Solvolysis of 1-oxo-2,8-diphenyl-2,5,8-triaza-1λ 5-phosphabicyclo[3.3.0]octane: New rearrangement of an eight- To a five-membered phosphodiamidate system

Article abstract of DOI:10.1039/a800836a

The alcoholysis of the title compound with RO^-/ROH gives the 1,3,2-diazaphospholidine derivative via the cleavage of the P-N(2) bond, while under acidic catalysis the P-N(5) bond is broken leading to the eight-membered monocyclic product, which

Full text of DOI:10.1039/a800836a

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5
Solvolysis of 1-oxo-2,8-diphenyl-2,5,8-triaza-1l -phosphabicyclo[3.3.0]octane:
new rearrangement of an eight- to a five-membered phosphodiamidate system
Xavier Y. Mbianda, Tomasz A. Modro*† and Petrus H. Van Rooyen
Centre for Heteroatom Chemistry and Department of Chemistry, University of Pretoria, Pretoria 0002, South Africa
The alcoholysis of the title compound with RO2/ROH gives
the 1,3,2-diazaphospholidine derivative via the cleavage of
the P–N(2) bond, while under acidic catalysis the P–N(5)
bond is broken leading to the eight-membered monocyclic
product, which can isomerize via a new type of rearrange-
ment to the former five-membered system.
We have recently reported the preparation of the bicyclic
phosphoric triamides 1 via the base-promoted cyclization of the
corresponding
3-(2-chloroethyl)-2-oxo-1-aryl-2-arylamino-
1,3,2-diazaphospholidines.1 Nucleophilic cleavage of one of the
P–N bonds in 1 can lead to another 1,3,2-diazaphospholidine
derivative [‘exo’ departure of N(2)], or to a novel, eight-
membered heterocyclic system 2 [‘endo’ departure of N(5)]
(Scheme 1). We present here the results of the acid-catalyzed or
base-promoted alcoholysis of 1a (Ar = Ph). It was expected
that under acidic conditions the regioselectivity governed by the
first protonation site of the substrate2 should involve the
departure of the more basic N(5) atom. Our recent 15N NMR
spectroscopic studies3 indicated a high degree of ‘p3’ character,
hence high basicity, of N(5) in 1. Alcoholysis of 1a carried out
in an alcohol containing 1 equiv. of dry HCl led, as expected, to
the exclusive cleavage of the P–N(5) bond, yielding the
Fig. 1 ORTEP plot of the structure of the N-benzoyl derivative of 2b
When free cyclic diamido phosphates 2 were stored as neat
substances, or as solutions in aprotic solvents, they underwent
slow change yielding another phosphorus-containing product.
Full conversion could be achieved by refluxing 2 in benzene or
THF and, for 2b, the product, after isolation and purification,
was identified as the isomeric 3-[2-(phenylamino)ethyl]-2-oxo-
corresponding
1-oxo-1-alkoxy-2,8-diphenyl-2,5,8-triaza-
5
1l -phosphacyclooctane 2a (Ar = Ph; Nu = OMe) or 2b
(Ar = Ph; Nu = OEt).‡ Amido esters 2 are, however, rather
unstable compounds and undergo further changes upon purifi-
cation (vide infra); they could be converted into stable
derivatives via acylation of the N(5) atom.§ Unambiguous
evidence for the structure of the primary product of the
solvolysis was obtained from the crystal structure of the N5-Bz
derivative of 2b (Fig. 1).¶ Structural parameters of the
phosphodiamidate function in N5-Bz2b are similar to those
reported for related structures, except for two points. First, we
observe the short P···N(2) non-bonded distance of 3.242 Å,
which should be even shorter in free, nonbenzoylated 2b.
Second, the two P–N bonds are non-equivalent: while one
(1.651 Å) lies well within a typical bond distance for
phosphoramidates,4 the other (1.688 Å) indicates a significantly
lower bond order.
5
2-ethoxy-1-phenyl-1,3,2l -diazaphospholidine 3b.∑ The struc-
ture of this product was determined by X-ray diffraction
(Fig. 2),** demonstrating unambigously the 8 ? 5 ring
contraction nature of the rearrangement. The only reported
structure closely related to 3b is that of Jones et al.,5 the
molecular parameters of both compounds correspond well to
each other.
This new ring contraction 2b ? 3b can be conveniently
followed via 31P NMR spectroscopy (DdP = 6.4 ppm).
Reactions carried out in refluxing THF with variable initial
concentrations of 2b showed clearly the first order kinetics, with
k1 = (4.1 ± 0.1) 3 1025 s21. The rearrangement can be
explained in terms of intramolecular 1,5-nucleophilic attack of
the amine nitrogen at the phosphoryl centre, followed by proton
transfer and P–N bond cleavage (Scheme 2); this mechanism is
also supported by the structural characteristics of N5-Bz2a
discussed above. Similar transannular N–P interaction in an
eight-membered heterocyclic system was postulated for the
Ar
N
O
P
Nu
N
O
Ar
Ar
NHAr
P
3
Nu
H
N
N
N
O
Ar
Nu
Ar
1
N
N
P
N
H
2
Scheme 1
Fig. 2 ORTEP plot of the structure of 3b
Chem. Commun., 1998
741

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Å, m(Mo-Ka) = 1.13 cm21, T = 295(1) K, Z = 4, Dc = 1.30 g cm23. Data
were collected on an Enraf Nonius CAD4 diffractometer in the range 3 @
q @ 30° (7072 reflections). The structure was solved by direct methods (ref.
8) and refinement, based on F, was by full-matrix least-squares methods
(ref. 9) to R = 0.057, Rw = 0.065 {weighting scheme [s22(Fo) + 0.000699
F2]} for 293 parameters using 4047 unique reflections with I > 3s(I).
∑ Rearrangement of 2b to 3b: 2a (0.345 g, 1 mmol) in dry benzene (15 ml)
was heated under reflux for 18 h. After concentrating to ca. 1/4 volume, the
solution was poured into dry Et2O (20 ml) with vigorous stirring. The
precipitate (0.318 g, 92%) was filtered off and crystallized from MeCN.
1-Phenyl-2-ethoxy-2-oxo-3-[2-(phenylamino)ethyl]-1,2,3l5-diaza-
phospholidine 3b, mp 129.4–130.1 °C; dH 1.17 (3 H, t, J 7.1), 3.24–3.46 (6
H, m), 3.57–3.70 (2 H, m), 3.97 (2 H, dt, J 7.1), 6.60–7.30 (10 H, m); dC 16.2
(d, J 7.2), 41.6 (d, J 2.4), 43.1 (s), 43.3 (s), 44.4 (d, J 4.9), 63.6 (d, J 7.2),
112.5 (s), 115.9 (s), 122.9 (s), 129.2 (s), 129.3 (s), 141.3 (d, J 6.3), 148.0 (s);
dP 18.5; Found: C, 62.18; H, 7.16; N, 12.08; C18H24N3O2P requires: C,
62.59; H, 7.00; N, 12.16%.
O
Ph
OEt
P
OEt
–
Ph
O
N
N
P
Ph
Ph
N
N
N
N
+
H
H
2b
Ph
OEt
P
H
–
N
O
N
Ph
O
Ph
N
P
+
OEt
N
N
NHPh
3b
Scheme 2
** Crystal data for 3b: C18H24N3O2P, M = 345.38, monoclinic, space
group P21/n (No. 14), a = 13.902(2), b = 6.046(5), c = 22.110(5) Å, b
= 94.59(3)°, U = 1852(1) Å3, F(000) = 736, l(Mo-Ka) = 0.7107 Å,
m(Mo-Ka) = 1.24 cm21, T = 295(1) K, Z = 4, Dc = 1.22 g cm23. Data
were collected on an Enraf Nonius CAD4 diffractometer in the range 3 @
q @ 30° (6077 reflections). The structure was solved by direct methods (ref.
8) and refinement, based on F2, was by full-matrix least-squares methods
(ref. 9) to R = 0.063, Rw = 0.040 {weighting scheme [s2(fo)]} for 221
parameters using 2522 unique reflections with I > 3s(I). An intermolecular
bond O(1)···H–N(3) of 2.042 Å is observed. Perspective drawings were
prepared using ORTEP (ref. 10). CCDC 182/772.
†† Base-promoted alcoholysis of 1a: a solution of 1a (0.300 g, 1 mmol) and
MeONa (3 mmol) in MeOH (20 ml) was kept at room temperature for 28
days (full conversion, as shown by 31P NMR spectroscopy), neutralised
with methanolic HCl, filtered and evaporated under reduced pressure. The
crude product (0.336 g, oil) consisted of two phosphorus-containing
compounds (dP 19.9, 55%; dP 14.4, 45%) which were separated by column
chromatography (SiO2, Et2O). Selected data for 3a, oil; dH 3.39 (6 H, m),
3.61 (3 H, d, J 12.3), 3.63 (2 H, m), 4.42 (1 H, br s), 6.63 (2 H, d, J 7.6), 6.68
(1 H, t, J 7.5), 6.98 (1 H, t, J 7.3), 7.15 (4 H, m), 7.29 (2 H, t, J 7.9); dC 41.7
(s), 43.2 (d, J 7.7), 43.4 (d, J 6.5), 44.5 (s), 54.3 (d, J 7.8), 112.8 (s), 115.7
(s), 117.4 (s), 121.7 (s), 129.3 (s), 129.4 (s), 137.6 (d, J 5.2), 147.8 (s); dP
19.9; Found: C, 63.20; H, 7.48; N, 11.45. C19H26N3O2P requires: C, 63.50;
H, 7.29; N, 11.69%. For 4a: oil; dH 3.28 (8 H, m), 3.69 (6 H, d, J 11.2), 6.56
(4 H, d, J 7.7), 6.68 (2 H, t, J 7.4), 7.15 (4 H, m); dC 41.5 (s), 45.8 (d, J 4.4),
53.5 (d, J 6.2), 112.7 (s), 117.9 (s), 129.3 (s), 147.8 (s); dP 14.2.
mechanism of the hydrolysis of medium-ring phosphate esters.6
In that case, however, as well as in other cases of transannular
interactions involving nitrogen and a carbonyl group,7 the ring
structure of the substrate remains intact, while for 2 we observe
a change in the cyclic skeleton of the molecule. To the best of
our knowledge, this is the first reported case of a rearrangement
of this type.
Methanolysis of 1a in MeO2/MeOH led directly to the
formation of 3a (Ar = Ph; Nu = OMe) as a result of
nucleophilic cleavage of the P–N(Ph) bond. In the absence of
the activation of the N(5) atom in 1 via protonation, it is the
leaving ability of the departing nitrogen (NPh) that determines
the regioselectivity of the P–N bond cleavage. In the presence of
an excess of MeO2 ions, 3a undergoes the opening of the
5
second 1,3,2l -diazaphospholidine ring, yielding dimethyl
di(2-phenylaminoethyl)phosphoramidate 4a.††
The 2 ? 3 rearrangement reported here indicates greater
thermodynamic stability of the latter heterocyclic system. The
structure and conformational behaviour of 2, as well as the
mechanism of its rearrangement to 3, is currently being studied
in this laboratory.
Notes and References
1 H. Wan and T. A. Modro, Synthesis, 1996, 1227.
2 J. Rahil and P. Haake, J. Am. Chem. Soc., 1981, 103, 1723 and
references cited therein.
3 A. M. Modro, T. A. Modro, P. Bernatowicz, W. Schilf and L. Stefaniak,
Magn. Reson. Chem., 1997, 35, 774.
4 S. A. Bourne, X. Y. Mbianda, T. A. Modro, L. R. Nassimbeni and
H. Wan, J. Chem. Soc., Perkin Trans. 2, 1998, 83.
5 P. G. Jones, H. Tho¨nnessen, A. Fischer, I. Neda, R. Schmutzler,
J. Engel, B. Kutscher and U. Niemeyer, Acta Crystallogr., Sect. C, 1996,
52, 2359.
6 R. K. Sharma and R. Vaidyanathaswamy, J. Org. Chem., 1982, 47,
1741.
7 Conformational Analysis of Medium-Sized Heterocycles, ed. R. S.
Glass, VCH, New York, 1988, ch. 3.8.
8 G. M. Sheldrick, SHELX86. A program for the solution of crystal
structures, University of Go¨ttingen, 1986.
9 G. M. Sheldrick, SHELX76. Program for crystal structure determina-
tion, University of Cambridge, 1976.
† E-mail: tamodro@scientia.up.ac.za
‡ Acid-catalysed alcoholysis of 1a: a solution of 1a (0.50 g, 1.67 mmol) in
anhydrous alcohol (15 ml) containing dry HCl (1.67 mmol) was kept at
room temperature for 16 h, diluted with water (10 ml) and neutralised with
aq. Na2CO3. The solution was extracted with CHCl3 (3 3 10 ml), dried
(Na2SO4) and evaporated under reduced pressure yielding 2 as a solid (2a)
or a viscous oil (2b). Data for 2a (0.55 g, 100%): mp 91.5–92.7 °C; dH (300
MHz, CDCl3) 2.04 (1 H, br s), 2.87 (4 H, ddd, J 14.6, 6.7, 3.1), 3.50 (3 H,
d, J 5.6), 3.60–3.85 (4 H, m), 7.08–7.50 (10 H, m); dC 47.4 (s), 51.8 (s), 53.2
(d, J 5.7 Hz), 123.5 (s), 124.1 (s), 129.2 (s), 143.3 (d, J 4.2); dP 13.6. For 2b
(0.58 g, 100%): oil; dH 0.99 (3 H, t, J 7.1), 2.06 (1 H, br s), 2.87 (4 H, ddd,
J 14.6, 6.7, 3.1), 3.55–3.80 (4 H, m), 3.87 (2 H, dt, J 7.1), 7.08–7.50 (10 H,
m); dC 15.6 (d, J 6.7), 47.3 (s), 51.5 (s), 62.9 (d, J 5.4), 123.4 (s), 123.9 (s),
129.1 (s), 143.2 (d, J 4.2); dP 12.1.
§ Selected data for N5-Bz2a: (66%), mp 148.2–149.7 °C (from MeCN–
hexane, 1:1); dP 12.0; Found: C, 66.22; H, 6.17; N, 9.50; C24H26N3O3P
requires: C, 66.19; H, 6.01; N, 9.64%. For N5-Bz2b: (74%), mp
144.2–145.6 °C (from MeCN); dP 10.6; Found: C, 67.07; H, 6.29; N, 9.34.
C25H28N3O3P requires: C, 66.80; H, 6.27; N, 9.34%.
¶ Crystal data for N5-Bz2b: C25H28N3O3P, M = 449.49, monoclinic, space
group P21/n (No. 14), a = 9.743(1), b = 12.443 (2), c = 19.334(2) Å,
b = 104.34(1)°, U = 2271(1) Å3, F(000) = 952, l(Mo-Ka) = 0.7107
10 C. K. Johnson, ORTEP, Report ORNL-3794, Oak Ridge National
Laboratory, Tennessee, USA, 1965.
Received in Cambridge, UK, 13th November 1997; revised manuscript
received 30th January 1998; 8/00836A
742
Chem. Commun., 1998