Solvent Removal by Yacuum Ivaporation NORMAN S. RADIN Radioisotope Service, Veterans Administration Rese srch Hospital and Biochemistry Department, Northwestern University Medical School, Chicago, 111.
Volatile solvents can be removed without loss of solute by vacuum distillation, in which bumping is prevented by imparting a swirling action to tlie solution. Up to 10 test tubes can be used simultaneously, or almost any vacuum-resistant container up to 1000 nil. in size. Flasks can be filled over half full. Continuous solution feeding is possible with one of the devices described.
tion when the pump is started. The stopcock is kept closed until the dissolved air has been pumped from the solution, or, in the case of low-boiling solvents, until the solution temperature has gone down sufficiently. This takes from 1 / 4 to 5 minutes, depending on the volume, solution, and speed of swirling. If splashing occurs even with the stopcock closed, the capillary should be constricted further by softening a t the middle with a hand torch. With certain solutions, the entire distillation must be run with the stopcock closed to avoid foaming. L is a tube filled with potassium hydroxide pellets, which are supported by an extra coarse sintered-glass disk, 50 mm. in diameter; this protects the pump against acidic vapors. The bottom of L i s connected to a vacuum pump (such as the Welch Duo-Seal pump, Model 1400-B) with pressure tubing 7/16 inch in inside diameter.
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I T H the devices described here it is possible to concentrate solutions to dryness a t reduced temperatures, in the absence of air and without loss, using a wide variety of containers. The basic apparatus, described previously ( 5 ) , uses a swirling motion to prevent splashing during the vacuum distillation. The following modifications increase its versatility, ease of use, and compactness. Figure 1 illustrates the arrangement used for high vacuum distillation. A is a size 13 rubber stopper attached to the shaft of a variable speed motor fitted with a gear reducer (such as the A. H. Thomas Co. stirrer, No. 9242). The 8-mm.-diameter hole in the stopper accommodates the solid glass rod ( 6 X 80 mm.) of the adapter, B. B has a 24/40 male joint on the bottom and a side arm 8 mm. in outside diameter and 15 mm. long. D is a connector, with a 24/40 female joint on top, and one to 10 legs, each fitted with a neoprene stopper. It is useful to have an assortment of connectors with two, six, and 10 legs, with different sizes of rubber stoppers. When fewer than two, six, or 10 containers are used, empty tubes are attached to make up the difference. The six- and 10-leg connectors are made readily from 50ml. Erlenmeyer flasks having a 24/40 joint. P a r t D can be replaced by a flask fitted with a 24/40 joint. Greasing the connection b e h e e n B and D improves the vacuum. Cis a length of rubber tubing, about 3/16 inch in inside diameter and 3 / ~ inch in outside diameter, which is twisted 4 times and attached a t each end to the arms of a metal The (not shown) is 3.5 inches between arms and 9 inches deep; it is attached by a clamp t o a heavy ring stand, which also sup orts the motor. Part D or a flask is inserted between the twistei tubing, which supports the weight while permitting a swirling action to take place. It is important to choose a grade of rubber tubing d i i c h is strong but reasonably elastic; otherwise i t is difficult to insert the glassware. E is a pot of water on a thermostatically controlled hot plate. The hot plate sits upon a support of adjustable height (such as the Cenco-Lerner Lab-Jack). Circular pots minimize splashing. F is a %inch length of rubber pressure tubing, '/a inch in inside diameter, connecting B and a rubber stopper which is inserted into the wide mouth of the condenser flask, G. G is a combination condenser and safety trap which is cooled by an isopropyl alcoholdry ice mixture contained in a Dewar flask, 145 mm. in inside diameter and 500 mni. deep. The short inner tube of the condenser portion permits the condenser under favorable conditions to fill up to its mouth, a total volume of 1150 ml. The attached trap has a long inner tube t o ensure complete condensation of vapors which escape the condenser part. Two wooden covers are used over the mouth of the Delvar flask to minimize condensation of atmospheric moisture, because ice makes the slurry of isopropyl alcohol-dry ice become sludgy. The slurry should cover the shoulder of the condenser. (The condenser can be used in lyophilization, in which case the slurry level should be below the mouth of the large entrance tube, and tube I" should be replaced by a short piece of large-bore tubing.) H , connected to G by a short rubber tube, lets air into the system when the evaporation is finished. A capillary constriction slows down the air to prevent carryover of the contents of G into the pump. The bubbler on H is convenient for signaling when the vacuum is completely broken. J is a 250-ml. bulb inserted into the line to prevent liquid condensate from splashing up into the pump from a prematurely filled trap. When splashing is noticed, the pump is stopped and the plug in the top of J is removed to let air in without forcing solvent into the pump. K is a bypass with a capillary tube and a 4-mm.-bore vacuum stopcock, intended to prevent splashing of the evaporating solu-
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L
Pump
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Figure 1. Apparatus for evaporation under high vacuum A.
Size 13 rubber stopper Adapter, 24/40 male joint Rubber tubing D. Connector, 24/40 female joint, with one t o 10 legs E . Heated water b a t h F . 9-inoh length of rubber pressure tubiug. l/r-inch i.d. G. Condenser-safety trail combination H . Air inlet a n d bubbler J. 250-ml. bulb K . Bypass L . Potassium hydroside t r a p
B. C.
Experience has shown that a surprisingly high swirling speed must be used if splashing is to be uniformly avoided. For some arrangements there is an optimum speed that gives maximum motion; this speed should be adjusted occasionally as the volume of solution decreases. The water bath should not be brought up to the tubes until the solution temperature has gone down appreciably, as evidenced usually by condensation of atmospheric moisture on the tubes. However, in the case of solvents which freeze readily, such as mater, the bath must be raised beforc the solution freezes. The bath temperature is usually kept below 40' C.; too high a temperature causes splashing or incomplete condensation and premature filling of the safety trap. The entire apparatus may be placed on a cart. When G becomes full, it is allowed to bvarm (but never by pouring hot mater on the cold glass) and most of the contents are poured out. A certain amount cannot be removed this way and it is necessary to aspirate out the rest with a rubber tube inserted 542
V O L U M E 28, N O . 4, A P R I L 1 9 5 6 through the large opening. The safety trap inner tube is then rinsed with a little acetone, which is removed; air is then sucked through until the inner tube is dry. If the condenser is very full, thawing will cause Borne of the condensate to flow out of the mouth; in this case, the thawing should take place in the sink. If the water bath is not raised or the heat not turned on, the large inner tube of G will freeze shut when water is being distilled. This is remedied by disconnecting F , squirting in some glycerol (rather than a less dense solvent), and raising G a bit. Glycerol is also used to lubricate the point of contact between A and B .
a
n
- 6 mm. Rod I
Figure 2. Sw-irler condenser for evaporation under aspirator vacuum
When a water aspirator can be used as the vacuum source, i t is possible to use parts A and F as described by connecting F to a long, efficient water-cooled condenser. The bottom of the condenser is connected by a short, downward sloping rubber tube to the aspirator. By using the condenser shown in Figure 2, it is possible to conserve a great deal of work space and speed the distillation. The condenser fits directly in the flask (or D, Figure 1) and moves with the flask just like B. The solid rod, I, fits inside the stopper, A. Tubes I1 are for the cooling water. Tube I11 carries the condensate via an 8-inch length of pressure tubing (1/4 inch in inside diameter) to a ahort vertical glass condenser whose lower end connects by a short, downward sloping rubber tube to the aspirator. The short condenser need be only about 6 inches long; it serves to condense vapors missed by the swirling condenser. Tube IV is closed at the top by a small rubber bulb or, when large volumes must be concentrated, is connected to a solution reservoir via a 6-inch length of neoprene tubing, 3/16 inch in inside diameter with a '/&nch wall. The tubing should be treated with chloroform-ethyl alcohol in a Soxhlet extractor if organic solvents are to be added. A screw clamp or stopcock on the reservoir controls the flow rate to match the evaporation. For the reservoir, a separatory funnel (the Fischer & Porter Ultramax funnel with Teflon stopcock is good for organic solvents) or an aspirator bottle having 5-mm. tubing sealed onto the outlet may
543 be used. The lower part of tube IV is widened t o help deaerate the incoming solution and prevent splashing up into the condensing section. It is vel1 to grease the joint between the condenser and flask (or D )if a good vacuum is desired. With this arrangement, it is usually unnecessary to evacuate slowly a t the beginning, but the flask should be swirling before the aspirator is turned on. With 500- and 1000-ml. flasks, smoother swirling action is obtained by inserting the flask near one end of the tubing twist, C, and placing an extension clamp under the tubing close to the other side of the neck. The clamp by a clamp holder is attached to the lower part of the metal and is slipped back when not needed; in effect, it shortens the length of C. As with the high vacuum arrangement, the water bath (contained in a 10-inch-diameter pot) is seated on a thermostatic hot plate and is raised into position by a Lab-Jack. I n setting up the apparatus, the distillate should be kept flowing down t o prevent impairment of the vacuum. I n a test run, using a 1000-ml. flask half filled with water and placed in a 63" C. water bath, a distillation rate of 340 ml. per hour was observed. The water inside remained a t room temperature. Higher distillation rates have been obtained by using a condenser larger than the one shown in Figure 2 (22-mm. inside tube, 45-mm. outside tube) and also by eliminating tube 117. When continuous evaporation is carried out, higher distillation speed results when the liquid level in the flask is kept low. A basic consideration in designing the swirlcr-condenser is the need to have a short, wide-bore tube to carry the vapors; subsequent travel paths, which carry the much smaller volume of condensate, can then be relatively narrow. Other devices for vacuum evaporation without capillary tubes have been described (l-,$,6),and several models are available commercially. Some of the devices described in this paper might be useful in conjunction with the other designs. Features of this design are (1) lack of rotary seals; (2) use of ordinary stirring motor which can be used for other purposes; (3) the fact that the high vacuum arrangement can be used for other vacuum work, such as ordinary distillation or lyophilization, without changing the trap; (4)the wide variety of vessels which can be used (standard test tubes, Erlenmeyer flasks up to 125 ml., flat-bottomed boiling flasks up to 300 ml., round-bottomed boiling flasks up t o 1000 ml.); ( 5 ) the fact that more than one of the smaller vessels can be used simultaneously; and (6) the ability to fill vessels, other than test tubes, more than half full.
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ACKNOWLEDGMENT
The author wishes to express his appreciation to John A. D. Cooper for suggestions on design. The glassware was made by the H. S. Martin Co., Evanston, Ill., and the Delmar Scientific Laboratories, Chicago, Ill. LITERATURE CITED
(1)
Craig, L.
c., Gregory, J. D., Hausmann, IV., ANAL.CHEM.22,
1462 (1950).
Lea, C. H., Hannan, R. S., Rhodes, D. N., Biochirn. et Biophys. Acta 7, 366 (1951). (3) Nemerof, P., Reinhardt, IC. ANAL.CIIEM.25, 364 (1953). (4) Partridge, S. M., J. Sci. Instr. 28, 28 (1951). (5) Radin, N. S., ANAL.CHEM.24, 1686 (1952). (6) Volk, M. E., Ibid., 27, 1207 (1955). (2)
RECEIVED for review October 13, 1955. Accepted February 1, 1956.
