药物合成反应闻韧第三版课后翻译

1、1、About 216 224 g. (1.621.68 moles) of powdered anhydrous aluminumchloride is added to a 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 isstirred (Note 3), 81 g. (0.67 mole) of acetophenone is added from the dropping funnel in a slow stream over

2、 a period of 2030 minutes.自由流动的催化剂边搅拌边用滴液漏斗缓慢滴加 81g 苯乙酰。Considerable heat is evolved, and, if the drops of ketoneare 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 the acetophenone has been added, themixture becomes a viscous ball-like mass that is dif

3、ficult 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。Turning of the stirrer by hand ormore 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 so rapid 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 t

4、he addition, the mass becomes molten and can be stirred easily without being either heated or cooled. The molten mass, in which the acetophenone is complexed with aluminum chloride, 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。Bromine (128 g., 0.80 mole) is added dr

5、opwise to the well-stirred mixture overa period of 40 minutes (Note 4).在 40 分钟内在搅拌下把溴缓慢滴加到混合物中。 After allthe bromine has been added, the molten mixture is stirred at 8085 on a steambath 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.

6、of cracked ice and 100 ml. of concentrated hydrochloric acid in a 2-l. beaker (Note 6).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 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

7、 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 themixture with four 150-ml. portions of ether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% aqueous sodium bicarbonate solution, dried with anhydro

8、us sodium sulfate, and transferred 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 ether is removed by distillation at atmospheric pressure, and crude 3-bromoacetophenone is stripped from a few乙醚在常压下蒸馏，grams of heavy dark residue by distillation at reduced pressur

9、e. 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 carefully fractionated to obtain 94100 g. 通过分馏，得到无色的流出液 94-100g2、Preparation of cyclopropane 1,L dicarboxylic 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 fl

10、ask, 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 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.

11、 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 with 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 b

12、y 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

13、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 layers 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

14、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 mi)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 (

15、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 equipped 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 solutio

16、n 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-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

17、;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 hydroquinone 认 added lo :hc methylene chloride Solution (Note 1) which is then dried over anhydrous Mxiiuin sulfate. X| ； A：f 休川入亍

18、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、11FC ； I linn 反应式：3、2-Methyl-4-ethoxalylcyclopentane-1,3,5-trione. A solution of sodium ethoxideis prepared in a 2-l. three-necked,

19、round-bottomed flask fitted with amercury-sealed stirrer, a reflux condenser carrying a drying tube, and a stopper bythe addition of 69.0 g. (3 moles) of sodium to 950 ml. of absolute ethanol. 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 an ice bath a

20、nd stirred.溶液在 0-5 下冰浴搅拌。 The stopper is replaced by a dropping funnel, and a cold mixture (515) of108 g. (1.50 moles) of freshly distilled 2-butanone and 482 g. (3.30 moles) ofdiethyl oxalate (Note 1) is 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

21、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 continued stirring to room temperature,heated under reflux for 30 minutes, and cooled again 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。 The mixture is decomposed by

22、 stirring with 165 ml. of sulfuric acid (1:1 by volume) added inportions. 将 165ml 浓硫酸(体积比 1:1 )在搅拌加入，分解混合物。 The sodium sulfateformed is filtered by suction and washed with ethanol (150200 ml.) (Note 2).硫酸钠抽滤后用乙醇( 150 200 ml )洗涤。 The washings and filtrate are combined and concentrated by evaporation

23、. 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, washedwith small quantities of ice-cold water, 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 evaporative concentration of the m

24、other liquor followed bycooling furnishes an additional 4050 g. 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%) 产品总共180-200g (产率 53-59%) (Note 2). This crude material (m.p. 120130 ) is used inthe next step.粗品（熔点120 130 )用于下一步中 A pure sample can be obtain

25、ed bycrystallization from ethyl acetate after treatment with Norit activated carbon, m.p.160 162 . 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- 吡咯甲醛In a 3-l. three-necked round-bottomed flask, fitted with a sealed stirrer, a dropping funnel, and a reflux condenser, is pla

26、ced 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 maintained at 10 20 , while 169 g. (1.1 moles) of phosphorus oxychloride is added through the dropping funnel over a period of

27、 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 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 bat

28、h 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 solution of 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,

29、 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 replaced with a heating mantle, and the mixture is stirred at the reflux temperature for 15 minutes, during which time there is copious evolu

30、tion 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) in about of water, cautiously at first, then as rapidly as possible. 当混合物降温到 25-3

31、0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 (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 3-l. separatory funnel, and the ethylene dichloride layer is removed. 冷却的混合物转移到

32、分液漏斗中，出去二氯乙烯层。The aqueous phase is extractedthree times with a total of about 500 ml. of ether. 水相用 500ml 乙醚分三次萃取。 The ether and ethylene chloride solutions are combined and washed with three 100-ml. portions of saturated aqueous sodium carbonate solution, which is added cautiously at first to avoid

33、 too rapid evolution 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 over anhydrous sodiumcarbonate, the solvents are distilled, and the remaining liquid is transferred to a Claisen flask and distilled from an oil bath under reduced pr

34、essure (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 78 at 2 mm.; there isvery 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%), as an almost water-white liquid which soon crystallizes. 当几乎透明的液体会马上结晶，

35、粗品产量 85-90(g 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。The crude product is purified by dissolving in boiling petroleum ether (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 room temperature,

36、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 pure aldehyde is obtained from the crude inapproximately 85% recovery.纯品醛是从粗品中得到，收率 85%。 The over-all yield from pyrrole is 7879% of pure 2-pyrrolealdehyde, m.p. 44 45 .总得率为 78-79%熔点 44-45 度

37、。(1)反应式4、(1)In a 3L. round-bottomed flask (Note 1) fitted with a reflux condenser are placed 625 cc. of 95 per cent alcohol (Note 2), 500 cc. of water, 500 g. (476 cc., 4.7 moles) of pure benzaldehyde (Note 3), and 50 g. of sodium cyanide (9698 percent). 在配有回流冷凝器的 3L 圆底烧瓶中加入 625ml 的 95% 酒精、 500ml 水、

38、 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 (Note 4).混合物加热并保持沸腾 1.5 小时。 In the courseof about twenty minutes, crystals begin to separate from the hot solution.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 is cooled

39、, 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 benzoin, 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 the theoretical amount). 理论产率 90-92% 。 In order to obtain it completely pure, the crude substanc

40、e is recrystallized from 95 per cent alcohol, 90 g. of crude material being dissolved in about 700 cc. of boiling alcohol; upon cooling, a yield of 83 g. of white, pure benzoin 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 700ml 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. t

41、hree-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 introductionof hydrogen chloride, are placed 50 g. (0.36 mole) of p-nitrophenol (Note 1), 650 ml. of concentrated hydrochloric acid, 5 ml.

42、 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 maintained at 70 2 for 4 5 hours by means of a water bath (N

43、ote 4). 在水浴中保持 702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 trap (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

44、 -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 liquors are either filtered or decanted from the crysta

45、ls (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 yield is 46 g. (69% based on p-nitrophenol) of a white product melting at 129 130 . 白色产物46g(对硝基苯酚含 69%

46、)熔点 129-130度5、 B. Benzyl trans-1,3- butadiene -1- carbamateA dry, 1-l., three-necked, round-bottomed flask is equipped with a magnetic stirring bar, a thermometer, and a 250-ml., pressure-equalizing dropping funnel bearing a nitrogen inlet. The flask is flushed with nitrogen and charged with 49 g.(0

47、.50 mole) of N,N -diisopropylethylamine, solution is stirred and cooled to 0of trans -2,4-pentadienoicacid, 80g. (0.62and 300 ml. of acetone (Note 6). The resulting in an ice salt bath. A solution of 55 g. (0.51 mole)mole)of ethyl chloroformate in 150 temperature is maintained below 030 minutes at 0

48、 , after which a chilled solution of 65 g. (1.0 mole) azide (Note 8) in 170 ml. of water is added over a 20-minute interval, keeping the temperature below 0. The contents of the flask are stirred for an additional 10minutes at 0ml.of acetone is added over 30 minutes (Note 7). Stirring is continued f

49、or an additionalwhile theof sodium15of ice-water.(Note 9) and poured into a 2-l. separatory funnelcontaining 500 ml. by extractionThe acyl azide is isolatedwith six 250-ml.portionsof toluene.The combined tolueneextractssulfate for20 minutesand concentratedevaporatorat a waterbath temperatureover anh

50、ydrous magnesiumof ca. 300 ml. on a rotary of 40 50 (Note 10). Caution! The acylare driedto a volumeazide isexplosive. Thesolution should not bedryness.potentiallyWhile the toluene solution is being concentrated, a dry, 2-l., three-necked,evaporated toflask equipped pressure-equalizing dropping funn

51、el, mantle is charged with 43round-bottomedwitha mechanicalstirrer, head,500-ml.simple distillation mole) ofbenzyl of 4- tert -butylcatechol (Note 11), and 200 ml. of toluene. About 30 ml. of toulene isg.(0.40distilled from the flask to remove trace amounts of water, and the distillation headand ahe

52、atingalcohol, 250mg.is replaced with a condenser fitted with a nitrogen inlet.The toluene solutionstirred and heated at a rapid reflux under a nitrogen atmosphere the toluene solution of the acyl azide is added over 30 minutes. The disappearanceisasof the acyl azide and isocyanate is followed by IR analysis (Note 12). Conversion to the carbamate is complete in 10 30 minutes, after which the rapidly to room temperature by immersing the flask in an ic