药物合成反应(闻韧_第三版)课后翻译

1、1、is added to aAbout 216 224 g. (1.62 1.68 moles) of powdered anhydrous 1Lthree-necked flask.在 1L 的三口烧瓶中加入大约 216-224g(1.621.68 moles) 的无水三氯化铝。 While the free-flowing catalyst is stirred , 81 g. (0.67 mole) ofis addedfrom the dropping funnel in a slow stream over a period of 2030 minutes.自由流动的催化剂边搅拌边

2、用滴液漏斗缓慢滴加 81g 苯乙酰。 Considerable heat is evolved, and, if the drops of ketone are not dispersed, darkening or charring occurs.放热反应，假如滴加的酮不能被分散，就会变黑或是碳化。When about one-third of thehas beenadded, the mixture becomes a viscous ball-like mass that is difficult to stir.当三分之一的乙酰苯被滴加，反应混合物变成一个很难搅拌的粘性的球状团块。T

3、urning of the stirrerby hand or more rapid addition of ketone is necessary at this point.在这时，改用手动搅拌或快速滴加酮是非常必要的。The addition of ketone, however, should not be sorapid as to produce a temperature above 180. 然而°，速度不能太快，当反应温度超过180 时。 Near the end of the addition, the mass becomes molten and can be

4、 stirred easily without being either heated or cooled. The molten mass, in which theiscomplexed with , ranges in color from tan to brown.当快滴加完时，团块开始融化，表明苯乙酰已经和三氯化铝混合完全，颜色也逐渐从黄褐色变为棕色。(128 g., 0.80 mole) is added dropwise to the well-stirred mixture over a period of 40 minutes . 在 40 分钟内在搅拌下把溴缓慢滴加到混合物

5、中。After all thehas beenadded, the molten mixture is stirred at 8085 ° on a steam bath for 1 hour.溴滴加完后，熔融混合物在 80-85 蒸气浴下搅拌 1 小时。 The complex is added in portions to a well-stirred mixture of 1.3 l. of cracked ice and 100 ml. of concentratedin a 2-l.beaker . 反应物加入到 1.3L 碎冰和 100ml 浓盐酸的混合物中在 2L 的烧

6、杯中混合均匀。 Part of the cold aqueous layer is added to the reaction flask to decompose whatever part of the reaction mixture remains there, and the resulting mixture is added to the beaker. 把部分的冰水层加入到烧瓶中洗涤残留物， 然后合并到烧杯中。 The dark oil that settles out is extracted from the mixture with four 150-ml. portio

7、ns of分四次把深色的油从混合物中用 150ml 萃取出来。 The extracts are combined, washed consecutively with 100 ml. of water and 100 ml. of 5% aqueoussolution, dried with anhydrous , andtransferred to a short-necked distillation flask.合并萃取液，用 100ml 水和 100ml 5%的小苏打洗涤，用无水硫酸钠干燥。 The is removed by distillation at atmospheric

8、pressure, and crude 3-bromoacetophenone is stripped from a few grams of heavy dark residue by distillation at reduced pressure. 乙醚在常压下蒸馏，微量的溴苯乙酮通过减压蒸馏的方法从大量深色残渣中被分离出来。The colorless distillate is carefully2、fractionated to obtain 94100 g. 通过分馏，得到无色的流出液94-100gPreParatiOn OfCyClQPrOPane 1,L dicarboxyli

9、c acid P 73二 1 IliftV 山> (1). TO a I-L SC)IUtlOn Of aqueous 50% SQdiUm hydroxide (NQte IX mechanically Stlrred in a 2L, three-necked flask, WaS addedr at 25114.0 g (0.5 mol) OfEethvlbenzvlammoriiijm Gloride (TEBA -乙(NOte 2Y IL ：|ZJ 50% I Mtt-WtUAf. 2L rj J t-c '如入TEBA 上 ftVi 114.0g «.O.5

10、mol> /f 25C *.1 4UkJ! To this VlgOrOUSly Stirred SUSPenSiOn WaS added a mixture of 80.0 g (0.5 mol) Of diethyl malonatc? and 141.0 g (0.75 mol) Of 1.2dibomoethane all at once. <r.5> 行.A酸 BSo.0g0.5mol l: lr2決乙炕 141.0个(O.75mol丿的混：>物.The reaction mixture WaS VigOrOUSly Stirred for 2 hr (NQt

11、e 3) EZW物 '：“；：2 小 I The COntentS Ofthe flask WeretranSferTedtO a 4-L ErIenmeyer flask by rinsing the flask With three 75mL POrtiOnS Of Water.!I'!,(Iti lt,v U f' 4L IYJItt !,. -H ! 75ml 冷 水,九总 妊 -.» C The mixture WaS magnetically stirred by dropwise addition OfILOf COnCentrated hydr

12、ocQric 3cd沿八白心 jJi 巧虛 加1体"甩 The temperature Of the flask WaS maintained between 15 and 25oC during acidification.使战化区山内的M保持H 15-259之厲。Te aqueous Iayer WaS POUred intoa 4-L SeParatOry funnel and extracted three times With 900 mL Of ether 捋的水I, 4L Iij ,i,1 90Oml 乙笊分 ¾ The aqueous Iayer WaS S

13、atUrated With SOdiUfn ChlOride and extracted three times With 500 mL Of ether./K UM Iiti. /1 I iI 50Oml 乙Af 分次农】l The ether IayerS Were COmbinedy WaShed With 1 L Of brlnef dried CMflSQOr and decolorized With activated CalbQn金 并乙M½.闵浓航水济涤 I滋.斥I浴tl炙脱O RemOVal Of the SOlVent by rotary evaporation

14、gave 55.2 g of a SemiSOIld residue. J. ； 55.2g JfjJfl8体.The residue WaS triturateed With IOO mL Of benzene, r*t U IOOml 翠i;f , FlItratlOn Of this mi)rture gave 43.1-47.9 g (66-73%) Of 1 as Whlte CryStaIs, mp 137-140GUM I椅为 43.1-47.9g(66-7%)f色IS体j点 137-14CrCPreParaIiOn Of IneMOldehyde (2v<6- trime

15、<hyl benzaldehyde) 2,4,6- 1I J M F A Ution Of 72 g. (0.60 InOIe) Of mesitylene in 575 ml. Of dr methylene ChI(Wide i placed in a I-L dIree necked ilask equipped WiIh a retlux CQiidenser. a SIin)r, and a dropping tunnel. 72g (0.6On)Ol) W15.三甲无水的二氯甲烷放入M冇冷礙H流、損样和i>iW4装为的 I !烧JBi中，TlIe solution is

16、 Cgkd in an kc ba(l. and 190 g. (I IO ml. 1.0 m>lc) Of titanium tetrachloride is added Over a PCriOd Of 3 minutcs 4 ； K浴Hj 杀fl b » :分 MIIl 滴.,JUl0g (I IOnIh 1.0mol)勺-I U /t i K WhiIC (he Mlhlti(W K UirTCd ZmC cooled. 57.5 g. (0.5 male) Of (Iiehk>roethyl AMChyletlB12 kAddeddroui<½O

17、VA25-tlnnute IfkKl.Z G讥負;召川攸扶卜 右25分计内it¾tJU57.5g (0.5IlWl)涌加.汕屮*甲腿.ThIe reaction begins US indicated by eVDludon Of hydrogen CiIloride) Wben the fira drop of chl) ether it added Tr P 勺丿蔗代 则 乂 V J l ( X化欤农'! tter d>e addition is complete, d>e mixture is Stirred for 5 nunutes in (IIC ic

18、c hath, tor 30 minutes WllbOLH gohng an<i tor 15 minutes ar 35° /l 汹川 J, '» l -fr1¾ 冰浴下搜样5分仲.移开冰浴氏应30分钟.再任35匸下反应15分仲.he reacikm mixture is poured into a SePanHOry tunnel Comaining about 0.5 kg. Of CnJShed ice aad is SialKn IbOroUghI) 足i3t1r 5 IhlO3g的禅冰充分振搖Q TcOrgaIIiC layer k W

19、ParatetI. and tl)e aqueous WIUtIoll k erced UIth two 50- ml. POlIiUHg Ut rt>ethykneChIOride.弃去有机足.木层再用50m啲二氯甲烷分网次承取Tl>e combined UranlC SoiUlK>n is WaSbed LIlree UnIeS HiIh 75-nl. IWrtk>ns>f WaUr Jl -v:?< 液.)H75nlR分 次況陈.A CTyMIl OT IIydn)quinone i added Io .hc mc(hylcnc ChlOridC So

20、lution (NOtC 1) WhiCh is then dried OVer anhydrous MxiiUln Milfate. X Z IWlIL 休川入亍 氯甲MMFTi * SjbUA无水SBH I AftCr CyJIXMaIKMl Of IhC SOhCnL IhC residue is <liSlillcd (o give IhC CrlIde PnXIuct, h.p. 68-74° (0.9 mm.). W l; i68-74C (0.9if)Afttt4rtdtillfltkaM dk6M it oUitMl 60-66 g. (8189%) Of ni

21、twitl<lly<te; b.>. IIM IISQ (I I nun.), n2OD 1.558.1BiM9½(M)1 89%> ft(J2.4.6 屮 ALXtPB 113-115,C Illmn> 反应式：3、2-Methyl-4-ethoxalylcyclopentane-1,3,5-trione. A solution ofis prepared in a2-l. three-necked, round-bottomed flask fitted with a mercury-sealed stirrer, areflux condenser

22、 carrying a drying tube, and a stopper by the addition of 69.0 g. (3moles) ofto 950 ml. of absolute . 69.0g( 3mol )钠和 950ml 无水乙醇在配有干燥回流冷凝管和汞封搅拌器的 2L 三口圆底烧瓶中制备乙醇钠。 The solution is cooled to 05° in anice bath and stirred.溶液在 0-5 下冰浴搅拌。 The stopper is replaced by a droppingfunnel, and a cold mixtu

23、re (515 °) of 108 g. (1.50 moles) of freshly distilledand482 g. (3.30 moles) ofis added gradually over a period of 30 minutes.瓶塞用分液漏斗取代， 108g (1.5mol )的丁二酮和 482g ( 3.3mol )的乙二酸二乙酯在 5-15 下低温混 合，在 30 分钟内逐步滴加到溶液中。After the addition is complete, the thick,orange-red mixture is allowed to warm with

24、continued stirring to room temperature,heated under reflux for 30 minutes, and cooled again to 0in an ice ba°th.完全加入后，橘红色的粘稠物继续搅拌至室温，加热回流 30 分钟后在冰浴中冷却至 0。 The mixture is decomposed by stirring with 165 ml. of(1:1 by volume) added in portions. 将165ml 浓硫酸(体积比 1:1 )在搅拌加入， 分解混合物。 The formed is filt

25、ered by suctionand washed with(150 200 ml.) . 硫酸钠抽滤后用乙醇( 150 200 ml )洗涤。 Thewashings and filtrate are combined and concentrated by evaporation .合并滤液和洗涤液后蒸发浓缩。 The yellowish brown product which accumulates by slow crystallization is collected by filtration, washed with small quantities of ice-cold wa

26、ter, and dried in air. 过滤缓慢析出的棕黄色产品用小剂量的冰水洗涤后在空气中干燥。 The crude product weighs 140150 g. 粗产品 140-150g 。 Further evaporativeconcentration of the mother liquor followed by cooling furnishes an additional 4050g. of the keto ester, 此外将母液用冷冻蒸发浓缩后又得到 40-50g 的酮酯。 bringing the total yield to 180200 g. (53 59

27、%) 产品总共 180-200g (产率 53-59% ) . This crudematerial (m.p. 120130 °) is used in the next step.粗品(熔点 120 130 )用于下一步中 A pure sample can be obtained by crystallization fromafter treatment withactivated , m.p. 160162 °. 纯品是经过活性炭处理后在乙酸乙酯中结晶得到，熔点160 162 。The procedure for 2- pyrrolealdehyde 2- 吡咯甲

28、醛In a 3-l. three-necked round-bottomed flask, fitted with a sealed stirrer, a dropping funnel, and a reflux condenser, is placed 80 g. (1.1 moles) of dimethylformamide (Note 1). 在配有封闭搅 拌器、 滴液漏斗和冷凝回流装置的三口圆底烧瓶中放入80g(1.1mol)的二甲基甲酰胺。 Theflask is immersed in an ice bath, and the internal temperature is m

29、aintained at 10 20 °, while 169 g. (1.1 moles) of phosphorus oxychloride is added through the dropping funnel over a period of 15 minutes. 烧瓶浸入冰浴中，内部温度保持在10-20， 169g( 1.1mol )的磷酰氯通过滴液漏斗在 15分钟内滴加。 An exothermic reaction occurs with the formation of the phosphorus oxychloride - dimethylformamide

30、complex. 放热反应生成磷酰氯二甲基甲酰胺化合物。 The ice bath is removed, and the mixture is stirred for 15 minutes (Note 2). 移去冰浴，在搅拌 15分钟。The ice bath is replaced, and 250 ml. of ethylene dichloride is added to the mixture.重新再冰浴下加入 250ml 的二氯乙烯。 When the internal temperature has been lowered to 5 , a solu°tion of

31、 67 g. (1.0 mole) of freshly distilled pyrrole in 250 ml. of ethylene dichloride is added through a clean dropping funnel to the stirred, cooled mixture over a period of 1 hour. 当内部温度降到 5度 时，把 67g( 1.0mol)新蒸馏的吡咯加入到 250二氯乙烯中，通过滴液漏斗在 1小时内低温下 边搅拌边滴加。 After the addition is complete, the ice bath is repl

32、aced with a heating mantle, and the mixture is stirred at the reflux temperature for 15 minutes, during which time there is copious evolution of hydrogen chloride. 滴加完后，用加热装置取代冰浴，搅拌回流15分钟， 直到有大量氯化氢产生。The mixture is then cooled to 25 30 °, and to it is added through the dropping funnel a solutio

33、n of 750 g. (5.5 moles) of sodium acetate trihydrate (Note 3) in about of water, cautiously at first, then as rapidly as possible. 当混合物降温到 25-30后，通过滴液漏斗加入 750g( 5.5mol)的三水 醋酸钠溶液，开始要小心，然后要尽可能地快。 The reaction mixture is again refluxed for 15 minutes, vigorous stirring being maintained all the while (N

34、ote 4).反应物在充分搅拌下重新回流15分钟。The cooled mixture is transferred to a 3-l. separatory funnel, and the ethylene dichloride layerThe aqueous phase isis removed. 冷却的混合物转移到分液漏斗中，出去二氯乙烯层。extracted three times with a total of about 500 ml. of ether. 水相用 500ml 乙醚分三次萃取。 Theether and ethylene chloride solutions ar

35、e combined and washed with three 100-ml. portions ofsaturated aqueous sodium carbonate solution, which is added cautiously at first to avoid too rapidevolution of carbon dioxide. 合并乙醚和氯乙烯溶液，用 100ml 饱和碳酸钠溶液分三次洗涤，然后通入二氧化碳，通入时要小心不要太快。 The non- aqueous solution is then dried overanhydrous sodium carbona

36、te, the solvents are distilled, and the remaining liquid is transferred to aClaisen flask and distilled from an oil bath under reduced pressure (Note 5). 非水溶液用无水碳酸钠干燥， 蒸馏溶剂， 余下的溶液移入克氏烧瓶在油浴中减压蒸馏。 The aldehyde boils at 78at 2 mm.; there is very little fore-run and very little residue. 醛沸点 78 度在 2mm；很少

37、有预留无和残渣。 The yield of crude 2-pyrrolealdehyde is 85 90 g. (89 95%), as an almost water-whiteliquid which soon crystallizes. 当几乎透明的液体会马上结晶，粗品产量85-90g（89-95% ）。A sample dried on a clay plate melts at 35 40 °. 样品在素烧瓷板上干燥，熔点 35-40 度。 Thecrude product is purified by dissolving in boiling petroleum e

38、ther (b.p. 40 60 °), in the ratio of 1 g.of crude 2-pyrrolealdehyde to 25 ml. of solvent, and cooling the solution slowly to roomtemperature, followed by refrigeration for a few hours. 粗品溶解在沸腾的石油醚中(沸点 40-60度），一克粗品 2-甲基吡啶加入 25ml 溶剂，在室温下冷却，这后再冷冻数小时。 The purealdehyde is obtained from the crude in

39、approximately 85% recovery. 纯品醛是从粗品中得到，收率 85% 。 The over-all yield from pyrrole is 78 79% of pure 2-pyrrolealdehyde, m.p. 44 45°. 总得率为 78-79% 熔点 44-45 度。1）反应式4、(1)In a 3L. round-bottomed flaskfitted with a reflux condenser are placed 625cc. of 95 per cent, 500 cc. of water, 500 g. (476 cc., 4.7

40、 moles) of pure, and 50g. of (96 98 per cent). 在配有回流冷凝器的 3L 圆底烧瓶中加入 625ml 的 95% 酒精、 500ml 水、500g ( 476ml ，4,7mol )的苯甲醛和 50g 96-98% 的氰化钠。 The mixture is then heated and kept boiling for one-half hour . 混合物加热并保持沸腾 1.5 小时。 In the course of about twenty minutes, crystals begin to separate from the hot s

41、olution.在20 分钟后晶体开始从热溶液中析出。At the end of the thirty minutes, the solution iscooled, filtered with suction, and washed with a little water.在最后的 30 分钟，冷却溶液，抽滤并用少量水洗涤 The yield of dry crude , which is white or light yellow, is450 460 g. 有 450-460g 白色或亮黄色的干燥的安息香。(90 92 per cent of thetheoretical amount)

42、. 理论产率 90-92% 。 In order to obtain it completely pure, the crude substance is recrystallized from 95 per cent , 90 g. of crude material being dissolved in about 700 cc. of boiling ; upon cooling, a yield of 83 g. of white, pure which melts at 129is° obtained. 为了得到纯度高的产品，粗产品要在酒精中重结晶， 90g粗品溶解在 70

43、0ml 沸腾的酒精中，冷却， 得到 83g 熔点为 129 摄氏度的白色安息香纯品。(2)In a 1L. three-necked round-bottomed flask equipped with a mechanical stirrer, short reflux condenser, and bent glass tube reaching below the surface of the liquid for the introduction of hydrogen chloride, are placed 50 g. (0.36 mole) of p-nitrophenol (N

44、ote 1), 650 ml. of concentrated hydrochloric acid, 5 ml. of concentrated sulfuric acid (Note 2), and 76 g. (1 mole) of methylal (Note 3). 在配有机械搅拌， 短期冷凝回流器和一个为的是深入液面下通氯化氢气体的弯曲的玻璃管三口圆底烧瓶中加入 50g(0.36mol )对硝基苯酚， 650ml的浓盐酸， 5ml的浓 硫酸和 76g( 1mol )的二甲氧基甲烷。 The mixture is stirred while the temperature is mai

45、ntained at 70 2±° for 4 5 hours by means of a water bath (Note 4). 在水浴中保持 70±2度搅拌 4-5小时。 During this time hydrogen chloride is bubbled into the reaction mixture through the bent glass tube, and the excess gas is carried away through the reflux condenser to a hood or gas- absorption tr

46、ap (Note 5). 在此期间通过玻璃弯管把氯化氢气体通入反应混合物中，过量的气体被带到回流冷凝器被气体吸收罩吸收。The 2- hydroxyl -5- nitrobenzyl chloride begins to separate as a solid about 1 hour after the beginning of the reaction. 在反应开始后的一个小时， 2-羟基 -5-硝基苯氯化物作为固体被分离。 At the end the mixture is cooled in ice for 1 hour whereby more crystals separate,

47、after which the acid liquors are either filtered or decanted from the crystals (Note 6).最后把混合物在冰中冷却1 小 时 ， 使 更 多 的 晶 体 析 出 ， 之 后 把 酸 性 液 体 过 滤 或 倾 析 得 到 晶 体 。 The 2-hydroxy-5-nitrobenzyl chloride is purified by recrystallization from 125 ml. of hot benzene 2-羟基-5- 硝基苯氯化物在热的苯中重结晶纯化。(Note 7). The yiel

48、d is 46 g. (69% based onp-nitrophenol) of a white product melting at 129 130 °.白色产物 46g(对硝基苯酚含 69%)熔点 129-130 度5、B. .A dry, 1-l., three-necked, round-bottomed flask is equipped with a magnetic stirring bar, a thermometer, and a 250-ml., pressure-equalizing dropping funnelbearing a nitrogen inle

49、t. The flask is flushed with and charged with 49 g. (0.50 mole) of , 80 g. (0.62 mole) of , and 300 ml. of . The resulting solution is stirred and cooled to 0in° an ice salt bath. A solution of 55 g. (0.51 mole) of in 150 ml.of is added over 30 minutes while the temperature is maintained below

50、0 . Stirring ° is continued for an additional 30 minutes at 0, after whic°h a chilled solution of 65g. (1.0 mole) of in 170 ml. of water is added over a 20-minute interval, keeping the temperature below 0. T°he contents of the flask are stirred for an additional10 15 minutes at 0a

51、6;nd poured into a 2-l. separatory funnelcontaining 500 ml. ofice-water. The acyl azide is isolated by extraction with six 250-ml. portions of . The combined extracts are dried over anhydrous for 20 minutes and concentrated to a volume of ca. 300 ml. on a rotary evaporator at a water bath temperatur

52、e of 40 50 ° . Caution! The acyl azide is potentially explosive. The solution should not be evaporated to dryness. While the solution is being concentrated,a dry, 2-l.,three-necked, round-bottomed flask equipped with a mechanical stirrer, a 500-ml.pressure-equalizing dropping funnel, a simple d

53、istillation head, and a heating mantle is charged with 43 g. (0.40 mole) of, 250 mg. of , and 200 ml. of . About 30 ml. of toulene is distilled from the flask to remove trace amounts of water, and the distillation head is replaced with a condenserfitted with a inlet. The solution isstirred and heated at a rapid reflux under a atmosphere as the solution of the acyl azide is added over 30 minutes. The disappearance of the