914
ANALYTICAL CHEMISTRY
Table I. Analysis of Synthetic Samples Containing Hydrazine Sulfate and Ammonia by the Iodate-Kjeldahl Method sample 1.
Sample NzH4.HnSO4, 0.1 gram: "a, 8.24 mg. (0.484 meq.)"
KO.
Ammonia Found Meq. Sfg.
0.482 8.21 0.487 8.29 0.485 8.26 0.489 8.33 0.487 8.29 0.489 8.33 0,484 8.24 2. N?Hi.HzSO4, 0.1 gram: 1 0.096 1.63 NHs, 1.65 mg. (0.0967 rneq.) 2 0.097 1.65 3 0.098 1.67 3. X?H1.H2SOll 0.1 gram, 1 0.044 0.75 NHs, 0.82 mg. (0.0484 meq.) 2 0.046 0.78 3 0.047 0.80 Characteristics of the samples in Group 1 were as follows: Average KHa found mg 8.28 Standard deviation '0.045 Standard deviation'of mean, sm, 0.017 Confidence limits at 95% level, 8.28 + 0.04 Confidence limits = z tam, t = 2.447 for 6 degrees of freedom.
*
dicated in series 2 and 3 of Table I Kith little sacrifice in precision. Samples with wide ranges of composition have been successfully determined by this procedure. The limit of ammonia in the above procedure is chosen so that convenient volumes are involved both in the iodate titration and in the ammonia distillation. In all cases attempted with alkyl and aryl hydrazines no sign of additional ammonia generation was observed. All guanidines interfered in this procedure yielding erratic evolution of the amino and imino nitrogen. LITERATURE ClTED
Bottger, W., "Tewer Methods of Volumetric Chemical Analysis," tr. by R. E. Oesper, New Yolk, D. Van Xostrand Co., 1938.
Fuchs. W.. and Xiszel. F.. Ber.. 60B. 209 (1927). Fuller: L. 'P., Lieber. ' E . , and ~ 'Smith, G. B. L.', J . A m . Chem. SOC.,59, 1150 (1937).
Hammock, E. W., Brown, R. A , , and Swift, E., ANAL.CHEM.. 20, 1048 (1948).
Keim, G. I., Henry, R. .1.,and Smith, G. B. L., J . Am. Chem. Soc., 72, 4944 (1950).
dah1 procedure. Hydrazine was incorporated in these samples by addition of weighed amounts of hydrazine sulfate. The hydrazine sulfate alone had been analyzed by this same procedure for ammonia with no ammonia being found. As indicated in series I, the precision of the method, shown by a standard deviation obtained from several values, is about 5 parts per thousand for samples in the range 8 milligrams of ammonia. Smaller amounts of ammonia were determined as in-
Lieber, E , and Smith, G. B. L., C h e n . Rea., 25, 213 (1939). Milligan, L. H., J . Phus. Chem.. 28, 544 (1924). Penneman, R. A , , and Audrieth, L. F., Ara~.CHEM.,20, 1058 (1 948).
Smith, G. B. L., and Wheat, T. G., ANAL.Cmbr.. 11,200 (1939). Wiebke, E. F., Zbid., 23, 922 (1951). RECEIVED f o r review January 1. 1953. Accepted February 12, 1953. Presented before the Division of Analytical Chemistry a t the 123rd Meeting of the . ~ M E R I C A S C H E M I C ASOCIETY, L Los Angeles, Calif.
Determination of Purity. of Compounds by an Extraction-Solubility Method V. A. STENGER, W. B. CRUMMETT, AND W. R. KRAMER The Dow Chemical Co., Midland, Mich.
the solubility of a pure compound under specified B conditions is a constant, one can evaluate purity by measIf two unequal quanECAUSE
uring differences in observed solubilities. tities of an absolutely pure compound are crystallized from equal volumes of a solvent a t the same temperature, the two mother liquors should be identical. When a soluble impurity is present, the mother liquor from the larger sample will contain more dissolved material. Several workers have made use of this principle and have discussed the advantages and limitations of the method (1-6). Ordinarily several solubility values are determined a t constant temperature with an increasing ratio of solute to solvent, and the data are plotted (9,IO). Changes in the slope of the line indicate the presence of impurities. A different version of the method makes use of changes in the temperature a t which the solution is just saturated (7). In general the previously proposed procedures are best suited for revealing the presence of impurities in compounds that are not highly purified. Experimental difficulties become great if one tries, for example, to ascertain whether or not a compound is better than 99.5% pure. Therefore the present authors have attempted to develop a modification which would be applicable to pure compounds. The problem was approached with the idea of increasing the relative variations in observed solubility in two ways: first, by using a solvent in which the compound to be tested is only slightly soluble a t room temperature, and second, by increasing the ratio of impurities to solvent through the Soxhlet extraction process. The procedure developed has been found applicable to several unrelated solid compounds of good stability and low volatility, for which solvents with suitable characteristics could be selected. No absolutely pure material is required for comparison. To illustrate the mode of operation an application to the analysis of tetrachloroquinone (chloranil) is
described below. The procedure is given in more general terms to allow for differences between individual compounds. APPARATUS
Extraction apparatus, Soxhlet, 100-ml., for 26 X 60 mm. thimbles. If thimbles of this size are not available, use a 25 X 80 mm. size and cut off enough from the top so that the remainder will fit in a 70-ml. weighing bottle. A section of glass tubing about 2.5 cm. long and 2.7 cm. in diameter is convenient for holding the thimble up from the siphon tube of the extractor, to allow more complete drainage with samples that clog the thimble. More rapid extraction may also be accomplished by shortening the siphon tube somewhat. Evaporating dishes, borosilicate glass, 100 nil. Filter crucibles, sintered glass, coarse or medium porosity. REAGENTS
Solvent. The solvent must be one in which thr compound is soluble to the extent of only 0.5 to 2.0 mg. per milliliter a t room temperature. The solubility range for various solvents is determined roughly by preliminary experiments with small amounts of a sample which need not be pure. To be suitable, a solvent should be chemically inert and should have a moderately low boiling point (50" to 90" C., depending on the stability of the compound). Moisture should be absent and nonvolatile impurities, if any, should be removed by distillation. Wash Solution. Warm about 1to 1.5 grams of the compound (using the purest material available) with 500 ml. of the chosen solvent. Mix well, cool to room temperature, and allow to stand for an hour or more. Make sure that a small excess of the solute is present; if not, add more and warm again. Record the temperature and filter out the undissolved compound. Measure 50 ml. of the filtrate in a graduated cylinder and pour it into a 100ml. glass evaporating dish that has been tared against a similar dish. Evaporate the filtrate nearly to dryness on the steam bath but remove in time so that the last of the solvent comes off a t a lower temperature. Finally dry under the conditions indi-
975
V O L U M E 25, NO. 6, J U N E 1 9 5 3 cated in the procedure. Weigh the dish plus residue against the tare dish dried similarly, and calculate the solubility in grams per milliliter of solution a t the recorded working temperature. Use the wash solution within a degree or so of this temperature. PROCEDURE
Preliminary Drying. Determine the best conditions for drying the compound by heating weighed small portions a t various temperatures. If the compound sublimes readily, it may be necessary to dry a t room temperature in a desiccator containing a suitable absorbent for the solvent that is to be used. In any case the drying should be continurd until the sample reaches a constant weight. Dry a 10-gram portion of the material under the determined conditions, cool, and weigh. Calculate the percentage of moisture plus other volatile impurities. Extraction. Heat two clean extraction thimbles with an excess of the chosen solvent, drain, and dry, first in air, then in an oven a t 80" C. Cool in weighing bottles in a desiccator and weigh. Divide the dry 10-gram sample between the thimbles and weigh thrm in the bottles again. Dry and weigh two Soxhlet flasks. Place each thimble in a Soxhlet apparatus and add 70 ml. of the solvent. Heat on a hot plate until extraction is complete, which may require several hours or several days depending upon t h r solubility. Make sure that none of the compound remains in the thimble, then dry the thimble and any residue in air and in the oven a t 80" C. Cool in a weighing bottle in the desiccator as before and weigh. Any gain in weight is calculated as the percentage of insoluble impurities. Treatment of the Extract. The recrystallized compound remains in the boiler flask with 40 to 60 ml. of solvent and the soluble impurities. Cool this mixture to, but not below, the temperature a t which the wash solution is saturated. It may be advisable to weigh the flask and contents a t this point, as a check on later evaporation losses. Stir well and filter, by gravity or with very gentle suction, on a coarse or medium sintered-glass crucible that has previously been tared after drying under the recommended conditions. Transfer as much of the precipitate as possible without washing and let it run fairly dry, but do not allow much time for evaporation. Measure the volume of the filtrate in a graduated cylinder, then place the filtrate in a 100ml. glass evaporating dish tared as in the solubility determination. Transfer the loose remaining crystals to the filter with four 5-ml. portions of wash solution, carefully measured, and follow these with 3 ml of pure solvent. Add the washings to the measured filtrate in the evaporating dish, evaporate and dry as before, and weigh. Dry the crucible and the flask in air and finally under the recommended conditions, cool each, and weigh. CALCULATION
The combined weight of crystals in the crucible and the flask is too low by the quantity required to saturate the original filtrate. Multiply the volume of filtrate (excluding washings) by the solubility in grams per milliliter and add this figure to the weight of crystals. Divide the corrected crystal weight by the original dry sample weight and multiply by 100 to find the percentage purity on the dry basis. The weight of soluble impurities found in the evaporating dish is too high by the solubility correction applied above, and by the amount of compound present in 20 ml. of wash solution. Subtract these corrections. Divide the corrected figure by the original dry sample weight and multiply by 100 to find the percentage of soluble impurities on the dry basis. Failure of the percentages of purity and impurities to total 100 may indicate a loss of impurities by volatilization or decomposition. High results may be attributed to incomplete drying of the crystallized product or to oxidation. APPLICATION TO TETRACHLOROQUINONE
Pure chloranil can be dried a t 80" C. for half an hour without appreciable loss; its solubility in carbon tetrachloride a t 25' C. is 0.96 mg. per milliliter. Lacking a sample of the pure compound one would determine an approximate solubility on the material at hand; this is done in connection with making the wash solution. If the chloranil sample were 99.0% pure and if 1.5 grams were dissolved in 500 ml. of warm solvent, up to 0.015 gram of impurity (along with 0.480 gram of chloranil) would remain in
solution after cooling to 25" C. The apparent solubility of chloranil would then be no more than 0.99 mg. per milliliter. Xext the Soxhlet extractions would be performed using a 5.0gram sample in each case. -4ssume that 60 ml. of mother liquor is obtained after filtration and that 20 ml. of wash solution is used. On the basis of the apparent solubility figure, the combined solutions would be calculated to contain 80 X 0.99 mg., or 79.2 mg. of chloranil. However, the impurities from 5.0 grams of sample will also be present if their solubilities are not exceeded. Five grams of 99.0% chloranil contains 50 mg. of impurities. (If this is all one compound whose solubility is the same as that of chloranil, up to 5i.6 mg. can be dissolved in 60 ml. of mother liquor. The presence of several compounds, or of one with a higher solubility, will increase the quantity that can be dissolved. Therefore, the probability is good that the impurity will remain in solution if it is soluble enough to pass through the Soxhlet thimble during extraction.) There will also be 57.6 mg. (60X 0.96) of pure chloranil in the mother liquor and 19.8 mg. (20 X 0.99) of chloranil plus impurity from the wash solution, making a total of 127.4 mg. of chloranil plus impurity to be weighed after evaporation.
Table I.
Analyses of Chlorariil and Mixtures
.Material Tested Recrystallized products
Impurities Chiorantl Purity Sample, Found, % Found. 70 Grams CClr- CCl4- Recov( D f y insolu- s o h ered, Appar- CorBasis) ble bleb Gramsb ent rected'
No. 1
4.9651 5.5186
0.09 0.05
0.00 0.07
KO. 1 plus 1.01% pentAchloropheno1
3.5248 4.0367
0.03 0.04
1.08
5.3433 4.7549
KO.
2
No.. 2 , plus
0.80% pentachlorophenol
Crude products Lot A
...
4.9604 5.5114
99.90 99.87
3.4857 1.06 3.9923
98.89 98.90
,,, ,,
0.00
0.04
5.3413
99.96
...
0.00
0.82
4.7117
99.12
... .
5.0000
0.19
0.56
4.9496
98.99
98.85
Crystals from 1st r u n of h
4.5000
0.00
0.19
4.4935
99.86
..,
Lot B
5.0000
0.20
1.08
4.9352
98.70
98.32
Crystals from 1 s t run 4.5000 0.14 0.17 4.4823 99.61 ... of B Apparent purity from first run, corrected for purity of crystals as found i n second run. Corrected for dissolved chloranil as explained under Calculation.
*
The apparent net weight of impurities recovered from the 5.0-gram sample is 127.4 - 70.2 mg., or 48.2 mg. The apparent percentage of impurities then is 0.964. This figure is to be compared with the actual value of 1.0%. Evidently a positive error of only 0.036y0 in the assay of chloranil is introduced by using a 99.07' product instead of absolutely pure material in the solubility determination. The validity of this conclusion rests upon the assumption that the impurities which are initially extracted by the solvent are not partially coprecipitated with chloranil. The conclusion can be tested in practice by reanalyzing the c r y 5 tals recovered in the first run. This has been done in two of the cases reported in Table I. So long as an appreciable amount of impurity remains, the observed solubility of the extracted portion will exceed the apparent solubility determined from the wash solution. The data of Table I illustrate the following points. A purified product can be shown to have a high purity by the proposed procedure. Presence of an impurity like pentachlorophenol, which is reasonably soluble in carbon tetrachloride, can be demonstrated almost quantitatively. A sample such as B, containing an impurity that is relatively insoluble in the chosen solvent, may show a high apparent purity unless the crystals obtained are reanalyzed.
976
ANALYTICAL CHEMISTRY Table 11. Analyses of Phenothiazine and Mixtures
Material Tested
PhenoApparent Sample Impurities thiazine Punty, % Grams' Found, 3 ' % Recov- From By ( D r y Insolu- S o h - ered recovdifBasis) ble blen Gram's" e r y ference
Recrystallized product (No. 3)
5.2463 6.5887
0.00 0 . 2 1 5.2359 0.00 0.16 6.5786
99.80 99.85
99.79 99.84
No. 3 plus 1.24% c p d e phenothiazine-5-oxide
5.4817 5.9213
1.00 0.94
0.38 0.44
5.4051 5.8434
98.60 98.69
98.62 98.62
Commercially purified phenothiazine (Lot C)
5.3059 5.1097
0.04 0 . 5 8 0.04 0.66
5.2722 5.0815
99.3T 99.40
99.38 99.30
Sublimates from S.F. powder: Lot D
2.0034
0.28
1.16
1.9792
98.79
98.56
2.4737
0.02
1.18 2.4439
98.79
98.80
Lot E Sublimates from drench mixtures :
a
Lot F
2.1240
0.25
1 . 5 1 2.0939
98.36
98.24
Lot G
4.8314
0.32
1.61
98.03
98.07
4.7364
Corrected for dissolved phenothiazine as explained under Calculation,
which the solubilities are too small. In water the solubility lies within the desired range, but hydrolysis takes place. Other solvents tested were found to dissolve too much or too little of this compound. Selection of an appropriate solvent is one of the greatest problems involved in the method. When the solubility of the compound tested is too large, the impurities become too small a fraction of the total dissolved material. The boiling point of the solvent is also a matter of importance. If low, evaporation during filtration of the mother liquor becomes serious; if high, drying is more difficult and decomposition or losses of the compound and impurities are more likely. In the case of 4-aminoantipyrine, a difference of 12" between boiling points of two solvents was sufficient to cause failure in one case and success in the other. Partial decomposition took place during extraction with the higher boiling solvent. Rlixed solvents are not to be recommended because of solubility variations a t different composition ratios. The method is inapplicable to compounds that melt a t 01 below the temperature of extraction and to those that are too volatile or unstable under the conditions required for extraction and drying.
APPLICATION TO PHENOTHlAZINE
DISCUSSION
The solubility of 99.8% phenothiazine in cyclohexane a t 21' C. is 1.35 mg. per milliliter. For drying the solid, a temperature of 105' C. is suitable for periods up to 2 hours. However, the compound appears to be subject to a slow surface decomposition from light or oxidation; the extraction-solubility method has not shown any sample to be better than 99.85% pure. Purity data on two fairly pure samples, and on a known mixture of one of them with phenothiazine-5-oxide, are reported in Table 11. It is to be noted that most of the oxide appeared with the insoluble fraction, but part came through as a soluble impurity. A crude sample of oxide was used in this test. An impurity present in the commercially purified phenothiazine behaved differently, being mostly soluble. Technical or N.F. phenothiazine, and drench mixtures based upon it, usually contain also a green, difficultly-solubleimpurity which is probably produced by oxidation and condensation during manufacture. This material interferes with the extraction procedure by clogging the thimble. To avoid the interference it has been found necessary to sublime such samples under vacuum and to analyze the sublimates. Correction would normally be made for the nonvolatile residues, but for the present purpose the purity percentages in Table I1 are expressed on the basis of the sublimed material. Since the purities are below 99%, it is likely that these results would be decreased slightly by second runs on the crystals from the first analyses.
The incorporation of an extraction step into the solubility method for purity determination offers several advantages:
APPLICATlON TO OTHER COMPOUNDS
A relatively large sample can be recrystallized from a small volume of solvent in which its solubility is limited, with assurance that all of the major component passes through the solution phase. The crystals are formed under good conditions for obtaining a pure product, from the standpoints of both a slow rate of formation and a favorable composition of the solution. If a nearly insoluble impurity is present, it does not reach its maximum concentration in the mother liquor until almost all the crystal growth has taken place. The possibility of working in a region of low solubility carries with it the benefits that supersaturation errors become less probable and the effects of small temperature variations are minimized. Even small errors in measuring the mother liquor are permissible; with a solubility of 1 mg. per milliliter, a deviation of 1 ml. in measurement introduces an error of only 0.02% on a %gram sample. The effects of small impurities on the solubility of the major component appear to be negligible. d convenient separation of insoluble impurities is accompli~hed. Errors in the determination of purity by this method are most likely to come from the following sources: Failure to extract the pure component completely from the thimble or to dry the thimble reproducibly. Evaporation of some solvent from the mother liquor during filtration. A correction for evaporation loss is possible if the flask and contents are weighed before filtration and if the density of the mother liquor is known. For practical purposes this is the same as the density of the pure solvent. Losses or gains of the components through volatility, chemical reactions, or mechanical errore.
Table I11 gives pertinent data for several compounds, some of which can be analyzed by the proposed procedure and others which cannot. Most of these Table 111. iipplicability to Various Solid Compounds were tested because decomDrying position during melting preSolubility Conditions cludes a reliable purity deterSolvent Mg,/ml. C. Hours C. Application Compound mination by the freezing point 80 Successful b u t exp,P'-IsopropylideqeCyclohexane 0.055 21 1 traction' required diphenol method (8). Where the exseveral days traction-solubility method also 105 Successful 1-(p-Biphenyly1oxy)Cyclohexane 0.94 24 1 2-propanol fails, the difficulty is caused 2,4,6-TribenzylCyclohexane 3.87 22 1 105 Kot tried either by lack of a suitable sol75 Successful 2.07 26 4 e-trioxane n-Hexane vent or by instability of the 4-Aminoantipyrine Cyclohexane 1.32 27 1 75 Slight decomposition c o m p o u n d e v e n below i t s 75 Successful 26 1 n-Hexane 0.65 melting point. Acetyl-D,LUnsuccessful, deAcetyl-D,L-tryptoCyclohexane 0.011 Vacuum composition durtryptophan, for example, turns phan Benzene O. 034 desiccator ing extraction Water 1.2 0 pink during the prolonged ex2-(o-Biphenylyloxy) Cyclohexane 9.26 24 1 105 Unsuccessful, too soluble ethanol tractions that are required with c y c l o h e x a n e or benzene, in
:i 1
i
V O L U M E 25, NO. 6, J U N E 1 9 5 3
917
Failure to obtain a saturated solution during preparation of the wash solution, or to bring the sample extract to the same temperature as the wash solution. Use of a poorly chosen solvent or failure to remove all solvent from the crystals. Coprecipitation of impurities with the crystals. This case has been considered above. In some cases the proposed procedure may be of assistance in the identification of impurities. An insoluble fraction in the thimble, if not dust, dirt, or filter fibers, can usually be extracted with a better solvent and recovered for examination, practically free from the major component. Soluble impurities are enriched perhaps ten- to 50-fold, depending upon the quantities employed and the solubility of the pure compound. Since the amount of known material in the soluble fraction can be calculated, one can determine the ultraviolet or infrared absorption spectrum of a solution, allow for the absorption of the known substance, and arrive a t an approximate spectrum of the impurities. Thus the
presence of one or more isomers has been indicated in some samples of p,p’-isopropylidenediphenol. LITERATURE CITED
Bennett, G. M., Analyst, 73, 191 (1948). (2) Butler, J. A. V., J . Gen. Phvsiol., 24, 189 (1940). (3) Cristol, S. J., Hayes, R. A., and Haller, H. L., IXD. ENG. CHEM.,ANAL.ED., 17, 470 (1945). (4)Herriot, R. M,, Chem. Revs., 30, 413 (1942). (5) hloore, S., Stein, W. H., and Bergmann, R I . , I h i d . , p. 423. (6) Northrop, J. H., and Kunitz, hl., J . Gen. Physiol., 13, 781
(1)
(1930). (7)
Reeve, Wilkins, and Adams, Rowland, B N ~ LCHEM., . 22,
755
(1950). (8) (9)
Stull, D. R., ISD. ENG.CHEY.,ANAL.ED.,18,234 (1946). Tarpley, William, and Yudis, Milton, ANAL CHEM.,25,
121
(1953). (10) Webb,
T. J.,Ibid., 20, 100 (1948).
RECEIVED for review December 13, 1952. Accepted February 13, 1953.
Construction and Calibration of Simple Semiautomatic Microburets U . L. UPSON General Electric Co., Richland, Wash. x
THE
routine performance of microtitrations, the use of screw-
1 feed mechanisms becomes tedious and time-consuming, since
no other operation can be performed during either the delivery or the refill period. I t was felt that a microburet offering the convenience and familiarity of stopcock control would be highly desirable. TKOsuch models were developed, covering the microand ultramicro ranges, and are described here. A method for the calibration of all Rehberg-type microburets which involves refinements yielding increased precision over previously reported methods is also given. AIR-CONTROLLED MlCROBURET
For microtitrations involving 200 pl. to 2 ml. of titrant, especially those of a repeated or routine nature, the easily constructed apparatus described here has been found equally precise and considerably more time-saving than the commercially available models employing the Rehberg-type control (2,3,4). Delivery is controlled by manipulation of a stopcock, just as for an ordinary semimicroburet, using the flip technique of incremental addition near the end point, and filling is accomplished semiautomatically. The device employed is not practical for increments of less than about 0.2 pl. but has been found highly satisfactory for capillaries of from 0.6 to 2.0 mm. inner diameter, giving capacities of from 200 pl. to 2 ml. for 25 to 35 cm. scale length. The delivery is controlled by regulating the flow of the air displacing the titrant in
the buret tube, and the air flow is throttled by means of a small piece of capillary tubing cemented into the bore of the stopcock. This tubing should be somewhat less than the bore length to prevent clogging with grease and should have an inner diameter of from 0.005 to 0.010 inches, depending upon the buret capacity, and hence permissible increment, chosen. Since the flow rate varies both with this throttling and with the hydrostatic head, the slope of the tube can be somewhat greater, or the tip longer, for the larger capacity burets than for those of less than 500 pl. volume. The buret tip should be drawn down and ground back to limit the flow, with the stopcock removed, t o about twice the desired maximum delivery rate, but in order to ensure equilibrium pressure and thus to retain control without overshoot, the bore of the stopcock plug must remain the ultimate flow rate limiting factor. For a maximum rate of about 4 cm. per minute, the precision is limited only by the reading error. To prevent dust from plugging the throttling capillary or contaminating the buret, a filter is attached to the air input tube. This can be a loose wad of long staple cotton in a drying tube (flushed with air before using). ADJUST
TO TO BURET
FILTERED ( I ATMOY
I i Figure 1. Air-Controlled Microburet For capacities from 200 PI. t o 2000 PI.
Figure 2. Device for Adjusting Vacuum
The original model (Figure 1) is filled by immersing the buret tip in a bottle or beaker containing the titrant and by turning the stopcock to apply a slight vacuum. This vacuum is adjusted (a device such as that shown in Figure 2 is suggested) so that the
