Phosphoramidates: Synthesis, spectroscopy, and X-Ray crystallography

Article abstract of DOI:10.1002/hc.21040

A series of novel phosphoramidates with a general formula P(O)X ₁X₂X₃, where X₁ = X₂ = X₃ = 1H-1,2,4-triazol (1); X₁ = X₂ = X ₃ = N-phenylhydrazine (2); X

Full text of DOI:10.1002/hc.21040

Heteroatom Chemistry
Volume 00, Number 0, 2012
Phosphoramidates: Synthesis, Spectroscopy,
and X-Ray Crystallography
Zahra Shariatinia,1 Marzieh Sohrabi,2 Mohammad Yousefi,2
Tomas Koval,3 and Michal Dusek3
1Department of Chemistry, Amirkabir University of Technology, Tehran, Iran
2Department of Chemistry, Islamic Azad University, Shahre-Rey Branch, Tehran, Iran
3Institute of Physics of the ASCR, 182 21 Praha 8, Czech Republic
Received 17 November 2011; revised 27 May 2012
INTRODUCTION
ABSTRACT: A series of novel phosphoramidates
with a general formula P(O)X1X2X3, where X1
=
In the past decades, there has been considerable
interest in the preparation of a large family of
phosphoramidates. The reason lies in their valu-
able and widely applicable properties like antiviral
[1–3], antibacterial [4], and anticancer drugs [5–8]
in medicine. In biology, such compounds are well
known to inhibit urease and acetylcholiesterase en-
zymes [9,10]. The synthesis and biological evalu-
ation of indolequinone phosphoramidate prodrugs
targeted to DT-diaphorase was also reported [11].
Moreover, the presence of P O bond (or other donor
substituents on the P atom) in these compounds
leads to their ability to form coordination com-
pounds [12,13]. They are also useful in the syn-
thetic chemistry [14–17]. In asymmetric synthesis,
the chiral phosphoramidates have been synthesized
using chiral amino substituents [18]. Among many
crystal structures of phosphoramidates studied up
to now, we mention for instance Chivers et al.
[19,20] and Gholivand et al. [21,22]. The stereoiso-
meric separation and bioassay of a new organophos-
phorus compound, O,S-dimethyl-N-(2,2,2-trichloro-
1-methoxyethyl) phosphoramidothioate, has been
X2 = X3 = 1H-1,2,4-triazol (1); X1 = X2 = X3
=
N-phenylhydrazine (2); X1 = Br, X2 = X3 = N-
phenylhydrazine (3), X1 = Br, X2 = X3 = dipropy-
lamine (4), and X1 = X2 = X3 = 1,4-dioxa-8-
azaspiro[4.5]decane (5) as well as [P(O)(NC4H8NH-
CH3)+3 .3Cl−] (6), were synthesized and characterized
by H, 13C, 31P NMR, IR spectroscopy, and elemen-
1
tal analysis. It is interesting that the P atoms of
compounds 3 and 4 are the most upfielded atoms
(δ(31P) = −23.00, −21.65 ppm) among molecules 1–
6. This indicates that the Br atom acts as a strong
electron donor to the P atom via a resonance inter-
1
action. The H and 13C NMR spectra of compound
5 reveal three separate sets of peaks for the aliphatic
CH2 protons of three four-membered rings. This can
be explained by different spatial orientations (confor-
mations) of the aliphatic rings. The crystal structure of
compound 6 was also determined by X-ray crystallog-
raphy. There are intermolecular N H· · ·Cl hydrogen
ꢀ
C
bonds in this structure.
2012 Wiley Periodicals, Inc.
Heteroatom Chem 00:1–8, 2012; View this article online at
wileyonlinelibrary.com. DOI 10.1002/hc.21040
done for its application as
agriculture [23].
a
pesticide in
In this work, following our previous studies, six
new phosphoramidates were synthesized and char-
acterized by 1H, 13C, 31P NMR, IR spectroscopy,
and elemental analysis. Because single crystals of
Correspondence to: Zahra Shariatinia; e-mail: shariati@aut
.ac.ir.
Contract grant sponsor: Research Council of Amirkabir Univer-
sity of Technology.
c
ꢀ
2012 Wiley Periodicals, Inc.
1

2
Shariatinia et al.
NMR (d6-DMSO): δ = −1.13 (s). 1H NMR (d6-DMSO):
δ = 8.37 (s, 6H, Ar-H). 13C NMR (d6-DMSO): δ =
164.48 (s, Ar-H). IR (KBr, cm−1): 3439, 3126 (CH),
2870 (CH), 1483, 1379, 1272 (P O), 1148, 1058 (P-
N), 979, 883, 679, 643, 508.
compound 6 were only obtained, we studied the X-
ray structure of this molecule. In fact, the structural
similarity between all compounds 1–6 is limited only
to the similar connectivity to the central phosphorus
atom in P( O)(NR1)(NR2)(X3) in which four bonds
to the P atom are look alike, but the substituents R1,
R2, and X3 are quite different.
N,Nꢁ,Nꢁꢁ-Tris(N-phenylhydrazinyl)
Triamide (2). To solution of phosphoryl-
Phosphoric
a
bromide (5 mmol, 1.44 g) in dry acetonitrile,
N-phenylhydrazine (30 mmol, 3.24 g) was added
dropwise at 0◦C and the mixture was stirred for
48 h. Then the solution was evaporated and the
precipitate was washed with acetone. mp = 218◦C.
Yield: 75%; Anal. Calcd. for C18H21N6OP: C, 58.69;
H, 5.75; N, 22.81. Found: C, 58.67; H, 5.74; N,
EXPERIMENTAL
Spectroscopic Measurements
1H, 13C, and 31P spectra were recorded on a
Bruker Avance DRS 500 spectrometer (Burladingen,
1
Germany). H and 13C chemical shifts were deter-
mined relative to internal TMS, 31P chemical shifts
relative to 85% H3PO4 as external standard. In-
frared (IR) spectra were recorded on a Shimadzu
model IR-60 spectrometer (Columbia, MD). Ele-
mental analysis was performed using a Heraeus
CHN-O-RAPID apparatus (Hanau, Germany). Melt-
ing points were obtained with an Electrothermal
instrument (Purdeys Industrial Estate, Rochford,
Essex, UK).
22.80. 31P{ H} NMR (d6-DMSO): δ = 15.11 (s). H
NMR (d6-DMSO): δ = 6.18 (s, 3H, NH), 6.24 (s,
3H, NH), 6.63 (t, 3 J(H,H) = 7.5 Hz, 3H, Ar-H),
6.88 (d, 3 J(H,H) = 7.5 Hz, 6H, Ar-H), 7.07 (t,
3 J(H,H) = 7.5 Hz, 6H, Ar-H). 13C NMR (d6-DMSO):
δ = 150.42 (d, 3 J(P,C) = 3.4 Hz, Cipso), 128.41 (s),
117.87 (s), 112.46 (s). IR (KBr, cm−1): 3427 (NH),
3317 (NH), 3053 (CH), 1602, 1496, 1199 (P O),
928 (P-N), 754, 695. MS (EI, 70 eV): m/z (%) =
368 (20) [M]+, 108 (97) [C6H5-NH-NH2]+, 93 (100)
[C6H5-NH2]+, 77 (98) [C6H5]+, 62 (42) [NHOP]+, 154
(38) [P(O)-C6H5-NH-NH2]+.
1
1
X-Ray Measurements
X-ray data of compound 6 were collected on a sin-
gle crystal diffractometer Gemini of Oxford Diffrac-
tion (now Agilent Technologies, Santa Clara, CA)
equipped with a CCD detector Atlas and mirror-
N,Nꢁ-Bis(N-phenylhydrazinyl) Phosphoramidic
Bromide (3). To a solution of phosphorylbromide
(5 mmol, 1.44 g) in dry acetonitrile, N-
phenylhydrazine (20 mmol, 2.16 g) was added
dropwise at 0◦C and the mixture was stirred for
10 h. Then the solution was evaporated and the
precipitate was washed with diethylether. mp =
220◦C. Yield: 67%; Anal. Calcd. for C12H14BrN4OP:
C, 42.25; H, 4.14; N, 16.42. Found: C, 42.24; H, 4.14;
˚
collimated Cu Kα radiation (λ = 1.5418 A). The struc-
tures were refined with Jana2006 [24], employing the
fixed weighting scheme based on the experiment.
The hydrogen atoms were placed to geometrically
expected positions, with C H distance restrained to
0.96 A, N H distances restrained to 0.87A, and not
refined. The isotropic temperature parameters of hy-
drogen atoms were calculated as 1.2∗U of the parent
atom. Absorption correction was performed with the
CrysAlisPro (Agilent Technologies), using spherical
harmonics implemented in SCALE3 ABSPACK scal-
ing algorithm.
1
N, 16.43. 31P{ H} NMR (d6-DMSO): δ = −23.00 (s).
1H NMR (d6-DMSO): δ = 6.69 (m, 6H, Ar-H), 7.30
3
(t, J(H,H) = 7.7 Hz, 4H, Ar-H), 8.22 (s, 2H, NH),
10.06 (s, 2H, NH). 13C NMR (d6-DMSO): δ = 146.76
(s), 129.81 (s), 122.05 (s), 115.12 (s). IR (KBr, cm−1):
3489 (NH), 3200 (NH), 3000 (CH), 1678, 1447, 1153,
1201 (P O), 887 (P-N), 855, 764, 679.
Synthesis
N,Nꢁ-Bis(dipropyl) Phosphoramidic Bromide (4).
To a solution of phosphorylbromide (5 mmol,
1.44 g) in dry acetonitrile, dipropylamine (20 mmol,
2.02 g) was added dropwise at 0◦C and the mixture
was stirred for 10 h. Then the solution was evapo-
rated and the precipitate was washed with CCl4. mp
= 186◦C. Yield: 52%; Anal. Calcd. for C12H28BrN2OP:
C, 44.04; H, 8.62; N, 8.56. Found: C, 44.02; H, 8.63;
N,Nꢁ,Nꢁꢁ-Tris(1H-1,2,4-triazol) Phosphoric Tri-
amide (1). To a solution of phosphorylchloride
(10 mmol, 1.54 g) in dry acetonitrile, 1H-1,2,4-triazol
(60 mmol, 4.14 g) was added dropwise at 0◦C and
the mixture was stirred for 48 h. Then the yellow so-
lution was evaporated and the residue was washed
with acetone and CHCl3. mp = 96◦C. Yield: 47%;
Anal. Calcd. for C6H6N9OP: C, 28.69; H, 2.41; N,
1
N, 8.55. 31P{ H} NMR (d6-DMSO): δ = −21.65 (s).
50.19. Found: C, 28.67; H, 2.40; N, 50.20. 31P{ H}
1H NMR (d6-DMSO): δ = 0.87 (t, J(H,H) = 7.0 Hz,
1
3
Heteroatom Chemistry DOI 10.1002/hc

Phosphoramidates: Synthesis, Spectroscopy and X-Ray Crystallography
N,Nꢁ,Nꢁꢁ-Tris(1-methylpiperazinyl
3
6H, CH3), 1.62 (m, 4H, CH2), 2.87 (m, 4H, CH2). IR
(KBr, cm−1): 2956 (CH), 2877 (CH), 2794 (CH), 1455,
1381, 1193 (P O), 1017 (P-N), 757, 521.
hydrochlo-
ride) Phosphoric Triamide (6). To a solution of
phosphorylchloride (10 mmol, 1.54 g) in dry
dichloromethane, 1-methylpiperazine (30 mmol,
0.30 g) was added dropwise at 0◦C and the mixture
was stirred for 14 h. Then the solution was evapo-
rated and the yellow oily product was washed with
diethylether and dried. Yield: 77%; Anal. Calcd. for
C15H36N6Cl3OP: C, 39.70; H, 7.80; N, 18.52. Found:
N,Nꢁ ,Nꢁꢁ -Tris(1,4-dioxa-8-azaspiro[4.5]decane)
Phosphoric Triamide (5). To a solution of phospho-
rylchloride (10 mmol, 1.54 g) in dry acetonitrile, 1,4-
dioxa-8-azaspiro[4.5]decane (60 mmol, 8.58 g) was
added dropwise at 0◦C and the mixture was stirred
for 24 h. Then the solution was evaporated and the
oily product was washed with n-heptane and CCl4.
Yield: 51%; Anal. Calcd. for C21H36N3O7P: C, 53.27;
H, 7.66; N, 8.87. Found: C, 53.25; H, 7.65; N, 8.86.
1
C, 39.68; H, 7.81; N, 18.53. 31P{ H} NMR (D2O): δ =
1.39 (s). 1H NMR (D2O): δ = 2.64 (s, 3 H, CH3), 2.82
(s, 4H, CH2-ring), 3.31 (s, 4H, CH2-ring). IR (KBr,
cm−1): 3414 (NH), 2950 (CH), 2809 (CH), 1626,
1454, 1219 (P = O), 1092, 770 (P-N), 675.
31P{ H} NMR (d6-DMSO): δ = 18.07 (s). 1H NMR (d6-
1
DMSO): δ = 1.26 (m, 4H, CH2), 1.37 (m, 2H, CH2),
1.65 (m, 12H, CH2), 1.83 (m, 2H, CH2), 2.67 (m, 4H,
CH2), 2.86 (m, 4H, CH2), 2.98 (m, 2H, CH2), 3.43
(m, 6H, CH2), 3.59 (m, 6H, CH2), 3.64 (m, 4H, CH2),
4.02 (m, 2H, CH). 13C NMR (d6-DMSO): δ = 25.25
(s), 25.53 (s), 28.21 (s), 28.75 (s), 43.10 (s), 44.73 (s),
67.60 (d, 3 J(P,C) = 2.7 Hz, CH2), 67.83 (s), 74.64 (s),
79.18 (d, 2 J(P,C) = 5.2 Hz, CH2), 79.21 (d, 2 J(P,C) =
4.8 Hz, CH2). IR (KBr, cm−1): 3424, 2969 (CH), 2873
(CH), 1630, 1448, 1166 (P O), 1123, 1071 (P-N), 920,
870, 809, 660.
RESULTS AND DISCUSSION
Spectroscopic Study
In this work, new phosphoramidates 1–6 were syn-
thesized from the reaction of POCl3 or POBr3 with
different amines (Scheme 1). A summary of the NMR
and IR parameters of these compounds is given in
Table 1. The phosphorus chemical shifts, δ(31P), of
compounds 1 and 2 appear at −1.13 and 15.11 ppm
and those of compounds 5 and 6 are observed at
18.07 and 18.50 ppm, respectively. It can be seen
SCHEME 1 Preparation pathway of compounds 1–6.
Heteroatom Chemistry DOI 10.1002/hc

4
Shariatinia et al.
TABLE 1 Selected Spectroscopic NMR and IR Data of Compounds 1–6
Compound
δ(31P) (ppm)
3J(P,C) (Hz)
ν(NH) (cm−1
)
ν(P O) (cm−1
)
ν(P N) (cm−1
)
[P(O)(NC2H2N2)3] (1)
−1.13
15.11
−23.00
−21.65
18.07
–
3.4
–
–
2.7
–
–
1272
1199
1201
1193
1166
1219
1058
928
887
1017
1071
770
[P(O)(NH-NH-C6H5)3] (2)
[BrP(O)(NH-NH-C6H5)2] (3)
[BrP(O)(N(C3H7)2)2] (4)
3427, 3317
3489, 3200
–
–
[P(O)(NC4H8-CO2C2H4)3] (5)
[P(O)(NC4H8NH-CH3)+3 .3Cl−] (6)
1.39
3414
that among compounds 1, 2, 5, and 6, the phospho-
rus atom is the most shielded in molecule 1 that
is due to the attachment of aromatic groups to it.
In compounds 5 and 6 containing aliphatic amido
moieties, the P atoms are the most deshielded. It is
interesting that the P atoms of compounds 3 and
4 are the most upfielded atoms (δ(31P) = −23.00,
−21.65 ppm) among molecules 1–6. This indicates
that the Br atom acts as a strong electron donor to
the P atom revealing that the Br atom shields the P
atom via resonance interaction.
CH2 groups in the aliphatic five-membered rings that
are because of their different conformational forms.
Thus, the 36 protons belong to the expected molecule
and additional 12 protons are related to three five-
membered rings with a different spatial orientation.
Similarly, the 13C NMR spectrum of molecule 5 dis-
plays eleven signals for three amido groups attached
to the phosphorus atom, five of which correspond to
the five carbon atoms of the three six-membered ring
and eight signals are related to the eight nonequiv-
alent carbon atoms of three five-membered rings.
These features of 5 are owing to the different spatial
orientations (conformations) of the aliphatic five-
membered rings relative to each other. The 3 J(P,C) =
The two NH groups in compounds 2 and 3 are
1
observed at two different chemical shifts in the H
1
NMR spectra. The peak integrals in the H NMR
2
spectrum of molecule 5 exhibit 48 protons instead
of 36 protons. This can be due to the nonequivalent
2.7 Hz and J(P,C) = 5.2 and 4.8 Hz were obtained
from the 13C NMR spectrum of 5. The 3 J(P,C) =
TABLE 2 Crystallographic Data for Compound 6
Chemical Formula
P(O)(NC4H8NH-CH3)+3 .3Cl−
Mr
453.8
Trigonal, R3c
112
Crystal system, space group
Temperature (K)
˚
a = b, c (A)
18.3070 (12), 11.5526 (6)
3353.1 (4)
3
˚
V (A )
Z
6
Radiation type
Absorption coefficient (mm−1
Crystal size (mm)
Diffractometer
Cu Kα
4.53
)
0.29 × 0.11 × 0.08
Gemini with Atlas CCD detector
Radiation source
Monochromator
Absorption correction
Tmin, Tmax
Enhance Ultra (Cu) X-ray Source
mirror
Multiscan
0.553, 1
No. of measured, independent and observed [I > 3 σ(I )] reflections
5118, 1147, 1098
Rint
0.031
R[F2 > 3σ(F2)], wR(F2), S
Number of reflections
Number of parameters
Number of restraints
H-atom treatment
0.022, 0.055, 0.97
1147
79
0
H-atom parameters were constrained
−3
˚
ꢀρmax, ꢀρ
(e A
)
0.08, −0.08
min
Absolute structure
Flack parameter
477 of Friedel pairs used in the refinement
0.012 (18)
Heteroatom Chemistry DOI 10.1002/hc

Phosphoramidates: Synthesis, Spectroscopy and X-Ray Crystallography
5
◦
˚
are presented in Table 2, and selected bond lengths
and angles are given in Table 3. Hydrogen bonding
data are given in Table 4. Molecular structure and
the unit cell packing including hydrogen bonds are
shown in Figs. 1 and 2.
TABLE 3 Selected Bond Lengths (A) and Angles ( ) for
Compound 6
Bond
Bond length
Angle
Bond angle
P1 O1
P1 N1
P1 N1i
P1 N1ii
N1 C1
N1 C4
N2 C2
N2 C3
N2 C5
1.480 (3)
1.647 (2)
1.647 (2)
1.647 (2)
1.461 (3)
1.461 (3)
1.496 (3)
1.496 (3)
1.488 (3)
O1 P1 N1
O1 P1 N1i
O1 P1 N1ii
N1 P1 N1i
N1 P1 N1ii
N1i P1 N1ii
Cl1iv N2 C3
Cl1iv N2 C5
Cl1iv N2 C2
112.45 (7)
112.45 (7)
112.45 (7)
106.34 (10)
106.34 (11)
106.34 (10)
109.82 (11)
102.52 (16)
110.62 (11)
Trigonal symmetry of 6 has not been observed
for phosphoramidates studied earlier [21,22,25,26].
The P O bond length in molecule 6 is 1.480 (3)
˚
A that is comparable with P O bond length in
P(O)(NH2)3 reported by Bullen et al. [27] and is
similar in length to that in molecules where hy-
˚
drogen bonding occurs (e.g., H3PO4 1.52 A),but it
is longer than in phosphoryl compounds such as
Symmetry code(s): (i) –y + 1, x–y, z; (ii) x + y + 1, –x + 1, z;
(iii) –y + 2/3, –x + 4/3, z −1/6; (iv) –y + 4/3, –x + 2/3, z + 1/6.
˚
˚
POCl3 (1.45 A) or PO(OPh)3 (1.43 A) [28]. The P
atom has a slightly distorted tetrahedral configu-
ration, i.e., with the N P N and O P N angles
106.34(10)◦ and 112.45 (7)◦, respectively. In our pre-
vious reports [21,22,25,26], all of the six angles
around the phosphorus atom were different whereas
in compound 6 the N P N and O P N angles are
equal due to symmetry. All of the P N bonds are
3.4 Hz was observed for the coupling of ipso carbon
with phosphorus atom in 2.
The IR spectra indicate that among compounds
1–6, the ν(P O) is the strongest in 1 whereas it is the
weakest one in 5. This can be due to the substitution
of three aromatic groups to the P atom in 1 whereas
three aliphatic groups in 5. Interestingly, the ν(P-N)
value is the strongest one in 5, exhibiting the most
contribution of nitrogen lone pairs in P-N partial
multiple bond formation.
˚
equal (1.647 (2) A) that are quite close to the P N
˚
bond lengths in P(O)(NH2)3 (∼1.65 A) [27]. Also, the
P N bonds have almost the same length as those in
˚
˚
H3BP(NH2)3 (1.650–1.658 A) [29] and are 0.11–0.12 A
˚
shorter than the single P N in Na[PO3·NH3] (1.77 A),
suggesting that there is partial π-bonding. In the
absence of more detailed calculations, one can only
estimate the π-bond order of the P N bonds as ap-
proximately 30% from a comparison with the P N
X-Ray Crystallography
To obtain more detailed information about the struc-
tural properties of phosphoramidates, we tried to
grow suitable single crystals of compounds 1–5, but
the crystallization did not yield appropriate objects.
However, we were able to obtain trigonal single crys-
tals of phosphoramidate 6 its structure is somewhat
similar to those of phosphoramidates 1–5. For this
reason, its structure was determined by X-ray crys-
tallography. Single crystals of the compound were
obtained from a solution of chloroform/hexane at
room temperature. The crystallographic data and
the details of the X-ray analysis of this compound
˚
lengths in phosphazenes (usually 1.56–1.60 A [30,31]
50% π-bond order), in N3H3P3O3(ONa)3·4H2O (1.68
˚
˚
A, 25% [32,33]), and Na[PO3·NH3] (1.77 A [34] 0%).
Recently, similar studies on the crystal structures
of phosphoric triamides bearing 3-, 4-nitrobenzoyl
substituents [35,36] (Table 5) reveal that the P O
and P N bond lengths and the angles around
phosphorus atom are comparable with those of
compound 6.
From the two endocyclic N C bonds, N2 C
˚
˚
(1.496 (3) A) is longer than N1 C (1.461 (3) A) due
TABLE 4 Selected Hydrogen-Bond Parameters for Compound 6
H· · · A (◦)
˚
˚
˚
D
H· · · A
D
H (A)
H· · · A (A)
D · · · A (A)
D
C3 H1c3· · ·Cl1i
C3 H2c3· · ·Cl1ii
C1 H2c1· · ·Cl1iii
C5 H1c5· · ·Cl1iv
C5 H2c5· · ·Cl1ii
C2 H2c2· · ·Cl1v
N2 H1n2· · ·Cl1vi
0.96
2.76
2.86
2.94
2.93
2.82
2.90
2.17
3.564 (2)
3.736 (2)
3.668 (2)
3.557 (3)
3.712 (3)
3.717 (3)
3.034 (2)
142.43
152.89
133.75
124.20
155.24
143.17
172.99
0.96
0.96
0.96
0.96
0.96
0.87
Symmetry code(s): (i) –y + 5/3, x– y + 4/3, z + 1/3; (ii) x + 2/3, x– y + 4/3, z–1/6; (iii) –x + y– 1/3, y– 2/3, z– 1/6; (iv) x + y, –x + 1, z; (v) x +
1/3, y–1/3, z– 1/3; (vi) –y + 4/3, –x + 2/3, z + 1/6.
Heteroatom Chemistry DOI 10.1002/hc

6
Shariatinia et al.
FIGURE 1 ORTEP view of the crystal structure of compound 6.
FIGURE 2 Unit cell packing including strong intermolecular N-H. . . Cl hydrogen bonds in compound 6.
Heteroatom Chemistry DOI 10.1002/hc

Phosphoramidates: Synthesis, Spectroscopy and X-Ray Crystallography
7
◦
˚
TABLE 5 The Bond Lengths (A) and Angles ( ) Obtained for the Phosphoric Triamides I–IV
Compounda
RP(O)[NH-C(CH3)3]2
RP(O)[NC4H8]2
RꢁP(O)[N(C2H5)2]2
RꢁP(O)[NC4H8O]2
Parameter
(I)b
(II)c
(III)c
(IV)c
P=O
1.4720 (15)
1.6293 (17)
1.7053 (17)
1.481 (3)
1.4840 (14)
1.6268 (16), 1.6351 (10)
1.6954 (14)
1.480 (2), 1.478 (3)
1.373 (2)
1.486 (6)
1.637 (2), 1.632 (2)
1.693 (2)
1.475 (3), 1.461 (3)
1.370 (3)
1.4811 (12)
1.6251 (15), 1.6443 (15)
1.6875 (14)
1.470 (2), 1.472 (3)
1.377 (2)
P Namine
P Namide
C Namine
C Namide
1.355 (3)
O=P-Namine
O=P-Namide
121.55 (9)
108.62 (9)
106.84 (9)
96.26 (8)
127.25 (15)
116.90 (16)
118.96 (7), 110.38 (7)
105.02 (7)
104.98 (7)
114.44 (7), 103.24 (6)
128.41 (10), 124.07 (11) 118.66 (16), 117.79 (18) 119.16 (11), 128.95 (11)
124.81 (12) 125.78 (17) 121.00 (11)
116.39 (11), 109.75 (10)
105.43 (10)
107.62 (11)
112.16 (10), 105.49 (10)
115.72 (8), 109.59 (7)
112.74 (7)
105.78 (8)
107.03 (7), 105.41 (7)
N
amine-P-Namine
Namine-P-Namide
P-Namine-C
P-Namide-C
aR=3-NO2-C6H4-C(O)NH, Rꢁ=4-NO2-C6H4-C(O)NH. bRef. [35]. cRef. [36].
to the presence of H+ on N2 atom. The length of
exocyclic N2 C bond (1.488 (3) A) lies between the
REFERENCES
˚
[1] McGuigan, C.; Kelleher, M. R.; Perrone, P.; Mulready,
S.; Luoni, G.; Daverio, F.; Rajyaguru, S.; LePogam,
S.; Na´jera, I.; Martin, J. A.; Klumpp, K.; Smith, D. B.
Bioorg Med Chem Lett 2009, 19, 4250–4254.
[2] McGuigan, C.; Daverio, F.; Na´jera, I.; Martin, J. A.;
Klumpp, K.; Smith, D. B. Bioorg Med Chem Lett
2009, 19, 3122–3124.
[3] Mehellou, Y.; McGuigan, C.; Brancale, A.; Balzarini,
J. Bioorg Med Chem Lett 2007, 17, 3666–3669.
[4] Vassiliou, S.; Grabowiecka, A.; Kosikowska, P.;
Yiotakis, A.; Kafarski, P.; Berlicki, Ł. J Med Chem
2008, 51, 5736–5744.
[5] Borch, R. F.; Liu, J.; Joswig, C.; Baggs, R. B.; Dexter,
D. L.; Mangold, G. L. J Med Chem 2001, 44, 74–77.
[6] Connors, T. A. FEBS Lett 1975, 57, 223–233.
[7] Jain, M.; Kwon, C.-H. J Med Chem 2003, 46, 5428–
5436.
endocyclic N1 C and N2 C bond lengths. In com-
pound 6, the sum of surrounding angles around
N(1) and N(2) atoms is 119.48◦ and 107.65◦, re-
spectively, indicating that the N(1) is almost pla-
nar whereas N(2) has a tetrahedral conformation.
There is a strong N2 H1n2· · ·Cl1 intermolecular hy-
drogen bond (Symmetry code = −y + 4/3, − x +
˚
2/3, z + 1/6, with N2 H1n2 = 0.87 A, H1n2· · ·Cl1 =
˚
˚
2.17 A, N2· · ·Cl1 = 3.034 (2) A and N2 H1n2· · ·Cl1
= 172.99◦) (Fig. 2).
SUPPLEMENTARY MATERIAL
[8] Tobias, S. C.; Borch, R. F. J Med Chem 2001, 44,
4475–4480.
[9] Gholivand, K.; Ghaziani, F.; Yaghoubi, R.; Hosseini,
Z.; Shariatinia, Z. J Enzyme Inhib Med Chem 2010,
25, 827–835.
[10] Stivers, J. T.; Nagarajan, R. Chem Rev 2006, 106,
3443–3467.
[11] Hernick, M.; Flader, C.; Borch, R. F. J Med Chem
2002, 45, 3540–3548.
Crystallographic data for the structure 6 have been
deposited with Cambridge Crystallographic Data
Center as supplementary publication no. CCDC
844409 (C15H36Cl3N6O1P1). Copies of the data may
be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK, (fax:
+44 1223 336033; E-mail: deposit@ccdc.cam.ac.uk
or www: http://www.ccdc.cam.ac.uk).
[12] Gholivand, K.; Shariatinia, Z. J Organomet Chem
2006, 691, 4215–4224.
[13] Dhia, M. T. B.; Sanhoury, M. A. M. K.; Owono, L. C.
O.; Khaddar, M. R. J Mol Struct 2008, 892, 103–109.
[14] Ai, T.; Li, G. Bioorg Med Chem Lett 2009, 19, 3967–
3969.
[15] Kattuboina, A.; Li, G. Tetrahedron Lett 2008, 49,
1573–1577.
[16] Palombi, L.; Acocella, M. R.; Celenta, N.; Massa, A.;
Villano, R.; Scettri, A. Tetrahedron: Asymmetry 2006,
17, 3300–3303.
[17] Denmark, S. E.; Ghosh, S. K. Tetrahedron 2007, 63,
8636–8644.
ACKNOWLEDGMENTS
The financial support of this work by the Research
Council of Amirkabir University of Technology is
gratefully acknowledged. Also, we acknowledge the
support from the Institutional research plan no.
AVOZ10100521 of the Institute of Physics and the
Praemium Academiae project of the Academy of Sci-
ences of the Czech Republic.
Heteroatom Chemistry DOI 10.1002/hc

8
Shariatinia et al.
[18] Ai, T.; Han, J.; Chen, Z.-X.; Li, G. Chem Biol Drug
Des 2009, 73, 203–208.
[19] Chivers, T.; Krahn, M.; Schatte, G.; Parvez, M. Inorg
Chem 2003, 42, 3994.
[20] Briand, G. G.; Chivers, T.; Krahn, M.; Parvez, M. In-
org Chem 2002, 41, 6808–6815.
[21] Gholivand, K.; Shariatinia, Z.; Mashhadi, S. M.;
Daeepour, F.; Farshidnasab, N.; Mahzouni, H. R.;
Taheri, N.; Amiri, S.; Ansar, S. Polyhedron 2009, 28,
307–321.
[27] Bullen, G. J.; Stephens, F. S.; Wade, R. J. J Chem Soc
A 1969, 1804–1812.
[28] Corbridge, D. E. C. In Topics in Phosphorus Chem-
istry, Vol. 3; Interscience: New York, 1966; p. 292,
Table V.2.
[29] Nordman, C. E. Acta Cryst 1960, 13, 535–539.
[30] Paddock, N. L. Quart Rev 1964, 18, 168–210.
[31] (a) Ansell, G. B.; Bullen, G. J. Chem Commun 1966,
430–431. (b) Wagner, A. J.; Vos, A. Acta Cryst B 1968,
24, 707–713.
[22] Gholivand, K.; Shariatinia, Z.; Pourayoubi, M. Z
Anorg Allg Chem 2006,632, 160–166.
[23] Zhou, S.; Wang, L.; Li, L.; Liu, W. J Agric Food Chem
2009, 57, 6920–6926.
[32] Ansell, G. B.; Bullen, G. J. J Chem Soc A 1968, 3026–
3036.
[33] Olthof, R.; Migchelsen, T.; Vos, A. Acta Cryst 1965,
19, 596–603.
[24] Petricek, V.; Dusek, M.; Palatinus, L. Jana2006. Struc-
ture Determination Software Programs. Institute of
Physics, Praha, Czech Republic, 2006.
[25] Gholivand, K.; Shariatinia, Z.; Ansar, S.; Mashhadi,
S. M.; Daeepour, F. Struct Chem 2009, 20, 481–488.
[26] Gholivand, K.; Pourayoubi, M.; Shariatinia, Z. Poly-
hedron 2007, 26, 837–844.
[34] Cruickshank, D. W. J. Acta Cryst 1964, 17, 671–672.
[35] Gholivand, K.; Mostaanzadeh, H.; Koval, T.; Dusek,
M.; Erben, M. F.; Ve´dova, C. O. D. Acta Cryst B 2009,
65, 502–508.
[36] Gholivand, K.; Mostaanzadeh, H.; Koval, T.; Dusek,
M.; Erben, M. F.; Stoeckli-Evansd, H.; Ve´dova, C. O.
D. Acta Cryst B 2010, 66, 441–450.
Heteroatom Chemistry DOI 10.1002/hc