药物合成反应闻韧第三版课后翻译

1、1、is added to aAbout 216-224 g. (1.62.68 moles) of powdered an hydrousILthree-necked flask.在 1L 的三口烧瓶中加入大约216-224g(1.62.68 moles) 的无水三氯化铝。While the free-flowi ng catalyst is stirred , 81 g. (0.67 mole) ofis addedfrom the dropp ing funnel in a slow stream over a period of 2030 min utes. 自由流动的催化剂边搅拌边用

2、滴液漏斗缓慢滴加81g苯乙酰。Considerable heat is evolved, and,if the drops of ket one are not dispersed, darke ning or charri ng 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 o ne-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。Tu

3、rni ng of the stirrerby hand or more rapid additi on of ket one is n ecessary 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 ket one, 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 C时。 Near the end of the addition, the mass becomes molten and can be s

4、tirredeasily without being either heated or cooled. The molte n mass, in which theiscomplexed with , ran ges in color from tan to brow n.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 periodof 40 minutes .在40分钟内在搅拌下把溴缓慢滴加到混合物中。 A

5、fter all the has 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 C蒸气浴下搅拌 1小时。 The complex is added in portio ns to awell-stirred mixture of 1.3 l. of cracked ice and 100 ml. of concen tratedin 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的烧杯中混合均匀。Part of

6、the cold aqueous layer is added to the reacti on 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 outis extracted from the mixture with four 150-ml. portio ns of分四次把深色的油从混合物

7、中用 150ml 萃取岀来。The extracts are comb in ed, washed con secutively with 100 ml.of water and 100 ml. of 5% aqueoussoluti on, dried with an hydrous , andtran sferred to a short- necked distillati on 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 atmosphericpressure, and

8、crude 3-bromoacetophe none 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岀来。The colorless distillate is carefullyfracti on ated to obta in 94TOO g.通过分馏，得到无色的流岀液94-100g2、Br；h AJCItPreparation of cyclopropane 1,L dicarboxylic

9、 acid P MS二 1 1限山 (1). To a1- L solution of aqueous 50% sodium hydroxide (Note IX rnechanically stirred in a2- L, three-necked flask, was added, at114.0 g (0.5 mol) oftriethvlbenzvlammonium chloride (TEBA -乙(Note 2Y IL:fj 50% 1 氣化钠til入化2L打丨 m 加入TEBA 上 壕氯化纹114.0g lOSmol)厶25X1MTo this vigorously stirr

10、ed 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. 物.The reaction mixture was vigorously stirred for 2 hr (Note 3) EZW物 ：“；：2 小 i The contents of the flask were transferred to a 4-L Erienmeyer flask by rinsing the flask w

11、ith three 75mL portions of water.IX!1 ffj It1 U 线乳 4L iYjItt U融 P . H ! 75ml ： ：(水，九总妊社 次。 The mixture was magnetically stirred by dropwise addition of 1 L of concentrated hydrocfilonc jcid沿八白心：戊屮” 巧虛 加1加甩 The temperature of the flask was maintained between 15 and 25C during acidification.使战化过:密 区山内

12、的卜反保持H 15-259之厲。The aqueous layer was poured intoa 4-L separatory funnel and extracted three times with 900 mL of ether 捋的水I, 4L i巾升?I 广u：| 900ml 乙笊分 坟？ -X The aqueous layer was saturated with sodium chloride and extracted three times with 500 mL of ether./K UM. ；i I i;l 500ml 乙瞇分次农】l The ether laye

13、rs were combinedwashed with 1 L of brine, dried (匕flSQJ. and decolorized with activated carbon.命 并乙秫戒.闵浓賦水济涤 I滋.斥I浴十1炙脱4 Removal of the solvent by rotary evaporation gave 55.2 g of a semisolid residue.J. -55.2g体.The residue was triturateed with 100 mL of benzene.农血 H 100ml 翠i;f, Flitration of this m

14、i)rture gave 43.1-47.9 g (66-73%) of 1 as white crystals, mp 椅为 43.1-47.9g(66-73%)f|色iB体垢点 137-I4CTCPreparation of mesioldehyde (2V6- nimediyl benzaldehyde) 2,4,6- 4 M l .b rA solution of 72 g. (0.60 mole) of mesitylene in 575 ml. of diy methylene chloride h placed in a 1-1. diree necked ilask equip

15、ped with a retlux cundenser. a siinisr, and a dropping tunnel. 72g (O.dOmol)的15三甲卑荒和无水的二氯甲烷放入M冇冷礙H流、損样和滴池漏斗装为的 10烧机中，Tlie solution is cexiled in an icc bath, and 190 g. (110 ml. 1.0 mole) of titanium tctmchloridc is added over a period of 3 minuter. 4 ； K浴Hl 杀fl b ?f :分 讨1勺滴 *JUlOg (I lOmh I .Omol)勺

16、-I /t i K While (hek Mined anc cooled. 57.5 g. (0.5 male) ofdiehloroiiidthyl methyldtlr 2 kAddeddfopvsovra25-tninute periud.上 G讥負;召川攸扶卜 右25分计内滿加57；5 (0.5mul)涌加.汕屮*甲腿.The reaction begins e combined uranic suiulion is washed lliree times with 75-ml. |wrtkns of waler r JI 液.)H75nil/R分 次況陈.A crMal of hy

17、droquinone 认 added lo :hc methylene chloride Solution (Note 1) which is then dried over anhydrous Mxiiuin sulfate. X| ； A：f 休川入亍 氯甲在Jfa入无水SW#1的 I After cvj|xi aiioti of lhe sohcnl. die residue is 68-74 C(0.9mm) Aft ft4 rditslUlk n dkfiM it obUiiidcl 60-66 g. (8189%) f mziml(怙 hy 的2.46 屮丛文甲H掬心 11、11F

18、C ； I linn 反应式:I KA(0:11反卿机理二亲検取代(Hft)C 2) F Rieche A , el nl, SynEhhI Cn-IL WiL 3： 49t 反应式.Ji L.CILCL：tlMc3、2-Methyl-4-ethoxalylcyclope nta ne-1,3,5-tri one. A soluti on ofis prepared in a2-1. three-n ecked, rou nd-bottomed flask fitted with a mercury-sealed stirrer, areflux conden ser carry ing a

19、drying tube, and a stopper by the additi on of 69.0 g. (3moles) of to 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圭寸搅拌器的2L三口圆底烧瓶中制备乙醇钠。The solution is cooled to 0-5 in anice bath and stirred. 溶液在 0-5 C下冰浴搅拌。The stopper is replaced by a droppingfunnel, and a cold mixture (5T5 0) of 108

20、 g. (1.50 moles) of freshly distilledand482 g. (3.30 moles) ofis added gradually over a period of 30 min utes.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 C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 continued stirring to r

21、oom temperature,heated un der reflux for 30 min utes, and cooled aga in to 0in an ice bath. 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 Co The mixtureis decomposed by stirri ng with 165 ml. of(1:1 by volume) added in porti ons.将165ml 浓硫酸(体积比1:1 )在搅拌加入，分解混合物。 The formed is filtered by suctionand washed wi

22、th(150 -200 ml.).硫酸钠抽滤后用乙醇(150 -200 ml )洗涤。Thewash ings and filtrate are comb ined and concen trated by evaporati on .合并滤液和洗涤液后蒸发浓缩。The yellowish brow n product which accumulates by slowcrystallization is collected by filtration, washed with small quantities of ice-coldwater, and dried in air.过滤缓慢析岀

23、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 140T50 g.粗产品 140-150g。Further evaporativeconcen trati on of the mother liquor followed by cooli ng fur ni shes an additi onal 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。bri nging thetotal yield to 180-200 g. (53-59%)产品总共 180-200g (产率 53-59%) .

24、 This crudematerial (m.p. 120 T30 ) is used in the next step.粗品(熔点 120 T30 C)用于下一步中 A pure sample can be obtained by crystallization fromafter treatment withactivated , m.p. 160 T62 .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 CoThe procedure for 2- pyrrolealdehyde 2-吡咯甲醛In a 3-l. three-necked round-bottomed f

25、lask, fitted with a sealed stirrer, a dropping funnel, and a reflux conden ser, is placed 80 g. (1.1 moles) of dimethylformamide (Note 1).在配有圭寸闭搅拌器、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 maintained at 10 -20 , while 169 g. (1.1 m

26、oles) 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 C, 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 complex.放热反应生成磷酰氯二甲基甲酰胺化合物。The icebath is remo

27、ved, and the mixture is stirred for 15 mi nu tes (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 soluion of 67 g. (1.0 mole) of freshly distilled pyrrole in 2

28、50 ml. of ethylene dichloride is added through a clean dropping funnel to the stirred, cooled mixture over a period of 1 hour.当内部温度降至U 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 additi on is complete, the ice bath is replaced with a heat ing man tle, andthe mixture is stirred

29、 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 solution of 750 g. (5.5 moles) of sodium acetate trihydrate (Note 3)

30、in about of water, cautiously at first, then as rapidly as possible.当混合物降温到25-30 C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 15minu tes, vigorous stirri ng being maintained all the while (Note 4).反应物在充分搅拌下重新回流15分钟。The cooled mixture is transferred to a

31、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 are combined and washed with three 100-ml. portions ofsaturated aque

32、ous sodium carb on ate soluti on, 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，然后通入一氧化碳，通入时要小心不要太快。The non- aqueous solution is then dried overan hydrous sodium carb on ate, the solve nts are distilled, and the remai ning liquid is tr

33、an sferred 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;很少有预留无和残渣。The yield of crude 2-pyrrolealdehyde is 85 -90 g. (89 -95

34、%), 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 -0 样品在素烧瓷板上干燥，熔点35-40 度。Thecrude product is purified by dissolv ing in boili ng petroleum ether (b.p. 40-60 , in the ratio of 1 g.of crude 2-pyrrolealdehyde to 25

35、 ml. of solve nt, and cooli ng the soluti on 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 approximately 85% recovery. 纯品醛是从粗品中得至U，收率 85%。 The over-all yield from pyrrole i

36、s 78 -J79% of pure 2-pyrrolealdehyde, m.p. 44 -45.总得率为78-79%熔点44-45度。(1)反应式I g I 111IMSIII.UjS Ml 气I*九 k OK, fib* I El6 覽IwlI 航 y jhr HP反应机葺:制酯 三ac)舞春Cl) AffiCi+ mri,辰应机理帽一克反应活性芳歼竹甲战化)4、(1) 1 n a 3L. roun d-bottomed flaskfitted with a reflux conden ser are placed 625cc. of 95 per cent, 500 cc. of wa

37、ter, 500 g. (476 cc., 4.7 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 thenheated and kept boiling for one-half hour .混合物加热并保持沸腾1.5 小时。In thecourse of about twenty min utes, crystals beg in to separate f

38、rom the hot soluti on.在20 分钟后晶体开始从热溶液中析岀。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 thetheoret

39、ical amount).理论产率 90-92%。In order to obtain it completely pure, thecrude substa nee is recrystallized from 95 per cent , 90 g. of crude material being dissolved in about 700 cc. of boili ng ; upon cooli ng, a yield of 83 g. of white, purewhich 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7

40、00ml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 conden ser, and bent glass tube reach ing below the surface of the liquid for the in troducti onof hydrogen chloride, are placed 50 g. (0.36 mole) of p-nitrophenol (No

41、te 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 硫酸禾口 76g( 1mol) 的二甲氧基甲烷。 The mixture is stirred while the temperature is ma in t

42、ai ned at 702or 4 -5 hours by means of a water bath (Note 4).在水浴中保持 70 戈度搅拌 4-5小时。During this time hydroge n chloride is bubbled into the react ion mixture through the bent glass tube, and the excess gas is carried away through the reflux condenser to a hood or gas- absorption trap (Note 5).在此期间通过玻璃

43、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, after which the acid liq

44、uors are either filtered or deca nted 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-n itrobe nzyl chloride is purified by recrystallizati on 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 yield is 46 g. (69% based onp-nitrophenol) of a white p

45、roduct melting at 129 30 白色产物 46g (对硝基苯酚含 69%)熔点 129-130 度(I参考答案:反应式：Xa( Anoli, A來反应机理捉示匕安息香缩合反应式二*反应机理捉示：氯中基化反应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 iniet. The

46、 flask is flushed with and charged with 49 g. (0.50 mole) of , 80 g. (0.62 mole) of , and 300 ml. of . The result ing soluti on is stirred and cooled to 0 in an ice-salt bath. A solution of 55 g. (0.51 mole) of in 150 ml.of is added over 30 mi nutes while the temperature is mai ntai ned below 0. Sti

47、rri ngis con ti nued for an additi onal 30 min utes at 0, after which a chilled soluti on of 65g. (1.0 mole) of in 170 ml. of water is added over a 20-min ute in terval, keep ing the temperature below 0. The contents of the flask are stirred for an additi onal10 -15 minutes at 0and poured into a 2-l

48、. separatory funnelcontaining 500 ml. ofice-water. The acyl azide is isolated by extraction with six 250-ml. portions of . The comb ined extracts are dried over an hydrous for 20 min utes and concen trated to a volume of ca. 300 ml. on a rotary evaporator at a water bath temperature of 40 -50 . Caut

49、ion! The acyl azide is potentially explosive. The solution should not be evaporated to dryn ess.While the soluti on is being concen trated, a dry, 2-l.,three-necked, round-bottomed flask equipped with a mechanical stirrer, a 500-ml.pressure-equalizingdropping funnel, a simple distillation head,and a

50、 heatingma ntle is charged with 43 g. (0.40 mole) of, 250 mg. of , and 200 ml. of . About 30ml. of toulene is distilled from the flask to remove trace amounts of water, and the distillati on head is replaced with a conden serfitted with a inl et. The soluti on isstirred and heated at a rapid reflux under a atmosphere as the solution of the acyl azide is added over 30 min utes. The di