藥物合成反應(yīng)(聞韌第三版)課后翻譯

1、1、About 216 224 g. (1.621.68 moles) of powdered anhydrous aluminumchloride is added to a 1Lthree-necked flask.在 1L的三口燒瓶中加入大約216-224g(1.621.68 moles)的無水三氯化鋁。While the free-flowing catalyst isstirred (Note 3), 81 g. (0.67 mole) of acetophenone is added from the droppingfunnel in a slow stream over a p

2、eriod of 2030 minutes.自由流動的催化劑邊攪拌邊用滴液漏斗緩慢滴加81g 苯乙酰。Considerable heat is evolved, and, if the drops of ketoneare not dispersed, darkening or charring occurs.放熱反應(yīng)，假如滴加的酮不能被分散，就會變黑或是碳化。 When about one-third of the acetophenone has been added, themixture becomes a viscous ball-like mass that is difficul

3、t to stir.當(dāng)三分之一的乙酰苯被滴加，反應(yīng)混合物變成一個很難攪拌的粘性的球狀團塊。Turning of the stirrer by hand ormore rapid addition of ketone is necessary at this point.在這時，改用手動攪拌或快速滴加酮是非常必要的。 The addition of ketone, however, should not be so rapid as toproduce a temperature above 180. °然而，速度不能太快，當(dāng)反應(yīng)溫度超過180 時。Near the end of th

4、e addition, the mass becomes molten and can be stirred easilywithout being either heated or cooled. The molten mass, in which the acetophenoneis complexed with aluminum chloride, ranges in color from tan to brown.當(dāng)快滴加完時，團塊開始融化，表明苯乙酰已經(jīng)和三氯化鋁混合完全，顏色也逐漸從黃褐色變?yōu)樽厣?。Bromine (128 g., 0.80 mole) is added dropw

5、ise to the well-stirred mixture overa period of 40 minutes (Note 4).在 40分鐘內(nèi)在攪拌下把溴緩慢滴加到混合物中。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蒸氣浴下攪拌 1 小時。 The complex isadded in portions to a well-stirred mixture of 1.3 l. of

6、 cracked ice and 100 ml. ofconcentrated hydrochloric acid in a 2-l. beaker (Note 6).反應(yīng)物加入到 1.3L 碎冰和100ml 濃鹽酸的混合物中在 2L的燒杯中混合均勻。 Part of the cold aqueous layer is addedto the reaction flask to decompose whatever part of the reaction mixture remainsthere, and the resulting mixture is added to the beake

7、r.把部分的冰水層加入到燒瓶中洗滌殘留物，然后合并到燒杯中。The dark oil that settles out is extracted from themixture with four 150-ml. portions of ether分四次把深色的油從混合物中用150ml 萃取出來。 The extracts are combined, washed consecutively with 100 ml. of water and100 ml. of 5% aqueous sodium bicarbonate solution, dried with anhydrous sodiu

8、msulfate, and transferred to a short-necked distillation flask.合并萃取液，用 100ml水和 100ml 5%的小蘇打洗滌， 用無水硫酸鈉干燥。 The ether is removed by distillation atatmospheric pressure, and crude 3-bromoacetophenone is stripped from a fewgrams of heavy dark residue by distillation at reduced pressure.乙醚在常壓下蒸餾，微量的溴苯乙酮通過

9、減壓蒸餾的方法從大量深色殘渣中被分離出來。The colorless distillate iscarefully fractionated to obtain 94100 g.通過分餾，得到無色的流出液94-100g2、反應(yīng)式：3、2-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 co

10、ndenser carrying a drying tube, and a stopper by the addition of 69.0 g. (3 moles) of sodium to 950 ml. of absolute ethanol. 69.0g（3mol ）鈉和 950ml 無水乙醇在配有干燥回流冷凝管和汞封攪拌器的2L三口圓底燒瓶中制備乙醇鈉。 The solution is cooled to 05° in an ice bath and stirred.溶液在 0-5 下冰浴攪拌。 The stopper is replaced by a dropping fu

11、nnel, 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 ）的乙二酸二乙酯在 5-15下低溫混合，在 30分鐘內(nèi)逐步滴加到溶液中。After the addition is complete,

12、 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，橘紅色的粘稠物繼續(xù)攪拌至室溫，加熱回流30 分鐘后在冰浴中冷卻至0 。 The mixtureis decomposed by stirring with 165 ml. of sulfuric acid (1:1 by volume) adde

13、d inportions. 將 165ml 濃硫酸（體積比1:1 ）在攪拌加入，分解混合物。The sodium sulfateformed is filtered by suction and washed with ethanol (150200 ml.) (Note 2).硫酸鈉抽濾后用乙醇（150 200 ml）洗滌。 The washings and filtrate are combined andconcentrated by evaporation .合并濾液和洗滌液后蒸發(fā)濃縮。The yellowish brownproduct which accumulates by sl

14、ow crystallization is collected by filtration, washedwith small quantities of ice-cold water, and dried in air.過濾緩慢析出的棕黃色產(chǎn)品用小劑量的冰水洗滌后在空氣中干燥。The crude product weighs 140150 g. 粗產(chǎn)品140-150g。 Further evaporative concentration of the mother liquor followed bycooling furnishes an additional 4050 g. of the

15、 keto ester,此外將母液用冷凍蒸發(fā)濃縮后又得到40-50g的酮酯。 bringing the total yield to 180200 g. (5359%) 產(chǎn)品總共180-200g（產(chǎn)率53-59% ） (Note 2). This crude material (m.p. 120130 °) is used inthe next step.粗品（熔點 120 130 ）用于下一步中A pure sample can be obtained bycrystallization from ethyl acetate after treatment with Norit a

16、ctivated carbon, m.p.160 162 °. 純品是經(jīng)過活性炭處理后在乙酸乙酯中結(jié)晶得到，熔點160 162 。The procedure for 2- pyrrolealdehyde 2- 吡咯甲醛In a 3-l. three-necked round-bottomed flask, fitted witha sealed stirrer, a dropping funnel,and a reflux condenser, is placed 80 g. (1.1 moles) of dimethylformamide (Note 1).在配有封閉攪拌器、滴液漏

17、斗和冷凝回流裝置的三口圓底燒瓶中放入80g（ 1.1mol ）的二甲基甲酰胺。 Theflask is immersed in an ice bath, and the internal temperature is maintained at 1020°,while 169 g.(1.1 moles) of phosphorus oxychloride is added through the dropping funnel over a period of 15minutes. 燒瓶浸入冰浴中，內(nèi)部溫度保持在10-20 ， 169g （ 1.1mol ）的磷酰氯通過滴液漏斗在 1

18、5分鐘內(nèi)滴加。 An exothermic reaction occurs with the formationof thephosphorusoxychloride - dimethylformamide complex.放熱反應(yīng)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，在攪拌15分鐘。The ice bath is replaced, and 250 ml. of ethylene dichloride is added to the mix

19、ture.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 aclean dropping funnel to the stirred, cooled mixture over a period of 1 hour.當(dāng)內(nèi)部溫度降到 5度時，把 67g（ 1.0mol

20、）新蒸餾的吡咯加入到250二氯乙烯中，通過滴液漏斗在1小時內(nèi)低溫下邊攪拌邊滴加。 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 copiousevolution of hydrogen chloride. 滴加完后，用加熱裝置取代冰浴，攪拌回流15分鐘，直到有大量氯化氫產(chǎn)生。The mixtu

21、re 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. 當(dāng)混合物降溫到 25-30 后，通過滴液漏斗加入 750g （ 5.5mol）的三水醋酸鈉溶液，開始要小心，然后要盡可能地快。The reaction mixt

22、ure is again refluxed for 15minutes, vigorous stirring being maintained all the while (Note 4). 反應(yīng)物在充分攪拌下重新回流15分鐘。40-60 The pureThe cooled mixture is transferred to a 3-l. separatory funnel, and the ethylene dichloride layeris removed. 冷卻的混合物轉(zhuǎn)移到分液漏斗中，出去二氯乙烯層。The aqueous phase isextracted three times

23、 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 too rapidevolution of carbon dioxide. 合并乙醚和氯乙烯溶液，用100m

24、l 飽和碳酸鈉溶液分三次洗滌，然后通入二氧化碳，通入時要小心不要太快。The non- aqueous solution is then dried overanhydrous sodium carbonate, the solvents are distilled, and the remaining liquid is transferred to a Claisen flask and distilled from an oil bath under reduced pressure (Note 5). 非水溶液用無水碳酸鈉干燥， 蒸餾溶劑， 余下的溶液移入克氏燒瓶在油浴中減壓蒸餾。Th

25、e aldehyde boils at 78°at 2 mm.; there is very little fore-run and very little residue. 醛沸點 78 度在 2mm；很少有預(yù)留無和殘渣。 The yield of crude 2-pyrrolealdehyde is 85 90 g. (8995%), as an almost water-whiteliquid which soon crystallizes. 當(dāng)幾乎透明的液體會馬上結(jié)晶，粗品產(chǎn)量85-90g（ 89-95% ）。A sample dried on a clay plate me

26、lts at 35 40°. 樣品在素?zé)砂迳细稍?，熔點35-40 度。 Thecrude product is purified by dissolving in boiling petroleum ether (b.p. 4060°), 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

27、沸騰的石油醚中（沸點度），一克粗品 2-甲基吡啶加入 25ml 溶劑，在室溫下冷卻，這后再冷凍數(shù)小時。aldehyde is obtained from the crude in approximately 85% recovery. 純品醛是從粗品中得到，收率 85%。 The over-all yield from pyrrole is 78 79% of pure 2-pyrrolealdehyde, m.p. 44 45°. 總得率為 78-79% 熔點 44-45 度。（1）反應(yīng)式4、(1)In a 3L. round-bottomed flask (Note 1) fit

28、ted with a reflux condenser areplaced 625 cc. of 95 per cent alcohol (Note 2), 500 cc. of water, 500 g. (476 cc., 4.7moles) of pure benzaldehyde (Note 3), and 50 g. of sodium cyanide (9698 percent).在配有回流冷凝器的3L圓底燒瓶中加入 625ml 的 95% 酒精、 500ml 水、 500g（476ml， 4,7mol）的苯甲醛和50g 96-98%的氰化鈉。 The mixture is the

29、n heated andkept boiling for one-half hour (Note 4).混合物加熱并保持沸騰1.5小時。 In the courseof about twenty minutes, crystals begin to separate from the hot solution.在 20分鐘后晶體開始從熱溶液中析出。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分鐘，冷卻溶液

30、，抽濾并用少量水洗滌 The yield of dry crude benzoin, which is white or light yellow, is450 460 g. 有 450-460g白色或亮黃色的干燥的安息香。(90 92 per cent of thetheoretical amount).理論產(chǎn)率 90-92% 。 In order to obtain it completely pure, thecrude substance is recrystallized from 95 per cent alcohol, 90 g. of crude materialbeing d

31、issolved in about 700 cc. of boiling alcohol; upon cooling, a yield of 83 g. ofwhite, pure benzoin which melts at 129is obtained°.為了得到純度高的產(chǎn)品，粗產(chǎn)品要在酒精中重結(jié)晶，90g 粗品溶解在 700ml 沸騰的酒精中，冷卻，得到 83g 熔點為 129 攝氏度的白色安息香純品。(2)In a 1L. three-necked round-bottomed flask equipped with a mechanical stirrer, short r

32、eflux 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. ofconcentrated hydrochloric acid, 5 ml. of concentrated sulfuric acid (Note 2), and 76 g. (1 mole) of methylal (Note 3

33、). 在配有機械攪拌， 短期冷凝回流器和一個為的是深入液面下通氯化氫氣體的彎曲的玻璃管三口圓底燒瓶中加入50g（ 0.36mol ）對硝基苯酚， 650ml 的濃鹽酸， 5ml的濃硫酸和 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 (Note 4). 在水浴中保持 70±2度攪拌 4-5小時。 During this time hydrogen chlorid

34、e 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- absorptiontrap (Note 5).在此期間通過玻璃彎管把氯化氫氣體通入反應(yīng)混合物中，過量的氣體被帶到回流冷凝器被氣體吸收罩吸收。The 2- hydroxyl -5- nitrobenzyl chloride begins to separate as a solid about 1

35、hour after the beginning of the reaction. 在反應(yīng)開始后的一個小時， 2-羥基 -5-硝基苯氯化物作為固體被分離。 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 crystals (Note 6). 最后把混合物在冰中冷卻1 小 時 ， 使 更 多 的 晶 體 析 出 ， 之 后 把 酸 性 液 體

36、 過 濾 或 傾 析 得 到 晶 體 。 The2-hydroxy-5-nitrobenzyl chloride is purified by recrystallization from 125 ml. of hot benzene 2-羥基 -5- 硝基苯氯化物在熱的苯中重結(jié)晶純化。(Note 7). The yield is 46 g. (69% based onp-nitrophenol) of a white product melting at 129 130 °.白色產(chǎn)物 46g（對硝基苯酚含 69%）熔點 129-130 度5、 B. Benzyltrans-1,3-

37、butadiene-1- carbamate .A dry, 1-l., three-necked, round-bottomed flask is equipped with a magneticstirring bar, a thermometer, and a 250-ml., pressure-equalizing dropping funnelbearing a nitrogen inlet. The flask is flushed with nitrogen and charged with 49 g.(0.50mole)of trans -2,4-pentadienoicaci

38、d, 80g.(0.62mole)ofN,N -diisopropylethylamine,and 300ml.of acetone (Note6).Theresultingsolution is stirred and cooled to 0in an ice°salt bath. A solution of 55 g. (0.51 mole)of ethylchloroformate in 150ml.of acetone isaddedover30minuteswhilethetemperature is maintained below 0(Note°7). Sti

39、rring is continued for an additional30minutesat0°,afterwhichachilledsolutionof 65g.(1.0mole)of sodiumazide (Note 8) in 170 ml. of water is added over a 20-minute interval, keeping thetemperature below 0. °The contents of the flask are stirred for an additional 1015minutes at 0(Note°9)

40、 and poured into a 2-l. separatory funnelcontaining 500 ml.ofice-water.Theacylazideis isolatedbyextractionwithsix 250-ml.portionsof toluene.Thecombined tolueneextractsaredriedover anhydrous magnesiumsulfate for20minutesandconcentratedtoavolumeofca.300ml.ona rotaryevaporatoratawaterbathtemperatureof4

41、0 50 °(Note10).Caution!Theacylazideispotentiallyexplosive.Thesolutionshouldnotbeevaporatedtodryness.While the toluene solution is being concentrated, a dry, 2-l., three-necked,round-bottomedflaskequippedwithamechanicalstirrer,a500-ml.pressure-equalizingdroppingfunnel,asimpledistillationhead,and

42、aheatingmantle ischargedwith 43g.(0.40mole)ofbenzylalcohol, 250mg.of 4- tert-butylcatechol (Note 11), and 200 ml. of toluene. About 30 ml. of toulene isdistilled from the flask to remove trace amounts of water, and the distillation headisreplacedwithacondenserfitted witha nitrogen inlet.The toluene

43、solutionisstirredandheatedatarapidrefluxundera nitrogen atmosphereasthe toluene solution of the acyl azide is added over 30 minutes. The disappearanceof the acyl azide and isocyanate is followed by IR analysis (Note 12). Conversion tothecarbamateis completein10 30minutes,afterwhichthesolutioniscooledrapidly to room temperature by immersing the flask in an ice bath. The toluene israpidly removed on a rotary evaporator with the water bath at 4050 °, producing ayellowsolidresidue (Note13) whichisdissolvedin 50ml.of95% ethanol andallowed to crystallize in a freezer at -25° for seve