GUANIDINE AKD NITROUS ACID. I* BY WILDER D. BANCROFT AKD BURTON C. BELDES 1. Introduction Organic chemists apparently have little idea and very little information as to what compound is formed when one removes a nitrogen atom from guanidine by the action of nitrous acid. This seems rather surprising in the light of the number of investigations n-hich have dealt with guanidine and nitrous acid, and also in view of the fact that the guanidine molecule is certainly not a large one (one carbon, three nitrogen, and five hydrogen atoms) and its two-nitrogen derivative must be a reasonablv simple conipound. The only definite information, as far as the authors are aware, which the literahre affords on this point, is in the work of Pellizzari,2 which is reported in Chemical Abstracts as follows:3 By addition of one mol ammonium hydroxide, cyanamide is converted into guanidine and dicyanodiamide into biguanide. The only known reaction in the opposite sense is the transformation of o-phenylenediguanide into P-cyano-o-phenyleneguanidine by treatment of nitrous acid. This treatment is now being extended to other compounds and it is found that nitrous acid converts diguanide into cyanoguanidine (dicyandiamide) and guanidine similarly yields a small proportion of cyanamide. In the data which Pelliezari presents to show the conversion of guanidine to cyanamide, the highest yield which he obtained appears to be 0.37 grams silver cyanamide per gram guanidine carbonate. This weight of silver cyanamide is equivalent to about 0.13 grams guanidine carbonate; the conversion to cyanamide has thereby been 13% complete. This seemed hardly a proper way to leave the matt,er. If cyanamide is the two-nitrogen derivative of guanidine, when one nitrogen has been removed by the action of nitrous acid, it should be possible to obtain a much higher yield of cyanamide. It should be possible to obtain nearly 1007~ conversion to cyanamide and to find the remaining few percent as unchanged guanidine. This then is the purpose of the present investigation: to show that cyanamide is the principal product formed when nitrous acid removes one nitrogen from guanidine (and not perhaps the product of a side reaction, as the 13% yield of Pellizeari might indicate). * This work is done under the programme now being carried out at Cornell University and sup orted in part by a grant from the Heckscher Foundation for the Advancement of Researc! established by August Heckscher at Cornell University. Krall: J. Chem. SOC., 107, 1396 (191j); Hale and Vibrans: J. Am. Chem. Soc., 40, 1059 (1918); Plimmer: J. Chem. SOC., 127, 265 (1yzj);HyndandMacFarlane: Biochem. J., 20, 1264 (1926). ZGazz., 51 I, 224 (1921); Atti -4ccad. Lincei, 30 I, 171 (1921). Chem. Abstracts, 15, 3982 (1921).
GUANIDISE AND NITROUS ACID 2685 Professor Tenney L. Davis suggests that nitrous acid, in an acid solution, acting on a guanidine salt, might produce nitrosoguanidine. In this case? the nitrosoguanidine would dearrange to form cyanamide and nitrosoamide. He suggests also that if nitrosoguanidine is not so formed, the guanidine itself might dearrange to form cyanamide and ammonia, the ammonia reacting with nitrous acid to yield nitrogen gas. 2. Experimental Study For the qualitative analysis of nitrogen compounds of the cyanamide and related types there is available the very satisfactory procedure of B~chanan,~ whereby these compounds can be readily identified: ammonia and its salts, cyanamide, hydrocyanic acid and its salts, dicyandiamide, guanidine and its salts, guanylurea and its salts, thiourea, and urea. Of these we are interested in the test for cyanamide (precipitation of pale yellol? silver cyanamide on the addition of ammoniacal silver nitrate), dicyandiamide (precipitation from slightly acid solution of the white silver compound of dicyandiamide which is moderately soluble at 60 ), and guanidine (precipitation on addition of alcoholic picric acid). The picric acid would also precipitate melamine, a polymer of cyanamide, and guanyl urea. In the first case, however, the precipitate consists of very characteristic, canary-yellow, needles which no one would ever confuse with guanidine picrate. In this investigation guanyl urea almost certainly would be arrived at through the formation of dicyandiamide, for which this compound is a test, and in the absence of any positive test for dicyandiamide we will conclude that none of our picrate precipitate results from the presence of guanyl urea. Dicyandiamide, incidentally, is a polymer of cyanamide formed n-hen cyanamide is heated, and one might expect some dicyandiamide to be found in this present study. Ke need, finally, a qualitative test for urea and instead of using the method suggested by Buchanan (the conversion of urea to ammonia by the ureolytic enzyme in soy-bean flour) we will employ the Fosse method of precipitation by xanthydrol. The quantiative determination of guanidine was made according to the method of T-0zarik.j The precipitating agent consists of 8 grams ammonium picrate and 5 cc KH40H (Sp. G. 0.91) in a liter of water, plus 0.075 grams guanidine picrate to compensate for the solubility of the latter in the pre- cipitating reagent. To 5 cc of the guanidine solution (containing not more than I gram guanidine per IOO cc) is added 20 cc of the precipitating reagent and 0.5 cc concentrated,oh. After standing ten minutes, the solution is filtered through a Gooch crucible, and the residue washed with further precipitating reagent, dried, and weighed. To duplicate conditions which Private communication. 2 Davis and Abrams: Proc. Am. Acad., 61, 443 (1926). Ind. Eng. Chem., 15, 637 (1923). Werner: The Chemistry of Urea, 188 (1923). 2. angew. Chem., 15, 670 (1902).
2686 WILDER D. BANCROFT AND BURTON C. BELDEN will appear later in this paper, this quantitative test m-as tried also in the presence of sodium sulphate (about two grams in IOO cc guanidine solution); the presence of the salt was found to have no interfering action on the determination. Our quantitative determination of cyanamide was essentially that of Perotti. X 5 cc sample of cyanamide solution (containing not more than one gram cyanamide per IOO cc) is diluted to IOO cc, made alkaline with 2 cc concentrated by KH,OH, and standard S / IO silver nitrate solution added in excess. The precipitated silver cyanamide is filtered out on a Gooch crucible and washed with very dilute SH,OH. The final step is the titration of the silver remaining in the filtrate. Titration with standard ammonium thiocyanate with ferric alum indicator was unreliable under the conditions of the experiment (probably due to the presence of considerable sodium sulphate). Titration with standard sodium chloride with 5Yc potassium chromate indicator proved a satisfactory procedure, provided care was taken to have the ph of the filtrate between 6. j and 7.2. The exact procedure, then, was to neutralize the filtrate with sulphuric acid, using brom thymol blue as indicator, add a measured excess of standard sodium chloride sohtion, and back titrate the filtrate nith further standard silver nitrate in the presence of the potassium chromate. Our first idea was to treat a guanidine sample with nitrous acid in a Tan Slyke apparatus (in the presence of a strong mineral acid) until nittogen gas equivalent to one nitrogen atom of the guanidine had been liberated, and then remove the contents of the apparatus, neutralize, and test at least qualitatively to determine what nitrogen compound or compounds had been derived from guanidine. However, the amount of guanidine which can be properly used in a Van Slyke apparatus (j cc of a 17~ solution, or about 50 milligrams guanidine) is so small in comparison to the several inorganic substances also present (sodium nitrite, acetic acid, and sulphuric acid) that the qualitative tests are badly interfered with, if not completely masked. The next move was to take a one-gram sample of guanidine carbonate in a beaker, make strongly acid with sulphuric acid, place in an ice bath, and add dropwise and with constant stirring a solution of sodium nitrite. This should yield the decomposition product of guanidine in large enough amounts to be readily detected and perhaps estimated. This proved a rather ineffective means of treating guanidine with nitrous acid, for in the course of an hour perhaps 5yc of the original guanidine would have disappeared. However, in every qualitative examination of the results of such treatment cyanamide was found to be present and urea and dicyandiamide absent. This appears to be at least approximately the method used by Pellizzari in obtaining the results reported above. The final step was to treat acidified guanidine solutions with nitrogen trioxide produced according to the method described in Houben-Weyl.* Gazz., 35 11, 228 (1905). * Die hlethoden der organischen Chemie, 4, 595 (1924).
GUANIDINE AND NITROUS ACID 2687 111 this procedure 25 grams of arsenic trioxide is treated with 25 cc nitric acid (Sp.G. 1.3 j) in a generator flask. After a rather slow start, this reaction proceeds rapidly enough at room temperature for fifteen or twenty minutes, producing a brown gas which contains nitrogen trioxide. When this gas is passed into an ice-cold water solution, the solution becomes greenish-blue as nitrous acid is formed. It became quickly apparent that by this treatment guanidine could be converted rapidly (that is, within a few minutes) into its twonitrogen derivative. In fact, it required rather careful attention to stop the reaction with an 80 or 90% conversion of the guanidine, which was what we wanted. This is the method followed in obtaining the data reported below. In this work Eastman Kodak Company best-grade guanidine carbonate was used. It so happened that the sample we received was far from bestgrade, for the quantitative precipitation of guanidine by the picrate method outlined above showed the sample to be 79.7Tc guanidine carbonate. When a difficulty soluble portion of the sample has been removed by filtration, the guanidine carbonate content was raised to 84.0%. Inasmuch as the 20% impurity did not appear to interfere with our experiments, the guanidine carbonate was used as received. Our procedure was this: take a one-gram sample of guanidine carbonate, add a solution of 18 cc water and z cc concentrated sulphuric acid (whereupon the carbonate is decomposed with the evolution of carbon dioxide), cool the solution in an ice-salt bath, bubble a stream of gas from the nitrogen trioxide generator through the solution for a given number of minutes, allow to stand for an additional number of minutes, and then neutralize the solution with KO. I Weight guanidine carbonate Volume conc. H2S04 2 cc. Treatment with NzOs 5 mins. Allowed to stand j mins. Qualitative : guanidine considerable cyanamide slight Quantitative : guanidine (calculated as guanidine carbonate) cyanamide (calculated as guanidine carbonate) guanidine carbonate in the original sample (79.7 pure) c guanidine unchanged TABLE I yc guanidine converted to cyanamide yc guanidine unaccounted for No. 2 2 cc. 6 mins. 8 mins. slight considerable 58 j mgr. 797 mgr. 20.07c 73.4 6.6 No. 3 2 cc. 6 mins. 12 mins. nil considerable nil
2688 WILDER D. BANCROFT ASD BURTON C. BELDEN sodium hydroxide solution to halt the action of nitrous acid. The resulting solution is made up to IOO cc in a volumetric flask and is ready for qualitative and quantitative examination. The data for three typical runs are given below in Table I. It will be noted that the first run did not permit a sufficient conversion of the guanidine to its two-nitrogen derivative, while in the third run all the guanidine was consumed. The second run is approximately!that we wanted. It should be stated that the time for treatment xith N2Os is of course some-vvhat dependent upon the speed with which the generator is operating. Further, the rate of the reaction of guanidine Jyith nitrous acid naturally increases as the solution becomes more saturated with the gas, so that the interval between the fifth and sixth minutes is of more consequence in the reaction than the first minute. Sample No. z was also tested qualitatively for the following compounds, none of which was found to be present: urea, cyanide, and clicyandianiide. The conclusions we draly from this investigation are these:- I. An effective method for removing one nitrogen from guanidine by the action of nitrous acid (other than in the 1-an Slyke apparatus) is to treat the cold, acidified solution with nitrogen trioxide. 2. When guanidine is so treated, cyanamide is the two-nitrogen compound formed. Cornell rnioersity.