428
INDUSTRIAL AND ENGINEERING ChEMISTRY
of nitrate concentrations from 0 to 50 p.p.m. as NOa,an accuracy of approximately 0.5 p.D.m. can be obtained. ACKNOWLEDGMENT
The author wishes to express appreciation to W. H. & L. D. Beta, in whose laboratories this investigation was conducted. The assistance of H. L. Kahler, E. C. Feddern, and J. J. Maguire is a130 gratefully acknowledged.
Vol. 17, No, 7
LITERATURE CITED
Jordan, H. E., ed., “Standard Methods of Water Analysis”, 8th ed., pp. 48-50, New York, American Public Health Association, 1936. (2) Schroeder, W. C., and Berk, A. A., U.S. Bur. Mines, Bull. 443, p. 83 (1941). (3) SnelL F. D., and Snell, C. T.,“Colorimetric Methods of Analysis”, 2nd ed., Vol. 1, p. 635, New York, D. Van Nostrand Co., 1936. (4) Wolf, B., IND. ENS.CHEM.,ANAL.ED.,16, 446 (1944). (1)
Determination of Active Hydrogen Using the Grignard Reagent in Pyridine ROBERT A. LEHMAN AND HELEN BASCH N e w York University Ccllege of Medicine, N e w York 16, N. Y
A method i s described for determining active hydrogen by means of the reaction of the unknown substance with a suspension in pyridine of the Grignard-pyridine complex. The apparatus and procedure are derived from those of Fuchs, Ishler, 4nd Sandhoff (2) with substantial modifications. The results are satisfactory and the use of pyridine makes the technique available for the analysis of an extensive series of organic compounds.
T
HE application of the Grignard reagent to the gasometric determination of active hydrogen p’as first described by Zerewitinoff (IO), who showed &s early as 1907, in connection with the necessary determination of the blank, that when carefully dried pyridine is used in the procedure, it forms a precipitate with methyl magnesium iodide in amyl ether. This precipitate has the probable formula (CsH6N)2.CH3MgI.’(C5H11)?0.A considerable quantity of gas is evolved a t the same time, and additional gas is liberated on standing or heating. By operating rapidly and a t room temperature Zerewitinoff was nevertheless able to report satisfactory results with this solvent. Odd0 (6) obtained similar data using ethyl magnesium iodide in pyridine. Tanberg (8), on the other hand, using various specimens of pyridine, concluded that, it was not a satisfactory solvent for this purpose. Flaschentrager ( 1 ) developed a micromethod using a mixture of amyl ether and pyridine. His results were reasonably accurate but the gas evolved from the blank in some cases amounted to 50% of that from the sample. Recently a convenient method and apparatus for the microdetermination of active hydrogen hm been described by Soltys (7). I n this procedure, however, as in that of Flaschentrager, the first rush of gas evolved when the Grignard resgent is mixed with pyridine is inherently included in the blank, thus making the blank high and not altogether reproducible. The method of Fuchs, Ishler, and Sandhoff (2) A for the determination of active hydrogen was tested and found to be simple and rapid but useful only for the limited group of organic compounds which are soluble in butyl ether. I n attempting to substitute pyridine as a solvent of wider range of applicability, the authors obtained low results which approached nearer and nearer to the theory as more samples were run in the same charge of reagent. This error appeared to be due to the solubility of methane in pyridine and was eliminated when purified methane was used as the inert atmosphere. The apparatus of Fuchs and co-workers ( 2 ) , which, for convenience, is shown in Figure 1, was modified in several respects. The gas buret and reaction chamber were waterjacketed. Pressure tubing connections were
inserted a t B , D, and F , so that it was possible to shake the reaction chamber during the reaction and the equilibration of the gases. Since it was usually necessary to raise the temperature and this led to condensation of the solvent in the iron reagent cups, the cups were provided with loosely fitted brass caps about 4 mm. deep, which prevented the condensate from washing the sample into the chamber during determination of the blank. A small thermometer was hung on the gas inlet tube. At the end of the gasdrying train a reservoir for pyridine was added. This was filled with about 30 cc. of pyridine and connected to the gas inlet stopcock. Thus, the gas was saturated with pyridine vapor a t all times and liquid pyridine could be forced into the reaction chamber by tilting the reservoir. Diethylphthalate was found t o be a suitable manometer liquid. MATERIALS
Methane gas, 92% pure, was obtained from the Matheson Company, East Rutherford, N. J., and purified further by the washing train of Kohler, Stone, and Fuson ( 3 ) . Approximately 0.6 N methyl magnesium iodide solution was prepared as described by the same authors, using diethyl instead of diisoamyl ether. Reagent grade pyridine was refluxed several hours over potassium hydroxide pellets and redistilled. PROCEDURE
Samples were dried in the oven a t 110’ C. when possible, or otherwise in a desiccator over phosphorus pentoxide. Ten cubic centimeters of Grignard reagent were transferred to the reaction chamber with a pipet. The sample was then quickly weighed
D
n G
--J
7
Figure 1.
Diagram of Apparatus
A N A L Y T I C A L EDITION
July, 1945
into the m e t d cup, capped, and hung on the glass hook on the. gas inlet tube. The reaction chamber was carefully inserted into the system using Van Slyke sto cock grease to seal the groundglass joint. Stopcocks A and (?were closed and the three-way stopcock, E, was turned to position ac. .4water aspirator was attached a t C and the ether gently boiled off. When the boiling slowed, the jacket around the reaction chamber was filled with water a t about 90' C. and the evaporation continued until the evolution of gas in the fused methyl magnesium iodide subsided. I n this way as much of the solvent ether as possible was removed from the Grignard reagent. The water pump was disconnected, stopcock E was turned to ab, C was opened, and the reaction chamber flushed several times with methane by alternately raising and lowering the mercury bulb and manipulating stopcock G . Stopcock E was then turned to ac and the pyridine reservoir was tilted to allow about 20 cc. of pyridine to run into the reaction chamber. The Grignardpyridine complex precipitated out and a considerable volume of gas was immediately evolved which was allowed to escape through c. The three-way sto cock was then turned to ab, C was closed, and 0 turned to df. !'he reaction vessel was put under reduced pressure by lowering the mercury in the gas buret and the temperature of the water in the jacket of the reaction chamber was maintained at 90" C. for 45 minutes. The evolved gas was discarded from time to time through e. Stopcock G was now closed, C opened, and methane allowed to bubble through the reaction chamber until the vacuum was relieved. Stopcock E was then turned to ac and methane was passed through for 45 minutes to saturate the system completely. During this time the water jackets were adjusted to about 20' C. Now with E a t ab the gas buret was washed out twice with methane and left about half full of gas. Stopcock C was then closed. Sto cock A was opened with care and after allowing a short time k r equilibration, the manometer was adjusted to zero by means of the mercury bulb. The excess gas was discarded through e. The blank was determined by closing A , turning G to df, and filling the jacket of the reaction chamber with water a t 90" C. The expansion took place into the gas buret against the pressure of the mercury. After 30 minutes, the hot water was replaced by cold water, the reacfion chamber shaken to facilitate cooling, and stopcock A opened. Water adjusted to the same temperature as that in the buret jacket waa placed in the reaction chamber jacket and the whole system allowed to equilibrate. The gas volume was recorded and the gas discarded through e. Stopcock G was then turned to df, A was closed, the jacket temporarily removed, and the sample cup pulled down from its hook with the electromagnet, and turned over, and the cup and contents were allowed to disperse freely into the pyridine. Finally the cup was used to stir the entire reaction mixture by means of the magnet. Since the reaction is usually incomplete a t room temperature, the jacket was again filled with water a t 90"C. and the mercury bulb lowered whenever the difference in mercury levels exceeded 3 to 4 cm. The reaction was allowed to continue for 30 minutes with heating; then the reaction chamber was cooled rapidly and allowed to equilibrate in the same way as in the blank. The gas volume, temperature, and barometric pressure were recorded and the gas was discarded. A second blank was determined as before. For convenience the volume of gas produced by the sample should be 30 to 45 cc. and the average of the two blanks is subtracted from this volume. I n the analyses here reported, the mean blank was 1.9 cc. and constituted on the average 5.7% of the gas evolved by the sample. The volume is further corrected to 760 mm. of mercury, using Table I for the vapor pressure of pyridine. I t is then reduced to grams of methane by the appropriate factor given by Fuchs ( 2 ) for the temperature a t which the gas was measured. These values are also given in Table I. Thus, phloroglucinol gave the following values: Weight of sample Temperature Barometric pressure Volume of first blank Volume from sample Volume of second blank
Then 44.90
-
(3.95
0.2146 gram 20.00 c. 766 mrn. of mercury 3.95 CC. 44.90 CC. 3.35 cc.
+ 3.35) = 2
41.25 cc. of gas corrected for blank
429
Table I. Constants for Calculation of Results Temperature
c.
Vapor Pressure of Pyridine (0) Mm. of mercury
0.667 0.665 0.662 0.660 0.658 0.656 0.654 0.652 0.649 0.647 0.045 0.643 0.640
15.5 15.9 16.8 18.3 19.3 20.5 21.6 22.8 24.3 25.5 26.9 28.4 30.0
20 21 22 23 24 25 26 27 28 29 30 31 32
Density of Methane ($1 G./cc. X 10.'
Table II. Results of Analysis of Various Compounds Number of Active Hydrogen Atoms
Substance Picric acid Hydroquinone Resorcinol Phloroglucinol Pyrogallol Phenolphthalein Aurin 3,3',3"-Trimethoxy-4,4',4"-trihydroxy triphenylmethane 3,3',3 "-Trimethoxy-4,4'-dihydroxyfuchsone
1.00 2.01 0.96 1.00 2.80 2.07 1.97 3.03 2.95 2.03 2.09 2.06 0.99 0.99 0.97
Phthalimide
Theoretica Number
1 2 2 3
3 2 2 3
2 1
0.97
DISCUSSION
When the determination was carried out in butyl ether Fuchs and co-workers (2) failed to get satisfactory results with a number of polycarboxylic acids and polyhydric phenols. This was attributed to the insolubility of the samples. It seems probable that the reaction product is also insoluble in butyl ether and the reaction may then take place only on the surface of the solid phase, I n the method here described, both sample and reaction product are soluble and the insoluble pyridine-Grignard reagent complex breaks down progressively until the reaction is complete. From Table I1 it will be noted that picric acid and hydroquinone gave theoretical results, whereas in Fuchs' procedure no reaction took place. His conclusion that, in the case of picric acid, the failure was not due to steric hindrance thus appears justified. The observation that resorcinol in butyl ether behaves as a monoketomonoenol is confirmed for pyridine. The symmetrical trihydroxybenzene acts, in like manner, as a diketomonoenol, while the vicinal trihydroxybenzene reacts in the expected way. Results with phenolphthalein indicated the theoretical number of active hydrogen atoms for the structure as conventionally written. This is in agreement with the work of Lin (4) and contrary to that of Odd0 and Vassallo (6) who used ethyl magnesium halide. Three other triphenyl methane derivatives and phthalimide all gave results in agreement with the accepted structures. The only limitation to the method which has been noted so far is that the sample must not sublime nor distill a t 90" C. with the pressure partially reduced. LITERATURE CITED
Flaschentrager, B., 2.physiol. C h a . , 146, 219 (1925). Fuchs, W., Ishler, N. H., and Sandhoff, A. G . , IND.ENG.CHEM., ANAL.ED., 12, 507 (1940). Kohler, E. P., Stone. J. F., and Fuson, R. C,, J . Am. Chem. Soc., 49,3181 (1927).
Lin, Che Kin, Ann. Chim., 13, 317 (1940). Oddo, B., Ber., 44,2048 (1911). Oddo, B.,and Vassallo, E., G a m chim. itat., 42,11, 204 (1912). Since the theory for this substance is 13.48 for one hydroxyl group in the molecule, the number of active hydrogen atoms is 1 .oo.
Soltys, A., Mikrochem., 20, 107 (1936). Tanberg, A . P.,J . Am. Chem. Soc., 36, 335 (1914). Van Meulan, P.H., and Mann, R. F., J . Am. Chem. SOC.,53,451. (1931). Zerewitinoff. T., Ber., 40,2023(1907); 41,2236(1908).
