1-Oxo-2,8-diaryl-2,5,8-triaza-1λ5-phosphabicyclo[3.3.0]octanes as substrates for the preparation of bis(2-arylaminoethyl)amines

Article abstract of DOI:10.1055/s-2000-6421

A series of bis(2-arylaminoethyl)amines was prepared by hydrolysis of the corresponding bicyclic phosphoric triamides, followed in some cases by further functionalization.

Full text of DOI:10.1055/s-2000-6421

PAPER
1315
1-Oxo-2,8-diaryl-2,5,8-triaza-1l5-phosphabicyclo[3.3.0]octanes as Substrates
for the Preparation of Bis(2-arylaminoethyl)amines
Daniel P. Pienaar, Tom A. Modro,* Agnes M. Modro
Centre for Heteroatom Chemistry, Department of Chemistry, University of Pretoria, Pretoria 0002, South Africa
Fax 27(12)3625297; E-mail tamodro@scientia.up.ac.za
Received 8 February 2000
tical route to 1a, since the major product of the reaction is
Abstract: A series of bis(2-arylaminoethyl)amines was prepared by
N-phenylpiperazine (Scheme 1). We have repeated Prel-
hydrolysis of the corresponding bicyclic phosphoric triamides, fol-
og’s experiment by reacting bis(2-chloroethyl)ammoni-
um chloride with 5.1 mol equivalents of aniline in boiling
lowed in some cases by further functionalization.
Key words: diethylenetriamines, phosphoric triamides, hydrolysis
of P-N bond
toluene, and analyzsing the reaction product by high-res-
1
olution H NMR spectroscopy. After neutralization, the
reaction mixture consisted of N-phenylpiperazine, some
1a, and aniline; the integration of the 1H NMR signals in-
dicated the preference for the intermediate monosubstitu-
tion product (Scheme 1) to undergo intramolecular
cyclization (piperazine formation) rather than the second
substitution (formation of 1a) in a ratio of approximately
7:1.
Ammonia and amines represent one of the most common
types of F-donors ligands in coordination chemistry, and
the polyamines with the typically 1,2- or 1,3-location of
the amino groups are widely used as polydentate chelating
ligand structures.1 Bis-(2-aminoethyl)amine and its deriv-
atives can coordinate a metal via two five membered che-
late rings and should, according to their steric
requirements,2 show selectivity towards fairly large metal
ions. The complexation of Cu2+ with 3,6,9-triazaundecane
and its 1,11-disubstituted derivatives has been studied by
potentiometric and spectrophotometric titrations.3 The
terdentate ligand derived from 3,9-diethyl-3,6,9-triazaun-
decane was used in a study of complexes of metals of the
Ti and V triads.4
The obvious way to ethyleneamines and higher
polyamines is to react ethylene dihalide with ammonia or
with amines. The reaction was studied in late 1860’s by
Hofmann,5 and the complexity of the reaction and its
product was soon acknowledged. The reaction was rein-
vestigated by Mann,6 who demonstrated that the parent
Scheme 1
triamine, bis(2-aminoethyl)amine (“diethylenetriamine”)
can be obtained in pure state as a hydrochloric acid salt
In this paper, we report an efficient and general method
for the preparation of the triamines 1 from the correspond-
ing bicyclic phosphoric triamides 2 (Scheme 2).
Substrates 2 have been first prepared in our laboratory,10
(Scheme 3) and their structure and chemistry are being ex-
tensively studied.11 Individual P-N bonds in 2 can be
cleaved selectively,11 but the exhaustive acid catalyzed
hydrolysis of the P-N bonds, known to be a facile pro-
cess,12 seemed an obvious way to products 1. The tri-
only indirectly, via the Gabriel’s method. The N,N¢-diaryl
substituted “diethylenetriamine”, Ar-NH-CH2CH2- NH-
CH2CH2-NH-Ar 1, is an interesting example of that parent
system because of the possibility of wide variations of its
electronic and steric effects that may be achieved by intro-
ducing substituents to the aromatic groups, as well as at
the nitrogen atoms of the 1,4,7-triazaheptane skeleton.
The N,N¢-diphenyl derivative 1a (Ar = Ph), although a
simple compound, is difficult to prepare. The patent liter-
ature reports formation of small quantities of 1a, together
with other amines, in the reduction of the nitrile of N-phe-
nylglycine; the mixture of amines can be used as a vulca-
nization accelerator, antioxidant, or as an insect poison.7
Compound 1a is also formed as a side product (35%) to-
gether with N-phenylethylenediamine (65%) in the reac-
tion of N-(2-chloroethyl)aniline with liquid NH3.8 Prelog
and Driza have demonstrated long ago9 that the reaction
between bis(2-chloroethyl)amine and aniline is not a prac-
amines
1
were isolated in the form of their
trihydrochloride salts (highly insoluble, crystalline mate-
rials, easy to isolate and purify), and/or as free bases, and
they were identified by NMR (1H, 13C) spectroscopy, MS,
elemental analysis, and by conversion to the tri-N-acetyl
derivatives. The latter compounds, unlike simple acetanil-
1
ides, are rather low-melting solids or oils, and their H
NMR spectra show more than the expected number of sig-
nals of the N-acetyl methyl groups, as well as of other
Synthesis 2000, No. 9, 1315–1319 ISSN 0039-7881 © Thieme Stuttgart · New York

1316
D. P. Pienaar et al.
PAPER
followed by the hydrolytical removal of the N-acetyl
groups. The prepared products 1 and their derivatives are
listed in the Table.
NMR spectra were recorded from CDCl3 solutions on a Bruker AC
300 spectrometer. Mass spectra were recorded on a Varian MAT-
212 double focusing direct inlet spectrometer at an ionization poten-
tial of 70 eV. IR spectra were recorded from CCl4 solutions on a
Bomem Michelson 100 spectrophotometer. Mps are uncorrected.
Elemental analysis was performed at the department of Chemistry,
University of Cape Town.
Substrates 2
Bicyclic phosphoric triamides 2a (2, Ar = C6H5) and 2c (2,
Ar = C6H4-p-OMe) were prepared as described before.10
1-Oxo-2,8-di(4-methylphenyl)-2,5,8-triaza-1l5-phoshabicyclo-
[3.3.0]octane (2b) (Ar = C6H4-p-Me)
The synthesis was carried out as described for 2a,10 using N-bis(2-
chloroethyl)-N¢,N¢¢-di(4-methylphenyl)phosphotriamidate (4.89 g,
12.2 mmol) [prepared from N-bis(2-chloroethyl)phosphoramidod-
ichloridate and p-toluidine; 76%; mp 124-129 °C, 31P NMR: d =
5.3], NaH (1.20 g, 48.8 mmol), and tetrabutylammonium bromide
(TBAB) (0.194 g, 2.4 mmol) in anhyd THF (20 mL) without isola-
tion of the monocyclic intermediate (see Scheme 3). The product
was purified by dissolving it in a minimum volume of CHCl3 and
precipitating with a large volume of cold hexane.
Scheme 2
groups in the molecule. It seems that the restricted rotation
about the terminal amide bonds makes the tri-N-acetyl 1
to exist as a mixture of the possible E/E, E/Z, and Z/Z ste-
reoisomers.
In the case of weakly nucleophilic anilines, some experi-
mental problems were encountered. With p-bromoaniline,
although the bicyclic amide 2d was prepared in pure state
and was hydrolyzed to 1d, the formation of the intermedi-
ate noncyclic triamide (step (ii), Scheme 3) proceeded
with very low yields. For the p-aminobenzonitrile, step
(ii) did not present problems, but the last cyclization lead-
ing to 2e required drastic conditions and 2e was found to
be rather unstable. It was therefore more convenient not to
isolate 2e, but to convert it in situ to the triamine 1e. For
the p-nitroaniline, we were not able to complete step (ii)
because only the substitution of the first (p-nitrophe-
nyl)amino group at the phosphoryl center proceeded with
satisfactory rate. The triamine 1f was however successful-
Yield = 3.60 g (90%), mp 186-187 °C.
31P NMR: d = 33.7.
1H NMR: d = 2.40 (s, 6H, 2 CH3), 3.09-3.21 (m, 2H, 2 NCH),
3.59-3.80 (m, 4H, 4 NCH), 3.84-3.94 (m, 2H, 2 NCH), 7.00 (d,
4H, JHH = 8.5 Hz, 4 m-Harom), 7.06 (d, 4H, JHH = 8.5 Hz, 4 o-Harom).
13C NMR: d = 21.0 (s, CH3), 48.3 (d, JCP = 7.1 Hz, NCH2), 49.4 (d,
JCP = 19.8 Hz, NCH2), 119.4 (s, Carom), 129.9 (s, Carom), 132.0 (s, Car-
om), 139.8 (s, Carom).
Anal. Calcd for C18H22N3OP: C, 66.04; H, 6.77; N, 12.84. Found:
C, 65.88; H, 6.90; N, 12.49.
1-Oxo-2,8-di(4-bromophenyl)-2,5,8-triaza-1l5-phosphabicyclo-
[3.3.0]octane (2d) (Ar = C6H4-p-Br)
Prepared by converting N-bis(2-chloroethyl)phosphoramidodichlo-
ly prepared by the nitration of the tri-N-acetylated 1a un- ridate (5.0 g, 19 mmol) with 4-bromoaniline (3.27 g, 19 mmol) in
CH2Cl2 (90mL) in the presence of the excess of Et3N into the corre-
der conditions of highly selective para orientation,
Scheme 3
Synthesis 2000, No. 9, 1315–1319 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
1-Oxo-2,8-diaryl-2,5,8-triaza-1l5-phosphabicyclo[3.3.0]octanes as Substrates
1317
Table Triamines 4-XC6H4NHCH2CH2NHCH2CH2NHC6H4-4-X 1 and their Derivatives
Com-
pound
X
H
Preparation
Data for 1
Derivatives
Yield; 1H, 13C NMR (CDCl3),
d, J (Hz)
Mp; 1H, 13C NMR (CDCl3), d, J (Hz)
1a
Hydrolysis of
2a (0.84 g,
2.8 mmol)
Yield: 0.72 g (100%); oil. 1H NMR:
2.88 (t, 4 H, JHH = 5.7, 2 NCH2), 3.21 3.28 t, 4 H, JHH = 5.9, 2 NCH2), 3.49 (t, 4 H, JHH = 6.0, 2
(t, 4 H, JHH = 5.7, 2 ArNCH2), 4.01
(br s, 3 H, 3 NH), 6.63 (d, 4 H, JHH
8.0, 4 o-Harom), 6.71 (t, 2 H, JHH = 7.5,
2 p-Harom), 7.18 (dd, 4 H, JHH = 8.0,
7.5, 4 m-Harom); 13C NMR: 44.3
(s, NCH2), 49.1 (s, ArNCH2), 113.6
(s, o-Carom), 118.1 (s, p-Carom), 129.9
Trihydrochloride. Mp 203-206 °C. 1H NMR (MeOD):
ArNCH2), 6.67-6.71 (m, 6 H, 4 o-Harom, 2 p-Harom), 7.15
(t, 4 H, JHH = 6.0, 4 m-Harom); 13C NMR: 41.1 (s, NCH2),
48.1 (s, ArNCH2), 114.3 (s, o-Carom), 119.1 (s, p-Carom),
130.3 (s, m-Carom), 149.1 (s, ipso-Carom).
=
N,N’,N”-triacetyl (63%). Mp 111-113°C (CHCl3/pet.
ether, 2:1). 1H NMR: 1.78 (s, 3H, NAc), 1.85 (s, 3H,
NAc), 2.03 (s, 3 H, NAc), 3.43 (t, 2 H, JHH = 6.5, NCH2),
3.61 (t, 2 H, JHH = 7.1, NCH2), 3.76 (t, 2 H, JHH = 6.5,
ArNCH2), 3.80 (t, 2 H, JHH = 7.2, ArNCH2), 7.16 (d, 2 H,
JHH = 7.2, 2 o-Harom), 7.20 (d, 2 H, JHH = 7.0, 2 o-Harom),
7.28-7.47 (m, 6 H, 2 p-Harom, 4 m-Harom); 13C NMR: 21.9
(s, CH3 of Ac), 23.2 (s, CH3 of Ac), 44.0, 46.8, 47,4, 48.8
(s, NCH2), 128.1, 128.3 (s, o-Carom), 128.4, 128.8 (s, p-
Carom), 130.3, 130.6 (s, m-Carom), 143.87, 143.93 (s, ipso-
Carom), 171.3, 171.4, 171.8 (s, C=O)a
(s, m-Carom), 149.0 (s, ipso-Carom
)
1b
CH3
Hydrolysis of
2b (2.00 g,
6.11 mmol)
Yield: 1.15 g (67%); oil. 1H NMR:
2.25 (s, 6 H, 2 ArCH3), 2.89 (t, 4 H,
JHH = 5.8, 4 NCH2), 3.21 (t, 4 H, JHH
= 5.8, 4 ArNCH2), 3.71 (s, 3 H, 3
NH), 6.56 (d, 4 H, JHH = 8.3, 4 o-
Harom), 6.99 (d, 4 H, JHH = 8.0, 4 m-
Harom); 13C NMR: 21.0 (s, ArCH3),
44.7 (s, NCH2), 49.2 (s, ArNCH2),
113.8 (s, o-Carom), 127.4 (s, p-Carom),
N,N¢,N¢¢-triacetyl (81%). Purified by column chromato-
graphy (SiO2, acetone/CHCl3, 1:1); oil. 1H NMR: 1.71 (s,
3 H, ArCH3), 1.77 (s, 3 H, ArCH3), 1.97 (s, 3 H, NAc),
2.28 (s, 3 H, NAc), 2.31 (s, 3 H, NAc), 3.36 (t, 2 H, JHH
=
6.1, 2 NCH2), 3.53 (t, 2 H, JHH = 7.0, 2 NCH2), 3.65-3.73
(m, 4 H, 4 ArNCH2), 6.98 (d, 2 H, JHH = 8.0, 2 o-Harom),
7.02 (d, 2 H, JHH = 8.3, 2 o-Harom), 7.10 (d, 2 H, JHH = 8.0,
2 m-Harom), 7.14 (d, 2 H, JHH = 8.2, 2 m-Harom); 13C NMR:
21.5 (s, ArCH3), 21.8 (s, CH3 of NAc), 23.0 (s, CH3 of
NAc), 43.8, 46.7, 47.3, 48.7 (s, NCH2), 127.8, 127.9 (s,
o-Carom), 130.8, 131.1 (s, m-Carom), 138.2, 138.6 (s, p-Car-
om), 141.2, 141.3 (s, ipso-Carom), 171.4, 171.5, 171,7 (s,
C=O)c
130.4 (s, m-Carom), 146.8 (s, ipso-
b
Carom
)
1c
OCH3 Hydrolysis of
2c (0.30 g,
Yield: 0.25 g (95%); oil. 1H NMR:
2.88 (t, 4 H, JHH = 5.7, 2 NCH2), 3.18
(t, 4 H, JHH = 5.8, 2 ArNCH2), 3.70
(br s, 3 H, 3 NH), 3.75 (s, 6 H, 2
OCH3), 6.60 (d, 4 H, JHH = 8.8, 4 m-
Harom), 6.78 (d, 4 H, JHH = 9.0, 4 o-
Harom); 13C NMR: 45.4 (s, NCH2),
49.3 (s, ArNCH2), 56.5 (s, OCH3),
115.0 (s, m-Carom), 115.6 (s, o-Carom),
143.4 (s, ipso-Carom), 152.9 (s, p-
Trihydrochloride. Mp 207-209.5 °C. 1H NMR
(CD3OD): 3.49 (t, 4 H, JHH = 6.3, 2 NCH2), 3.73 (t, 4 H,
JHH = 6.2, 2 ArNCH2), 3.96 (s, 6H, 2OCH3), 7.04 (d, 4 H,
JHH = 8.8, 4 m-Harom), 7.36 (d, 4 H, JHH = 8.8, 4 o-Harom);
13C NMR: 45.3 (s, NCH2), 47.2 (s, ArNCH2), 56.3 (s,
0.83 mmol)
OCH3), 116.6 (s, m-Carom), 123.3 (s, o-Carom), 125.2 (s,
d
ipso-Carom), 160.7 (s, p-Carom
)
N,N¢,N¢¢-triacetyl (90%). Oil.1H NMR: 1.68 (s, 3H, NAc),
1.74 (s, 3 H, NAc), 1.95 (s, 3 H, NAc), 3.35 (t, 2 H, JHH
=
6.1, 2 NCH2), 3.51 (t, 2 H, JHH = 6.9, 2 NCH2), 3.62-3.67
(m, 4 H, 4 ArNCH2), 3.71 (s, 3 H, OCH3), 3.74 (s, 3 H,
OCH3), 6.80 (d, 2 H, JHH = 8.5, 2 m-Harom), 6.84 (d, 2 H,
JHH = 8.8, 2 m-Harom), 6.99 (d, 2 H, JHH = 8.8, 2 o-Harom),
7.01 (d, 2 H, JHH = 8.8, 2 o-Harom); 13C NMR: 21.7 (s, CH3
of NAc), 22.9 (s, CH3 of NAc), 43.7, 46.5, 47.3, 48.6 (s, 4
NCH2), 55.88 (s, OCH3), 55.92 (s, OCH3), 115.2, 115.6 (s,
2 m-Carom), 129.1, 129.2 (s, 2 o-Carom), 136.4, 136.5 (s, 2
ipso-Carom), 159.4, 159.6 (s, 2 p-Carom), 171.75 (s, C=O),
171.84 (s, C=O)
Carom
)
1d
Br
Hydrolysis of
2d (0.10 g, 0.22
mmol)
Yield: 0.075 g (83%); mp 60-61.5
°C. 1H NMR: 2.97 (t, 4 H, JHH = 5.7,
4 NCH2), 3.27 (t, 4 H, JHH = 5.5, 4
ArNCH2), 4.15 (br s, 3 H, 3 NH),
6.58 (d, 4 H, JHH = 8.8, 4 o-Harom),
7.33 (d, 4 H, JHH = 8.5, 4 m-Harom);
13C NMR: 44.3 (s, NCH2), 49.0 (s,
ArNCH2), 109.8 (s, ipso-Carom),
115.2 (s, o-Carom), 132.6 (s, m-Carom),
Trihydrochloride. Mp 214−216 °C. 1H NMR (CD3OD):
3.26 (t, 4 H, JHH = 5.9, 4 NCH2), 3.46 (t, 4 H, JHH = 5.9, 4
ArNCH2), 6.62 (d, 4 H, JHH = 8.5, 4 o-Harom), 7.23 (d, 4 H,
JHH = 8.8, 4 m-Harom); 13C NMR: 41.1 (s, NCH2), 47.8 (s,
ArNCH2), 110.8 (s, ipso-Carom), 116.1 (s, o-Carom), 133.0
e
(s, m-Carom), 148.0 (s, p-Carom
)
148.0 (s, p-Carom
)
Synthesis 2000, No. 9, 1315–1319 ISSN 0039-7881 © Thieme Stuttgart · New York

1318
D. P. Pienaar et al.
PAPER
Table (continued)
Com-
pound
X
Preparation
Data for 1
Derivatives
Yield; 1H, 13C NMR (CDCl3),
d, J (Hz)
Mp; 1H, 13C NMR (CDCl3), d, J (Hz)
1e
CN
Neutralisation
of the trihydro-
chlo-ride salt,
prepared by
hydrolysis of
the corre-
Yield: 0.050 g (82%); mp 118 °C. 1H
NMR: 2.93 (t, 4 H, JHH = 5.7, 4
NCH2), 3.26 (t, 4 H, JHH = 5.4, 4
ArNCH2), 4.61 (br s, 3 H, 3 NH),
6.56 (d, 4 H, JHH = 8.3, 4 o-Harom),
7.42 (d, 4 H, JHH = 8.5, 4 m-Harom);
13C NMR: 43.4 (s, NCH2), 48.6 (s,
ArNCH2), 99.8 (s, ipso-Carom), 113.0
(s, o-Carom), 121.0 (s, CN), 134.5 (s,
Trihydrochloride. Mp 211−212 °C 1H NMR (CD3OD):
3.30 (t, 4 H, JHH = 6.1, 4 NCH2), 3.58 (t, 4 H, JHH = 6.1, 4
ArNCH2), 6.76 (d, 4 H, JHH = 8.5, 4 o-Harom), 7.46 (d, 4 H,
JHH = 8.8, 4 m-Harom); 13C NMR: 40.2 (s, NCH2), 47.7 (s
ArNCH2), 99.8 (s, ipso-Carom), 113.8 (s, o-Carom), 121.2
(s, CN), 134.8 (s, m-Carom), 152.9 (s, p-Carom); IR: νCN
=
sponding
2213.8 cm−1 f
1,3,2-diaza-
phospho-li-
dine (see
m-Carom), 152.0 (s, p-Carom
)
Discussion)
1f
NO2
From triacetyl
derivative of
1a, via nitra-
tion followed
by hydrolysis
(0.20 g, 0.42
mmol)
Yield: 0.083 g (57%). Yellow pow-
der, mp 145-147.5 °C. 1H NMR:
2.97 (t, 4 H, JHH = 5.7, 4 NCH2), 3.32
(t, 4 H, JHH = 4.8 Hz, ArNCH2), 4.89
N,N¢,N¢¢-triacetyl. (100%). Yellow powder, mp 99-102
°C. 1H NMR:1.87 (s, 3 H, NAc), 1.94 (s, 3 H, NAc), 2.05
(s, 3 H, NAc), 3.43 (t, 2 H, JHH = 6.5, 2 NCH2), 3.63 (t, 2
H, JHH = 7.2, 2 NCH2), 3.79 (t, 2 H, JHH = 6.3, 2 ArNCH2),
(br s, 3H, 3 NH), 6.54 (d, 4 H, JHH
=
3.87 (t, 2 H, JHH = 7.2, 2 ArNCH2), 7.40 (d, 2 H, JHH =
9.3, 4 o-Harom), 8.09 (d, 4 H, JHH
=
9.0, 2 o-Harom), 7.44 (d, 2 H, JHH = 9.0, 2 o-Harom), 8.28 (d,
2 H, JHH = 9.0, 2 m-Harom), 8.32 (d, 2 H, JHH = 8.8, 2 m-
Harom); 13C NMR: 22.0 (s, CH3 of NAc), 23.4 (s, CH3 of
NAc), 44.1, 46.9, 47.8, 49.2 (s, 4 NCH2), 125.9, 126.2 (s,
o-Carom), 129.0, 129.2 (s, m-Carom), 128.2, 130.8 (s, ipso-
Carom), 147.5, 149.5 (s, p-Carom), 170.8, 172.0 (s, C=O);
IR: nNO2 = 1521.8 cm−1
9.3, 4 m-Harom); 13C NMR: 43.6 (s,
NCH2), 48.6 (s, ArNCH2), 111.9 (s,
o-Carom), 127.1 (s, m-Carom), 139.1 (s,
g
ipso-Carom), 153.9 (s, p-Carom
)
a Anal. Calcd (C22H27N3O3): C, 69.27; H, 7.13; N, 11.01. Found: C, 69.50; H, 7.31; N, 10.86.
b Anal. Calcd (C18H25N3): C, 76.28; H, 8.89; N, 14.83. Found: C, 76.10; H, 9.00; N, 14.65.
c Anal. Calcd (C24H31N3O3): C, 70.39; H, 7.63; N, 10.26. Found: C, 70.15; H, 7.80; N, 10.14.
d Anal. Calcd (C18H28Cl3N3O2): C, 50.89; H, 6.64; N, 9.89. Found: C, 50.61; H, 6.99; N, 9.35.
e Anal. Calcd (C16H22Br2Cl3N3): C, 36.78; H, 4.24; N, 8.04. Found: C, 36.48; H, 4.38; N, 7.91.
f Anal. Calcd (C18H22Cl3N5): C, 52.13; H, 5.35; N, 16.88. Found: C, 51.85; H, 5.50; N, 16.42.
g Anal. Calcd (C16H19N5O4): C, 55.65; H, 5.54; N, 20.28. Found: C, 55.40; H, 5.61; N, 19.89).
sponding
3-(2-chloroethyl)-2-oxo-1-(4-bromophenyl)-1-(4-bro-
Yield = 0.08 g (64%), mp 189-191 °C (acetone/hexane, 1:1).
31P NMR: d = 32.1.
mophenyl)amino-1,3,2-diazaphospholidine (0.55 g, 6%; mp 221-
222.5 °C; 31P NMR: d = 13.5, 1H and 13C NMR and mass spectra in
full agreement with the expected structure), which was then con-
verted to 2d with NaH (1.5 mol-equiv.) in THF (20 mL) at r.t.
1H NMR: d = 3.19-3.31 (m, 2H, 2 NCH), 3.61-3.75 (m, 2H, 2
NCH), 3.79-4.01 (m, 4H, 4 NCH), 7.30 (d, 4H, JHH = 8.5 Hz, 4 o-
Harom), 7.49 (d, 4H, JHH = 8.6 Hz, 4 m-Harom).
Yield = 0.22 g (79%), mp 203-204 °C (CHCl3/hexane, 1:1).
31P NMR: d = 32.9.
1H NMR: d = 3.12-3.24 (m, 2H, 2 NCH), 3.56-3.67 (m, 2H, 2
NCH), 3.73-3.93 (m, 4H, 4 NCH), 7.06 (d, 4H, JHH = 9.0 Hz, 4 o-
Harom), 7.30 (d, 4H, JHH = 8.8 Hz, 4 m-Harom).
13C NMR: d = 48.6 (d, JCP = 7.2 Hz, NCH2), 49.9 (d, JCP = 19.8 Hz,
ArNCH2), 115.8 (s, ipso-Carom), 121.1 (d, JCP = 3.6 Hz, o-Carom),
132.6 (s, m-Carom), 141.6 (s, p-Carom).
13C NMR: d = 48.7 (d, JCP = 7.2 Hz, NCH2), 50.1 (d, JCP = 19.7 Hz,
ArNCH2), 106.1 (s, ipso-Carom), 119.0 (d, JCP = 3.6 Hz, o-Carom),
119.5 (s, CN), 134.0 (s, m-Carom), 146.7 (s, p-Carom).
Anal. Calcd for (C18H16N5OP): C, 61.89; H, 4.62; N, 20.05. Found:
C, 61.66; H, 4.70; N, 19.88.
Triamines 1 (Hydrolysis of Triamides 2); General Procedure
To a solution of 2 (approx 0.10 g) in 1,4-dioxane (10 mL) was added
dropwise with stirring HCl (3-6 equiv, as a 10% aq solution, or as
concd aq solution), and the solution was stirred at r.t. for 24 h. For
1a, 1c, 1d the corresponding trihydrochloride salts precipitated out,
and were isolated by cooling the mixture to 10 °C and filtration. For
a direct isolation of free amines 1 most of dioxane and H2O was re-
moved under reduced pressure, NaOH (at least 6 equiv, as a 5%
aqueous solution) was added to the residual paste (pH >9), and the
mixture was stirred at r.t. for 1 h. The mixture was diluted twice
with H2O, extracted with CHCl3, and the CHCl3 solution was
washed with H2O until pH 8 was reached. After drying (MgSO4)
and evaporation of the solvent under reduced pressure, the product
was kept under a vacuum of approx 10-2 mm Hg for 1 h.
MS: m/z 458, 457, 456 (77, 99, 100 %, M+).
Anal. Calcd for C16H16Br2N3OP: C, 42.02; H, 3.53; N, 9.19. Found:
C, 41.98; H, 3.65; N, 9.05.
1-Oxo-2,8-di(4-cyanophenyl)-2,5,8-triaza-1l5-phosphabicyclo-
[3.3.0]octane (2e) (Ar = C6H4-p-CN):
Synthesized by initial preparation of 3-(2-chloroethyl)-2-oxo-1-(4-
cyanophenyl)-1-(4-cyanophenyl)amino-1,3,2-diazaphospholidine
as described above (1.58 g, 19%; mp 233-234 °C; 31P NMR: d =
11.4. 1H and 13C NMR spectra and mass spectra in full agreement
with the expected structure), which was then converted to 2e with
LDA (1.5 mol-equiv.) in refluxing toluene (20 mL).
Synthesis 2000, No. 9, 1315–1319 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
1-Oxo-2,8-diaryl-2,5,8-triaza-1l5-phosphabicyclo[3.3.0]octanes as Substrates
1319
Acetylation of Triamines 1; General Procedure
References
A solution of amine 1 in acetic anhydride (approx 8 mL/g of 1) was
heated under reflux for 2 h and poured into cold water (approx
6 mL/mL of Ac2O). The solution was extracted with CHCl3 (approx
1 mL per 3 mL of H2O used), the CHCl3 solution was washed twice
with equal volume of H2O and once with half of the volume of 5%
aq Na2CO3 (pH X8). After drying (MgSO4) and evaporation of the
solvent under reduced pressure, the triacetate was purified by crys-
tallization.
(1) Houghton, R. P. Metal Complexes in Organic Chemistry;
Cambridge University Press: Cambridge, 1979.
(2) Hancock, R. D. In Perspectives in Coordination Chemistry;
Williams, A. F.; Floriani, C.; Merbach, A. E., Eds.; VCH:
Weinheim, 1992; p 129.
(3) Gampp, H.; Haspra, D.; Maeder, M.; Zuberbuehler, A. D.
Inorg. Chem. 1984, 23, 3724.
(4) Wills, A. R.; Edwards, P. G.; Short, R. L.; Hursthouse, M. B.
J. Chem. Soc., Chem. Commun. 1988, 115.
(5) Hofmann, A. W. Ber. Dtsch. Chem. Ges. 1890, 23, 3711; and
preceding papers of this series.
(6) Mann, F. G. J. Chem. Soc. 1934, 461.
(7) Munch, E.; Schlichting, O. German Patent 561156, 1930;
Chem. Abstr.1933, 27, 995.
Nitration of N,N’,N”-Triacetyl 1a
Tri-N-acetyl derivative of 1a (1.0 g, 2.62 mmol) was dissolved in
glacial HOAc (6 mL) and concd H2SO4 (6 mL) was added with stir-
ring. A mixture of HNO3 (0.5 mL) and concd H2SO4 (0.4 mL) was
added dropwise with stirring and cooling (inside temperature below
10 °C). The solution was allowed to warm to r.t. and stirred for fur-
ther 48 h. Cold H2O (50 mL) was added slowly with cooling the
flask in ice; the precipitated yellow product was filtered off, washed
with H2O and dried. The product crystallized after keeping it in a re-
frigerator; yield 1.23 g (100%).
Salzberg, P. L. U. S. Patent 2067291, 1937; Chem. Abstr.
1937, 31, 1657.
(8) Van Braun, J.; Lotz, R.; Warne, K. C.; Pinkernell, W.;
Rohland, W. Pohl, A.; Dengel, F.; Arnold, H. Ber. Dtsch.
Chem. Ges. 1937, 70B, 979.
(9) Prelog, V.; Driza, G. J. Collect. Czech. Chem. Commun. 1933,
5, 497; Chem. Abstr. 1934, 28, 1347.
(10) Wan, H.; Modro, T. A. Synthesis 1996, 1227.
(11) He, Z.; Laurens, S.; Mbianda, X. Y.; Modro, A. M.; Modro, T.
A. J. Chem. Soc., Perkin Trans. 2 1999, 2589; and references
cited therein.
Hydrolysis of the Nitration Product (Preparation of 1f)
A suspension of the above product (0.20 g, 0.42 mmol) in 20% aq
HCl (3 mL) was heated under reflux for 1 h. The hot mixture was
poured into cold H2O (20 mL) and neutralized with 10% aq NaOH
with cooling. The mixture was kept in a refrigerator overnight and
the precipitated product was filtered off and dried.
(12) Rahil, J.; Haake, P. J. Am. Chem. Soc. 1981, 103, 1723; and
references cited therein.
Acknowledgement
We gratefully acknowledge financial support of this work by the
University of Pretoria and the National Research Foundation.
Article Identifier:
1437-210X,E;2000,0,09,1315,1319,ftx,en;P01500SS.pdf
Synthesis 2000, No. 9, 1315–1319 ISSN 0039-7881 © Thieme Stuttgart · New York