United States Patent O?

ice
1
2,884,437
PROCESS FOR THE PRODUCTION OF GUANIDINE AND DERIVATIVES THEREOF Elwyn Roberts, London, England, assignor to the Min
ister of Supply, in His Majestys Government of the United Kingdom of Great Britain and Northern Ire

02,884,437
Patented Apr. 28, 1959

2
agents in a one to one molar ratio with urea, it has been

land, London, England No Drawing. Application September 4, 1951

Serial No. 245,081 9 Claims. (Cl. 260-459)
- The present invention relates generally to a method
10

found that the conversions of urea to guanidinium alkyl sulfate are ca. 65, 73, 72 and 73%, respectively. The use of diethyl sulfate is, however, preferred because of its nontoxic nature and availability. It has been further found that the etheri?cation or alkylation using a dialkyl sulfate proceeds best in the absence of any diluent or alkali; indeed if water or alkali be employed no alkylation takes place, which is contrary to the usual experience of

for producing guanidine and derivatives thereof, and is 15 The reaction mixture is maintained at a temperature of related to my copending application for substituted between 85 and 130 C., external cooling being necessary guanidines Serial Number 245,080, ?led September 4, after the reaction is initiated owing to the slight exo
1951, now abandoned, which is a continuation in part thermic character thereof. Completion of the reaction hereof. is effected by maintaining the above temperature range for Guanidine and many of its derivatives have become of 20 a further period, the time necessary being a function of considerable interest in the art of military explosives. temperature. The lower the reaction temperature the more For example, nitroguanidine is itself a high explosive, prolonged the period. For example, about one hour heat and when suitably mixed with a nitrocellulose carrier it ing period is required at 100 C., a 30 minute period serves as an excellent projectile propellant. As a high at 110 C., and a 15-20 minute period at 120 C. Best explosive, nitroguanidine is characterized by a flashless 25 results are obtained, however, by employing a tempera

alkylation using this kind of reagent. The production of alkyl isourea allyl hydrogen sulfate is advantageously carried out by gradually adding urea to heated anhydrous alkyl sulfate in substantially equi molar proportions under conditions of vigorous agitation.

explosion of obvious strategic advantage in military use,

and as a propellant it is found to reduce gun barrel cor

ture of 100 to 110 C.

rosion by a substantial amount from that obtained with other common propellant explosives. These character istics therefore make nitroguanidine a highly desirable

Amination of the alkyl isourea alkyl hydrogen sulfate is effected by treating the mixture resulting from the
above reaction with ammonia at a temperature not

explosive from the military standpoint, While other de

rivatives of guanidine impart similar attributes to con

exceeding 65 C. and preferably of about 60 C. The ammonia may be employed in any desired form, for ex
ample as an aqueous or alcoholic solution, but it is pre

ferred to employ the gas, passing it into the alkylated re action product at such a rate that it is completely absorbed guanidine and its derivatives have been attempted and 35 and until amination is complete. Since the gaseous amina suggested in the prior art, no method has heretofore tion is exothermic, it is carried out with cooling to main

ventional explosive compositions when mixed therewith. Although a plurality of methods for the production of
been found which enables the practical large scale produc

tain the desired reaction temperature. When using diethyl

tion of guanidine and its derivatives. It is accordingly one sulfate as the etherifying agent for example, amination object of the present invention to provide a commercially is usually complete after passing ammonia for 'a further feasible, economical, and practical process for the pro 40 period of one hour at 60 C. following the conclusion of duction of gu'anidine and its derivatives, which lends itself the exothermic stage of the reaction. The concentration to large scale production thereof. of ammonia in the system when amination is complete Another object of the present invention is to provide is ca. 2.6%. Finally, the reaction mixture is freed from a process for the production of guanidine and derivatives the alcohol by-product of amination and excess ammonia
thereof from urea. 45

Another object of the present invention is to provide a process for the production of guanidine and such deriva tives thereof as guanidinium salts, guanidinium alkyl

by distillation, leaving a residue comprising primarily guanidinium alkyl sulfate.

If an aqueous ammoniacal solution is employed, the

alkylated reaction product is advantageously treated with

an excess of ammonia, preferably up to 20% excess, and

sulfate, and nitrogu'anidine.

Other objects and advantages of the present invention 50 heated to 60 C. for a period of about three hours. will become apparent to those skilled in the art from a Guanidinium alkyl sulfate is obtained by evaporating the consideration of the following description of the process solution under vacuum to dryness. and variations therein embraced by the present invention. The isolation of guanidine is effected according to the According to the present invention there is provided a invention by dissolving the residue of guanidinium alkyl process for the production of guanidine and derivatives 55 sulfate in anhydrous ethyl alcohol and treating the alco
thereof which includes the steps of interacting urea and dialkyl sulfate to form lan alkyl isourea alkyl hydrogen
holic solution with an alkali such as a solution of an alkali

alcoholate. The resultant alkali alkyl sulfate precipitates sulfate, and aminating this reaction product with ammonia and can be separated by ?ltration, leaving a solution of to form gu'anidinium alkyl sulfate, as may be represented guanidine in alcohol. The alcoholic solution can be by the following equations wherein R is used to denote 60 distilled in vacuo to yield a residue of guanidine con taining but slight impurity. The loss of guanidine by
this treatment is almost negligible. This reaction may be

represented by the following equation, using potassium

ethylate as representative of the alkali alcoholates in gen eral, and wherein R denotes an alkyl radical:

15H:

llq?z

Such dialkyl sulfates as dimethyl-, diethyl-, di-n-propyl 70

and di-n-butyl sulfate have been found to be advantageous

etherifying agents. When using these several etherifying

2,884,437

The isolation of various guanidine salts is effected according to the invention by neutralization of the alco holic solution of guanidine with the appropriate acid, followed by crystallization. When neutralization is ef

4
The aqueous reaction solution contains 48.5 parts by

weight of O-methyl isourea, as the salt of methyl hydro

gen sulfate, corresponding to a yield of 66% of theory based on urea; the solution also is acidic, the acidity cor

fected, forexample, with nitric acid, the corresponding

salt, guanidinium nitrate, is formed and can be isolated

responding to 25-26 parts by weight of methyl hydrogen

sulfate. The aqueous reaction mixture is next neutralized

almost quantitatively by the usual procedure of fractional crystallization, as represented by the following equation:
GENO;

with concentrated (0.880) ammonia using methyl red in dicator, and to the neutral solution is added 50 parts by

volume of concentrated (0.880) ammonia, approximately

10 20% excess ammonia on the methyl isourea content.

Nitroguanidine may be produced using guanidine pre

pared as disclosed above, but it is advantageously pro~ duced by a simple modi?cation which does not involve 15 methyl hydrogen sulfate, corresponding to a yield of about

The resultant mixture is then heated to 60 C. and held at this temperature for three hours, then cooled to room temperature. After this treatment, the aqueous solution contains 37.7 parts by weight of guanidine as the salt of
64% of theory based on urea. The aqueous solution

isolating the guanidine itself. Ihave found that guani

dine alkyl sulfate may be treated directly with a nitrat

ing mixture and nitroguanidine thereby obtained in good

yield, as indicated by the following equation wherein R
denotes an alkyl radical:
NE NH

containing guanidinium methyl sulfate is evaporated to dryness in vacuo (bath temperature 60l00 C., pres
sure 20-30 mm. of mercury). The residue, 173 parts by
20 weight, which is molten at 100 C., is a waxy solid at

room temperature and consists of fairly pure guanidinium

II
NH:

HNO;

ll
NHz

methyl sulfate. .Example II

(H2504) |

Free guanidine may be obtained from the guanidinium Although nitroguanidine is obtained as one product of 25 methyl sulfate residue obtained as in Example I as follows: the above reaction, the precise identity of the remaining The guanidinium methyl sulfate residue is dissolved in by-product or by-products is not known at the present 1000 parts by volume of ethyl alcohol (grade I) by time. warming, and the alcoholic solution then cooled to ordi~ Alternatively, guanidinium alkyl sulfate may be sub nary room temperature. With stirring and cooling to 30 jected to mold hydrolysis, followed by removal of water lO-20 C., 470 parts by volume of a solution containing

and alcohol by fractionation, yielding guanidinium hy

drogen sulfate, and then treated with a nitrating mixture to produce nitroguanidine, as indicated by the following equation wherein R denotes an alkyl radical:

11.34 parts potassium hydroxide in 100 parts by volume of ethyl alcohol (grade I) is added to the alcoholic

lguanidinium solution. Potassium methyl hydrogen sul

35 fate, 139 parts by weight, is precipitated by this treatment, separated by ?ltration, and washed with cold alcohol un

NR2
NH
||

(H2304)
fractionation ,

til free from occluded guanidine. The alcoholic ?ltrate contains 35.9 parts by weight of guanidine, corresponding
--

CNH2 ~H2SO4 + ROH

to a yield of about 61% of theory based on urea. The 40 alcoholic solution of guanidine can, if desired, be evap orated in vacuo to small bulk, or even until all alcohol is

expelled, with no loss of yield of guanidine.

HNO: [I r

Example III
'

->
(H2804)

C-NHNOr + E20 + H280

NH:

To prepare a guanidine salt, for example guanidine

45 nitrate, the alcoholic solution of guanidine obtained in

The conversion of guanidinium ethyl sulfate to guanidi nium hydrogen sulfate and alcohol by acid hydrolysis is
rapid and quantitative, and removal of alcohol and water

Example II is neutralized in the cold using about 39.6 parts by volume of 70% (by weight) nitric acid, and the
neutral solution is evaporated almost to dryness with re covery of the alcohol solvent. The solid is recovered

may be conveniently effected owing to the considerable 50 from the mother liquor by ?ltration and washed sparingly stability of guanidine solution in concentrated sulphuric with alcohol, the weight ratio of solid to mother liquor acid at elevated temperature. This latter process, although being about 1:1. The yield of solid guanidine nitrate is longer than the former process for producing nitroguani 5354% based on urea. A further quantity of guanidine dine, has the advantage thereover of enabling recovery nitrate can be recovered by fractional crystallization from as alcohol of both alkyl radicals from the dialkyl sulfate 55 the mother liquor. ~ employed, which can then be recycled if necessary, and the Example IV further advantage that after the hydrolysis step the sul fate radical of the dialkyl sulfate is present in the form To prepare nitroguanidine, guanidinium methyl sulfate of sulfuric acid and is advantageously employed at the is prepared as set forth in Example I, the product being a nitration stage. ' ' 60 waxy solid consisting predominantly of the guanidinium The present invention is further illustrated by the fol methyl sulfate. 10 parts by Weight of this solid are slow
ly added to a nitrating mixture of 20 parts of 99% sul phuric acid and 3 parts by weight of 99% nitric acid at 10-15" C. with stirring. The time of addition is about 5 Dimethyl sulfate, 126 parts by weight, is heated to 100 65 minutes. The reaction mixture is warmed to 40 C. and held at this temperature for 30 minutes. It is then cooled C., and urea, 60 parts by weight, is added thereto with ef?cient stirring within a period of about 15 minutes, to 20 C. and poured on to 110 parts of a mixture of ice keeping the temperature constant by slight cooling as the and water. A precipitate is thrown down which is col reaction between the two ingredients, once started, be lected, washed with water, and then transferred to a vessel comes exothermic. After addition of the urea, the reac 70 and again treated with 30 parts of water, insuring that any tion mixture is held at 110 C. for 5 minutes and then nitrogtuanidine sulfate present is converted to nitro cooled to 80 C. Water, 100 parts by weight, is added guanidine. The solid is again collected, washed Well with fairly rapidly to the well stirred reaction mixture when water, and dried. The weight of the solid product is 1.82 the temperature drops appreciably. The diluted reaction parts, corresponding to a yield of 31.2% of nitroguanidine mixture is then cooled to ordinary room temperature. 75 based on urea. The melting point of the resulting nitro

lowing speci?c examples:

Example I

games-"1
not intended to limit the scope of the present invention to the details of the speci?c embodiments described, as modi (uncorrected) . ?cations thereof within the spirit and scope of the ap Example V pended claims will be apparent to those skilled in the art. As an alternative process of producing nitrognanidine, 5 What is claimed is: urea, 240 parts by weight, is added to diethyl sulfate, 616 1. The process for the production of guanidinium alkyl parts by weight, at ordinary room temperature and the sulfates comprising the steps of reacting urea with a di suspension heated with efficient stirring to a temperature alkyl sulfate chosen from the group consisting of di of 100 C. to produce O-ethyl isourea. The mixture methyl-, diethyl-, di-n-propyl-, and di-n-butylsulfate to becomes clear after about v9 minutes. Reaction at produce an alkyl isourea alkyl hydrogen sulfate, and re this state is somewhat exothermic but the temperature is acting the said alkyl isourea alkyl hydrogen sulfate with

guanidine when recrystallized 5 from water is 225' C.

readily controlled.
it is cooled to 60 C.

All evolution of heat ceases after

The conversion of urea to O-ethyl

ammonia for 1-3 hours at about 60 C. to produce the

about 16 minutes, but the reaction mixture is maintained at 100 C. for a total period of 60 minutes, after which

corresponding guanidinium alkyl sulfate thus obtained to

produce guanidinium alkyl sulfate.

2. The process for the production of nitroguanidine comprising the steps recited in claim 1 and in addition the step of reacting the said guanidinium alkyl sulfate with a nitrating mixture comprising nitric and sulphuric acids to

isourea is 73%. Dry ammonia gas is then passed fairly rapidly into the well stirred slightly super cooled reaction mixture (F.P. 64 C.) at 60 C., ef?cient cooling being

necessary to maintain this temperature, to produce produce nitroguanidine. guanidinium ethyl sulfate. Ammonia gas is passed for a 20 3. In a process for producing nitroguanidine the steps total period preferably of two and one half hours, during described in claim 1 and in addition reacting the said

which time 86.4 parts by weight should be absorbed. The

guanidinium alkyl sulfate with a nitrating mixture to pro

mixture is then allowed to stand at 60 C. for a period of ,duce nitroguanidine. one hour. On cooling crystallization commences at 47 4. In a process for producing nitroguanidine the steps C. The reaction mixture is ?nally heated to 100 C. un~ 25 described in claim 1 and in addition the steps of hy der a pressure of 1 cm. of mercury, whereby all the alco drolyzing the said guanidinium alkyl sulfate to produce

hol, 149.9 parts by weight, and excess ammonia, 15.0 parts

by weight, contained in the reaction mixture are distilled,
and may be collected in cold trap if desired. The con

guanidinium hydrogen sulfate, and nitrating the said

guanidinium hydrogen sulfate with a mixture comprising nitric and sulphuric acids to produce nitroguanidine. version of O-ethyl isourea to guanidinium ethyl sulfate is 30 5. In a process for producing nitroguanidine the steps quantitative. The residue (F.P. 94 C.), 772.5 parts by described in claim 1 and in addition the steps of hy weight, consisting primarily of guanidinium ethyl sulfate, drolyzing the said guanidinium alkyl sulfate to produce
may be converted into guanidine as in Example II, or if a

guanidinium hydrogen sulfate, and nitrating the said

guanidine derivative such as nitroguanidine is desired, guanidinium hydrogen sulfate to produce nitroguanidine. hydrolysis of the guanidinium ethyl sulfate may be per 35 6. In a process for producing guanidine the steps de formed as follows. Sulphuric acid, 76.7 parts by weight, scribed in claim 1 and in addition reacting the said guan and water, 155.4 parts by weight, are added to the idinium alkyl sulfate with an alkali alcoholate to produce guanidine ethyl sulfate, and-the mixture is boiled with re guanidine. ?uxing for about 30 minutes. The boiling point of the 7. In a process for producing guanidine the steps de liquid falls from about 118 to 104 C., and the hydrolysis 40 scribed in claim 1 and in addition reacting the said is judged to be complete when a steady minimum for the guanidinium alkyl sulfate with an alkali to produce boiling point of the liquid is attained. The liquid is then guanidine. carefully fractionated at normal atmospheric pressure un 8. In a process for producing guanidine salt the steps til the boiling point reaches 120-125 C., indicating that described in claim 1 and in addition reacting the said a large proportion of alcohol liberated during hydrolysis guanidinium alkyl sulfate with an alkali alcoholate to pro is recovered. All remaining alcohol and water is then duce an alcoholic solution of guanidine, and neutralizing distilled under diminished pressure down to 20-30 mm. of the said solution with an acid to produce the correspond
mercury at a bath temperature of 100 C. This hydroly

sis of guanidinium ethyl sulfate to guanidinium hydrogen sulfate is quantitative. The resulting residue (F.P. 64 C.), 757.7 parts by weight, and consisting primarily of 5 O guanidinium hydrogen sulfate is then converted to nitro guanidine by adding thereto concentrated (98%) sul phuric acid, 844.3 parts by weight, with stirring, cooling to 10 C., and then adding 98.5% nitric acid, 258.6 parts by weight, slowly with efficient stirring, the temperature be 55 ing maintained below 25 C. by external cooling. Best
results are obtained by nitrating at 10 C. for 30 minutes. The resultant nitroguanidine is isolated from the nitration mixture by adding it slowly to a mixture of ice and water,

ing guanidine salt.

9. The process for the production of guanidinium alkyl sulfates comprising the steps of reacting urea with
an anhydrous dialkyl sulfate selected from the group con

sisting of dimethyl-, diethyl-, di-n-propyl-, and di-n-butyl

sulfate to produce an alkyl isourea alkyl hydrogen sul fate, passing ammonia gas through the said alkyl isourea
alkyl hydrogen sulfate for about one hour at about 60 C.

to produce the corresponding guanidinium alkyl sulfate.

References Cited in the ?le of this patent UNITED STATES PATENTS
1,672,029 2,286,364 2,567,676
448,796 117,054

5093 parts by weight, whereby the crude nitroguanidine, 00 273.8 parts by weight, is precipitated. The solid product
ably with a saturated aqueous solution of nitroguanidine at normal room temperature. This crude nitroguanidine 65

is recovered by ?ltration and freed from acid mother

Heyn _________________ .... June 5, 1928 Jayne ________________ .. June 16, 1942 Marsh _______________ .._ Sept. 11, 1951

liquor (ca. 20% H2804 concentration) by washing prefer

is puri?ed by recrystallization from water saturated at normal room temperature with nitroguanidine, yielding 262.6 parts by weight of pure nitroguanidine. The con

FOREIGN PATENTS
Great Britain _________ .._ June 15, 1936 Australia ____________ .. June 17, 1943

OTHER REFERENCES
Werner: Jour. Chem. Soc.," London, vol. 105 (1914),

version of guanidinium hydrogen sulfate to elude nitro 923-932. guanidine on nitration is 90-91%; and the yield of puri?ed 70 pp. Davis et al.: Jour. Amer. Chem. Society, vol. 55 nitroguanidine based on urea is ca. 63%. (1933), pp. 731-740. Having thus disclosed generally a process for produc Stettbacher: Nitrocellulose, vol. 7 (1936), pp. 141 ing guanidine and the nature of variations in that process 145. which may be employed for producing derivatives of guanidine, together with speci?c examples thereof, it is 75 Barker: Jour. Chem. Soc." (1943), pages 101-104.