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(30) McGinnis, J., Stevens, J. M., and Groves, K., Poultry Sci., 26,432 (1947). (31) MoLeod, R. A., and Snell, E. E., J . Bid. Chem., 176,39 (1948). (32) Ned, G. H., Thompson, J. H., Garibaldi, J. A., and Brown, A. H., unpublished manuscript. (33) Peeler, H. T., and Norris, L. C., J . Bid. Chem., 188, 75 (1951). (34) Peeler, H. T., Yacowitz, H., and Norris, L. C., Proc. SOC.Exptl. Biol. Med., 72,515 (1949). (35) Petty, M. A., U. S. Patent 2,515,135 (July 11, 1950). (36) Reilly, H. C., Harris, D. A., and Waksman, S. A., J. Duct., 54, 451 (1947). (37) Rickes, R. L., Brink, N. G., Koniuszy, F. R., Wood, T. R., and Folkers, K., Science, 108, 034 (1948). (38) Roberts, E. C., and Snell, E. E., J . Bid. Chem., 163, 499 (1946). (39) Sarrett, H. P., and Cheldelin, V. H., Ibid., 155, 153 (1944). (40) Skeggs, H. R., Huff, J. W., Wright, L. D., and Bosshardt, D. K., Ibid., 176, 1459 (1948). (41) Skeggs, H. R., Nepple, H. M., Valentik, K. A., Huff, J. W., and Wright, L. D., Ibid., 184,211 (1950). (42) Smith, N. R., Gordon, R. E., and Clark, F. E., E. S. Dept. Agr., Mise. Pub. 559 (1946). (43) Snell, E. E., Bio2. Symposia, 12, 183 (1947). (44) Stokes, J. L., and Gunness, M.,J . Bact., 52, 195 (1946). (45) Stokstad, E. L. R., Dornbush, -4.C., Franklin, A. L., Hoffman,
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C. E., Hutchings, B. L., and Jukes, T. II.,Federation Proc., 8,257 (1949). Stubbs, J. J., Feeney, R. E., Lewis, J. C., Feustel, I. C., Lightbody, H. D., and Garibaldi, J. A , , Arch. Biochem., 14, 427 (1947). V e e r , W. L. C., Edelhausen, J. H., Wijmenga, H. G., and Lens, J., Biochim. et Biophys. Acta, 6, 225 (1950). Waring, W. S., and Werkman, C. H., Arch. Biochem., 1, 303 (1942). Wijmenga, H. G., Veer, W. L. C., and Lens, J., Biochim. et Biophys. Acta., 6, 229 (1950). Wolf, F. J., U. S. Patent 2,530,416 ( S o v . 21, 1950). Wood, T. R., and Hendlin, D., Ibid., 2,895,499 (May 6, 1952). Woodruff, H. B., and Foster, J. C., J . B i d . Chem., 183, 569 (1950). Woodruff, H. B., Nunheimer, T. D., and Lee, S. B., J . Duct., 54,535 (1947). Wright, L. D., Biol. S y m p o s i a , 12,290 (1947). Yacowitz, H., Norris, L. C., and Hauser, G. F., Proc. SOC.Ezptl. Bid. Med., 71,372 (1949). RECEIVED for review July 21, 1952. ACCEPTED November 24, 1952. Presented in preliminary form before the Fermentation Group, Division of Agricultural and Food Chemistry, a t the 117th Meeting of the AMXRICAN CHEMICAL SOCIETY, Philadelphia, Pa.
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e
Guanidine from Urea and
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e GEORGE W. WATT AND ROY G. POST1 The Universify o f Texas, Austin, T e x .
I
NTEREST in methods for the synthesis of nitroguanidine has prompted the study of reactions potentially competitive with existing processes for the production of guanidine salts (6, 11). As it is known that guanidine nitrate may be converted readily to nitroguanidine ( I $ ) , the direct production of the former by the interaction of urea and liquid ammonia solutions of ammonium nitrate suggests a possible route to the production of nitroguanidine from starting materials of relatively low cost. Basis for the belief that urea might react with liquid ammonia to form guanidine is found in the status of urea in its relation to the nitrogen system of compounds. In terms of the views of Franklin (4),urea is an aquoammonocarbonic acid and as such it might be expected to be ammonolyzed to the ammonocarbonic acid, guanidine. This reaction has indeed been observed by Blair (W),who determined the extent of conversion resulting from reactions in the presence of ammonium chloride a t 300' C. and a pressure of approximately 10,000 pounds per square inch. The work described in the present paper has been concerned with the establishment of optimum conditions for the production of guanidine from urea and ammonia. Certain other experiments mere conducted with a viev t o elucidating the mechanism of the reactions that occur above the critical temperature of ammonia.
Materials Commercial ammonia was dried over sodium amide in the manner described by Johnson and Fernelius (9). Ammonium reineckate, NH,Cr(NH,),(SCN),.H,O, was prepared by the method of Dakin (a), hexammine nickel(I1) nitrate by the method of King, Cruse, and Angel1 (IO),and tetrammine copper(I1) nitrate as described by Horn (7). Ammonium acetate was prepared by adding anhydrous hydrogen acetate to an1 Present
address, General Electric Co , Richland, Wash.
hydrous liquid ammonia a t -65'. 811 other materials employed were reagent grade chemicals that were used without further purification,
Analytical Methods Ammonium ion was determined by the formaldehyde method described by Grammont ( 5 ) . Three methods potentially useful for the determination of guanidine in mixtures of the type encountered in this work were evaluated. Precipitation of guanidine with Z-nitro-l,3-indandione was eliminated when it was found that this reagent also forms a precipitate with urea. Precipitation of guanidine reineckate gave results that were in good agreement but uniformly low; onlv 88 to 90% of the guanidine was precipitated in this manner. The method finally adopted for the determination of guanidine in the presence of urea and ammonium nitrate consisted of precipitation with saturated ammonium picrate solution ( I S ) . The precipitated guanidine picrate a as waqhed with water and dried a t 100" for 12 hours. A predetermined correction factor necessitated by the measurable solubility of guanidine picrate nas applied in each case. Several reaction products and/or unchanged starting materials were identified by comparison of x-ray powder diffraction patterns with the corresponding data obtained from the ASTM index of x-ray diffraction patterns. As data were not availahle for potassium picrate, guanidine picrate, guanidine nitrate, and ammeline [CsX,OH(NH,),]. patterns were obtained using pure samples (-100 mesh) of these compounds. These data were obtained using a Hayes x-ray spectrograph n-ith automatic recording, CuK, x-rays, nickel filter, a t a tube voltage of 40 kv. and a filament current of 15 ma. Interplanar spacings in Angstrom units and relative intensities are given in Table I.
INDUSTRIAL AND ENGINEERING CHEMISTRY
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Effect of Concentration Table 1. X-Ray Diffraction Data for Potassium Picrate, Guanidine Picrate, Guanidine Nitrate, and Ammeline Potassium
Guanidine
Picrate Picrate ~d I/Ii d 1/11 1.00 1.00 3.19 4.78 0.33 3.35 0.83 3.84 4.03 0.20 2.37 0.66 3.87 0.20 1.94 0.44 0.19 6.48 0.43 3.14 0.14 3.77 0.42 2.72 0.13 1.31 0.39 2.98 0.13 1.30 2.83 0.35 0.34 2.21 0.11 0.29 9.16 5.41 0.11 0.23 8.62 3.48 0.11 7.62 0.22 3.38 0.11 0.22 4.69 2.24 0.11 0.21 4.50 2.11 0.11 4.47 0.19 6.57 0 .loa 5.22 0.18 2.67 0.17 2.16 3.32 0.16 4 12 less intense lines not indexed. 25 less intense lines not indexed.
Guanidine Nitrate d 1/11 1.00 3.08 0.85 5.19 0.84 3.70 0.48 2.99 0.25 2.32 0.24 2.61 0.13 5.98 0.12 2.41 0.10 2.12 0.10 1.73 0.09 12.70 0.09 11.25 0.07 10.21 0.07 9.71 0.07 9.11 0.07 8.84 0.06 8.50 0.06 7.82
Ammeline I/Il 3.04 1.00 6.89 0.74 0.44 7.76 0.41 3.38 3.18 0.40 2.90 0.33 0.33 2.89 0.32 5.60 2.14 0.32 3.47 0.29 4.48 0.26 0.22 2.34 0.19 3.61 0.16 1.67 0.16 1.30 0.15 2.72 2.39 0 15 0:14b 14.72 d
.
Effect of Temperature and Time upon Yield of Guanidine Unless otherwise indicated, all reactions in ammonia were carried out in sealed 50 X 1.8 cm. borosilicate glass tubes, 1 mm. in wall thickness. I n a typical case, 4.4 grams of dry ammonium nitrate (0.055 mole) and 3.0 grams of dry urea (0.05 mole) were placed in a dry reaction tube. Air was displaced by a stream of anhydrous ammonia gas, after which the tube was immersed in a dry ice bath and ammonia was condensed until the total volume of liquid in the tube was 25 ml. The reaction tube was sealed and transferred to htn autoclave ( 1 ) containing commercial liquid ammonia; the autoclave was then sealed and allowed to warm to room temperature.
Table II. Yield o f Guanidine as Function of Temperature and Time Time, Yield, Hours % 0 17 30 0 24 100 0 8 200 Trace 16 250 9 4 300 17 300 8a 18 16 300 21 8 350 QAfter reaction for 8 hours a t 300°, presence of unchanged urea and ammonium nitrate was demonstrated by means of x-ray diffraction patterns. No extraneous lines were observed. Temp., O
...
The influence of changes in the concentration of ammonia and ammonium nitrate upon the yield of guanidine is shown by the results given in Table 111. All runs employed 3.0 grams of urea, 4.4grams of ammonium nitrate, and varied quantities of ammonia. When the concentration of ammonium nitrate was varied, 3.0 grams of urea in 25 ml. of liquid ammonia was used. All reaction mixtures were heated for 16 hours a t 300".
Effect of Acid Anions Experiments in which urea (3.0 grams) and various ammonium salts (acids in liquid ammonia) in 1 t o 1 mole ratio in 25 ml. of liquid ammonia solution were heated for 16 hours a t 300" were carried out in order to determine the influence of different acid anions upon the yield of guanidine. The results were as follows (guanidine yields in parentheses) : ammonium nitrate (18), ammonium chloride (21), ammonium bromide (20), ammonium iodide (18), ammonium sulfate (17), and ammonium acetate (trace). The results in experiments employing ammonium acetate were the same when i t was introduced as the reagent grade salt or formed in situ by the addition of anhydrous hydrogen acetate to the liquid ammonia solution.
Effect of Transitional Metal Ions I n experiments similar to those described above, 4.4 grams of ammonium nitrate, 3.0 grams of urea, and 0.5 gram of appropriate transitional metal nitrates were heated for 16 hours a t 300' in the presence of excess ammonia. Two of these salts were added in the form of ammines in order to avoid introduction of water into the reaction mixture. I n the determination of guanidine formed in these runs, the weight of picrate precipitate formed was corrected for the presence of the corresponding heavy metal picrate. The salts used and the corresponding guanidine yields (in parentheses) were as follows: Hg(N03)2 (161, Ni(NHddNOd2 (111, and Cu(NH3)dNOa)2(16).
e.
For reactions a t 100' C., the autoclave was heated in a steam jacket, an oil bath was used for reactions a t 200" C., and for all higher temperatures the autoclave was heated in the heating jacket of an American Instrument Co. hydrogenation apparatus. A t the end of the desired reaction time, the autoclave was cooled to room temperature, the ammonia contained therein was vented, and the reaction tube was removed and placed in a dry ice bath. One end of the tube was drawn out to a fine capillary to permit slow evaporation of the ammonia, after which the tube was evacuated for a few hours with a water aspirator. A section of the tube containing the solid reaction products was removed under conditions that obviated absorption of water from the atmosphere, evacuated with an oil pump t o ensure removal of volatile products, and weighed. I n most cases, very small samples were removed for use in obtaining x-ray diffraction patterns, while the bulk of the solid product was dissolved in water and made up to volume for analysis following centrifugation if any water-insoluble products were present. The section of the reaction tube was dried and weighed, and the total weight of nonvolatile reaction products was obtained by difference. The results from runs involving variation of temperature or time are given in Table 11. Material balances in these experiments were of the order of 98 to 99%.
Table 111.
Variation in Yield of Guanidine with Change in Concentration of Reactants
NHs, Yield, Moles % 0.0 20 Trac ea 0.5 20 14 1.1 20 18c 2.0 20 18; 1.1 6 25 1.1 1.6 26d 1.0 1.1 1.0 . 2ld 1.0 1.1 0.98 29 1.0 1.1 0.08 29 a Laree auantitv of ammeline formed: identified bv x-rav diffraction pattern; b fmall quantity of ammeline. a, Substantially same quantities of ammeline were formed in series of experiments in which ammonium chloride was substituted for ammonium nitrate. No ammeline. Material balances ranged from 82 t o 91% CO(NHd1, Mole 1.0 1.0 1.0 1.0 1.0 1.0
NHdNOs, Moles
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Effect of Added Water Because a probable product of the interaction of urea and ammonia is water, its influence upon the formation of guanidine was determined by adding 2.0 ml. of water and 4.4 grams of ammonium nitrate to the products resulting from treatment of 3.0 grams of urea in 25 ml. of ammonia for 16 hours a t 300'. The tube was then heated for an additional 16 hours a t 300". The resulting reaction mixture contained no detectable quantity of guanidine, whereas an 18% yield was obtained in a parallel control experiment which differed only in that water was not added.
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INDUSTRIAL AND ENGINEERING CHEMISTRY
Effect of Barium(l1) Oxide I n an effort to increase the yield of guanidine by the removal of water by means of a dehydratjon agent, reactions similar to those described above were carried out in the presence of a large excess of barium(I1) oxide. Guanidine formation was not observed in any of these cases and the only product identified was carbonate ion.
Reactions Involving Mono- and Disodium Ureas In order to determine Rhether urea could be converted to guanidine in media more basic than ammonia, reactions emplo:-ing both mono- and disodium urea were carried out in a manncr strictly analogous to that described above. The alkali ureas were prepared a9 described by Jacobson (8) and the initial reaction mixtures consisted of ( a ) urea plus monosodium urea, ( b ) monosodium urea, and ( e ) disodium urea plus sodium amide, each in the presence of eycess liquid ammonia under strictly anhydrous conditions. After 16 hours a t 300°, the ammonia was evaporated, and the residues were dissolved !n water and analyzed for guanidine, cyanic acid, and carbonate ion. The two former substances were shown to be absent; carbonate ion was found in all three reaction products and y a s at a niaximum in case (c), in which it wa? formed in a quantity equivalent to 70Vc of the urea used. 4 small quantitv of ammeline was isolated from the reaction product in case ( a ) and wss identified by its x-ray diffraction pattern,
Reaction Mechanism Studies The foregoing results suggest that the initial reaction is the thermal decomposition of urea and that the formation of guanidine and/or ammeline depends upon the presence of ammonium nitrate. Numerous experiments designed to establish the conditions necessary for the formation of guanidine were carried out: the more important of these are described helow. E F r E C T O F QUASTITY A Y V ORDER O F A D D I T I O N O F AWvTOYIVV NITRZTE. Reaction mixtures which differed only as indicated below were heated for 16 hours a t 300'. In one case, addition of ammonium nitrate mas omitted, in another the ratio of animonium nitrate to urea mas 0.5 to 1, while in another urea was heated in the presence of a quantity of ammonia gas on13 sufficient to displace the air in the reaction tube Guanidine was not formed in any of these reactions and the onlv material identified (other than unchanged urea) was ammeline. This product was isolated in two distinctly different crystalline forms, yellow needles and white plates; both were identified by means of x-ray diffraction patterns. I n subsequent experiments three reaction mixtures containing 3.0 grams of urea in 25 ml. of liquid ammonia solution were prepared. To one was added 4.4 grams of ammonium nitrate and the tube containing this mixture received normal treatment except for extent of heating. All three tubes were heated for 16 hours a t 300"; the two containing no ammonium nitrate contained a white ammonia-insoluble solid. One of these tubes was opened, 4.4 grams of ammonium nitrate was addzd, and all three tubes were again heated for 16 hours a t 300 The yield of guanidine from the reaction niixture which involved ammonium nitrate initially was PO%, that from the reaction mixture to which ammonium nitrate was added after the first heating period was 18%, while the reaction mivture to which n o ammonium nitrate was added gave no guanidine and only a small quantity of ammeline. A fourth eypeliment differed from those described above onlv in that, a t the end of the first heating period, the tube was opened, the solvent was evaporated, and all volatile products were removed by evacuation with a n oil pump. Ammonium nitrate (4.4grams) was then added, ammonia w 1s condensed to give a total solution volume of 25 ml., and the tithe was sealed and heated for an additional 16 hours a t 300". The yield of guanidine in this case was 9Vo.
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EFFECT OF ADDITION OF WATER. The last of the experimeuts described in the preceding paragraph shows that the yield of guanidine is decreased by the removal of volatile products (including water) prior to the addition of ammonium nitrate. &4ecordingly, two additional runs were made; they differed only in that volatile products were not removed after the first heating
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period, to one tube 4.4 grams of ammonium nitrate and 2.0 ml. of water were added, and t o the other tube 2.0 ml. of water only were added. After an additional period of 16 hours a t 300", guanidine was not found as a product of either reaction.
Discussion The data presented above show that, over the temperature range 200" to 350", guanidine may be produced from urea and ammonia in yields not evceeding 30% based on urea. The yield increases with increase in temperature and with decrease in the concentration of ammonia. The presence of an ammonium salt is essential for the formation of guanidine and the yield of the latter decreases if the mole ratio of ammonium salt to urea is
