Fore-run

Neutralise the cold contents of the flask with 500-600 ml. of 40 per cent, aqueous sodium hydroxide solution, equip the flask for steam distillation and steam distil until about 1 litre of distillate is collected. The steam distillate separates into two layers. Add solid sodium hydroxide (< 100 g.) to complete the separation of the two layers as far as possible. Remove the upper (organic) layer and extract the aqueous layer with three 50 ml. portions of chloroform. Dry the combined organic layer and chloroform extracts with anhydrous potassium carbonate and distil the mixture through a short fractionating column (e.g., an 8 Dufton column) after a fore run of chloroform, followed by pyridine, collect the crude 4-ethylpyridine at 150-166° (49 g.). Redistil through a Fenske-... 

Chlorobenzoyl chloride (m.p. 14-15°) is readily obtained by refluxing and stirring 156 g. (1.0 mole) of -chlorobcnzoic acid (obtained by the procedure for the n-isomer ) and 200 g. (1.7 moles) of thionyl chloride until solution is complete. The unused thionyl chloride is distilled, under slightly reduced pressure, and the product at 10 to 25 mm. the yield of -chlorobenzoyl chloride, b.p. 119-120°/22 mm. is 131-142 g. (75-81%). An additional amount can be secured by working up the fore-run and residue. 

The fore-run amounts to 90-180 g. and consists mostly of bromine, bromoacetaldehyde, and dibromoacetaldehyde. An additional quantity of bromal may be obtained by treating this... 

The distillate is extracted with five 50-cc. portions of benzene, and the benzene solution is dried thoroughly with powdered sodium hydroxide and distilled (Note 5). Most of the amine distfls at 184-186°, but the fraction distilling at 180-190° is sufficiently pure for most purposes (Note 6). The yield of this fraction is 80-88 g. By combining the benzene fore-run with the distillation residue, extracting with dilute acid, and recovering the amine as above, an additional 10-12 g. of material can be obtained (Note 7), making the total yield po-ioo g. (60-66 per cent of the theoretical amount based on the acetophenone taken) (Note 8). 

The viscous magnesium compound formed is cautiously decomposed with dilute acetic acid (75 cc. in 300 cc. of water), the flask being cooled under the tap. Two clear layers are formed, and after separation, the aqueous layer is extracted with 100 cc. of ether, the combined ethereal solution is washed with water and dried with sodium sulfate, and the ether is distilled on the steam bath. The residue is distilled vmder reduced pressure. After a small fore-run the temperature rapidly rises to 130 at 10 mm. when the pure tricarbethoxymethane begins to distil. The yield of material collected over a five-degree interval is 204-215 g. (88-93 per cent of the theoretical amount). The product solidifies at 25°. The melting point of the pure substance is 28-29°. 

The melt is cooled to 0°, 50 ml. of 10% aqueous sodium hydroxide solution is added, and the mixture is extracted with four 50-ml. portions of chloroform. The combined chloroform extracts are washed with two 25-ml. portions of water, and these in turn are extracted with 10 ml. of chloroform. The organic layers are combined and dried partially over anhydrous sodium sulfate. The solvent is removed by distillation on the steam bath, and the residue is distilled at reduced pressure from a 50-ml. distilling flask. After a fore-run of about 4 g. (Note 3), b.p. 60-70°/ 1.5 mm. (bath temperature taken up to 125°), the cyanoethyl-aniline is collected at 115-120°/0.01 mm. The product solidifies in the form of colorless plates, m.p. 48-51° (Note 4). The yield is 10.5-11.4 g. (72-78%) (Note 5). 

The cooled mixture is transferred to a 3-1. separatory funnel, and the ethylene dichloride layer is removed. The aqueous phase is extracted three times with a total of about 500 ml. of ether. 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. 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). The aldehyde boils at 78° at 2 mm. there is very little fore-run and very little residue. The yield of crude 2-pyrrolealdehyde is 85-90 g. (89-95%), as an almost water-white liquid which soon crystallizes. A sample dried on a clay plate melts at 35 0°. The crude product is purified by dissolving in boiling petroleum ether (b.p. 40-60°), 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. The pure aldehyde is obtained from the crude in approximately 85% recovery. The over-all yield from pyrrole is 78-79% of pure 2-pyrrolealdehyde, m.p. 44 5°. 

The purity of the 2-cyclohexenone may be assayed by gas chromatography on an 8 mm. x 215 cm. column heated to 125° and packed with di-(2-ethylhexyl) sebacate suspended on ground firebrick. This method of analysis indicates that the 3-cyclo-hexenone in the product amounts to no more than 3%. The fore-run from this fractional distillation contains substantial amounts of 2-cyclohexenone accompanied by ether, ethanol, and minor amounts of other lower-boiling impurities. Additional quantities of pure 2-cyclohexenone can be recovered by redistillation of this fore-run. The preparation of 2-cyclohexenone has been run on twice the scale described with no loss in yield. The ultraviolet spectrum of an ethanol solution of the 2-cyclohexenone obtained has a maximum at 226 m/i (s = 10,400). 

A 250-cc. flask fitted with an inlet tube reaching to the bottom, a thermometer, and an exit tube for conducting away unused gas, is immersed in an icc-water bath, and to it is added 80 g- (0.69 mole) of freshly distilled indene (Note 1). With the temperature of the liquid kept at 5-10°, dry hydrogen chloride (Org. Syn. Coll. Vol. 1, 287) is passed in at a moderate rate until 24-27 g. of the gas has been absorbed. The addition takes from eight to ten hours and requires little attention from the operator. The crude a-chlorohydrindene is then transferred to a 250-cc. Claisen flask and distilled at diminished pressure. After a small fore-run (5-10 g.) containing indene, the fraction of a-chlorohydrindene boiling at 9o-io3°/i5 mm. is collected the yield is 80-90 g. (Note 2). 

Usually. almost the entire crude product distils in this range with practically no fore-run or residue. Occasionally, however, as much as 30 g. of high-boiling residue, chiefly unchanged nitrile, is obtained. When this happens the yield is correspondingly decreased. 

The fore-run of phenyl ether, b. p. 98-ioi°/5 mm., may be used in subsequent runs. Other boiling points are phenyl ether, i34-T37°/i5 mm., 259-262°1745 mm. and phenoxthin, 180-183°/i5 mm., 3n°/745.mm. Fractionation at 15mm. gives a lower yield with a larger amount of tarry residue remaining in the flask than when the lower pressure (5 mm.) is used. 

The quantity of fore-run depends on the amount of polymerization of vinyl acetate. Distillation of the product through a packed column goes more smoothly, with less heat having to be applied to the distillation flask, if the product has been separated from high-boiling material by a quick preliminary distillation. 

The crude anhydride is carefully fractionated through a 13-mm. x 1.2-m. Nester still at a pressure of 25 mm. (Note 4) and a reflux ratio of at least 10 1. After a fore-run of maleic anhydride, b.p. 50-100°/25 mm., and a small intermediate fraction, there is obtained 75-90 g. (22-26%) of 3-methylenecyclobutane-l,2-dicar-boxylic anhydride b.p. 155-159°/25 mm. 1.4935-1.4952 (Note 5). This material is of sufficient purity for most uses, but it contains approximately 2-5% of propargylsuccinic anhydride. Redistillation through the Nester still gives 65-80 g. (19-23%) of 3-methylenecyclobutane-l,2-dicarboxylic anhydride b.p. 155°/25 mm. 1.4946-1.4955. 

This fore-run turns black on standing, but if stored no more than a few days it may be assumed to be an equimolar mixture of furfural and acetic anhydride and may be used as starting material for subsequent runs. If no additional runs are to be made, the yield may be increased by 5-10% by redistilling the fore-run. 

The checkers obtained essentially no fore-run and only trace amounts of solid residue. The refractive index of the first 200 mg. was n1.5800 of the center fractions, d 1.5802 and of the last 700 mg., 1.5800. 

The amount of fore-run and the yield depend on the efficiency of the fractionation. With a 7-cm. distilling head, a fore-... 

It is imperative that the pressure be maintained at 1 mm. or lower. Decomposition is usually extensive at higher pressures however, the removal of the acetic acid may be initiated at 5-10 mm. pressure. The oil-bath temperature must not exceed 130° if decomposition is to be avoided. A fore-run of 15-20 g., b.p. 90-98°/0.5 mm., can be saved and redistilled in combination with similar cuts from successive runs. About 9-10 g. (7%) of additional crystalline pyridine-N-oxide is obtained per run in this manner. 

The presence of 0.5% of trichloroethylene as impurity in tetrachloroethylene during unheated drying over solid sodium hydroxide caused generation of dichloroacety-lene. After subsequent fractional distillation, the volatile fore-run exploded. 

After removal of the drying agent, the ester is fractionally distilled through an efficient fractionating column (Note 2). A fore-run of 21-37 g. is collected up to a temperature of 95°. The pure ester distils between 95° and 96° and amounts to 129-148 g. (53-60%) (Note 3). 

A tarry residue of 10-17 g. is obtained. If an efficient column is not used in the distillation, the fore-runs will contain... 

In a 500-ml. flask attached to a reflux condenser is placed a mixture of 67 g. (104 ml., 1 mole) of allyl cyanide1 (Note 1) and 100 ml. (1.2 moles) of concentrated hydrochloric acid (sp. gr. 1.19). The mixture is heated by a small flame and is shaken frequently. After 7 to 8 minutes, the reaction begins, a voluminous precipitate of ammonium chloride appears, the temperature rises rapidly, and the mixture refluxes. After 15 minutes the flame is removed, 100 ml. of water is added, and the upper layer of the acid is separated (Note 2). The aqueous layer is extracted with two 100-ml. portions of ether. The extracts and the acid are combined and distilled. Most of the ether is removed at atmospheric pressure (Notes 3, 4, and 5), and the remainder is removed as the pressure is diminished. The acid is collected at 70-7 2°/9 mm. after a fore-run of approximately 40 g. The yield of crude acid is 50-53 g. (52-62%) (Note 5). 

The dried solution is distilled, first at atmospheric pressure to remove most of the solvent, and then under reduced pressure (Note 5). A fore run of unused naphthalene amounting to 35-40 g. is collected at 90-110°/5 mm. (Note 6). This is followed by 195-204 g. of 1-chloromethylnaphthalene which boils at 128 133°/5 mm. or at 148-153°/14 mm. (74-77% based on naphthalene consumed) (Notes 7 and 8). 

This acid is quite pure. The checkers distilled 52.5 g. of it through an analytical column except for a fore-run of 1.5-2.0 g., all the material had a constant boiling point and index of refraction. 

While still warm, the reaction mixture is transferred to a 250-cc. modified Claisen flask (Org. Syn. Coll. Vol. 1, 1941, 130) fitted fox distillation under reduced pressure. Any hydrogen bromide remaining in the reaction mixture is removed by heating at 120° under the vacuum of a water pump. The product is then distilled "under reduced pressure. The fore-run of less than 15 g. 

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