药物合成反应(闻韧_第三版)课后翻译

1、1、About 216224 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 a

2、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 difficul

3、t 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力口酉同是非常必要的。The addition of ketone, however, should not be so rapid as toproduce 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 add

4、ition, 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 dropwise

5、 to the well-stirred mixture overa period of 40 minutes (Note 41 在40分钟内在搅拌下把澳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.澳滴加完后，熔融混合物在 80-85 C蒸气浴下搅拌1小时。The complex isadded in portions to a well-stirred mixture of 1.3 l. of crac

6、ked 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 beaker

7、.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 and100 ml. of 5% aqueous sodium bicarbonate solution, dried with anhydrous sodium

8、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 ethers removed by distillation atatmospheric pressure, and crude 3-bromoacetophenone is stripped from a few乙醴在常压下蒸播,grams of heavy dark residue by distillation at reduced pressure.微量的澳苯乙酮通过减压蒸储的

9、方法从大量深色残渣中被分离出来。The colorless distillate iscarefully fractionated to obtain 94100 g.通过分储，得到无色的流出液94-100gO SH h2、Preparation of cyclopropane lrl- dicarboxylic acid ” qb=H花;的!否(1). To a1-L solution of aqueous 50% sodium hydroxide (Note 11 mechanically stirred in a 2-L. three-necked flask, was added, a

10、t 25, 114.0 g (0.5 mol) of triethylbenzvlammoniurn chloride (TEBA 乙基工工三条化核 J (Note 2), IL fj 50% i. 宜化轴加入到2L的三口烧瓶中,加入TEBA 一乙墓K基懿化铉114.0g (0.5mol)在25C机 丁尹 To this vigorously stirred suspension was added a mixture of 80.0 g (0.5 mol) of diuthvl malonate and 141.0 g (0.75 mol) of IZdibromouthane all at

11、 once.欠4、 搅拌至混悬状， 次H3八寸 的 乙位80.0g(。5moi加1,2以乙烷141.0个(0.75mol) 的 IEC物.The reaction mixture was vigorously stirred for 2 hr (Note 3).反它;足含物 /？乂旭I 2 小小.The contents of the flask were transferred to a 4-L Erlenmeyer flask by rinsing the flask with three 75-mL portions of water.H M . 的物妩H 移和 4L 的搐 一，3 II

12、 HI 75ml 清水洗涤烧嗔 二次。The mixture was magnetically stirred by dropwise addition of 1 L of concentrated hydrochloric acid.出 N? ' (安力 KJf口力il 太林版，The temperature of the flask was maintained between 15 and 25 during acidification, fiftvk t .烧瓶内的温度保持在 1525P之间.The aqueous layer was poured into a 4-L sep

13、aratory funnel and extracted three tires with 900 mL of ether. 反应物的力J 4L的分屋出I - 'I I 900ml乙必分 A?。The aqueous layer was saturated with sodium chloride and extracted three times with 500 mL of ether. 4c500ml 乙修 'The ether layers were combined,washed with 1 L of brine, dried (MaSOd and decolori

14、zed with activated carbon. T? 并乙型液.用浓株水7d I燥，同泡H实脱色 Removal of the solvent by rotary evaporation gave 55.2 g of a semisolid residue.力 k'：Slil 去淮剂用 55.2g 的!体.The residue was triturateed with 100 mL of benzene,及软用 100ml 不IP 界. Filtration of this mixture gave 43.1-47.9 g (66-73%) of 1 as white crys

15、tals, mp 137-140.过池的施冷物为43.1-47.9g(6673%)门色晶体培点137140 CPreparation of inesi(aldehy<le (2,4,6- tri methyl hen/akiehycie) 2.4.6- H H，、卜卒:匕!J r$A solution of 72 g. (0.60 mole of mesitylene in 375 ml. of dry methylene chloride is placed in a 1-1. three-necked tlask equipped with a reflux condenser, a

16、 sdner. and a dropping tunnel. 72g ()0inol ! ,3.5” 一和无木！汉甲烷放入配有冷凝回流、搅拌和滴液漏斗装置的J1 烧瓶中 The solution is cooled in an kc bath, and 190 g. (110 ml” 1.0 mole) of (iianium tetrachloride is added over a period of 3 minutes, /l 冰浴 为条件卜，/l分 t中内滴 U 190g< I 10ml. I.Omol)的叫血化汰 While (he solution is stirred an

17、d cooled. 57.5 g. (0.5 mole) of ciichk)n)niethyl niediyl ether 2 is added dropwise over a 25-minute jieriod. 内冰浴 和拽抒卜. I 芋.I 6滴,157,笃 i 0.5nM>l)酒'川：M l L 甲髓.The reaction begins (as indicaied by evolution of hyxlrogen chloride) when the first drop of chloro ether is added, i 开的滴 口 M代社. 则反应开始Gf

18、-化式放山)After the addition is complete, the mixture is stirred for 5 minutes in the ice bath, tor 30 minutes withemt cooling, and for 15 minutes at 35°. 4 ；W ；川完成：物4 冰浴下搅拌5分钟，移开冰浴反应30分钟,再在35t下反应15分钟.The reaction mixture is poured into a separatory funnel containing about 0.5 kg. of cnished ice an

19、d is shaken thoroughly.反用改漏斗,占机lO.5kg的碎冰.充分瓶插,Theorganic layer is separated, and die aqueous solution is extracted with two 50- ml. portions ofmethylene chloride,弃去有机层,水层再用50ml的 氧甲烷分两次萃取The combined organic solution is washed three times with 75-nil. jxirtiun of water. ) ¥ 】K ;液,用751nl水分 次洗涤。A

20、crystal of hydniquinone is added lo the methylene chloride solution (Note 1) which is then dried over anhydrous sodium sulfate.对 4酚品体 Ul入刃 IK甲烷溶液中，在加卜、罐酸钠干燎 After evaporauon of the solvent, the residue is distilledto give (he cmcie pnxiuct. b.p. 68-74° (0.9 mm.).蒸去溶剂使得到巾 济白68-74( (0.9mm) After

21、tedisiillation diere is obtained 60-66 g. (81-8998 )of mesitaldehyde； b.p. 115-115° (11 nini.). n20D 1.5538.币因匐利6(K66g (8I-89<；( > 的2W& 川14乂中带沸13/15C (Unim) 反应式:BrHtfI IHA(Oj H反应机即二亲核取代£略)ncucibcii(2)然1: Riechc A., el ；il. Org. Sytuh., Cull Vd. 5: 4. 反同式工反底机理：余电取代(停一克反应一 中俄化)3、2-

22、Methyl-4-ethoxalylcyclopentane-1,3,5-trione. A solution of sodium ethoxide is prepared in a 2-l. three-necked, round-bottomed flask fitted with a mercury-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 etha

23、nol. 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 and stirred.溶液在0-5 C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) ofdieth

24、yl 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,in an ice ba th.完全力口入后，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0C。The mixtureorange-red mixture is allowed to warm with co

25、ntinued stirring to room temperature, heated under reflux for 30 minutes, and cooled again to 0is decomposed by stirring with 165 ml. of sulfuric acid (1:1 by volume) added inThe sodium sulfateportions.将165ml浓硫酸(体积比1:1 )在搅拌加入，分解混合物。formed is filtered by suction and washed with ethanol (150200 ml.) (

26、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 .合并滤液和洗涤液后蒸发浓缩。The yellowish brownproduct which accumulates by slow crystallization is collected by filtration, washed with 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

27、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 mother 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. (5359%)产品总共180-200g (产率 53-59% ) (Note 2). This crud

28、e 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 obtained bycrystallization from ethyl acetate after treatment with Norit activated carbon, 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 C。The procedure for 2- pyrrolealdehyde 2- 口比咯甲醛In a 3-l.

29、 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 maintained

30、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 C , 169g (1.1mol)的磷酰氯通过滴液漏斗在 15分钟内滴力口。An exothermic reaction occurs with the formation of the phosphorusoxychloride - dimethylformamide complex.放

31、热反应生成磷酰氯二甲基甲酰胺化合物。The icebath 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 冰浴下力口入 250ml 的二氯乙烯。 When the internal temperature has been lowered to 5 , a solulion of 67 g. (1.0 mol

32、e) 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.当内音B温度降至U 5度时，把67g (1.0mol)新蒸储的口比咯加入到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力口。After the addition is complete, the ice bath is replaced with a heatin

33、g mantle, andthe 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 solution of 750 g. (5.5 mol

34、es) 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 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 15minutes, 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

35、。The cooled mixture is transferred to a 3-l. separatory funnel, and the ethylene dichloride layeris removed.冷却的混合物转移到分液漏斗中，出去二氯乙烯层。The aqueous phase isextracted three times with a total of about 500 ml. of ether. 水相用 500ml 乙醛分三次萃取。Theether and ethylene chloride solutions are combined and washed with

36、 three 100-ml. portions of saturated aqueous sodium carbonate solution, which is added cautiously at first to avoid too rapid evolution of carbon dioxide.合并乙醛和氯乙烯溶液，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 sodium carbonate, the solvents are dis

37、tilled, and the remaining liquid is transferred to a Claisen flask and distilled from an oil bath under reduced pressure (Note 5).非水溶液用无水碳酸钠干燥，蒸储溶剂，余下的溶液移入克氏烧瓶在油浴中减压蒸储。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

38、 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，粗品产量85-90g (89-95%)。A sample dried on a clay plate melts at 35 W0 °.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 th

39、e ratio of 1 g.of crude 2-pyrrolealdehyde to 25 ml. of solvent, and cooling the solution slowly to room temperature, followed by refrigeration for a few hours.粗品溶解在沸腾的石油醒中(沸点 40-60 度)，一克粗品2-甲基口比咤加入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 in approximately 85% recovery. 纯品醛

40、是从粗品中得至L 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)反应式反向机母炯炯（三次）缩门反应式工4、(1)In a 3L. round-bottomed flask (Note 1) fitted with a reflux condenser areplaced 625 cc. of 95 per cent alcohol (Note 2), 500 cc. of water, 500 g. (

41、476 cc., 4.7moles) of pure benzaldehyde (Note 3), and 50 g. of sodium cyanide (9698 percent).在配有回流7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% 的富化钠。 The mixture is then heated andkept 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,

42、 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,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

43、的安息香。(90 92 per cent of thetheoretical amount). 理论产率 90-92% 。 In order to obtain it completely pure, thecrude substance is recrystallized from 95 per cent alcohol, 90 g. of crude materialbeing dissolved in about 700 cc. of boiling alcohol; upon cooling, a yield of 83 g. ofwhite, pure benzoin which m

44、elts 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. 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 introductionof hydrogen chlori

45、de, are placed 50 g. (0.36 mole) of p-nitrophenol (Note 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

46、mixture is stirred while the temperature is maintained at 70 2±° for 4 -5 hours by means of a water bath (Note 4).在水浴中保持 70 立度搅拌 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

47、 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 -5- nitrobenzyl chloride begins to separate as a solid about 1 hour after the beginning of the reaction.在反应开始后白一个小时，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

48、hour whereby more crystals separate, 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).

49、 The yield is 46 g. (69% based on p-nitrophenol) of a white product melting at 129 T30 .白色产物 46g (对硝基苯酚含 69%)熔点 129-130 度U）参考答案: 反应式：*反应机理提示：安息香缩合参考答案: 反应式：学反应机理提示:氯甲基化反屈5、B. Benzyl trans-1,3- butadiene -1- carbamateA dry, 1-l., three-necked, round-bottomed flask is equipped with a magnetic stirring

50、 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.(0.50mole)of trans -2,4-pentadienoicacid, 80g.(0.62mole)of N,N -diisopropylethylamine,and 300 ml. of acetone (Note6). The resultingsolution is st

51、irred and cooled to 0in an ice ° yalt bath. A solution of 55 g. (0.51 mole)of ethyl chloroformate in 150temperature is maintained below 0ml.of acetone is added over 30 minutes(Note 7). Stirring is continued for an additionalwhile theof sodiumtemperature below 0.The contents of the flask are sti

52、rred for an additional 101530 minutes at 0°, 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 theminutes at 0of ice-water.of toluene.The acyl azide is isolatedThe combined tolueneextractsby extractionare driedwith

53、six 250-ml.portionssulfate for20 minutesand concentratedto a volumeover anhydrous magnesium of ca. 300 ml. on a rotaryevaporatorazide isat a waterpotentiallybath temperature explosive. Theof 40 50 ° (Note 10). Caution! The acylsolution should not beevaporated to(Note 9) and poured into a 2-l. s

54、eparatory funnelcontaining 500 ml.dryness.round-bottomedpressure-equalizingmantle ischargedflask equipped with a mechanical dropping funnel, a simple distillationwith 43 g. (0.40 mole) ofbenzylstirrer,head,and aalcohol, 250500-ml.heatingmg.While the toluene solution is being concentrated, a dry, 2-l

55、., three-necked,of 4- tert -butylcatechol (Note 11), and 200 ml. of toluene. About 30 ml. of toulene is distilled from the flask to remove trace amounts of water, and the distillation headis replaced with a condenser fitted with a nitrogen inlet.The toluene solutionisstirred and heated at a rapid reflux under a nitrogen atmosphereasthe toluene solution of the acyl azide is added over 30 minutes. The disappearance of the acyl azide and isocyanate is followed by IR analysis (No