Reactions of α-aminoalkylphosphonates with iso(thio) cyanatophosphates(phosphonates, phosphinates). Synthesis of 1,3,4- diazaphospholidines and 1,3,4-oxaza(thiaza)phospholines

Article abstract of DOI:10.1023/B:RUGC.0000007644.95638.fc

Phenyl α-aminoalkylphosphonates add to phenyl iso(thio)cyanates to give saturated heterocycles, 1,3,4-diazaphospholidin-2-(thi)ones. The reaction of diphenyl (α-methylamino)benzylphosphonate with diethyl isothiocyanatophosphate involves initial formation of 1,3,4-tiazaphospholidine- 2-thiones containing exo- and endocyclic phosphorus atoms. These products are readily hydrolyzed in air, yielding diethyl isothiocyanatophosphate and phenyl hydrogen (α-methylamino)benzylphosphonate. The final products of the reaction of chloromethyl isocyanatophosphonates with aminoalkylphosphonates are 1,3,4-oxazaphospholines. Phenyl aminoalkylphosphonates react with chloromethyl isocyanatophosphonates to give saturated heterocycles, 1,3,4- diazaphospholidines, whereas with chloromethyl isothiocyanatophosphonates 1,3,4-thiazaphospholines are formed.

Full text of DOI:10.1023/B:RUGC.0000007644.95638.fc

Russian Journal of General Chemistry, Vol. 73, No. 8, 2003, pp. 1213 1226. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 8, 2003,
pp. 1284 1298.
Original Russian Text Copyright
Chmutova, M. Pudovik, A. Pudovik.
2003 by Khailova, Shaimardanova, Saakyan, Zyablikova, Azancheev, Krivolapov, Gubaidullin, Litvinov, Musin,
Reactions of -Aminoalkylphosphonates
with Iso(thio)cyanatophosphates(phosphonates, phosphinates).
Synthesis of 1,3,4-Diazaphospholidines
and 1,3,4-Oxaza(thiaza)phospholines
N. A. Khailova, A. A. Shaimardanova, G. M. Saakyan,
T. A. Zyablikova, N. M. Azancheev, D. B. Krivolapov,
A. T. Gubaidullin, I. A. Litvinov, R. Z. Musin,
G. A. Chmutova, M. A. Pudovik, and A. N. Pudovik
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center,
Russian Academy of Sciences, Kazan, Tatarstan, Russia
Received October 3, 2001
Abstract Phenyl -aminoalkylphosphonates add to phenyl iso(thio)cyanates to give saturated heterocycles,
1,3,4-diazaphospholidin-2-(thi)ones. The reaction of diphenyl ( -methylamino)benzylphosphonate with di-
ethyl isothiocyanatophosphate involves initial formation of 1,3,4-tiazaphospholidine-2-thiones containing
exo- and endocyclic phosphorus atoms. These products are readily hydrolyzed in air, yielding diethyl isothio-
cyanatophosphate and phenyl hydrogen ( -methylamino)benzylphosphonate. The final products of the reaction
of chloromethyl isocyanatophosphonates with aminoalkylphosphonates are 1,3,4-oxazaphospholines. Phenyl
aminoalkylphosphonates react with chloromethyl isocyanatophosphonates to give saturated heterocycles,
1,3,4-diazaphospholidines, whereas with chloromethyl isothiocyanatophosphonates 1,3,4-thiazaphospholines
are formed.
The chemistry of -aminoalkylphosphonates have
been vigorously progresses over the past decade.
Synthetic approaches to these compounds have been
devised and improved [1], and their biological ac-
tivity has been studied. Much emphasis has been paid
to chemical modification of -aminophosphonates [2].
It is known that in the presence of a catalyst, triethyl-
amine, they add to alkyl iso(thio)cyanates, affording
N,N -disubstituted (thio)ureas. The latter are stable
compounds, and only under rigid conditions in the
presence of a catalyst, 1,4-diazabicyclo[2.2.2]octane,
they undergo cyclization into 1,4,2-diazaphosphol-
idinones [3]. Proceeding with searching for methods
of synthesis of new heterophosphacyclanes with
endocyclic P C bonds, derived from alkylphos-
phonates bearing functional substituents in the
position [4, 5], we turned to reaction of -amino-
alkylphosphonates with aromatic and phosphorylated
iso(thio)cyanates. To induce cyclization of the addi-
tion products, we used as protic nucleophiles amino-
alkylphosphonates having the relatively readily
leaving phenoxy groups.
phosphonate (I) readily adds to phenyl isocyanate
(IIa) or phenyl isothiocyanate (IIb) in the presence of
catalytic amounts of triethylamine, yielding 1,3,4-di-
azaphospholidines IIIa, IIIb. The reaction involves
intermediate formation of N,N -disubstituted (thio)-
ureas IV which we failed to detect spectrally because
of their fast cyclization.
The structure of compounds IIIa, IIIb was proved
1
by their H, 13C, and 31P NMR and IR spectra. The
phosphorus signals were found in a region character-
istic of this type of compounds [16.30 (IIIa) and
18.65 ppm (IIIb)]. The IR spectrum of 1,3,4-diaza-
phospholidine IIIa contains absorptions bands at
1200 1210 (P O Ph), 1270 1280 (P=O), 1590 (Ph),
1
and 1710 cm (C=O). The carbonyl carbon signal in
the 13C NMR spectrum of compound IIIa (Table 1)
appears at 154.82 ppm, which is typical of compounds
of this type. The 2JPNC geminal constant of the P N C
1
fragment is 29.3 Hz, and the JPC constant of the P C
fragment is 116.1 Hz. The molecules of 1,3,4-diaza-
phospholidines IIIa, IIIb include two asymmetric
centers, predetermining formation in the course of
cyclization of a mixture of two diastereomers. Ho-
It was found that diphenyl ( -methylamino)benzyl-
1070-3632/03/7308-1213$25.00 2003 MAIK Nauka/Interperiodica

1214
KHAILOVA et al.
Ph
O
X
O
O
CH
(PhO)2PCHNHMe + PhNCX
Ph
(PhO)2PCH N CNHPh
PhO P
N Me
PhOH
N C
Ph
Me
X
Ph
I
IIa, IIb
IV
IIIa, IIIb
Hf(IIIa) 250.92
Hf 90.37
Hf(IIa) 49.47
Hf(IIb) 278.31
Hf 310.30
Hf(IIIb)
Hf(a)
54.66
80.46
3.72
Hf(b)
II, III, X = O (a), X = S (b).
wever, the above spectral data for individual com-
Table 1. 13C NMR spectra ( C, ppm; J, Hz) of diazaphos-
pholidine IIIa
1
pounds, as well as the N and 31P NMR spectra of the
reaction mixtures of aminoalkylphosphonate I with
phenyl iso(thio)cyanates IIa, IIb reveal formation of a
single diastereomer, which suggests a high stereo-
oselectivity of the reaction in study. This, in its turn,
gives an opportunity to prepare optically pure organo-
phosphorus compounds.
9
10
8
7
13 12
O
11O
14
P4 3N
C
6
2
C5
1
N
H
16
15
CH3
The molecular and crystal structure of 1,3,4-diaza-
phospholidines IIIa, IIIb was determined by means
of X-ray diffraction. Since IIIa and IIIb has isostruc-
tural crystals and, therefore, similar molecular con-
formations, we show in Fig. 1 the geometry of only
one of the molecules. The heteroring in IIIa, IIIb has
a twist conformation: The deviations of N1 and N4
from the P2C3C5 plane are 0.227(2) and 0.212(2)
in IIIa and 0.211(2) and 0.203(2) in IIIb, respec-
tively. The phenoxy group at phosphorus is pseudo-
axial, and the other substituents at the ring are pseudo-
equatorial. The planes of the phenyl substituents at N1
and C3 form with the heteroring mean plane dihedral
angles of 65.6(1) and 61.2(1) in IIIa and 66.1(1) and
61.8(1) in IIIb. The conformation of the phenoxy
groups at phosphorus is practically orthogonal: The
dihedral angle between the P2O3C12 and C12 C17
63.2(2) planes is 63.2(2) in both molecules. It
should be noted that this is a usual conformation of
phenoxyl at the phosphorus atom in medium-size
heterocycles [6]. The equatorial P=O bond length in
both molecules is the same within experimental error
[1.461(2) (mean)] and coincides with that found in
oxazaphospholanes [7]. The axial P2 O3 bond length
17
18
Atom
J
C
C2
C5
C6
C7
C8
154.82 29.3 (2JPNC
)
2
61.22 116.1 (1JPC ), 140.1 (1JC H )
30.27 11.2 (3JC NC ), 139.6 (1JC H )
5
5 5
5
6
6 6
132.67 9.6 (3JC C C H )
7
8 9 9
119.81 163.6 (1JC H ), 4.3 (3JC C C
8
8
8 9
10H10),
3.6 (3JC C C H
)
8
7
8
8
C9
129.04 161.7 (1JC H ), 8.1 (3JC C
)
9
9
9
10C9 H9
C10
C11
C12
124.90 161.9 (1JC
7.5 (3JC
10H10),
10C9C8H8)
4.5 (3JC
11C12C13H13
149.79 11.2 (2JPOC
11),
)
119.85 163.3 (1JC
12H12),
4.3 (3JC
3.6 (3JC
12C13C14H14),
12C11C12 H12
)
C13
C14
129.21 162.2 (1JC
7.8 (3JC
13H13),
13C14C13 H13
)
127.63 161.6 (1JC
14H14),
7.4 (3JC
in IIIa and IIIb is the same [1.578(2)
(mean)],
14C13C12H12
)
which, too, coincides within experimental error with
the axial P O bond length in a methoxy-substituted
oxazaphospholane [8]. The axial position of the
phenoxy group at phosphorus in molecules III is
stabilized by the anomeric effect [9]. In whole the
C15
C16
C17
C18
131.06 8.5 (2JPC C
5
15
)
127.60 5.0 (3JPC C
15C16
)
5
127.39 1.9 (4JPC C
15C16C17
)
5
129.21 162.2 (1JC
18H18
)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

REACTIONS OF -AMINOALKYLPHOSPHONATES
S
1215
O
C15
(EtO)2PNCS + (RO)2PCHNHMe
C16
C14
Ph
C17
C12
V
VIa, VIb
Me
C13
O2
S
S
O
C22
O3
C23
(EtO)2PNHC N CH P(OR)2,
C21
C10
P2
C3
C6
C7
C11
C8
Ph
C18
N1
C9
C20
VIIa, VIIb
C19
N4
C4
VI, VII, R = Et (a), i-Pr (b).
C5
X5
Phosphorylated ureas of the same structure have
been described in [11]. Compounds VIIa, VIIb are
thermally stable and undergo no cyclization.
Fig. 1. Steric structure of 1-methyl-4-phenoxy-3,5-di-
phenyl-1,3,4 -diazaphospholidine-2-one 4-oxide (IIIa)
and 1-methyl-4-phenoxy-3,5-diphenyl-1,3,4 -diaza-
phospholidine-2-thione 4-oxide (IIIb).
5
Aminobenzylphosphonate I adds to isothiocyanato-
thiophosphate V much harder than aminoalkylphos-
phonates VI (within some days at 20 C). In the
presence of catalytic amounts of triethylamine, the re-
action time decreases to several hours. According to
31P NMR data, the primary reaction product is thio-
5
geometric parameters of molecules III, listed in
Tables 2 4, are normal.
urea VIII (
62.03 and 12.71 ppm) which fast
cyclizes into cPompound IX ( P 61.12 and 21.83 ppm).
N-Phosphorylated diazaphospholidine IX is hydroly-
tically unstable and easily converts in air into isothio-
The stabilities of the participants of the reaction,
calculated by the PM3 method [10] and reflected in
the enthalpies of formation (in the scheme we give
Hf, kJ/mol, for the most stable conformers), provide
evidence showing that the processes in question are
favored by energy. Therewith, the reaction with
phenyl isocyanate (IIa) is more exothermic [ Hf (a)
80.46 kJ/mol] than the reaction with phenyl isothio-
cyanate (IIb) [ Hf (b) 3.72 kJ/mol]. Generally,
formation of diazaphospholidine structures with a
C=O group (type IIIa) is favored over formation of
their C=S analogs (type IIIb). We have found
abundant evidence for the latter conclusion and will
discuss this problem in a separate publication. The
point to be noted here is that the X-ray structures of
IIIa and IIIb are the most stable in the gas phase, too.
The molecular conformations of the compounds are
similar: The phenoxy group at phosphorus is pseudo-
axial in both cases, and the phenyl substituents at N1
and C3 are strongly rotated with respect to the hetero-
cyanatothiophosphate V ( 46.29 ppm) and phenyl
( -methylamino)benzylphosphonate
internal salt XI). Special experiments showed that
phenol fails to react with isothiocyanatothiophosphate
V in our experimental conditions.
P
X
(exists as
O
S
S
I + V
(PhO)2PCH N CHNP(OEt)2
Ph Me
VIII
Ph
O
CH
PhO P
N Me
PhOH
N C=S
S=P(OEt)2
ring plane (the P2N1C6C11 and P2C3C18C23 torsion
angles are 74.5 and 74.0 in IIIa and 84.3 and 71.9
in IIIb, respectively).
IX
OPh
O
PhO
+
H2O
P CH NH2Me
P CH NHMe
V
The reactions of diethyl isothiocyanatothiophos-
phate (V) with dialkyl ( -methylamino)benzylphos-
phonates VIa, VIb occur exothermically without
catalysts to give N-(diethoxythiophosphoryl)-N -
methyl-N -( -dialkoxyphosphoryl)benzylthioureas
VIIa, VIIb. The structure and composition of the
products were proved by their elemental analyses and
1H and 31P NMR and IR spectra.
O
HO
Ph
Ph
X
XI
The reactions of chloromethyl isocyanatophos-
phonates(phosphinates) XIIa, XIIb with -amino-
alkylphosphonates XIIIa, XIIIb might be expected to
form N-phosphorylated ureas XIVa XIVc capable
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

1216
KHAILOVA et al.
Table 2. Bond lengths d ( ), bond angles
(deg), and torsion angles
(deg) in molecules IIIa and IIIb
Parameter
Bond
IIIa
IIIb
Parameter
Angle
IIIa
IIIb
d
P2 O2
P2 O3
P2 N1
P2 C3
O3 C12
Œ5 C5
N1 C5
N1 C6
N4 C3
N4 C24
N4 C5
C3 C18
1.462(2)
1.579(2)
1.655(2)
1.823(3)
1.398(3)
1.206(3)
1.417(3)
1.437(4)
1.464(3)
1.462(4)
1.356(4)
1.510(4)
1.460(2)
1.577(2)
1.673(2)
1.807(3)
1.405(2)
1.654(2)
1.390(3)
1.445(3)
1.474(3)
1.353(3)
1.464(3)
1.514(3)
O2P2O3C12
N1P2O3C12
C3P2O3C12
O2P2N1C5
O2P2N1C6
O3P2N1C5
O3P2N1C6
C3P2N1C5
C3P2N1C6
O2P2C3N4
O2P2C3C18
O3P2C3N4
O3P2C3C18
N1P2C3N4
9.3(2)
138.3(2)
124.8(2)
139.9(2)
51.9(2)
93.1(2)
75.2(2)
14.2(2)
177.6(2)
140.9(2)
93.9(2)
87.4(2)
37.7(2)
16.4(2)
15.9(2)
145.5(2)
117.9(2)
137.5(2)
53.0(2)
95.1(1)
74.4(2)
13.3(2)
177.3(2)
139.7(1)
94.5(2)
88.4(2)
37.5(2)
15.4(4)
Angle
O2P2O3
O2P2N1
O2P2C3
O3P2N1
O3P2C3
N1P2C3
P2O3C12
P2N1C5
P2N1C6
C5N1C6
C3N4C5
C3N4C24
C24N4C5
P2C3N4
P2C3C18
P2C3H3
N4C3C18
O5C5N1
O5C5N4
N1C5N4
114.85(9)
117.9(1)
119.4(1)
102.4(1)
106.1(1)
93.0(1)
127.3(2)
113.8(2)
123.4(2)
121.8(2)
117.4(2)
120.0(2)
119.8(2)
102.2(2)
112.8(1)
107.(1)
114.94(9)
118.3(1)
118.3(1)
102.29(9)
107.3(1)
92.6(1)
125.7(1)
114.1(2)
120.3(1)
124.6(2)
116.8(2)
119.0(2)
121.9(2)
102.8(2)
113.0(1)
103.(1)
N1P2C3C18
P2O3C12C13
P2O3C12C17
P2N1C5O5
P2N1C5N4
C6N1C5O5
C6N1C5N4
P2N1C6C7
P2N1C6C11
C5N1C6C7
C5N1C6C11
C4N4C3P2
C4N4C3C18
C5N4C3P2
C5N4C3C18
C3N4C5O5
C3N4C5N1
C4N4C5O5
C4N4C5N1
P2C3C18C19
P2C3C18C23
N4C3C18C19
N4C3C18C23
141.6(2)
119.3(2)
66.2(3)
173.5(2)
6.6(3)
141.2(2)
112.8(2)
72.8(3)
174.5(1)
6.1(3)
5.0(4)
5.6(3)
175.1(2)
99.4(3)
79.2(3)
68.0(3)
113.5(3)
177.7(2)
59.2(3)
16.5(3)
139.6(2)
172.2(3)
7.7(3)
10.9(4)
169.0(2)
91.2(3)
86.1(3)
26.1(4)
156.5(2)
175.0(2)
99.0(3)
77.2(3)
69.3(3)
114.5(3)
178.6(2)
57.6(3)
15.7(2)
139.5(2)
172.1(2)
7.3(3)
115.9(2)
123.3(3)
126.5(2)
110.2(2)
116.0(2)
124.1(2)
125.1(2)
110.8(2)
9.7(4)
169.7(2)
91.8(3)
84.3(3)
26.6(3)
157.3(2)
for heterocyclization involving the chloromethyl and
urea C=O groups. Compounds XIVa XIVc were
isolated analytically pure in high yields. Their IR
spectra display absorption bands characteristic of
phosphorylated ureas, , cm : 1645 (C=O), 3100
(NH).
hydrogen chloride and formation of 1,3,4-oxazaphos-
phol-2-ines XVa XVc. Compounds XVa XVc are
transparent light yellow nonfluid liquids which were
characterized crude, since they decomposed on at-
tempted isolation by chromatography or high-vacuum
distillation. According to 1H and 31P NMR data,
1,3,4-oxazaphospholines XVa XVc are formed as
mixtures of two diastereomers. Thus, in the 31P NMR
spectrum of compound XVa we observe a double set
1
Treatment of phosphorylated ureas XIVa XIVc
with equimolar amount of triethylamine produces
intramolecular alkylation of the carbonyl oxygen with
the chloromethyl group, resulting in elimination of
of signals assigned to endocyclic (
50.76 and
50.41 ppm) and exocyclic (17.86 andP 18.04 ppm)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

REACTIONS OF -AMINOALKYLPHOSPHONATES
1217
Table 3. Atomic coordinates in diazaphospholidine IIIa,
Table 4. Atomic coordinates in diazaphospholidine IIIb,
equivalent isotropic temperature factors of non-hydrogen
equivalent isotropic temperature factors of non-hydrogen
3
3
3
3
atoms B = 4/3
(aiaj)B(i,j) ( 2) and isotropic tempera-
atoms B = 4/3
(aiaj)B(i,j) ( 2) and isotropic tempera-
i=1 j=1
i=1 j=1
2
2
ture factors of hydrogen atoms Biso
(
)
ture factors of hydrogen atoms Biso
(
)
Atom
x
y
z
B
Atom
x
y
z
B
P2
0.60821(7)
0.5442(2)
0.5114(2)
0.8361(2)
0.6582(2)
0.8490(2)
0.7825(3)
0.9954(3)
0.7887(3)
0.5667(3)
0.4988(3)
0.4106(3)
0.3890(3)
0.4562(3)
0.5453(3)
0.3825(3)
0.3723(3)
0.2432(3)
0.1244(3)
0.1372(3)
0.2658(3)
0.7752(2)
0.7737(3)
0.7642(3)
0.7528(3)
0.7522(3)
0.7639(3)
0.830(2)
0.17348(4)
0.24238(9) 0.0874(2)
0.10929(9) 0.0596(2)
0.12743(6) 3.02(1)
S5
0.86199(8)
0.59581(6)
0.5296(2)
0.4973(2)
0.6535(2)
0.8451(2)
0.7701(2)
0.7864(3)
0.5582(3)
0.5309(3)
0.4320(4)
0.3652(3)
0.3921(3)
0.4896(3)
0.3710(2)
0.2494(3)
0.1234(3)
0.1206(3)
0.2433(3)
0.3709(3)
0.7614(2)
0.7650(3)
0.7498(3)
0.7285(3)
0.7238(3)
0.7406(3)
0.9942(3)
0.809(2)
0.07911(4) 0.95596(6)
0.17173(3) 0.63674(5)
0.24041(9) 0.6081(1)
0.10838(8) 0.5758(1)
0.1475(1) 0.7867(2)
0.1156(1) 0.7204(2)
0.1576(1) 0.6110(2)
0.1144(1) 0.8178(2)
0.1504(1) 0.8664(2)
0.2142(1) 0.9118(2)
0.2188(2) 0.9816(3)
0.1601(2) 1.0062(3)
0.0964(2) 0.9610(3)
0.0915(2) 0.8903(2)
0.1129(1) 0.4770(2)
0.1403(1) 0.4991(2)
0.1397(2) 0.4038(3)
0.1111(2) 0.2891(3)
0.0833(2) 0.2693(2)
0.0836(2) 0.3627(2)
0.1259(1) 0.4844(2)
0.0547(1) 0.4654(2)
0.0285(1) 0.3462(2)
0.0729(2) 0.2457(2)
0.1434(2) 0.2632(2)
0.1705(1) 0.3827(2)
0.0948(2) 0.7343(3)
4.66(2)
2.74(1)
3.59(4)
3.36(4)
3.14(4)
3.31(4)
2.89(5)
3.21(5)
3.21(5)
4.25(6)
5.52(7)
5.61(7)
5.29(7)
4.25(6)
2.97(5)
3.60(5)
4.90(7)
5.59(8)
5.28(7)
4.26(6)
2.85(5)
3.59(5)
4.31(6)
4.66(7)
4.81(7)
4.00(6)
4.63(7)
3.2(5)
4.4(6)
5.1(6)
5.9(7)
6.4(7)
5.5(7)
4.1(6)
6.7(8)
6.4(7)
7.3(8)
10(1)
5.3(7)
4.6(6)
6.3(7)
5.6(7)
3.7(5)
15(1)
O2
3.94(4)
3.69(4)
4.81(5)
3.46(5)
3.66(5)
3.19(6)
5.28(8)
3.56(6)
3.41(6)
4.42(7)
5.47(8)
5.50(8)
5.28(8)
4.39(7)
3.20(6)
4.29(7)
5.39(8)
5.50(8)
5.19(8)
4.08(7)
3.15(6)
3.91(6)
4.37(7)
4.43(7)
4.77(7)
3.82(6)
2.9(5)
P2
O3
O2
O5
0.0917(1)
0.1527(1)
0.1139(1)
0.1551(1)
0.0903(2)
0.1163(1)
0.1583(1)
0.1004(2)
0.1072(2)
0.1718(2)
0.2295(2)
0.2234(2)
0.1114(1)
0.0770(2)
0.0729(2)
0.1043(2)
0.1384(2)
0.1420(2)
0.1204(1)
0.0486(1)
0.0195(2)
0.0608(2)
0.1327(2)
0.1623(1)
0.198(1)
0.054(1)
0.062(2)
0.174(2)
0.276(2)
0.261(1)
0.054(1)
0.051(1)
0.109(1)
0.158(2)
0.163(1)
0.021(1)
0.027(1)
0.041(1)
0.162(1)
0.210(1)
0.079(2)
0.057(2)
0.134(2)
0.4458(2)
0.2888(2)
0.2365(2)
0.1148(2)
0.2682(3)
0.3346(2)
0.3692(2)
0.3961(3)
0.4726(3)
0.5206(3)
0.4930(3)
0.4171(3)
0.0453(2)
0.1632(3)
0.2619(3)
0.2446(3)
0.1273(3)
0.0266(3)
0.0162(2)
0.0321(3)
0.1534(3)
0.2629(3)
0.2484(3)
0.1264(3)
0.123(2)
0.356(2)
0.498(2)
0.589(3)
0.533(3)
0.399(2)
0.165(2)
0.344(2)
0.317(2)
0.113(3)
0.056(2)
0.042(2)
0.161(2)
0.350(2)
0.324(2)
0.115(2)
0.373(3)
0.202(3)
0.257(4)
O3
N1
N1
N4
N4
C3
C3
C4
C5
C5
C6
C6
C7
C7
C8
C8
C9
C9
C10
C11
C12
C13
C14
C15
C16
C17
C18
C19
C20
C21
C22
C23
C24
H3
C10
C11
C12
C13
C14
C15
C16
C17
C18
C19
C20
C21
C22
C23
H3
0.204(1)
0.254(1)
0.262(1)
0.160(1)
0.055(1)
0.051(1)
0.160(1)
0.163(1)
0.108(1)
0.061(1)
0.060(2)
0.023(1)
0.021(1)
0.053(1)
0.176(1)
0.219(1)
0.132(2)
0.090(2)
0.050(2)
0.616(2)
0.895(2)
1.010(2)
1.053(2)
0.976(2)
0.859(2)
0.582(2)
0.418(2)
0.228(2)
0.190(2)
0.357(3)
0.532(2)
0.334(2)
0.163(2)
0.201(2)
0.397(2)
0.773(4)
0.657(3)
0.756(3)
H7
0.505(2)
0.365(3)
0.340(3)
4.4(6)
7.1(8)
10(1)
8.8(9)
H7
0.572(2)
0.409(3)
0.298(3)
H8
H8
H9
H9
H10 0.447(3)
H11 0.598(3)
H13 0.455(3)
H14 0.232(2)
H15 0.031(3)
H16 0.048(3)
H17 0.277(3)
H19 0.780(3)
H20 0.763(3)
H21 0.745(2)
H22 0.746(3)
H23 0.772(2)
H41 1.044(4)
H42 0.989(3)
H43 1.059(4)
H10 0.345(3)
H11 0.502(3)
H13 0.256(2)
H14 0.033(3)
H15 0.021(3)
H16 0.238(3)
H17 0.461(4)
H19 0.784(3)
H20 0.746(3)
H21 0.711(3)
H22 0.700(3)
H23 0.742(2)
H241 1.055(5)
H242 1.014(4)
H243 1.001(4)
5.7(7)
5.1(6)
4.3(6)
5.7(7)
7.6(8)
4.7(6)
4.9(6)
6.2(7)
3.5(5)
5.7(7)
4.7(6)
10(1)
10(1)
13(1)
10(1)
11(1)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

1218
KHAILOVA et al.
phosphorus atoms. The proton of the CH group at the
O
O
1
exocyclic phosphorus atom appears in the H NMR
R
spectrum as two doublets at 5.61 (2JHCP 23.01) and
6.00 ppm (2JHCP 22.26 Hz); protons of the methylene
group at the endocyclic phosphorus atom give a
complex multiplet at 3.95 4.28 ppm. The IR spectra
of the phosphacyclanes show absorption of the endo-
PNCO + (EtO)2PCHNHMe
ClCH2
R
XIIa, XIIb
XIIIa, XIIIb
Me
O
O
R
1
cyclic C=N bond (1610 cm ) and lack absorption of
PNHC(O)N CH P(EtO)2
the urea C=O group.
ClCH2
R
Of particular interest was to study the reaction of
aminophosphonate I with chloromethyliso(thio)cyana-
tophosphonates(phosphinates) XIIa XIId. We sug-
gested that the primarily formed ureas XVIa XVId
can take two cyclization pathways depending on their
structure. The first pathway (a) involves elimination
of phenol to form saturated heterocycles XVIIa,
XVIIb having exo- and endocyclic phosphorus atoms.
The second pathway (b) is cyclization involving the
chloromethyl and thiocarbonyl groups and yielding
unsaturated heterocycles XXa, XXb.
O
XIVa XIVc
O
R P N
Et3N
Et3N HCl
C N CH P(EtO)2
O
MeR
XVa XVc
XII, R = PhO (a), ClCH2 (b); XIII, R = Ph (a), i-Pr (b);
XIV, XV, R = PhO, R = Ph (a); R = PhO, R = i-Pr (b);
R = ClCH2, R = Ph (c).
O
Y
X
Y
Ph
R
R
PNCX + I
PNHCN CHP(OPh)2
ClCH2
ClCH2
Me
XIIa XIId
XVIa XVId
Ph
Ph
O
O
CH
CH
O
R
PhO P
R
N Me
PhO P
N Me
O
PhOH
X, Y = O
PhOH
POPh
+
N C
N C
ClCH2
O
P
H
ClCH2
a
b
O
XVIIa, XVIIb
XVIII
XIXa, XIXb
O
X, Y = S
HCl
Me
O
R P N
S
C N CH P(OPh)2
Ph
XXa, XXb
XII, R = PhO, X = Y = O (a); R = ClCH2, X = Y = O (b); R = PhO, X = Y = S (c); R = ClCH2, X = Y = S (d). XIX, XX,
R = PhO (a), R = ClCH2 (b).
It was found that, actually, the nature of the hetero-
cumulene (phosphorylated isocyanate or isothio-
cyanate) strongly affects the synthetic result of the
reaction. Aminoalkylphosphonate I preferentially adds
to chloromethyl isocyanatophosphonates(phosphi-
nates) XIIa, XIIb by the first pathway with elimina-
tion of phenol and formation of phosphacyclanes
XVIIa, XVIIb. Under the action of the phenol elimi-
nated, the latter undergo exocyclic P N cleavage to
give esters XIXa, XIXb and 1,3,4-diazaphospholidine
XVIII. The reaction products were isolated pure, and
their composition and structure were proved by ele-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

REACTIONS OF -AMINOALKYLPHOSPHONATES
1219
1
mental analysis and H and 31P NMR and IR spec-
tion of a phenyl group from the molecular ion. Further
fragmentation of the m/z 225 and 120 ions gives rise
to the following ions: [PhOPO]+ m/z 140, [PO]+ m/z
47, [PhCHNMe]+ m/z 119, [PhCNMe]+ m/z 118,
[PhCHN]+ m/z 104, [PhCH2]+ m/z 91, and [Ph]+ m/z
77. For all the fragment ions the experimental m/z
values are nicely consistent with those calculated from
the elemental composition.
troscopy, and mass spectrometry. The H and 31P
NMR spectra of diazaphospholidine XVIII contain
two sets of signals from two diastereomers. One of
them ( 20.80 ppm) was isolated in the individual
1
P
state by fractional crystallization from acetonitrile.
Evidence for the structure of product XVIII was ob-
tained by high-resolution mass spectrometry. In the
electron impact mass spectrum, the peak at m/z 302
relates to the molecular ion [M]+ of 1-methyl-4-
phenoxy-5-phenyl-1,3,4 5-diazaphospholidin-2-one
4-oxide (XVIII). The exact mass of this ion 302.0834
is nicely consistent with calculation (302.0822) for
the elemental composition C15H15N2O3P. The base
peak at m/z 120 is assignable to the ion [PhCHNHMe]+
which is likely to be formed by P C and C N bond
cleavage in the five-membered ring of XVIII with at-
tendant migration of one hydrogen atom to the
charged fragment. The major fragmentation pathways
of molecule XVIII under electron impact are as-
sociated with OPh expulsion. This fragmentation
pathway gives rise to a peak at m/z 209. The ion with
m/z 166 is probably formed by further fragmentation
of the m/z 209 ion, involving P N and C N bond
cleavage. The ion with m/z 225 is formed by elimina-
The cyclization by pathway b took place in cases,
where isothiocyanates XIIc, XIId were used as hetero-
cumulenes. The resulting phosphorylated thioureas
prefer intramolecular alkylation of the thiocarbonyl
sulfur atom with the chloromethyl group, resulting in
elimination of hydrogen chloride and formation of
1,3,4-thiazaphosphol-2-ines XXa, XXb. Accoring to
13C and 31P NMR data, compounds XXa, XXb are a
mixture of diastereomers. The signals of endocyclic
phosphorus atoms are located downfield ( 104
P
117 ppm), which is characteristic of 1,3,4-thiazaphos-
pholines [4]. Moreover, in the 13C NMR spectra of
phosphonates XXa, XXb, because of the presence of
an asymmetric carbon atom, respective signals of the
two phenyl rings at the second phosphorus atom have
different chemical shifts (Tables 5 and 6). It should
Table 5. 13C NMR spectra [(CD3)2CO] ( C, ppm; J, Hz) of compound XXa
13
16 17
12
11
S
21 20
O15
6
18
O
P N
22
19 O
10
7
9 14
4 3
5
2
C
C N CH P
16
17
18
1
H
8CH3
O15
S
H
Atom
P4
J
C
114.86 (main)
115.29
9.85 (main)
10.44
P14
C2
C5
C8
C9
172.45
36.71
13.8 (2JP C ), 6.5 (3JP
2.2 (3JC N C H ), 5.0 (3JC SC H )
4
2
2
7
8
8
2
5 5
14C9N7C2),
57.9 (1JP C ), 146.1, 148.0 (1JC H )
4
5
5 5
33.94
140.7 (1JC H ), 5.3 ( 3J$IXC8N7C9H9)
8
8
59.6 (1JP
136.2 (1JC H
)
14C9),
9
9
60.20
C10
C11
C12
C13
C15
132.21
125.78
129.56
130.20
150.30
4.5 (2JP
162.9 (1JC
161.5 (1JC
14C9C10
)
), 2.9 (3JP
7.2 (3JC
3.3 (3JC
11H11
12H12),
14C9C10C11),
11C12C13H13),
11C10C11 H11
)
7.5 (3JC
)
12C13C12 H12
Not determined because of signal overlap
9.6 (2JP 9.7 (3JC 2.4 (3JC
15C16C17H17
)
14OC15),
15C16C17H17),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

1220
KHAILOVA et al.
Table 5. (Contd.)
Atom
J
C
3
C15
C16
C16
150.93
120.55
120.80
8.8 (2JP
4.3 (3JP
4.3 (3JP
4.4 (3JC
), 1.7 (2JC
14OC15C16),
14OC15 C16
), 9.6 ( JC
15
15
14OC15
C16 H16
C16 C17 H17
)
164.3 (1JC
7.9 (3JC
4.4 (3JC16C15C16 H16
)
16H16),
16C17C18H18),
1
3
H16
C17 C18 H18
),
16
16
), 163.0 ( JC
), 7.9 ( JC
C15 C16 H16
16
)
C17
C17
C18
C18
C19
C20
C21
C22
130.80
130.07
129.41
129.41
151.47
121.85
129.78
125.16
163.5 (1JC
100.4 (1JC
160.0 (1JC
160.0 (1JC
4
7.9 (3JC
17H17),
17C18 C17 H17
)
3
H17
C18 C17 H17
17
17
), 8.3 ( JC
)
8.1 (3JC
18H18),
18C17C16H16
)
3
H18
C17 C16 H16
18
18
), 8.1 ( JC
)
10.4 (2JP OC
5.8 (3JC
19),
19C20C21H21
163.9 (1JC
)
4.4 (3JP OC
8.4 (3JC
5.0 (3JC
20C19C20 H20
)
19C20),
21H21),
22H22),
20H20),
20C21C22H22),
4
162.5 (1JC
162.8 (1JC
8.8 (3JC
1.2 (2JC
21C22C21 H21
)
22C21H21),
7.5 (3JC
0.8 (5JP OC
19C20C21C22
22C21C20H20),
)
4
Table 6. 13C NMR spectra [(CD3)2CO] ( C, ppm; J, Hz) of compound XXb
13
16 17
12
11
S
H
O15
Cl 6C
H
18
O
P N
10
7
9 14
4 3
5
C
2
C N CH P
16
17
18
1
H
8CH3
O15
S
H
Atom
P4
J
C
104.25 (main)
104.06
P14
10.08 (main)
10.92
C2
C5
173.33
34.13 (main) 32.7 (1JP C ), 147.6 (1JC H ), 3.0 (3JC P C H )
4
5
5
5
5 4 6 6
34.2 (1JP C ), 146.6 (1JC H ), 3.0 (3JC P C H )
4
5
5
5
5 4 6 6
34.00
43.42 (main) 70.2 (1JP C ), 154.0 (1JC H )
C6
4
6
6 6
70.2 (1JP C ), 154.0 (1JC H )
4
6
6 6
43.07
34.32
60.22
C8
C9
C10
139.3 (1JC H )
8
8
135.3 (1JC H ), 161.7 (1JP
9
9
14C9)
132.46 (main) 4.0 (2JP
14C9C10
5.6 (2JP
14C9C10
162.9 (1JC
162.0 (1JC
)
132.45
125.80
129.55
130.04
)
C11
C12
C13
C15
7.4 (3JP
8.2 (3JC
7.5 (3JC
3.3 (3JC
11H11),
12H12),
14C9C10C11),
12C13C12 H12
11C12C13H13),
11C10C11 H11
)
)
Not determined because of signal overlap
J
140.0 (main) 9.9 (2JP
9.6 (3
9.6 (3
1.6 (4JC
1.6 (4JC
14OC15),
9.6 (2JP
14OC15),
C15C16C17H17),
C15C16C17H17),
15C16C17
15C16C17
¢
¢
18H18
18H18
)
)
J
140.61
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

REACTIONS OF -AMINOALKYLPHOSPHONATES
1221
Table 6. (Contd.)
Atom
J
C
C16
C17
C18
110.31 (main) 162.1 (1JC
4.2 (3JP
4.1 (3JP
7.6 (3JC
7.6 (3JC
7.6 (3JC
6.1 (3JC
16H16),
16H16),
17H17),
17H17),
17H17),
18H18),
14OC15C16
14OC15C16
)
)
110.48
119.68 (main) 160.7 (1JC
119.60
160.7 (1JC
118.96 (main) 160.7 (1JC
119.01
160.5 (1JC
162.1 (1JC
17C18C17 H17
17C18C17 H17
)
)
160.5 (1JC
6.1 (3JC
18C17C16H16
17C18C17 H17 ),
18C17C16H16
18H18),
)
)
be noted that the signals of endocyclic methylene
protons in the H NMR spectra of compounds XXa,
XXb have different chemical shifts and coupling
constants, which we earlier observed with similar
compounds [12].
and oxazaphospholine is unfavorable (the correspond-
ing reactions are endothermic). Thus, the difference
in the major cyclization pathways of ureas and thio-
ureas reveals itself: The former tend to form saturated
heterocycles of the diazaphospholidine type and the
latter, unsaturated heterocycles (thiazaphospholines).
1
The molecular structure of 1,3,4-thiazaphosphol-2-
ine XXa was examined by means of X-ray diffraction.
The heteroring in molecule XXa has a twist conforma-
tion: The deviations of S1 and N3 from the P4C5C3
plane are 0.2613(7) and 0.174(2) , which cor-
responds to a torsion of 5 along the C2=N3 double
bond [the P4N3C2S1 torsion angle is 5.2(3) ]. The
phenoxy group at P4 is axial, and the thiophosphoryl
group is pseudoequatorial (Fig. 2). The conformation
of the phenoxy group is usual, close-to-orthogonal,
like in molecules III (see torsion angles in Tables 7
EXPERIMENTAL
The IR spectra were measured on a UR-20 spec-
1
trophotometer at 400 3600 cm in mineral oil or in
thin film. The 31P NMR spectra were obtained on a
Bruker MSL-400 Fourier spectrometer at 161.97 MHz
and on a KGU-4 spectrometer at 10.2 MHz, external
1
reference 85% H3PO4. The H NMR spectra were
taken on a Varian T-60 spectrometer at 60 MHz
(internal reference TMS) and a Bruker WM-250 spec-
and 8). The N8 atom has a planar trigonal coordination, trometer at 250.132 MHz. The 13C NMR spectra were
and its substituents are in the plane of the thiourea
fragment: The S1C2N8C8 torsion angle is 4.1(3) ,
which is determined by conjugation of the lone elec-
tron pair of N8 with the C2=N3 double bond. This
conclusion is supported by the fact that the C2 N8
bond is slightly shortened and the C2=N3 bond is
slightly lengthened. In whole the geometric param-
eters of molecule XXa are normal.
run on a Bruker MSL-400 Fourier spectrometer at
100.6 MHz. The mass spectrum was obtained on an
MX-1310 instrument; ionizing energy 70 eV, collector
C26
C27
C25
C20
C19
C28
C23
C21
C13
C12
C24
Along with the experimental study of the latter
reaction, we performed, by the PM3 method, a theo-
retical analysis of the energy changes associated with
the formation of diazaphospholidine XVIII at X, Y =
O (pathway a) and thiazaphospholine XX at X, Y = S
(pathway b). We also calculated the heat effects of
theoretically possible alternative processes, such as
formation of a thiazaphospholidine structure from iso-
thiocyanate XIIc and of an oxazaphospholine struc-
ture from isocyanate XIIa. As seen from the enthal-
pies of formation of individual compounds and the
heat effects of the reactions (Table 9), the isolated
compounds XVIII and XX are formed by thermo-
dynamically favorable exothermic reactions. The
formation of the other structures, thiazaphospholidine
C14
C22
C17
C18
C9
C8
O11
C15
C16
O10
C34
C11
P10
N8
O12
C30
N3
C2
S1
C29
P4
C33
C32
C31
S6
C5
Fig. 2. Steric structure of diphenyl [N-(4-phenoxy-4-
2
5
thioxo- -1,3,4 -thiazaphospholidin-2-yl)-N-methyl-
amino](phenyl)methylphosphonate (XXa).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

1222
KHAILOVA et al.
Table 7. Bond lengths d ( ), bond angles
(deg), and torsion angles
(deg) in molecule XXa
Bond
d
Bond
d
S1 C2
1.787(2)
1.793(3)
1.923(1)
1.608(2)
1.634(2)
1.821(3)
1.455(2)
1.577(2)
1.580(2)
O7 C11
O11 C23
O12 C29
N3 C2
1.404(3)
1.411(3)
1.400(2)
1.298(3)
1.337(3)
1.466(3)
1.480(3)
1.512(3)
1.814(2)
S1 C5
S6 P4
P4 O7
P4 N3
P4 C5
N8 C2
N8 C8
P10 O10
P10 O11
P10 O12
N8 C9
C9 C17
P10 C9
Angle
Angle
C2S1C5
94.8(1)
114.31(8)
116.07(9)
117.7(1)
107.2(1)
98.1(1)
101.1(1)
114.8(1)
117.52(9)
118.5(1)
102.05(9)
103.05(9)
98.2(1)
P10O11C23
P10O12C29
P4N3C2
124.7(1)
128.9(2)
115.4(2)
121.4(2)
118.2(2)
120.0(2)
120.0(2)
116.7(2)
123.3(2)
106.5(2)
111.4(1)
114.0(2)
114.3(2)
S6P4O7
S6P4N3
S6P4C5
C2N8C8
C2N8C9
C8N8C9
S1C2N3
O7P4N3
O7P4C5
N3P4C5
O10P10O11
O10P10O12
O10P10C9
O11P10O12
O11P10C9
O12P10C9
P4O7C11
S1C2N8
N3C2N8
S1C5P4
P10C9N8
P10C9C17
N8C9C17
124.4(2)
Angle
Angle
C5S1C2N3
5.2(2)
174.3(2)
11.7(2)
63.9(2)
66.2(2)
170.6(2)
141.4(2)
89.5(2)
12.7(2)
142.5(1)
94.5(2)
14.96(0.17)
20.7(2)
149.0(2)
109.5(2)
30.5(2)
95.9(2)
158.8(2)
64.8(2)
O11P10C9N8
O11P10C9C17
O12P10C9N8
O12P10C9C17
P4O7C11C12
P4O7C11C16
P10O11C23C24
P10O11C23C28
P10O12C29C30
P10O12C29C34
P4N3C2S1
167.2(1)
61.7(2)
62.7(2)
166.2(2)
102.2(3)
82.4(3)
81.9(3)
101.4(2)
150.9(2)
30.3(3)
5.2(3)
175.4(2)
4.1(3)
176.5(2)
176.1(2)
4.5(3)
C5S1C2N8
C2S1C5P4
S6P4O7C11
N3P4O7C11
C5P4O7C11
S6P4N3C2
O7P4N3C2
C5P4N3C2
S6P4C5S1
O7P4C5S1
N3P4C5S1
P4N3C2N8
O10P10O11C23
O12P10O11C23
C9P10O11C23
O10P10O12C29
O11P10O12C29
C9P10O12C29
O10P10C9N8
O10P10C9C17
C8N8C2S1
C8N8C2N3
C9N8C2S1
C9N8C2N3
C2N8C9P10
C2N8C9C17
C8N8C9P10
C8N8C9C17
125.9(2)
103.2(2)
62.0(2)
69.0(3)
66.3(2)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

REACTIONS OF -AMINOALKYLPHOSPHONATES
1223
Table 8. Atomic coordinates in structure XXa, equivalent isotropic temperature factors of non-hydrogen atoms B =
3
3
2
4/3
(aiaj)B(i,j) ( 2) and isotropic temperature factors of hydrogen atoms Biso
(
)
i=1 j=1
Atom
x
y
z
B
Atom
x
y
z
B
S1
0.97655(4)
1.14439(4)
1.11204(4)
0.89388(3)
1.1859(1)
0.35732(9) 0.58554(3)
0.0763(1) 0.54954(3)
0.1210(1) 0.59075(3)
0.11141(8) 0.72672(2)
0.2485(2) 0.62553(8)
0.0332(2) 0.74140(7)
0.2707(2) 0.76899(7)
0.1934(3) 0.66100(7)
0.0721(3) 0.63908(8)
0.1677(3) 0.67914(8)
0.1807(3) 0.6397(1)
0.2890(4) 0.5443(1)
0.2993(4) 0.6804(1)
0.0302(3) 0.7271(1)
0.1958(3) 0.6749(1)
0.2456(3) 0.7327(1)
0.2092(4) 0.7808(1)
0.1224(4) 0.7709(1)
0.0705(4) 0.7131(1)
0.1077(4) 0.6640(1)
0.1007(3) 0.7895(1)
0.1861(3) 0.8273(1)
0.2464(4) 0.8842(1)
0.2195(4) 0.9039(1)
0.1335(4) 0.8671(1)
0.0747(3) 0.8102(1)
0.3032(3) 0.8277(1)
0.3897(3) 0.8338(1)
0.4295(4) 0.8913(1)
0.3826(4) 0.9421(1)
0.2961(4) 0.9350(1)
0.2553(3) 0.8779(1)
4.75(2)
5.49(2)
4.11(1)
3.02(1)
4.73(4)
3.92(4)
3.55(3)
4.56(4)
3.79(4)
3.41(4)
3.39(5)
5.49(7)
5.04(6)
2.95(5)
3.64(5)
4.20(6)
4.83(6)
4.82(7)
4.56(6)
4.18(6)
3.00(5)
3.77(5)
4.55(6)
4.82(6)
4.46(6)
3.54(5)
3.17(5)
3.89(5)
4.70(6)
4.74(6)
4.70(6)
3.97(6)
C29
C30
C31
C32
C33
C34
H9
0.8095(1)
0.8005(2)
0.7336(2)
0.6780(2)
0.6881(2)
0.7543(1)
1.018(1)
1.209(1)
1.321(2)
1.431(1)
1.427(1)
1.316(1)
0.927(1)
1.001(1)
1.147(1)
1.209(1)
1.134(1)
0.813(1)
0.805(1)
0.906(1)
1.025(2)
1.031(1)
0.838(2)
0.724(2)
0.633(2)
0.655(1)
0.761(1)
1.019(1)
1.081(1)
0.865(2)
0.855(2)
0.917(2)
0.2724(3) 0.6233(1)
0.2569(4) 0.5623(1)
0.3362(5) 0.5219(1)
0.4279(5) 0.5435(1)
0.4408(4) 0.6044(1)
0.3618(3) 0.6456(1)
3.20(5)
5.05(7)
6.85(9)
5.98(8)
4.60(6)
3.73(5)
2.0(4)
5.2(6)
8.0(8)
6.1(7)
5.3(6)
5.7(6)
4.2(5)
4.3(5)
6.1(7)
5.4(6)
3.3(5)
6.3(7)
5.5(6)
5.4(6)
7.7(8)
3.7(5)
6.7(7)
10(1)
S6
P4
P10
O7
O10 0.82382(8)
O11 0.93481(9)
O12 0.87978(9)
0.047(2)
0.297(3)
0.238(4)
0.094(4)
0.012(3)
0.078(3)
0.203(3)
0.303(3)
0.261(4)
0.113(3)
0.028(3)
0.428(4)
0.473(3)
0.411(3)
0.264(4)
0.198(3)
0.205(4)
0.332(5)
0.481(4)
0.489(3)
0.364(4)
0.246(3)
0.386(4)
0.325(4)
0.254(4)
0.385(6)
0.7144(8)
0.740(1)
0.819(1)
0.803(1)
0.706(1)
0.619(1)
0.813(1)
0.909(1)
0.943(1)
0.882(1)
0.7835(9)
0.798(1)
0.895(1)
0.982(1)
0.969(1)
0.8721(9)
0.550(1)
0.484(1)
0.514(1)
0.620(1)
0.691(1)
0.508(1)
0.537(1)
0.639(2)
0.699(1)
0.708(2)
H12
H13
H14
H15
H16
H18
H19
H20
H21
H22
H24
H25
H26
H27
H28
H30
H31
H32
H33
H34
H51
H52
H81
H82
H83
N3
1.0606(1)
0.9573(1)
1.0019(1)
1.0465(2)
0.8945(2)
0.9799(1)
1.2513(1)
1.2507(2)
1.3184(2)
1.3848(2)
1.3829(1)
1.3162(1)
1.0246(1)
0.9859(1)
1.0305(2)
1.1131(2)
1.1527(2)
1.1087(1)
0.9262(1)
0.8581(1)
0.8530(2)
0.9145(2)
0.9818(2)
0.9887(1)
N8
C2
C5
C8
C9
C11
C12
C13
C14
C15
C16
C17
C18
C19
C20
C21
C22
C23
C24
C25
C26
C27
C28
8.3(8)
5.0(6)
6.1(7)
5.9(7)
6.1(7)
9.6(9)
8.9(9)
13(1)
current 30 A, ion source temperature 120 C. An
SVP-5 direct inlet probe was used, R 10000. The
exact masses were determined automatically against
prefluorokerosene to an accuracy of no higher than
9.994(2), b 19.070(3), c 10.528(2)
;
108.99(2) , V
1897.1(8) 3, Z 4, dcalc 1.33 g/cm3, space group P21/a.
The unit cell parameters and the intensities of 4202
reflections, 2263 of which had I 3 , were measured
5
10 amu.
under MoK
radiation ( MoK
0.71073
26.3 ).
,
graphite monochromator, /2 scanning,
Single-crystal X-ray diffraction analysis of com-
pounds IIIa, IIIb and XXa was performed at the
Department of X-ray studies, Center for Collective
Use, North-Caucasian Analytical Center (Russian
Foundation for Basic Research, project no. 00-03-
40133) on an Enraf Nonius CAD-4 automatic dif-
fractometer at 20 C. Crystal data for compound IIIa,
C21H19N2O2P, mp 273 C, monoclinic: at 20 C, a
Crystal data for compound IIIb, C21H19N2OPS,
mp 205 207 C, isostructural to crystals of IIIa: a
9.681(9), b 19.149(9), c 11.118(4)
;
105.88(6) , V
1982(2) 3, Z 4, dcalc 1.32 g/cm3, space group P21/a.
The unit cell parameters and the intensities of
4411 reflections, 2984 of which had I
measured under CuK radiation ( CuK 1.54184
3 , were
,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

1224
KHAILOVA et al.
Table 9. Enthalpies of formation of reagents and products
( Hf, kJ/mol) and heat effects ( Hf, kJ/mol) of the reac-
tion of aminophosphonate I with chloromethyliso(thio)-
cyanatophosphonates XII
with full geometry optimization with no symmetry
constraints using the MOPAC 6 program package [16].
The matrix of second derivatives of total energy in
coordinates was calculated in all cases for character-
ization of stationary points as energy minima. Con-
sideration was only given to the points for which all
second derivatives were positive.
Comp. no.
Hf
Reaction
Hf
I
310.30 I + XIIa
516.73 XVIII + XIXa
23.46 I + XIIc
406.41 XVIII + XIX
21.33 I + XIIa
471.81 XXa + HCl
160.71 I + XIIc
264.39 XXa + HCl
707.76
5
1-Methyl-4-phenoxy-3,5-diphenyl-1,3,4 -diaza-
XIIa
XIIc
51.19
+147.46
+33.71
62.98
phospholidin-2-one 4-oxide (IIIa). Phenyl iso-
cyanate (IIa), 0.34 g, was added to a solution of 1 g
of phosphonate I in 5 ml of dry chloroform. After
12 h, the solvent was removed in a vacuum (0.02 mm),
and the crystalline residue was recrystallized from
acetonitrile to obtain 0.72 g (67%) of compound IIIa,
XVIII
XVIII(S)a
XIXa
XIX(S)a
XXa
1
mp 273 C. IR spectrum (KBr), , cm : 1210 (Ph O
P), 1275 (P=O), 1590 (Ph), 1710 (C=O). H NMR
XXa(O)b
HCl
1
85.56
spectrum (CDCl3), , ppm (J, Hz): 2.93 s (3H, MeN),
4.93 d (1H, PCH, JPH 20.0), 7.3 m (15H, Ph). 31P
2
a
XVIII(S) is the thio analog of compound XVIII, containing
two sulfur atoms instead of oxygen atoms and XIX(S) is the
thio analog of compound XIX contains a thiophosphoryl group
instead of phosphoryl.
compound XXa containing oxygen atoms in the ring and at
NMR spectrum, P, ppm: 16.30. Found, %: C 65.95;
H 4.96; N 7.23; P 8.45. C21H19N2O3P. Calculated,
%: C 66.65; H 5.07; N 7.41; P 8.18.
b
XXa(O) is the oxygen analog of
5
1-Methyl-4-phenoxy-3,5-diphenyl-1,3,4 -diaza-
the phosphorus atom in the heterocyclic fragment.
phospholidine-2-thione 4-oxide (IIIb) was prepared
in a similar way from 1 g of phosphonate I and 0.38 g
of phenyl isothiocyanate (IIb). Yield 1.05 g (94%),
graphite monochromator, /2 scanning,
76.3 ).
1
mp 205 207 C. IR spectrum (KBr), , cm : 1200
1
Crystal data for phosphonate XXa, C28H26N2O4
P2S2, mp 126 127 C, monoclinic: at 20 C, a
(Ph O P), 1270 (P=O), 1590 (Ph). H NMR spectrum
(CDCl3), , ppm (J, Hz): 3.0 s (3H, MeN), 4.7 d (1H,
2
PCH, JPH 16), 7.1 m (15H, Ph). 31P NMR spectrum,
17.074(5), b 7.538(4), c 22.867(5)
;
106.27(2) , V
2825(2) 3, Z 4, dcalc 1.37 g/cm3, space group P21/n.
The unit cell parameters and the intensities of 4938
reflections, 3856 of which had I 3 , were measured
under CuK radiation ( CuK 1.54184 , graphite
P, ppm: 18.65. Found, %: C 63.56; H 4.87; N 7.07;
P 7.49; S 7.58. C21H19N2O2PS. Calculated, %: C
63.94; H 4.87; N 7.10; P 7.85; S 8.13.
N-(Diethoxythiophosphoryl)-N -[( -diethoxy-
phosphoryl)benzyl]-N -methylthiourea (VIIa). Di-
ethyl isothiocyanatothiophosphate (V),4.1 g, was
added dropwise with stirring to a solution of 4.99 g
aminobenzylphosphonate VIa in 30 ml of dry diethyl
ether, and the reaction mixture was left to stand for
1 day at 20 C. The crystals that formed were se-
parated and recrystallized from chloroform to obtain
monochromator, /2 scanning,
76.3 ).
No intensity decay of control reflections was ob-
served during measurements. For IIIa, no absorption
1
corrections ( Mo 1.62 cm ) and for IIIb and XXa,
empirical absorption corrections were applied ( Cu
1
23.41 and 30.69 cm , respectively). The structures
were solved by direct methods using the SIR program
[13] and refined first isotropically and then aniso-
tropically. All hydrogen atoms were revealed by dif-
ference synthesis and refined isotropically in final
cycles. The final divergence factors were as follows:
IIIa: R 0.042 and RW 0.048, on 2266 unique reflec-
tions; IIIb: R 0.039 and RW 0.048, on 2802 unique
reflections; and XXa: R 0.037 and RW 0.051, on
3664 unique reflections with F2 3 . All calculations
were performed on an Alpha Station 200 computer
using the MolEN program package [14]. Molecular
drawings were performed and intramolecular contacts
were analyzed using the PLATON 98 pogram [15].
1
7.42 g (82%) of compound VIIa, mp 103 104 C. H
NMR spectrum (CCl4), , ppm (J, Hz): 1.28 m (12H,
MeC), 3.13 s (3H, MeN), 4.10 m (9H, PCH, CH2OP),
7.27 m (5H, Ph). 31P NMR spectrum, P, ppm: 17.64,
60.22. Found, %: C 43.56; H 7.11; N 5.96; P 12.84;
S 14.06. C17H30N2O5P2S2. Calculated, %: C 43.57;
H 6.47; N 5.98; P 13.22; S 13.68.
N-[Di eth o x y (th i o )p h o s p h o ry l ]- N [( -
diisopropoxyphosphoryl)benzyl]-N -methylthio-
urea (VIIb) was obtained in a similar way from
1.05 g of phosphonate VIb and 0.78 g of isothiocy-
1
anate V. Yield 1.8 g (98%), mp 96 97 C. H NMR
The quantum-chemical calculations were performed
spectrum (CCl4), , ppm (J, Hz): 1.24 m (18H, MeC),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

REACTIONS OF -AMINOALKYLPHOSPHONATES
1225
3.13 s (3H, MeN), 4.44 m (7H, PCH, CH2OP),
7.37 m (5H, Ph). 31P NMR spectrum, P, ppm: 16.29,
59.94. Found, %: C 46.04; H 7.13; N 5.42; P 13.03;
S 13.02. C19H34N2O5P2S2. Calculated, %: C 45.95;
H 6.91; N 5.64; P 12.47; S 12.91.
was synthesized in a similar way from 1.82 g of
phosphonate XIIIa and 1.33 g of isocyanate XIIb.
Yield 2.68 g (85%), mp 115 116 C. IR spectrum
1
(KBr), , cm : 1025 (P O Alk), 1250 (P=O), 1585
1
(Ph), 1655 (C=O), 3100 (NH). H NMR spectrum
(CCl4), , ppm (J, Hz): 1.21 m (6H, MeCH2), 3.0 s
(3H, MeN), 3.98 m (6H, PCH2, POCH2), 5.73 d (1H,
PCH, 2JPH 22.0), 7.2 m (10H, Ph). 31P NMR spectrum,
P, ppm: 32.56, 19.11. Found, %: C 40.52; H 5.56; N
6.47; P 13.92. C15H24Cl2N2O5P2. Calculated, %: C
40.46; H 5.44; N 6.29; P 13.91.
Phenyl hydrogen ( -methylamino)benzylphos-
phonate (XI). Isothiocyanate V, 1.1 g, was added
dropwise to a solution of 1.8 g of phosphonate I in
10 ml of dry benzene. After 2 days, the precipitate
that formed was separated to obtain 0.6 g (43%) of
compound XI, mp 220 221 C. IR spectrum (KBr), ,
cm : 1090 (P O Ph), 1230 1250 (PO2), 1590 (Ph),
1-Methyl-4-phenoxy-5-phenyl-1,3,4 5-diaza-
phospholidin-2-one 4-oxide (XVIII). a. Isocyanate
XIIa, 2 g, was added to a solution of 3 g of phos-
phonate I in 10 ml of dry acetonitrile. After 1 day,
1.2 g (46%) of compound XVIII was separated, mp
1
1620, 2500, 3400 (NH+2). H NMR spectrum (D2O),
1
, ppm (J, Hz): 2.7 s (3H, MeN), 4.5 d (1H, PCH,
2JPCH 21.4), 7.21 m (10H, Ph). 31P NMR spectrum,
P, ppm: 5.0. Found, %: C 60.15; H 6.14; N 5.26; P
10.86. C14H16NO3P. Calculated, %: C 60.64; H 5.83;
N 5.05; P 11.17.
1
194 196 C. IR spectrum (KBr), , cm : 1245, 1255
(P=O), 1585 (Ph), 1705, 1740 (C=O), 3100 3230
1
(NH). H NMR spectrum [(CD3)2CO], , ppm (J, Hz):
N-[(Chloromethyl)phenoxyphosphoryl]-N -[( -
diethoxyphosphoryl)benzyl]-N -methylurea (XIVa).
Isocyanate XIIa, 1.53 g, was added dropwise with
stirring to a solution of 1.7 g of aminobenzylphos-
phonate XIIIa in 10 ml of dry diethyl ether, and the
reaction mixture was left to stand for 1 day at 20 C.
The crystals that formed were separated and recrystal-
lized from chloroform to obtain 1.48 g (45%) of com-
pound XIVa, mp 134 135 C. IR spectrum (KBr), ,
2.88 s (3H, MeN), 2.95 s (3H, MeN), 5.20 d (1H,
2
2
PCH, JPH 18.33), 5.24 d (1H, PCH, JPH 19.43),
2
6.67 d (1H, PNH, JPH 7.5), 7.40 m (10H, Ph), 8.59
br.s (1H, PNH). 31P NMR spectrum, P, ppm: 20.70,
17.90. Mass spectrum, m/z (Irel, %): 303 (9.8), 302
+
(64.0) [C15H15N2O3P] ([M] ), 225 (2.2) [M Ph]+,
+
210 (4.6), 209 (45.4) [M
PhO]+, 182 (3.5), 166
(38.4) [M PhO CONH]+, 152 (4.1) [C7H7NOP]+,
140 (9.4) [PhO2P] , 121 (10.1), 120 (100) [C8H10N] ,
+
+
1
cm : 1030 (P O Alk), 1170 (Ph O P), 1260 (P=O),
+
+
119 (10.6) [C8H9N] , 118 (70.2) [C8H7N] , 91 (20.6)
1
1590 (Ph), 1670 (C=O), 3185 (NH). H NMR spec-
[C7H7]+, 77 (43.0) [Ph]+, 47 (6.8) [PO]+, 42 (28.2).
Found, %: C 60.22; H 5.45; N 9.24; P 10.67.
C15H15N2O3P. Calculated, %: C 59.60; H 5.01; N
9.27; P 10.25.
trum (CCl4), , ppm (J, Hz): 1.2 m (6H, MeC), 2.8 s
(3H, MeN), 3.93 m (6H, PCH2, CH2OP), 5.77 d (1H,
2
PCH, JPH 22), 7.1 m (10H, Ph), 7.9 br.s (1H, PNH).
31P NMR spectrum, P, ppm: 19.00, 17.87. Found, %:
C 49.20; H 6.13; Cl 7.29; N 5.45; P 12.12. C20H27
ClN2O6P2. Calculated, %: C 49.13; H 5.58; Cl 7.25;
N 5.73; P 12.67.
Fractional crystallization of compound XVIII from
acetonitrile gave an individual diastereomer, mp 205
1
207 C. IR spectrum (KBr), , cm : 1255 (P=O),
1
1585 (Ph), 1710 (C=O), 3100 (NH). H NMR spec-
N-[(Chloromethyl)phenoxyphosphoryl]-N -[( -
diethoxyphosphoryl)isobutyl]-N -methylurea
(XIVb) was synthesized in a similar way from 2.23 g
phosphonate XIIIb and 2.15 g of isocyanate XIIa.
Yield 2.2 g (50%), mp 129 130 C. IR spectrum
trum [(CD3)2CO], , ppm (J, Hz): 2.74 s (3N, MeN),
2
5.10 d (1N, PCH, JPH 19.5), 7.35 m (10H, Ph), 8.52
br.s. (1H, PNH). 31P NMR spectrum, P, ppm: 20.80.
Distillation of the filtrate gave 0.85 g (35%) of
phosphonate XXa, bp 90 C (0.02 mm). 31P NMR
spectrum, P, ppm: 13.0 [17].
1
(KBr), , cm : 1020 (P O Alk), 1210 (Ph O P),
1
1250 (P=O), 1590 (Ph), 1665 (C=O), 3200 (NH). H
NMR spectrum [(CD3)2CO], , ppm (J, Hz): 0.68 d
(6H, MeCN, JHH 5.4), 1.31 m (6H, MeCH2), 2.9 s
b. Isocyanate XIIb, 1.4 g, was added to a solution
of 2.6 g of phosphonate I in 10 ml of dry acetonitrile.
After 1 day, 1.84 g (82%) of compound XVIII was
3
(3H, MeN), 4.21 m (8H, PCH2, POCH2, PCH),
7.13 m (5H, Ph), 8.61 br.s (1H, PNH). 31P NMR spec-
trum, P, ppm: 23.22, 18.00. Found, %: C 44.80; H
6.72; Cl 7.76; N 5.69; P 13.34. C17H29ClN2O6P2.
Calculated, %: C 44.89; H 6.44; Cl 7.79; N 6.16;
P 13.62.
1
separated, mp 196 C. IR spectrum (KBr), , cm :
1245, 1255 (P=O), 1585 (Ph), 1705, 1740 (C=O),
3100 3230 (NH). 31P NMR spectrum, P, ppm: 20.80,
18.0. Distillation of the filtrate gave 0.5 g (28%) of
1
phosphinate XIXb, bp 120 C (0.02 mm). H NMR
N-[Bis(chloromethyl)phosphoryl]-N -[( -di-
ethoxyphosphoryl)benzyl]-N -methylurea (XIVc)
spectrum (CCl4), , ppm (J, Hz): 3.52 d (2H, PCH2,
2
2JPH 9), 3.73 d (2H, PSH2, JPH 9), 7.1 m (5H, Ph).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 8 2003

1226
KHAILOVA et al.
3. Merten, R. and Weber, C., Chem. Ber., 1969, vol. 102,
31P NMR spectrum, P, ppm: 38.0 [17].
no. 6, p. 2143.
Diphenyl [N-(4-thioxo-4-phenoxy- 2-1,3,4-
thiazaphospholin-2-yl)-N-methylamino](phenyl)-
methylphosphonate (XXa). Isothiocyanate XIIc, 1 g,
was added with stirring to a mixture of 1.34 g of
phosphonate I and 1 ml of triethylamine in 20 ml of
dry benzene. After 3 days, triethylamine hydrochlo-
ride was separated, the solvent was removed in a
vacuum (0.02 mm), and the residue was recrystallized
from acetonitrile to obtain 1.9 g (86%) of compound
4. Kamalov, R.M., Khailova, N.A., Gazikasheva, A.A.,
Chertanova, L.F., Pudovik, M.A., and Pudovik, A.N.,
Dokl. Akad. Nauk SSSR, 1991, vol. 306, no. 6,
p. 1406.
5. Pudovik, M.A., Saakyan, G.M., Khairullin, V.K.,
Khailova, N.A., and Pudovik, A.N., Izv. Ross. Akad.
Nauk, Ser. Khim., 1999, no. 4, p. 810.
1
XXa, mp 126 127 C. IR spectrum (KBr), , cm :
6. Naumov, V.A. and Vilkov, L.V., Molekulyarnye
struktury phosphororganicheskikh soedinenii (Mole-
cular Structures of Organophosphorus Compounds),
Moscow: Nauka, 1986.
695 (P=S), 1220 (P O Ph), 1270 (P=O), 1545 (C=N),
1
1585 (Ph). H NMR spectrum [(CD3)2CO], , ppm (J,
Hz): 3.11 s (3N, MeN), 3.64 m (1H, P1CHANB,
2
2
6
1
B
A
B
2 B
JP H 4.3, JH H 13.0, JP H 1.2), 4.06 m (1H,
7. Turdybekov, K.M., Lindeman, S.V., Struchkov, Yu.T.,
Gazaliev, A.M., Nurkenov, O.A., and Zhurinov, M.Zh.,
Khim. Prirod. Soedin., 1989, no. 2, p. 291.
PCHANB, JH H
13.0, JP H 13.7), 6.90 d (1N,
2
A
B
1 A
P2CH, JP H 23.0), 7.47 m (20H, Ph). 31P NMR spec-
trum, P, ppm: 114.86, 9.85. Found, %: C 57.36; H
4.27; N 4.54; P 11.02. C28H26N2O4P2S2. Calculated,
2
2
8. Batsanov, A.S., Struchkov, Yu.T., Pudovik, M.A.,
Kibardina, L.K., and Pudovik, A.N., Kristallografiya,
1982, vol. 27, no. 2, p. 262.
%: C 57.92; H 4.52; N 4.83; P 10.67.
2
Diphenyl [N-(4-chloromethyl-4-thioxo-4-
-
1,3,4-thiazaphospholin-2-yl)-N-methylamino](phe-
nyl)methylphosphonate (XXb) was obtained in a
similar way from 1.6 g of phosphonate I, 1 ml of tri-
ethylamine, and 1 g isothiocyanate XIId. Yield 2.13
9. Kirby, A., The Anomeric Effect and Related Stereo-
electronic Effects of Oxygen, Heidelberg: Springer,
1983.
1
10. Stewart, J.J.P., J. Computer Aided Molecular Design,
g (87%), mp 136 C. IR spectrum (KBr), , cm : 680
1990, vol. 1, no. 4, p. 1.
(P=S), 1210 (P O Ph), 1275 (P=O), 1380 (ClCH2),
1550 (C=N), 1585 (Ph). 1H NMR spectrum
[(CD3)2CO], , ppm (J, Hz): 3.04 s (3N, MeN),
3.84 m (4N, PCH2S, PCH2Cl), 6.88 d (1N, PCH, 2JPH
22.7), 7.46 m (15H, Ph). 31P NMR spectrum, P, ppm:
104.06, 10.08. Found, % : C 51.46; H 4.50; Cl 6.64;
N 4.74; P 11.77; S 11.87. C23H23ClN2O3P2S2.
Calculated, %: C 51.44; H 4.33; Cl 6.60; N 5.22;
P 11.53; S 11.94.
11. Zimin, M.G. and Burilov, A.R., Zh. Obshch. Khim.,
1980, vol. 50, no. 10, p. 2203.
12. Khailova, N.A., Krepysheva, N.E., Saakyan, G.M.,
Bagautdinova, R.Kh., Shaimardanova, A.A., Zyabli-
kova, T.A., Azancheev, N.M., Litvinov, I.A., Gubai-
dullin, A.T., Zverev, V.V., Pudovik, M.A., and Pu-
dovik, A.N., Zh. Obshch. Khim., 2002, vol. 72, no. 7,
p. 1145.
ACKNOWLEDGMENTS
13. Altomare, A., Cascarano, G., Giacovazzo, C., and
Viterbo, D., Acta Crystallogr., Sect. A, 1991, vol. 47,
no. 4, p. 744.
The work was financially supported by the Russian
Foundation for Basic Research (project no. 00-03-
32837).
14. Straver, L.H. and Schierbeek, A.J., MolEN. Structure
Determination System, vol. 1, Nonius, B.V., 1994.
REFERENCES
15. Spek, A.L., Acta Crystallogr., Sect. A, 1990, vol. 46,
1. Cherkasov, R.A. and Galkin, V.I., Usp. Khim., 1998,
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2. Prishchenko, A.A., Livantsov, M.V., Kustrya, D.N.,
Novikova, O.P., Grigor’ev, E.V., and Goncharo-
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no. 1, p. 34.
16. Stewart, J.J.P., MOPAC, Ver. 6.12.QCPE 455., Bloo-
mington: Indiana Univ., 1988.
17. Edmundson, R.S., Dictionary of Organophosphorus
Compounds, London, 1988, pp. 152, 50.
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