Synthesis of substituted N-formylaminomethylenediphosphonates and their derivatives

Article abstract of DOI:10.1002/hc.21274

The convenient methods for the synthesis of new trimethylsilyl esters of aminomethylenediphosphonic acids are elaborated. The new substituted N-formylaminomethylenediphosphonates are obtained via the interaction of trimethylsilyl esters of methylenediphosphonic acids with a mixture of triethyl orthoformate and ethanol. Also boron trifluoride-diethyl etherate as an effective catalyst is used for the interaction of hydrochlorides of ethoxymethylene imines with diethyl trimethylsilyl phosphite. The corresponding aminomethylenediphosphonic acids are presented.

Full text of DOI:10.1002/hc.21274

Heteroatom Chemistry
Volume 26, Number 6, 2015
Synthesis of Substituted
N-Formylaminomethylenediphosphonates
and Their Derivatives
Andrey A. Prishchenko, Mikhail V. Livantsov, Olga P. Novikova,
Ludmila I. Livantsova, Gleb M. Averochkin, and Valery S. Petrosyan
Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow 119991, Russia
Received 15 April 2015; revised 21 May 2015; accepted 24 May 2015
these diphosphonic acids are good complexones
ABSTRACT: The convenient methods for the syn-
and widely used in medicine [2]; also some of
thesis of new trimethylsilyl esters of aminomethy-
these compounds are used by us as successful
lenediphosphonic acids are elaborated. The new
antioxidants and cytoprotectors with multifunctio-
substituted N-formylaminomethylenediphosphonates
nal mode of action [3]. Recently, some of the
are obtained via the interaction of trimethylsilyl
substituted aminomethylenediphosponic acids and
esters of methylenediphosphonic acids with a mixture
their derivatives have been synthesized by us using
of triethyl orthoformate and ethanol. Also boron
various formamides and substituted ethoxymethy-
trifluoride–diethyl etherate as an effective catalyst is
lene imines [4]; also we have obtained some
used for the interaction of hydrochlorides of ethoxy-
functionalized N-formylaminomethylphosphonates
methylene imines with diethyl trimethylsilyl
as perspective bidentate ligands [5]. In this con-
phosphite. The corresponding aminomethylenedi-
tribution, we develop a convenient organosilicon-
ꢀC
phosphonic acids are presented.
2015 Wiley Peri-
based method for the synthesis of substituted
N-formylaminomethylenediphosphonates using
specially prepared tetra(trimethylsilyl) aminometh-
ylenediphosphonates and their derivatives.
odicals, Inc. Heteroatom Chem. 26:405–410, 2015;
View this article online at wileyonlinelibrary.com.
DOI 10.1002/hc.21274
RESULTS AND DISCUSSION
INTRODUCTION
We found that tetra(trimethylsilyl) aminome-
thylenediphosphonates 1,2 are obtained in high
yields directly from the reaction mixtures of phos-
phorous acid, phosphorus trichloride, and for-
mamide or carboxylic acids nitriles (cf [6]).
So, N-formylaminomethylenediphosphonate 1
was obtained in high yield by subsequent treatment
of corresponding mixture with an excess of water
and bis(trimethylsilyl)amine (Scheme 1).
The functionalized methylenediphosponic acids and
their derivatives are the perspective organophos-
phorus biomimetics of natural pyrophosphates
and hydroxy or amino acids; also these substances
are widely used as effective polydentate ligands
and promising bioactive compounds with the
multifactor activity [1]. So various derivatives of
The substituted aminomethylenediphospho-
nates 2 were similarly synthesized in high yields via
carboxylic acids nitriles (Scheme 2).
Obviously, the both reactions proceed un-
der mild conditions due to activation of starting
Correspondence to: Andrey A. Prishchenko; e-mail:
aprishchenko@yandex.ru.
Contract grant sponsor: Russian Foundation for Basic
Research.
Contract grant numbers: 14-03-00001 and 15-03-00002.
2015 Wiley Periodicals, Inc.
ꢀC
405

406 Prishchenko et al.
0C; 2. H
1. H3PO , PCl3 , 5-80
2O, 800C; 3. (Me Si) NH, 1200
C
3
3
2
[(Me3SiO)
HC(O)NH
2P] 2CHNHCHO
2
O
1
SCHEME 1 Synthesis of diphosphonate 1.
1. H3PO3, PCl3, 5-800C; 2. H2O, 800C;3. (Me3Si)2NH, 1200C
[(Me3SiO)2P]2C(R)NH2
O
RC
N
2a-c
R = Me (2a), Ph (2b),
(2c).
N
SCHEME 2 Synthesis of diphosphonates 2a–c.
HC(Cl)=NH HCl
H3PO3, PCl3
2 (HO)3P
- 2 HCl
[(HO)2P]2CHNH2
HC=NH HCl
2
HC(O)NH
- HCl
O
Cl
B
A
1. H2O, 2. (Me3Si)2NH
[(HO)2P]2CHNHCH=NH HCl
O
1
- NH4Cl
(Me3Si)2NH
- NH4Cl
H3PO3, PCl3
2 (HO)3P
[(HO)2P]2CNH2
O R
RC=NH HCl
RC
N
2 a-c
- 2 HCl
Cl
C
R = Me, Ph,
N
SCHEME 3 The possible routes of the formation of diphosphonates 1,2.
4 MeOH, 10-500C
- 4 Me3SiOMe
formamide or nitriles with a mixture of phospho-
rous acid and phosphorus trichloride via formation
of highly reactive immonium salts A, C (Scheme
3), which was consistent with the known data
(cf [4c, 6]).
It should be noted that the formation of N-
formylaminomethylenediphosphonate 1 was fol-
lowed by the formylation of intermediate B contain-
ing the unsubstituted amino group. The treatment
of diphosphonate 1,2 with methanol excess results
in formation of water-soluble corresponding diphos-
[(HO)2P]2CHNHCHO
1
O
3
10-500C
4 MeOH,
2a,b
[(HO)2P]2C(R)NH2
O
- 4 Me3SiOMe
4a-c
R = Me (a), Ph (b),
(c).
N
SCHEME 4 Synthesis of acids 3,4.
phonic acids 3,4 as white hygroscopic crystals in
high yields (Scheme 4).
Some similar aminomethylenediphosphonic
acids have been described previously as their crys-
tal hydrates; these acids were obtained in poor
yields (cf [6a,c]). Also diphosphonates 1,2 were
smoothly transformed into N-formylaminomethy-
lenediphosphonate 5 in high yields by treatment
with an excess of triethyl orthoformate and ethanol
(Scheme 5).
unsubstituted amino group is synthesized by us
via the interaction of substituted hydrochlorides
of ethoxymethylene imines D with an excess di-
ethyl trimethylsilyl phosphite and diethyl phosphite
in methylene chloride at the presence of boron
trifluoride–diethyl etherate as a catalyst (Scheme 6)
(cf [4c, 8]).
Evidently, the formation of diphosphonates
5 is a result of two or three parallel reactions
of ethanolysis, esterification, and formylation of
diphosphonates 1,2 (cf [7]). Nevertheless, hardly
available aminomethylenediphosphonate 6 with the
Evidently, the catalytic effect of boron
trifluoride–diethyl etherate is based on activation
of the C=N groups via generation of electrophilic
intermediates E in the course of this reaction
(Scheme 7) (cf [4c]).
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Substituted N-Formylaminomethylenediphosphonates and Their Derivatives 407
HC(OEt)3, EtOH, CH2Cl2, 10-1200C
[(EtO)2P]2CHNHCHO
[(Me3SiO)2P]2CHNHCHO
- Me3SiOEt, - HCOOEt
O
O
5a
1
HC(OEt)3, EtOH, CH2Cl2, 10-1200C
- Me3SiOEt, - HCOOEt
[(EtO)2P]2C(R)NHCHO
[(Me3SiO)2P]2C(R)NH2
O
O
2a,b
5b,c
R = Me (5b), Ph (5c).
SCHEME 5 Synthesis of N-formyl diphosphonates 5a–c.
1. 2 (EtO)2POSiMe3, (EtO)2P(O)H, BF3 Et2O, CH2Cl2, 200C; 2. (Me3Si)2NH, 1200C
- Me3SiCl, - Me3SiOEt
[(EtO)2P]2C(R)NH2
EtOC(R)=NH HCl
O
D
6a,b
R = Me (6a), Ph (6b).
SCHEME 6 Synthesis of diphosphonates 6a,b.
BF3 Et2O
[EtOC(R)NH2]+[BF3Cl]-
[EtOC(R)NH2]+Cl-
EtOC(R)=NH HCl
Et2O
-
D
E
2 (EtO)2POSiMe3, (EtO)2P(O)H
- Me3SiCl, - Me3SiOEt, - BF3
6a,b
SCHEME 7 Catalytic activation of imines D.
FIGURE 1 The moieties F of compounds 1–6.
The structures of obtained diphosphonates and
synthons for the preparation of various functional-
ized aminomethylenebisphosphorus containing sub-
stances. Also, these compounds are perspective poly-
dentate ligands and biologically active substances
with versatile properties.
1
their derivatives 1–6 are confirmed by H, 13C, and
31P NMR spectra. The NMR spectra of compounds
1–6 contain the characteristic signals of the F moi-
eties (Fig. 1) whose parameters are listed in the
Experimental.
According to NMR data, the compounds 1,3,5
containing N-methylformamide moieties were ob-
tained as two stereoisomers mixtures; their compo-
sitions were determined by 31P NMR.
EXPERIMENTAL
1
The H, 13C, and 31P NMR spectra were registered
on a Bruker Avance-400 spectrometer (400, 100, and
162 MHz, respectively) against TMS (1H and 13C)
and 85% H3PO4 in D2O (31P). All reactions were car-
ried out under dry argon in anhydrous solvents. The
starting trimethylsilyl esters of trivalent phosphorus
acids were prepared as described in [9], and the start-
ing hydrochlorides of ethoxymethylene imines were
discussed in [6b].
CONCLUSIONS
So the convenient synthetic routes to N-formyl-
substituted or N-unsubstituted aminomethylenedip-
hosphonates and their derivatives starting from
available reagents were developed by us. The
resulting compounds 1–6 are the promising
Heteroatom Chemistry DOI 10.1002/hc

408 Prishchenko et al.
1
O,O,O,O-Tetra(trimethylsilyl) N-formylaminome-
thylenediphosphonate (1). Phosphorus trichloride
(124.0 g, 903.0 mmol) was added to a mixture of
formamide (27.0 g, 600.0 mmol) and phosphorous
acid (50.0 g, 609.8 mmol) under stirring at 10°С. The
mixture was stirred for 1 h, then the mixture was
kept at 20°С during 24 h and was heated at 80°С for
1 h. Water (400 mL) was added to a mixture, which
was heated at 80°С for 1 h. Water was removed in
a vacuum of 7 mmHg, and bis(trimethylsilyl)amine
(320 mL) was added to the residue. The mixture
was refluxed to complete sublimation of ammonium
chloride and was distilled to give 112.6 g of diphos-
phonate 1, yield 74%, bp 142°С (0.5 mmHg). The first
(1 mmHg). H NMR (CDCl3, 400 MHz), δ, ppm: –
4
0.21 d (2 Ме3Si, JРH 2.8 Hz), − 0.18 d (2 Ме3Si,
4JРH 2.8 Hz), 1.74 t (NH2, JРH 13.2 Hz), 6.8–7.6 m
3
(С6Н5). 13C NMR (CDCl3, 100 MHz), δ, ppm: 59.74
t (С1, JPС 147.9 Hz), 135.82 br. s (С2), 127.21 s and
1
127.29 s (С3, С4), 126.85 s (С5), 0.49 s (2 Me3Si), 0.58
s (2 Me3Si). 31P NMR (CDCl3, 162 MHz), δ, ppm:
2.26 s.
O,O,O,O-Tetra(trimethylsilyl 1-amino-1-(pyrid-3-
yl)methylenediphosphonate (2c). Yield 85%, bp 152°С
1
(0.5 mmHg). H NMR (CDCl3, 400 MHz), δ, ppm: –
0.17 s (2 Me3Si), – 0.14 s (2 Me3Si), 1.83 t (NH2,
3JРH 14.0 Hz), 6.94 d d (С4H, JНH 4.8 Hz and 8.0
3
Hz), 7.88 d (С3H, 3JНH 8 Hz), 8.19 d (С5H, 3JНH 4.8
Hz), 8.71 s (С6H). 13C NMR (CDCl3, 100 MHz), δ,
ppm: 0.13 s (2 Me3Si), 0.17 s (2 Me3Si), 58.04 t (С1,
1
isomer, content 55%. H NMR (CDCl3, 400 MHz),
δ, ppm: – 0.09 to –0.07 m (4 Ме3Si), 2.71 t (С1Н,
2JРH 22.8 Hz), 7.28 br s (СНО). 13C NMR (CDCl3,
100 MHz), δ, ppm: 50.61 t (С1, 1JPС 154.1 Hz), 156.08
1JPС 147.3 Hz), 151.26 s (С2), 131.94 t (С3, JPС 4.4
3
Hz), 134.62 s (С4), 147.52 s (С5), 148.14 t (С6, 3JPС 4.8
Hz). 31P NMR (CDCl3, 162 MHz), δ, ppm: 1.62 s.
Anal. calcd for С18Н42N2О6P2Si4 С 38.83; Н 7.60.
Found: С 38.68; Н 7.52.
3
t (СНО, JPС 13.5 Hz), 0.78 s (2 Me3Si), 0.81 s (2
Me3Si). 31P NMR (CDCl3, 162 MHz), δ, ppm: 3.37 s.
1
The second isomer, content 45%, H NMR (CDCl3,
400 MHz), δ, ppm: to 0.09 to –0.07 m (4 Ме3Si), 2.74
N-Formylaminomethylenediphosphonic acid (3).
A solution of diphosphonate 1 (9.9 g, 19.5 mmol)
in ether (15 mL) was added with the stirring to
methanol (40 mL) cooled to 10°С. The mixture was
heated to boiling. The solvent was removed, and
white crystals were kept in a vacuum (1 mmHg)
for 1 h to give 4.3 g of acid 3, yield 97%, mp
159°С (with decomposition). The first isomer, con-
tent 85%. 1H NMR (CDCl3, 400 MHz), δ, ppm: 2.83 t
(С1Н, 2JPН 17.4 Hz), 7.14 s (СНО). 13C NMR (CDCl3,
2
t (С1Н, JРH 22.4 Hz), 7.28 br s (СНО). 13C NMR
1
(CDCl3, 100 MHz), δ, ppm: 49.64 t (С1, JPС 150.1
Hz), 155.94 br s (СНО), 0.65 s (2 Me3Si), 0.67 s (2
Me3Si). 31P NMR (CDCl3, 162 MHz), δ, ppm: 2.60
s. Anal. calcd for С14Н39NО7P2Si4 С 33.12; Н 7.74.
Found: С 32.94; Н 7.68.
O,O,O,O-Tetra(trimethylsilyl) 1-aminoethylidene-
diphosphonate (2a). Phosphorus trichloride (42.0 g,
305.8 mmol) was added dropwise to a mixture of
acetonitrile (6.2 g, 151.0 mmol) and phosphorous
acid (39.0 g, 475.6 mmol), and methylene chloride (5
mL) under stirring at 5°С. The mixture was stirred
for 3 h and was kept at 20°С for 24 h, then was
heated at 80°С for 2 h. Water (300 mL) was added
to a mixture, which was heated at 80°С for 1 h. Wa-
ter was evaporated in a vacuum of 7 mmHg, and
bis(trimethylsilyl)amine (300 mL) was added to the
residue. The mixture was refluxed to complete sub-
limation of ammonium chloride and was distilled
to obtain 59.7 g of diphosphonate 2a, yield 80%,
bp 144°С (2 mmHg). 1H NMR (CDCl3, 400 MHz),
100 MHz), δ, ppm: 47.40 т (С1, JPС 123.7 Hz),
1
153.45 s (СНО). 31P NMR (CDCl3, 162 MHz), δ, ppm:
1
8.58 s. The second isomer, content 15%. H NMR
(CDCl3, 400 MHz), δ, ppm: 3.56 t (С1Н, JPН 18.8
2
Hz), 7.17 s (СНО). 13C NMR (CDCl3, 100 MHz), δ,
ppm: 51.04 t (С1, JPС 125.3 Hz), 157.19 s (СНО).
1
31P NMR (CDCl3, 162 MHz), δ, ppm: 9.50 s. Anal.
calcd for С2Н7NО7P2 С 10.97; Н 3.22. Found: С 10.85;
Н 3.26.
Acids 4a–c were prepared similarly. The con-
stants of acids 4a,b are consistent with the known
data (cf [4c]).
4
δ, ppm: – 0.03 d (2 Ме3Si, JРH 2 Hz), – 0.04 d
1-Aminoethylidenediphosphonic acid (4a). Yield
4
3
(2 Ме3Si, JРH 1.6 Hz), 1.04 t (С2Н3, JРH 16.4 Hz),
98%, mp 250°С. 1H NMR (D2O and C5D5N, 400
1.20 t (NH2, JРH 12.6 Hz). 13C NMR (CDCl3, 100
3
MHz), δ, ppm: 1.15 t (С2H3, JPH 13.3 Hz). 13C
3
MHz), δ, ppm: 51.64 t (С1, JPС 152.4 Hz), 20.10 s
1
NMR (D2O and C5D5N, 100 MHz), δ, ppm: 51.74 t
(С1, 1JPС 122.7 Hz), 15.69 s (С2). 31P NMR (D2O and
C5D5N, 162 MHz), δ, ppm: 10.95 s.
(С2), 0.79 s (2 Me3Si), 0.84 s (2 Me3Si). 31P NMR
(CDCl3, 162 MHz), δ, ppm: 6.68 s.
Diphosphonates 2b,c were prepared similarly.
The constants of diphosphonates 2a,b are consistent
with the known data (cf [4c]).
1-Aminobenzylidenediphosphonic acid (4b).
Yield 96%, mp 225°С. 1H NMR (D2O and C5D5N,
400 MHz), δ, ppm: 6.8–7.6 m (С6Н5). 13C NMR
(D2O and C5D5N, 100 MHz), δ, ppm: 60.48 t (С1,
1JPС 121.2 Hz), 131.26 s (С2), 125.58 s (С3), 126.23
O,O,O,O-Tetra(trimethylsilyl) 1-aminobenzylide-
nediphosphonate (2b). Yield 82%, bp 149°С
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Substituted N-Formylaminomethylenediphosphonates and Their Derivatives 409
s (С4), 124.30 s (С5). 31P NMR (D2O and C5D5N,
162 MHz), δ, ppm: 8.59 s.
(СН3), 17.20 s (С2), 53.46 t (С1, 1JPC 147.6 Hz), 62.95
s (СН2) and 63.19 s (СН2), 163.98 br. s (СНО). 31P
NMR (CDCl3, 162 MHz), δ, ppm: 18.86 s. Anal. calcd
for С11Н25NО7P2 С 38.26; Н 7.30. Found: С 38.12; Н
7.23.
1-Amino-1-(pyrid-3-yl)methylenediphosphonic
acid (4c). Yield 95%, mp 191°С (with decomposi-
tion). 1H NMR (D2O and C5D5N, 400 MHz), δ, ppm:
7.0–8.1 m (С6Н4N). 13C NMR (D2O and C5D5N,
O,O,O,O-Tetraethyl N-formyl-1-aminobenzylide-
1
°
100 MHz), δ, ppm: 60.83 t (С1, JPС 114.2 Hz),
nediphosphonate (5c). Yield 84%, bp 198 С (2 mm
151.31 s (С2), 133.89 s (С3), 137.96 s (С4), 145.19 s
(С5), 147.21 s (С6). 31P NMR (D2O and C5D5N, 162
MHz), δ, ppm: 10.94 s. Anal. calcd for С6Н10N2О6P2
С 26.88; Н 3.76. Found: С 26.74; Н 3.80.
Hg). The first isomer, content 80%. 1H NMR (CDCl3,
400 MHz), δ, ppm: 0.5 – 0.6 m (4 СН3), 3.3 – 3.6 m
(4 СН2), 6.6 – 7.5 m (С6Н5), 7.86 s (СНО). 13C NMR
3
(CDCl3, 100 MHz), δ, ppm: 15.16 d (СН3, JPC 3.0
O,O,O,O-Tetraethyl N-formylaminomethylenedi-
phosphonate (5a). Triethyl orthoformate (60.0 g,
404.9 mmol) was added to a solution of diphospho-
nate 1 (14.0 g, 27.6 mmol) in methylene chloride
(20 mL) under stirring at 10°С; then ethanol (20.0
g, 434.1 mmol) was added dropwise to the mixture
at the same conditions. The solvent and by-products
were removed from a mixture via distillation of mix-
ture until the beginning of triethyl orthoformate dis-
tillation. The excess of triethyl orthoformate was re-
moved in vacuum of 7 mmHg, and the residue was
distilled to obtain 7.6 g of diphosphonate 5a, yield
83%, bp 182°С (2 mmHg). The first isomer, content
60%. 1H NMR (CDCl3, 400 MHz), δ, ppm: 0.75–0.86
Hz) and 15.14 d (СН3, 3JPC 2.5 Hz), 62.48 s (СН2) and
1
62.68 s (СН2), 65.45 t (С1, JPC 132.2 Hz), 135.00 t
2
3
(С2, JPC 4.7 Hz), 127.95 t (С3, JPC 4.0 Hz), 126.31
s (С4), 127.29 s (С5), 158.80 t (СНО, 3JPC 7.7 Гц). 31
P
NMR (CDCl3, 162 MHz), δ, ppm: 15.83 s. The second
isomer, content 20%. 1H NMR (CDCl3, 400 MHz), δ,
ppm: 0.5–0.6 m (4 СН3), 3.3–3.6 m (4 СН2), 6.6–7.5 m
(С6Н5), 7.76 s (СНО). 13C NMR (CDCl3, 100 MHz), δ,
ppm: 14.95 s (СН3) and 14.99 s (СН3), 62.40 s (СН2)
and 62.75 s (СН2), 62.33 t (С1, 1JPC 131.8 Hz), 135.00
t (С2, 2JPC 4.7 Hz), 127.95 t (С3, 3JPC 4.0 Hz), 126.31
s (С4), 127.29 s (С5), 164.69 br s (СНО). 31P NMR
(CDCl3, 162 MHz), δ, ppm: 15.23 s. Anal. calcd for
С16Н27NО7P2 С 47.18; Н 6.68. Found: С 47.03; Н 6.59.
O,O,O,O-Tetraethyl 1-aminoethylidenediphosph-
onate (6a). Boron trifluoride–diethyl etherate
(1.2 g, 7.9 mmol) was added with the stirring to a
mixture of diethyl phosphite (15.0 g, 108.6 mmol),
diethyl trimethylsilyl phosphite (25.0 g, 118.9
mmol), and hydrochloride of 1-ethoxyethylidene
imine (11.7 g, 94.7 mmol) in methylene chloride
(35 mL). The mixture was refluxed for 1 h, the
solvent was removed, and bis(trimethylsilyl)amine
(40 mL) was added. The mixture was refluxed to
complete ammonium chloride sublimation. The ex-
cess of bis(trimethylsilyl)amine was removed, and
the residue was distilled to obtain 12.7 г diphospho-
2
m (4 СН3), 3.6–3.7 m (4 СН2), 4.53 t (С1Н, JPH 22.0
Hz), 7.79 s (СНО). 13C NMR (CDCl3, 100 MHz), δ,
ppm: 15.77 s (СН3), 57.88 t (С1, 1JPC 150.9 Hz), 62.54
3
с (СН2) and 62.84 s (СН2), 160.31 t (СНО, JPC 14.4
Hz). 31P NMR (CDCl3, 162 MHz), δ, ppm: 16.32 s.
1
The second isomer, content 40%, H NMR (CDCl3,
400 MHz), δ, ppm: 0.75–0.86 m (4 СН3), 3.6–3.7 m
2
(4 СН2), 4.51 t (С1Н, JPH 22.0 Hz), 7.26 (СНО). 13C
NMR (CDCl3, 100 MHz), δ, ppm: 15.68 s (СН3), 41.43
t (С1, 1JPC 146.1 Hz), 62.45 s (СН2) and 62.71 s (СН2),
160.79 br s (СНО). 31P NMR (CDCl3, 162 MHz), δ,
ppm: 15.57 s. Anal. calcd for С10Н23NО7P2 С 36.26.
Н 7.00. Found: С 36.03; Н 6.94.
1
nate 6a. Yield 42%, bp 128°С (1 mmHg). H NMR
3
(CDCl3, 400 MHz), δ, ppm: 0.75 t (4 СН3, JHH 7.6
3
3
Hz), 0.92 t (С2Н3, JPH 16.4 Hz), 1.13 t (NH2, JPH
12.4 Hz), 3.5–3.6 m (4 СН2). 13C NMR (CDCl3, 100
MHz), δ, ppm: 15.87 с (СН3), 19.30 br s (С2), 52.31 t
(С1, 1JPC 144.5 Hz), 62.38 s (СН2) and 62.59 s (СН2).
31P NMR (CDCl3, 162 MHz), δ, ppm: 22.96 s. Anal.
calcd for С10Н25NО6P2 С 37.86; Н 7.94. Found: С
37.55; Н 7.87.
Diphosphonates 5b,C Were Prepared Similarly
O,O,O,O-Tetraethyl N-formyl-1-aminoethylidenediph-
osphonate (5b). Yield 80%, bp 139°С (0.3 mmHg).
The first isomer, content 85%. 1H NMR (CDCl3,
400 MHz), δ, ppm: 0.67–0.72 m (4 СН3), 3.5–3.6 m
3
(4 СН2), 1.04 t (С2Н3, JPH 15.6 Hz), 7.18 t (СНО,
4JPH 2.8 Hz). 13C NMR (CDCl3, 100 MHz), δ, ppm:
1
15.75 s (СН3), 17.76 s (С2), 59.90 t (С1, JPC 149.3
Hz), 62.43 s (СН2) and 62.63 s (СН2), 157.31 t (СНО,
Diphosphonate 6b Was Prepared Similarly
3JPC 12.0 Hz). 31P NMR (CDCl3, 162 MHz), δ, ppm:
1
19.74 s. The second isomer, content 15%. H NMR
O,O,O,O-Tetraethyl 1-aminobenzylidenediphospho-
1
(CDCl3, 400 MHz), δ, ppm: 0.67 – 0.72 m (4 СН3), 3.5
nate (6b). Yield 34%, bp 165°С (1 mmHg). H NMR
3
3
– 3.6 m (4 СН2), 1.10 t (С2Н3, JPH 15.6 Hz), 7.03 s
(CDCl3, 400 MHz), δ, ppm: 0.77 t (2 СН3, JHH 7.2
(СНО). 13C NMR (CDCl3, 100 MHz), δ, ppm: 15.56 s
Hz) and 0.92 t (2 СН3, JHH 7.2 Hz), 1.99 t (NH2,
3
Heteroatom Chemistry DOI 10.1002/hc

410 Prishchenko et al.
3JPH 12.8 Hz), 3.5–3.7 m (4 СН2), 6.9–7.6 m (С6Н5).
13C NMR (CDCl3, 100 MHz), δ, ppm: 15.85 s (2СН3)
(c) Prishchenko, A. A.; Livantsov, M. V.; Novikova,
O. P.; Livantsova, L. I.; Petrosyan, V. S. Heteroatom
Chem 2012, 23, 32–40; (d) Berberova, N. T.; Osipova,
V. P.; Kolyada, M. N.; Antonova, N. A.; Zefirov, N. S.;
Milaeva, E. R.; Filimonova, S. I.; Gracheva, Yu. A.; Pr-
ishchenko, A. A.; Livantsov, M. V.; Livantsova L. I.;
Novikova, O. P. Patent RU 2405032 C 1, Rus Patent
Bull 2010, 33 (in Russian); (e) Berberova, N. T.; Cher-
nushkina, I. M.; Osipova, V. P.; Kolyada, M. N.; Pi-
menov, Yu. I.; Gracheva, Yu. A.; Prishchenko, A. A.;
Livantsov, M. V.; Livantsova, L. I.; Novikova, O. P.;
Milaeva, E. R.; Zefirov, N. S. Patent RU 2457240 C 2,
Rus Patent Bull 2012, 21 (in Russian).
1
and 15.99 s (2СН3), 60.05 t (С1, JPC 139.7 Hz),
63.19 s (2 СН2) and 63.49 s (2 СН2), 133.80 br s (С2),
3
127.18 t (С3, JPС 4.8 Hz), 127.35 s (С4), 128.15 s
(С5). 31P NMR (CDCl3, 162 MHz), δ, ppm: 18.97 s.
Anal. calcd for С15Н27NО6P2 С 47.50; Н 7.17. Found:
С 47.26; Н 7.02.
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