U.S. patent application number 10/161619 was filed with the patent office on 2002-11-21 for method for producing 1-methyl-3-nitroguanidine.
Invention is credited to Kern, Norbert.
Application Number | 20020173675 10/161619 |
Document ID | / |
Family ID | 7629122 |
Filed Date | 2002-11-21 |
United States Patent
Application |
20020173675 |
Kind Code |
A1 |
Kern, Norbert |
November 21, 2002 |
METHOD FOR PRODUCING 1-METHYL-3-NITROGUANIDINE
Abstract
The invention relates to a method for producing
1-methyl-3-nitroguanidine. According to said method, nitroguanidine
is reacted with methylamine and/or a methylammonium salt in an
aqueous solution, at temperatures of 30 to 60.degree. C. and at a
pH value of 9.5 to 12.3. In this way, yields of
1-methyl-3-nitroguanidine of at least 80% and degrees of purity
>99% can be obtained in a particularly environmentally friendly
and technically simple way.
Inventors: |
Kern, Norbert; (Haltern am
See, DE) |
Correspondence
Address: |
Gary M. Nath
NATH & ASSOCIATES PLLC
6th Floor
1030 15th Street, N.W.
Washington
DC
20005
US
|
Family ID: |
7629122 |
Appl. No.: |
10/161619 |
Filed: |
June 5, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10161619 |
Jun 5, 2002 |
|
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PCT/EP01/00351 |
Jan 12, 2001 |
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Current U.S.
Class: |
564/108 |
Current CPC
Class: |
C07C 277/08 20130101;
C07C 277/08 20130101; C07C 279/36 20130101 |
Class at
Publication: |
564/108 |
International
Class: |
C07C 279/32 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 28, 2000 |
DE |
100 03 834.4 |
Claims
1. A method for producing 1-methyl-3-nitroguanidine, characterized
in that nitroguanidine is reacted with methylamine and/or a
methylammonium salt in an aqueous solution at temperatures of 30 to
60.degree. c and at a pH value of 9.5 to 12.3.
2. A method according to claim 1, characterized in that the
reaction is performed at a pH value of 11.0 to 12.0.
3. A method according to claim 1 or claim 2, characterized in the
respective sulfate, hydrochloride, nitrate or phosphate is used as
methyl ammonium salt.
4. A method according to one of the claims 1 to 3, characterized in
that the pH value adjustment is undertaken with the help of a
strong acid or base.
5. A method according to claim 4, characterized in that a mineral
acid, selected from the group sulfuric acid, hydrochloric acid,
nitric acid or phosphoric acid is used as mineral acid.
6. A method according to claim 4, characterized in that a sodium
hydroxide solution or a potassium hydroxide solution is used as a
strong base.
7. A method according to one of the claims 1 to 6, characterized in
that the methylamine or the methylammonium salt is used in an
amount that the molar amount of the sum of the two components,
based on nitroguanidine, corresponds to an excess of 5 to 50
mol-%.
8. A method according to one of the claims 1 to 7, characterized in
that the reaction is carried out at a temperature of 40 to
45.degree. C.
Description
TECHNICAL FIELD
[0001] The present invention relates to a method for producing
I-methyl-3-nitroguanidine which is an important intermediate
product for the production of biologically active compounds, in
particular insecticides (cf. "Nicotinoid Insecticides and the
Nicotinic Acetylcholine Receptor", I. Yamamoto, J. E. Casida (ed.),
Springer Verlag, Tokyo, 1999).
PRIOR ART
[0002] A series of proposals has already been made in the prior art
regarding the production of 1-methyl-3-nitroguanidine. One known
method of production is the dehydration of methyl guanidine nitrate
with the help of sulfuric acid (cf. J. Amer. Chem. Soc., 1933, pp.
55, 731). The corresponding methyl guanidine nitrate is, according
to U.S. Pat. No. 2,425,341, available from an aqueous cyanamide
solution and methylammonium nitrate, however the method is
unsatisfactory due to the relative minor yield and the necessary
post-purification.
[0003] According to the method variant described in WO 98/43 951
methyl guanidine nitrate is obtained by reacting methylammonium
nitrate with water-free cyanamide in organic solvents, such as
ether or alcohols, and thereafter is reacted directly into
1-methyl-3-nitroguanidine. The use of water-free cyanamide is not,
however, economical as compared to aqueous cyanamide solutions.
[0004] It is furthermore known that 1-methyl-3-nitroguanidine can
be obtained by nitration of methyl guanidine sulfates (cf. J. Amer.
Chem. Soc., 1933, pp. 55, 731). This method of production also has
the disadvantage of a unsatisfactory yield as well as a relative
large amount of waste water.
[0005] The reaction of methylammonium nitrate with calcium
cyanamide or dicyandiamide (cf. Can. J. Chem., 1958, 36, 737) also
leads to unsatisfactory results since the purity of the methyl
guanidine nitrate obtained by this means is less than 90%.
[0006] A further method for the production of
1-methyl-3-nitroguanidine is that methyliso-thiourea sulfate is
first nitrated and thereafter the methylmercapto group is
substituted by a methyl amino residue (cf. J. Amer. Chem. Soc.,
1954, 76, 1877). The splitting of methyl mercaptan, especially when
performing the method on a large industrial scale, causes
considerable operational problems.
[0007] Moreover it is known that 1-methyl-3-nitroguanidine can be
obtained in that a greatly alkaline nitroguanidine solution is
reacted at 60.degree. C. with a large excess of methylammonium
chloride (cf. J. Amer. Chem. Soc., 1947, 69, 3028 and J. Chem. Soc.
1957, 70). With this process, the purity of the final products
which must be purified in complicated methods, and in particular
the individual yields attained of pure product of between 43 and
66% are very unsatisfactory. Very large amounts of urea or
guanidine derivates results as by-products with a development of
gaseous N.sub.2O. Moreover large amounts of waste water also
result.
[0008] The direct reaction of aqueous methyl amine solutions with
nitroguanidine at temperatures of >60.degree. C. (cf. J. Amer.
Chem. Soc., 1927, pp. 49, 2304, and Proc. Am. Acad. Arts Sci.,
1926, pp. 61, 437) results with only insufficient yields of 36 to
45% in 1-methyl-3-nitroguanidine.
[0009] The same disadvantages are also shown by the direct reaction
described in EP-A 798 293 of a methylamine solution with
nitroguanidine at 0-40.degree. C. The desired final product is
obtained also with this manner of procedure with only a maximum
yield of 60%. The method is moreover very uneconomical due to the
long reaction times of about 24 hours and the high dilution which
leads, with the insufficient yields of space/time, to very large
amounts of waste water.
REPRESENTATION OF THE INVENTION
[0010] The present invention was therefore based on the object to
develop a method for the production of 1-methyl-3-nitroguanidine
which does not have the disadvantage of the prior art, but that
allows the desired final product to be acquired with at good yields
and high purity in an especially environmentally sound manner and
by a technically simple means.
[0011] This object was solved according to the invention in that
nitroguanidine was reacted with methylamine and/or a methylammonium
salt in an aqueous solution at temperatures of 30 to 60.degree. C.
and at a pH value of 9.5 to 12.3. It was surprisingly found that
the formation of N.sub.2O was also considerably reduced along with
an increase in yields, by means of which the danger of formation of
explosive mixtures with the ammoniac formed as a by-product is
considerably reduced.
[0012] Thus nitroguanidine with methylamine and/or a methyl
ammonium salt is reacted in methods according to the invention in
an aqueous solution at temperatures of 30 to 60.degree. C., in
particular 40 to 45.degree. C.
[0013] The salts of strong mineral acids, such as e.g. the sulfate,
hydrochloride, nitrate or phosphate, are used as methylammonium
salts.
[0014] It is to be considered essential to the invention that the
pH value is adjusted during the reaction to a value of 9.5 to 12.3.
Surprisingly, it was found that the yields obtainable depend to a
great extent on the pH value during the reaction. When the method
according to the prior art was reproduced, it was found that pH
values of 13.0 to 14.0 occur thereby which always lie above the
pK.sub.a value of nitroguanidine (12.4). With such reaction
conditions, yields of clearly above 60% cannot be obtained due to
the side reactions. If the reaction is performed on the other hand
at a pH value below the pK.sub.a value of nitroguanidine, yields
amounting to 80 to 95% are obtained. pH values of 11.0 to 12.0
during the reaction have proven to be especially advantageous here.
The yields are again reduced if the pH values lie clearly below
9.5.
[0015] The adjustment of the pH value takes place either by the
addition of the methyl amine and the methylammonium salt in such a
molar ratio that the desired pH value adjusts itself, or by the
usual use of strong bases or acids. A mineral acid, selected from
the group sulfuric acid, hydrochloric acid, nitric acid or
phosphoric acid, is used preferably as the strong acids, while, for
example, sodium hydroxide solution or potassium hydroxide solution
are used as strong bases. According to a preferred embodiment, the
methylamine and/or the methylammonium salt are used in such an
amount that the molar amount of the sum of the two components,
based on the nitroguanidine used, corresponds to an excess of 5 to
50 mol-%.
[0016] Principally, a higher excess of methylamine and/or
methylammonium salt with up to 100% can be used without a
substantial formation of the dialkylated product
1.2-dimethyl-3-nitroguanidine being observed thereby. A higher
increase than the preferred 5 to 50% by weight of methylamine
and/or methylammonium salt, however, decreases the economicability
of the method according to the invention.
[0017] After the reaction is concluded, which is ended as a rule
after 2 to 3 hours, the final product is separated, preferably by
filtration. A neutralization of the reaction mixture before the
filtration is also possible without this acting negatively in any
form on the yield. Optionally, the final product can be
subsequently rinsed with some cold water and dried.
[0018] The advantages of the method according to the invention
consist essentially in that 1-methyl-3-nitroguanidine can be
obtained with yields of at least 80% und purities >99% in a
manner especially friendly to the environment and technically
simple, which is why this method is suited especially for large
industrial use.
[0019] The following examples should better illustrate the
invention.
EXAMPLE 1
[0020] 100 g (0.63 mol) methylammonium sulfate is dissolved in 400
ml H.sub.2O. A pH value of 11.5 is adjusted with about 53 g (0.66
mol) 50% sodium hydroxide solution. In this solution 100 g (0.96
mol) nitroguanidine is stirred at 40 to 42.degree. C. After 3 hours
of stirring at 40 to 42.degree. C., the reaction mixture is
neutralized at max. 30.degree. C. After being cooled to 5.degree.
C. the suspension is filtered off, is washed with 120 ml cold
H.sub.2O and dried. 108 g methyl nitroguanidine is obtained
(content >99% per HPLC, m.p.: 158-159.degree. C.), corresponding
to a yield of 95%.
EXAMPLE 2
[0021] While being strongly stirred, 19.8 kg (152 mol)
nitroguanidine having a water content of 20% by wt. is added at
40-42.degree. C. to a mixture of 2.65 kg (16.5 mol) methyl ammonium
sulfate and 15.4 kg (165 mol) 40%-methylamine solution in 41 l
H.sub.2O, with the reaction mixture having a pH value of 11.3.
After 2 hours the reaction mixture is cooled to 3.degree. C.,
filtered off, washed and dried 3 times with 6 l cooled H.sub.2O
each time. 14.8 kg methyl nitroguanidine (content >99% per BPLC,
m.p.: 159.degree. C.) is obtained, corresponding to a yield of
82%.
* * * * *