnohh2o mg(oh)x6、與甲醛（或其它醛類）反應(yīng)生成醇類hchorch2omgxrch2ohmg(oh)xh2orchorrchohrcorrrrcoh7、與co2、cs2、so2反應(yīng)生成羧酸、硫羥羧酸、亞磺酸等8、與o2、s反應(yīng)生成醇、硫醇9、與酸酐反應(yīng)co2rcoomgxrcoohh2ocs2rcsshso2rsooh1/2o2romgxrohh2os

31、rsmgxh2orsh（ch3co)2och3cromgxococh3ch3coomgxch3corh2och3coohmg(oh)x10、與腈類、異腈反應(yīng)生成醛、酮11、與酰胺反應(yīng)生成烴、醛、酮等hcnrchnmgxrchnhrchorcnrcorrncrncomgxrrnchrh2orchornh2hcnr2orchomgxnr2rchorconh2rrcomgxnh2rhrrcorcon(r)2rrcomgxnr2rrco12、與酯反應(yīng)生成醇、醛、酮等hcoorrchomgxorrchoromgxrohrchromgxrmgxromgxr2chohrohrcooc2h5rrcomgxoc

32、2h5r2rcohrmgxh2orrcoclcooc2h5rcomgxoc2h5clrcoc2h5omgclxrcoohh2o c2h5ohhc(oc2h5)3rch(oc2h5)2rchoh2oh+ oc(oc2h5)2同上13、與酰鹵反應(yīng)生成醇、酮等ch3coclrcch3omgxclrcch3orrcomgxch3rmgx mgxclr2cohch3h2o4c2h5mgcl2pbcl2(c2h5)4pb4mgcl2pb3c6h5mgbrsbcl3(c6h5)3sb汽油抗震劑4ch3mgclsncl4(ch3)4sn2 ch3mgclsicl4(ch3)2sicl2(ch3)2si(oh)

33、2sich3ch3on硅橡膠14、與無機鹵化物反應(yīng)two quotations he who knows and under- stands grignard reactions has a fair grasp of organic chemistry. every chemist has carried out the grignard reaction at least once in his life time.1、methods of activation1.1 iodine-activated magnesium turnings (mg/i2)a. one of the earl

34、ist catalysts.b. a simplified and convenient.c. safe and large scaled.formation of the grignard reagent by heating.mgi2mgi2mgmgi22mgirxmgir xmgixmgimgmgimgxr mgxrmgxpreparation of iodine activated magnesium5gmgn2benzene100ml2.5gi2ether5mldist.solvents5mincooleddrystore150 160。c1.2 activated magnesiu

35、m by entrainmentto provide continuous activation of the metal surfacech2brch2brmgbrmgch2ch2brh2cch2mgbr2clcooh1.mg/brch2ch2br,35。c2.co21.mg/c2h5br2.co256%16%clclclclclcl1.mg/brch2ch2br,35。c2.co271%clclcoohclclclothers was usedin noreactionprocedure:1 naphthoic acid1 chloronaphthalenedissolved in dry

36、 ether50mlmgn2reflux1,2 dibromoethanein dry etherdry ice 10%hcldisadvantage:1.formation of a second grignard reagent2.undesired by productsentrainer:methyl iodide, ethyl bromide, 1,2 dibromoethane1.3 finely powdered activated magnesium increasing the surface area of the magnesiummgx22kmg(activated)2

37、kik , na .a.magnesium chloride is commerially available.b.the best ratio of magnesium chloride to potassium is between 1.01:1 and 1.05:1 .c.the best solvent is tetrahydrofuran . other solvents such as diglyme , dimethoxyethane ,triethylamine and benzene can also be used .brcl1.mgcl2/k , 78。c2.co260%

38、1.mgcl2/k , 25。c2.co262%(low temperature)coohat r.t. ordinary mgcan not react with clmg, 25。cn c5h11ch2f1.mgcl2/k , 66。c2.nh4cl71%n c5h11ch3unreactived. the addition of a metal salt to the system further increases the reactivity. ki is best and the amount varied in different reaction . h3ccl1.mgcl2/

39、k/ki ,25。c2.nh4cl100%h3c1.mgcl2/k , 25。c2.nh4cl50%n c5h11ch2f1.mgcl2/k/ki , 25。c2.co288%n c5h11ch2coohbrbr2.nh4cl1.mgcl2/k/ki ,25。c100%di grignard reagent2、application2.1 aliphatic halides2.1.1. primary halides n c7h15ch2brn c7h15ch2cooh1.mgcl2/k,25。 ,5(100%)c2.co281%nnh3c(ch2)3cl2.so1.mg/brch2ch2br

40、,66。,(3 7h) (mg 80h)cnnh3c(ch2)3shoh3c(ch2)9brothp1.mg/brch2ch2br,35。c2.ochooh3c(ch2)9othpoh63%och3ooocooch3macrolideantibiotic60%n c5h11ch2f1.mg/brch2ch2br,35。,7.5hc89%88%71%1.mgcl2/k/ki,25。 ,3hc2.nh4cl2.nh4cl1.mgcl2/k,66。cn c5h11ch3ch2cc6h5ch2ch2cl1.mg/brch2ch2br,35。c2.co2ch2cc6h5ch2ch2coohch2cch(

41、ch2)3clchh2ch3cch2clch3ch3cch2clooh3ch3cch2iall failed to gr2.nh4cl61%2.2 secondary halidesbr1.mg/brch2ch2br,35。c2.co225%coohordinary magnesium give a less satisfactoryyieldch3ch3br1.mgcl2/k,25。c2.(ch3)2co48%ch3ch3cohch3h3cwith ordinary magnesiumwartz like coupledproductch3hoch3nclthf,reflux1.mgcl2/

42、k,66。c2.h3o 12%intramolecularch3hoch3n烏頭生物堿ordinary magnesiumonly recovered thestarting material.clclooch3ooch31.mgcl2/k2.h3o oo35%ooch3ooch3di grignard reagentstandard methodfailed to generatethe di grignard reagent2.3 tertiary halidescl1.mgcl2/k,66。c2.co263%hooclithium salt 51%ordinary magnesiumno

43、t readily formedbr1.mg/brch2ch2br,66。c2.h3o76%use of ethylbromide failed toyield the g.r.t c4h9cl1.mgcl2/k,25。c2.co252%t c4h9coohbrhooch3cco2ch3i2.4 allylic halidesch3ch2cch2cl82%1.mgcl2/k,25。 ,10c2.co2ch3ch2cch2coohordinary magnesium10h,15。 ,40%ccl82%1.mgcl2/k, 60。 c2.co2coohordinary method 10。,55%

44、cch3ch3cchch2brmg1.mgcl2/k, 20。 c2.ch3ch3cchchoch3ch3cchch2mgbrh2cch3h3cch3ohch3h3cch3brmgch2rearragement69%ch3ch3cchch2brcn(ch3)3sioo1.mgcl2/k, 22。 c2.nh4clcn(ch3)3siohoh3cch3ch2agf/h2ohoh3cch3ch2o3,3 sigmatropichooh3cch3oooch3ch339%regiospecific quinone isoprenylationcn(ch3)3siooch3ro1.h3cch3brmgc

45、h22.nh4cl/h2ocn(ch3)3siooch3rhoh3cch3ch2agf/h2ooch3rhoh3cch3ch2o3,3 sigmatropicrearrangementoch3rhooh3cch3 ch3ohroch3ch3oa.r=h 71%b.r=och3 62%c.r=ch3 71%vitamin k2(5)ch2csi(ch3)3ch2brmgcl2/k,35。cch2csi(ch3)3ch2mgbrch3ch3ch2o1.reagent/cubr (ch3)2s2.ch3i/hmpt40%ch3ch3och3ch2si(ch3)32.5 aromatic halide

46、s2.5.1 halobenzenoid compoundsbr1.mg/brch2ch2br,35。c2.ncch2ch2c(ch3)2cho86%chohcch3ch3ch2ch2cnbrh3c1.mgcl2/k,25。 ,30c2.ch3ch3cch(ch2)2cch3o3.li/nh34.nh4clchch2ch2chh3cch3cch3ch390 92% 姜黃烯fh3c1.mgcl2/k/ki,66。 c2.co265%coohh3cunreactivebrcl1.mgcl2/k/ki,25。 c2.nh4cl100%completely unreactiveusing ordina

47、ry magnesiumclcl1.mgcl2/k/ki,25。,2h c2.nh4clnormal conditionmono grignard reagentclcl1.mgcl2/k/ki,25。 c2.co289%coohclcontrol the ratio of mg to holide mono gr2 : 1brclcl1.mg/brch2ch2br,35。c2.cl3ccho3.koh/ch3oh4.h2so4chclcloch3cooh33%selectivelycompounds having ether, hydroxy, amino , and othersimila

48、r groups seem to have the tendency to form an insoluble coating on the magnesium surface in their grignard preparations.nh3ch3cbr1.mg/brch2ch2br,35。c2.co248%nh3ch3ccoohordinary conditiononly recovered theunchanged arylhalidesoobr1.mg/brch2ch2br,35。c2.co236%oocoohclsobrch3och3ch3recovered halidessch3

49、h3chobr1.mgcl2/k,25。 c2.(f3c)2co(n buli)sch3h3chocf3ccf3ohbrnch3clclbr1.mg/brch2ch2br,35。c2.h3o 42%nch3clclselectiveoch3ch3obrmgcl2/k/ki,85。 coch3ch3omgbrhch3ch2o1.reagent/cui2.ac2o3.koh/meoh70%hch3ch2ooch3ch3ousing ordinarymagnesiumgave unsatifactoryand capricious(unstable) results抗真菌clch3h2ch3co1.

50、mg/brch2ch2br,66。c2.choch3ch2och377%chch3h2ch3coohh3cch2och3using other condition onlygave starting materialcl1.mg/brch2ch2br,25。c2.3.h3o cn49%corather unreactivehalideunreactivenh3cch3br1.mg/brch2ch2br,35。cncn(ch3)22.3.h3o nh3cch3onch3h3c15%clbr1.mg/brch2ch2br,35。cooo2.86%clcocohomono gr selectivel

51、yclclsame condition33%cocohoclthe higher reactivityof the system led to formation of thedi gr due to adecrease in selectivitybr1.mg/brch2ch2br,35。c2.(h3c)2co3.h3o 38%cch3ch2ch3ch3br1.mg/brch2ch2br2.co285%ch3ch3coohbr1.mg/brch2ch2br,35。c2.ncch3h3cooch3h3cooo82%nnbr1.mg/brch2ch2br,35。c2.co262%nncoohoo

52、(ch2)6cl1.mg/brch2ch2br,66。c2.chc4h9 tc4h9 tohoo(ch2)6ohcc4h9 tc4h9 t80%3. h3ooch3iooo1.mg/brch2ch2br,35。c2.oooch3och3ohoocbrfh3c1.mg/brch2ch2br,35。c2.68%fh3cohooch3c44%ih3co1.mg/brch2ch2br,35。cooo2.oh3cohoocch3ch3broch31.mg/brch2ch2br,66。c2.clcooch398%70%ch3ch3cooch3och3sbr1.mg/brch2ch2br,35。c2.(h3c)3sicl60%ssi(ch3)32.5.2 haloheteroaromatic compoundsnbr1.mg/brch2ch2br2.(n c4h9o)3b28%nbohohmgcl2/k 20%nnbrc6h51.mg/brch2ch2br2.co2/c6h582%nncoohc6h5nnbrch3same