Synthesis of phosphorus-substituted amides of acetic and diethyl phosphoric acids containing OCHN fragments [4]

Full text of DOI:10.1023/B:RUGC.0000025161.93030.b9

Russian Journal of General Chemistry, Vol. 73, No. 12, 2003, pp. 1947 1949. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 12, 2003,
pp. 2058 2060.
Original Russian Text Copyright
2003 by Prishchenko, Novikova, Livantsov, Livantsova, Koval’, Grigor’ev.
LETTERS
TO THE EDITOR
Synthesis of Phosphorus-substituted Amides of Acetic
and Diethyl Phosphoric Acids Containing OCHN Fragments
A. A. Prishchenko, O. P. Novikova, M. V. Livantsov,
L. I. Livantsova, Ya. N. Koval’, and E. V. Grigor’ev
Lomonosov Moscow State University, Moscow, Russia
Received March 21, 2003
Substituted N-chloromethylamines(amides) are
widely used for preparing various aminomethyl
organophosphorus compounds [1]. In the present work
we showed that adducts of benzal(alkyl)amines with
acetyl chloride (adduct A) or acetic anhydride (adduct
B) are convenient aminomethylating synthons for
preparing a series of phosphorus-substituted acet-
amides. Hence, adducts A and B which are easily
formed in methylene chloride (cf. [2]) react with di-
ethyl trimethylsilyl phosphite to give phosphonates I.
Note that the reaction with adduct B was carried out
in the presence of a chlorotrimethylsilane catalyst.
(EtO)2POSiMe3
(EtO)2PCH(Ph)NAc
Me3SiX
AcX
PhCH=NR
XCH(Ph)NAc
R
R
O
A, B
Ia, Ib
X = Cl (A), OAc (B); R = Me (a), CH2CH=CH2 (b).
The reaction of adduct A with bis(trimethylsiloxy)-
Me
ClCH(Ph)NP(OEt)2
O
phosphine allows preparation of a highly reactive
phosphonite II. Its subsequent reaction with bis(di-
methylamino)methane leads to phosphinate III con-
taining different aminomethyl fragments.
(EtO)2P(O)Cl
PhCH=NMe
C
Me
A, Et3N
(Me3SiO)2PH
(Me3SiO)2PCH(Ph)NAc
(EtO)2POSiMe3
Et3N HCl
(EtO)2PCH(Ph)NP(OEt)2
Me3SiCl
Me
O
O
II
IV
Me
CH(Ph)NAc
of sodium methylate in methanol gives water-soluble
sodium salt V as white hygroscopic crystals.
CH2(NMe2)2
Me3SiOP
Me3SiNMe2
CH2NMe2
O
Products I V present interest as promising ligands
III
and biologically active compounds.
The adduct of benzal(methyl)amine and diethyl
chlorophosphate B, prepared under analogous condi-
tions, reacts with diethyl trimethylsilyl phosphite to
form phosphorus-substituted amidophosphate IV.
1
The H NMR spectra of compounds I V contain
characteristic signals of the PC1H(C2)N(C3Hn)Ac,
PC4H2NC5H3, and P1C1H(C2)N(C3H3)P2 fragments,
whose parameters are listed below. Compounds I III
and V consist of two stereoisomers. The contents of
Treatment of phosphinate III with a dilute solution
1070-3632/03/7312-1947$25.00 2003 MAIK Nauka/Interperiodica

1948
PRISHCHENKO et al.
the second isomers of compounds Ib and V are low,
and, therefore, we give for them 31P NMR parameters
(cf. [3]).
6.3 g of triethylamine was added, and the mixture was
left to stand for 24 h. The solvent was removed, and
150 ml of hexane was added to the residue. A preci-
pitate formed and was filtered off, the solvent was
removed, and the residue was distilled in a vacuum to
give 10.2 g (55%) of phosphonite II, bp 139 C
Diethyl [(N-methylacetylamino)(phenyl)me-
thyl]phosphonate (Ia). a. To a solution of 8.5 g of
benzal(methyl)amine in 30 ml of methylene chloride,
a solution of 5.6 g of acetyl chloride in 10 ml of
methylene chloride was added dropwise with stirring
at 0 C. After 1 h, diethyl trimethylsilyl phosphite,
16.5 g, was added. The reaction mixture was left to
stand for 24 h at 20 C. The solvent was distilled off,
and the residue was distilled in a vacuum. Phos-
phonate Ia, 13.6 g (64%), was obtained, bp 176 C
1
(1 mm). First isomer (75%). H NMR spectrum, ,
2
ppm: 5.87 d (C1H, JPH 23.6 Hz), 2.55 s (C3H3). 13C
1
NMR spectrum, C, ppm: 72.51 d (C1, JPC 36.9 Hz),
2
136.19 d (C2, JPC 16 Hz), 35.79 s (C3), 169.28 s
1
(CO).
139.79 ppm. Second isomer. H NMR spec-
P
trum, , ppm: 5.16 d (C1H, JPH 17.9 Hz), 2.61 s
2
(C3H3). 13C NMR spectrum, C, ppm: 70.61 d (C1,
(2 mm), n2D0 1.5060. First isomer (90%). H NMR
2
1
1JPC 27.7 Hz), 135.65 d (C2, JPC 16 Hz), 31.83 s
2
spectrum, , ppm: 6.08 d (C1H, JPH 22.8 Hz), 2.69 s
(C3), 168.37 s (CO).
142.80 ppm.
(C3H3). 13C NMR spectrum, C, ppm: 51.60 d (C1,
P
2
1JPC 159.3 Hz), 132.85 d (C2, JPC 4.5 Hz), 32.24 d
Trimethylsilyl (dimethylaminomethyl)[(N-
methylacetylamino)(phenyl)methyl]phosphinate
(III). A mixture of 6.9 g of phosphonite II, 3.1 g of
bis(dimethylamino)methane, and 0.1 g of zinc chlo-
ride was heated to 110 130 C for 1.5 h and then dis-
tilled to give 4.7 g of phosphinate III, yield 71%, bp
3
3
(C3, JPC 4.2 Hz), 169.86 d (CO, JPC 5.4 Hz).
P
,
1
18.22 ppm. Second isomer. H NMR spectrum,
ppm: 4.89 d (C1H, JPH 24 Hz), 2.62 s (C3H3). 13C
NMR spectrum, C, ppm: 58.58 d (C1, 1JPC 157.8 Hz),
2
132.42 d (C2, JPC 4.5 Hz), 29.83 s (C3), 170.26 d
2
1
160 C (1 mm), n2D0 1.5020. First isomer (80%). H
3
(CO, JPC 3.5 Hz).
17.68 ppm.
P
2
NMR spectrum, , ppm: 5.91 d (C1H, JPH 13.9 Hz).
Phosphonate Ib was obtained analogously,
yield 68%.
2
13C NMR spectrum, C, ppm: 6.05 d (C1H, JPH
1
15.2 Hz). 13C NMR spectrum, C, 54.25 d (C1, JPC
a. To a solution of 7.5 g of benzal(methyl)amine in
10 ml of methylene chloride, a solution of 6.4 g of
acetic anhydride in 10 ml of methylene chloride was
added dropwise with stirring at 10 C. After 2 h,
diethyl trimethylsilyl phosphite, 13.9 g, and 4 g of
chlorotrimethylsilane were added. The reaction mix-
ture was left to stand for 48 h at 20 C. The solvent
was removed, and the residue distilled in a vacuum to
give 14.7 g (78%) of phosphonate Ia.
2
106.5 Hz), 133.63 d (C2, JPC 6.6 Hz), 32.51 s (C3),
58.13 d (C4, 1JPC 113.5 Hz), 47.46 d (C5, 3JPC 6.1 Hz),
3
170.43 d (CO, JPC 3.9 Hz).
30.36 ppm. Second
P
isomer. H NMR spectrum, , ppm: 6.05 d (C1H, 2JPH
1
15.2 Hz). 13C NMR spectrum, C, ppm: 53.82 d (C1,
1JPC 101.1 Hz), 133.51 d (C2, JPC 7.6 Hz), 33.33 s
2
(C3), 57.18 d (C4, JPC 111.4 Hz), 47.02 d (C5, JPC
1
3
3
8.9 Hz), 170.02 d (CO, JPC 2.4 Hz).
34.80 ppm.
P
Phosphonate Ib was obtained analogously,
yield 83%.
Diethyl [{N-methyl-N-(diethoxyphosphoryl)-
amino}(phenyl)methyl]phosphonate (IV). To a solu-
tion of 4.5 g of benzal(methyl)amine in 15 ml of
methylene chloride, a solution of 6.4 g of diethyl
chlorophosphate in 10 ml of methylene chloride was
added dropwise with stirring at 10 C. After 30 min,
diethyl trimethylsilyl phosphite, 8.6 g, was added. The
resulting mixture was left to stand for 48 h at 20 C.
The solvent was removed, and the residue was dis-
tilled in a vacuum to give 9.4 g (64%) of phosphonate
Diethyl [(N-allylacetylamino)(phenyl)methyl]-
phosphonate (Ib). bp 172 C (1 mm), n2D0 1.5115.
First isomer (97%). 1H NMR spectrum, , ppm:
2
6.58 d (C1H, JPH 22.8 Hz). 13C NMR spectrum,
,
C
ppm: 52.80 d (C1, JPC 158.1 Hz), 135.22 d (C2, JPC
1
2
5.2 Hz), 48.98 s (C3), 170.70 d (CO, JPC 4.4 Hz).
3
18.31 ppm. Second isomer,
18.68 ppm. Found, %P:
P
C 58.89; H 7.29; P 9.40. C16H24NO4P. Calculated, %:
C 59.07; H 7.44; P 9.52.
IV, bp 178 C (1 mm), n2D0 1.4981. 1H NMR spectrum,
2
3
Bis(trimethylsilyl) [(N-methylacetylamino)-
(phenyl)]phosphonite (II). To a solution of 17 g of
bis(trimethylsiloxy)phosphine in 50 ml of diethyl
ether, a solution of adduct A prepared from 6 g of
benzal(methyl)amine and 3.9 g of acetyl chloride in
40 ml of acetyl chloride was added with stirring at
0 C. The resulting mixture was stirred for 1 h, then
, ppm: 4.81 d.d (C1H, JPH 23.6, JPH 11.2 Hz),
2.27 d (C3H3, JPH 9.6 Hz). 13C NMR spectrum,
,
3
C
ppm: 55.53 d.d (C1, JPC 158.9, JP2C 5 Hz), 133.29 d
1
2
(C2, JPC 7.1 Hz), 29.11 d.d (C3, JPC 6.2 Hz, JPC
2
3
3 Hz). 31P NMR spectrum, , ppm: 19.03 d (P1),
3
7.09 d (P2, JPP 29.2 Hz). Found, %: C 48.64; H 7.26;
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 12 2003

SYNTHESIS OF PHOSPHORUS-SUBSTITUTED AMIDES OF ACETIC
1949
P 15.57. C16H29NO6P2. Calculated, %: C 48.85; H
7.43; P 15.75.
Found, %: C 50.74; H 6.65. C13H20N2NaO3P. Cal-
culated, %: C 50.98; H 6.58.
The NMR spectra were measured on a Varian
VXR-400 spectrometer in CDCl3 or D2O for salt V
against TMS (1H, 13C) and 85% H3PO4 in D2O (31P).
Sodium (dimethylaminomethyl)[(N-methyl-
acetylamino)(phenyl)methyl]phosphinate (V). To a
solution of 0.7 g of sodium methylate in 20 ml of
methanol, a solution of 4.7 g of phosphinate III in
10 ml of ether was added at 10 C. The resulting mix-
ture was heated to boil, the solvent was removed, and
the residue was kept in a vacuum for 1 h (1 mm) to
REFERENCES
1. Prishchenko, A.A., Livantsov, M.V., and Petro-
syan, V.S., Zh. Obshch. Khim., 1994, vol. 64, no. 8,
pp. 1316 1330.
2. Achiwa, K. and Sekiya, M., Chem. Lett., 1981, no. 9,
pp. 1213 1216.
3. Prishchenko, A.A., Novikova, O.P., Livantsov, M.V.,
Kustrya, D.N., and Grigor’ev, E.V., Zh. Obshch. Khim.,
1998, vol. 68, no. 3, pp. 514 516.
1
give 3.9 g (96%) of salt V. First isomer (95%). H
2
NMR spectrum, , ppm: 5.80 d (C1H, JPH 13.1 Hz).
1
13C NMR spectrum, C, ppm: 57.02 d (C1, JPC
103.4 Hz), 135.16 s (C2), 34.12 s (C2), 34.12 s (C3),
1
57.50 d (C4, JPC 108.2 Hz), 46.80 s (C5), 174.10 s
(CO).
27.75 ppm. Second isomer, 28.14 ppm.
P
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 12 2003