Synthesis of new types of aminomethylenediphosphorus-containing acids and their derivatives

Article abstract of DOI:10.1134/S1070363215020048

Convenient methods for synthesis of various aminomethylenediphosphorus-containing acids and their derivatives starting from available trimethylsilyl esters of hypophosphorous and phosphorous acids, ethoxymethyleneimine hydrochlorides, and N-substituted formamides have been proposed. Selected properties of the obtained compounds have been examined.

Full text of DOI:10.1134/S1070363215020048

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 2, pp. 370–379. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © A.A. Prishchenko, M.V. Livantsov, O.P. Novikova, L.I. Livantsova, I.S. Ershov, V.S. Petrosyan, 2015, published in Zhurnal
Obshchei Khimii, 2015, Vol. 85, No. 2, pp. 196–205.
To the 80th Anniversary of B.I. Ionin
Synthesis of New Types of Aminomethylenediphosphorus-
Containing Acids and Their Derivatives
A. A. Prishchenko, M. V. Livantsov, O. P. Novikova,
L. I. Livantsova, I. S. Ershov, and V. S. Petrosyan
Lomonosov Moscow State University, Moscow, 119991 Russia
e-mail: aprishchenko@yandex.ru
Received December 8, 2014
Abstract—Convenient methods for synthesis of various aminomethylenediphosphorus-containing acids and
their derivatives starting from available trimethylsilyl esters of hypophosphorous and phosphorous acids,
ethoxymethyleneimine hydrochlorides, and N-substituted formamides have been proposed. Selected properties
of the obtained compounds have been examined.
Keywords: aminomethylenediphosphonite, diphosphonate, imine, diphosphonic acid, silylation, trimethylsilyl
triflate
DOI: 10.1134/S1070363215020048
Functionalized aminomethylenediphosphorus-con-
taining compounds are organophosphorus analogs of
natural pyrophosphates and are of interest as promising
ligands and biologically active substances with
different properties [1–5]. Previously, convenient syn-
thesis methods using dialkylformamide dialkylacetals
[6] and N-phenyl-substituted derivatives of form-
amidine [7] have been proposed for some compounds
of this class. In order to prepare new types of tri-
methylsilyl-substituted derivatives of aminomethylene-
diphosphorus-containing acids we studied the interac-
tion of a number of trimethylsilyl esters of phos-
phorous and hypophosphorous acids with available
substituted ethoxymethyleneimines hydrochlorides
(the Pinner adducts) [8] and various N-substituted
formamides; the present contribution discusses those
methods in detail.
Reaction of highly reactive bis(trimethylsiloxy)phos-
phine (taken in excess) with substituted ethoxy-
methyleneimine hydrochlorides in methylene chloride
medium led to intermediate diphosphonites I; those
Scheme 1.
(ХO)2PH, CH2Cl2, 10oC
_ХOP(O)H2, _ХCl
(ХO)2PH
EtOC(R)=NH HCl
EtOC(R)=NH
(ХO)2PС(R)NH2
OEt
C
A
B
NH2
ХО
Х2NH, ХCl, 120oC
(ХO)2PH
_ХOEt
Х2NH, ХCl
_NH4Cl
PC(R)P(OХ)2
[(ХO)2P]2C(R)NH2
IIa−IId
[(ХO)2P]2C(R)NHХ
IIIa−IIId
_NH4Cl
H
O
Ia−Id
(d).
Х = Me3Si; R = H (a), Me (b), Ph (c),
N
370

SYNTHESIS OF NEW TYPES OF AMINOMETHYLENEDIPHOSPHORUS-CONTAINING ACIDS
371
Scheme 2.
SiMe3
CF3SO3
CF3SO3SiMe3, CH2Cl2
EtOC(R)=NH HCl
C(R)NH HCl
EtO
A
D
2(Me3SiO)3P, CH2Cl2, 40oC
(Me3SiO)2P C(R)NH2
2
_Me3SiCl, _CF3SO3SiMe3, _Me3SiOEt
O
IV
t-Bu
(d).
R = H (a), Me (b), Ph (c),
OH
t-Bu
Scheme 3.
Me3SiO
CF3SO3SiMe3
+
HC(O)NR2
CHNR2
Me3SiOCH=NR2
CF3SO3_
CF3SO3
E
2(Me3SiO)3P
_(Me3Si)2O, _CF3SO3SiMe3
(Me3SiO)2P CHNR2
2
O
Va_Ve
(e).
(d),
O
NR = NHMe (a), NHPh (b), NMe (c),
N
2
2
COOSiMe3
N
compounds gave diphosphonites II in high yield upon
refluxing with a mixture of bis(trimethylsilyl)amine
and trimethylchlorosilane. Obviously, formation of
diphosphonites I resulted from of a series of three
reactions: dehydrochlorination of the adduct A,
addition of bis(trimethylsiloxy)phosphine to imine B,
and substitution of ethoxy function in aminal C; the
mechanism was consistent with the known data [6, 7]
(Scheme 1).
stituted ethoxymethyleneimines A proceeded under
catalysis with trimethylsilyl trifluoromethanesulfonate
(trimethylsilyl triflate) to afford diphosphonates IV in
good yields (Scheme 2).
Obviously, the mild reaction conditions were
possible due to catalytic activation of the starting
imines with trimethylsilyl triflate capable of forming
highly reactive intermediate adducts D (cf. [9]).
We successfully used trimethylsilyl triflate for
activation of N-substituted formamides in the reactions
with trimethylsilyl esters of phosphorous and hypo-
phosphorous acids; the latter being known to readily
add at carbonyl group of various aldehydes and
ketones, but the analogous reaction with formamide
has been unknown so far [10].
Note that the intermediate diphosphonites Ia and Ib
were purposefully isolated in good yields by
distillation. Original formation of diphosphonites Ic
31
and Id was detected by P NMR study of the reaction
mixture. Further trimethylsilylation of diphosphonites
II using a mixture of bis(trimethylsilyl)amine and
trimethylchlorosilane proceeded slowly; as a result, no
more that 5–15% of the N-trimethylsilylaminome-
thylenediphosphonites III was isolated.
We found that N-substituted formamides reacted
exothermally with excess of tris(trimethylsilyl) phos-
phite in methylene chloride medium in the presence of
trimethylsilyl triflate to form bisphosphonates V in
high yields (Scheme 3).
Similarly, the reaction of excess of tris(tri-
methylsilyl)phosphite with hydrochlorides of sub-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015

372
PRISHCHENKO et al.
Scheme 4.
2(EtO)2POSiMe3
_Me3SiCl
SOCl2
COOSiMe3
COCl
C[P(O)(OEt2)]2
OSiMe3
_Me3SiCl, _SO2
N
N
N
C(O)H
C(O)H
H(O)C
VII
EtOH
_Me3SiOEt
C[P(O)(OEt2)]2
OH
N
C
H(O)
VI
Scheme 5.
(1) HCOOH, (2) (Me3Si)2NH, Me3SiCl
COOH
COOSiMe3
N
H
N
C(O)H
VII
Scheme 6.
ХО
Х2NH, ХCl
HC(O)NR2, CF3SO3Х
_Х2O
2(ХO)2PH
P
2CHNR2
[(ХO)2P]2CHNR2
VIIIa−VIIIc
_NH3
H
O
F
(c).
O
Х = Me3Si, NR2 = NHPh (a), NMe2 (b),
N
Undoubtedly, the catalytic effect of trimethylsilyl
triflate was associated with formation of highly
reactive immonium salts E during the reaction.
trimethylsilyl triflate as a catalyst forming intermediate
diphosphonites F. Refluxing of the latter with bis-
(trimethylsilyl)amine in the presence of trimethyl-
chlorosilane resulted in formation of diphosphonites
VIII in good yields (Scheme 6).
Note that a structural analog of aminomethylene-
diphosphonate Vd containing pyrrolidine fragment,
hydroxymetylenediphosphonate VI, was generated
with high yield via sequential interaction of func-
tionalized formamide VII with thionyl chloride, excess
of diethyl(trimethylsilyl)phosphate, and ethanol (cf.
[11]) (Scheme 4).
The obtained aminomethylenediphosphonites are
key parent compounds for preparation of new amino-
methylenediphosphorus-containing species. In parti-
cular, diphosphonite VIIIa containing highly reactive
fragment POSi was readily attached at the carbonyl
group of aromatic aldehydes (the latter being taken in
excess) in methylene chloride to form intermediate
diphosphinates G. After treating the reaction mixture
with methanol, new functionalized aminomethylene-
diphosphinic acids IX were isolated in high yields
(Scheme 7).
We purposefully prepared the previously described
formamide VII via proline formylation followed by
treating the reaction mixture with bis(trimethylsilyl)
amine and trimethylchlorosilane as silylating agents
under heating at 130°C (Scheme 5).
Reaction of excess of bis(trimethylsiloxy)phos-
phine with N-substituted formamides also occurred
readily in methylene chloride only in the presence of
The readily oxidized diphosphonites II and VIII
were treated with a diluted solution of sodium
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SYNTHESIS OF NEW TYPES OF AMINOMETHYLENEDIPHOSPHORUS-CONTAINING ACIDS
373
Scheme 7.
Ar(Me3SiO)CH
Me3SiO
Ar(HO)CH
HO
4MeOH
2ArCHO
VIIIa
P CHNHPh
P CHNHPh
2
2
_4Me3SiOMe
O
O
IХa, IXb
G
(a),
Ar =
4-MeOC6H4 (b).
N
methoxide in methanol to form stable disodium salts of
diphosphonous acids X and XI in the form of white
hygroscopic crystals (Scheme 8).
isomers of VI and IX resonated as characteristic AB-
system.
To conclude, we elaborated convenient approaches
towards synthesis of new types of aminomethylene-
diphosphorus-containing acids and their derivatives,
promising ligands and biologically active substances.
The resulting compounds contained active fragments
(NH, POSi, or PH) and are suitable synthons for
preparation of novel functionalized aminomethylene-
diphosphorus-containing substances such as diphos-
phorus-containing peptides.
Similarly, trimethylsilyl-containing diphosphonates
IV and V reacted under mild conditions with excess of
methanol to form diphosphonic acids XII and XIII in
high yields (Scheme 9).
Crystal hydrates of the previously obtained amino-
methylenediphosphonic acids XIIIc and XIIId have
been described in [12].
NMR spectra of compounds I–XIII contained
characteristic signals of the fragments H (see Experi-
mental, Scheme 10).
EXPERIMENTAL
1Н (400 MHz), 13С (100 MHZ), and 31Р (162 MHz)
NMR spectra were registered with a Bruker Avance
400 spectrometer relative to internal TMS (1Н and 13С)
According to NMR data, the compounds containing
asymmetric atoms were obtained as stereoisomers
1
mixtures; their compositions were determined by H
and 31P NMR. Noteworthily, in 31P NMR spectrum the
two diastereotopic phosphoryl groups of the major
Scheme 9.
4MeOH, 10oC
IV
(HO)2P C(R)NH2
2
_4Me3SiOMe
Scheme 8.
O
ХIIа−XIId
NaО
2MeONa, 4MeOH, 5oC
t-Bu
II
P C(R)NH2
2
_4Me3SiOMe
H
(d).
R = H (a), Me (b), Ph (c),
OH
t-Bu
O
Ха−Xd
(d).
R = H (a), Me (b), Ph (c),
4MeOH
(HO)2P CHNR2
2
V
_4Me3SiOMe
NaО
O
2MeONa, 4MeOH
_4Me3SiOMe
ХIIIа−XIIIe
VIII
P CHNH2
2
H
O
(d),
O
NR = NHMe (a), NHPh (b), NMe (c),
N
2
2
ХIа−XIc
(c).
NR2 = NHPh (a), NMe2 (b), N
O
(e).
COOH
N
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015

374
PRISHCHENKO et al.
NMR spectrum, δ, ppm: from –0.03 to –0.05 m
Scheme 10.
3
(2Ме3Si), 0.03–0.05 m (Ме3Si), 0.88 d.d (Ме, JРH
3
6
3
4
4
3
1
13.2, JРH 17.4 Hz), 6.58 d (2РН, JРH 550.8 Hz), 1.12–
1.32 m (NH2). 13С NMR spectrum, δС, ppm: 55.81 d.d
2
2
5
5
P2C1(R)NCH2, R =
,
,
(С1, JPС 34.3, JPС 67.0 Hz), 15.18 d (Ме, JPС
19.1 Hz), 0.8–1.2 m (3Me3Si). 31Р NMR spectrum, δР,
ppm: 145.83 d (Р, 2JРР 53.6 Hz), 30.74 d (РН, 2JРР 53.6 Hz).
N
1
1
2
t-Bu
4
3
2
5
;
OH
1
The second isomer, content 30%. H NMR spectrum,
δ, ppm: from –0.03 to –0.05 m (2Ме3Si), 0.03–0.05 m
t-Bu
1
(Ме3Si), 0.90–1.10 m (Ме), 6.64 d (2РН, JРH
551.2 Hz), 1.12–1.32 m (NH2). 13С NMR spectrum, δС,
4
5
1
1
ppm: 56.15 d.d (С1, JPС 34.4, JPС 68.7 Hz), 15.29 d
2
P2C1HNC2Hn(C3Hm),
3
C6
.
(Ме, JPС 18.3 Hz), 0.8–1.2 m (3Me3Si). 31Р NMR
2
N
spectrum, δР, ppm: 146.34 d (Р, 2JРР 51.5 Hz), 29.05 d
H
C1H
2
1
(РН, JРР 51.5 Hz). The third isomer, content 20%. H
NMR spectrum, δ, ppm: from –0.03 to –0.05 m
(2Ме3Si), 0.03–0.05 m (Ме3Si), 0.9–1.1 m (Ме), 6.57
d (2РН, 1JРH 545.2 Hz), 1.12–1.32 m (NH2). 13С NMR
or external 85% H3PO4 in D2O (31P) references, using
CDCl3 (I–VIII), D2O (IX–XI), or mixtures of D2O,
CD3OD, and C5D5N (XII, XIII) as solvents. All the
reactions were carried out under argon atmosphere
using anhydrous solvents. Elemental analysis of easily
oxidized diphosphonites I–III and VIII was performed
using their stable derivatives X, XI, and XIIa.
spec-trum, δС, ppm: 55.47 d.d (С1, JPС 32.7, JPС
1
1
2
66.3 Hz), 14.04 d (Ме, JPС 22.4 Hz), 0.8–1.2 m
(3Me3Si). 31Р NMR spectrum, δР, ppm: 145.39 d (Р,
2JРР 41.6 Hz), 28.14 d (РН, JРР 41.6 Hz). The fourth
2
isomer, content 15%. 1H NMR spectrum, δ, ppm: from
–0.03 to –0.05 m (2Ме3Si), 0.03–0.05 m (Ме3Si), 0.9–
O,O,O-Tris(trimethylsilyl)aminomethylenedi-
phosphonite (Ia). A solution of 24 g of bis(trimethyl-
siloxy)phosphine in 10 mL of methylene chloride was
added upon stirring to a suspension of 2.5 g of ethoxy-
methyleneimine hydrochloride in 25 mL of methylene
chloride. After stirring the mixture during 1 h, the
solvent was evaporated. 20 mL of bis(trimethylsilyl)-
amine was added to the residue, and the mixture was
stirred until ammonia evolution ceased. Excess of bis-
(trimethylsilyl)amine was removed, and the residue
was distilled. Yield 7.9 g (78%), bp 122°С (1 mmHg).
1
1.1 m (Ме), 6.54 d (2РН, JРH 546.8 Hz), 1.12–1.32 m
(NH2). 13С NMR spectrum, δС, ppm: 54.73 d.d (С1,
1JPС 34.3, JPС 71.1 Hz), 13.61 d (Ме, JPС 20.8 Hz),
0.8–1.2 m (3Me3Si). 31Р NMR spectrum, δР, ppm:
144.97 d (Р, 2JРР 55.4 Hz), 31.91 d (РН, 2JРР 55.4 Hz).
From NMR data, diphosphonite Ib contained 10% of
diphosphonite IIb.
1
2
O,O,O,O-Tetra(trimethylsilyl)aminomethylene-
diphosphonite (IIa). A mixture of 7.9 g of diphos-
phonite Iа, 20 g of bis(trimethylsilyl)amine, and 7 g of
trimethylchlorosilane was refluxed until ammonium
chloride sublimation ceased. The residue was distilled.
1
The first isomer, content 60%. H NMR spectrum, δ,
ppm: 2.4–2.7 m (С1H), 0.7–0.8 m (NН2), 6.91 d (РН,
1JРH 551.2 Hz), 0.02–0.06 m (Ме). 13С NMR spectrum,
1
Yield 7.7 g (84%), bp 126°С (1 mmHg). H NMR
δС, ppm: 59.24 d.d (С1, JPС 91.0, JPС 38.0 Hz), 0.35–
1.13 m (Me). 31Р NMR spectrum, δР, ppm: 23.88 d and
147.25 d (2JPР 39.7 Hz). The second isomer, content
1
1
spectrum, δ, ppm: 2.6–2.7 m (С1H), 2.21 d. t (NН2,
3
13
3JРH 6.4, JНH 12 Hz), 0.10 s, and 0.11 s (4Ме3SiO). С
NMR spectrum, δС, ppm: 68.98 t (С1, JPС 38.0 Hz),
1
40%. H NMR spectrum, δ, ppm: 2.4–2.7 m (С1H),
1
1.37 (4Ме3SiO). 31Р NMR spectrum: δР 153.83 ppm.
From NMR data, diphosphonite IIa contained 5% of
diphosphonite IIIa, δР 151.33 ppm.
1
0.7–0.8 m (NН2), 6.92 d (РН, JРH 551.2 Hz), 0.02–
0.06 m (Ме). 13С NMR spectrum, δС, ppm: 59.90 d.d
1
1
(С1, JPС 94.0, JPС 40.0 Hz), 0.35–1.13 m (Me). 31Р
NMR spectrum, δР, ppm: 25.58 d and 146.32 d (2JPР
50.2 Hz). From NMR data, diphosphonite Ia contained
10% of diphosphonite IIa.
Diphosphonites IIb–IId were prepared similarly.
O,O,O,O-Tetra(trimethylsilyl)-1-aminoethylidene-
diphosphonite (IIb). Yield 88%, bp 124°С (1 mmHg).
3
1H NMR spectrum, δ, ppm: 0.92 t (NH2, JРH 10.2 Hz),
O,O,O-Tris(trimethylsilyl)-1-aminoethylidene-
phosphonite Ib was obtained similarly. Yield 68%, bp
121°С (1 mmHg). The first isomer, content 35%. H
3
0.76 t (Ме, JРH 12.4 Hz), 0.01 br.s (4 Ме3Si). 13С
1
1
NMR spectrum, δС, ppm: 60.30 t (С1, JPС 32.8 Hz),
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SYNTHESIS OF NEW TYPES OF AMINOMETHYLENEDIPHOSPHORUS-CONTAINING ACIDS
375
2
3
3
14.55 t (Ме, JPС 17.6 Hz), 1.24 s (4Me3Si). 31Р NMR
(NH2, JРH 13.6, JНH 8.0 Hz), 0.01 s and –0.02 s
(4Ме3Si). 13С NMR spectrum, δС, ppm: 50.66 t (С1,
1JPС 155.0 Hz), 0.72 and 0.87 (Me3Si). 31Р NMR
spectrum: δР 3.43 ppm. Found, %: С 34.64; Н 8.49.
С16Н47NО6P2Si5. Calculated, %: С 34.82; Н 8.58.
spectrum: δР 154.54 ppm. From NMR data, diphos-
phonite IIb contained 15% of diphosphonite IIIb. 31С
NMR spectrum, δС, ppm: 62.36 t (С1, JPС 33.5 Hz),
1
13.09 t (Ме, JPС 19.2 Hz). 31Р NMR spectrum: δР
2
151.21 ppm.
Diphosphonates IVb–IVd were prepared similarly.
O,O,O,O-Tetra(trimethylsilyl)-1-aminobenzyl-
idenediphosphonite (IIc). Yield 74%, bp 144°С
(1 mmHg). 1H NMR spectrum, δ, ppm: –0.16 s
O,O,O,O-Tetra(trimethylsilyl)-1-aminoethylidene-
diphosphonate (IVb). Yield 73%, bp 127°С (1 mmHg).
4
1H NMR spectrum, δ, ppm: –0.09 d (2Ме3Si, JРH
3
(2Me3Si), 0.04 s (2Me3Si), 1.60 t (NH2, JРH 7.6 Hz),
4
2.0 Hz), –0.08 d (2Ме3Si, JРH 1.6 Hz), 0.99 t (СН3,
6.9–7.4 m (С6H5). 13С NMR spectrum, δС, ppm:
3
3JРH 16.8 Hz), 1.13 t (NH2, JРH 12.8 Hz). 13С NMR
2
138.75 t (С2, JPС 10.4 Hz), 127.43 (С4), 126.73 t (С3,
1
spectrum, δС, ppm: 51.58 t (С1, JPС 152.5 Hz), 20.03
1
3JPС 8.8 Hz), 125.26 (С5), 70.35 t (С1, JPС 41.5 Hz),
(Ме), 0.73 (2Me3Si), 0.78 (2Me3Si). 31Р NMR spec-
trum: δР 6.65 ppm. Found, %: С 33.78; Н 8.23.
С14Н41NО6P2Si4. Calculated, %: С 34.05; Н 8.37.
1.35 (2Me3Si), 0.92 (2Me3Si). 31Р NMR spectrum: δР
149.74 ppm. From NMR data, diphosphonite IIc
contained 5% of diphosphonite IIIc, δР 141.14 ppm. In
the spectrum of the reaction mixture, the signals of Ic
were observed, δР, ppm: the first isomer (content
O,O,O,O-Tetra(trimethylsilyl)-1-aminobenzyl-
idenephosphonate (IVc). Yield 72%, bp 152°С
(1 mmHg). 1H NMR spectrum, δ, ppm: –0.24 d
2
2
80%), 142.45 d (Р, JРР 65.4 Hz), 28.88 d (РН, JРР
65.4 Hz); the second isomer (content 20%), 141.04 d
(Р, 2JРР 71.4 Hz), 24.96 d (РН, 2JРР 71.4 Hz).
4
4
(2Ме3Si, JРH 2.8 Hz), –0.20 d (2Ме3Si, JРH 2.8 Hz),
1.72 t (NH2, JРH 13.0 Hz), 6.8–7.6 m (С6Н5). 13С
3
NMR spectrum, δС, ppm: 135.77 br.s (С2), 127.18 and
O,O,O,O-Tetra(trimethylsilyl)-1-amino-1-(pyrid-
3-yl)methylenediphosphonite (IId). Yield 72%, bp
127.25 (С3, С4), 126.79 (С5), 59.63 t (С1, JPС
1
147.7 Hz), 0.52 (2Me3Si), 0.45 (2Me3Si). 31Р NMR
spectrum: δР 2.23 ppm. Found, %: С 40.74; Н 7.72.
С19Н43NО6P2Si4. Calculated, %: С 41.06; Н 7.80.
1
145°С (1 mmHg). H NMR spectrum, δ, ppm: –0.28 s
3
(2Me3Si), –0.13 s (2Me3Si), 1.42 t (NH2, JРH 9.6 Hz),
3
3
6.92 d.d (С4H, JНH 4.8, 8.0 Hz), 7.52 d (С3H, JНH
8.0 Hz), 8.10 d (С5H, JНH 4.8 Hz), 8.48 s (С6H). 13С
3
O,O,O,O-Tetra(trimethylsilyl)-1-amino-1-(3,5-di-
tert-butyl-4-hydroxyphenyl)methylenephosphonate
NMR spectrum, δС, ppm: 151.61 (С2 ), 148.28 t (С6,
3JPС 9.6 Hz), 146.07 (С5 ), 135.03 (С4), 134.05 t (С3,
1
(IVd). Yield 89%, mp 52°С. H NMR spectrum, δ,
3JPС 7.2 Hz), 69.16 t (С1, JPС 41.5 Hz), 1.14 (2Me3Si),
1
ppm: 0.06 s (2Me3Si), 0.07 s (2Me3Si), 1.19 br.s
(NH2), 1.34 s (Ме3С), 5.08 br.s (ОН), 7.63 s (С6Н2).
13С NMR spectrum, δС, ppm: 152.31 (С5), 139.46 (С4),
0.80 (2Me3Si). 31Р NMR spectrum: δР 148.07 ppm.
From NMR data, diphosphonite IId contained 5% of
diphosphonite IIId, δР 141.18 ppm. In the spectrum of
the reaction mixture, the signals of Id were observed,
δР, ppm: the first isomer (content 70%), 142.15 d (Р,
1
126.42 (С2), 125.03 (С3), 59.65 t (С1, JPС 149.3 Hz),
35.12 (Ме3С), 30.98 (Ме3С), 0.68 (2Me3Si), 0.77
(2Me3Si). 31Р NMR spectrum: δР 3.27 ppm. Found, %:
С 47.26; Н 8.61. С27Н59NО7P2Si4. Calculated, %: С
47.41; Н 8.69.
2JРР 61.4 Hz), 27.51 d (РН, JРР 61.4 Hz); the second
2
2
isomer (content 30%), 141.24 d (Р, JРР 65.4 Hz),
23.61 d (РН, 2JРР 65.4 Hz).
O,O,O,O-Tetra(trimethylsilyl)dimethylamino-
methylenediphosphonate (Vc). Trimethylsilyl triflate
(3 mL) was added upon stirring to a solution of 15 g of
tris(trimethylsilyl)phosphite and 1.5 g of DMF in 8 mL
of methylene chloride. The mixture was incubated at
20°С during 24 h, and then the solvent was evaporated.
3 mL of hexane was added to the residue. After
cooling to 5°С, the solvent was decanted. White
crystals were kept in vacuum at 0.5 mmHg. Yield 8.8 g
O,O,O,O-Tetra(trimethylsilyl)aminomethylene-
diphosphonate (IVa). Ethoxymethyleneimine hyd-
rochloride (2.4 g) and trimethylsilyl triflate (0.2 mL)
were added to a solution of 15 g of tris(trimethylsilyl)
phosphite in 10 mL of methylene chloride. The
mixture was refluxed during 1 h, then the solvent was
removed. Bis(trimethylsilyl)amine (15 g) was added to
the residue, and the mixture was refluxed during 1 h.
The solvent was removed, and the residue was
distilled. Yield 8.4 g (69%), bp 139°С (0.5 mmHg). 1H
NMR spectrum, δ, ppm: 2.6–2.9 m (С1H), 1.19 d. t
1
(87%), mp 42°С. H NMR spectrum, δ, ppm: –0.08 s
2
(Me3Si), 2.40 s (2С2Н3N), 3.05 t (С1H, JPH 24.4 Hz).
1
13С NMR spectrum, δС, ppm: 62.77 t (С1, JPС
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015

376
PRISHCHENKO et al.
3
147.7 Hz), 43.53 t (С2, JPС 4.3 Hz), 0.48 (Me3Si). 31Р
NMR spectrum: δР –2.87 ppm. Found, %: С 35.26; Н
8.49. С15Н43NО6P2Si4. Calculated, %: С 35.48; Н 8.53.
%: С 38.72; Н 8.14. С21Н53NО8P2Si5. Calculated, %: С
38.96; Н 8.22.
O,O,O,O-Tetraethyl-(N-formylpyrrolidin-2-yl)-
hydroxymethylenediphosphonate (VI). A solution of
3.6 g of thionyl chloride in 5 mL of methylene chloride
was added upon stirring at 5°С to a solution of 6.1 g of
ester VII in 10 mL of methylene chloride. The mixture
was heated to reflux, and then evaporated. The residue
was kept in vacuum at 1 mmHg during 0.5 h and
dissolved in 15 mL of methylene chloride. After
cooling to 5°С, a solution of 18 g of diethyl(tri-
methylsilyl)phosphite in 15 mL of methylene chloride
was added. Next, the solvent was removed, the residue
was dissolved in 30 mL of ethanol, and the mixture
was heated to 40°С. Trimethyl(ethoxy)silane and
ethanol were distilled off; the residue was dissolved in
15 mL of diethyl ether and mixed with 10 mL of
hexane and 10 mL of water. The formed oily substance
was separated and incubated in vacuum at 1 mmHg
Diphosphonates Vа, Vb, Vd, and Ve were prepared
similarly; diphosphonates Vа and Vb were isolated by
distillation.
O,O,O,O-Tetra(trimethylsilyl)methylamino-
methylenediphosphonate (Va). Yield 78%, bp 139°С
(1 mmHg). 1H NMR spectrum, δ, ppm: –0.06 s
2
(Me3Si), 2.35 s (С2Н3N), 2.57 t (С1H, JPH 21.6 Hz).
1
13С NMR spectrum, δС, ppm: 58.25 t (С1, JPС
3
151.3 Hz), 37.20 t (С2, JPС 6.4 Hz), 0.35 (Me3Si). 31Р
NMR spectrum: δР 1.77 ppm. Found, %: С 33.89; Н
8.26. С14Н41NО6P2Si4. Calculated, %: С 34.05; Н 8.37.
O,O,O,O-Tetra(trimethylsilyl)-N-anilinomethyl-
enediphosphonate (Vb). Yield 84%, bp 157°С
1
(0.5 mmHg). H NMR spectrum, δ, ppm: 0.04 s and
2
0.06 s (Me3Si), 3.70–3.85 m (NH), 4.21 t (С1H, JРH
3
27.2 Hz), 6.41 d (2С3H, JНH 8.0 Hz), 6.51 t (2С4H,
1
3
3JНH 8.0 Hz), 6.96 t (2С4H, JНH 8.0 Hz). 13С NMR
during 0.5 h. Yield 10.3 g (91%). H NMR spectrum,
δ, ppm: 0.9–1.0 m (4СН3), 1.3–1.6 m (С4Н2), 1.9–2.3
m (С5Н2), 3.15–3.65 m (С3Н2), 3.6–4.0 m (С2H,
4СН2ОР), 7.84 s (С1H). 13С NMR spectrum, δС, ppm:
164.22 (С1), 62.7–64.3 m (С2, СH2ОР), 77.90 t (С6H,
2JРС 154.9 Hz), 48.50 (С3), 24.18 (С4), 27.71 (С5),
15.9–16.2 m (Me). 31Р NMR spectrum: 15.87 and
spectrum, δС, ppm: 149.39 (С2); 129.08, 118.15 and
1
112.96 (С3, С4, С5), 58.16 t (С1, JPС 153.3 Hz), 0.74 s
and 0.86 s (Me3Si). 31Р NMR spectrum: δР –1.67 ppm.
Found, %: С 40.94; Н 7.74. С19Н43NО6P2Si4. Cal-
culated, %: С 41.06; Н 7.80.
2
O,O,O,O-Tetra(trimethylsilyl)-N-morpholino-
16.22 (АВ-system, JPР 28.7 Hz). Found, %: С 41.71;
1
methylenediphosphonate (Vd). Yield 85%, oil. H
Н 7.22. С14Н29NО8P2. Calculated, %: С 41.90; Н 7.28.
NMR spectrum, δ, ppm: 0.07 s (4Me3Si), 2.76 t (С1H,
2JРH 25.6 Hz), 2.7–2.8 m (2С2H2), 3.3–3.4 m (2С3H2).
Trimethylsilyl ester of N-formylproline (VII). A
mixture of 20 g of proline and 50 g of formic acid was
heated upon stirring in boiling water bath during 5 h,
and then evaporated in vacuum at 7 mmHg. A mixture
of 56 g of bis(trimethylsilyl)amine and 8 g of tri-
methylchlorosilane was added to the residue; the
mixture was refluxed until ammonium chloride
sublimation ceased and then distilled. Yield 27 g
(72%), bp 133°С (2 mmHg). The first isomer, content
60%. 1Н NMR spectrum, δ, ppm: –0.06 s (Me3Si), 1.5–
2.0 m (С4Н2, С5Н2,), 3.25–3.35 m (С3Н2), 4.08 d.d
1
13С NMR spectrum, δС, ppm: 63.82 t (С1, JPС
3
148.9 Hz), 51.33 t (С2, JPС 4.4 Hz), 67.11 (С3), 0.75
(Me3Si). 31Р NMR spectrum: δР –0.62 ppm. Found, %:
С 36.94; Н 8.16. С17Н45NО7P2Si4. Calculated, %: С
37.14; Н 8.25.
O,O,O,O-Tetra(trimethylsilyl)-N-(O-trimethyl-
silylprolino)methylenediphosphonate (Ve). Yield
89%, oil. The first isomer, content 60%. 1H NMR spec-
trum, δ, ppm: : –0.17 s (4Me3Si), 2.6–2.8 m (С3H2),
1.3–1.7 m (С4H2, С5H2), 3.42 br.t (С1H, 2JРH 26.2 Hz),
3.6–3.8 m (С2H). 13С NMR spectrum, δС, ppm: 171.82
3
3
(С2Н, JНН
А
8.4, JНН
3.6Hz), 7.91 s (С1Н). 13С NMR
В
spectrum, δС, ppm: 171.43 (С6), 160.18 (С1), 57.17
1
(С6), 63.8–64.5 m (С2), 58.41 t (С1, JPС 155.7 Hz),
(С2), 45.90 (С3), 29.03 (С5), 23.63 (С4). The second
48.9–49.6 m (С3), 22.97 (С4), 27.98 (С5), 0.43 (Me3Si).
31Р NMR spectrum: δР –0.42 ppm. The second isomer.
1H NMR spectrum, δ, ppm: –0.17 s (4Me3Si), 1.3–1.7
m (С4H2, С5H2), 2.6–2.8 m (С3H2), 3.42 br.t (С1H, 2JРH
26.2 Hz), 3.6–3.8 m (С2H). 13С NMR spectrum, δС,
1
isomer (content 40%). Н NMR spectrum, δ, ppm:
–0.06 s (Me3Si), 1.5–2.0 m (С4Н2, С5Н2,), 3.08–3.19 m
(С3Н2), 3.99 d.d (С2Н, JНН
А
8.4, JНН 4 Hz), 7.86 s
В
3
3
(С1Н). 13С NMR spectrum, δС, ppm: 171.82 (С6),
161.21 (С1), 59.27 (С2), 43.43 (С3), 29.31 (С5), 22.43
(С4). Found, %: С 49.97; Н 7.82. С9Н17NО3Si.
Calculated, %: С 50.20; Н 7.96.
1
ppm: 171.54 (С6), 63.8–64.5 m (С2), 58.16 t (С1, JPС
156.5 Hz), 48.9–49.6 m (С3), 27.98 (С5), 22.97 (С4),
0.43 (Me3Si). 31Р NMR spectrum: δР 3.16 ppm. Found,
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SYNTHESIS OF NEW TYPES OF AMINOMETHYLENEDIPHOSPHORUS-CONTAINING ACIDS
377
1
2
O,O,O,O-Tetra(trimethylsilyl)-N-anilinomethyl-
enediphosphonite (VIIIa). Trimethylsilyl triflate
(1 mL) was added upon stirring to a solution of 18 g of
bis(trimethylsiloxy)phosphine and 2.4 g of formanilide
in 10 mL of methylene chloride. The mixture was
incubated at 20°С during 4 h, and then evaporated.
20 g bis(trimethylsilyl)amine and 2 mL of trimethyl-
chlorosilane were added to the residue. The mixture
was refluxed during 1 h and distilled. Yield 7.7 g
30%. H NMR spectrum, δ, ppm: 4.31 t (С1H, JPH
16 Hz), 4.97 d (С3H, JPH 12.4 Hz). 13С NMR
2
spectrum, δС, ppm: 69.97 d (С3, 1JPС 106.4 Hz), 48.51 t
(С1, JPС 86.9 Hz). 31Р NMR spectrum: δР 30.22 ppm.
1
1
The third isomer, content 20%. H NMR spectrum, δ,
ppm: 3.92 t (С1H, JPH 16.3 Hz), 5.05 d (С3H, JPH
2
2
12.4 Hz). 13С NMR spectrum, δС, ppm: 69.13 d (С3,
1JPС 97.8 Hz), 51.89 t (С1, JPС 87.6 Hz). 31Р NMR
1
spectrum: δР 30.67 ppm. The signals of aromatic
1
1
(74%), bp 152°С (1 mmHg). H NMR spectrum, δ,
moieties of all the stereoisomers in the H and 13С
ppm: 0.1–0.2 m (12СН3), 3.2–3.3 m (С1H), 4.44 d
NMR spectra were overlapped being located in
characteristic spectral regions. Found, %: С 50.57; Н
4.78. С19Н21N3О6P2. Calculated, %: С 50.79; Н 4.71.
3
3
(NH, JH3H 8.0 Hz), 6.60 t (2СНPh, JHH3 8.0 Hz), 6.68 d
(2СНPh, JHH 8.0 Hz), 7.07 t (2СНPh, JHH 8.0 Hz). 13С
NMR spectrum, δС, ppm: 151.03 (С2); 128.53, 115.67
1
and 112.56 (СPh), 71.78 t (С1, JPС 38.5 Hz), 1.31
N-Anilinomethylenebis[hydroxy(anisyl)methyl-
phosphinic] acid (IХа) was obtained similarly. Yield
87%, mp >150°С (decomp.). The first isomer, content
(CH3). 31Р NMR spectrum: δР 155.78 ppm.
1
2
50%. H NMR spectrum, δ, ppm: 4.71 t (С1H, JPH
Diphosphonites VIIIb and VIIc were prepared
similarly.
16.2 Hz), 4.89 d (С3H, JPH 16.1 Hz). 13С NMR spec-
2
trum, δС, ppm: 70.27 d (С3, 1JPС 103.3 Hz), 48.39 t (С1,
1JPС 78.7 Hz). 31Р NMR spectrum, δР, ppm: 38.17 d
(2JPР 24.3 Hz), 39.07 d (2JPР 24.3 Hz). the second
isomer, content 30%. 1H NMR spectrum, δ, ppm: 4.78
O,O,O,O-Tetra(trimethylsilyl)dimethylamino-
methylenediphosphonite (VIIIb). Yield 52%, bp
1
119°С (1 mmHg). H NMR spectrum, δ, ppm: 0.15 s
2
(4Me3Si), 2.11 t (С1H, JРH 5.6 Hz), 2.67 s (2С2H3N).
t (С1H, JPH 16 Hz), 4.89 d (С3H, JPH 16.1 Hz). 13С
2
2
1
13С NMR spectrum, δС, ppm: 82.37 t (С1, JPС
NMR spectrum, δС, ppm: 70.96 d (С3, JPС 105.2 Hz),
1
3
41.6 Hz), 45.19 t (С2, JPС 7.2 Hz), 1.39 (Me3Si). 31Р
48.59 t (С1, JPС 81.2 Hz). 31Р NMR spectrum: δР
1
NMR spectrum: δР 166.82 ppm.
1
39.80 ppm. The third isomer, content 20%. H NMR
spectrum, δ, ppm: 4.41 t (С1H, JPH 16.2 Hz), 4.89 d
2
O,O,O,O-Tetra(trimethylsilyl)-N-morpholinome-
thylenediphosphonite (VIIIc). Yield 72%, bp 144°С
(1 mmHg). 1H NMR spectrum, δ, ppm: 0.17 s (4Me3Si),
2
(С3H, JPH 16.1 Hz). 13С NMR spectrum, δС, ppm:
69.20 d (С3, JPС 106.4 Hz), 49.64 t (С1, JPС 79.8 Hz).
31Р NMR spectrum: δР 39.08 ppm. The signals of
methoxyl and aromatic moieties of all the stereo-
1
1
2
2.08 t (С1H, JРH 6.2 Hz), 3.0–3.1 m (2С2H2), 3.4–3.5
m (2СH2О). 13С NMR spectrum, δС, ppm: 82.34 t (С1,
3
1JPС 42.8 Hz), 53.11 t (С2, JPС 6.8 Hz), 67.73 (СН2О),
isomers in the H and 13С NMR spectra were over-
1
1.35 (Me3Si). 31Р NMR spectrum: δР 165.33 ppm.
lapped being located in characteristic spectral regions.
Found, %: С 54.26; Н 5.28. С23Н27NО8P2. Calculated,
%: С 54.44; Н 5.36.
N-Anilinomethylenebis[hydroxy(pyrid-3-yl)me-
thyphosphinic] acid (IXb). A solution of 1.6 g of 3-
pyridinylcarbaldehyde in 10 mL of methylene chloride
was added upon stirring to a solution of 3.5 g of
diphosphonite VIIIа in 10 mL of methylene chloride
under cooling to 10°С. Then the solvent was removed,
and a mixture of 10 mL of methanol and 20 mL of
diethyl ether was added to the residue. The mixture
was heated to reflux. After cooling, the formed crystals
were filtered off, washed with diethyl ether, and kept
in vacuum at 1 mmHg during 1 h. Yield 2.7 g (89%),
mp >150°С (decomp.). The first isomer, content 50%.
Disodium salt of aminomethylenediphosphonous
acid (Ха). A solution of 6.5 g of diphosphonite IIа in
20 mL of diethyl ether was added upon stirring at 10°С
to a solution of 1.57 g of sodium methoxide in 30 mL
of methanol. After the solvent removal, white crystals
were kept in vacuum at 1 mmHg during 1 h. Yield
2.8 g (95%). H NMR spectrum, δ, ppm: 2.67 t (С1H,
1
2JPH 15.6 Hz), 6.90 d (2РН, JPH 528.8 Hz). 13С NMR
1
spectrum, δС, ppm: 53.20 t (С1, JPС 84.6 Hz). 31Р
1
NMR spectrum: δР 22.40 ppm. Found, %: С 5.79; Н
2.52. СН5NNa2О4P2. Calculated, %: С 5.91; Н 2.48.
2
1H NMR spectrum, δ, ppm: 4.14 t (С1H, JPH 16.4 Hz),
2
4.95 d (С3H, JPH 12.4 Hz). 13С NMR spectrum, δС,
1
1
ppm: 69.74 d (С3, JPС 104.2 Hz), 50.24 t (С1, JPС
84.8 Hz). 31Р NMR spectrum: 29.98 d (2JPР 20.3 Hz),
31.19 d (2JPР 20.3 Hz). The second isomer, content
The salts Хb–Xd, XIа–XIc were obtained
similarly. Sodium salts X and XI decomposed upon
heating above 100°С.
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378
PRISHCHENKO et al.
Disodium salt of 1-aminoethylidenediphosphonous
reflux, and then evaporated. White crystals were
filtered off and kept in vacuum at 1 mmHg during 1 h.
1
acid (Хb). Yield 97%. H NMR spectrum, δ, ppm:
1.07 t (Ме, 3JPH 16 Hz), 6.67 d (2РH, 1JPH1 524 Hz). 13С
NMR spectrum, δС, ppm: 51.99 t (С1, JPС 89.4 Hz),
15.26 (Ме). 31Р NMR spectrum: δР 29.45 ppm. Found,
%: С 10.88; Н 3.13. С2Н7NNa2О4P2. Calculated, %: С
11.07; Н 3.25.
Yield 2.5 g (96%), mp 159°С. H NMR spectrum, δ,
1
2
ppm: 3.82 t (С1H, JPH 19.2 Hz). 13С NMR spectrum,
1
δС, ppm: 54.89 t (С1, JPС 147.4 Hz). 31Р NMR
spectrum: δР 15.83 ppm. Found, %: С 6.12; Н 3.74.
СН7NО6P2. Calculated, %: С 6.29; Н 3.70.
Disodium salt of 1-aminobenzylidenediphosphonous
The acids XIIb–XIId and XIIIa–XIIIe were
prepared similarly.
1
acid (Хc). Yield 96%. H NMR spectrum, δ, ppm:
1
6.92 d (2РH, JPH 538.4 Hz), 7.2–7.5 m (С6Н5). 13С
NMR spectrum, δС, ppm: 135.93 (С2), 128.55 (С4),
127.04 (С5), 126.15 (С3), 60.62 t (С1, 1JPС 85.4 Hz). 31Р
NMR spectrum: δР 27.10 ppm. Found, %: С 29.98; Н
3.28. С7Н9NNa2О4P2. Calculated, %: С 30.13; Н 3.25.
1-Aminoethylidenediposphonic acid (XIIb).
1
Yield 96%, mp 252°С. H NMR spectrum, δ, ppm:
3
1.12 t (Ме, JPH 13.2 Hz). 13С NMR spectrum, δС,
ppm: 51.69 t (С1, 1JPС 122.2 Hz), 15.64 (Ме). 31Р NMR
spectrum: δР 11.15 ppm. Found, %: С 11.58; Н 4.47.
С2Н9NО6P2. Calculated, %: С 11.71; Н 4.42.
Disodium salt of 1-amino-1-(pyrid-3-yl)methylene-
diphosphonous acid (Хd). Yield 94%. 1H NMR
spectrum, δ, ppm: 6.82 d (2РH, 1JPH 541.2 Hz), 7.2–8.5
m (С5Н4N). 13С NMR spectrum, δС, ppm: 151.59 (С2),
147.43 (С6), 146.30 (С5), 136.14 (С4), 135.90 (С3),
1-Aminobenzylidenediphosphonic acid (XIIc).
1
Yield 97%, mp 223°С. H NMR spectrum, δ, ppm:
6.8–7.6 m (С6Н5). 13С NMR spectrum, δС, ppm:
131.22 (С2), 126.20 (С4), 125.52 (С3), 124.27 (С5),
1
60.34 t (С1, JPС 75.9 Hz). 31Р NMR spectrum: δР
1
60.26 t (С1, JPС 120.5 Hz). 31Р NMR spectrum: δР
27.84 ppm. Found, %: С 25.59; Н 2.97. С6Н8N2Na2О4P2.
Calculated, %: С 25.73; Н 2.88.
8.54 ppm. Found, %: С 31.32; Н 4.19. С7Н11NО6P2.
Calculated, %: С 31.48; Н 4.15.
Disodium salt of N-anilinomethylenediphos-
1
phonous acid (XIa). Yield 95%. H NMR spectrum,
1-Amino-1-(3,5-di-tert-butyl-4-hydroxyphenyl)-
methylenediphosphonic acid (XIId). Yield 98%, mp
183–184°С. 1H NMR spectrum, δ, ppm: 1.30 s
(Ме3С), 5.29 br.s (ОН), 7.50 s (С6Н2). 13С NMR spec-
trum, δС, ppm: 151.09 (С5), 138.65 (С4), 126.89 (С2),
124.43 (С3), 62.84 t (С1, 1JPС 118.2 Hz), 34.35 (Ме3С),
30.08 (Ме3С). 31Р NMR spectrum: δР 11.06 ppm.
Found, %: С 45.43; Н 6.94. С15Н27NО7P2. Calculated,
%: С 45.57; Н 6.88.
2
3
δ, ppm: 3.64 t (С1H, JРН 16.0 Hz), 6.70 t (С1HPh, JHН
8.0 Hz), 6.77 d (2С1HPh, JHН 8.0 Hz), 7.04 d (2РН,
3
1JРН 532.0 Hz), 7.16 t (2СHPh, JНН 8.0 Hz). 13С NMR
3
spectrum, δС, ppm: 147.80 (С2); 129.52, 118.13 and
113.72 (СPh), 56.24 t (С1, JРС 85.7 Hz). 31Р NMR
1
spectrum: δР 20.10 ppm. Found, %: С 29.90; Н 3.26.
С7Н9NNa2О4P2. Calculated, %: С 30.13; Н 3.25.
Disodium salt of dimethylaminomethylenedi-
phosphonous acid (XIb). Yield 95%. 1H NMR
Methylaminomethylenediphosphonic acid (ХIIIa).
2
spectrum, δ, ppm: 2.59 t (С1H, JРН 15.2 Hz), 7.16 d
1
Yield 96%, mp 178°С. H NMR spectrum, δ, ppm:
(РН, 1JРН 563 Hz). 13С NMR spectrum, δС, ppm: 65.16
t (С1, 1JРС 70.2 Hz), 44.21 (С2). 31Р NMR spectrum: δР
9.78 ppm. Found, %: С 15.46; Н 3.98. С3Н9NNa2О4P2.
Calculated, %: С 15.59; Н 3.93.
2
2.50 s (С2Н3), 2.94 t (С1H, JPH 17.2 Hz). 13С NMR
1
spectrum, δС, ppm: 55.95 t (С1, JPС 117.4 Hz), 34.07
(С2). 31Р NMR spectrum: δР 7.78 ppm. Found, %: С
11.57; Н 4.51. С2Н9NО6P2. Calculated, %: С 11.71; Н
4.42.
Disodium salt of N-morpholinomethylenedi-
phosphonous acid (XIc). Yield 94%. 1H NMR
N-Anilinomethylenediphosphonic acid (ХIIIb).
2
spectrum, δ, ppm: 2.55 t (С1H, JРН 15.8 Hz), 7.09 d
1
Yield 97%, mp 182°С. H NMR spectrum, δ, ppm:
1
(РН, JРН 557.0 Hz). 13С NMR spectrum, δС, ppm:
2
3
4.20 t (С1H, JPH 22.0 Hz), 6.69 t (С5H, JНH 8.0 Hz),
6.81 d (2С3H, 3JНH 8.0 Hz), 7.15 t (2С4H, 3JНH 8.0 Hz).
13С NMR spectrum, δС, ppm: 147.03 (С2); 128.63,
1
64.98 t (С1, JРС 72.4 Hz), 52.83 (С2). 31Р NMR
spectrum: δР 12.05 ppm. Found, %: С 21.73; Н 4.11.
С5Н11NNa2О5P2. Calculated, %: С 21.99; Н 4.06.
117.75 and 113.41 (С3, С4, С5), 50.95 t (С1, JPС
1
142 Hz). 31Р NMR spectrum: δР 16.99 ppm. Found, %:
С 31.37; Н 4.19. С7Н11NО6P2. Calculated, %: С 31.48;
Н 4.15.
Aminomethylenediphosphonic acid (XIIа). Di-
phosphonate IVa (7.7 g) was added upon stirring at
10°С to 30 mL of methanol. The mixture was heated to
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015

SYNTHESIS OF NEW TYPES OF AMINOMETHYLENEDIPHOSPHORUS-CONTAINING ACIDS
REFERENCES
379
Dimethylaminomethylenediphosphonic
acid
1
(ХIIIc). Yield 97%, mp 212°С. H NMR spectrum, δ,
2
ppm: 2.57 s (2С2Н3), 3.05 t (С1H, JPH 18.4 Hz). 13С
1. Kukhar, V.P. and Hudson, H.R., Aminophosphonic and
Aminophosphinic Acids. Chemistry and Biological
Activity, New York: Wiley, 2000.
1
NMR spectrum, δС, ppm: 62.24 t (С1, JPС 115.8 Hz),
43.67 (С2). 31Р NMR spectrum: δР 6.29 ppm. Found,
%: С 16.23; Н 4.92. С3Н11NО6P2. Calculated, %: С
16.45; Н 5.06.
2. Ebetino, F.H., Phosphorus, Sulfur, Silicon, Relat. Elem.,
1999, vols. 144–146, p. 9. DOI: 10.1080/
10426509908546169.
3. Grigoriev, E.V., Yashina, N.S., Prishchenko, А.А.,
Livantsov, M.V., Petrosyan, V.S., Pellerito, L., and
Schafer, M.J., Appl. Organometal. Chem., 1993, vol. 7,
p. 353. DOI: 10.1002/aoc.590070509.
4. Krasovskaya, S.M., Uzhinova, L.D., Andrianova, M.Y.,
Prishchenko, А.А., and Livantsov M.V., Biomaterials,
1991, vol. 12, p. 817. DOI: 10.1016/0142-9612(91)
90067-K.
N-Morpholinomethylenediphosphonic acid (ХIIId).
1
Yield 96%, mp 202°С. H NMR spectrum, δ, ppm:
2
2.54 s (2С2H2), 3.08 t (С1H, JРH 17.6 Hz), 3.2–3.3 m
(2С3H2). 13С NMR spectrum, δС, ppm: 62.99 t (С1, 1JPС
31
111.0 Hz), 64.07 (С3), 51.74 (С2). Р NMR spectrum:
δР 6.22 ppm. Found, %: С 22.83; Н 4.92. С5Н13NО7P2.
Calculated, %: С 23.00; Н 5.02.
5. RU Patent no. RU 2405032, 2010, Bull. Izobret., 2010,
no. 33; RU Patent no. 2457240, 2012, Bull. Izobret.,
2012, no. 21.
N-Prolinomethylenediphosphonic acid (ХIIIe).
Yield 95%, mp 187°С. The first isomer, content 55%.
1H NMR spectrum, δ, ppm: 2.0–2.5 m (С4H2, С5H2),
6. Prishchenko, А.А., Livantsov, M.V., and Petrosyan, V.S.,
Zh. Obshch. Khim., 1994, vol. 64, no. 8, p. 1316.
7. Prishchenko, A.A., Livantsov, M.V., Novikova, O.P.,
and Livantsova, L.I., Russ. J. Gen. Chem., 2009, vol. 79,
no. 9, p. 1936. DOI: 10.1134/s1070363209090230.
8. Li, J.J., Name Reactions: A Collection of Detailed
Mechanisms and Synthetic Applications, Berlin:
Springer, 2009.
2
3.95–4.05 m (С3H2), 4.29 t (С1H, JРH 20.0 Hz), 5.1–
5.2 m (С2H). 13С NMR spectrum, δС, ppm: 170.20
3
1
(С6), 67.54 t (С2, JPС 5.6 Hz), 58.31 t (С1, JPС
127.7 Hz), 54.09 (С3), 28.06 (С5), 22.84 (С4). 31Р
NMR spectrum: δР 7.04 ppm. The second isomer,
1
9. Dilman, A.D. and Ioffe, S.L., Chem. Rev., 2003, vol. 103,
p. 733. DOI: 10.1021/cr020003.
content 45%. H NMR spectrum, δ, ppm: 2.0–2.5 m
(С4H2, С5H2), 4.1–4.2 m (С3H2), 4.32 t (С1H, JРH
2
10. Wozniak, L. and Chojnowski, J., Tetrahedron, 1989,
vol. 45, p. 2465. DOI: 10.1016/S0040-4020(01)80083-1;
Romanenko, V.D., Shevchuk, M.V., and Kukhar, V.P.,
Curr. Org. Chem., 2011, vol. 15, p. 2774. DOI:
10.2174/138527211796378505.
11. Kolodyazhnaya, O.O. and Kolodyazhnyi, O.I., Russ. J.
Gen. Chem., 2011, vol. 81, no. 1, p. 145. DOI: 10.1134/
S1070363211010245.
12. Gross, H., Costisella, B., Gnauk, T., and Brennecke, L.,
J. Pr. Chem., 1976, vol. 318, p. 116; Gross, H.,
Medved’, T.Ya., Costisella, B., Bel’skii, F.I., and
Kabachnik, M.I., Zh. Obshch. Khim., 1978, vol. 48,
no. 9, p. 1914.
20 Hz), 5.1–5.2 m (С2H). 13С NMR spectrum, δС, ppm:
168.97 (С6), 67.21 t (С2, 3JPС 5.4 Hz), 58.39 t (С1, 1JPС
128.5 Hz), 54.21 (С3), 27.78 (С5), 22.64 (С4). 31Р
NMR spectrum: δР 7.89 ppm. Found, %: С 24.69; Н
4.42. С6Н13NО8P2. Calculated, %: С 24.93; Н 4.53.
ACKNOWLEDGMENTS
This work was financially supported by Russian
Foundation for Basic Research (project nos. 14-03-
00001 and 15-03-00002).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015