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ANALYTICAL CHEMISTRY
transfers and a large number of stages are readily achieved. Thus, with Craig's present apparatus, 3000 to 4000 quantitative extractions per hour can be performed. ACKNOWLEDGMENT
The author gratefully acknowledges certain suggestions made by John R . Anderson of Mellon Institute and Lyman C. Craig of the Rockefeller Institute for Medical Research. LITERATURE CITED (1) Baxter, G. P., and Behrens, E. E., J . A m . Chem. SOC.,54, 591 (1932). (2) Beckmann, E., 2. physik. Chem., 22, 609 (1897). (3) Bowman, J. R. (to Gulf Oil and Development Co.), U. S. Patent 2,427,042 (Sept. 9 , 1947). (4) Bruni, G., Gazz. chim. ital., 28, 249, 259 (1898). (5) Bush, M. T., and Densen, P. RI., ANAL.CHEM., 20, 121 (1948). (6) Craig, L. C., Federation Proc., 7 , Yo. 3, 469 (1948). (7) Craig, L. C . . J . Bid. Chem., 155, 519 (1944). (8) Craig, L. C., Mighton. H., Titus, E., and Golumbic, C., ANAL. CHEM.,20, 134 (1948). (9) Crookes, William, Chem. News, 54, 131, 155 (1886). (10) Doerner, H. A., and Hoskins, W. M., J . Am. Chem. Soc., 47, 662 (1925). (11) Harkins, W. D., and Mortimer, B., Phil. Mag. 171, 6 , 601 (1928). (12) Hunter, T. G., and Nash, A. W., Ind. Eng. Chem.. 2 7 , 8 3 6 (1935).
International Critical Tables, Vol. IV, p. 177, New York, McGraw-Hill Book Co., 1928. James, C., J . Am. Chem. Soc., 30, 182 (1908). Kading, H., Mumbrauer, R., and Riehl, N., 2. physik. Chem., A 161, 362 (1932).
Martin, A. J. P., and Synge, R. L. M., Biochem. J., 35, 1358 (1941).
Meyer, G., Rec. trav. chim., 42, 301 (1923). Mulliken, R. S., and Harkins, W. D., J . Am. Chem. Soc., 44, 37 (1922).
Rayleigh, Lord, Phil. Mag. 151, 42, 493 (1896). Richards, T. W., and Hall, N. F., J . Am. Chem. Soc., 39, 531 (1917).
Riehl, N., 2. physik. Chem., A177, 224 (1936). Rushton, J. H., I d . Eng. Chem., 29, 309 (1937). Schlundt, H., U . S. BUT.Mines, Tech. Paper 265, 31 (1922). Scholl, C. E., J . Am. Chem. Sor.. 42, 889 (1920). Sunier, A. A., J . Phys. Chem., 33, 577 (1929). Varteressian, K. A., and Fenske, M. R., I d . Eng. Chem., 28, 1353 (1936); 29, 270 (1937).
U'illiamson, B., and Craig, L. C., J . Biol. Chem., 168, 687 (1947). RECEIVED July 1, 1949. Based on a paper presented before the Division of Physical and Inorganic Chemistry. Symposium on Separation and PurificaCHEMItion of Organic Compounds, at the 115th Meeting of the AMERICAN CAL SOCIETY, San Francisco, Calif.
Purification by Fractional Melting J. G . ASTON A N D S. V. R. MASTRANGELO Pennsylvania State College, State College, Pa. The use of the solid-liquid equilibrium for purification by the method of fractional melting is shown to he highly efficient. This method makes it possible to observe the progress of purification inasmuch as the liquid fraction is always separated from the solid fraction under equilibrium conditions. Examples of the progress of purification of several materials are given.
A
LTHOUGH crystallization from a solvent is, of course, one of the oldest and most widely used methods of separation, the possibility of using solid-liquid equilibria in a manner analogous t o vapor-liquid equilibria for efficient separation has not been widely recognized. The separation of a single pure solid from a liquid of two components is similar to the removal of the vapor of a pure substance from a liquid mixture with a nonvolatile substance. Whenever the solid-liquid equilibrium has been used for separations similar to those that are possible in the various types of liquid-vapor equilibria, the process used has been essentially crystallization ( 3 ) . Such separations can be carried out by fractional melting with much greater convenience and ease of control. The present paper describes the work on the single-step separation of a purer substance as a solid from a liquid mixture in equilibrium with it, usually where no solid solution occurred, by fractional melting, and points out its advmtages over fractional crystallization. In theory, the substance may be obtained 1 0 0 ~ o pure and the maximum possible yield of pure substance by such a process is easily calculated by a material balance from the initial composition, if the eutectic diagram is known or can be c o m p u t d using Raoult's law. In practice, if this process is carried out by cooling and removing the crystals which separate until the eutectic is reached, such yields of pure material are frequently not obtained. The reason for this is illustrated best by an attempt to free cis-2-butene from the accompanying trans-2-butene by freezing. Starting with a sample of cis-2-butene with 3.1 mole yoimpurity, of which 2.9 mole % was the trans variety, about 10% of the liquid was frozen wlth vigorous stirring, using a bath no colder
than necessary to get a convenient rate of cooling. In spite of the fact that the impurities (including the trans-2-butene) were both shown not to form solid solutions with the cis-2-butene, the solid that separated contained 3.4 mole % impurity. This was shown to be due to the fact that the eutectic mixture separated at the walls and while the liquid was poured off some crystals of the pure cis-2-butene melted by conduction down the stirring mechanism and were poured off as liquid, and the impurity remained behind as eutectic on the supercooled walls. Efforts to eliminate the temperature gradients responsible, by customary methods, such as an imposition of an air bath between the sample tube and refrigerant, produced little improvement. The role of the solvent in fractional crystallization is to make it easier to get equilibrium by stirring, and this offsets the disadvantage of introducing a third component. The present paper shows how these difficulties can be removed by fractional melting of the solidified sample, under equilibrium conditions throughout. APPARATUS
Four batch-type purifiers have been built and used a t one time or another. A411consist of a vessel with a large conducting surface inside to produce thermal equilibrium, and a heater. In this vessel the system is first entirely frozen and then fractionally melted. A predetermined amount of heat can be added electrically to this vessel; adiabatic conditions are maintained by an electrically heated shield which surrounds it to eliminate radiation and conduction. The radiation shield is surrounded by a copper sheath to equalize temperature and the whole is immersed in a refrigeration bath. Adiabatic conditions are maintained by keeping the shield a t the same temperature as the melting vessel with the aid of copper-constantan difference thermocouples. Apparatus 1. This has a capacity of 100 ml. and has conduction vanes in the form of a spiral stirrer similar to that used
V O L U M E 22, NO. 5, M A Y 1 9 5 0
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bottom ai the temperature equalizer is clmed by means oi a copper disk inch thick. 'The outer envelope, 10, is made of Monel metal '/,6 inch thiok, and is provided with a Mono1 tube for evacuation. This reduces the heat leak by gaseous conduction to and from the nielting chamber. Cork sheet insulation, 17 and 18, between the melting chamber and the shield, and between the shield and nnd temperature equalizer, is also provided for this purpose, so th fe
Figure 1. Fractional \ldting Apparatus 1 Spiral a t i m r and hourioa removed
in ~ m n emeat grinders. Figure 1 is a photagraph of this ap paratus with spiral stirrer and housing remove? (right of photo graph). Aooaratus 2. This also has a capacity of 100 ml.. but hea
Figure 2.
Fractional Melting Apparatus 4
W i t h brsckct for mounting on large Dcxnr
I
A calibrated copper-constantan thermocouple which is it?bedded in paraffin contained in a long, thin-walled gla~stube IS used for observing the temperature of the sample in thc mclting chamber. The glass tube containing the thermocouple pa?se into the apparatttus through tube 9. A copper-constantan Aiference thermooouple registers the difference in tempera!ure between the melting chamber and the shield. The two junctions of this difference thermocouple are soldered to the walls under the respec$ye heaters: T h e s e - ~ h ~ r ~ o m u p will l e e register temDerature ainerences ot s m u t u.wi5". . Thee1itire apparatus is suspended inside a glass Dewar, which contains the refrigerating bath.
n the warm ~fegion. The cylindried radiation and condurtion shield, 12, is close< i st the top and bottom with disks of copper I/a inch thick. Th e r d g chamber. The temperature equalizer, 11, consists of a copper cylinde I I/,. inch thick. The cover is soldered to the tap and is provide,d with four omnines which w e lame enoueh to allow the Mom!I tubes, 6, 7,'8, aield f i t material with this purity. H ~ 3ver, M the second liquid fractioii w:ts withdrawn and a new fraction mcltcd. The rquilihrium tc’mperature indicates that this sample was 99.92 mole 7epure and : ~ I I 80% >+irltf was obtainable. After only 3Oyeof the sample was wmoved the purity rose to 99.996 mole %, and after the 1;t.t frartioii was removed a purity drtermination madt’ in t,hr uiu:il c:tlol i-
Progress of Purification of n-Heptane Equilibrium Temperature. O C. 182 108 182 498 182 514 182 577
Purity. % ’ 99 5 99 91 99 92 99 996
Yield 100 90 80 70 60
( (
As a typical example which demonstrates the great efficiency of this process with apparatus 3, the progress of purification of a 500ml. sample of %-heptane is given (Table I). Column 1 lists the total quantity of liquid sample removed after each step. Column 2 lists the absolute temperature of equilibrium before the corresponding liquid fraction is removed. Column 3 lists the corresponding total purity of the sample remaining in the sample container, including the solid and liquid fractions. This is obtained from the mole fraction of impurity in the liquid and the amounts of liquid and solid using the following equations :
P% = 100 Lf (To - Tn) Yn/’RT,1
where p% is the total mole
% impurity
L j is the heat of fusion in calories per mole of the major com-
ponent T, is the melting point of the pure major component in degrees Kelvin T, is the absolute temperature of equilibrium at the nth step Y , is the corresponding fraction of material melted based on the total amount of material in the melting chamber a t this step R is the ideal gas constant, 1.987 calories per mole Qn is the amount of energy used for heating and melting the material in the melting chamber for the nth step f C,,dT is the amount of energy which produces the rise in temperature during the energy input (Cpn is the average heat capacity of the nth fraction based on interpolation of the solid and liquid heat capacity curves in the region of melting, and d T is the rise in temperature during the energy input) Qtotai is the total energy input required to melt the original quantity of material placed in the melting chamber In Table I, column 4 lists the yield corresponding to the purity listed in column 3 based on the original weight of material. Reference to Table I shows that the original purity of the sample is 99.5 mole % (row 1, with all the material present). After one 10% fraction was melted, the liquid fraction withdrawn
Figure 3.
Fractional Melting Apparatus 3
Monel tube for evacuation Stuffing box Activator rod for vane system No. 18 copper wire conduction heater 5 . Transfer tube 6. Monel tube for electrical supply wires 7. Monel tube for transfer tube exit 8. Monel tube for activator rod exit 9. Monel filling tube and thermocouple exit 10. Outer envelope (cryostat) 11. Temperature equalizer 12. Shield 13. Meltine- chamber 14. Vane 15. Guide rod 16. Spring 17 18 Cork sheet ineulation 19: Glsm wool filter 20. Drilled plug 1. 2. 3. 4.
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Table 11. Yields Obtained for cis-2-Butene Yield, % Purity, %
60
70
99.83
99.94
50 99.998
Table 111. Progress of Purification of Other Samples Compound
Cyclohexane
Original Purity, % 85.0 99.22 99.6 99.4 95.7 99.6
Purity, % 98.95 99.14 99.22 99.75 99.99 100 99.96 99.99 99.98 99.99
Yield, % ' 53.4 45.5 37.8 33.0 78.0 78.0 70.0 80.0 80.0 70.0
metric way indicated that the purified sample had a purity of 100% within the accuracy of the measurement (*0.005 mole %). A sample of cis-2-butene [melting point 134.260" K., AH, = 1746.8 calories per mole ( 6 ) ]containing an impurity of 3.9 mole % [mostly trans-2-butene melting point 167.61" K., AH! = 2331.9 calories per mole ( a ) ]was purified in apparatus 1, which employs a spiral stirring mechanism in place of the compressible vanes. The yields obtainable for the corresponding purities, based on the total quantity of material, are listed in Table 11. Such yields would be very difficult t o obtain by distillation. It is interesting to compare with the theoretical yield the possible yields obtainable for cis-2-butene by stopping the process at any step in the procedure with the theoretical yield. A calculation made by solving the melting point equations for cis-2-butene and trans-2-butene at the eutectic temperature, using the above values for the melting point, shows that the eutectic temperature is 131.17' K. and the eutectic mixture consists of 1.43 trans-2butene and 85.70/, cis-2-butene. Hence, the per cent of eutectic mixture in a sample of cis-2-butene containing a 3.9 mole yo impurity of trans-2-butene is 27.3 mole % and the theoretical
yield of pure cis-2-butene is 72.7%. From Table I it is apparent that, although a 60% yield of the 99.94 mole % material based on the original weight of material is obtainable, this is 82.5% of the theoretically possible yield for this type of process. The results of purifying other samples in various types of fractional melting apparatus are given in Table 111. Column 1 lists the compound being purified; column 2 lists the original purity; and columns 3 and 4 list the corresponding purities and yields obtained, the latter based on the total quantity of material used. The materials corresponding to the yields in column 4 were not removed each time but were instead used for further melting to give the next corresponding purity and yield. The results for cyclohexane are of doubtful validity, because the sample is reputed t o contain about 1 mole % of methylcyclopentane, which forms solid solutions with cyclohexane (6). Combined with the rough fractional distillation of the eutectic mixture and of early liquid fractions withdrawn, this method should, in most cases, prove superior t o precise fractionation when only the major component is to be separated in the pure state. The truth of this statement can be seen in the separation of the geometric isomers of 2-butene and of 2-pentene. ACKNOWLEDGMENT
The authors wish to thank the Phillips Petroleum Companv for the financial help which made this work possible. LITERATURE CITED (1) Aston, J. G., Fink, H . L., Tooke, J. W., and Cines, M. R.. ANAL.CHEM.,19, 218 (1947). (2) Guttman, L., and Pitzer, K. S., J . A m . Chem. SOC.,67, 324 (1945). (3) Hicks, M. M., BUT.Standards J . Research. 2 , 483 (1929). (4) Johnston, H. L., and Giauque, W. F., J . A m . Chem. SOC.,51, 3194 (1929). (5) Scott, R. B., Ferguson, W. J., and Brickwedde, F. G . , J . Research Natl. BUT.Standards, 33, 1 (1944). (6) Tooke, J. W., and A&on, J. G., J . Am. Chem. SOC.,67, 2275 (1945).
RECEIVED August 6, 1949.
Criteria of Analytical Methods for Clinical Chemistry R. M. ARCHIBALD The Hospital of the Rockefeller Institute f o r Medical Research, New York 21, A'. Y . .4nalytical reports from most clinical laboratories are unreliable, sometimes because of errors in the collection and labeling of specimens, but more often because of inadequate procedures within the laboratory. Unreliability results largely from inadequate supervision of analysts who may lack proper technical training or personality qualifications. Some improvement should result from selection of simple methods capable of giving accurate results in the hands of the personnel available. Explicit typed or
s XOVEMBER
1947, Belk and Sundermsn ( 4 )reported on a survey of the accuracy of measurements of calcium, urea, sodium chloride, hemoglobin, glucose, and serum protein as carried out in 40 t o 50 hospitals in Pennsylvania, New Jersey, and Delaware. Aliquots of solutions of known strength for each substance to be measured were sent to the laboratories included in the survey; reports were made anonymously. The survey showed that almost two thirds of the laboratories reported results that were unsatisfactory from the point of view of accuracy. In the case of calcium, the concentrations reported ranged
printed directions free of ambiguity should be in the hands of each analyst. An aliquot from a large stock pool should be carried through all steps, including calculations, with each set of determinations. Calculations should be checked by some responsible individual in addition to the analyst. The laboratory director must be provided with adequate motivation devote the necessary time to supervise the analytical staff properly. Attributes of suitable analytical methods are considered.
from less than one third to more than twice the csorrect value; with urea, from one tenth of the correct value up to 35% too high. Similar unsatisfactory results were reported for sodium chloride, hemoglobin, and serum protein. For glucose there waa more than a 14-fold difference between the highest and lowest values reported. Shuey and Cebel (9) found similar unsatisfactory results reported from U. S.Army and Air Force hospital laboratories not only for chemical analysis of blood, urine, and milk but also for identification of parasites or cultures of bacteria and fungi.
