A phosphoryl to spiro-bicyclophosphorane transformation via β-amidic proton elimination in phosphorylated hydrazides

Article abstract of DOI:10.1016/j.tetlet.2012.08.105

The reaction between phosphoryl-containing reagents and hydrazides has been studied. The tetrahedral phosphoryl structure is transformed into a spiro-bicyclophosphorane system with trigonal bipyramidal geometry by the elimination of a β-amidic proton in t

Full text of DOI:10.1016/j.tetlet.2012.08.105

Tetrahedron Letters 53 (2012) 5944–5947
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A phosphoryl to spiro-bicyclophosphorane transformation via b-amidic
proton elimination in phosphorylated hydrazides
⇑
Khodayar Gholivand , Hamid R. Mahzouni, Foroogh Molaei, Ali A. Kalateh
Department of Chemistry, Faculty of Basic Sciences, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction between phosphoryl-containing reagents and hydrazides has been studied. The tetrahedral
phosphoryl structure is transformed into a spiro-bicyclophosphorane system with trigonal bipyramidal
geometry by the elimination of a b-amidic proton in the reaction between a hydrazide and phosphoryl
reagents with at least two leaving groups (Cl) bound to the phosphorus atom, such as POCl3 or PhPOCl2.
In the spiro-bicyclophosphorane structure, the C@N imine bond is formed upon b-amidic proton elimi-
nation, leading to the conversion of the C@O into a C–O bond and the formation of a P–O bond. All of
these structural rearrangements are supported by X-ray crystallography data, and NMR and IR
experiments.
Received 25 June 2012
Revised 13 August 2012
Accepted 24 August 2012
Available online 1 September 2012
Keywords:
2JPH Coupling constant
Hydrazide
Ó 2012 Elsevier Ltd. All rights reserved.
Phosphoryl
Spiro-bicyclophosphorane
The structures of cyclic pentacoordinate phosphoranes have at-
tracted significant interest because they serve as models for biolog-
ically active compounds and intermediates.1–4 Heterocyclic
phosphoranes with a P–N–N@C–O unit have been previously pre-
pared via the redox coupling of a trialkyl- or triarylphosphine
(PR3) and a dialkyl azodicarboxylate (ROOCN@NCOOR).5,6 Such
N- and O-cycloadditions also occur in the reaction of a simple
hydrazide (RCONHNH2) with phosphorus(III) mono- or triamides
to form cyclophosphorane systems.7,8 Moreover, there are reports
on the synthesis and reactivities of phosphorus hydrazides
[P(X)(NRNH2)2, X = O and S],9–16 although these compounds do
not transform into products with the phosphorane structure. To
the best of our knowledge, phosphoryl-containing reagents have
never been used for the formation of spiro-bicyclophosphoranes.
Here, we present the synthesis of such compounds based on the
reaction of simple hydrazides (benzhydrazide and 4-pyridinecarb-
oxylic acid hydrazide) with phosphoryl-containing reagents
(POCl3, PhPOCl2 and Ph2POCl). The molecular geometry of the
products depends on the number of appropriate leaving groups
(Cl) bound to the phosphoryl functional group in the reactant. A
simple acid-base reaction between benzhydrazide and a phos-
phoryl-containing reactant with only one chlorine atom (Ph2POCl)
produces a product with tetrahedral structure at the phosphorus
atom. On the other hand, products with a trigonal bipyramidal
structure (spiro-bicyclophosphorane) are formed, when phos-
phoryl reagents with at least two chlorine atoms (PhPOCl2 or
POCl3) are used.
O
O
P
O
Et3N
β
NH NH2
Ph POCl
+
2
Ph
Ph
NH N
MeCN, 0 °C
H
α
Scheme 1. Synthesis of 1.
Compound 1 was prepared by the reaction between a mixture
of benzhydrazide, Ph2POCl, and triethylamine in acetonitrile17
(Scheme 1). Figure 1 shows the X-ray crystal structure of 1. The
P@O (1.489(2) Å), P1–N2 (1.659(2) Å), and C@O (1.235(2) Å) dis-
tances are similar to those in other well-known phosphoramides18
and carbacylamidophosphates19 with tetrahedral configurations at
the phosphorus atom. The chemical shift of the b-amidic proton in
the 1H NMR spectrum of 1 appeared at 10.17 ppm (Table 1), imply-
ing its high acidity and ability to undergo elimination in basic med-
ia. The chemical shifts of 21.80 and 166.93 ppm in the 31P and 13
C
NMR spectra, respectively, and the bands at 1198 (P@O) and 1655
(C@O) cmÀ1 in the IR spectrum confirm the presence of P@O and
C@O functional groups in 1. We have recently shown that the 2JPNH
coupling constant increases when the P–N distance is shortened.20
2
Here, the JPNH value (21.9 Hz) in 1 is relatively high in magnitude
compared with other phosphoramide compounds previously re-
ported,18,20 although the P1–N2 distance is not too short.
The phosphoryl structure is transformed into a spiro-bicyclo-
phosphorane system by a dehydration–cyclization rearrangement,
when at least two Cl leaving groups are bound to the P@O func-
tional group in the starting material. The reaction between benzhy-
drazide and POCl3 (2:1), in acetonitrile under reflux conditions,
⇑
Corresponding author. Tel.: +98 21 82883443.
E-mail address: gholi_kh@modares.ac.ir (K. Gholivand).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.08.105

K. Gholivand et al. / Tetrahedron Letters 53 (2012) 5944–5947
5945
O
O
O
reflux in MeCN
β
α
H
2
NH NH2 + POCl3
H
HN P NH N C Ph
Cl
N
C O
Ph
H2O+
Cl
HO
P
Cl
NH
H
H
N
H+
N
P
NH
N
H
H
N
N
N
O
O
C
O
C
O
Ph
Ph
Ph
Ph
H2O
H+
Ph
R
NH
N
and
Ph
R =
Figure 1. ORTEP representation of compound 1. Selected bond lengths (Å) and
bond angles (°): P1–N2, 1.6587(15); P1–O2, 1.4886(12); P1–C8, 1.7981(18); P1–
C14, 1.7941(17); N1–N2, 1.4048(19); C1–N1, 1.346(2); C1–O1, 1.235(2); O1–P1–
O2, 170.12(8); O2–P1–N2, 118.55(7); O2–P1–C14, 110.93(7); O2–P1–C8, 111.42(8);
C8–P1–C14, 108.41(8); N2–P1–C14, 103.67(7); N2–P1–C8, 103.10(8).
O
H
N
O
N
O
N
N
H
P
2 RH
r.t.
N
H
N
P
N
H
O
N
Cl
O
leads to intermediate I. Compounds 2 and 3 were prepared by
treatment of the appropriate amines (morpholine and tert-
butylamine) with intermediate I (2:1),21 Scheme 2. The proposed
synthetic pathway for products 2 and 3 (Scheme 2) indicates that
cyclization of the initial phosphorylated hydrazide is started by
elimination of the b-amidic proton followed by dehydration.
Compound 2 was recrystallized from a mixture of methanol and
acetonitrile (4:1) at room temperature to obtain crystals suitable
for X-ray analysis.
Ph
N
NH
Ph
Intermediate I
, 3: R=
2: R =
O
Scheme 2. Synthesis of compounds 2 and 3 and the proposed reaction mechanism.
NH
protons (2JPNH = 45.2 Hz)
and
one
NHtert-butylamine
a
(2JPNH = 12.1 Hz) proton lead to a doublet of triplets for the 31P
2
Figure 2 shows the molecular structure of compound 2. The
phosphorus atom adopts a distorted trigonal bipyramidal geome-
try in spiro-bicyclophosphorane 2 with the oxygen atoms in axial
and nitrogen atoms in equatorial positions. The C1–N2 distance
(1.282(3) Å) in 2 is considerably shorter than a typical C–N single
bond, while the C1–O1 distance (1.351(2) Å) in 2 is longer than
the C@O bond in 1. This is in good agreement with the b-amidic
proton elimination and the changes in the C1–N2 and C1–O1 bond
lengths upon cyclization. In the 31P NMR spectrum of 2, a triplet of
triplets appeared at À37.72 ppm. This splitting pattern arises from
NMR signal in compound 3. The JPNH coupling constants in com-
pounds 2 and 3 are larger than the corresponding values in 1.
The decrease in d (13C) values, from 166.93 ppm in 1 to 152.54
and 151.68 ppm, respectively, in compounds 2 and 3 (Table 1),
confirms the formation of a CO–P connection between the carbonyl
oxygen atom and the phosphorus atom upon cyclization. The CO–P
bond leads to spin couplings for the phosphorus and carbon nuclei
2
with JPOC values in the range of 14.1–14.6 Hz. The sharp bands at
ꢀ1330 cmÀ1 in the IR spectra of compounds 2 and 3 confirm the
decrease in the bond order from C@O to C–O on cyclization and
that the oxygen atom is bound to the phosphorus atom.
the spin couplings between the phosphorus nucleus and two NH
a
(2JPNH = 40.4 Hz) and two axial N–CHmorpholine (3JPNCH = 8.9 Hz) pro-
Compounds 4–6 were synthesized by the reaction of a mixture
of triethylamine and benzhydrazide or 4-pyridinecarboxylic acid
tons. The spin couplings between the phosphorus nucleus and two
Table 1
Selected spectroscopic data of products 1–8
Product
1
da
(
31P) in ppm
1H: db,c (ppm)/2JPNH (Hz)
13C: db,c (ppm)/2JPOC (Hz)
m
(C@O) in cmÀ1
1655
a
21.80
H :7.76/21.9
166.93/–
Hb:10.17/–
1H: db,c/2JPNH (Hz)
13C: db,c/2JPOC (Hz)
m
(C@O/C–O) in cmÀ1
2
3
À37.72
À43.31
8.57/40.4
3.69/12.1
8.17/45.2
8.85/36.9
7.15/13.4
8.58/39.9
7.32/13.3
8.99/40.9
6.75/36.6
8.48/39.6
9.88/–
152.54/14.1
151.68/14.6
–/1330
–/1328
4
5
À36.19
À47.40
154.20/10.9
152.52/15.1
–/1324
–/1324
6
7
À46.92
À45.23
150.71/15.4
–/1326
152.06/14.6
166.39/–
1669/1329
8
À45.31
7.12/37.3
8.98/41.1
10.38/–
150.41/15.4
164.91/–
1686/1323
a
b
c
The 31P NMR spectra were recorded for DMSO-d6 solutions at 202.45 MHz.
The 31H and 13C NMR spectra were recorded for DMSO-d6 solutions at 500.13 and 125.77 MHz, respectively.
The chemical shifts for the amidic protons and carbonyl (or imine) carbon atoms are provided.

5946
K. Gholivand et al. / Tetrahedron Letters 53 (2012) 5944–5947
Figure 2. ORTEP representation of compound 2. Selected bond lengths (Å) and bond angles (°): P1–N1, 1.6588(18); P1–N3, 1.6562(18); P1–N5, 1.662(2); P1–O1, 1.7296(15);
P1–O2, 1.7150(14); C1–N2, 1.282(3); C8–N4, 1.285(3); C1–O1, 1.351(2); C8–O2, 1.357(2); O1–P1–O2, 170.12(8); O1–P1–N1, 86.08(8); O1–P1–N3, 88.61(8); O1–P1–N5,
95.73(9); O2–P1–N1, 90.22(8); O2–P1–N3, 86.23(8); O2–P1–N5, 94.13(9); N1–P1–N3, 126.46(10); N3–P1–N5, 118.39(10); N1–P1–N5, 115.14(10).
showed two doublets at 6.75 and 7.48 ppm confirming the pres-
N
2
ence of two types of
a-amidic protons with JPNH values of
39.6 Hz (for the endocyclic NH proton) and 36.6 Hz (for the exo-
a
cyclic NH proton), respectively. Two signals at 152.06 and
a
H
N
H
N
H
N
N
N
N
N
O
O
N
N
O
166.39 ppm in the 13C NMR spectrum of 7 corresponded to the car-
bon atom in the ring (C–O) and the free carbonyl group (C@O),
respectively. Two bands at 1329 and 1669 cmÀ1 in the IR spectrum
of 7 were assigned to the C–OP and C@O bonds. Similar spectro-
scopic features were observed for compound 8.
N
N
N
P
P
P
H
H
H
O
O
NH
O
NH
In summary, the products of the reactions between hydrazides
and different phosphoryl-containing reagents have been com-
pared. The phosphoryl to spiro-phosphorane transformation was
observed when using phosphoryl reactants with at least two chlo-
rine atoms. The synthesis, characterization, structural determina-
tion, and quantum mechanical calculations are now being
performed in our laboratory for a number of additional phosphor-
ylated hydrazides in order to investigate the question of why the
2JPNH values in these compounds are surprisingly high in
magnitude.
N
4
5
N
6
H
N
H
N
N
O
N
O
N
N
N
P
N
P
H
H
O
NH
NH
O
NH
NH
N
O
O
Acknowledgements
N
7
8
Scheme 3. Structures of compounds 4–8.
Financial support of this work by the Tarbiat Modares Univer-
sity research council is gratefully acknowledged.
hydrazide with PhPOCl2 and PhNHPOCl2 (Scheme 3). The formation
Supplementary data
of the CO–P bond was again confirmed by the values observed for d
2
(
13C) in the range of 150.71–154.20 ppm with JPOC couplings of
Crystallographic data (excluding structure factors) for the struc-
tures in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication nos.
817641 (1) and 786389 (2). Copies of these data can be obtained,
free of charge, on application to CCDC, 12 Union Road, Cambridge
about 10–15 Hz. The 31P NMR signal of compounds 4 appeared
as a triplet of triplets at À36.19 ppm, as a result of spin coupling
of the phosphorus nucleus with two NHhydrazide and two ortho-
phenyl protons. A doublet of triplets splitting pattern was observed
for the 31P NMR signal in compounds 7 and 2, due to spin coupling
between the phosphorus and the NHaniline and NHhydrazide protons.
In the 1H NMR spectrum of compound 5, two signals at 7.15 and
8.58 ppm correspond to the NHaniline and NHhydrazide amide protons
CB2
1EZ,
UK,
(fax:
+44-(0)1223-336033
or
e-mail:
deposit@ccdc.cam.ac.uk).
Supplementary data (the experimental procedures and charac-
terization data for compounds 4–8) associated with this article
can be found, in the online version, at http://dx.doi.org/10.1016/
j.tetlet.2012.08.105.
2
with JPNH coupling constant values of 13.4 and 39.9 Hz, respec-
tively. Similarly, the chemical shifts of 7.32 and 8.99 ppm were as-
signed to the NHaniline and NHhydrazide protons, respectively, with
2JPNH values of 13.3 and 40.9 Hz in compound 6.
Products 7 and 8 were obtained by the reaction between POCl3
and a mixture of triethylamine and benzhydrazide (7) or 4-
pyridinecarboxylic acid hydrazide (8). A quartet splitting pattern
was observed for the 31P NMR signal in compounds 7 and 8, due
References and Notes
1. Timosheva, N. V.; Chandrasekaran, A.; Holmes, R. R. J. Am. Chem. Soc. 2005, 127,
12474–12475.
2. Timosheva, N. V.; Chandrasekaran, A.; Holmes, R. R. Inorg. Chem. 2006, 45,
3113–3123.
3. Holmes, R. R.; Deiters, J. A. Inorg. Chem. 1994, 33, 3235–3238.
4. Chen, Z.-Z.; Tan, B.; Li, Y.-M.; Zhao, Y.-F. J. Org. Chem. 2003, 68, 4052–4058.
to spin coupling between the phosphorus nucleus and three NH
a
(endocyclic and exocyclic) protons. The 1H NMR spectrum of 7

K. Gholivand et al. / Tetrahedron Letters 53 (2012) 5944–5947
5947
5. Kumar, N. S.; Kumar, K. P.; Pavan Kumar, K. V. P.; Kommana, P.; Vittal, J. J.;
Kumara Swamy, K. C. J. Org. Chem. 2004, 69, 1880–1889.
6. Kumar, N. S.; Kommana, P.; Vittal, J. J.; Kumara Swamy, K. C. J. Org. Chem. 2002,
67, 6653–6658.
7. Nifantiev, E. E.; Grachev, M. K.; Burmistrov, S. Y. Chem. Rev. 2000, 100, 3755–
3799.
(DMSO-d6): d 127.3 (s), 128.2 (s), 128.3 (s), 131.4 (s), 131.5 (s), 131.8 (s), 132.1
(d, 2JPC = 9.5 Hz, Cortho), 132.5 (d, 1JPC = 63.4 Hz, Cipso), 166.9 (s) ppm. Selected IR
data (KBr, cmÀ1): 3155 (s), 3005 (m), 2840 (m), 1655 (s), 1544 (m), 1434 (s),
1319 (m), 1198 (s), 1123 (s), 1067 (m), 908 (m), 725 (s), 689 (s), 523 (m).
18. Gholivand, K.; Mahzouni, H. R.; Pourayoubi, M.; Amiri, S. Inorg. Chim. Acta.
2010, 363, 2318–2324.
8. Schmidpeter, A.; Luber, J.; Riedl, H.; Volz, M. Phosphorus Sulfur 1977, 3, 171–
174.
19. Gholivand, K.; Mostaanzadeh, H.; Koval, T.; Dusek, M.; Erben, M. F.; Vedova, C.
O. D. Acta Crystallogr., Sect. B 2009, B65, 502–508.
9. Majoral, J. P.; Kraemer, R.; Navech, J.; Mathis, F. Tetrahedron 1976, 32, 2633–
2644.
20. Gholivand, K.; Mahzouni, H. R.; Esrafili, M. D. Dalton Trans. 2012, 41, 1597–
1608.
10. Pandurangi, R. S.; Kuntz, R. R.; Volkert, W. A.; Barnesa, C. L.; Katti, K. V. J. Chem.
Soc., Dalton Trans. 1995, 565–569.
21. General procedure for synthesis of compounds 2 and 3: 10 mmol (1.362 g) of
benzhydrazide was added to
a cooled solution of 5 mmol (0.766 g) of
11. Chandrasekhar, V.; Azhakar, R.; Bickley, J. F.; Steiner, A. Cryst. Growth Des. 2006,
6, 910–914.
12. Katti, K. V.; Ge, Y. W.; Singh, P. R.; Date, S. V.; Barnes, C. L. Organometallics 1994,
13, 541–547.
13. Delavaux-Nicot, B.; Douziech, B.; Mathieu, R.; Lavigne, G. Inorg. Chem. 1995, 34,
4256–4261.
14. Chandrasekhar, V.; Azhakar, R.; Andavan, G. T. S.; Krishnan, V.; Zacchini, S.;
Bickley, J. F.; Steiner, A.; Butcher, R. J.; Kogerler, P. Inorg. Chem. 2003, 42, 5989–
5998.
15. El-Deek, M.; El-Sawi, E.; Mohamed, M. J. Chem. Eng. Data 1981, 26, 340–342.
16. Ovrutskii, V. M.; Protsenko, L. D. Russ. Chem. Rev. 1986, 55, 343–356. and
references therein.
17. Synthesis and characterization of 1: 5 mmol (1.183 g) of diphenylphosphinic
chloride was added dropwise to a mixture of 5 mmol (0.506 g) of Et3N and
5 mmol (0.681 g) of benzhydrazide in dry MeCN at 0 °C and the mixture was
stirred for 10 h. The resulting white product was filtered off and crystals
phosphoryl chloride in CCl4 at 0 °C and the mixture was stirred for 1 h. The
resulting white product was filtered off and treated with a solution of 10 mmol
of morpholine (2) or tert-butylamine (3) in 40 ml MeCN at room temperature
for 8 h. The resulting suspension was filtered and the solvent evaporated under
vacuum to afford an oily residue. The product was washed with H2O followed
by MeCN to give a white powder. (a) Characterization data of 2: Yield 67%
(1.287 g), m.p. 237–240 °C, Anal. Calcd for C18H20N5O3P (385.36): C 56.09, H
5.23, N 18.17; Found C 56.23, H 5.44, N 18.33. 31P NMR (DMSO-d6): d À37.72 (t
of t, 2JPNH- = 40.4 Hz and 3JPNCH = 8.9 Hz) ppm. 1H NMR (DMSO-d6): d 2.76 (m,
a
4H, CH2), 3.50 (m, 4H, CH2), 7.42 (m, 6H, Ar-H), 7.70 (d, 3JHH = 7.1 Hz, 4H, Ar-H),
8.57 (d, 2JPNH = 40.4 Hz, 2H, NH ) ppm. 13C{1H} NMR (DMSO-d6): d 45.9 (s), 66.6
a
2
(d, JPC = 6.5 Hz), 124.6 (s), 128.5 (s), 128.7 (s), 129.4 (s), 152.5 (d,
2JPOC = 14.1 Hz) ppm. Selected IR data (KBr, cmÀ1): 3370 (s), 1668 (m), 1444
(m), 1330 (s), 1110 (m), 1066 (s), 956 (s), 707 (s). (b) Characterization data of 3:
Yield 63% (1.166 g), m.p. 244–248 °C, Anal. Calcd for C18H22N5O2P (371.36): C
58.21, H 5.97, N 18.86; Found C 58.11, H 5.80, N 18.97%. 31P NMR (DMSO-d6): d
suitable for X-ray diffraction were obtained from
a
CH3OH/CH3CN (1:2)
À43.31 (d of t, 2JPNH- = 45.2 Hz and 2JPNH-tert-butylamine = 12.1 Hz) ppm. 1H NMR
a
2
solution of 1 at room temperature. Yield 74% (1.237 g), m.p. 165–168 °C, Anal.
Calcd for C19H17N2O2P (336.32): C 67.84, H 5.09, N 8.33; Found C 67.63, H 5.17,
N 8.44. 31P NMR (DMSO-d6): d 21.80 (m) ppm.1H NMR (DMSO-d6): d 7.36 (t,
(DMSO-d6): d 1.17 (s, 9H, CH3), 3.69 (d, JPNH = 12.4 Hz, 1H, NHtert-butylamine),
7.41 (m, 6H, Ar-H), 7.71 (d, 3JHH = 7.3 Hz, 4H, Ar-H), 8.17 (d, 2JPNH = 45.2 Hz, 2H,
NH ) ppm. 13C{1H} NMR (DMSO-d6): d 31.8 (d, 2JPC = 5.6 Hz), 50.6 (s), 124.6 (s),
a
3
2
3JHH = 7.5 Hz, 2H, Ar-H), 7.46 (m, 5H, Ar-H), 7.52 (t, JHH = 7.1 Hz, 2H, Ar-H),
128.29 (s), 129.0 (s), 129.3 (s), 151.7 (d, JPOC = 14.6 Hz) ppm. Selected IR data
3
2
7.63 (d, JHH = 7.9 Hz, 2H, Ar-H), 7.76 (d, JPNH = 21.9 Hz, 1H, NH ), 7.94 (dd,
(KBr, cmÀ1): 3435 (s), 1606 (m), 1328 (s), 1224 (m), 1070 (s), 1046 (m), 868
(m), 720 (s), 688 (s).
a
3JHH = 7.6 Hz, 2JPCH = 11.3 Hz, 4H, CHortho), 10.17 (s, 1H, NHb) ppm. 13C{1H} NMR