藥物合成反應(yīng)課后翻譯

1、1、About 216224 g. (1.621.68 moles) of powdered anhydrous aluminum chloride 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(wú)水三氯化鋁。 While the free-flowing catalyst is stirred (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. 自由流動(dòng)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 ketone are not dispersed, darkening or charring occurs. 放熱反應(yīng)，假如滴加的酮不能被分散，就會(huì)變黑或是碳化。When about one-third of the acetophenone has been added, the mixture becomes a viscous ball-like mass that is diff

3、icult 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(gè)很難攪拌的粘性的球狀團(tuán)塊。 Turning of the stirrer by hand or more rapid addition of ketone is necessary at this point. 在這時(shí)，改用手動(dòng)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 to produce a temperature above 180°. 然而，速度不能太快，當(dāng)反應(yīng)溫度超過(guò)180時(shí)。Near the end

4、 of the 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.當(dāng)快滴加完時(shí)，團(tuán)塊開(kāi)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 add

5、ed dropwise to the well-stirred mixture over a 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 all the bromine has been added, 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蒸氣浴下攪拌1小時(shí)。 The complex is added in portions to a well-stirred mixture of 1

6、.3 l. of cracked ice and 100 ml. of concentrated 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 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 the mixture 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(lái)。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%的小蘇打洗滌，用無(wú)水硫酸鈉干燥。The ether is removed by distillation at atmospheric pressure, and crude 3-bromoacetophenone is stripped from a few grams of heavy dark residue by distillation at reduced pressure. 乙醚在常壓下蒸餾，

9、微量的溴苯乙酮通過(guò)減壓蒸餾的方法從大量深色殘?jiān)斜环蛛x出來(lái)。The colorless distillate is carefully fractionated to obtain 94100 g.通過(guò)分餾，得到無(wú)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

10、 reflux condenser 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(wú)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 droppin

11、g funnel, and a cold mixture (515°) of 108 g. (1.50 moles) of freshly distilled 2-butanone and 482 g. (3.30 moles) of diethyl 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 0° in 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 mixture is decomposed by stirring with 165 ml. of sulfuric acid (1:1 by volume) add

13、ed in portions.將165ml濃硫酸（體積比1:1）在攪拌加入，分解混合物。 The sodium sulfate formed is filtered by suction and washed with ethanol (150200 ml.) (Note 2). 硫酸鈉抽濾后用乙醇（150200 ml）洗滌。The washings and filtrate are combined and concentrated by evaporation .合并濾液和洗滌液后蒸發(fā)濃縮。The yellowish brown product which accumulates by s

14、low crystallization is collected by filtration, washed with small quantities of ice-cold water, and dried in air. 過(guò)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 by cooling furnishes an additional 4050 g. of

15、 the 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 in the next step.粗品（熔點(diǎn)120130）用于下一步中 A pure sample can be obtained by crystallization from ethyl acetate after treatment with Norit

16、activated carbon, m.p. 160162°.純品是經(jīng)過(guò)活性炭處理后在乙酸乙酯中結(jié)晶得到，熔點(diǎn)160162。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 placed 80 g. (1.1 moles) of dimethylformamide (Note 1).在配有封閉攪拌器、滴液漏斗和

17、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。 The flask 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 15 minutes. 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(guò)滴液漏斗在15分鐘內(nèi)滴加

18、。An exothermic reaction occurs with the formation of the phosphorus oxychloride - dimethylformamide complex. 放熱反應(yīng)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，在攪拌15分鐘。The ice bath is replaced, and 250 ml. of ethylene dichloride is added to the mixtu

19、re. 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, cooled mixture over a period of 1 hour. 當(dāng)內(nèi)部溫度降到5度時(shí)，把67g（1.0mol）新蒸餾的

20、吡咯加入到250二氯乙烯中，通過(guò)滴液漏斗在1小時(shí)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 copious evolution 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 mixture is

21、 then cooled to 2530°, 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(guò)滴液漏斗加入750g（5.5mol）的三水醋酸鈉溶液，開(kāi)始要小心，然后要盡可能地快。The reaction mixture is aga

22、in refluxed for 15 minutes, vigorous stirring being maintained all the while (Note 4). 反應(yīng)物在充分?jǐn)嚢柘轮匦禄亓?5分鐘。The cooled mixture is transferred to a 3-l. separatory funnel, and the ethylene dichloride layer is 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 is extracted three times with a total of abou

23、t 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 rapid evolution of carbon dioxide.合并乙醚和氯乙烯溶液，用100ml飽和碳酸鈉溶液分三次洗滌，然后通入二氧化碳，通

24、入時(shí)要小心不要太快。 The non- aqueous solution is then dried over anhydrous 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(wú)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。The aldehyde boils at 78

25、76; at 2 mm.; there is very little fore-run and very little residue. 醛沸點(diǎn)78度在2mm；很少有預(yù)留無(wú)和殘?jiān)he yield of crude 2-pyrrolealdehyde is 8590 g. (8995%), as an almost water-white liquid which soon crystallizes. 當(dāng)幾乎透明的液體會(huì)馬上結(jié)晶，粗品產(chǎn)量85-90g（89-95%）。A sample dried on a clay plate melts at 3540°. 樣品在素?zé)砂迳细稍铮?/p>

26、熔點(diǎn)35-40度。The crude 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 room temperature, followed by refrigeration for a few hours.粗品溶解在沸騰的石油醚中（沸點(diǎn)40-60度），一克粗品2-甲基吡啶加入2

27、5ml溶劑，在室溫下冷卻，這后再冷凍數(shù)小時(shí)。 The pure 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 7879% of pure 2-pyrrolealdehyde, m.p. 4445°. 總得率為78-79%熔點(diǎn)44-45度。（1）反應(yīng)式4、(1)In a 3L. round-bottomed flask (Note 1) fitted with a reflux condenser

28、 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 per cent). 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 then heated and kept boiling for on

29、e-half hour (Note 4). 混合物加熱并保持沸騰1.5小時(shí)。In the course of about twenty minutes, crystals begin to separate from the hot solution. 在20分鐘后晶體開(kāi)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，抽濾并用少量水洗滌The yield of dry cr

30、ude benzoin, which is white or light yellow, is 450460 g.有450-460g白色或亮黃色的干燥的安息香。 (9092 per cent of the theoretical amount). 理論產(chǎn)率90-92%。In order to obtain it completely pure, the crude substance is recrystallized from 95 per cent alcohol, 90 g. of crude material being dissolved in about 700 cc. of bo

31、iling alcohol; upon cooling, a yield of 83 g. of white, pure benzoin which melts at 129° is 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(diǎn)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 reflux condenser, and bent glass tub

32、e reaching below the surface of the liquid for the introduction of hydrogen chloride, 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). 在配有機(jī)械攪拌，短期冷凝回流器和一個(gè)為的是深入液面下通氯

33、化氫氣體的彎曲的玻璃管三口圓底燒瓶中加入50g（0.36mol）對(duì)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 45 hours by means of a water bath (Note 4). 在水浴中保持70±2度攪拌4-5小時(shí)。During this time hydrogen chloride is bubbled into the reaction mixture thr

34、ough the bent glass tube, and the excess gas is carried away through the reflux condenser to a hood or gas- absorption trap (Note 5). 在此期間通過(guò)玻璃彎管把氯化氫氣體通入反應(yīng)混合物中，過(guò)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 hour after the beginning of the reaction

35、.在反應(yīng)開(kāi)始后的一個(gè)小時(shí)，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(shí)，使更多的晶體析出，之后把酸性液體過(guò)濾或傾析得到晶體。The 2-hydroxy-5-nitrobenzyl chloride is purified by r

36、ecrystallization 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 on p-nitrophenol) of a white product melting at 129130°.白色產(chǎn)物46g（對(duì)硝基苯酚含69%）熔點(diǎn)129-130度5、B. Benzyl trans-1,3-butadiene-1-carbamate. A dry, 1-l., three-necked, round-bottomed

37、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. (0.50 mole) of trans-2,4-pentadienoic acid, 80 g. (0.62 mole) of N,N-dii

38、sopropylethylamine, and 300 ml. of acetone (Note 6). The resulting solution is stirred and cooled to 0° in an icesalt bath. A solution of 55 g. (0.51 mole) of ethyl chloroformate in 150 ml. of acetone is added over 30 minutes while the temperatu

39、re is maintained below 0° (Note 7). Stirring is continued for an additional 30 minutes at 0°, after which a chilled solution of 65 g. (1.0 mole) of sodium azide (Note 8) in 170 ml. of water is added over a 20-minute interval, keeping the temperature below 0°.

40、The contents of the flask are stirred for an additional 1015 minutes at 0° (Note 9) and poured into a 2-l. separatory funnelcontaining 500 ml. of ice-water. The acyl azide is isolated by extraction with six 250-ml. portions of toluene. The combined tolueneextracts

41、are dried over anhydrous magnesium sulfate for 20 minutes and concentrated to a volume of ca. 300 ml. on a rotary evaporator at a water bath temperature of 4050° (Note 10). Caution! The acyl azide is potentially explosive. The solution should not be evaporated

42、 to dryness. While the toluene 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 distillation head, and a heating mantle is charged with 43 g. (0.40

43、 mole) ofbenzyl alcohol, 250 mg. 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 head is replaced with a condenser fitted with a nitrogen inlet. Th

44、e toluene solution is stirred and heated at a rapid reflux under a nitrogen atmosphere as the toluene solution of the acyl azide is added over 30 minutes. The disappearance of the acyl azide and isocyanate is followed by IR analysis (Note 12). Conversion to the car

45、bamate is complete in 1030 minutes, after which the solution is cooled rapidly to room temperature by immersing the flask in an ice bath. The toluene is rapidly removed on a rotary evaporator with the water bath at 4050°, producing a yellow solid residue (Note 13) which

46、 is dissolved in 50 ml. of 95% ethanol and allowed to crystallize in a freezer at 25° for several hours. Two crops of pale yellow crystals, m.p. 6972°, are isolated which total 3946 g. after drying under reduced pressure. Concentration of the mother liquor affords an oily residue that is placed on a 6 × 80-cm. column packed with 500 g. of silica gel