Synthesis, spectroscopic and configurational study, and ab initio calculations of new diazaphospholanes

Article abstract of DOI:10.2478/s11696-011-0047-9

New 2-substituted diazaphospholane-2-oxides (I-III, V-VIII ) and diazaphosphorinane-2-oxide (IV ) were synthesised and characterised by ¹H, ¹³C, and ³¹P NMR, IR spectroscopy, and elemental analysis. The presence of chiral

Full text of DOI:10.2478/s11696-011-0047-9

Chemical Papers 65 (5) 691–699 (2011)
DOI: 10.2478/s11696-011-0047-9
ORIGINAL PAPER
Synthesis, spectroscopic and configurational study, and ab initio
calculations of new diazaphospholanes
Khodayar Gholivand*, Fatemeh Ghaziani
Department of Chemistry, Tarbiat Modares University, P. O. Box 14115-175, Tehran, Iran
Received 30 December 2010; Revised 16 March 2011; Accepted 16 March 2011
New 2-substituted diazaphospholane-2-oxides (I–III, V–VIII ) and diazaphosphorinane-2-oxide
(IV ) were synthesised and characterised by 1H, 13C, and 31P NMR, IR spectroscopy, and elemental
analysis. The presence of chiral diamino groups in compounds II and V–VIII gives rise to various
1
diastereomers so that the 31P{ H} NMR spectra demonstrated three and two peaks with different
1
ratios, respectively. Also, the 1H and 13C{ H} NMR spectra of compounds II and V–VIII revealed
three and two sets of signals for the related conformers (diastereomers). Interestingly, the 31P NMR
spectrum of V in D2O indicated a great upfield shift (∆δ = 19.0) for 31P relative to the value
obtained in DMSO-d6 (solvent effect). The two signals in V split further to three signals in the
presence of β-cyclodextrin. Moreover, conformational analysis of diazaphospholane V was studied
by ab initio calculations at the HF and B3LYP levels of theory using the Gaussian 98 program.
Results indicated that among four suggested diastereomers (C1–C4) of V, C1 and C3 containing
methyl group in the equatorial position are the most stable forms.
c
ꢀ 2011 Institute of Chemistry, Slovak Academy of Sciences
Keywords: diazaphospholane, diastereomers, NMR, ab initio calculations
Introduction
et al., 1996; Denmark et al., 1991; Gholivand et al.,
2009a; Setzer et al., 1989), and X-ray crystal struc-
ture of 1,3,2-diazaphosphorinanes and some diaza-
phospholanes (Dutasta et al., 1990; Gholivand et al.,
2005a, 2005b, 2007a, 2009b) have been recently re-
ported. NMR data can help to interpret the conforma-
tional equilibrium involving twist-envelope and half-
chair conformations (Setzer et al., 1989). Although
structures of 1,3,2-dioxa- (Dutasta et al., 1979; Nielsen
& Dahl, 1984) and 1,3,2-oxaza-phospholane (Devillers
et al., 1971; Hall et al., 1983) have been widely in-
vestigated, less attention has been paid to confor-
mational analysis of 1,3,2-diazaphospholanes. Berlicki
et al. (2003) studied the enantio differentiation of
aminophosphonic and aminophosphinic acids using α-
and β-cyclodextrins.
1,3,2-Diazaphospholanes and 1,3,2-diazaphospho-
rinanes constitute a class of interesting mimetics of
amino acids whose importance derives from their
promising and diverse biological activity (Lucet et
al., 1998; Saibabu Kotti et al., 2006; Wang et al.,
2008; Olson & Du Bois, 2008). In fact, the vicinal
diamino functionality is a significant structural unit
that can make molecules biologically active (Du et al.,
2008; Kim et al., 2008). This activity is usually based
on the action of only one enantiomer of a diastere-
omer and thus in order to prepare efficient drugs in
medicine it is of great significance to isolate the enan-
tiomeric mixtures. The chiral α,β-diamino acid deriva-
tives bearing vicinal diamino framework are widely
found as antibiotics and natural products (Viso et al.,
2005). Synthesis (Khaikin et al., 1988; Nifantiev et
al., 1981; Peyronel et al., 1987; Zalán et al., 2003; De
la Cruz et al., 1998), conformational analysis (Kranz
In this work, seven new 1,3,2-diazaphospholanes
and one diazaphosphorinane were synthesised and
characterised by multinuclear 1H, 13C, and 31P NMR,
and IR spectroscopy to investigate the effect of chiral-
*Corresponding author, e-mail: gholi kh@modares.ac.ir

692
K. Gholivand, F. Ghaziani/Chemical Papers 65 (5) 691–699 (2011)
O
O
H
N
H2N
H2N
CH3
O
O
S
S
H
N
H
N
O
O
P
O
O
N
H
N
P
P
H
N
H
N
H
N
H
N
H
O2N
VIII
I
II
O
H2N
H
CH3
S
O
O
H
N
N
Cl
Cl
O
2 diamine
+
O
P
R
P
P
N
H
N
H
N
H
O
N
H
VII
III
O
O
H2N
H2N
S
O2N
S
H
H
CH3
CH3
H
N
O
O
O
N
N
O
O
P
P
P
N
HHN
N
H
VI
N
H
N
H
N
H
IV
V
Fig. 1. Synthesis pathway for compounds I–VIII.
ity and different substituents on the structures. High
Compounds I–VIII were synthesised according to
1
temperature dynamic 31P{ H} NMR spectra of com-
the general method as follows: To a solution of cor-
responding phosphoramidic dichloride (10 mmol) (4-
sulphamoylphenylphosphoramidic dichloride for I–V;
4-nitrophenylphosphoramidic dichloride for VI; ben-
zoylphosphoramidic dichloride for VII; 4-nitrobenzo-
ylphosphoramidic dichloride for VIII ) (Warnat, 1941;
Amirkhanov et al., 1997) in dry acetonitrile, corre-
sponding diamine (20 mmol) (benzene-1,2-diamine for
I; cyclohexane-1,2-diamine for II; ethane-1,2-diamine
for III; propane-1,3-diamine for IV; propane-1,2-
diamine for V–VIII ) was added dropwise at about 0◦C
(in an ice bath) and the mixture was stirred for 8 h.
The precipitate was filtered and the solvent was evap-
orated under diminished pressure to yield the product
which was washed with distilled water and ethyl ac-
etate and dried.
pounds II and V in DMSO-d6 were also studied. In
addition, quantum chemical calculations were done us-
ing the Gaussian 98 program to describe structures of
four possible diastereomers of V including C1 (RR),
C2 (RS), C3 (SR), C4 (SS) and their corresponding
enantiomers C5 (SS), C6 (SR), C7 (RS), and C8 (RR).
Experimental
1H, 13C, and 31P NMR spectra were recorded on
a Bruker Avance DRS 500 spectrometer using TMS
1
(for H and 13C) as the internal standard and 85 %
H3PO4 (for 31P) as the external standard. IR spec-
tra (in KBr pellets) were recorded on a Shimadzu
model IR-60 spectrometer. Elemental analyses were
performed using a Heraeus CHN-O-RAPID appara-
tus. Melting points were obtained with an Electrother-
mal instrument.
Results and discussion
In the present study, seven novel diazaphospho-
lanes and one diazaphosphorinane were synthesised by
the reaction of corresponding phosphoramidic dichlo-
ride and diamine (Fig. 1). Characterisation and spec-
tral data of the prepared compounds I–VIII are sum-
marised in Tables 1 and 2.
2-(4-Sulphamoylphenylamino)-1,3,2-
benzodiazaphospholan-2-one (I), 2-(4-
sulphamoylphenylamino)-1,3,2-cyclo-
hexodiazaphospholan-2-one (II), 2-(4-
sulphamoylphenylamino)-1,3,2-diazaphos-
pholan-2-one (III), 2-(4-sulphamoylphenyl-
amino)-1,3,2-diazaphosphorinan-2-one
(IV), 2-(4-sulphamoylphenylamino)-4-
methyl-1,3,2-diazaphospholan-2-one (V),
2-(4-nitrophenylamino)-4-methyl-1,3,2-
diazaphospholan-2-one (VI), 2-benzoylamino-
4-methyl-1,3,2-diazaphospholan-2-one (VII),
and 2-(4-nitrobenzoylamino)-4-methyl-1,3,2-
diazaphospholan-2-one (VIII)
31P NMR spectroscopy is a very convenient tool
for the determination of the enantiomeric purity of
organophosphorus compounds due to the large chemi-
cal shift dispersion and simplicity of the broad band in
the 1H decoupled spectra (Parker, 1991). In molecules
I and III–IV, the diamino moiety is not chiral and
there is only one signal for the phosphorus atom. Com-
parison of the δ(31P) values of compounds I and II in-
dicates that the phosphorus atom is deshielded when

K. Gholivand, F. Ghaziani/Chemical Papers 65 (5) 691–699 (2011)
Table 1. Characterisation data of newly prepared compounds
693
wi(calc.)/mass %
wi(found)/mass %
Yield
M.p.
Compound
Formula
Mr
C
H
N
%
69
72
69
69
49
63
53
53
◦C
I
II
C12H13N4O3PS
C12H19N4O3PS
C8H13N4O3PS
C9H15N4O3PS
C9H15N4O3PS
C9H13N4O3P
C10H14N3O2P
C10H13N4O4P
324.29
330.34
276.25
290.28
290.28
256.20
239.21
284.21
44.40
44.50
43.60
43.60
34.80
34.60
37.20
37.21
37.20
37.60
42.20
42.16
50.20
50.21
42.30
42.16
4.04
4.10
5.80
5.85
4.74
4.90
5.21
5.18
5.21
5.15
5.11
5.15
5.90
5.92
4.61
4.70
17.30
17.30
17.00
16.88
20.30
20.60
19.30
19.25
19.30
19.80
21.90
21.68
17.60
17.56
19.70
19.68
192–194
224–225
219–221
192–194
220–221
210–212
190–192
191–193
III
IV
V
VI
VII
VIII
substituted by an aliphatic ring (δ = 11.63 in I, δ =
21.74, δ = 21.87, and δ = 23.30 in II ). Endocyclic
nitrogen atoms of the NH groups in compound I are
bonded to carbon atoms with sp2 hybridisation and
to sp3 carbon atoms in compound II. Therefore, as it
through chair-antichair inversions of the cyclohexane
ring. These findings confirm the presence of a meso
form and SSS + RRR + SSR + RRS isomers (two
diastereoisomeric mixtures) in compound II, which re-
sults in three peaks in the 31P NMR spectrum. The
2
1
was expected, the J(P,NH) in compound I (17.2 Hz)
is higher than those in compound II (9.9 Hz, 10.0
high temperature dynamic 31P{ H} NMR spectra of
compound II (Fig. 2) revealed only small differences in
shifts and therefore, the signals overlapped at 333 K.
The situation with compound V is simpler as a
mixture of two diastereoisomers was obtained (two
Hz, 10.2 Hz, 10.7 Hz). The ring size affected both
2
the phosphorus chemical shift and the J(P,NH) cou-
pling constant. This means that the phosphorus atom
is more shielded with the increasing ring size from
a 5-membered ring in diazaphospholane III (δ(31P)
= 23.28) to a 6-membered one in diazaphosphorinane
IV (δ(31P) = 5.13). Conversely, 2J(P,NH) coupling con-
stant increased from 11.7 Hz in III to 24.9 Hz in IV.
Chiral diamino groups in compounds II and V–
VIII enable the formation of several diastereomers in
1
peaks in 31P NMR spectrum). The dynamic 31P{ H}
NMR spectra of V did not reveal significant changes.
1
Interestingly, the 31P{ H} NMR spectrum of V in
D2O showed a great upfield shift (∆δ ≈ 19.0) for
δ(31P) relative to the δ(31P) value observed in DMSO-
d6 (solvent effect on the phosphorus shielding). Two
signals at δ = 3.72 and δ = 2.17 with the ratio of 0.9
: 1 were observed in D2O (Fig. 3). For enantiomeric
resolution of the diastereomeric forms of compound
V, β-cyclodextrin in a D2O solution was used. In the
presence of β-cyclodextrin, one of the two signals (at
δ = 2.17) split to two signals indicating the separation
of the two enantiomeric forms of one diastereomer. In
this case, three signals at δ = 3.25, δ = 1.80, and δ
= 1.76 were observed. The signal at δ = 3.25, corre-
sponding to the second diastereotopic form, did not
split further.
1
the solution. In this respect, the 31P{ H} NMR spec-
tra revealed three and two peaks with different ra-
tios for II and V–VIII, respectively. Compounds V,
VII, and VIII exhibited the ratio of diastereomers of
1 : 0.9 while the ratio of 1 : 0.4 was observed for
VI indicating that synthesis of VI (containing the
nitro group) is stereoselective. The 31P NMR spec-
trum of II showed three separated signals (ratio of
peaks of 3 : 1 : 0.8) at δ = 21.74, δ = 21.87, and δ
2
= 23.3, respectively, with different J(P,NH) coupling
constants in the range of 9.9–10.7 Hz. In addition, the
1H and 13C NMR spectra of II showed three sets of
signals for individual stereoisomers. It was found that
the trans-1,2-diaminocyclohexane of the C2 symme-
try is a chiral compound, whereas symmetrical cis-
1,2-diaminocyclohexane is an optically inactive one.
However, this compound can exist in chiral confor-
mations which interconvert rapidly into each other
Replacement of the 4-sulphamoylphenyl group
with 4-nitrophenyl, benzoyl, or 4-nitrobenzoyl did not
change the stereochemistry of VI–VIII. In addition,
comparing the spectra of compounds I–V with those
of compounds VI–VIII it can be concluded that the
conformational diversity originates from the chiral di-
amines only.
—
In the IR spectra of compounds I–VIII, ν(P O)
—

694
K. Gholivand, F. Ghaziani/Chemical Papers 65 (5) 691–699 (2011)
Table 2. Spectral data of newly prepared compoundsa
Compound
Spectral data
IR, ν˜/cm−1: 3160 (s, NH), 3035 (s, NH), 2640 (m), 1588 (m), 1488 (m), 1399 (w), 1299 (m), 1242 (w), 1179 (s,
I
—
P
O), 1147 (s, SO2), 1092 (m), 950 (s, PN), 898 (w), 828 (m), 739 (m, PN), 584 (m), 537 (m)
—
1H NMR (DMSO-d6), δ: 6.61 (d, 2H, 3J = 8.4 Hz, ArH), 6.74 (s, 4H, ArH), 7.04 (s, 2H, NH2), 7.88 (d, 2H, 3J =
2
2
7.85 Hz, ArH), 8.40 (d, 1H, J(P,NH) = 8.1 Hz, NH), 8.59 (d, 2H, J(P,NH) = 17.2 Hz, NHP(O)NH)
13C NMR (DMSO-d6), δ: 109.59 (d, J(P,C) = 12.5 Hz), 116.39 (d, J(P,C) = 7.78 Hz), 119.13, 126.60, 131.75 (d,
3
3
2J(P,C) = 13.49 Hz), 135.35, 145.46
2
2
31P NMR (DMSO-d6), δ: 11.63 (dt, J(P,NH) = 16.9 Hz, J(P,NH )
ꢀ
= 8 Hz)
II
IR, ν˜/cm−1: 3385 (s, NH), 3215 (s, CH), 3070 (s, CH), 2940 (m), 1596 (m), 1499 (m), 1459 (m), 1301 (s), 1196 (m,
—
—
—
P
O), 1173 (s, P O), 1150 (s, SO2), 1079 (m), 948 (m), 833 (m), 710 (m), 540 (m), 425 (w)
—
1H NMR (DMSO-d6), δ: 1.20 (m, 2H, CH2), 1.29 (m, 2H, CH2), 1.50 (m, 2H, CH2), 1.61 (m, 2H, CH2), 1.66 (m,
2
4H, CH2), 1.80 (m, 2H, CH2), 2.89 (m, 2H, CH), 3.40 (m, 2H, CH), 4.64 (d, 1H, J(P,NH) = 10.7 Hz, NH), 4.71 (d,
2
2
2
1H, J(P,NH) = 9.9 Hz, NH), 4.82 (d, 1H, J(P,NH) = 10.0 Hz, NH), 4.83 (d, 1H, J(P,NH) = 10.2 Hz, NH), 6.62
(s, 2H, NH2), 6.64 (s, 2H, NH2), 7.22 (d, 2H, 3J = 8.8 Hz, ArH), 7.25 (d, 2H, 3J = 8.8 Hz, ArH), 7.35 (d, 2H, 3J
= 8.9 Hz, ArH), 7.52 (d, 1H, J(P,NH) = 7.1 Hz, NH), 7.55 (d, 1H, J(P,NH) = 7.2 Hz, NH), 7.57 (d, 2H, 3J = 8.8
2
2
Hz, ArH)
3
3
13C NMR (DMSO-d6), δ: 20.91, 20.94, 23.89, 23.97, 29.64 (d, J(P,C) = 6.6 Hz, CH2), 30.10 (d, J(P,C) = 5.0 Hz,
3
3
2
CH2), 30.49 (d, J(P,C) = 12.2 Hz, CH2), 30.72 (d, J(P,C) = 13.6 Hz, CH2), 52.34 (d, J(P,C) = 8.3 Hz), 52.42 (d,
2J(P,C) = 8.4 Hz), 59.97 (d, J(P,C) = 7.8 Hz), 60.12 (d, J(P,C) = 6.7 Hz), 116.65 (d, J(P,C) = 6.7 Hz, Cortho),
116.68 (d, J(P,C) = 6.6 Hz, Cortho), 116.97 (d, J(P,C) = 6.6 Hz, Cortho), 126.30, 126.33, 126.49, 134.36, 134.39,
134.45, 146.73, 146.88, 147.00
31P NMR (DMSO-d6), δ: 21.74 (m), 21.87 (m), 23.30 (m)
2
2
3
3
3
III
IV
IR, ν˜/cm−1: 3390 (s, NH), 3385 (s, NH), 3210 (m, CH), 3040 (w, CH), 2880 (w), 1595 (m), 1500 (m), 1418 (m),
—
1318 (m), 1283 (s), 1203 (m), 1178 (s, P O), 1148 (s, SO2), 1100 (s), 946 (m), 910 (m), 835 (m), 710 (m), 646 (m),
—
538 (m), 409 (w)
3
2
1H NMR (DMSO-d6), δ: 3.23 (d, 4H, J(P,H) = 9.8 Hz, CH2), 4.60 (d, 2H, J(P,NH) = 11.7 Hz, NH), 7.01 (bs, 2H,
NH2), 7.12 (d, 2H, 3J = 8.2 Hz, ArH), 7.54 (d, 1H, J(P,NH) = 9.8 Hz, NH), 7.57 (d, 2H, 3J = 8.3 Hz, ArH)
13C NMR (DMSO-d6), δ: 41.00 (d, J(P,C) = 9.9 Hz, CH2), 116.45 (d, 2C, J(P,C) = 6.9 Hz), 126.59, 134.40, 146.76
2
2
3
31P NMR (DMSO-d6), δ: 23.28 (m)
IR, ν˜/cm−1: 3320 (s, NH), 3195 (s, NH), 2930 (m), 1588 (m), 1490 (m), 1468 (w), 1332 (w), 1305 (w), 1178 (s,
—
P
O), 1143 (s, SO2), 1086 (m), 918 (m, PN), 825 (m, PN), 536 (m)
—
3
1H NMR (DMSO-d6), δ: 1.54 (s, 2H, CH2), 3.04 (d, 2H, J(P,H) = 24.9 Hz, CH), 3.15 (s, 2H, CH), 4.46 (s, 2H,
NH), 6.80 (bs, 2H, NH2), 7.19 (d, 2H, 3J = 8.45 Hz, ArH), 7.58 (d, 3J = 8.35 Hz, ArH), 7.66 (d, 1H, J(P,H) = 9.85
2
Hz, NH)
3
3
13C NMR (DMSO-d6), δ: 26.78 (d, J(P,C) = 7.57 Hz, CH2), 41.71, 116.45 (d, 2C, J(P,C) = 6.71 Hz), 126.49,
134.21, 146.63
31P NMR (DMSO-d6), δ: 5.13 (m)
V
IR, ν˜/cm−1: 3390 (s, NH), 3325 (s, NH), 3207 (m, NH), 3052 (m, NH), 2975 (m, NH), 2973 (m, CH), 2874 (m, CH),
—
1499 (m, CH), 1473 (m, SO2), 1299 (m, SO2), 1179 (s, P O), 1153 (s, SO2), 1098 (m, CH), 900 (m, SN), 540 (m,
—
SO2)
1H NMR (DMSO-d6), δ: 1.12 (d, 3H, 3J = 6.4 Hz, CH3), 1.14 (d, 3H, 3J = 6.4 Hz, CH3), 2.50 (m, CH2), 2.79 (m,
2
2
CH2), 3.35 (m, CH), 3.64 (m, CH), 4.55 (d, 1H, J(P,NH) = 10.3 Hz, NH), 4.61 (d, 1H, J(P,NH) = 10.9 Hz, NH),
4.73 (d, 1H, J(P,NH) = 10.6 Hz, NH), 4.76 (d, 1H, J(P,NH) = 10.3 Hz, NH), 7.04 (s, 2H, NH2), 7.14 (d, 2H, 3J =
2
2
8.8 Hz, ArH), 7.18 (d, 2H, 3J = 8.8 Hz, ArH), 7.48 (d, 1H, J(P,NH) = 6.9 Hz, NH), 7.53 (d, 1H, J(P,NH) = 7.4
2
2
Hz, NH), 7.56 (d, 2H, 3J = 8.5 Hz, ArH), 7.59 (d, 2H, 3J = 8.5 Hz, ArH)
13C NMR (DMSO-d6), δ: 21.31 (d, J(P,C) = 10.4 Hz, CH3), 22.14 (d, J(P,C) = 5.6 Hz, CH3), 48.23 (d, J(P,C)
=
3
3
2
2
2
2
10.0 Hz), 48.61 (d, J(P,C) = 6.0 Hz), 48.73 (d, J(P,C) = 5.8 Hz, CH2), 48.83 (d, J(P,C) = 10.6 Hz, CH2), 116.45
(d, J(P,C) = 7.0 Hz), 116.56 (d, J(P,C) = 7.0 Hz), 126.51, 126.58, 134.31, 134.37, 146.76, 146.82
31P NMR (D2O), δ: 21.76 (m), 22.52 (m)
3
3
31P NMR (DMSO-d6), δ: 2.17 (m), 3.72 (m)
31P NMR (D2O with β-cyclodextrin), δ: 1.76 (m), 1.80 (m), 3.25 (m)
IR, ν˜/cm−1: 3260 (m, NH), 2930 (w, CH), 1595 (s), 1516 (s, NO2), 1340 (s, NO2), 1295 (s, P O), 1173 (s, P O),
—
—
—
—
VI
1110 (m, SO2), 953 (m, PN), 835 (m, PN), 746 (m), 630 (m), 551 (w), 412 (w)
2
1H NMR (DMSO-d6), δ: 1.14 (m, CH3), 2.81 (m, CH2), 3.34 (m, CH), 3.67 (m, CH), 4.74 (d, 1H, J(P,NH) = 11.1
2
2
2
Hz, NH), 4.80 (d, 1H, J(P,NH) = 11.8 Hz, NH), 4.91 (d, 1H, J(P,NH) = 10.6 Hz, NH), 4.94 (d, 1H, J(P,NH)
=
11.1 Hz, NH), 7.2 (d, 2H, 3J = 9.1 Hz, ArH), 7.25 (d, 2H, 3J = 9.3 Hz, ArH), 8.05 (m, 2H, ArH), 8.11 (d, 1H,
2J(P,NH) = 7.3 Hz, NH)
13C NMR (DMSO-d6), δ: 21.20 (d, J(P,C) = 9.8 Hz, CH3), 22.02 (d, J(P,C) = 5.7 Hz, CH3), 48.08 (d, J(P,C)
3
3
2
=
2
2
2
9.7 Hz), 48.43 (d, J(P,C) = 8.8 Hz), 48.60 (d, J(P,C) = 9.0 Hz, CH2), 48.70 (d, J(P,C) = 9.2 Hz, CH2), 116.44
3
3
(d, J(P,C) = 7.0 Hz, ArC), 116.56 (d, J(P,C) = 6.9 Hz, ArC), 124.96, 125.02, 139.13, 139.19, 150.71, 150.75
31P NMR (DMSO-d6), δ: 21.33 (m), 22.11 (m)

K. Gholivand, F. Ghaziani/Chemical Papers 65 (5) 691–699 (2011)
695
Table 2. (continued)
Compound
Spectral data
VII
IR, ν˜/cm−1: 3300 (m, NH), 3209 (m, NH), 2970 (m, CH), 2875 (m), 1657 (s, C O), 1503 (m), 1458 (s), 1437 (s),
—
—
—
1196 (s, P O), 1059 (s, PN), 711 (s), 542 (m)
—
1H NMR (DMSO-d6), δ: 1.12 (d, 6H, 3J = 6.35 Hz, 2 × CH3), 2.73 (m, 1H, CH), 3.17 (m, 1H, CH), 3.36 (m, 2H,
2
2
CH2), 3.63 (m, 2H, CH2), 4.62 (d, 1H, J(P,NH) = 11.40 Hz, NH), 4.71 (d, 1H, J(P,NH) = 12.35 Hz, NH), 4.87 (d,
1H, J(P,NH) = 13.1 Hz, NH), 7.44 (t, 2H, 3J = 7.6 Hz, ArH), 7.55 (t, 2H, 3J = 7.30 Hz, ArH), 7.91 (d, 2H, 3J =
2
7.30 Hz, ArH), 7.94 (d, 2H, 3J = 7.8 Hz, ArH), 9.13 (s, 2H, NH)
13C NMR (DMSO-d6), δ: 21.13 (d, J(P,C) = 8.45 Hz, CH3), 22.39 (d, J(P,C) = 7.1 Hz, CH3), 48.33, 48.41, 48.47
3
3
2
2
3
(d, J(P,C) = 12.1 Hz, CH2), 48.73 (d, J(P,C) = 11.56 Hz, CH2), 127.37, 127.61, 127.95 (d, J(P,C) = 3.39 Hz),
128.11 (d, J(P,C) = 3.04 Hz), 131.73, 134.0 (d, J(P,C) = 7.55 Hz, C-1), 167.65 (s, C O), 167.85 (s, C O)
3
3
—
—
—
—
31P NMR (DMSO-d6), δ: 21.45 (m), 21.55 (m)
IR, ν˜/cm−1: 3402 (m), 3374 (m), 3313 (m, NH), 3065 (m, CH), 2904 (m, CH), 1665 (s, C O), 1602 (m), 1519 (s,
—
—
VIII
—
NO2), 1494 (s), 1461 (s), 1349 (s, NO2), 1200 (s, P O), 1069 (s), 976 (m), 849 (m), 780 (m), 722 (s), 705 (m), 547
—
(m)
1H NMR (DMSO-d6), δ: 1.12 (d, 6H, 3J = 5.8 Hz, 2 × CH3), 2.75 (m, 1H, CH), 2.78 (m, 1H, CH), 3.42 (m, 2H,
2
2
CH2), 3.63 (m, 2H, CH2), 4.73 (d, 1H, J(P,NH) = 11.8 Hz, NH), 4.82 (d, 1H, J(P,NH) = 11.8 Hz, NH), 4.84 (d,
1H, J(P,NH) = 11.9 Hz, NH), 4.98 (d, 1H, J(P,NH) = 13.5 Hz, NH), 8.14 (d, 4H, 3J = 8.9 Hz, ArH), 8.26 (d, 4H,
2
2
3J = 8.9 Hz, ArH), 9.11 (s, 2H, NH)
13C NMR (DMSO-d6), δ: 21.13 (d, J(P,C) = 8.4 Hz, CH3), 22.40 (d, J(P,C) = 7.2 Hz, CH3), 48.29, 48.38, 48.50
3
3
2
2
3
(d, J(P,C) = 12.1 Hz, CH2), 48.72 (d, J(P,C) = 11.7 Hz, CH2), 123.11, 123.26, 129.18, 129.45 (d, J(P,C) = 4.5
3
3
—
—
Hz), 139.70 (d, J(P,C) = 6.3 Hz, C-1 in Ar), 148.83 (d, J(P,C) = 7.5 Hz, C-4 in Ar), 166.25 (s, C O), 166.47 (s,
—
—
C
O)
31P NMR (DMSO-d6), δ: 21.04 (m), 21.17 (m)
a) Intensity of peaks in IR spectra: strong (s), medium (m), weak (w). In NMR spectra, Ar means aryl.
vibrations were in the range of 1173–1205 cm−1
For compounds containing a benzamide moiety, the
.
—
ν(P O) values appeared at higher wavenumbers than
—
for those possessing an aniline moiety (Table 2). The
—
value of ν(P O) of VIII containing a 4-nitrobenzoyl
—
moiety is the highest. It should be mentioned that the
IR spectra of chiral diazaphospholanes II and V–VIII
—
displayed only one or two peaks for ν(P O). As the
—
peaks are broad and with a shoulder, it is assumed
that the other bands overlapped with the broad band.
In order to gain insight into the molecular struc-
ture and different conformations of the diazaphospho-
lane V, ab initio calculations were performed using
the Gaussian 98 software at the HF and B3LYP lev-
els. Several conformations are feasible depending on
the orientation of the methyl group in five-membered
ring. The molecule of V has two chiral centres giv-
ing rise to four RS, SR, RR, and SS diastereomers. If
the methyl group in V is in axial or equatorial posi-
—
tions with trans conformation of P O and NH
—
exocyclic
bonds, then four diastereomers C1–C4 can be drawn.
Four diastereomers, C1 (RR), C2 (RS), C3 (SR), C4
(SS), are presented in Fig. 4 for diazaphospholane
V. These model molecules were optimised at the HF
and B3LYP levels using the standard 6-311G* and 6-
311+G** basis sets.
Energy differences for conformers C1–C4 and their
corresponding enantiomers C5–C8 are small and vary
at about 0.0–4.479876 kJ mol−1 (Table 3). The en-
ergies of conformers C1–C4 are equal to those of
their corresponding enantiomers C5–C8. Conformers
C3 and C1 are the most stable forms using the HF and
1
Fig. 2. High temperature dynamic 31P{ H} NMR spectra of
compound II in DMSO-d6 at temperatures: 313 K (1);
323 K (2); 333 K (3); 343 K (4); 353 K (5); 363 K (6).

696
K. Gholivand, F. Ghaziani/Chemical Papers 65 (5) 691–699 (2011)
in the HF and B3LYP methods, corresponding to
˚
—
the P O bond length (1.45 A) (Corbridge, 1995). In
—
conformers C1–C4, phosphorus atoms have distorted
tetrahedral geometries. For example, surrounding an-
gles around the P atom in C1 are in the range from
101.084◦ to 122.886◦. The P—N bond lengths (ca.
˚
1.68 A) are shorter than the standard P—N bond
˚
length (1.78 A) (Corbridge, 1995), suggesting the exis-
tence of partial multiple bond character between phos-
phorus and nitrogen atoms that has been confirmed
by the crystallographic data of previous similar com-
pounds (Gholivand et al., 2006, 2007b, 2007c).
Exocyclic nitrogen atoms as well as endocyclic ni-
trogen atoms of conformer C1 deviate from planarity.
That is, the sum of the surrounding angles around
Nexocyclic and two Nendocyclic atoms at HF/6-311G**
are 357.38◦, 347.33◦, and 347.77◦, with the averages
of 119.1◦, 115.8◦, and 115.9◦, respectively. It is clear
that the two Nendocyclic atoms have very distorted con-
figurations and they are not planar which results in a
puckered shape of the five membered rings. As sug-
gested previously, the trigonal geometry around the
N atoms and the small N—P—N angle caused by the
cyclic structure (92–93◦) enable stabilising the inter-
actions between vacant d orbitals of phosphorus and
the two 2p non-bonding orbitals of the nitrogen atoms
in the ring. Similar results were obtained using the
B3LYP/6-311G** method. This can be related to the
strain of the five membered rings.
1
Fig. 3. 31P{ H} NMR spectra of compound V: in D2O (1);
with an addition of 5 mass % of β-cyclodextrin (2);
with an addition of 25 mass % of β-cyclodextrin (3).
The analysis of calculated harmonic vibration fre-
quencies can be useful in the assignment of vibration
data. Assignment of vibration bands, obtained at the
B3LYP/6-311+G** level for the four proposed con-
formers of compound V was carried out. The result-
ing vibration wavenumbers for optimised geometries of
the C1–C4 conformers and the proposed assignments
are given in Table 4. In the IR spectrum of compound
V, strong absorptions in the range of 2975–3330 cm−1
B3LYP methods. In both forms, the methyl group is
located in the equatorial position. Differences in bond
lengths, bond angles, and torsion angles of conformers
C1–C4 are negligible but there are differences in their
spatial arrangements. These results are also valid for
corresponding enantiomers C5–C8.
˚
˚
—
The P O bond lengths vary from 1.45 A to 1.49 A
—
C1
C3
C2
C4
Fig. 4. Molecular structures of four diastereomers C1–C4 of compound V computed by HF and B3LYP methods.

K. Gholivand, F. Ghaziani/Chemical Papers 65 (5) 691–699 (2011)
697
Table 3. Calculated energies (Eh) and energy differences for eight conformers of compound V
HF/6-311+G**
Ea/(kJ mol−1 ∆Eb/(kJ mol−1
B3LYP/6-311+G**
Conformer
ꢀ
ꢀ
)
)
Ea/(kJ mol−1
)
∆Eb/(kJ mol−1
)
C1 (RR)
C2 (RS)
C3 (SR)
C4 (SS)
C5 (SS)
C6 (SR)
C7 (RS)
C8 (RR)
−6406.378848
1.046700
4.479876
0.000000
3.433176
1.046700
4.479876
0.000000
3.433176
−6431.920840
−6431.914978
−6431.922096
−6431.917072
−6431.920840
−6431.914978
−6431.922096
−6431.917072
0.795492
4.479876
0.000000
3.140100
0.795492
4.479876
0.000000
3.140100
−6406.373405
−6406.380522
−6406.375080
−6406.378848
−6406.373405
−6406.380522
−6406.37508
ꢀ
a)
E – sum of electronic and zero point energies; b) ∆E – energy differences; energies of other seven conformers were obtained
relative to the most stable conformer C3.
Table 4. Selected observed (for V) and calculated (for C1–C4) wavenumbers of diazaphospholane V at B3LYP/6-311+G**
Wavenumber/cm−1
Assignmenta
V
C1
C2
C3
C4
3390
3325
3207
3052
2975
2973
2874
1499
1473
1299
1179
1153
1098
900
3467
3459
3450
3447
3365
3086
3074
1460
1433
1254
1178
1159
1080
1043
758
3472
3469
3462
3448
3367
3085
3075
1464
1434
1253
1170
1157
1080
1052
752
3469
3465
3451
3450
3366
3087
3074
1445
1439
1252
1164
1155
1079
1047
751
3471
3467
3456
3450
3368
3086
3074
1451
1438
1254
1164
1155
1079
1046
752
νas(NH2)sulph
νs(NH)endo
νas(NH)anil
νs(NH)endo
νs(NH2)sulph
ν(CH)arom
ν(CH)arom
δ(CH)
νas(SO2)
νas(SO2)
—
ν(P O)
—
νs(SO2)
ν(CH)aliph
S—N
540
ω(SO2)
a) Assignment is approximate; as = antisymmetric; s = symmetric; sulph = sulphonamide; endo = endocyclic; anil = aniline; arom
= aromatic ring; aliph = aliphatic.
dominate for the NH stretching modes. The peaks at
3390 cm−1 and 2975 cm−1 were assigned to the an-
tisymmetric and symmetric N—H stretching modes
of sulphonamide, respectively, which is in agreement
with reported data (Topacli & Topacli, 2003; Varghese
et al., 2003). Calculations showed that these vibrations
are located in the range of 3364–3472 cm−1. Therefore,
theoretical calculations predict nearly similar values
for the antisymmetric and symmetric N—H stretch-
ing mode. In addition, the strong intensity band near
azaphospholane derivatives depends on the presence
or absence of chirality in the diamine moiety. Stereo-
chemical and conformational analyses were done using
1
NMR spectroscopy (31P{ H} spectra). In addition,
computational methods were found to be a useful al-
ternative for conformation studies since they revealed
the most stable conformers of V as those bearing a
methyl group in the equatorial position.
Acknowledgements. The authors are grateful to the Re-
search Office of the Tarbiat Modares University for financial
support of this work.
1153 cm−1 can be assigned to the S O stretching vi-
—
—
—
—
brations. The calculated values for the ν(S O) mode
were in the range of 1155–1159 cm−1. At 1197–1164
References
cm−1, the other characteristic modes of vibrations are
Amirkhanov, V. M., Ovchynnikov, V. A., Glowiak, T.,
&
—
the P O stretching modes appearing in the region of
—
1208–1179 cm−1 as bands of medium intensity.
Kozlowski, H. (1997). Crystal and molecular structures
of N,Nꢀ-diphenyl-Nꢀꢀ-trichloroacetyl-phosphorictriamide and
N,Nꢀ-tetraethyl-Nꢀꢀ-benzoylphosphorictriamide. The effect of
various substituents on the structural parameters of the
[C(O)N(H)P(O)] moiety. Zeitschrift fu¨r Naturforschung B
– A Journal of Chemical Sciences, 52, 1331–1336.
Conclusions
It can be concluded that the stereochemistry of di-

698
K. Gholivand, F. Ghaziani/Chemical Papers 65 (5) 691–699 (2011)
Berlicki, Lꢀ ., Rudzin´ska, E., & Kafarski, P. (2003). Enantiodif-
ferentiation of aminophosphonic and aminophosphinic acids
with α- and β-cyclodextrins. Tetrahedron: Asymmetry, 14,
1535–1539. DOI: 10.1016/S0957-4166(03)00273-8.
Corbridge, D. E. C. (1995). Phosphorus: An outline of its chem-
istry, biochemistry, and technology (5th ed., pp. 55, 57). Am-
sterdam, The Netherlands: Elsevier.
De la Cruz, A., Koeller, K. J., Rath, N. P., Spilling, C. D.,
& Vasconcelos, I. C. F. (1998). The synthesis, structure
and properties of diazaphospholes: Reagents and ligands for
asymmetric synthesis. Tetrahedron, 54, 10513–10524. DOI:
10.1016/S0040-4020(98)00502-X.
Gholivand, K., Shariatinia, Z., Pourayoubi, M., & Farshadian,
S. (2005b). Syntheses and spectroscopic study of some new
diazaphospholes and diazaphosphorinanes. Crystal struc-
ture of 4-F-C6H4C(O)N(H)P(O)[NHC6H4NH]. Zeitschrift
fu¨r Naturforschung B – A Journal of Chemical Sciences,
60, 1021–1026.
Gholivand, K., Shariatinia, Z., Yaghmaian, F., & Faramarzpour,
H. (2006). Substituent effects on the spectroscopic and struc-
tural parameters of several new 1,3,2-diazaphosphorinanes.
Syntheses, spectroscopic characterization, and X-ray crys-
tallography. Bulletin of the Chemical Society of Japan, 79,
1604-1606.
Denmark, S. E., Miller, P. C., & Wilson, S. R. (1991). Con-
Hall, C. R., Inch, T. D., Pottage, C., Williams, N. E., Campbell,
M. M., & Kerr, P. F. (1983). Use of carbohydrate derivatives
for studies of phosphorus stereochemistry. Part 8. Prepa-
ration and some reactions of 1,3,2-oxazaphospholidine-2-
ones and -2-thiones derived from 2-deoxy-3,4,6-tri-O-methyl-
2-methylamino-D-glucopyranose. Journal of the Chemical
Society, Perkin Transactions 1, 1983, 1967–1975. DOI:
10.1039/P19830001967.
Khaikin, L. S., Grikina, O. E., Vilkov, L. V., & Boggs, J.
E. (1988). Structure of 1,2,3-diazaphosphole and several of
its derivatives. Use of the results of nonempirical quan-
tum chemical calculations in the electron diffraction inves-
tigation of 2-acetyl-5-methyl- and 5-methyl-2-phenyl-1,2,3-
diazaphospholes. Journal of Structural Chemistry, 28, 607–
611. DOI: 10.1007/BF00749603.
figuration, conformation, and colligative properties of
a
phosphorus-stabilized anion. Journal of the American Chem-
ical Society, 113, 1468–1470. DOI: 10.1021/ja00004a089.
Devillers, J., Navech, J., & Albrand, J.-P. (1971). Heterocy-
cles contenant du phosphore—V. Analyse des spectres de
resonance magnetique protonique des oxo-2 methoxy ou
phénoxy-2, methyl-3, oxazaphospholanes-1,3,2: Exemples de
spectres du type ABXY. Organic Magnetic Resonance, 3,
177–186. DOI: 10.1002/mrc.1270030203.
Du, H., Zhao, B., & Shi, Y. (2008). Catalytic asymmetric allylic
and homoallylic diamination of terminal olefins via formal
C–H activation. Journal of the American Chemical Society,
130, 8590–8591. DOI: 10.1021/ja8027394.
Dutasta, J. P., Esteban-Calderon, C., Tinant, B.,
& De-
clercq, J.-P. (1990). Structure of bis(1,3-di-o-anisyl-2-thioxo-
1,3,2λ5-diazaphosphorinan-2-yl) oxide. Acta Crystallograph-
ica Section C: Crystal Structure Communications, C46, 68–
71. DOI: 10.1107/S0108270189005172.
Kim, H., Nguyen, Y., Yen, C. P.-H., Chagal, L., Lough, A.
J., Kim, B. M., & Chin, J. (2008). Stereospecific synthe-
sis of C2 symmetric diamines from the mother diamine by
resonance-assisted hydrogen-bond directed diaza-Cope rear-
rangement. Journal of the American Chemical Society, 130,
12184–12191. DOI: 10.1021/ja803951u.
Kranz, M., Denmark, S. E., Swiss, K. A., & Wilson, S. R.
(1996). An ab initio study of the P-C bond rotation in
phosphoryl- and thiophosphoryl-stabilized carbanions: Five-
and six-membered heterocycles. The Journal of Organic
Chemistry, 61, 8551–8563. DOI: 10.1021/jo9602783.
Lucet, D., Le Gall, T., & Mioskowski, C. (1998). The chem-
istry of vicinal diamines. Angewandte Chemie Interna-
tional Edition, 37, 2580–2627. DOI: 10.1002/(SICI)1521-
3773(19981016)37:19<2580::AID-ANIE2580>3.0.CO;2-L.
Nielsen, J., & Dahl, O. (1984). Stereochemistry of substitu-
tion at trico-ordinate phosphorus. Journal of the Chemi-
cal Society, Perkin Transactions 2, 1984, 553–558. DOI:
10.1039/P29840000553.
Dutasta, J. P., Grand, A., Guimares, A. C., & Robert, J.
B. (1979). Dioxaphospholanes-1,3,2, dimerisation, obtention
de composes heterocycliques phosphores et oxygenes a dix
chainons: tetra-oxa-1,3,6,8 diphosphecanes-2. Tetrahedron,
35, 197–207. DOI: 10.1016/S0040-4020(01)99482-7.
Gholivand, K., Oroujzadeh, N., Erben, M. F., & Della Vé-
dova, C. O. (2009a). Synthesis, spectroscopy, computational
study and prospective biological activity of two novel 1,3,2-
diazaphospholidine-2,4,5-triones. Polyhedron, 28, 541–547.
DOI: 10.1016/j.poly.2008.11.024.
Gholivand, K., Pourayoubi, M., Farshadian, S., Molani, S., &
Shariatinia, Z. (2005a). Synthesis and crystal structure of 5,5-
dimethyl-2-(p-methylanilino)-2-oxo-1,3,2-diazaphosphorina-
ne. Analytical Sciences: X-ray Structure Analysis Online,
21, x55–x56.
Gholivand, K., Pourayoubi, M., & Shariatinia, Z. (2007a).
2,3J(P,X) [X = H, C] coupling constants dependency to
the ring size, hybridization and substituents in new di-
azaphospholes and diazaphosphorinanes, NMR and X-ray
crystallography studies. Polyhedron, 26, 837–844. DOI:
10.1016/j.poly.2006.09.092.
Gholivand, K., Shariatinia, Z., Afshar, F., Faramarzpour, H.,
& Yaghmaian, F. (2007b). New 1,3,2-diazaphosphorinanes;
syntheses, spectroscopic characterization, X-ray crystallog-
raphy and ab initio calculations. Main Group Chemistry, 6,
231–248. DOI: 10.1080/10241220801994742.
Nifantiev, E. E., Sorokina, S. F., Borisenko, A. A., Zavalishina,
A. I., & Vorobjeva, L. A. (1981). Cyclic organic derivatives
of hypophosphorous acid. Tetrahedron, 37, 3183–3194. DOI:
10.1016/S0040-4020(01)98852-0.
Olson, D. E., & Du Bois, J. (2008). Catalytic C–H amina-
tion for the preparation of substituted 1,2-diamines. Journal
of the American Chemical Society, 130, 11248–11249. DOI:
10.1021/ja803344v.
Parker, D. (1991). NMR determination of enantiomeric purity.
Chemical Reviews, 91, 1441–1457. DOI: 10.1021/cr00007a0
09.
Gholivand, K., Shariatinia, Z., Ansar, S., Mashhadi, S. M., &
Daeepour, F. (2009b). The first naphthodiazaphosphorinane
in the solid phase; syntheses, spectroscopic studies and X-ray
crystallography of some new 1,3,2-diheterophosphorus com-
pounds. Structural Chemistry, 20, 481–488. DOI: 10.1007/
s11224-009-9445-9.
Gholivand, K., Shariatinia, Z., Mahzouni, H. R., & Amiri,
S. (2007c). Phosphorus heterocycles: synthesis, spectro-
scopic study and X-ray crystallography of some new di-
azaphosphorinanes. Structural Chemistry, 18, 653-660. DOI:
10.1007/s11224-007-9197-3.
Peyronel, J. F., Samuel, O., & Fiaud, J. C. (1987). New chi-
ral bicyclic phosphoramides derived from (L)-glutamic acid.
The Journal of Organic Chemistry, 52, 5320–5325. DOI:
10.1021/jo00233a004.
Saibabu Kotti, S. R. S., Timmons, C., & Li, G. (2006). Vici-
nal diamino functionalities as privileged structural elements
in biologically active compounds and exploitation of their
synthetic chemistry. Chemical Biology & Drug Design, 67,
101–114. DOI: 10.1111/j.1747-0285.2006.00347.x.
Setzer, W. N., Black, B. G., Hovanes, B. A., & Hubbard, J. L.
(1989). Conformational analysis of 1,3,2-oxazaphospholanes

K. Gholivand, F. Ghaziani/Chemical Papers 65 (5) 691–699 (2011)
699
derived from ephedrine and pseudoephedrine. The Journal of
Wang, B., Du, H. F.,
&
Shi, Y. (2008).
A
palladium-
Organic Chemistry, 54, 1709–1713. DOI: 10.1021/jo00268a
038.
Topacli, C., & Topacli, A. (2003). Ab initio calculations and
vibrational structure of sulfanilamide. Journal of Molecular
Structure, 644, 145–150. DOI: 10.1016/S0022-2860(02)00473-
8.
Varghese, H. T., Panicker, C. Y., & Philip, D. (2006). Vibra-
tional spectroscopic studies and ab initio calculations of sul-
fanilamide. Spectrochimica Acta Part A, 65, 155–158. DOI:
10.1016/j.saa.2005.09.040.
Viso, A., Fernández de la Pradilla, R., García, A., & Flores, A.
(2005). α,β-Diamino acids: Biological significance and syn-
thetic approaches. Chemical Reviews, 105, 3167–3196. DOI:
10.1021/cr0406561.
catalyzed dehydrogenative diamination of terminal olefins.
Angewandte Chemie International Edition, 47, 8224–8227.
DOI: 10.1002/anie.200803184.
Warnat, K. (1941). Sulphanilamide phosphoric acid derivative
and process for the manufacture thereof. U.S. Patent No.
2245539. Washington, D.C., USA: U.S. Patent and Trade-
mark Office.
Zalán, Z., Martinek, T. A., Lázár, L., & Fu¨l¨op, F. (2003). Syn-
thesis and conformational analysis of 1,3,2-diazaphosphorino
[6,1-a]isoquinolines, a new ring system. Tetrahedron, 59,
9117–9125. DOI: 10.1016/j.tet.2003.09.062.