The Separatory Funnel

Following this procedure, the funnel is positioned in a padded ring in a ring stand and left undisturbed for a period of time to allow the two immiscible layers to once again separate. The purpose of the specific design of the separatory funnel is mostly to provide for easy separation of the two immiscible liquid layers after the extraction takes place. All one needs to do is remove the stopper, open the stopcock, allow the bottom layer to drain, and then close the stopcock when the interface between the two layers disappears from sight in the stopcock. The denser of the two liquids is the bottom layer and will be drained through the stopcock first. The entire process may need to be repeated several times, since the 

The analysis of human plasma for acetaminophen, the active ingredient in some pain relievers, involves a unique extraction procedure. Small-volume samples (approximately 200 fiL) of heparinized plasma, which is plasma that is treated with heparin, a natural anticoagulant found in biological tissue, are first placed in centrifuge tubes and treated with 1 N HC1 to adjust the pH. Ethyl acetate is then added to extract the acetaminophen from the samples. The tubes are vortexed, and after allowed to separate, the ethyl acetate layer containing the analyte is decanted. The resulting solutions are evaporated to dryness and then reconstituted with an 18% methanol solution, which is the final sample preparation step before HPLC analysis. The procedure is a challenge because the initial sample size is so small. 

Randy Karl of MDS Pharma Services in Lincoln, Nebraska, examines a centrifuge tube containing a heparinized plasma sample prior to performing an extraction procedure using ethyl acetate. 

FIGURE 11.2 A drawing of a separatory funnel, containing two immiscible liquids, held in an iron ring clamped to a ring stand. 

FIGURE 11.3 Illustrations of the shaking and venting procedures with the separatory funnel. 

Before going on to some practical examples, you might want to know more about where all this washing and extracting is carried out. I ve mentioned that it s a special funnel called a separatory funnel (Fig. 53) and that you can impress your friends by calling it a sep funnel. Here are a few things you should know. 

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If it is desired to carry out the combined operations of stirring, refluxing, and addition of a liquid in a stream of gas, the apparatus of Fig. 77, 7, 12, a may be used the side tube for the gas is sealed on to the separatory funnel. For the passage of a gas into a stirred liquid, the aperture carrying the modified separatory funnel may be fitted with the device shown in Fig. 77, 7, 12, 6 the glass rod inside the tube is held in position by a short length of heavy-wall rubber tubing and is employed to clear the lower end of the gas delivery tube, should it become blocked with solid reaction product. 

Place 35 ml. of water in the separatory funnel and run it into the vigoroiisly stirred reaction mixture at such a rate that rapid refluxing occurs. Follow this by a cold solution of 15-5 ml. of concentrated sulphuric acid in 135 ml. of water. Two practically clear layers will now be present in the flask. Decant as much as possible of the ethereal layer A) into a 500 ml. round-bottomed flask. Transfer the remainder, including the aqueous layer, into a separatory funnel wash the residual solid with two 10 ml. portions of ether and combine these washings with the liquid in the separatory funnel. Separate the ethereal portion and combine it with (A). Distil off the ether through an efficient fraction-... 

Place 179 g. (109-5 ml.) of redistilled thionyl chloride in the 250 ml. Claisen flask and 51 g. (62-6 ml.) of n-hcxyl alcohol, b.p. 156-158°, in the separatory funnel. Add the nr-hexyl alcohol during 2 hours there is a slight evolution of heat, sulphur dioxide is evolved (hence carry out the... 

Allyl Bromide. Introduce into a 1-litre three-necked flask 250 g. (169 ml.) of 48 per cent, hydrobromic acid and then 75 g. (40-5 ml.) of concentrated sulphuric acid in portions, with shaking Anally add 58 g. (68 ml.) of pure allyl alcohol (Section 111,140). Fit the flask with a separatory funnel, a mechanical stirrer and an efficient condenser (preferably of the double surface type) set for downward distillation connect the flask to the condenser by a wide (6-8 mm.) bent tube. Place 75 g. (40 5 ml.) of concentrated sulphuric acid in the separatory funnel, set the stirrer in motion, and allow the acid to flow slowly into the warm solution. The allyl bromide will distil over (< 30 minutes). Wash the distillate with 5 per cent, sodium carbonate solution, followed by water, dry over anhydrous calcium chloride, and distil from a Claisen flask with a fractionating side arm or through a short column. The yield of allyl bromide, b.p. 69-72°, is 112 g. There is a small high-boiling fraction containing propylene dibromide. 

Equip a 1-litre three-necked flask with a powerful mechanical stirrer, a separatory funnel with stem extending to the bottom of the flask, and a thermometer. Cool the flask in a mixture of ice and salt. Place a solution of 95 g. of A.R. sodium nitrite in 375 ml. of water in the flask and stir. When the temperature has fallen to 0° (or slightly below) introduce slowly from the separatory funnel a mixture of 25 ml. of water, 62 5 g. (34 ml.) of concentrated sulphuric acid and 110 g. (135 ml.) of n-amyl alcohol, which has previously been cooled to 0°. The rate of addition must be controlled so that the temperature is maintained at 1° the addition takes 45-60 minutes. AUow the mixture to stand for 1 5 hours and then filter from the precipitated sodium sulphate (1). Separate the upper yellow n-amyl nitrite layer, wash it with a solution containing 1 g. of sodium bicarbonate and 12 5 g. of sodium chloride in 50 ml. of water, and dry it with 5-7 g. of anhydrous magnesium sulphate. The resulting crude n-amyl nitrite (107 g.) is satisfactory for many purposes (2). Upon distillation, it passes over largely at 104° with negligible decomposition. The b.p. under reduced pressure is 29°/40 mm. 

Into a 500 ml. three-necked flask, provided with a mechanical stirrer, a gas inlet tube and a reflux condenser, place 57 g. of anhydrous stannous chloride (Section 11,50,11) and 200 ml. of anhydrous ether. Pass in dry hydrogen chloride gas (Section 11,48,1) until the mixture is saturated and separates into two layers the lower viscous layer consists of stannous chloride dissolved in ethereal hydrogen chloride. Set the stirrer in motion and add 19 5 g. of n-amyl cyanide (Sections III,112 and III,113) through the separatory funnel. Separation of the crystalline aldimine hydrochloride commences after a few minutes continue the stirring for 15 minutes. Filter oflF the crystalline solid, suspend it in about 50 ml. of water and heat under reflux until it is completely hydrolysed. Allow to cool and extract with ether dry the ethereal extract with anhydrous magnesium or calcium sulphate and remove the ether slowly (Fig. II, 13, 4, but with the distilling flask replaced by a Claisen flask with fractionating side arm). Finally, distil the residue and collect the n-hexaldehyde at 127-129°. The yield is 19 g. 

Treat the distillate with 2 drops of glacial acetic acid (to destroy the phosphorus esters present) and redistil using the same apparatus as before except that the separatory funnel is replaced by a thermometer. Collect the liquid which passes over at 50-56°. Transfer the acetyl chloride to a weighed glass-stoppered bottle (since cork and rubber stoppers are attacked) and determine the weight. The yield is 22 g. 

Fit a reflux condenser into the short neck of a 125 ml. Claisen flask, a separatory funnel into the long neck, and plug the side arm with a small cork (compare Fig. Ill, 31, 1). Place 58 g. (62 ml.) of commercial n-caproic acid (1) in the flask and heat on a water hath. Add 75 g. (46 ml.) of redistilled thionyl chloride through the separatory funnel during 45 minutes shake the flask from time to time to ensure thorough mixing. Reflux the mixture for 30 minutes. Arrange the apparatus for distillation from an air bath (Fig. II, 5, 3) the excess of thionyl chloride passes over flrst, followed by n-caproyl chloride at 145-155° (mainly at 150-155°). The yield of acid chloride is 56 g. 

Into a 2-litre, three-necked flask, fitted with a separatory funnel, a mechanical stirrer and a reflux condenser, place a hot solution of 200 g. of potassium hydroxide in 200 ml. of water. Stir the solution and add slowly 200 g. of ethyl n-butylmalonate (Section 111,154). A vigorous reaction occurs and the solution refluxes. When all the ester has been added, boil the solution gently for 2-3 hours, i.e., until hydrolysis is complete a test portion should dissolve completely in water. Dilute with 200 ml. of water and distil oflF 200 ml. of liquid in order to ensure the complete removal of the alcohol formed in the hydrolysis (1) it is best to connect the flask by means of a wide delivery tube to a condenser set for downward distillation (compare Fig. II, 41, 1 but with a mercury-sealed stirrer in the centre neck). Replace the separatory funnel and the reflux condenser. 

Use a 500 ml. three-necked flask equipped as in Section IV,19, but mounted on a water bath. Place 128 g. of naphthalene and 45 ml. of dry carbon tetrachloride in the flask, and 177 g. (55 ml.) of bromine in the separatory funnel. Heat the mixture to gentle boiling and run in the bromine at such a rate that little, if any, of it is carried over with the hydrogen bromide into the trap this requires about 3 hours. Warm gently, with stirring, for a further 2 hours or until the evolution of hydrogen bromide ceases. Replace the reflux condenser by a condenser set for downward distillation, stir, and distil off the carbon tetrachloride as completely as possible. Mix the residue with 8 g. of sodium... 

Equip a 500 ml. three necked flask with a reflux condenser, a mercury-sealed mechanical stirrer and separator funnel, and support it on a water bath. Attach an absorption device (Fig. II, 8, 1, c) to the top of the condenser (1). Place 134 g. (152 ml.) of A.R, benzene and 127 g. of iodine in the flask, and heat the water bath to about 50° add 92 ml. of fuming nitric acid, sp. gr. 1-50, slowly from the separatory funnel during 30 minutes. Oxides of nitrogen are evolved in quantity. The temperature rises slowly without the application of heat until the mixture boils gently. When all the nitric acid has been introduced, reflux the mixture gently for 15 minutes. If iodine is still present, add more nitric acid to the warm solution until the purple colour (due to iodine) changes to brownish-red. 

Equip a 500 ml. three-necked flask with a powerful mechanical stirrer and a separatory funnel leave the third neck open or loosely stoppered. Introduce, while the flask is cooled in a freezing mixture of ice and salt, 90 ml. of concentrated ammonia solution (sp. gr. 0 -88) and 54 g. (43 ml.) of pure (e.g., A.R.) carbon disulphide. Stir the mixture and run in 56 g. (55ml.)of pure aniline from the separatory funnel during about 20minutes stir for a further 30 minutes, and allow to stand for another 30 minutes. A heavy precipitate of ammonium phenyldithiocarbamate separates. Transfer the salt to a 5 litre round-bottomed flask by four extractions with 200 ml. portions of water. Add to the resulting solution, with... 

Equip a 500 ml, three-necked flask with a separatory funnel, a mercury-sealed mechanical stirrer and a reflux condenser. Place a solution of 21 g. of sodium hydroxide in 200 ml. of water and also 47 g. of pure phenol in the flask, and stir the mixture cool the warm mixture to about 10° by immersing the flask in an ice bath. Place 63 g. (47 ml.) of dimethyl sulphate in the separatory funnel. 

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