Synthesis of phosphorus-substituted dialkylamides of organophosphorus acids, containing PCH2NP fragments

Article abstract of DOI:10.1007/s11176-005-0003-x

Reactions of [N-(trimethylsilyl)aminomethyl]phosphonates with organophosphorus acid chlorides was studied, which allowed to develop convenient synthetic approaches to novel phosphorus-substrituted dialkylamides of organophosphorus acids, including a PCH₂NP fragment. Certain properties of the resulting compounds are presented. 2004 MAIK "Nauka/Interperiodica".

Full text of DOI:10.1007/s11176-005-0003-x

Russian Journal of General Chemistry, Vol. 74, No. 9, 2004, pp. 1317 1320. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 9, 2004,
pp. 1422 1425.
Original Russian Text Copyright
2004 by Prishchenko, Livantsov, Novikova, Livantsova, Koval’, Grigor’ev.
Synthesis of Phosphorus-substituted Dialkylamides
of Organophosphorus Acids, Containing PCH2NP Fragments
A. A. Prishchenko, M. V. Livantsov, O. N. Novikova,
L. I. Livantsova, Ya. N. Koval’, and E. V. Grigor’ev
Lomonosov Moscow State University, Moscow, Russia
Received December 3, 2002
Abstract Reactions of [N-(trimethylsilyl)aminomethyl]phosphonates with organophosphorus acid chlorides
was studied, which allowed to develop convenient synthetic approaches to novel phosphorus-substrituted
dialkylamides of organophosphorus acids, including a PCH2NP fragment. Certain properties of the resulting
compounds are presented.
Organophosphorus acid amides of various structure
are widely used in organic synthesis as highly reactive
2A
MePCl2
O
MeP NCH2P(OEt)2
2Me3SiCl
synthons [1] and ligands in a series of catalytic
systems. They are also of interest as biologically
active compounds [3]. In the present work we have
developed convenient methods for preparing novel
organophosphorus acid amides containing PCH2NP
fragments. It was previously shown that easily
available N-(trimethylsilyl)aminomethylphosphonates
(A) [4] are convenient synthons for preparing promis-
ing phosphorus-containing carboxamides and sul-
fonamides containing PCH2NC(O) and PCH2NSO2
fragments [5]. We found that the reaction of phos-
phonates A with chlorides of three- and four-co-
ordinate organophosphorus acids in methylene chlo-
ride leads to phosphorus-substituted amides I VI in
high yields.
Me
O
O
2
VII
tion with phosphonates A could only be effected on
heating at 130 C in the presence of a catalyst, zinc
chloride. As a result, amides IIa and IIb were ob-
tained in high yields.
A + (EtO)2POP(OEt)2
(EtO)2PCH2NP(OEt)2,
(EtO)2POSiMe3
R
O
IIa, IIb
R = Me (a), Et (b).
P Cl
The reaction of tetraethyl pyrophosphite with
symmetrical hexahydrotriazines B under similar con-
ditions leads to amides IIa and IIb in high yields.
Along with these products, bis(phosphonomethyl)-
amines VIII were isolated in low yields (10 15%),
and the 31P NMR spectra of low-boiling fractions
displayed signals of amides IX.
(EtO)2PCH2NSiMe3
(EtO)2PCH2N P ,
Me3SiCl
R
O
R
O
I VI
A
O
O
P
O
P =Cl2P (Ia, Ib), (EtO)2P (IIa, IIb),
(IIc),
P
O
(IId), Et2P (III), Bu2P (IV), (EtO)2P(O) (V), Bu2P(O)
(VI); R = Me (Ia, IIa, IV VI), Et (Ib, IIb IId, III).
NR
RN
3(EtO)2POP(OEt)2 +
N
Phosphorus-substituted methylphosphonic diamide
VII was prepared by the reaction of an excess of
phosphonate A with methylphosphonic dichloride
under mild conditions.
R
B
ZnCl2
3IIa, IIb + [(EtO)2PCH2]NR + [(EtO)2P]2NR,
O
Amides IIa and IIb were also prepared from tetra-
ethyl pyrophosphite, but the latter proved to be less
reactive in analogous transformations. Thus its reac-
VIIIa, VIIIb
IXa, IXb
R = Me (a), Et (b).
1070-3632/04/7409-1317 2004 MAIK Nauka/Interperiodica

1318
PRISHCHENKO et al.
Hence, under conditions of this reactions, ring
cleavage in compounds B occur mainly by a sym-
metric pathway (cf. [4]).
(EtO)2PCH2NPCl2
R
O
Ia, Ib
Substituted amidophosphorous dichlorides I were
prepared in quantitative yields, but, unlike amides II
VII, they are thermally unstable. They can be stored
for a long time at 20 C but polymerize on distillation.
Treatment of amidochlorides I with a mixture of etha-
nol and triethylamine gives phosphoroamidites IIa
and IIb in high yields.
2EtOH, 2Et3N
2Et3N HCl
(EtO)2PCH2NP(OEt)2,
R
O
IIa, IIb
R = Me (a), Et (b).
The reaction of amidochloride Ia with an excess
of triethyl orthoformate involves cleavage of the P N
bond. Subsequent reactions of the intermediates and
triethyl orthoformate lead to N-formylaminomethyl-
phosphonate X and diethoxymethylphosphonate XI.
2HC(OEt)3
Ia
(EtO)2PCH2NCHO
Me
+
(EtO)2PCH(OEt)2
2EtCl
O
O
X
XI
HC(OEt)3
EtCl
HC(OEt)3
EtCl
(EtO)2PCH2NCH(OEt)2 + EtOPCl2
Me
(EtO)2PCH2NCH(Cl)OEt + (EtO)2PCl
Me
O
O
The presented reaction scheme agrees with data in
[6]. Amides II IV containing a three-coordinate
phosphorus atom were used by us to prepare novel
interest as promising ligands and biologically active
compounds. Their structure was confirmed by the H,
1
123C, and 31P NMR spectra containing characteristic
signals of the P1C1H2N(C2Hn)P2 fragments (see table).
The 31P NMR signals of the obtained compounds are
located in the ranges characteristic of their simplest
analogs with the same coordination of the phosphorus
atoms. The elemental analyses of a series of the ob-
tained compounds, confirmatory of their composition,
were also presented in the preliminary publication [7].
four-coordinate phosphorus compounds with
PCH2NP fragment.
a
Amides IIb IV smoothly take up sulfur in benzene
to form thio derivatives XII.
R
S
IIb, III, IV
(EtO)2PCH2NPX2,
O
S
EXPERIMENTAL
XIIa XIIc
The H, 13C, and 31P NMR spectra were obtained
on a Varian VXR-400 spectrometer (400, 100, and
162 MHz, respectively) in CDCl3 (15 20% solutions)
against TMS (1H, 13C) and 85% H3PO4 in D2O (31P).
1
X = EtO (a), Et (b), Bu (c): R = Et (a, b), Me (c).
Amide IIb reacts with an excess of methyl iodide
under mild conditions by an Arbuzov reaction scheme,
yielding amidophosphonate XIII.
All reactions were carried out under argon in an-
hydrous solvents.
Et
Me
MeI
IIb
(EtO)2PCH2NP
Diethyl [N-(dichlorophosphino)-N-methyl-
amino]methylphosphonate (Ia). To a solution of
10 g of diethyl [N-methyl-N-(trimethylsilyl)amino]-
methylphosphonate in 40 ml of methylane chloride, a
solution of 6.5 g of phosphorus trichloride in 20 ml
of methylene chloride was added dropwise with stir-
EtI
OEt
O
O
XIII
The novel phosphorus-substituted organophos-
phorus acid amides I VII, XII, and XII present
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004

SYNTHESIS OF PHOSPHORUS-SUBSTITUTED DIALKYLAMIDES
1319
Physicochemical characteristics of compounds I XIIIa and NMR spectral data for the P1C1H2N(C2Hn)P2 fragments
( , ppm, J, Hz)
bp,
(p,
mm Hg)
C
(P1),
d
2
n2D0
(C1H2) 2JPH 3JPH
(C1)
1JPC JPC
(C2) 2JPC
(P2)
2JPP
Ia
Ib
98
98
3.4 3.5 m
3.4 3.5 m
46.54 d.d 160.5 28.1 37.43 d 14.3 18.54 162.49 d 12.9
41.92 d.d 159.4 22.9 43.81 d 19.7 18.90 163.13 d 8.5
8.0 42.97 d.d 159.3 24.1 32.17 d 13.7 22.29 142.72d 18.3
6.8 37.86 d.d 157.9 17.3 38.80 d 20.5 22.59 143.19 d 12.2
8.6 39.09 d.d 158.3 22.6 39.35 d 16.7 21.24 141.25 d 9.7
37.95 d.d 158.0 15.7 39.54 d 23.5 21.85 142.37 d 8.6
8.0 44.47 d.d 156.0 15.1 43.83 d 11.3 23.02 67.89 d 7.0
IIa
IIb
IIc
IId
III
IV
V
84 111 (1) 1.4472 2.98 t
86 115 (1) 1.4485 3.01 d.d
81 129 (1.5) 1.4742 3.03 t
74 123 (1) 1.4735 2.9 3.1 m
85 108 (1) 1.4672 2.90 t
83 128 (1) 1.4680 2.87 t
81 139 (1) 1.4418 3.06 t
81 168 (1) 1.4630 3.02 t
8.0
8.4
8.6
8.0
8.0
9.2
8.0
8.8
8.0 51.28 d.d 157.1 28.4 34.88 s
9.2 44.05 d.d 159.7 4.8 34.34 s
22.54 63.71 d 23.8
20.97 6.96 d 19.5
VI
8.0 41.31 d
8.8 42.29 d
9.2 40.57 d.d 158.6 6.6 40.54 s
9.2 39.09 d.d 157.8 3.1 40.63 s
160.6
159.9
33.35 s
32.83 s
21.10 48.23 d 15.3
21.19 34.41 t 18.5
21.23 73.60 d 12.9
21.83 84.55 d 8.3
21.44 81.16 d 14.7
4.6 21.69 30.79 d 8.5
VII 78 202 (1) 1.4705 3.05 t
XIIa 89 138 (1) 1.4718 3.34 d.d 12.0
XIIb 87 160 (2) 1.5018 3.35 t
XIIc 85 169 (1)b
3.30 t
XIII 74 152 (2) 1.4498 2.9 3.1 m
9.2
8.6
8.6 43.75 d
160.8
34.87 s
38.26 d.d 156.2 4.5 39.11 d
a
2
1
3
4
3
4
Fragment C H . H NMR spectrum, , ppm (J, Hz): IIa: 2.37 d.d ( J
7.6,
J
1.2); IV: 2.54 d.d ( J
5.2,
J
1.6); V:
PH
3
PH
PH
PH
3
4
3
4
3
4
2
2.40 d.d ( J 9.2,
J
1.2); VI: 2.35 d.d ( J 9.2, J 1.2); VII: 2.43 d.d ( J 4dH 9.6, J 2.8); XIIb: 2.52 d ( J 10.4);
PH
PH
PH
PH
P
PH
PH
2
the signals of the C H fragments of the other compounds appear as multiplets in the range 2.6 3.1 ppm. Fragment PCH , , ppm
(J, Hz): VII:
2
3
2
1
2
1
b
1.25 d ( J 15.2),
9.37 d ( J 116.3); XIII:
1.32 d ( J 16.8),
11.40 d ( J 134). mp 43 C.
H
PH
C
PC
H
PH
C PC
ring at 0 C. The solvent was removed at 20 C, and
the residue was kept in a vacuum (1 mm Hg) at 20 C
to give 10.9 g of phosphonate Ia.
c. A mixture of 6.3 g of tetraethyl pyrophosphite,
1 g of 1,3,5-trimethylhexahydrotriazine, and 0.2 g of
zinc chloride was heated at 135 C for 1 h and then
distilled to give 5.2 g of phosphonate IIa, yield 74%.
Repeated distillation of the high-boiling fraction gave
Phosphonate Ib was obtained analogously.
Diethyl [N-(diethoxyphosphino)-N-methyl-
amino]methylphosphonate (IIa). a. To a solution of
6.5 g of diethyl [N-methyl-N-(trimethylsilyl)amino]-
methylphosphonate in 10 ml of methylane chloride, a
solution of 4.1 g of diethyl phosphorochloridite in
5 ml of methylene chloride was added dropwise with
stirring at 10 C. The solvent was removed, and the
residue was distilled in a vacuum to give 6.5 g of
phosphonate IIa. Found, %: C 39.65; H 8.26; P 20.28.
C10H25NO5P2. Calculated, %: C 39.87; H 8.36; P
20.56.
0.5
g
of N,N-bis(diethoxyphosphinoylmethyl)-N-
methylamine (VIIIa). Yield 20%, bp 155 C (1 mm
Hg), n2D0 1.4530. PC1H2NC2H3 fragment: H NMR
1
spectrum, , ppm: 3.01 d (C1H2, JPH 9.6 Hz); 13C
2
NMR spectrum, C, ppm: 54.02 d.d (C1, JPC 157.5,
1
3JPC 10.4 Hz), 46.22 t (C2, JPC 7.9 Hz); 31P NMR
spectrum, , ppm: 21.55 s (cf. [8]). The 31P NMR
spectrum of the low-boiling fraction [bp 75 85 C
(1 mm Hg)] contains, together with the signal of the
starting tetraethyl pyrophosphite ( 125.5 ppm), a
signal of N,N-bis(diethoxyphosphino)-N-methylamine
3
P
Compounds IIb, IIc, IId VII were obtained
analogously.
(IXa),
143.22 ppm (cf. [9]).
P
b. A mixture of 5.1 g of diethyl [N-methyl-N-(tri-
methylsilyl)amino]methylphosphonate, 5.4 g of tetra-
ethyl pyrophosphite, and 0.2 g of zinc chloride was
heated at 130 C for 1 h and then distilled to give
4.9 g of phosphonate IIa, yield 81%.
Phosphonate IIb (yield 72%) and N,N-bis(di-
ethoxyphosphinoylmethyl)-N-ethylamine (VIIIb)
were obtained analogously, yield 15%, bp 159 C
1
(1 mm Hg), n2D0 1.4480. PC1H2NC2H2 fragment: H
2
NMR spectrum, , ppm: 3.10 d (C1H2, JPH 9.2 Hz);
Phosphonate IIb was obtained analogously, yield
83%.
1
13C NMR spectrum, C, ppm: 49.00 d.d (C1, JPC
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004

1320
PRISHCHENKO et al.
3
3
156.9, JPC 7.5 Hz), 49.97 t (C2, JPC 7.8 Hz). 31P
NMR spectrum, P, ppm: 22.01 s (cf. [8]). The 31P
NMR spectrum of the low-boiling fraction contains a
signal of N,N-bis(diethoxyphosphino)-N-ethylamine
37.89; H 7.72; P 17.68. C11H27NO5P2S. Calculated,
%: C 38.04; H 7.83; P 17.83.
Compounds XIIb and XIIc were obtained analo-
gously.
(IXb),
143.72 ppm (cf. [9]).
P
Diethyl [N-[ethoxy(methyl)phosphinoyl]-N-
ethylamino]methylphosphonate (XIII). To a solu-
tion of 4.2 g of phosphonate IIb in 15 ml of ether, a
solution of 6 g of methyl iodide in 5 ml of ether was
added dropwise with stirring at 10 C. The resulting
mixture was refluxed for 1 h, the solvent was removed,
and the residue was distilled to give 3 g of phos-
phonate XIII. Found, %: C 39.69; H 8.22; P 20.30.
C10H25NO5P2. Calculated, %: C 39.67; H 8.36;
P 20.56.
d. To a solution of 10.9 g of phosphonate Ia in
50 ml of diethyl ether, a solution of 3.6 g of ethanol
and 8.2 g of triethylamine in 30 ml of ether was added
dropwise with stirring at 0 C. The resulting mixture
was left for a day at 20 C, the triethylamine hydro-
chloride was filtered off, the solvent was removed,
and the residue was distilled to give 8.9 g of phos-
phonate IIa, yield 76%.
Phosphonate IIb was obtained analogously,
yield 78%.
REFERENCES
1. Purdela, D. and Vilceanu, R., Chimia Compulsor
Organici ai Fosforului si ai Acizilor lui, Bucharest:
Acad. Rep. Socialiste Romania, 1965.
2. Dunina, V.V. and Beletskaya I.P., Zh. Org. Khim, 1992,
vol. 28, no. 9, p. 1930; Zh. Org. Khim., 1992, vol. 28,
no. 11, p. 2368; Zh. Org. Khim., 1993, vol. 29, no. 4,
p. 806.
3. Mel’nikov, N.N., Novozhilov, K.B., and Belan, S.R.,
Pesticidy i regulatory rosta rastenii (Pesticides and
Plant Growth Regulators), Moscow: Khimiya, 1995.
4. Prishchenko, A.A., Livantsov, M.V., Kustrya, D.N.,
Grigor’ev, E.V., and Luzikov, Yu.N., Zh. Obshch.
Khim., 1994, vol. 64, no. 9, p. 1575.
5. Prishchenko, A.A., Livantsov, M.V., Kustrya, D.N.,
Novikova, O.P., Grigor’ev, E.V., and Goncharo-
va, Zh.Yu., Zh. Obshch. Khim., 1997, vol. 67, no. 11,
p. 1914; Prishchenko, A.A., Novikova, O.P., Livan-
tsov, M.V., Kustrya, D.N., and Grigor’ev, E.V., Zh.
Obshch. Khim., 1997, vol. 67, no. 10, p. 1746.
6. Petrov, K.A., Chauzov, V.A., and Agafonov, S.V., Usp.
Khim., 1982, vol. 51, no. 3, p. 412; Prishchenko, A.A.,
Livantsov, M.V., and Lutsenko, I.F., Vestn. Mosk. Univ.,
Ser. 2: Khim., 1988, vol. 29, no. 1, p. 3.
Reaction of phosphonate Ia with triethyl ortho-
formate. To a solution of 10.9 g of phosphonate Ia
in 20 ml of methylene chloride, a solution of 12.6 g of
triethyl orthoformate in 20 ml of methylene chloride
was added dropwise with stirring at 0 C. The result-
ing mixture was left for a day at 20 C, the solvent
was removed, and the residue was distilled to give
6.3 g (78%) of diethyl [(N-formyl-N-methyl)amino]-
methylphosphonate (X), bp 125 C (1 mm Hg), nD20
1.4570. According to NMR data, phosphonate X is a
4:1 ratio of two stereoisomers. First isomer. PC1H2N
1
(C2H3)C3(O)H fragment: H NMR spectrum, , ppm:
2
3.25 d (C1H2, JPH 11.3 Hz), 2.65 s (C2H3), 7.56 s
(C3H); 13C NMR spectrum, C, ppm: 38.40 d (C1,
1JPC 155.2 Hz), 34.35 s (C2), 161.20 s (C3); 31P NMR
spectrum, P, ppm: 18.61 s. Second isomer. PC1H2N
1
(C2H3)C3(O)H fragment: H NMR spectrum, , ppm:
2
3.15 d (C1H2, JPH 10.0 Hz), 2.45 s (C2H3), 7.53 s
(C3H); 13C NMR spectrum, C, ppm: 43.95 d (C1,
1JPC 158.0 Hz), 30.10 s (C2), 162.00 s (C3); 31P NMR
spectrum, , ppm: 18.20 s (cf. [10]). Repeated distilla-
tion of the low-boiling fraction gave 6.7 g of diethyl
(diethoxymethyl)phosphonate (XI), yield 72%, bp
7. Livantsov, M.V., Prishchenko, A.A., Novikova, O.P.,
Livantsova, L.I., Koval’, Ya.N., and Grigor’ev, E.V.,
Zh. Obshch. Khim., 2002, vol. 72, no. 11, p. 1927.
8. Prishchenko, A.A., Livantsov, M.V., Kustrya, D.N.,
and Grigor’ev, E.V., Zh. Obshch. Khim., 1995, vol. 65,
no. 9, p. 1571.
79 C (1 mm Hg), n2D0 1.4255. PCH fragment: H
1
NMR spectrum, , ppm: 4.55 d (2JPH 5.0 Hz); 13C
NMR spectrum, C, ppm: 98.19 d (1JPC 207.0 Hz);
P
9. Nikonorova, L.K., Grechkin, N.P., and Nuretdinov, I.A.,
Zh. Obshch. Khim., 1978, vol. 46, no. 5, p. 1015.
10. Prishchenko, A.A., Livantsov, M.V., Goncharo-
va, Zh.Yu., Novikova, O.P., and Grigor’ev, E.V., Zh.
Obshch. Khim., 1998, vol 68, no 7, p. 1217.
11. Razumov, A.I. and Moskva, V.V., Zh. Obshch. Khim.,
1964, vol. 34, no. 4, p. 3125; Prishchenko, A.A., Li-
vantsov, M.V., Moshnikov, S.A., and Lutsenko, I.F.,
Zh. Obshch. Khim., 1987, vol. 57, no. 8, p. 1910.
11.15 ppm (cf. [11]).
Diethyl [N-(diethoxyphosphinothioyl)-N-ethyl-
amino]methylphosphonate (XIIa). A mixture of
3.2 g of phosphonate IIb, 0.4 g of sulfur, and 10 ml
of benzene was heated on a water bath for 1 h and
then cooled. The residual sulfur was then filtered off,
the solvent was removed, and the residue was distilled
to give 2.9 g of phosphonate XIIa. Found, %: C
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004