October 15, 1932
I N DU STR I AL AN D EN GI N EER IN G C H E MI STRY
(6) Metcalf and Thompson, Phys. Rev., 36,1489-94 (1930). (7) Morecroft, J. H., “Principles of Radio Communication,” 2nd ed., Chap. VI, Wiley, 1927. (8) Nottingham, W. B., J . Franklin Inst., 208, 469 (1929); 209, 287 (1930). (9) Stadie, W. C., J. Biol. Chem., 83, 477 (1929).
401
(10) Stadie, W. C., O’Brien, H., and Laug, E. P., Ibid., 91, 243 (1931). (11) Van Der Biil, H. J., “The Thermionic Vacuum Tube,” 1st ed., McGraw-Hill, 1920. RECBIVEDApril 2 5 , 1932. This work was aided by a grant from The Chemical Foundation.
Determination of Metals in Organic Combination D. L. TABERN AND E. F. SHELBERG, Abbott Laboratories, North Chicago, Ill. knowledge perhydrol-sulfuric S POINTED out in the A study has been made of the action of fuming acid decomposition has not been report of the Sub-Comsulfuric acid and 30 per cent hydrogen peroxide applied to the systematic demittee on Synthetic Orupon organo-metallic compounds containing composition of organo-metallic ganic Chemicals of the American mercury, arsenic, antimony, bismuth, gold, silver, compounds. Drug Manufacturers Associaand germanium. Decomposition of all organic tion, “organic c om p o u n d s of MERCURY mercury are assuming an ever matter is rapid and complete, leaving a solution increasing importance in mediSeveral methods were studied containing only the metal, usually as sulfate. f o r t h e c o m p l e t i o n of t h e cine as antiseptics, anti-syphiTo this solution, customary melhods of analysis analysis in each instance. In litics, and diuretics.” During the may be readily applied; precipitation as suljide the absence of halogen, dilution year 1930, ten selected methods has been found useful particularly in the cases with water and titrationof for the analysis of organic mermercury with potassium sulfocury compounds were studied in of mercury, antimony, bismuth, and germanium, cyanate in the presence of nitric five different laboratories under as has a modification of the Newberry method acid was found to be satisfactory the supervision of this committee. in the case of arsenic. and apparently accurate. Variations of surprising magniWhere speed is important, this tude were found to occur. Using the same method for a given compound, differences as great technic has many advantages, enabling the complete analysis as 2 or 3 per cent were noted. The results for a different to be carried out in 15 to 30 minutes. Precipitation by mercurial by different methods show even greater variation, Jamieson’s reagent and either titration with potassium being as much as 7 per cent in the cases of mercury salicylate iodate or weighing as mercury zinc sulfocyanate (3) were and mercurochrome. About this time, during the course of looked upon with favor until, in the case of mercury salicylate, a study of certain synthetic organo-metallic compounds in the titration gave low and inconsistent results; the reason for this laboratory, it became very desirable to secure a more this has not been found. repid method of metal analysis. Since the chief aim of this study was the elaboration of a Experience in the foregoing analyses suggested strongly method applicable with equal accuracy to all types of organic that greatest progress could be made by devising a simpler mercurials, with and without halogens, precipitation as sulfide and more satisfactory mode of decomposing the organic com- seemed to offer the greatest possibilities. pound than the sulfuric acid-permanganate, sulfuric-nitric It was-found that the oxidation mixture, after dilution acid, hydrochloric acid, perchloric acid, and persulfate mix- and cooling, could be precipitated directly by hydrogen sultures commonly employed in the past. This was found in the fide; in the absence of inorganic salts, the authors not only use of fuming sulfuric acid and 30 per cent hydrogen peroxide failed to observe the inaccuracies reported by Fenimore and (Superoxol). The fuming acid (I5 per cent SOa) dissolved the Wagner ( I ) , but found that precipitation was complete organic compounds either in the cold or on gentle warming, within 15 minutes. No formation of sulfur was observed. facilitating complete oxidation, and the excess hydrogen per- If the precipitate was washed successively with alcohol, oxide on spontaneous decomposition left no residue of in- carbon disulfide, and ether, drying was complete in 20 minutes organic salts. With nearly all of the compounds studied, at 105” C. oxidation was found to be complete within 3 to 5 minutes, PROCEDURE IN ABSENCE OF IODINE. The sample containgiving a water-white solution containing only sulfuric acid and ing approximately 0.1 gram of mercury is placed in a Kjeldahl the metal as sulfate. flask with 7 to 10 cc. of 15 per cent fuming sulfuric acid. The use of hydrogen peroxide for hastening decomposition (With easily decomposable substances, ordinary sulfuric during Kjeldahl digestions was first suggested by Kleeman (5) acid is satisfactory.) The substance is dissolved, if possible, in 1921, and has subsequently found application in biological by gentle warming. Thirty per cent hydrogen peroxide assays (6, 7, 12). Oakdale and Powers (9) have employed it (Superoxol) is added drop by drop, being allowed to flow as a secondary oxidizing agent in a new method of halogen down the side of the flask, which is agitated gently by hand. determination. Oxidation takes place a t once. Addition of hydrogen perSince the completion of most of the following work, the oxide is continued until the liquid is the most straw colored, authors have found that Graham (8) employed a sulfuric- when warming is increased until fumes of SO3 are abundant. peroxide mixture of the decomposition of mercurial insecticide Sometimes a little more hydrogen peroxide is required for samples, and Schulek and Villecz ( I O ) have utilized it in the complete decolorization; the total amount required will determination of arsenic. These methods do not, however, vary from 1 to 5 cc. It is essential that everything be in seem to be well known in this country, and to the best of our solution at this point. I n the absence of halogen, no loss of
A
Vol. 4, No. 4
ANALYTICAL EDITION
402
mercury was observed on heating, but in the presence of chlorine or bromine, too much warming is to be avoided. If desired, the reaction may be carried out under a reflux condenser as described subsequently. The reaction is complete when no more oxygen is evolved. The water-white solution is diluted with water and precipitated directly with hydrogen sulfide, the mercuric sulfide filtered through a Gooch crucible, washed with carbon disulfide, alcohol, and ether, dried a t 105" C. for 20 to 30 minutes, and weighed. PROCEDURE IN PRESENCE OF IODINE. I n the presence of iodine the decomposition must be carried out in a 200-cc. flask connected by a ground-glass joint to a spiral reflux condenser through which the hydrogen peroxide is added. During the oxidation as tested upon a mixture of mercurosal and sodium tetraiodophenolphthalein, some iodine and mercuric iodide sublimes, and the solution is colored by dissolved iodine. The portion in the condenser is washed back several times with small amounts of water, and a little more hydrogen peroxide added to insure complete oxidation. A small final sublimate of iodine does no harm if it does not contain yellow mercuric iodide. To the diluted liquid in the flask is added about 0.1 to 0.2 gram of aluminum powder (c. P.); on warming, a vigorous reaction takes place and a black sediment of amalgam settles out. Warming is continued (a little more aluminum may be added) gently for 15 to 30 minutes until the precipitation of mercury is complete and a small residue of aluminum metal remains unchanged. After cooling, this is filtered (suction) through a small folded filter which is returned to the flask in which the reduction has taken place. Under the reflux, 2 cc. of concentrated nitric acid and 3 to 5 cc. of bromine water are added. When the main reaction is over, a small drop of liquid bromine may be employed to dissolve the residual globules of mercury, which sometimes resist even prolonged warming without the bromine water. TABLE I. ANALYSISOF MERCURIALSBY VARIOUS METHODS CALCD. JAMIESON JAMIESON HzS, GRA~. Av (KNOWN) TITR.
%
%
%
.
%
Mc'--L-ene 57.42 Ilia uell 0 1 .u1 01.1 49.05 M,srtfiolate 49.44 49 55 24.88 Mercurochrome 24.93 24.84 58.25 Mercury salicvlate 58.5" 58.81 (KCNS) 59.1 43.95 43.3 Merourbsal 43-43.8" 51.71 52.14 Mercurophen (51.5)5 56.94 56.3 Mercuric diphenyl 56.57 Mercurosal tetraiodo43.17 phenolphthalein 43-43.8 those substances not completely pure, the average metal con(1 With tent as determined by several laboratories was selected. I
~
+
The diluted contents of the flask are warmed to remove most of the bromine, filtered, and carefully decolorized with dilute sodium acid sulfate. Hydrogen sulfide is then passed in and the mercuric sulfide determined as described above. The methods outlined have been tested upon standard samples of the six pharmaceutical mercurials listed below, upon pure mercury diphenyl, and upon more than a dozen synthetic mercury compounds to be described in a separate paper. The results of duplicate or triplicate determinations were in each case close either to theory, or to the known mercury content. During the past three months, the method described above has been applied by the cooperating laboratories to the standard samples of the mercurials with '(distinctly encouraging" results. In the analysis of mercury ointments, the peroxide-sulfuric acid decomposition has been found more satisfactory than the official U. S. P. method employing nitric acid. I n this analytical laboratory, it is now routinely applied t o pharmaceutical preparations involving organic mercurials such as "Tincture Metaphen" and "Metaphen 2500." These
are merely concentrated rapidly to a small volume and the above procedure applied as usual.
ARSENIC The decomposition of organic arsenicals is carried out in a similar manner. Because of the ease with which arsenic is determined volumetrically, volumetric methods have been employed almost exclusively, and that of Newberry (8) has been best adapted to the conditions a t hand. The solution after cooling is diluted with 100 to 150 cc. of water, and 10 cc. of 10 per cent potassium iodide are added. The liberated iodine is expelled by boiling and the liquid concentrated to about 40 to 50 cc. Any iodine is decolorized by one drop of sodium sulfite, the solution is made just alkaline with 20 per cent sodium hydroxide, then slightly acid with dilute sulfuric acid, and finally alkaline with 5 to 10 grams of sodium bicarbonate. It is then titrated with 0.1 N iodine, employing starch indicator a t the end. The Lehman method (U. 8. P.) may also be used. The results are given in Table 11. TABLEI1 KNOWNARSENIC Arsphenamine Neoarsphenamine Sulfarsphenamine Stovariol
FOUND, Av.
%
%
31.2 20.3 21.6 27.6
31.0 20.5 21.4 27.5
BISMUTHAND ANTIMONY After decomposition as above, employing an excess of hydrogen peroxide, the bismuth and antimony exist as -ic sulfates. With hydrogen sulfide, precipitation was complete within 15 minutes, and no difficulty was encountered in filtration upon a Gooch crucible. The sulfides were precipitated in the presence of carbon disulfide, washed with this solvent, then with alcohol and ether, and dried a t 100" C. for 30 minutes, or to the lowest weight observed. Although this procedure was satisfactory in the case of antimony, it was found better to reduce the dilute bismuth solution with sulfur dioxide solution, expel the excess of the latter by boiling, and precipitate as bismuth sulfide. As alternative methods, precipitation of bismuth as basic carbonate and as metal (formaldehyde in alkaline solution) were tried with only moderate success. The results are given in Table 111. TABLEI11 KNOWN METALCONTDNT FOUND
+
Potassium antimony tartrate sugar Bismuth subsalicylate Bismuth camphor carboxylate Potassium bismuth tartrate 3- sugar
%
%
+
36.7 54.5 40.7 64.8
36.4 54 40.5 64.95
SILVER The Superoxol decomposition was employed on several samples of silver protein in place of .the more tedious nitric acid method. The diluted solution was titrated directly with potassium sulfocyanate after the addition of nitric acid and ferric sulfate. The results are given in Table IV. TABLEI V KNOWNAg
% Silver protein A Silver protein B
19.9 19.9
FOUND
% 19.75 19.93
GOLD With gold, the reaction is different, hydrogen peroxide precipitating metallic gold.' It is therefore preferable to dis1 N. A. Hansen of this organiiation has developed a similar method employing nitric acid.
October 15, 1932
INDUSTRIAL AND ENGINEERING CHEMISTRY CALCD.
solve soiuble gold salts in dilute sulfuric acid, add 3 to 5 cc. of hydrogen peroxide, and warm. The precipitated mass of gold is washed with water, then with alcohol, dried a t 105" C., and finally ignited. The results are as follows: CALCD.Au Gold sodium thiosulfate
FOUND
%
%
37.0
37.0
GERMANIUM The germanium compound is oxidized by sulfuric acid and hydrogen peroxide in a Kjeldahl flask, the sulfide precipitated from strongly acid solution, filtered as soon as coagulation is complete, and dissolved in strong ammonium hydroxide. This ammonia solution is filtered directly into a large crucible, the sulfide decomposed by Superoxol, evaporated to dryness, and ignited to germanium dioxide as in the method of Johnson and Dennis (4). The results are as follows:
403 %
Tetrabenryl germanium
16.62
FOUND % 16.45
LITERATURE CITED (1) (2) (3) (4) (5) (6) (7)
(8) (9) (10) (11) (12)
Fenimore and Wagner, J . Am. Chem. Soc., 53, 2468 (1931). Graham, J. Assoc. O$ciaZ Agr. Chem., 13, 156 (1930). ENG.CHEX.,11, 296 (1919). Jamieaon, J. IND. Johnson and Dennis, J . A m . Chem. Soc., 47, 790 (1925). Kleeman, 2. angew Chem., 34, 625 (1921). Koch and McMeekin, J . Am. Chem. Soc., 46, 2066 (1924). Myers, J. Lab. Clin. Med., 16, 272 (1931). Newberry, J. Chem. Soc., 127, 1751 (1925). Oakdale and Powers, J . A m . Pharm. Assoc., 20, 881 (1931) Schulek and Villecz, 2. anal. Chem., 76, 81 (1929). Willard and Thompson, J . Am. Chem. Soc., 52, 1893 (1930). Youngberg and Farber, J . Lab. Clin. Med., 17, 363 (1932).
RECEIVEDJune 9, 1932. Presented before the Division of Medicinal Chemistry at the 83rd Meeting of the American Chemical Society, New Orleans, La., March 28 to April 1, 1932.
Microdetermination of Carbon Improvements in Nicloux Method PAULL. KIRK AND PEARL A. WILLIAMS,University of California Medical School, Berkeley, Calif. HE method for microdetermination of carbon developed by Nicloux (3) would appear to have many possibilities, particularly in the field of biochemistry, since it, is a comparatively rapid and moderately accurate method which can be applied both to organic compounds and to mixtures containing carbonaceous compounds either in the solid state or in solution. In its original form, the Nicloux method had many shortcomings, part of which were chemical and part technical. Boivin (1) has so modified the method as to overcome most of the difficulties which arose from faulty combustion and absorption of the resulting carbon dioxide. Various other modifications have been developed, as by Osuka (4), and Schadendorff and Zacherl (6), both of whom have improved the method of handling carbon-containing solutions, such as urine, etc. From the technical standpoint, the method remained clumsy and difficult to carry out. I n this paper, further modifications are reported, aiming a t the reduction of these technical difficulties and the simplification of the procedure. These modifications also make possible an increase in the accuracy and decrease the time necessary to carry out an analysis.
T
APPARATUS UBED The apparatus is shown in Figure 1. It is essentially the apparatus used by Boivin, except that instead of having a bulb blown directly in the upper chamber to hold the absorbing caustic solution, a detachable absorption chamber is introduced. The rubber tube at G in the Nicloux and Boivin apparatus is replaced by a stopcock, as well as the plunger type of stopcock in funnel D. Originally Nicloux used an ordinary stopcock in funnel D and later replaced it with the plunger type to prevent entrance of carbon from the stopcock grease. Such a replacement may be desirable but does not seem to be necessary from the authors' experience, I n addition to the changes in design, it has been found advantageous to use the microfilters to be obtained from the Central Scientific Co., Chicago, Ill., previously described by Kirk and Schmidt (5') for separating the barium
carbonate precipitate, instead of centrifuging as in the original method.
PROCEDURE A sample of dry material containing 2 mg. of carbon is weighed. Unless the percentage content of carbon is very low, this must be carried out on a microbalance, or by dilution of a weighed quantity of the unknown material with a larger weighed quantity of noncarbonaceous solid material and subsequent weighing of a sample of the mixture on an analytical balance. Dry sodium sulfate may serve for such a diluting material if allowance is made for it in adding the reagent later. The dry material is transferred to sample tube A . To this is added 0.6 gram of silver chromate and 0.1 gram of anhydrous sodium sulfate. The sample tube is attached to the upper part of the apparatus and 3 ml. of concentrated carbon-free sulfuric acid placed in funnel D. The sulfuric acid is rendered free from carbon by heating it under a good vacuum on a boiling water bath with a little chromate, This heating should take place behind a protective glass screen because of a certain risk from explosions. In one case out of a considerable number of such heatings, the reagent exploded with considerable violence. No reference to this hazard has been found in the literature. If a stopcock is used, as shown here, it should be greased scantily with vaseline. The sulfuric acid apparently does not dissolve or attack the trace of vaseline with which it comes in contact. Another alternative is to use a phosphoric acid mixture as a lubricant, as described by Stevens (6).
The absorption cup, C, which is made from the bottom of a test tube, is now charged with 0.6 ml. of 2 N sodium hydroxide which must be carbonate-free. This is insured by the previous addition of a little barium hydroxide to the sodium hydroxide solution. The cup, inserted in the stopper containing a hole bored partly through, is inserted into chamber B. The system is now thoroughly evacuated and closed. I n case any leakage develops, a little clear lacquer has been found to be very effective in sealing i t without introduc-
