Fractional distillation under reduced pressure

The following is a modification of the process described and gives quite satisfactory results. Wash the crude mixture of benzonitrile and dibromopentane with sodium carbonate solution until the latter remains alkaline, and then with water. Distil it under reduced pressure and collect the fraction boiling up to 120°/18 mm. Dissolve this in twice its volume of light petroleum, b.p. 40-60°, which has previously been shaken with small volumes of concentrated sulphuric acid until the acid remains colourless. Shake the solution with 6 per cent, of its volume of concentrated sulphuric acid, allow to settle, and run ofi the sulphuric acid layer repeat the extraction until the acid is colourless or almost colourless. Wash successively with water, sodium carbonate solution and water, dry over anhydrous calcium chloride or calcium sulphate, and distil off the solvent. Distil the residue under diminished pressure and collect the 1 6-dibromopentane at 98- 100°/13 mm. 

The ether is distilled on a steam bath (Note 3) and the residue fractionated under reduced pressure by means of a 20-cm. column (Org. Syn. 1, 40). After three fractionations, there is obtained 32-44 g. of a product boiling up to ioo /25 mm., which is mainly unchanged dibromopropene (b.p. 42-43°/i8 mm.), and... 

The potassium sulfate which has separated is then removed by filtration and washed with two loo-cc. portions of chloroform. The faintly alkaline aqueous solution is extracted with about five 200-CC. portions (Note 5) of chloroform, and the combined chloroform solutions are washed once with 50 cc. of water to remove any alkali. The chloroform is then distilled and the product fractionated under reduced pressure. The yield of 2-ketohexamethylenimine, boiling at i27-i33°/7 mm. and melting at 65-68°, amounts to 71-78 g. (59-65 per cent) (Note 6). 

The water layer is extracted with two 100-cc. portions of ether. The combined ether solutions are dried with calcium chloride, the ether distilled, and the residue fractionated under reduced pressure, using a modified Claisen flask (Org. Syn. 1, 40). Ten to twelve grams may be obtained in this way. The total yield is 72-75 g. (71-74 per cent of the theoretical amount). 

To obtain the trimethylene chlorohydrin, the distillate from this operation is heated for about one hour on a steam bath in order to drive out most of the excess hydrogen chloride. The distillate is then fractionated under reduced pressure (Note 3) in a modified Claisen flask (Org. Syn. 1, 40). The fractionating side arm should be 25 cm. in length. The fractions collected under 10 mm. are to 55°, 55-57°, 57-65°, 65-85°, 85-105°, residue. 

In a 2-1. round-bottomed flask, fitted with a reflux condenser and mechanical stirrer, are placed 675 g. (8.3 moles) of 37% formalin, 48 g. of sulfuric acid (sp. gr. 1.84), and 312 g. (3 moles) of styrene. The resulting mixture is gently refluxed and stirred for 7 hours. The mixture is cooled, and 500 ml. of benzene is stirred in. The layers are separated, and the aqueous layer is extracted with 500 ml. of benzene. The benzene solutions are combined and washed with two 750-ml. portions of water. The benzene is removed by distillation, and the residual liquid is fractionated under reduced pressure. At 2 mm. pressure a forerun is collected separately, up to a temperature of 96° (Note 1) then the main fraction is collected at 96-103°/2 mm. The yield of 4-phenyl-m-dioxane amounts to 353-436 g. (71-88%) wf 1.5300-1.5311 df 1.092-1.093 (Note 2). 

The dried benzene extract is placed in a 500-ml. round-bottomed flask with a ground-glass joint. The flask is fitted with a Vigreux column, and the benzene is distilled from the solution at atmospheric pressure, an oil bath maintained at 100-110° being the source of heat. The crude 7-di-w-butyl-aminopropylamine is fractionated under reduced pressure from a 250-ml. Claisen flask heat is supplied by an oil bath maintained at 170-180°. The yield of product boiling at 108-110.5°/ 5-6 mm. or 98-100°/2 mm. amounts to 57-60 g. (77-80%) (Note 4). 

The reaction mixture is distilled rapidly under reduced pressure through a short Vigreux column (Note 5). The yield of crude product, b.p. 50-80° (5-10 mm.), n20d 1.4410-1.4416, is 310— 330 g. (88 93%). This material is sufficiently pure for most purposes (Note 6). Fractionation through a 1 X 36-in. column packed with 8 X 8-mm. glass helices gives, after removal of a small amount of forerun, pure 2,2,4-trimethyI-3-oxovaleryl chloride, b.p. 86° (23 mm.), n20d 1.4418. 

The crude bromo acids may be freed from impurities by fractionation under reduced pressure. The fraction distilling below 1250 at 10 mm. (io5°/3 mm.) is discarded the remainder distils at 125-128° at 10 mm. (io5-io7°/3 mm.) and consists of a mixture of stereoisomeric acids. The yield is 75-85 per cent of the theoretical amount based on the crotonic acid used in the first step. 

The ether layer is separated, and the solvent is removed by distillation under atmospheric pressure, and the dark-colored residue is fractionated under reduced pressure through a 25-cm. column packed with glass helices. The fraction boiling at 37-38.5°/6 mm. is collected it weighs 44-45 g. (63-65%) 1.4626 1.404... 

The ether extract is washed with four 100-ml. portions of water and dried over anhydrous sodium sulfate or magnesium sulfate. The mixture is filtered, the ether is removed by distillation, and the residual liquid is fractionated under reduced pressure from a modified Claisen flask. The yield of colorless 4,4 -dichlorodibutyl ether, b.p. 84-86°/0.5 mm. (116-118°/10 mm.), Mq 1.4562, 1.0690, is 257-268 g. (52-54% based on tetrahydrofuran) (Note 6). 

B. 2-Iodoethyl benzoate. A mixture of 170 g. of anhydrous sodium iodide and 1.2 1. of methyl ethyl ketone (Note 2) is heated on a steam bath for 1 hour with occasional shaking in a 3-1. round-bottomed flask fitted with a water-cooled reflux condenser. 2-Chloroethyl benzoate (162 g., 0.88 mole) is added to the mixture, and heating is maintained for an additional 22-24 hours with occasional shaking. The mixture is cooled to room temperature and filtered through a 15-cm. Buchner funnel with suction. The inorganic salts on the filter are washed with 200 ml. of methyl ethyl ketone, and the filtrate is concentrated by distillation of about 1 1. of the solvent. The residue is poured into 1 1. of water contained in a separatory funnel, which is shaken, and the lower layer is withdrawn. The latter is washed successively with 200 ml. of 10% sodium bisulfite solution, 200 ml. of 5% sodium bicarbonate solution, and 100 ml. of water. It is dried with anhydrous magnesium sulfate (5-7 g.) and fractionated under reduced pressure. The yield of material boiling at 133 -136°/2.5 mm., 1.5820, is 190 -196 g. (78-81%). 

The alcoholic distillate is diluted to 2 1. with distilled water, and extracted with a 500-cc. and then a 300-cc. portion of ether. The steam distillate is extracted twice with this ether extract, and twice more with 250-cc. portions of fresh ether. The ether extracts are combined and dried with 150 g. of anhydrous sodium sulfate. The space above the solution is filled with nitrogen. The ether solution is decanted, and the sodium sulfate washed three times with distilled ether. The ether is then distilled, the temperature of the bath about the flask being raised finally to 130°. The kryptopyrrole is then fractionated under reduced pressure (Note 9). The yield of water-white product boiling within a 1.50 range (85.s-87°/i2.5 mm. 92.5-94°/i8 mm.) is 22-25.5 g- 50-58 per cent of the theoretical amount). 

The dimethyl sulfate was distilled carefully under reduced pressure, and a i° fraction was used in this preparation. Dimethyl sulfate is extremely toxic and great care must be taken to avoid breathing the vapors and spilling the liquid on the hands or clothes. 

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