SYNTHESIS OF AMINOMETHYLPHOSPHONIC ACID

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• Collection: General CIA Records
• Document Number (FOIA) /ESDN (CREST): CIA-RDP80-00809A000600390686-8
• Release Decision: RIPPUB
• Original Classification: S
• Document Page Count: 5
• Document Creation Date: December 22, 2016
• Document Release Date: October 18, 2011
• Sequence Number: 686
• Publication Date: June 19, 1951
• Content Type: REPORT

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'1
CUISSIFlCATION s-g_-~a;-R-E_-T_ ~~CRET
CENTRAL INTELLIGENCE AGENCY REPOR~
INFORMATION FROM
FOREIGN DOCUMENTS OR RADIO BROADCA8T8 CD t:0.
COUNTRY USSR
SUBJECT Scientific -Chemicals, orgenophosphorue
co~mpounde
HOW
PUBLISHED Bimonthly periodical
WHERE
PUBLISHED Moscow
DATE
PUBLISHED Jan 1951
LANGUAGE
niaroerrnt eorrua nraunw urarnra na nnoru. aararaa
o- ma rnm Warn nnu rra runrr or unorua rcr N
a. a. e.. ai ire a, a ~ouna, m iruwuawr oa na rnwnor
iiamo n u~ uunonei we w nu ruorru riaiuni. u ~
DATE OF
INFORMATION 1950
DATE DIST. / 9 'J'un 1951
N0.OF PAGES 5
SUPPLEMENT TO
REPORT N0.
THIS IS UNEVALUATED INFORMATION
.SOURCE Ievestiya Akademii Nauk SSSR, Otdeleniye Khimicheskikh ftauk,
No 1, 1951, PP 95-97?
SYNTHESIS OF AMINOME'PHYLPHOSPHONIC ACID
M. I. Kabachnik and T. Ys. Medved'
Inat of OrP Chem, Acad 3ci USSR
~ecause aminomethylphosphonic acid is a nev'y synthesized com-
pound, its physiological action is not known. The Russian authors
have not indicated the purpose of the 7.nvestigation of which this
report dorms a part. From the viewpoint of potential applications
in the field of cholinesterase inhibitors, one may assume, that
aminomethylphosphonic acid may, under appropriate conditions, serve
as a starting material for the preparation of persistent nerve
gases in which two phosphonic acid residues are connected by means
of abridge, or some group other than a phosphonic acid residue is
introduced into the amino group of the original compounds Because
chlorine in the chioromethyl group attached to the phosphorus is
extremed.y unreactive, its replacement with an amino oup may con-
ceivably offer better possibilities in that respect_~
In a previous communication ~ we showed that when ammonia acted on the
ethyl eater of chloro- and iodomethylphosphonic acid (I) the monoethyi ester
oP aminomethylphosphonic acid (II) was formed. .When II was saponified, free
aninomethylphoaphonic acid (III) was easily obtained. The total. yield of
the latter, on the basis of the original ester of the halogen methylphosphonic
acid, comprised 2596 of theoretical:
.., ,. .,... ~ ~2H5
c1ca2PO(oc2H5)2a NH2cH~~ ---os; NH2cH2PO(o1a)a?
0
(I) (II) (III)
ruw
'Ne
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Becar~P aminomethylphosphonic acid is of very great interest to us as
the first member of a aeries of aminophosphonic acids, analogous to the
aminocarboxylic acid aeries, we examined the reaction of its formation Yrom
chloromethylphosphanic acid in great detail.
It is well. known that the conversion of chloroacetic acid into glycine is
easily accomplished by simply dissolving it in a strong aqueous solution of
ammonie.~ Proceeding Pram the concept that there is an analogy expectedtthat
carboxylic group COOH and oue on0theomabil~itypofOthe)ch~ine atom in chloro-
the effect of a PO(OH)2-gr P
methylphosphanic acid would be similar to the effect of the carboxyl in
chloroacetic acid However, we have already noted that chloromethylphosphonic
acid is considerably inferiar to chloroacetic as far as the reactive capacity
of the chlorine atom is cancerned. The present paper describes the results
obtained by measuring the rate of the reactior_ of chloromethylphosphonic acid
with aqueous and alcoholic ammonia It was found that its rate of conversion
was so far exceeded by that of chloroacetic acid that one can speak of an
analogy between them only very ::onditionally~
Thus, for example, when the ammonium salt of chloromethylphosphonic c.:ld
is heated with a saturated. anhydrous alcoholic solution of a~nonia in a
sealed tube in a boiling wate~? bath even for as long as 30 hours, absolutely
no splitting off of the chlorine inn occurs= With strong aqueous ammonia,
the complete splitting is reached only after 25 hours of heating at a temper-
ature of. 1000 {cf curve 1 in appended Figure 1; the pseudomolecular reaction
constant K == 0 108). Mo:~over, under these canditiona the splitting off of
i"?? ;.'a the formation of oxymethylphosphonic rather than
chlorine ieisd3 c.`.ia~ ~,,
aminomethylphosphonic acid.
The ethyl ester of chloromethylphoaphonic acid reacts even more slowly
with strong aqueous ammonia To achieve a complete splitting off of the
chlorine ion requires heating at 1000 for more than 40 hours (cf curve II;
K = 0.,057)? However, in this case the reaction proceeds chiefly in the di-
rection of replacing the chlorine with an amino group and forming the acid
ester of the amino acid II. At 1500 the reaction wfth aqueous ammonia natu-
rally proceeds more rapidly, being completed in one hour with the formation
of the acid Ester oP aminamethylphoaphonic acid with a yield of up to 5~
of the theoretical (curve III; K ~ 2.7)~" The reaction proceeds more slowly
in an absolute ether solution, where at a temperature of 1500 20 hours are
required for its completion (curve N; K ' 0.17).
A camparison should be made of the above-cited data with the results
obtained by measurement of the rate of the reaction of chloroacetic acid
with concentrated aqueous ammonia ~. In the latter reaction, even with
a somexhat smaller excess of ammonia and at a temperath ~8f 10e. tthecreac-
plete splitting off of chlorine is attained in only 3 r ~
tion proceeds much more rapidly?
Furthermc+re, data from the literature show that methyl chloridQ;rgacts
mare easily wi.. ammauia in an alcoholic solution that either chlnromethyl-
phosphonic acid or its estero Although in,the litereture_we have found ao:;:~
quantitative data on the rate of reaction of methyl chloride with ammonia ins.
an alcoholic solution, according to the old. dataof`Viaeent and Chappuis ~]n
wlzea saturated solution of ammonia:ia alcohol stands with methyl chloride .ia.~
s-closed veasel_at a low temperature foi 24 hours a crystalline p~eipitate
eonsisting of tetramethylammonium chloride and trimethylamin~ hydrpcl}loride
is formed profueelyo Thus, the action of the phosphono group in chloromethyl-
" phosphonic acid on the reactive capacity of the chlorine atom?csn~be sais7.p~
~'~"!ed paeaivating rather than activatinge On tht'baid'is 31''~~~~ abovee=~'~'d"
results, we"considerably improvedrour,.met1;Q~. fo; produc~lYg aio~ndm~tf~l9`~i~a~=;y1
pho~iiG' acid. (ar ,its aci.c} ethyl ester)',i. increasiag,,tha"yiexa to 48-5096 and
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1
s~cREr
greatly shortening the duration of the synthesis. The method now copsists
of heating the ethyl eater oP chloramethylphoephonic acid with 25$ aqueous
es~onia in sealed tubes to 1500, elimination of the ammonium chloride, which
is formed at the same time by the action of aqueous silver oxide, and, finally,
precipitation of the aniline salt of the acid ethyl ester of aminomethylphos-
ghonic acid {H2NCH2P0(OC2H )OH)2aC6H5NH2. This salt is extremely unstable and
when recrystallized or hewed in vacuum, loses aniline to form the inner salt.
Determinat~,on of Time for Completing Reaction
Portions containing 0.08-0=1 g chloromethylphosphonic acid or its ethyl
ester were sealed in tubes with 5 ml aqueous ammonia or saturated ammonia in
absolute alcohol.. The tubes were heated to 100 or 150? for the stated length
of time, then opened. The contents were dissolved in water, acidified with
nitric acid, and the ionic chlorine titrated by the Vollhard method. The fol-
lowing results were obtained?
1. C1CH2P0(OA)2; anhydrous alcoholic euunonia; 1000; from 5 to 30 hours.
No ionic chlorine?
2. C1CH2P0(OA)2; 2596 aqueous ammonia; 100? (curve I):
Time (hr) 2 4 6 8 10 14 18 22 25
cl (y6) 172 34.8 41.2 62.6 72.0 79.9 a6.7 .2 loo
Monomolecular rate constant K = 0.108
3. C1CH2P0(OC2H5)2; 2596 aqueous ammonia; 1000 (curve II)?
'Dime (hr) 2 4 7 10 14 18 28 38
C1 ('~) 11.2 20. 31. ?3 55= 1.3 =9 9.2
Rate constant K = 0.057
4. C1CA?PO(OC2Ei5)2; 25~ aqueous ammonia; 150? (curve III). After only
an hour, 92~ ionic chlorine is obtainedo The reaction rate was not deter-
mined here, but it is clear that its constant cannot be less than 2.7.
5. C1CH2POr~h;2H5)2; anhydrous alcoholic ammonia; 1500 (curve Iv).
Time (hr) 5 10 20
cl (9~) 3.2 7 .0 9 .
Rate constant K s 0.17.
Synthesis of Monoethyl Ester of ,aminomethylphoaphonic Acid
Fourteen and four tenths gra~ of the ethyl ester of chloromethylphos-
phonic acid (bp 89-910 at 4 mm; h D 1.4408) sud 80 ml of 2596 aqueous ammonia
were heated in four sealed tubes (the use of a steel autoclave sharply re-
duces the yield and contaminates the reaction 'product) at 150? for one hour.
To avoid completely the frequent accidental bursting of tubes, it is best
to place them in an autoclave in which the required external pressure rela-
tive to the tubes can be produced.) Then the contents of the tubes were evap-
orated in a dish on a water bath to a constant volume. The residue, a syrupy
liquid, was dissolved in a small amount of water and shaken up with 9.6 g of
freshly prepared, moist silver oxide. The precipitate of silver chloride and
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t _e?excess of silver oxide were filtered out. The eacens of silvex was elim-
inated from the filtrate by hydrogen sulfide, the silver sulfide'?wae filtered
out,-end the filtrate was evaporated to a-constant volume. The residue, a
yello eh syrup, was dissolved in a small amount oP 9596 alcrohol, end to this
solution was added an alcohol solution oP aniline (15.5 g of aninlie was taken,
which-corresponds to two soles of aniline to one mole oY the original sub-
stance). On prolonged standing the precipitate was drawn aff-and wash~fl with
alcohol. There was obtained 7.8 g of a w':ite crystalline substance with a .
melting point of 2300 which was a salt of the compositions (NH2CH2P0(OC2H5)OH)2?
C6H5NH2?
0.1192 g substance; 0.0708 g M82P207
0,1214 g substance; 0.0708 g Mg2P20
(by melting with soda and saltpeter3
Found P 16.25, 16.5496
C12x2~t306P2. Calculated P 16,7096
The substance can be freed of aniline either by recrystallization Prom
aqueous alcohol or by heating the aniline salt to 100? is a vacuum at 2-4 mm
Hg for several hours to a constant weight. Recrystallization of the aniline
salt from the aqueous alcohol yielded 4.8 g of the acidic ethyl ester of
aminomethylphosphonic acid with a melting point of 2400. The yield was 4596
oP the theoretical.
By this method in six experiments 87.7 g (NH2CH2P0(OC2H5)OH)2?C6Fi5NH2
were obtained from 183 g C1CH?PO(OC~H~)p, which corresponds on the average
to 4896 of the theoretical.
1. M? I? Kabachnik and T. Ya. Medved', Izvestiya AN SSSR, OKhN, No 6,
p 635 (1950)
2. A. Ye? Arbuzov, ZhRFKhO, 59, P 243 (1927)=
3. G. R? Robertson, J Am Chem Soc, 49, p 2889 (1927).
4. G? Vincent and I? Chappuis, B1, (2), 45, p 501 (1886)?
~igure follows_7
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sEC~~r __
JO ,20 30 40
Time (~r~
I - C1CH2P0 {ONH~)2; aqueous aarmon~.a; 100?
II - C1CH2P0 (OC~HS)2;
III - C1CH2P0 (OC2H5)2;
N - C1CHpPC (OC2H5)g;
aqueous s~nonia; 100?
aqueous ammonia; 150?
alcoholic ammonia; 150?
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