脂肪鹵代物的合成

1、經(jīng)典合成反應標準操作脂肪鹵代物的合成 經(jīng)典化學合成反應標準操作脂肪鹵代物的合成1. 前 言2. 脂肪族氯化物的制備2.1醇的氯代 2.1.1醇和氯化氫反應的方法示例2.1.2醇和氯化亞砜的反應2.1.3醇和氯化磷的反應2.1.4醇和有機磷氯化物的反應示例2.1.5醇和三苯基膦和四氯化碳加合物的反應2.1.6醇和三苯基膦和六氯代丙酮加合物的反應2.2 磺酸酯的氯置換反應氯化鋰作為氯化劑的磺酸酯氯置換反應2.3其他的一些制備脂肪族氯代烴的方法3.脂肪族溴化物的制備3.1 醇的溴代3.1.1醇和溴化氫反應的方法示例3.1.2醇和氯化磷的反應3.1.3醇和三苯基膦和四溴化碳加合物的反應3.1.4醇和三

2、苯基膦和溴的加合物的反應3.1.5醇和三苯基膦和NBS加合物的反應3.2磺酸酯或氯素的溴置換反應例3.2.1磺酸酯的溴置換反應例3.2.2氯素交換反應3.3其他的一些制備脂肪族氯代烴的方法4.脂肪族碘化物的制備4.1 前言4.2脂肪型醇的直接碘代 4.2.1 (PhO)3P, CH3I體系 4.2.2 Ph3P, I2, imidazole體系 4.2.3 P, I2體系 4.2.4 H3PO4, KI體系4.3脂肪型氯代物或溴代物的碘交換 4.3.1氯代物系列4.3.2溴代物系列4.4磺酸酯或鹵素素的碘置換反應例4.5其他的一些制備脂肪族碘代烴的方法5參考文獻1. 前 言鹵代烴是不僅是很多工

3、業(yè)生產(chǎn)的重要產(chǎn)品，也是合成其他化合物的重要中間體，通過不同的反應可以將鹵原子轉(zhuǎn)變成各種其他官能團，也可以進行碳鏈的增長。除了由烴基氫直接鹵代可得到鹵代烴外，還有很多種方法將其他的官能團轉(zhuǎn)變成鹵代烴，如醇羥基鹵代，醛酮鹵代，羧酸脫羧后鹵代，磺酸酯的鹵素交換，有機金屬化合物鹵代。其中醇羥基的鹵置換反應是制備鹵化物的重要方法，常用的鹵化試劑有氫鹵酸、含磷鹵化物和含硫鹵化物等，極大多數(shù)屬于醇羥基被鹵素負離子親核取代的機理。以下按照氯化物，溴化物，碘化物的制備分別加以討論。氟代烴的制備容以后討論2脂肪族氯化物的制備2.1 醇的氯代2.1.1醇與氯化氫反應在親核取代反應中，醇羥基的活性順序為叔羥基仲羥基伯

4、羥基，芐位和烯丙位的羥基也很活波，這是由于碳正離子穩(wěn)定性差別的結(jié)果。同樣理由，活性較大的叔醇、芐醇的氯置換反應傾向于SN1機理，而其他醇的反應，大多數(shù)以SN2反應機理為主。醇和HCl的反應屬于可逆性平衡反應，其反應難易程度取決于醇和HCl的濃度以及平衡點的移動方向。若增加醇和HCl的濃度，以及能夠不斷移去產(chǎn)物和反應生成的水，則均有利于加速氯置換反應和提高收率。在醇的氯置換反應中，活性較大的叔醇、芐醇等可以直接用濃鹽酸或氯化氫氣體，而伯醇常用盧卡斯試劑（濃煙酸-氯化鋅）進行氯置換反應。在某些仲醇、叔醇和位具有叔碳取代基的伯醇的反應中，若反應溫度過高，會產(chǎn)生重排、異構(gòu)化和脫氯等副反應。Exampl

5、e A: the preparation of t-Butyl Chloride (2-Chloro-2-Methylpropane)In a 250 ml of separatory funnel place 25 g (0.34 mol) of 2-methylpropan-2-ol and 85 ml of concentrated hydrochloric acid and shake the mixture from time to time during 20 min. After each shaking, loosen the stopper to relieve any in

6、ternal pressure. Allow the mixture to stand for a few minutes until the layers have separated sharply; draw off and discard the lower acid layer. Wash the halide with 20 ml of 5% sodium hydrogen carbonate solution and then with 20 ml of water. Dry the preparation with 5 g of anhydrous calcium chlori

7、de or anhydrous calcium sulphate. Decant the dried liquid through a funnel supporting a fluted filter paper into a 100 ml distilling flask and distil. Collect the fraction boiling at 49-51. The yield of t-butyl-chloride is 28 g (90%).Ref: Practical Organic Chemistry, 4th edition, 556Example B: the p

8、reparation of Butyl Chloride (1-Chlorobutane)Fit a 250 ml of round-bottomed flask with a reflux condenser, the top of which is connected to a device for absorbing hydrogen chloride. Place 68 g (0.5 mol) of anhydrous zinc chloride and 40 ml (47.5 g) of concentrated hydrochloric acid in the flask, add

9、 18.5 g (23 ml, 0.25 mol) of butane-1-ol and reflux the mixture gently for 2 hours. Arrange the condenser for downward distillation, and distil the reaction product, collecting the material which boils below 115. Separate the upper layer of the distillate, mix it with an equal volume of concentrated

10、 sulphuric aced and transfer the mixture to a 250 ml of flask fitted with a reflux condenser. Reflux gently for 15-30 min, and then distil the chloride from the acid; it will pass over at 76-79. Wash the distillate successively with 25 ml of water, 10 ml of 5% sodium hydroxide solution and 25 ml if

11、water, dry over 1-2 g of anhydrous calcium chloride, filter and distil from a small distilling flask. Collect the butyl chloride at 75-78. The yield is 15-16 g (65-69%). Ref : Practical Organic Chemistry, 4th edition, 5572.1.2 醇和氯化亞砜的反應氯化亞砜是醇的氯置換反應中一種常用的良好試劑，主要是反應中生成的氯化氫和二氧化硫均為氣體，易揮發(fā)除去而無殘留物，經(jīng)直接蒸餾可得到

12、純凈的氯代烴。醇和氯化亞砜的反應過程，首先形成氯化亞硫酸酯(4)，然后斷裂C-O鍵，釋放出二氧化硫生成氯代烴。(4)的分解方式與溶劑極性有關，同時又決定了醇碳原子構(gòu)型在氯化反應中的變化。如在二氧六環(huán)中反應，由于二氧六環(huán)的氧原子上未共用電子對從酯基的反位和酯碳原子形成微弱的鍵，增加了反位方向的位阻，促使氯離子作SNi取代，結(jié)果保留了醇碳原子原有的構(gòu)型；但是如果是在吡啶中反應時，由于氯化氫和吡啶成鹽而貯存于反應液中，離解后的氯離子可從酯基的反應作SN2取代，得到構(gòu)型翻轉(zhuǎn)的產(chǎn)物；如果沒有溶劑，在某些催化劑（如氯化鋅）作用下，(4)直接分解成離子對形式，于是按照SN1機理得到外消旋產(chǎn)物。例如，光學活性

13、的2-正辛醇用氯化亞砜在不同溶劑中進行反應，得到不同構(gòu)型的相應氯化物，若添加氯化鋅作為催化劑，反應速率明顯加快，SNi機理轉(zhuǎn)化為SN1機理，得到外消旋產(chǎn)物。烯丙醇和氯化亞砜在乙醚中進行反應時，烯丙位重排產(chǎn)物的比例與所用的氯化亞砜濃度有關系。例如，化合物2-丁烯-1-醇(5)在5.6 mol 氯化亞砜醚溶液中得到兩種雙鍵位置不同的異構(gòu)體混合物；而用0.7 mol氯化亞砜時，幾乎完全得到重排產(chǎn)物，這可能由于在稀溶液中無水乙醚易和干燥氯化氫生成氫鍵連接的復合物，從而有利于SN1反應和雙鍵重排。在氯化亞砜的反應中，若加入有機堿（如吡啶）作為催化劑，或者醇本身分子內(nèi)存在氨基等堿性基團，因能與反應中生成的

14、氯化氫結(jié)合，故有利于提高氯代反應速率。此外，該反應也適宜于一些對酸敏感的醇類的氯置換反應。例如，2-羥甲基四氫呋喃(6)用二氯亞砜和吡啶在室溫下反應，可得到預期的2-氯甲基四氫呋喃，而不影響酯環(huán)醚結(jié)構(gòu)。在SOCl2和DMF或HMPA（催化劑兼溶劑）合用時，其氯化劑的實際形式為（7）或（8）。由于它們具有活性大、反應迅速、選擇性好以及能夠有效的結(jié)合反應中生成的HCl等優(yōu)點，故特別適宜于某些特殊要求的醇羥基氯置換反應，亦可作為良好的羧羥基氯置換試劑。Example A: the preparation of 10-(4-Chlorobutyl)phenothiazineTo a solution

15、of 1 (2.03 g, 7.5 mmol) in 100 ml of dry benzene was added dropwise thionyl chloride (2 ml, 10 mmol). The mixture was stirred at room temperature overnight. The solvent was evaporated to dryness under reduced pressure. The residue was applied on a silica gel column and eluted with 10% ethyl acetate/

16、hexanes to yield 2.17 g (62%) of 2.Journal of Medicinal Chemistry, 2002, 45, 13, 2741-2748Example B: the preparation of 1-ChlorohexaneAssemble in a fume cupboard a 500 ml three-necked flask equipped with a sealed stirred unit, a double surface reflux condenser and a separatory funnel; fit the conden

17、ser and the funnel with calcium chloride guard-tubes. Place 179 g (109.5 ml, 1.5 mol) of redistilled thionyl chloride in the flask and 51 g (62.5 ml, 0.5 mol) of hexan-1-ol in the separatory funnel. Add the acolhol with stirring during 2 hours; the excess evolution of heat, sulphur dioxide is evolve

18、d and the liquid darkens considerably. When all the alcohol has been added, reflux the mixture for 2 hours. Rearrange the apparatus for distillation, and distil slowly; the excess of thionyl chloride passes over below 80, followed by a small fraction up to 120; and finally the crude 1-chlorohexane a

19、t 132-134. Wash the las-named successively with water, 10% sodium carbonate solution, and twice with water. Dry with anhydrous calcium chloride and distil through a short fractionating column. Pure 1-chlorohexane passes over at 133-134. The yield is 36 g (60%). Practical Organic Chemistry, 4th editi

20、on, 5582.1.3. 醇和氯化磷的反應用三氯化磷、五氯化磷對醇羥基做親核取代反應也是經(jīng)典的氯置換反應。這類氯化劑的活性比氫氯酸大，與后者相比，重排副反應也較少。其中，三溴化磷和三氯化磷應用最多，前者效果比較好，也可以由溴和磷在反應中直接生成，使用方便。三氯化磷和醇進行反應時，首先生成亞磷酸的單、雙或三酯的混合物（9）和氯化氫，然后，由于傾向于形成磷酰基（P=O）而使（9）中烷氧鍵發(fā)生斷裂，于是氯素負離子對酯分子中親電性烷基作親核取代反應，生成氯化物。上述親核取代過程，大多屬于SN2機理，因此，光學活性醇在與三氯化磷反應后的主要產(chǎn)物常常為構(gòu)型翻轉(zhuǎn)的氯化物。但是，由于亞磷酸酯反應的立體選擇性

21、不高，故會發(fā)生一定比例的外消旋化。對于某些易發(fā)生重拍的醇（仲醇、位具有叔碳取代基的伯醇等），由于SN1機理可能性增加，則隨著所用三氯化磷以及其用量、反應條件不同，其收率和重排副產(chǎn)物的比例也不同。五氯化磷和DMF反應也生成氯代亞氨鹽（7）（Vilsmeier-Haack試劑），在二氧六環(huán)或者是乙腈等溶劑中和光學性仲醇（10）加熱反應，可得到高收率、構(gòu)型翻轉(zhuǎn)的氯代烴。五氯化磷一般很少直接用于醇的氯代，但可以將酮或醛轉(zhuǎn)變成氯代烯烴。Example A: the preparation of Benzyl-chloromethyl-3-(quinolin-2 -ylmethoxy)-phenyl -a

22、mineA solution of 3-(2'-quinolylmethoxy)-N-benzyl-N-hydroxymethylaniline (8.4 g) and phosphorous trichloride (2.5 ml) in dichloromethane (100 ml) is stirred at ambient temperature for 24 hours and is then washed once with water (100 ml) and twice with 5percent aqueous sodium carbonate solution (

23、200 ml).The organic layer is separated, dried over magnesium sulphate and evaporated in vacuo to give the crude title compound, which is used in the following step without further purification.US4826987 A1 (1989/05/02), Example B: The preparation of 4-3-(Chloromethyl)phenylamino-6,7- dimethoxy-3- qu

24、inoline carbonitrileTo 14 ml of DMF was added phosphorous trichloride (0.70 ml, 8.0 mmol) with stirring at 25-30.deg. C. After 60 m, the mixture was cooled to 0.deg. C., and a suspension of -3-(hydroxymethyl)phenylamino-6,7-dimethoxy-3-quinolinecarbonitrile (1.34 g, 4.0 mmol) in 6 ml of DMF was adde

25、d.The mixture was warmed to 25.deg. C., stirred 15 m, recooled in ice bath, and partitioned with methylene chloride-aqueous sodium bicarbonate.The organic layer was washed with water, dried, and concentrated to give 1.15 g of an amber solid; NMR (CDCl3) d 4.79(s, CH2Cl). US6002008 A1 (1999/12/14), A

26、ppl.: US1998-49718 (1998/03/27)Example C: The preparation of (E)-1-2-(2-bromo-4-chlorophenyl) -2-chloroethenyl-1H-imidazole mononitrateA mixture of 23.0 parts of 1-(2-bromo-4-chlorophenyl)-2- (1H-imidazol-1-yl) ethanone, 23.0 parts of pentachlorophosphorane and 17 parts of phosphoryl chloride was st

27、irred and refluxed for 4 hours.The reaction mixture was cooled and diluted with 260 parts of dichloromethane.This solution was added dropwise, during a 2 hours period, to a solution of 300 parts of potassium carbonate in 500 parts of water.The whole was stirred overnight at room temperature.The prod

28、uct was extracted twice with 2,2'-oxybispropane.The combined extracts were dried, filtered and evaporated. The residue was converted into the nitrate salt in ethyl acetate and 2,2'-oxybispropane.The salt was filtered off and purified by reversed phase chromatography over LiChroprep. RP 18 us

29、ing a mixture of methanol (containing 0.1percent of N-(1-methylethyl)-2-propanamine) and water (containing 0.5percent of ammonium acetate) (65:35 by volume) as eluent.The first fraction was collected and the eluent was evaporated.The residue was converted into the nitrate salt in a mixture of ethyl

30、acetate and 2,2'-oxybispropane.The salt was filtered off and crystallized from 4-methyl-2-pentanone, yielding 2.9 parts (10percent) of (E)-1-2-(2-bromo-4-chlorophenyl) -2-chloroethenyl-1H-imidazole mononitrate; mp. 162.9.deg. C. US4539325 A1 (1985/09/03)2.1.4 醇和有機磷氯化物的反應三苯膦氯化物，如Ph3PX2, PH3P+CX3X

31、- 以及亞磷酸三苯酯氯化物如(PhO)3PX2、(PhO)3P+RX-，在和醇進行氯置換反應是，具有活性大，反應條件溫和等特點。由于反應中產(chǎn)生的氯化氫很少，因此不容易發(fā)生氯化氫引起的副反應。三苯膦和六氯代丙酮（HCA）復合物和Ph3P/CCl4相似，也能將光學活性的烯丙醇在溫和條件下轉(zhuǎn)化成為構(gòu)型翻轉(zhuǎn)的烯丙氯代物，而且不發(fā)生異構(gòu)、重排等副反應。這個試劑比Ph3P/CCl4更溫和，反應迅速，特別適宜于用其他方法易引起重排的烯丙醇。此外，三苯膦或亞磷酸酯和N-氯代酰胺組成的復合氯化劑與上述試劑相似，但特別適宜于對酸不穩(wěn)定的醇或者是甾體醇的氯置換反應，也可用于缺電子的體系的羥基氯置換。 醇和有機磷氯化

32、物的反應示例 Example A: The preparation of Geranyl chlorideA dry, 300-ml., three-necked flask is equipped with a magnetic stirring bar and reflux condenser (to which is attached a Drierite-filled drying tube) and charged with 90 ml. of carbon tetrachloride and 15.42 g. of geraniol (0.1001 mole). To this s

33、olution is added 34.09 g. (0.1301 mole) of triphenylphosphine, and the stirred reaction mixture is heated under reflux for 1 hour. This mixture is allowed to cool to room temperature; dry pentane is added (100 ml.), and stirring is continued for an additional 5 minutes.The triphenylphosphine oxide p

34、recipitate is filtered and washed with 50 ml. of pentane. The solvent is removed from the combined filtrate with a rotary evaporator under water aspirator pressure at room temperature. Distillation of the residue through a 2-cm. Vigreux column attached to a short-path distillation apparatus provides

35、 13.014.0 g. (7581%) of geranyl chloride, b.p. 4749° (0.4 mm.), n23D = 1.4794.Organic Syntheses, Coll. Vol. 6, p.634 (1988); Vol. 54, p.63 (1974).Example B: The preparation 5-(5-Chloropentyl)-5H-dibenzob,fazepineTo a cooled 25 ml round-bottom flask containing 1 (50 mg, 0.16 mmol) and Ph3P (51 m

36、g, 0.2 mmol) was added hexachloroacetone (HCA, 0.05 ml, 0.3 mmol) in 1 ml of CH2Cl2. The reaction mixture was allowed to come to room temperature and stirred overnight. The mixture was subjected to purification by flash silica gel column chromatography, with elution first by hexane to remove the HCA

37、 and then by 5% ethyl acetate/hexanes to give 49 mg (93%) of 2. Journal of Medicinal Chemistry, 2002, 45, 13, 2741-27482.1.5 醇和其他氯化劑的反應氯硅烷類試劑可以在溫和的條件下進行醇羥基氯置換反應，高收率地得到氯代物。N-氯代酰胺與二甲硫醚反應生成的氯代硫鎓鹽，對烯丙位或芐位的羥基的取代具有高度的選擇性，在低溫和中性條件下進行反應，不會發(fā)生雙鍵的異構(gòu)化，且不影響脂肪族伯、仲羥基。用四氯化錫也可在溫和的條件下高收率的將烯丙位、芐位羥基分別置換為溴和氯。四甲基-氯代烯胺（te

38、tramethyl-haloenamines）(13)可將伯、仲羥基及烯丙位、芐位、炔丙位羥基在溫和的條件下轉(zhuǎn)化為相應的氯代物。若將具有較大空間位阻的取代基替代氮原子上的甲基（14）或改用結(jié)構(gòu)類似物CMPA（chloro-phenylthio-methylene）dimethylammonium chloride(15)，則對伯羥基及烯丙位、芐位羥基的選擇性提高，特別是（15）不會影響底物結(jié)構(gòu)中存在的敏感基團。其反應歷程為SN2機理：2-氯代-3-乙基苯并噁唑四氟硼酸鹽（2-chloro-3-ethylbenzoxazolium tetrafluoroborate）（16），也為一較新發(fā)展的氯

39、化劑，他是由鄰氨基苯酚在EtOCS2K和HCl作用下環(huán)合，再季銨化而制得。采用（16）對醇羥基進行氯置換反應的特點是在選用含不同氯素負離子的氨鹽條件下，將許多類型的醇包括甾體醇、糖類化合物等溫和地轉(zhuǎn)化成不同氯素取代的產(chǎn)物，并在大多數(shù)情況下發(fā)生了構(gòu)型翻轉(zhuǎn)。例如，在前列腺素合成中采用這個方法，以區(qū)域和立體選擇性地將前列腺素母體結(jié)構(gòu)（17）上三個羥基置換成所需構(gòu)型的不同氯素原子，得到關鍵中間體（18）。 醇和其他氯化劑的反應的合成實例Example A: The preparation Benzyl Chloride by TMSCl/DMSOA 10 ml flask was charged wi

40、th a mixture of 0.01 mol (1.1 g) of benzyl alcohol and 0.02 mol (2.2 g) of TMSCl. To the stirred solution was added 0.2 g (0.0026 mmol) of DMSO in a single portion. The flask grew warm immediately, vented HCl (g) and within 1 min a two-phase system had formed. The mixture was stirred for an addition

41、al 10 min and then distilled through a short-path mircohead to remove the volatiles (81-98) and leave 1.2 g (95%) of product.J.Org.Chem., 1995, 60, 8, 2638-2639 2.2 磺酸酯的氯置換反應 為了避免醇羥基在直接氯置換反應中可能產(chǎn)生的副反應，可先將醇用磺酰氯轉(zhuǎn)化成為相應的磺酸酯，再與親核性氯化試劑反應，生成所需的氯化烴。由于磺酰氯及其酯的活性較大，磺酰氯和氯置換反應均在較溫和的條件下進行，且常比氯素交換反應更加有效。常用的氯化劑有氯化鈉、

42、氯化鋰、氯化鎂等。反應溶劑為丙酮、醇、DMF等極性溶劑。 磺酸酯的氯置換反應合成示例 Example A: The preparation Geranyl chlorideA dry, 1-L., three-necked, round-bottomed flask is equipped with an overhead mechanical stirrer, a 125-ml. pressure equalizing dropping funnel fitted with a rubber septum, and a nitrogen inlet tube. The system is f

43、lushed with nitrogen, and 15.4 g. (0.100 mole) of geraniol, 35 ml. of dry hexamethylphosphoric triamide, 100 ml. of anhydrous diethyl ether, and 50 mg. of triphenylmethane are placed in the flask. The stirred solution is cooled to 0° with an ice bath, and 63 ml. (0.1 mole) of 1.6 M methyllithiu

44、m in ether is injected into the addition funnel. The methyllithium solution is added dropwise over a period of 30 minutes. After the addition is complete, the funnel is rinsed by injecting 5 ml. of dry ether.A solution of 20.0 g. (0.105 mole) of p-toluenesulfonyl chloride in 100 ml. of anhydrous eth

45、er is injected into the addition funnel and added over a period of 30 minutes to the stirred, red, 0° reaction mixture. The red color immediately disappears upon addition. After addition is complete, 4.2 g. (0.0990 mole) of anhydrous lithium chloride is added. The reaction mixture is warmed to

46、room temperature and stirred overnight (1820 hours), during which time lithium p-toluenesulfonate precipitates.After a total of 2022 hours, 100 ml. of ether is added, followed by 100 ml. of water. The layers are separated, and the organic phase is washed four times with 100-ml. portions of water, an

47、d finally with 100 ml. of saturated sodium chloride. After drying the organic phase over anhydrous magnesium sulfate, the solvent is removed on a rotary evaporator. The crude product is transferred to a 50-ml. flask and distilled through a 20-cm. Vigreux column, yielding 14.114.6 g. (8285%) of geran

48、yl chloride as a colorless liquid, b.p. 7879° (3.0 mm.). Organic Syntheses, Coll. Vol. 6, p.638; Vol. 54, p.682.3 其他的一些制備脂肪族氯代烴的方法 丙烯及芳烷基的-氯代，醛酮，羧酸及酯的-氯代，通過其他鹵代物如溴化物與KCl，BiCl反應，可以得到相應的的氯化物，但由于一般情況下鹵代烴參與的取代反應中，溴化物，碘化物比相應的氯化物活潑，所以當以鹵代烴作為中間體或原料時，沒有必要將溴化物，碘化物轉(zhuǎn)變?yōu)橄鄳穆然?。將烷基烴直接氯代，也是制備脂肪族氯代烴的方法，在此不一一列舉

49、。31 醇的溴代3.1.1醇和溴化氫反應與醇和氯化氫反應類似，醇也可以和氫溴酸反應制備溴化物，而醇羥基的活性順序為叔羥基仲羥基伯羥基，芐位和烯丙位的羥基也很活波，這是由于碳正離子穩(wěn)定性差別的結(jié)果。同樣理由，活性較大的叔醇、芐醇的溴置換反應傾向于SN1機理，而其他醇的反應，大多數(shù)以SN2反應機理為主。在某些仲醇、叔醇和位具有叔碳取代基的伯醇的反應中，若反應溫度過高，會產(chǎn)生重排、異構(gòu)化和脫溴等副反應。分子量小的伯醇可與氫溴酸及濃硫酸一起反應。分子量比較大的伯醇溴代時可以將溴化氫通到加熱至100-110的醇中，可以直接得到溴代烷烴。醇和溴化氫反應的方法示例：Example A: The prepar

50、ation Isopropyl Bromide (2-bromopropane)Mixture 40 g (51 ml, 0.67 mol) of propan-2-ol with 460 g of constant boiling-point hydrobromic acid in a 500 ml flask fitted with a double surface condenser, add a few boiling chips and distil slowly (1-2 drops per second) until about half of the liquid has pa

51、ssed over. Separate the lower alkyl bromide layer (70 g), and redistill the aqueous layer when a further 7 g of the crude bromide will be obtained. Shake the crude bromide in a separatory funnel successively with an equal volume of concentrated hydrochloric acid, water, 5% sodium hydrogen carbonate

52、solution and water, and dry with anhydrous calcium chloride. Distil from a 100 ml of flask; the isopropyl bromide passes over at 59. The yield is 66 g (81%). Practical Organic Chemistry, 4th edition, 561Example B: The preparation of Butyl Bromide (1-Bromobutane)To 250 g of 48% hydrobromic acid conta

53、ined in a 500 ml round bottomed flask add 75 g (41 ml) of concentrated sulphuric acid in portions with shaking; some hydrogen bromide may be evolved. Add 88 g (110 ml, 1.2 mol) of butan-1-ol followed by 60 g (32.5 ml) of concentrated sulphuric acid in several portions with shaking, and finally a few

54、 chips of porous porcelain. Attach a reflux condenser to the flask and reflux the mixture gently for 2-3 hours. During this period the formation of butyl bromide is almost complete and a layer separates above the acid. If the preparation is carried out in the open laboratory, fit an absorption devic

55、e to the top of the condenser in order to absorb any hydrogen bromide and sulphur dioxide which may be evolved. Allow the contents of the flask to cool, remove the condenser and set it for downward distillation, distil the mixture until no more oily drops of butyl bromide pass over (30-40 min). Tran

56、sfer the distillate to a separatory funnel and remove the halide which forms the lower layer. Wash it successively with water, an equal volume of concentrated hydrochloric acid, water, 5% sodium hydrogen carbonate or sodium carbonate solution, and water. Separate the water as completely as possible

57、and dry with 2-3 g of anhydrous calcium chloride, the desiccant should be left in contact with the bromide for at least 30 min and shaken occasionally. Filter paper into a 200 ml of flask and distil either from an air bath. Collect the portion boiling at 100-103. The yield is 155 g (95%). Practical

58、Organic Chemistry, 4th edition, 561-562Example C: The preparation decamethylene bromideA 2-l. three-necked flask, supported in an oil bath, is fitted with a mechanical stirrer and an inlet tube which reaches almost to the bottom of the flask. In it is placed 696 g. (4 moles) of decamethylene glycol, and, after the o