of a Bunsen burner. The resulting dark brown product produced copper(I1) and copper metal when added to dilute mineral acid solution. No carbonaceous residue remained, however. These observations provided additional evidence that the yellow precipitate was indeed cuprous hydroxide. Addition of a small amount of the freshly prepared cuprous hydroxide precipitate to a solution of the isopolymolybdate immediately produced the molybdenum blue color. The reducing agent operating in the analytical method for
copper based on the molybdate isopoly is copper(1) produced by reduction of copper(I1) by ascorbic acid. The data presented here verify the postulated reaction scheme of the catalytic reduction of the molybdate isopoly by ascorbic acid in the presence of copper(I1). RECEIVED for review June 10, 1968. Accepted July 5, 1968. R. L. Heller is grateful for support under the Carl Bauer Research Fellowship.
Solvent Extraction of Some Lanthanides with 2,2,6,6=TetramethyI=3,5=Heptanedione Thomas R. Sweet and Henry W. Parlett’ Department of Chemistry, Ohio State University, Columbus, Ohio
43210
A NUMBER of studies of the solvent extraction of the lanthanides with P-diketones have been reported (1-3). Pure P-diketones have been described as both the chelating reagent and the nonaqueous solvent in several solvent extraction studies (4-6). Eisentraut and Sievers (3have shown that the chelates formed by the lanthanides with 2,2,6,6-tetramethyl-3,5-heptanedione-hereafter referred to as H(thd)-are stable, anhydrous, and can be successfully gas chromatographed without decomposition. The present study was undertaken to determine whether a number of the lanthanides will undergo quantitative extraction using this reagent and to determine the stabilities of the chelates formed in the aqueous phase by means of solvent extraction techniques.
which were obtained from American Potash and Chemical Corp. These solutions were standardized by titration with EDTA using xylenol orange indicator and also by igniting an evaporated aliquot at 1000 “C and weighing the metal oxide. Dilutions to the desired strengths were made from these stock solutions and the appropriate radioactive tracer was added. Solutions (5.0 X 10-6M) of the metal chelate in pure H(thd) were prepared by shaking for 30 minutes a 2.5 X 10-5M aqueous solution of the metal at a pH of about 11 with pure H(thd) in a 2 :1 volume ratio. Procedure. A 10.0-ml volume of a 0.1M (C2H&NC104 aqueous solution, adjusted to the desired initial pH, was placed in an extraction bottle and 5.0 ml of the 5.0 x 10-6M metal chelate in H(thd) solution was added and shaken for the desired length of time. After centrifuging to separate the layers, the equilibrium pH of the aqueous phase was determined and 2.0-ml aliquots of each phase were taken for counting the radioactivity present. Perchloric acid and tetraethyl ammonium hydroxide solutions were used to make all pH adjustments. The (CzH&NC104 was used to maintain the ionic strength constant at 0.1. The temperature was 24 z!= 1 “C.
EXPERIMENTAL Apparatus. A Model G Beckman pH meter equipped with a Thomas 4858-L60 combination glass silver-silver chloride electrode was used for all pH measurements. Solvent extractions were performed in 30-1111 Duraglass vials equipped with polyseal caps. A Burrell wrist action shaker was used to achieve equilibria in batch extractions. Radioactivity measurements were made with a RIDL 34-12B 400-channel pulse height analyzer. Spectrophotometric measurements were made with a Bausch and Lomb Spectronic 505 recording spectrophotometer. Reagents. 2,2,6,6-Tetramethyl-3,5-heptanedionewas obtained from Pierce Chemical Co. The fraction boiling at 104105 “C at 35 mm was collected. Aqueous stock solutions 0.1M with respect to the lanthanides were prepared from the metal nitrate hexahydrates Present address, U. S. Air Force FC/DASA, Lawrence Radiation Laboratory, Livermore, Calif. 94550 (1) J. Stary, “The Solvent Extraction of Metal Chelates,” Pergamon
Press, New York, 1964. (2) T. Moeller, D. F. Martin, L. C . Thompson, R. Ferrus, G. R. Feistel, and W. J. Randall, Chem. Rev., 65, 1 (1965). (3) T. Moeller, “The Chemistry of the Lanthanides,” Reinhold,
New York, 1963. (4) J. F. Steinback and H. Freiser, ANAL.CHEM., 26,881 (1953). (5) W. F. Wagner, Recordof Chem. Prog., 23, 155 (1962). (6) G. K. Schweitzer and W. Van Willis, Anal. Chim. Acta, 36, 77 (1966). (7) K. Eisentraut and R. E. Sievers, J. Amer. Chem. Soc., 87, 5254 (1965).
RESULTS AND DISCUSSION Although essentially complete extraction was obtained by forward extraction in 0.5 hour at equilibrium pH values from 7 to about 12.5, distribution ratios were so highly scattered at D values of about 5 x loa or greater that it was not possible to define adequately the log D us. pH curves in this region. By using the back extraction technique, high D values were obtained with much greater precision. In the process of adjusting the initial pH of the aqueous solution in the forward extraction, it was necessary to precipitate the lanthanide hydroxides. Although no precipitate was visible after extraction, the observed erratic behavior at high D values was attributed to the formation of a very small amount of an irreversible precipitate on the colloidal level that is presumably formed during initial pH adjustment in the forward extraction. A time and concentration study was made with europium. Using metal concentrations that were 5.0 X 10-*M with respect to the organic phase (and pH values of 6,lO-11, and 12) it was found that 5 hours shaking time was sufficient to obtain D values that remained constant with time. By maintaining the shaking time constant at 5 hours and varying the metal concentration (at constant pH values of 6, 10-11, and 12), it VOL. 40, NO. 12, OCTOBER 1968
1885
IxlO-lL
1x10-41
I
I
I
3
4
5
6
I
I PH
I
9
8
I
IO
I
I1
I
12
All of the elements studied showed essentially 100% extraction from a pH of about 7 to 12.5 (see Figure 2). Eu and Gd are not given in the figure because they are quite close to the curve shown for Sm. Both Eu and Gd have HI/^ values of 5.6. The log D L'S. pH curves for all of the metals studied showed the same general shape. The initial slope in the low pH region below about pH 6 was +3. This was followed by a gradual change in slope through a maximum and then a rapid change until a -2 slope was attained above about pH 11.5 (see Figure 3). It appears that the neutral extractable species that exists in the organic phase is not an ion association complex, because negative results were obtained when the organic phase was concentrated and tested for nitrogen and perchlorate. In addition, the initial slope of the extraction curve was +3 and not the +4 or +2 that would be expected if {MR4-, (CzH5)4N+]or { MR2+, C1O4-f were the extracted species. It was concluded that the neutral species in the organic phase is MR3. The other possible neutral chelate species, MR2(OH) and MR(OH)2 were ruled out on the basis that there was a very large excess of reagent in the organic phase which would tend to drive any hydroxy species to the MRI form. The lower solubility of hydrolyzed species in organic solvents also leads to the same conclusion. The [OH-] to [R-] ratio in the aqueous phase varies from 6.2 to 1.08 from pH 3.0 to 12.0 for a 0.1M (C2HJ4NC1O4 aqueous solution in equilibrium with pure H(thd). This can be calculated from the dissociation constant and the solubility of H(thd). Therefore, there is no pH region where the R- ion concentration predominates over the hydroxide ion, and thus the possibility of hydroxide complexes in the aqueous phase of the type MRj(OH), must be considered throughout the pH regions investigated. In the pH region where the log D us. pH curve has a + 3
I
Figure 1. Solubility of 2,2,6,6-tetramethyl-3,5-heptanedione in 0.1M tetraethyl ammonium perchlorate was found that the distribution ratio was independent of metal concentration when the metal concentration was in the region of 10-4M and below. The 5-hour shaking time was checked at 10d5Mand was used for the backextraction studies of all the metals. The pK, of the reagent H(thd) was reported by Guter and Hammond (8) as 11.77 at an ionic strength of 0.01, and Porell (9) found the pK, to be 11.76 & 0.02 at an ionic strength of 0.1 maintained with (C2Hs)4NC10a. Using this value, the solubility of H(thd) at 24 "C as a function of pH was determined spectrophotometrically. A plot of the solubility of H(thd) against pH is shown in Figure 1. (8) G. A. Guter and G . S. Hammond, J. Amer. Chern. Soc., 78, 5166 (1956). (9) A. L. Porell, M. Ohio, 1967. I
I
S. Thesis, Ohio State University, Columbus, I
I
I
1
I
I
I
I
I
1pH v2= 6 2
.bi 3
4
5
d l
6
I
I
I
I
I
I
I
7
8
9
IO
II
12
I 13
PH
Figure 2. Extraction curves for praseodymium, samarium, and terbium 1886
ANALYTICAL CHEMISTRY
,
P I ,
4. 5
6
I
p8H
,
,
9
10
, II
12
13
Figure 3. Log D us. pH curve for europium
Table I. Log of Overall Formation Constants Pr Sm Eu Gd Tb 610 8.20 i 0.15 8.30 f 0.15 8.35 f 0.15 8.30 i 0.15 8.46 i 0.15 PI1 15.52 f 0.05 15.73 i 0.05 15.86 i 0.05 15.73 f 0.05 16.07 f 0.05 020 16.30 5 0.05 16.50 f 0.05 16.60 f 0.05 16.53 f 0.05 16.86 f 0.05 a 22.05f0.06 22.08i0.06 22.10i0.06 22.57f0.06 PZl a 22.28 f 0.06 22.34 i 0.06 22.37 rt 0.06 22.93 f 0.06 030 a 24.7 zk 0 . 2 5 24.7 i 0.25 24.7 f 0 . 2 5 2 5 . 0 rtO.25 831 a 24.7 f 0.25 24.7 f 0.25 24.7 f 0.25 25.0 f 0.25 P22 27.79 f:0.09 27.90 i 0.09 28.12 i 0.09 28.47 i 0.10 P32 27.76 f 0.09 27.87 i 0.09 28.09 f 0.09 28.43 &- 0.10 P23 KDhi~$30 26.20 f 0.07 27.45 f 0.07 27.62 rt 0.07 27.62 f 0.07 2 8 . 4 0 f 0.07 * KDMR, 5.17 f 0.09 5.28 f 0.09 5.25 f 0.09 5.47 dz 0.09 Note: With the exception of PZ1and p30, all values were calculated on the assumption that that species was the only one of that charge present. a Because of the low radiometric counting rates and short half-life of the isotope used in this study (143Pr), the counting errors were so large that these constants were not calculated. Species MR2+ MROH+ MRz+ MRzOH MR3 MRxOHMW0H)zMRa(0H)z2MRz(0H)sZ-
Constant
Q 0
slope, the free hydrated +3 metal ion is the only species that could be present to any appreciable extent in the aqueous phase. As the pH increases, MR2+ and/or M(OH)2+ might account for the observed decrease in slope. However, the M(OH)+ form was neglected on the basis of constants given for the monohydroxide species by Moeller (IO), Larsen ( I I ) , and Tobias and Garrett (12). In order to calculate the formation constants, a series of distribution equations can be written in the form
where KD,,, is the distribution coefficient for the species MR3, p 3 0 and P j P represent overall formation constants, and D is the distribution ratio. This equation may be written in terms of the species known or suspected to exist in appreciable concentrations in a specific pH region. A series of such equations for a p H region may be written by substituting experimental D values at known pH values. These equations may then be used to solve for the unknown formation constants. In order to solve for the Pl0 and PZO or @IO and constants, the difference between the observed and the calculated D value was determined when values of Pl0 and PZO(or 010and PI1) were varied. The differences were squared and summed over the data points. These values were plotted for each combination of Plo and Pz0 used and contour lines were drawn through points of equal sum square values. In this way a pit map was drawn and by repeated calculations the best values for the combination of @IO and PZO(or @IO and Pll) were determined as the combination that gave the least sum square of the deviations. A precise value for 010could not be obtained. The probable reason is that the species MR2+never is predominant over an appreciable pH range and thus does not affect the log D BS. pH data sufficiently. It was not possible to distinguish between MR2+ or MR(OH)+ in this system. If either were assumed, the corresponding /3 value (B20 or PI1) could be determined and then used in the distribution equation to describe adequately this part of the extraction curve. Formation constants for the remainder of the possible combinations were evaluated by iterative techniques. One distribution equation was written for each possible combination (10) T. Moeller, J. Phys. Chem., 50, 242 (1946). (11) E. M. Larsen, “Transitional Elements,” Benjamin, New York, 1965, p 103. (12) R. S. Tobias and A. B. Garrett, J. Amer. Chem. SOC.,80, 3532 (1958).
of species with the limitation that only one species of each charge be used in any one distribution equation. However, in the region between MR,+ or MROH+ and the -2 speciesLe., where MR(OH)%, MRzOH, or MR3 and a negative 1 species are predominant-calculated curves could not be made to agree with the experimental curve throughout the entire region, assuming the presence of only one neutral species. Excellent agreement was obtained if both MR20H and MR3 were assumed present in the aqueous phase and no other combination of zero charged species was found satisfactory. Therefore, it was concluded that both the neutral species MRzOH and MR3 exist in this pH region and that MR(OH)z is not present. Hence MR(OH), and MR(OH)42-, which would form by stepwise addition of OH- to MR(OH)z, were also ruled as unlikely in the higher pH regions. It was not possible, mathematically, to eliminate any of the -1 and -2 charged species. However, the MR4- species is considered unlikely for the following reasons: (1) the steric effects involved in placing a fourth dipivaloyl methane with its bulky t-butyl groups on a trivalent lanthanide, and (2) the fact that Bauer, Blanc, and Ross (13) were unable to prepare Eu(thd)4- using their technique involving the reaction of a mixture of 4 : l ligand to metal. The other two possible singly-charged negative species-Le., MR30H- and MR2(OH)z--are both likely and either one can be used to describe this system. The most probable negative two species are MR3(OH)22and MRQ(OH)~~-, and the use of either explains the data in the pH region above 11.5. In view of the difficulty in making MR4-, it is not likely that either MRb2-or MR40H2- exist. Thus, as the pH is increased from low values of about 4 up to about 13, the following species are considered present in the aqueous phase: M3+,MR2+,MR(OH)+ or MRz+,MRzOH and MR3, MR30H- or MR2(OH)2,and MR,(OH)2z- or MR2(OH)3’-. The results are summarized in Table I, where the formation constants for praseodymium, samarium, europium, gadolinium, and terbium with H(thd) are given. KD,MR$BBO values are also given in the table and were calculated directly from data in the straight line portion of the extraction curve in the low pH region, using the relationship D = KDBIRaPS0~
1
3
.
The stability of these lanthanide complexes with H(thd) is greater than the corresponding acetylacetonate ( 2 ) and benzoylacetonate ( 2 ) complexes. This is reasonable because even though more steric hindrance would be expected as a (13) H. Bauer, J. Blanc, and D. L. Ross, J . Amer. Chem. Sac., 86,
5125 (1964). VOL. 40, NO. 12, OCTOBER 1968
a
1887
result of the bulky t-butyl groups, the pK. value of H(thd) is much larger than the pK, value for either acetylacetone or benzoylacetone. The high distribution ratios that were observed can be attributed, to a large extent, to the highly substituted @-diketone that was used as reagent. Brown, Steinback, and Wagner (14) have attributed poor extraction (28% for neodymium, 49% for terbium, and 84% for ytterbium) with acetylacetone to the formation of hydrates of the lanthanide chelates which are not as highly extracted as the anhydrous chelates, nor as stable. They suggest that highly substituted P-diketones have additional bulky groups which sterically hinder the attachment of water to the chelate and, therefore, tend to increase the distribution coefficient of the chelate. This concept of blocking of coordination sites by the bulky t-butyl groups and prevention of hydrate formation was also used by Sievers (15) in his ligand shell concept to explain the formation of anhydrous dipivaloylmethane lanthanide chelates. This shield(14) W. B. Brown, J. F. Steinback, and W. F. Wagner, J. Inorg. Nucl. Chem., 13, 119 (1960). (15) R. E. Sievers, K. J. Eisentraut, C. S.Springer, and D. W. Meek, “Advances in Chemistry,” No. 71, R. F. Gould, Ed., American Chemical Society, Washington, 1967, p 141.
ing of the central metal ion leads to high stability constants as shown by Van Uitert and Fernelius (16) and together with the high pK. of H(thd) explains the stability constants of the complexes studied in this work. Using the KDpoovalues in Table I, separation factors for a number of element pairs were calculated. These are: Pr-Sm, 18; Sm-Eu, 1.5; Gd-Tb, 6; Eu-Tb, 6; Pr-Tb, 160; Sm-Tb, 9; Gd-Eu, 1. Although praseodymium, samarium, europium, gadolinium, and terbium cannot be quantitatively separated from each other by a one-stage extraction with this extraction system, it does appear, on the basis of the separation factors shown, that many of these metals could be separated very well by a multiple extraction technique. RECEIVED for review February 5 , 1968. Accepted June 25, 1968. Work supported by the Aerospace Research Laboratories, Office of Aerospace Research, U. S. Air Force, WrightPatterson Air Force Base, Ohio, under contract number AF33(615)-3441. Taken in part from the Ph.D. dissertation of Henry W. Parlett, The Ohio State University, Columbus, Ohio, 1967. (16) L. G. Van Uitert and W. C. Fernelius, J. Amer. Chem. SOC., 75, 3862 (1953).
Determination of Steric Pulrity and Configuration of Diketopiperazines by Gas-Liquid Chromatography, Thin-Layer Chromatography, and Nuclear Magnetic Resonance Spectrometry J. W. Westley, V. A, Close, D. N. Nitecki, and Berthold Halpern Department of Genetics, Stanford University School of Medicine, Palo Alto Calf. 94304 SEVERAL authors have reported the isolation of optically active diketopiperazines from microbiological sources (1). While the chemical identity of most of these compounds has been established by classical methods, the optical purity and the absolute configuration of some of the isolated diketopiperazines is still in doubt. Since new sensitive techniques [thin-layer chromatography (2), gas-liquid chromatography (3), and nuclear magnetic resonance ($1 for the determination of optical purity and absolute configuration of diastereoisomers are now available, we have examined the relative merits of these methods for the steric analysis of diketopiperazines. EXPERIMENTAL
The diketopiperazines were prepared from the respective t-Boc-dipeptide methyl esters by treatment with formic acid (1) L. A. Mitscher, M. P. Kuntsmann, J. H. Martin, W. W. Andres, R. H. Evans, Jr., K. J. Sax, and E. L. Patterson, Experientia, 23, 796 (1967). (2) D. E. Nitecki, B. Halpern, and J. W. Westley, J. Org. Chem., 33, 864 (1968). (3) M. Raban and K. Mislow in “Topics in Stereochemistry,” Vol. 2, N. L. Allinger and E. L. Eliel, Eds., Interscience, New York, 1967, p 199. (4) N. S. Wulfson, V. A. Puchkov, U. V. Denison, B. V. Rozynov, V. N. Bocharev, M. M. Shemyakin, U. A. Ovchiwnikov, B. K. Antonov, Khim. Geterotsikl. Soedin., Akad. Nauk. Latv. SSR, 4, 614 (1966). 1888
ANALYTICAL CHEMISTRY
followed by cyclization of the intermediate formate salt in boiling toluene and sec butanol (4 :1) as described previously (2). All compounds were characterized by mass spectrometry and all diastereoisomers were examined using a Varian Aerograph gas chromatograph coupled to a Finnigan 1015 Quadrupole mass spectrometer. All compounds gave a molecular ion and the fragmentation pattern was in agreement with published data (4). The gas chromatographic conditions used for the separation of diastereoisomers are summarized in Table I. Thin-layer chromatograms (Table 11) were run on silica gel G plates using the solvent systems A (isopropyl ether-chloroform-acetic acid 6 :3 :1) and B (chloroform-methanol-acetic acid 14 :2 :1). Nuclear magnetic resonance spectra were determined on a Varian A-60 spectrometer and the results are summarized in Table 111. The racemization of echinulin (5) was achieved by refluxing XVII ( 5 mg.) in ethanol (0.5 ml.) and triethylamine (0.5 ml.) for 2 to 3 days under anhydrous conditions. The course of the reaction was followed by TLC on silica gel G plates using the solvent system described in Table 11. Final confirmation of the chemical identity of the more mobile product with echinulin (XVII) was made by eluting the material from a preparative TLC with chloroform and examining the residue by mass spectrometry (A.E.I., MS-9). The new product and XVII both showed a molecular ion at mle = 461 (6%) and a base peak at m/e = 334 (5) C. Cardani and F. Piozzi, Gazz. Chim. Ital., 86,211 (1956).
