Stereoselective synthesis of 2,4-dioxo-5-phenyl-1- phenylethylamino-4- phenoxy-1,3,4-dazaphospholidine

Full text of DOI:10.1134/S1070363208120190

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 12, pp. 2405–2406. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © M.A. Pudovik, N.A. Khailova, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 12, pp. 2059–2060.
LETTERS
TO THE EDITOR
Stereoselective Synthesis of 2,4-Dioxo-5-phenyl-1-
phenylethylamino-4-phenoxy-1,3,4-dazaphospholidine
M. A. Pudovik and N. A. Khailova
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences,
ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia
fax: (8432) 752253
e-mail: pudovik@iopc.knc.ru
Received May 27, 2008
DOI: 10.1134/S1070363208120190
Recently we showed that diphenyl (α-methylamino)
benzylphosphonate easily added to phenyl isocyanate
or phenyl isothiocyanate in the presence of a catalytic
amount of triethylamine affording N,N'-substituted
(thio)ureas; cyclization of the latter led to the
formation of 1,3,4-diazaphospholidines [1]. Now we
studied reaction of bis(chloromethyl)isocyanatophos-
phinate (I) with optically active diphenyl(α-methylamino)-
benzylphosphonate (II). Noteworthy that the formation
of the latter compound was registered recently in the
reaction of catalytic addition of diphenyl hydrogen phos-
phite to the optically active (S)-(–)-benzal(1-phenyl)ethyl-
amine (catalyst BF3) by 31Р NMR spectroscopy as a
mixture of stereoisomers which was not separated [2].
We obtained optically active aminophosphonate II in
the same reaction using sodium phenolate as a catalyst:
O
(PhO)2P
O
Ph
*
*
(PhO)2P
H + PhHC NCHMe
Ph
CHNHCHMe
Ph
II
20
The reaction mixture contained a mixture of amino-
phosphonate II diastereomers in the ratio 74:26%, with
chemical shifts of phosphorus nuclei 16.64 and
16.25 ppm respectively. By fractional crystallization
one diastereomer of the phosphonate II was isolated in
enantiomerically pure form ([α]D –53.7). By X-ray
structural analysis we established that configurations
of two chiral centers in this compounds were the same
(SC1SC2). Reaction of isocyanate I with aminophos-
phonate II proceeds stereoselectively.
O
O
O
O
O
H
H
N
*
(PhO)2P
(ClCH2)2PNCO + (PhO)2P CHNHCHMe
Ph
P(CH2Cl)2
C
N
C
Ph
Ph CH*
Ph
Me
II
III
I
Ph
Ph
O
Ph
O
Ph
CH
CH
O
*
*
N
P
CHMe
PhO
N
PhOH
P
CHMe
PhO
+ PhOP(CH2Cl)2
_PhOH
N
C
HN
C
(ClH2C)2P
O
O
O
IV
VI
V
2405

2406
PUDOVIK, KHAILOVA
In the 31P NMR spectrum of the reaction mixture
2,4-Dioxo-5-phenyl-1-phenylethylamino-4-phen-
oxy-1,3,4-diazaphospholidine (Vа). To a solution of
0.5 g of aminophosphonate II in 20 ml of anhydrous
acetonitrile was added at stirring 0.21 g of bis(chloro-
methyl)isocyanatophosphinate (I). After 45 days a
crystalline precipitate separated and was filtered off.
After triple recrystallization from acetonitrile 0.2 g
(45%) of diastereomer Vа was obtained, mp 182–183°С.
IR spectrum (KBr), ν, cm–1: 1190, 1215 (P–O–Ph),
appeared two signals of phosphorus nuclei, at 21.51
and 22.83 ppm, indicating the formation of diaza-
phospholidine V as a diastereomeric mixture in the
ratio 83:17 %, and a signal of phenyl bis(chloro-
methyl)phosphinate (VI) (δP 37.5 ppm). By the
fractional crystallization we isolated enantiomerically
pure 1-phenylethyl-2,4-dioxo-4-phenoxy-5-phenyl-1,3,4-
20
dizaphospholidine (V) with [α]D +31.0. We suggest
1
that the first step in the addition of aminophosphonate
II to isocyanate I leads to the formation of
diasteremerically uniform phpsphorylated urea III.
The subsequent intramolecular nucleophilic substitu-
tion at the tetracoordinated phosphorus atom forms a
five-membered cyclic frame with appearance of the
third chiral center on the phosphorus atom. Since the
cyclisation process proceeds stereoselectively, we
obtain final product as a diastereomeric mixture: Vа,
SC1SC2SP, and Vb, SC1SC2RP; the prevailing form Vа
was isolated.
1255 (P=O), 1595 (Ph), 1695 (C=O), 3070 (NH). H
NMR spectrum [(CD3)2CO], δ, ppm (J, Hz): 1.62 d
3
(3H, MeC, 3JHH 4.6), 4.86 q (1H, NCH, JHH 5.0), 5.07
2
d (1H, PCH, JPH 13.1), 7.2 m (15H, Ph), 8.54 s (1H,
31
NH). P NMR spectrum, δP, ppm: 21.60. [α]D +31.0.
Mass spectrum, m/z: 392 [М+]. Found, %: C 67.05; H
5.16; N 6.80; P 7.72. C22H21N2O3P. Calculated, %:
67.33; H 5.39; N 7.13; P 7.89.
IR spectra were registered on a UR-20 spectro-
photometer in the range 400–3600 cm–1 in mineral oil.
1H NMR spectra were registered on a Bruker WM-250
instument (250.132 МHz), internal reference TMS.
The 31Р NMR spectra were registered on a Fourier
NMR spectrometer Bruker MSL-400 (162.0 МHz).
Diphenyl (α-phenylethylamino)benzylphosphonate
(II). To a solution of 4.9 g of diphenylphosphite in
20 ml of anhydrous acetonitrile was added at stirring
4.38 g of (S)-(–)-benzalphenylethylimoine and 1 drop
of sodium phenolate. The reaction mixture was heated
for 4.5 h at 80°C, then the solvent was removed and
the residue was recrystallized from ether. 0.95 g (10%)
of phosphonate II was obtained, mp 122–123°С. IR
spectrum (KBr), ν, cm–1: 1195, 1220 (P–O–Ph), 1275
ACKNOWLEDGMENTS
This work was financially supported by the Russian
Foundation for Basic research (grant no. 06-03-
32085).
1
(P=O), 1590 (Ph), 3325 (NH). H NMR spectrum
REFERENCES
[(CD3)2CO], δ, ppm (J, Hz): 1.4 d (3H, MeC, 3JHH 6.3),
3
2
3.73 q (1H, NCH, JHH 6.7), 4.16 d (1H, PCH, JPH
23.6), 7.3 m (20 H, Ph). 31Р NMR spectrum, δP, ppm:
16.55. [α]D –53.7. Found, %: C 72.85; H 6.07; N 3.33;
P 6.88. C27H26NO3P. Calculated, %: C 73.12; H 5.91;
N 3.16; P 6.99.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 12 2008