Svnthesis of Guanidine and J
Nitroguanidine P
INTERACTION OF THIOUREA OR AMMONIUM THIOCYANATE AND AMMONIA INTERACTION OF NITROUREA AND GASEOUS OR LIQUID AMMONIA GEORGE W. WATT AND ROBERT C. MAICOSKY' The University of Texas, Austin, Tex.
E
ARLIER studies in these laboratories on possible methods
for the production of nitroguanidine have involved the interaction of urea and ammonia in the presence of ammonium nitrate ($6). The first part of the present paper is concerned with the action of ammonia (both below and above the critical temperature) upon thiourea and/or ammonium thiocyanate and more particularly with the establishment of conditions under which these reactants provide a substantially quantitative yield of guanidine, which may be converted readily to nitroguanidine (26). Another possible approach to the production of nitroguanidine lies in the conversion of urea to its nitrate salt, dehydration to nitrourea, and ammonolysis to nitroguanidine:
NHz
L o I
I
NHz NHNOz
I c=o I KHz
NHNOz "3+ &=I" + HzO -
I
iiHz
The first two of these steps are well known, but only very limited information is available relative to the interaction of ammonia and nitrourea. The second part of the present paper is concerned with this latter reaction.
GUANIDINE FROM THIOUREA OR AMMONIUM THIOCYANATE AND AMMONIA Franklin ( 4 ) has pointed out relationships which imply that thiourea may be looked upon as a thioammonocarbonic acid, and as such it should be expected to react with ammonia to form the ammonocarbonic acid, guanidine. The isomer, ammonium thiocyanate, should be expected to yield the same end product, although the rate of isomerization might be the rate-determining step. Both thiourea and ammonium thiocyanate react with ammonia to form guanidine (6-10,24, 20), and these reactions have been the subject of extensive process development studies. However, the existing literature provides only incomplete accounts of the effect of important variables upon this conversion, and the studies described below were carried out for the purpose of making this information available. MATERIALS
Guanylthiourea hydrochloride was prepared by the method of Bamberger ( I ). Thioammeline was prepared arcording to directions given by Rathke (18). I n order to provide for initially strictly anhydrous conditions, the commercial anhydrous ammonia used in these studies was predried over sodium amide 1
ANALYTICAL METHODS
Ammonium thiocyanate was determined by methods described by Williams ( $ 7 ) . That most often employed in the present studies involves oxidation of sulfur t o sulfate ion followed by precipitation as barium sulfate. I n the authors' experience, t h e alternative method involving precipitation of copper( I ) thiocyanate is much less satisfactory. Guanidine was determined by precipitation as the picrate ($6).
NH, 'N03" O 3 4 = IO ___ --HzO+ ___
NH,
( 1 3 ) . All other chemicals employed in this work were reagent grade and were used without further treatment except for thorough drying.
Present address, Bell Telephone Laboratories, Murray Hill, N. J.
Several components of reaction mixtures were qualitatively identified by means of x-ray diffraction patterns These were obtained using a Hayes x-ray spectrograph with automatic recording, Cu Koi radiation, a nickel filter, a tube voltage of 30 kv., and a filament current of 15 ma. Samples were mounted in cellulose acetate capillary tubes. I n most cases, the observed interplanar spacings were compared with those given in tho ASTM index of x-ray diffraction patterns. As this information was not available for thioammeline or guanylthiourea hydrochloride, patterns were obtained using authentic samples of these compounds; the resulting data are listed in Table I. EXPERIMENTAL METHODS
Unless otherwise indicated, all reactions in ammonia were carried out in sealed borosilicate glass tubes that were heated in an autoclave of the type described by Bergstrom ( 2 ) . These procedures have been described in detail (26). PYROLYSIS OF THIOUREA AND AMMONIUM THIOCYANATE IN PRESENCE O F LEAD(I1) CHLORlDE
Because most of the experiments dewxibed below involve the interaction of thiourea or ammonium thiocyanate and ammonia in the presence of lead(I1) chloride at elevated temperatures, it is necessary at the outset to determine whether guanidine may b e formed under these conditions in the absence of ammonia. In B typical experiment, 3.80 grams (0.050 mole) of thiourea and 15.30 grams (0.055 mole) of lead(11) chloride were intimately mixed and heated for 8 hours at 125" C. Guanidine was not produced as a result of this treatment, but when the experiment was repeated a t a temperature of 300°, guanidine mas produced in 17% yield. Similarly, ammonium thiocyanate and lead(11) chloride were heated for 8 hours a t 125' and 300". Guanidine was not formed a t 125" and only traces were produced a t 300". EFFECT OF TEMPERATURE
I n the study of this and other variables, typical quantities of thiourea (or ammonium thiocyanate) and added salt were those indicated above-i.e., a mole ratio of 1 to 1. 1. The quantity of
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involved 'rvere 0.11, 0.55, 1.00, and 1.50 moles of lead(I1) chloride per mole of thiourea, and the corresponding guanidine yields TABLEI. X-RAY DIFFRACTION DATA FOR THIOAMMEI.IXE AND GUANYLTHIOUREA HYDROCHLORIDE
a
Thioammeline __ d , A. I/Ii d, A. 1/11 2 61 0.10 8.99 0 . 3 3 2.54 0.11 7 . 1 7 0.63 2 50 0 . 1 2 6 . 9 8 0.88 2 41 0.17 4.88 0.72 2 26 0 . 1 3 4 . 6 5 0.19 2 12 0 . 1 3 4.50 0 . 5 3 2 06 0.10 4.03 0.23 2 02 0 . 1 8 3 . 9 4 0.13 1 87 0 . 1 7 3.86 0 . 1 4 3.81 0 . 1 4 3.61 0.21 3 . 4 2 0 75 3 . 2 6 0 51 3.04 1.00 2 . 8 2 0.1Oa 2.79 0 . 1 0 Less intense lines not indexed.
were 26, 58, 95, and 96%, respectively.
Guanylthiourea Hydrochloride d , A. I / I I d , A. I/1i 8.18 0 . 3 2 3 . 3 1 0.29 3.24 0.36 7.80 0.30 7.37 0.38 3.20 0.36 7 . 2 3 0.36 3.07 1.00 2.94 0 . 2 3 7.07 0 . 3 6 2 . 8 8 0.44 6.58 0 . 3 6 6.48 0.33 2.78 0.26 2.72 0.42 6.30 0.14 2.56 0 . 1 0 0.08 0 . 1 0 a 5.66 0 . 1 4 2.51 0.18 2.46 0 . 1 4 5 . 6 6 0.12 4.88 0.20 2.30 0.23 2.22 0 . 1 0 5 . 7 1 0 38 4.56 0.28 2.05 0.11 3 95 0 . 4 7 1.90 0.10 3.38 0.64 1.81 0 . 1 5
.
liquid amnionia condensed in t'he tube was such as to provide a total solution volunie of 25 ml. Upon completion of reactions not involving an added metal salt, the solvent was evaporated and the residual solids were dissolved in water and made up to liuon-n volume for analysis. If lead ion (or other metal ion) vias present, t,he n-ater-insoluble fraction was removed by filtration through a imighed fritted-glass filter, and the filtrate v\.as made up to known volume The \vater-insoluble product v a s dried a t 110" and n-eighed. In order to determine the effect of temperature upon the yield of guanidine produced by the interaction of thiourea and ammonia in both the presence and absence of added ammonium salts, runs were made a t three different temperatures and a total reaction time of 16 hours in each case. The results are given in Table 11.
ASD AlilMOSIl 11. Y I E L D O F GUASIDISEFROM THIOUREA FUKCTIOX OF TEXPERATURE ASD ADDEDA m i o ~ ~SALTS r~r
TABLE AS A
Temp., O
c.
100 200
300 a
Added Salt None NH&l "&SO3 h'one NIlrCl hXaN03 None h-HrC1 NIlaNOa
Yield,
%
0 Trace Trace 9
~
EFFECT OF LEAD SALTS
I n order to enhance the formation of guanidine through eliriiination of hydiogen sulfide formed in the reaction (and readily detectable by odor), lead salts were added in runs of 16 hours' duration. Aninioniuni salts were not employed in this series of ieactions. The requiting data m e listed in Table 111.
111.
EFFECT O F L E A D SALTS U P O S GLASIDI\EYIELD .4S A !?UXCTION O F TEMPERATURE Temp.,
c.
100 125 200 300 a
Added Salt PbC1, Pb(K0i)i PbIz PbCh P b ( S O s )Y PbCli Pb(NOd2
I n view of the marked effect of lead salts, it was considered worth while to study briefly the effectof salts of transitional metal ions such as silver, mercury, and cobalt. In runs employing 2.2 nioles of silver(1) chloride per mole of thiourea a t tempeyaturcs of 126" and 300°, the guanidine yields were 62 and 957,, respectively. In a similar run employing 1.1 moles of mercury(I1j chloride per mole of thiourea, reaction n-as evidenced at -70" during condensation of the ammonia. The reaction mixture assumed 2% black color, and continued reartion was evident as the contenbs of the sealed tube m r c allowed to warm to room temperature. After 21 hours a t room teinperat,ure,the ammonia mas evaporated and the solid residue was separated into a water-insoluble and ii water-soluble fraction. The former, a black solid, was dried at 110'. An x-ray diffraction pattern clearly demonstrated the presence of HgS, HgCla(SILC1j,, and HgCI,(Hg0)3. That thi, mixture was very complex is indicated by the fact that,, in addition to the 20 diffraction maxima attributable to the three mercury compounds indicat,ed, 16 other riiaxinia xwre recorded but not identified. The aqueous solution was evaporated to dryness, and the resultant solid ~ a recrystallized s from ethyl alcohol and diethyl ether. The x-ray difi'raction pattern obtained for this product was also complcu and aininonium chloride n-as the only component that could be ident'ified. It is significant, however, that this pattcrn gave no indication of the presence of nielaniine, dic~-antliamide, tliioarnrneline. or ~uii~i!-lthiourc:~. The pattern did include certain maxima possibly attributable to guanidine hydrochloride, but. the evidence was n o t :uffic.iently definite to constitute n positive identification. Use of 1.36 moles of hexamniinecobalt(II1j cliloi,itlc pcr mole of thiourea in a ruii of 8 hours' duration a t 123' yielded a very complex mixture which apparently did not include guilnitlinc. EFFECT O F TIME
15 13: 22 33
Reaction mixture exploded.
TABLE
EFFECT OF SALTS OF TRANSITIONAL METALS
Yield
93
33 14
78 67 58
9,2
Reaction mixture exploded.
In a related series of runs, the mole ratio of lead(I1) chloride to thiourea was varied over a wide range; the temperature was 300' and the heating time was 16 hours in all cases. The mole ratios
The extent to which the yield of guanidine is dependent upon time of reaction was determined in a series of reactiorip cai,ried out a t 125' and 300". -4t the Ion-er temperature, with thc arninonia in t'he liquid phase, the other reactants were thiourea and lead(I1) chloride. For a heating time of 0.5 hour, the quanidine yield was 51"/o: for eight timc intervals ranging from 1 to 16 hours, the yields showed no appreciable time dependencc and amounted to 64 i 3%. In the runs at 300" 120th thiourea and ammonium thiocyanate were employed as jtnrting materials and ammonium chloride and lead(I1j chloride were added. The data relative to these cases are given in Table 7 6 . EFFECT O F AMRIO\IA CONCERTR.iTIOK
I n these runs, the reactants vere thiourea and lead(I1) chloride in the presence of different quantities of ammonia; the heating time was 8 hours and the temperature 300'. In the first of these experiments the quantity of ammonia used was only that necessary to displace the air completely from the reaction tube; the guanidine yield was 10%. In subsequent runs, 4 to 1 and 8 to 1 mole ratios of ammonia to thiourea were employed and the quanidine yields found were 79 and $470, respectively. For a mole ratio of 20 to 1 (Table IV) i t is seen t h a t the yield is 92%. DETERMIKATION OF TOTAL SULFUR
A comparison of the weights of the black water-insoluble products of several runs with the weights of lead sulfide equivalent to the total available sulfur indicated that the insoluble product consisted principally of lead sulfide together with relatively small
INDUSTRIAL AND ENGINEERING CHEMISTRY
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O F TIUEU P O S YIELD O F GUANIDINE FROM TABLEIv. EFFECT THIOUREA OR AMMONIUM THIOCYANATE A N D AMMONIA IN PRES, ENCE OF AMMONIUMCHLORIDE OR LEAD(II)CHLORIDE AT 300
Time, Hours 1.5 2.0 2.5
3.0
4.0
Yield,
+
8.0 16.0
%
Reactants NHaCSNHa NHaCl PbClz NHzCSNHz NHaCl PbC1z NHzCSNHz hTHnC1 i- PbClz NHzCSiYHz "4C1 PbClz NHESNHz NHiCl PbClz NHaSCN PbClz NHzCSNHz NHaCl PbClz NllaSCN PbCls
++ ++ + ++ ++
18 79 19 85 23 89 29 96
35 89 95 36 92
+ ++ N H ~ C S N H ?+ N H ~ C I + PbClz NHrSCN + PbClz
87
30 95 89
quantities of unidentified impurities, and this was confirmed by means of x-ray diffraction patterns. It was found, however, that these impurities could be removed by leaching with 5% potassium hydroxide solution. In control experiments it was demonstrated that 1,his leaching treatment (as described below) does not dissolve any appreciable quantity of the lead sulfide; using freshly precipitated lead sulfide, recoveries of 99.4 and 99.3y0 were found. In other cases, the lead sulfide recovered did not account for -all of the sulfur used as thiourea or ammonium thiocyanate. Accordingly, runs employing lead(I1) chloride and thiourea and ammonium thiocyanate separately and together in a 1 to 1 mole ratio were carried out for 8 hours a t 125 and 300 ', and the reaction products were treated as follows: A known weight of the black water-insoluble product (of the order of 1.0 gram) was treated with 50 ml. of 5% potassium hydroxide, heated to boiling, filtered, washed with five 10-ml. portions of hot 5% potassium hydroxide solution, washed with water, dried, and weighed. Sulfur in the water-soluble fraction of the initial reaction product was determined as sulfate ion by precipitation as barium sulfate. The results are given in Table V; the data for sulfur accounted for are in terms of the percentage of the sulfur present in the st,arting material.
TABLE V. DISTRIBUTIOS O F SULFURBETWEEN SOLUBLE AND INSOLUBLE REACTION PRODUCTS T Reactants
+ PbClz NHzCSNHs + PbCIz NHdSCN + NHzCSNHz + PbClz NHaSCN
~ ~ C. 126 300 125 300 126 300
~Sulfur , , Accounted for, % As PbS ASSO*-- Total
0
98 91 95 65 87
0
0
9
0 98 100 99 103 99
2601
The gross solid product was triturated with anhydrous ether and filtered, and the ether was evaporated. There resulted a very small quantity of solid which, when dissolved in water, gave a distinctly positive qualitative test for guanylthiourea (19). Furthermore, an x-ray diffraction pattern for the ether-insoluble residue showed clearly the presence of guanylthiourea hydrochloride. This same pattern showed also the presence of thioammeline, although in this case the evidence was somewhat less satisfactory, owing to the fact that a number of the principal diffraction maxima for this compound coincide with maxima attributable to guanidine hydrochloride. If guanylthiourea and thioammeline are present in the samples analyzed for guanidine as the picrate, it is important to determine whether these two by-products form picrates under the same conditions. Accordingly, a 0.24-gram sample of guanylthiourea hydrochloride was dissolved in 50 ml. of water and treated with 85 ml. of saturated ammonium picrate solution. This mivture was allowed to stand for 30 minutes a t room temperature; there was no evidence of precipitation of a picrate. In a similar manner, it was found that thioammeline does not form an insoluble picrate under the conditions employed in the analysis for guanidine. AMMONOLYSIS OF THIOAXUELINE AND GUANYLTHIOUREA. With a view to determining whether these two substances are products of side reactions that operate to reduce the over-all yield of guanidine, or are intermediates that are convertible to guanidine, the following experiments were carried out. I n separate runs, thioammeline and guanylthiourea were heated with liquid ammonia in the presence of ammonium chloride for 8 hours, and the reaction produets were treated in the usual manner. With thioammeline a t 125 and 300°, the guanidine yields were 0 and 6%, respectively. K i t h guanylthiourea a t the same temperatures, the guanidine yields were 9 and 39Y0 ROLEOF AMMONIUM ION. As shown by the data in Table V, ammonium thiocyanate, lead(I1) chloride, and liquid ammonia do not react a t 125". Under the same conditions, however, a I to 1 mole ratio of thiourea and ammonium thiocyanate together with lead(I1) chloride and liquid ammonia leads to a guanidine yield of 46 to 48%. If it is assumed that, in the latter case, the ammonium thiocyanate does not react t o form guanidine, then the yield from thiourea is markedly greater than is obtained in the absence of the ammonium thiocyanate. In order to detprmine whether this enhancement of yield is attributable to the relatively higher concentration of ammonium ion, 0.025 mole of thiourea, 0.025 mole of ammonium thiocyanate, 0.055 mole of lead(I1) chloride, and 1 mole of liquid ammonia were heated for 8 hours a t 125" The yield of guanidine found was 84%, which is significantly greater than that obtained under the same conditions but in the absence of the ammonium thiocyanate. DISCUSSION
The preliminary experiments described above serve to establish that the high yields of guanidine found in subsequent experiments are not attributable t o either pyrolysis of thiourea or the interaction of thiourea and lead(I1) chloride in the absence of ammonia. The participation of ammonia in the reactions leading to REACTION MECHANISM STUDIES the formation of guanidine is also demonstrated by the studies that show the dependence of guanidine yield upon ammonia conAs earlier workers have postulated that, in the formation of guanidine from thiourea or ammonium thiocyanate and ammonia, centration. The yield of guanidine from thiourea and ammonia increases the primary process involves decomposition of thiourea or with increase in temperature and is enhanced also by the presence ammonium thiocyanate to form cyanamide and hydrogen of ammonium and lead salts. At any given temperature, the sulfide; extensive studies were made with a view t o isolating yield is time-dependent over only relatively short time intervals; cyanamide either as such or in the form of its metal salts. These the yield remains essentially constant after 1 hour at 126" or experiments are not described in detail here because the results 2 hours a t 300". were entirely negative. IDENTIFICATION OF GUANYLTHIOUREA AND THIOAMMELINE. For reactions in the presence of lead salts, maximum yields of guanidine are obtained only when thiourea and the lead salt are In an effort to identify reaction products other than guanidine, present in a t least a 1 to 1 mole ratio, showing that the lead salts the solid product of an 8-hour run involving thiourea, ammonium do not act catalytically but rather serve to remove hydrogen chloride, and liquid ammonia a t 200" was treated as follows: 4
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sulfide in a primary reaction essential to the formation of guanidine. The relatively greater effectiveness of lead(I1) iodide as compared with lead(I1) chloride can probably not be attributed to the greater solubility of the former in ammonia, since silver(1) chloride is very soluble and should be equally effective in removing hydrogen sulfide. This, of course, suggests a specific catalytic effect attributable to the iodide ion, and this view is supported by other evidence recently obtained in these laboratories. The explosions that were experienced vihen lead(I1) nitrate was used were undoubtedly due to the oxidizing action of the nitrate ion a t high temperatures toward a starting material, an intermediate, or a reaction product; similar results have been reported by Hill (9). Despite failure to isolate cyanamide as an intermediate, it seems likely that this substance is formed initially and is immediately consumed in reactions leading to the products identified. KHzC(=S)NHz 2s" NHpCN
4PbC1z
$-
+ NHcCl
+
NHzCN
HzS * PbS
-+
+ H,S + 2NH4C1
KHpC(=NH)XH,+Cl-
+ 2KHaC1
---t
2NH&(=P.;II)?jH,+Cl-
4 H2S
If thioammeline is produced a t 125" it would remain aa such; at 300 ', however, i t would undergo partial conversion to guanidine.
I
I
NHz
KHz
I
+ 3NH4C1 +- NH,
SH
HpS
4
$.
3NH,C(=NH)NH, +CI-
The substantially complete conversion of thiourea or ammonium thiocyanate to guanidine at 300" in the presence of lead salts would appear to provide a promising basis for the development of a practical process for the production of guanidine. Although the quantities of lead(I1) chloride required would bo great, the resultant lead(I1) sulfide could be reconverted to the chloride; and the hydrogen sulfide formed a t the same time could be used in the production of ammonium thiocyanate or thiourea. A much more serious limitation would probably arise as a result of excessive corrosion rates a t a temperature as high as 300" in conventional process equipment. INTERACTION OF NITROUREA AND GASEOUS OR LIQUID AMRIONIA
The analytical data for sulfur shorn-n in Table V indicate that a t 300" all of the thiourea or ammonium thiocyanate undergoes conversion. As strictly quantitative conversion to guanidine was not demonstrated, it follows that part of the cyanamide formed initially must participate in side reactions leading to the formation of products such as melamine, dicyandiamide, guanylthiourea, and thioammeline. Of such possible products, only guanylthiourea was unequivocally identified; the evidence for the presence of thioanimeline was not entirely satisfactory. The fact that guanylthiourea was found in both the ether-soluble and the water-soluhle fractions (as the hydrochloride) results from the fact that guanylthiourea is a Teak base and must compete for the proton with both ammonia and guanidine. Guanylthiourea may be formed by the addition of cyanamide to thiourea, or by the reaction between dicyandiamide and hydrogen sulfide. Thioammeline may result from the reaction of l mole of dicyandiamide (or 2 moles of cyanamide) with 1 mole of thiocyanic acid which could result from the dissociation of either thiourea or ammonium thiocyanate. I n reactions a t 300", ammonium thiocyanate may be substituted for thiouiea, but no conclusion may be drawn as to n-hich isomer is the precursor of cyanamide. At 125', however, ammonium thiocyanate does not react to form guanidine even in the presence of lead(1I) ion. On the other hand, thiourea in the presence of ammonium chloride a t 323" gave a smell yield of guanidine, but the x-ray diffraction pattern for the reaction product gave entirely satisfactory evidence of the presence of ammonium thiocyanate but no indication whatever of the presence of thiourea. If the equilibrium between the t n o isomers is established fairly slowly and if the thiourea reacts simultaneously t o form cyanamide, the isomerization of ammonium thiocyanate may be the rate-controlling step. This may account for the failure to produce guanidine TI hen ammonium thiocyanate was used as the starting material a t 125". At 300°, howver, the rate of isomerization must be markedly greater, since the tmo isomers give substantially the same yield of guanidine. Rate constants reported by Ure and de Lisle ( d l ) for this isomerization are: 0.024at 162.2",0.034at 178.3", and0.038at 184.4', The yields of guanidine obtained from the ammonolysis of guanylthiourea indicate that it is relatively unstable under the conditions used, and that it is a t least partially converted to guanidine : NH&(=S)WHC(=XH)Nflz
X$=C-K=C-X==d
Davis and Blanchard (3)have shown that nitrourea is hydrolyzed to urea by the action of aqueous ammonia and that if the aqueous solution is heated, nitramide and cyanic acid are produced. O&NHC(=O)NH2 S HOCN
+
0&3"2
The reversibility of this dearrangement was demonstrated by the preparation of nitrourea from cyanic acid and nitramide. At the outset of the work, it was consjdered possible that nitrourea could be converted to nitroguanidine by means of anhydrous liquid ammonia. However, it was found that nitrourea reacts also with the anhydrous gas even a t room temperature; and it was, therefore, considered desirable to study the reactions involving ammonia in both the gaseous and liquid phases. MATERIALS
KITROUREA was prepared from urea as follows: Reagent grade urea (37.5 grams) was dissolved in 500 ml. of glacial acetic acid, stirred, and treated dropwise wit'h 60 ml. of concentrated nitric acid for about 20 minutes. The precipitated urea nitrate Ras separated by filtration, recrystallized from 400 ml. of 95yo ethyl alcohol, filtered, washed with cold 95y0 alcohol, and dried in vacuo. Another crop of crystals was obtained by concentration of the mother liquor and was treated similarly. The combined crops melted a t 157-158°, corrected; the yield was 58.0 grams or 75yQ, The urea nitrate was converted to nitrourca by the method of Ingersoll and Armencit ( I t ) ; the melting points of the various batches of this product varied between 153" and 158'. In order to remove residual sulfuric acid completely, it was found necessary to recrystallize the nitrourea (3.5 grams) from a mixture of diethyl ether (245 ml.) and 95% ethyl alcohol (18 inl,). The resulting product gave an x-ray diffraction pattern that led to interplanar spacings and relative intensities that are essentially identical with those reported by Wright (88). h y ~was ~prepared ~ from ~ ethyl ~ initrite ~ according ~ ~ to the directions given by Uarlies, La Mer, and Greenspan (I?'). XAYTHYDROL, d6H4CHOHC&0, melting point, 121-123", corrected, was prepared by the method of Holleman ( 1 1 ) . All other materials ernphi-ed in this work were either reagent grade chemicals or were prepared for use in the manner previously deacribed (26). AYA LYTIC 4 L METHODS
Urea was determined as the dixanthydrol derivative as follows: A sample of known weight and of the order of 80 mg. was dissolved in 10 ml. of glacial acetic acid, treated with 0.63 gram of santhvdrol in 10 ml. of glacial acetic acid, and allowed to stand at 25' for 1 hour. The precipitate was removed by filtration, washed with three 3-nil. portions of glacial acetic acid, and dried to constant wcig!it a t 100". To results thus obtained thore was applied a correction factor (established by analysis of samples of known urea content) to compensate for the solubility of the dixanthydrol derivative in glacial acetic acid. The correction factors used were of the order of +3.57& [Since the work re-
INDUSTRIAL AND ENGINEERING CHEMISTRY
December 1954
ported in this paper was completed, a much more satisfactory (soectroohotometric) method for the determination of urea has b
