Reaction of 1,2-diaza-1,3-butadienes with aminophosphorus nucleophiles: A practical access to new phosphorylated pyrazolones

Article abstract of DOI:10.1002/ejoc.200800856

The reaction of 1,2-diaza-1,3-butadienes with dibenzyl diisopropylphosphoramidite, methyl tetraisopropylphosphorodiamidite or tris(dimethylamino)phosphane under solventfree conditions gave stable α-phosphoranylidene-hydrazones that, in turn, were transformed into the corresponding 5-oxo-4-phosphoranylidene-4,5-dihydro-1H-pyrazoles. X-ray diffraction analysis of one of these derivatives is reported. α-Phosphoranylidene-hydrazones, derived from the reaction between 1,2-diaza-1,3-butadienes with dibenzyl diisopropylphosphoramidite, were converted by hydrolytic cleavage into (E)-hydrazono-phosphonates, which are useful for the preparation of the corresponding (3-oxo-2,3-dihydro-1H-pyrazol-4- yl)phosphonamidates. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.

Full text of DOI:10.1002/ejoc.200800856

FULL PAPER
DOI: 10.1002/ejoc.200800856
Reaction of 1,2-Diaza-1,3-butadienes with Aminophosphorus Nucleophiles:
A Practical Access to New Phosphorylated Pyrazolones
Orazio A. Attanasi,*[a] Graziano Baccolini,[b] Carla Boga,[b] Lucia De Crescentini,*[a]
Gianluca Giorgi,[c] Fabio Mantellini,[a] and Simona Nicolini[a]
Keywords: Diazabutadienes / Phosphorus / Ylides / Michael addition / Hydrazones / Pyrazolones
The reaction of 1,2-diaza-1,3-butadienes with dibenzyl di-
isopropylphosphoramidite, methyl tetraisopropylphosphoro-
diamidite or tris(dimethylamino)phosphane under solvent-
free conditions gave stable α-phosphoranylidene-hydrazones
that, in turn, were transformed into the corresponding 5-oxo-
4-phosphoranylidene-4,5-dihydro-1H-pyrazoles. X-ray dif-
fraction analysis of one of these derivatives is reported. α-
between 1,2-diaza-1,3-butadienes with dibenzyl diisopro-
pylphosphoramidite, were converted by hydrolytic cleavage
into (E)-hydrazono-phosphonates, which are useful for the
preparation of the corresponding (3-oxo-2,3-dihydro-1H-pyr-
azol-4-yl)phosphonamidates.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Phosphoranylidene-hydrazones, derived from the reaction Germany, 2009)
olones IV[6,9] by intermolecular nucleophilic attack of the
C=N–NH nitrogen on the ester group in the γ-position and
Introduction
Organophosphorus compounds are noteworthy for their
biological activity,[1] especially when they are associated
with various heterocycles.[2] One of the most important of
these bioactive heterocycles is the pyrazole moiety.[3] In
spite of their importance, methods for the direct synthesis
of substituted pyrazoles containing phosphorus groups are
quite limited.[4] In particular, amino-phoshoranylidene- and
phosphonamido-pyrazolones have not been widely reported
in the literature.[5]
subsequent loss of an alcohol molecule (Scheme 1).
On the other hand, 1,2-diaza-1,3-butadienes have been
intensively studied by several researchers because of their
usefulness in organic synthesis.[6,7] Our group has employed
these substrates mainly as building blocks for the synthesis
of five- or six-membered heterocycles.[6,8] In particular, 1,2-
diaza-1,3-butadienes I readily react with a large variety of
nucleophiles II by 1,4-conjugate addition (Michael-type) of
the latter to the terminal carbon atom of the heterodiene
system to give 1,4-adduct hydrazone intermediates III.
These compounds can furnish polyfunctionalized pyraz-
Scheme 1.
Also, in the past few years, we have examined the phos-
pha-Michael (P-Michael) addition of some phosphorus nu-
cleophiles to 1,2-diaza-1,3-butadienes, which is one of the
most versatile tools for the formation of the P–C bond.[10]
In detail, the reaction of 1,2-diaza-1,3-butadienes with tri-
phenyl-[11a] or trialkylphosphanes[11b] gives pyrazoles or pyr-
[a] Istituto di Chimica Organica, Università degli Studi di Urbino azol-5-ones, whereas with trialkyl phosphites and dialkyl
“Carlo Bo”,
phenylphosphonites they furnish new 1,2,3-diazaphos-
Via I Maggetti 24, 61029 Urbino, Italy
pholes or (E)-hydrazono-phosphonates.[12]
Fax: +39-0722-303441
E-mail: orazio.attanasi@uniurb.it
lucia.decrescentini@uniurb.it
Based on these considerations and with the aim of syn-
thesizing new phosphorylated pyrazolones containing one,
two or three amino functions directly linked to the phos-
phorus atom, we describe herein the reaction between 1,2-
diaza-1,3-butadienes and dibenzyl diisopropylphosphor-
amidite, methyl tetraisopropylphosphorodiamidite or tris-
[b] Dipartimento di Chimica Organica “A. Mangini”, Università
degli Studi di Bologna,
Viale Risorgimento 4, 40136 Bologna, Italy
[c] Dipartimento di Chimica Organica, Università degli Studi di
Siena,
Via Aldo Moro, 53100 Siena, Italy
Eur. J. Org. Chem. 2008, 5965–5973
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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O. A. Attanasi, L. De Crescentini et al.
FULL PAPER
(dimethylamino)phosphane to form stable α-phosphor- perature (Scheme 2, path a, Table 1). Ring closure to the
anylidene-hydrazones. These ylide derivatives can be con- pyrazolone ring is ascribable to an intramolecular nucleo-
verted into the desired 5-oxo-4-phosphoranylidene-4,5-di- philic attack of the base-activated hydrazone nitrogen atom
hydro-1H-pyrazoles or (E)-hydrazono-phosphonates. These on the ester group with loss of an alcohol molecule (see
latter compounds have been demonstrated in recent years to Scheme 1).
The 13C NMR chemical shifts of the P–C signals of the
hydrazones 3 (δ = 45.9–56.7 ppm) and 5-oxopyrazoles 4 (δ
= 71.5–84.5 ppm) and the values of their coupling constants
(J = 119.1–198.8 Hz for 3 and J = 192.7–205.0 Hz for 4)
clearly supported the ylide nature of these compounds.[12,13]
However, the molecular structure of 5-oxo-4-phoshoranyl-
idene-4,5-dihydro-1H-pyrazoles was unequivocally estab-
lished by X-ray diffraction analysis of 4c (Figure 1).[14]
The conversion of the ylide derivatives 3j–n, derived from
be important tools in the synthesis of various heterocyclic
compounds.[12] In this work, they are employed in the prep-
aration of interesting (3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-
phosphonamidates.
Results and Discussion
1,2-Diaza-1,3-butadienes 1a–g readily reacted with di-
benzyl diisopropylphosphoramidite (2a), methyl tetraiso-
propylphosphorodiamidite (2b) or tris(dimethylamino)- 1a–d,g, with 2c into the corresponding 5-oxo-4-phoshoran-
phosphane (2c) under solvent-free conditions in 0.2–3.0 h ylidene-4,5-dihydro-1H-pyrazoles 4f–h also occurs in the
to give α-phosphoranylidene-hydrazones 3a–n, which pre- presence of some acidic resins,[15a] such as montmorillon-
cipitated from the reaction medium in good yields ite,[15b] zeolite,[15c] amberlyst 15 H[15d] or silica gel,[15e] in a
(Scheme 2, path a, Table 1).
mixture of tetrahydrofuran/methanol (95:5). For the con-
The ylide derivatives 3a–n are formed by nucleophilic version of ethyl 3-[(anilinocarbonyl)hydrazono]-2-[tris(di-
1,4-addition of the phosphorus atom to the terminal carbon methylamino)phosphoranylidene]butanoate (3m) into 3-
atom of the heterodiene system to form a zwitterionic inter- methyl-5-oxo-N-phenyl-4-[tris(dimethylamino)phosphor-
mediate I, which exists in equilibrium with its ylide form 3 anylidene]-4,5-dihydro-1H-pyrazole-1-carboxamide
(4g)
through a 1,4-proton shift (Scheme 2). different amounts of some of these resins were tested and
Ylide intermediates 3a–n can be easily converted into the also different temperatures. The results of this study are re-
corresponding 5-oxo-4-phoshoranylidene-4,5-dihydro-1H- ported in Table 2. Silica gel was found to be the best in
pyrazoles 4a–h by treatment with a catalytic (for 3a–i) or a terms of higher yields and shorter reaction times, even at
stoichiometric (for 3k–n) amount of sodium hydride in a room temperature. Thus, the use of these optimal condi-
mixture of tetrahydrofuran/methanol (1:1) at room tem- tions was extended to the conversion of α-phosphoranylid-
Scheme 2.
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Practical Access to New Phosphorylated Pyrazolones
Table 1. Yields and reaction times for the preparation of α-phosphoranylidene-hydrazones 3a–n and 5-oxo-4-phoshoranylidene-4,5-dihy-
dro-1H-pyrazoles 4a–h.
1
R1
R2
R3
2
X
Y
R4
3
Yield [%][a]
Time [h][b]
4[c]
Yield [%][d]
Time [h][e]
1a
1b
1c
1d
1a
1b
1c
1e
1f
1a
1b
1c
1d
1g
Me
Et
Me
Et
Me
Et
Me
Me
Et
Me
Et
Me
Et
Me
Me
Me
Me
Me
Me
Me
Et
Me
Me
Me
Me
Me
Et
NH2
NH2
NHPh
NHPh
NH2
NH2
NHPh
NH2
OtBu
NH2
NH2
NHPh
NHPh
NHPh
2a
2a
2a
2a
2b
2b
2b
2b
2b
2c
2c
2c
2c
2c
OBn
OBn
OBn
OBn
OMe
OMe
OMe
OMe
OMe
OBn
OBn
OBn
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
64
67
68
63
92
100
66
65
88
81
84
72
77
72
3.0
3.0
4.0
4.5
0.5
0.5
0.2
1.0
1.0
3.0
3.0
0.4
0.3
1.5
4a
4a
4b
4b
4c
4c
67
64
69
75
75
68
90
2.5
3.0
2.0
OBn
2.0
N(R4)2
N(R4)2
N(R4)2
N(R4)2
N(R4)2
48.0
48.0
48.0
4d
[f]
4e
4f
4f
4g
4g
4h
70
66
68
89
91
76
72.0
6.0
6.0
1.0
1.0
0.5
N(R4)2 N(R4)2 Me
N(R4)2 N(R4)2 Me
N(R4)2 N(R4)2 Me
N(R4)2 N(R4)2 Me
N(R4)2 N(R4)2 Me
Me
[a] Yields of the pure isolated products, based on 1a–g. [b] Time for the disappearance of 1a–g. [c] Prepared starting from 3a–n with
sodium hydride. [d] Yields of the pure isolated products, based on 3a–n. [e] Time for the disappearance of compounds 3a–n. [f] The
reaction gave a complicated mixture.
Table 2. Yields and reaction times for the conversion of ethyl
3-[(anilinocarbonyl)hydrazono]-2-[tris(dimethylamino)phosphor-
anylidene]butanoate (3m) into 3-methyl-5-oxo-N-phenyl-4-[tris-
(dimethylamino)phosphoranylidene]-4,5-dihydro-1H-pyrazole-1-
carboxamide (4g) by using different resins and temperatures.
Resin
Amount[a] T [°C]
Time [h]
Yield [%]
Montmorillonite
Montmorillonite
Zeolite
1.0 equiv.
2.0 equiv.
1.0 equiv.
2.0 equiv.
1.0 equiv.
2.0 equiv.
5.0 g
60
25
60
25
60
25
25
1.0
0.5
1.0
3.3
1.0
0.2
0.1
85
50
85
65
46
58
87
Zeolite
Amberlyst 15H
Amberlyst 15H
Silica gel
[a] Amount relative to 1 mmol of the starting 3m.
Table 3. Yields and reaction times for the preparation of 5-oxo-
4-phoshoranylidene-4,5-dihydro-1H-pyrazoles 4f–h with silica gel
starting from 3j–n.
3
4
Yield [%][a]
Time [h][b]
Figure 1. X-ray structure of compound 4c with 50% probability
thermal ellipsoids.
3j
3k
3l
3m
3n
4f
4f
4g
4g
4h
85
81
81
87
86
0.2
0.1
0.2
0.1
0.1
ene-hydrazones 3j–n into 4f–h. Yields and reaction times
are reported in Table 3. Under the mild acidic conditions
used in the reactions, the ester electrophilic centre is proba-
bly activated during the ring-closure step.
[a] Yields of the pure isolated products, based on 3j–n. [b] Time for
the disappearance of compounds 3j–n.
Acidic treatment of α-phosphoranylidene-hydrazones
3a–i, derived from 1a–h and 2a,b, with resins gave compli- d, by magnetically stirring in methanol/water (95:5) at room
cated reaction mixtures, probably because of the presence temperature (Scheme 2, path c, Table 4).
of one or two oxygen atoms linked to the phosphorus atom
that makes possible other concomitant reactions.
In the reactions between 1,2-diaza-1,3-butadienes 1a–g
and 2b,c, (E)-hydrazono-phosphonates 5 did not form, per-
When the temperature for the reaction between 1,2-di- haps because of electronic and/or steric effects caused by
aza-1,3-butadienes 1a–d and dibenzyl diisopropylphos- the additional nitrogen atoms bound to the phosphorus
phoramidite (2a) under solvent-free conditions was raised atom making it a poorer electrophile.
to 40 °C and the mixture allowed to stand at this tempera-
The hydrazone derivatives 5a–d have proven once again
ture for the appropriate time (7.0–12.0 h), (E)-hydrazono- their synthetic utility as they were converted in good yields
phosphonates 5a–d were formed in good yields (Scheme 2, into (3-oxo-2,3-dihydro-1H-pyrazol-4-yl)phosphonamidates
path b, Table 4). Compounds 5a–d can also be obtained by 6a and 7a by treatment with a catalytic amount of sodium
hydrolytic cleavage of α-phosphoranylidene-hydrazones 3a– hydride in tetrahydrofuran/methanol (1:1) (Scheme 2,
Eur. J. Org. Chem. 2008, 5965–5973
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O. A. Attanasi, L. De Crescentini et al.
FULL PAPER
Table 4. Yields and reaction times for the preparation of (E)-hydrazono-phosphonates 5a–d.
1
R1
R2
R3
2
3
5
Yield [%][a]
Time [h][b]
Yield [%][c]
Time [h][d]
1a
1b
1c
1d
Me
Et
Me
Et
Me
Me
Me
Me
NH2
NH2
NHPh
NHPh
2a
2a
2a
2a
3a
3b
3c
3d
5a
5b
5c
5d
78
87
67
70
7.0
12.0
12.0
8.0
68
62
66
76
7
12
15
27
[a] Yields of the pure isolated products, based on 1a–d (path b, Scheme 2). [b] Time for the formation of compounds 5a–d, refers to path b
of Scheme 2. [c] Yields of the pure isolated products, based on 3a–d (path c, Scheme 2). [d] Time for the disappearance of compounds 3a–
d refers to path c of Scheme 2.
Mass spectra (EI) were recorded at an ionizing voltage of 70 eV
Table 5) according to the same base-promoted mechanism
as described for the synthesis of 4a–h. The formation of 2-
unsubstituted 3-oxopyrazole 6a took place by base-pro-
moted hydrolytic cleavage of the aminocarbonyl group
linked to the nitrogen atom at the 2-position of the pyrazole
ring.
1
with a Shimadzu QP5000 spectrometer. H and 13C NMR spectra
were recorded at 400 and 100.32 MHz, respectively, with a Varian
Mercury 400VX spectrometer. All NMR spectra were recorded in
CDCl3 or [D6]DMSO, as specified below. 1H chemical shifts (δH)
are reported in parts per million (ppm) relative to TMS as the
internal standard. All coupling constant (J) values are given in Hz.
13C chemical shifts (δC) are reported in parts per million (ppm)
relative to CDCl3 or [D6]DMSO as the internal standard in broad-
band decoupled mode; the multiplicities were obtained by 135° and
90° DEPT experiments to aid assignment. The abbreviations used
are as follows: s, singlet; d, doublet; t, triplet; q, quartet, m, mul-
tiplet; br., broad. All the NH and NH2 groups exchanged with
D2O. Precoated silica gel plates (0.25 mm) were employed in analyt-
ical thin-layer chromatography and silica gel 35–70 µm for column
chromatography. All new compounds showed satisfactory elemen-
tal analysis (C Ϯ0.35, H Ϯ0.30, N Ϯ0.30). The nomenclature was
generated by using ACD/IUPAC Name.[16]
Table 5. Yields and reaction times for the preparation of (3-oxo-
2,3-dihydro-1H-pyrazol-4-yl)phosphonamidates 6a and 7a.
5
6
Yield [%] Time [h]
7
Yield [%] Time[h]
[a]
[b]
[c]
[d]
5a
5b
5c
5d
6a
6a
64
67
3.0
3.0
7a
7a
75
77
0.1
0.2
[a] Yields of the pure isolated products, based on 5a,b. [b] Time for
the disappearance of compounds 5a,b. [c] Yields of the pure iso-
lated products, based on 5c,d. [d] Time for the disappearance of
compounds 5c,d.
General Procedure for the Synthesis of α-Phosphoranylidene-hydraz-
ones 3a–n: 1,2-Diaza-1,3-butadienes 1a–g (1 mmol) as a mixture
of (E)/(Z) isomers[17] and dibenzyl diisopropylphosphoramidite
(2a), methyl tetraisopropylphosphorodiamidite (2b) or tris(di-
methylamino)phosphane (2c; 4 mmol) were magnetically stirred at
room temperature for 0.2–4.5 h until the red colour of the starting
material 1 had disappeared. The α-phosphoranylidene-hydrazones
3a–n precipitated from the reaction medium and were collected by
filtration.
Conclusions
We have implemented a practical procedure for the syn-
thesis of 5-oxo-4-phoshoranylidene-4,5-dihydro-1H-pyr-
azoles and (3-oxo-2,3-dihydro-1H-pyrazol-4-yl)phosphon-
amidates via α-phosphoranylidene-hydrazones and (E)-hy-
drazono-phosphonates, respectively. Pyrazoles directly sub-
stituted with phosphorus-containing groups are of interest
as a result of their biological activity.[1–3] Furthermore, to
the best of our knowledge, few examples of the synthesis of
amino-phosphorylated pyrazolones have been reported in
the literature,[5] and thus our investigation represents an im-
portant contribution to this field. The use of heterogeneous
catalysis in the conversion of (E)-hydrazono-phosphonates
into 5-oxo-4-phoshoranylidene-4,5-dihydro-1H-pyrazoles
makes this method advantageous by virtue of the easy re-
generation of the resins and the simple workup of the reac-
tion mixtures (only filtration).[15]
Methyl 3-[(Aminocarbonyl)hydrazono]-2-[bis(benzyloxy)(diisopro-
pylamino)phosphoranylidene]butanoate (3a): White powder; yield:
330.6 mg (64%); m.p. 118–120 °C. 1H NMR (400 MHz, [D6]-
DMSO, 25 °C): δ = 1.14 [d, J = 6.8 Hz, 12 H, 2 CH(CH3)2], 2.04 (s,
3 H, CH3), 3.42 (s, 3 H, CO2CH3), 3.78–3.86 [m, 2 H, 2 CH(CH3)2],
4.92–5.03 (m, 4 H, 2 OCH2Ph), 6.01 (br. s, 2 H, NH2), 7.30–7.36
(m, 10 H, CHarom), 8.72 (s, 1 H, NH) ppm. 13C NMR (100 MHz,
3
3
[D6]DMSO, 25 °C): δ = 15.2 (d, JCP = 8.4 Hz, CH3), 21.6 (d, JCP
3
2
= 23.5 Hz, CH3), 23.2 (d, JCP = 19.7 Hz, CH3), 47.8 (d, JCP
53.9 Hz, CH), 52.0 (s, CH3), 55.5 (d, JCP = 119.2 Hz, 1 C), 64.4
(d, JCP = 28.1 Hz, CH2), 127.0 (s, CH), 127.1 (s, CH), 127.8 (s,
CH), 128.3 (s, CH), 129.1 (s, CH), 129.4 (s, CH), 136.2 (d, JCP
=
1
2
3
=
=
3
2
8.3 Hz, 1 C), 136.8 (d, JCP = 8.8 Hz, 1 C), 140.6 (d, JCP
2
14.0 Hz, 1 C), 156.8 (s, 1 C), 167.1 (d, JCP = 5.3 Hz, 1 C) ppm.
MS: m/z (%) = 516 (14) [M]+, 441 (34), 426 (100). C26H37N4O5P
(516.56): calcd. C 60.45, H 7.22, N 10.85; found C 60.39, H 7.17,
N 10.91.
Experimental Section
General: Dibenzyl diisopropylphosphoramidite, methyl tetraisopro-
pylphosphorodiamidite, tris(dimethylamino)phosphane, sodium
hydride, Amberlyst 15 H, montmorillonite KSF, HY zeolite
(DAHY) and silica gel 35–70 µm were commercial materials and
were used without further purification. Solvents were purchased
and used without further purification with the exception of THF,
which was distilled from sodium hydroxide. Melting points were
determined in open capillary tubes with a Gallenkamp apparatus.
Ethyl 3-[(Aminocarbonyl)hydrazono]-2-[bis(benzyloxy)(diisopropyl-
amino)phosphoranylidene]butanoate (3b): White powder; yield:
355.5 mg (67%); m.p. 138–140 °C. 1H NMR (400 MHz, [D6]-
DMSO, 25 °C): δ = 1.09 (t, J = 7.2 Hz, 3 H, CO2CH2CH3), 1.14
[d, J = 6.8 Hz, 12 H, 2 CH(CH3)2], 2.09 (s, 3 H, CH3), 3.81–3.90
[m, 2 H, 2 CH(CH3)2], 3.95 (q, J = 7.2 Hz, 2 H, CO2CH2CH3),
4.93–5.08 (m, 4 H, 2 OCH2Ph), 6.08 (br. s, 2 H, NH2), 7.29–7.34
(m, 10 H, CHarom), 8.72 (s, 1 H, NH) ppm. 13C NMR (100 MHz,
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Practical Access to New Phosphorylated Pyrazolones
[D6]DMSO, 25 °C): δ = 13.8 (s, CH3), 15.3 (d, 3JCP = 8.3 Hz, CH3),
21.3 (d, JCP = 22.8 Hz, CH3), 23.4 (d, JCP = 20.0 Hz, CH3), 45.6
DMSO, 25 °C): δ = 1.07–1.22 [m, 27 H, CO2CH2CH3 and 4
CH(CH3)2], 1.95 (s, 3 H, CH3), 3.70–3.79 [m, 4 H, 4 CH(CH3)2],
3.72 (d, JHP = 12.0 Hz, 3 H, OCH3), 3.86 (q, J = 7.2 Hz, 2 H,
3
3
2
1
3
(d, JCP = 53.9 Hz, CH), 55.7 (d, JCP = 119.9 Hz, 1 C), 64.5 (d,
2JCP = 28.0 Hz, CH2), 68.1 (s, CH2), 127.0 (s, CH), 127.2 (s, CH), CO2CH2CH3), 5.76 and 6.21 (2 br. s, 2 H, NH2), 8.70 (s, 1 H, NH)
127.9 (s, CH), 128.1 (s, CH), 129.0 (s, CH), 129.4 (s, CH), 136.1 (d,
ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ = 14.9 (s, CH3),
3
2
2
3JCP = 8.3 Hz, 1 C), 136.7 (d, JCP = 8.2 Hz, 1 C), 140.8 (d, JCP
21.3 (s, CH3), 23.2 (d, 3JCP = 5.6 Hz, CH3), 46.9 (d, JCP = 6.8 Hz,
2
2
1
= 15.0 Hz, 1 C), 156.9 (s, 1 C), 167.3 (d, JCP = 5.5 Hz, 1 C) ppm. CH3), 47.9 (d, JCP = 29.6 Hz, CH), 55.9 (d, JCP = 198.8 Hz, 1
MS: m/z (%) = 530 (11) [M]+, 455 (39), 440 (100). C27H39N4O5P
(530.59): calcd. C 61.12, H 7.41, N 10.56; found C 61.19, H 7.38,
N 10.69.
C), 57.3 (s, CH2), 148.2 (s, 1 C), 157.0 (s, 1 C), 168.3 (d, JCP
= 17.5 Hz, 1 C) ppm. MS: m/z (%) = 447 (77) [M]+, 404 (100).
C20H42N5O4P (447.55): calcd. C 53.67, H 9.46, N 15.65; found C
53.71, H 9.33, N 15.73.
2
Methyl 3-[(Anilinocarbonyl)hydrazono]-2-[bis(benzyloxy)(diisoprop-
ylamino)phosphoranylidene]butanoate (3c): White powder; yield: Methyl
403.1 mg (68%); m.p. 123–125 °C. 1H NMR (400 MHz, [D6]- (methoxy)phosphoranylidene]butanoate (3g): Pale-yellow powder;
DMSO, 25 °C): δ = 1.14 [d, J = 6.8 Hz, 12 H, 2 CH(CH3)2], 2.14 (s,
yield: 336.3 mg (66%); m.p. 138–140 °C. 1H NMR (400 MHz, [D6]-
3 H, CH3), 3.45 (s, 3 H, CO2CH3), 3.81–3.90 [m, 2 H, 2 CH(CH3)2], DMSO, 25 °C): δ = 1.14 and 1.17 [2 d, J = 6.8 Hz, 24 H, 4
3-[(Anilinocarbonyl)hydrazono]-2-[bis(diisopropylamino)-
4.98–5.10 (m, 4 H, 2 OCH2Ph), 6.91–7.37 (m, 15 H, CHarom), 8.25
CH(CH3)2], 2.03 (s, 3 H, CH3), 3.38 (s, 3 H, CO2CH3), 3.70–3.79
[m, 4 H, 4 CH(CH3)2], 3.73 (d, JHP = 11.6 Hz, 3 H, OCH3), 6.95
(t, J = 8.0 Hz, 1 H, CHarom), 7.24 (t, J = 8.0 Hz, 2 H, CHarom),
3
(s, 1 H, NH), 9.25 (s, 1 H, NH) ppm. 13C NMR (100 MHz, [D6]-
3
DMSO, 25 °C): δ = 15.4 (s, CH3), 21.3 (d, JCP = 22.9 Hz, CH3),
3
2
23.4 (d, JCP = 20.1 Hz, CH3), 46.3 (d, JCP = 53.8 Hz, CH), 52.1 7.41 (d, J = 8.0 Hz, 2 H, CHarom), 8.24 (s, 1 H, NH), 9.24 (s, 1 H,
1
2
(s, CH3), 55.7 (d, JCP = 119.1 Hz, 1 C), 64.2 (d, JCP = 20.0 Hz,
CH2), 118.3 (s, CH), 119.0 (s, CH), 121.9 (s, CH), 127.2 (s, CH),
127.4 (s, CH), 127.9 (s, CH), 128.0 (s, CH), 128.3 (s, CH), 128.5 (s,
NH) ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ = 14.7 (s,
3
2
CH3), 23.1 (d, JCP = 5.1 Hz, CH3), 46.9 (d, JCP = 6.1 Hz, CH3),
2
1
48.7 (d, JCP = 21.9 Hz, CH), 54.5 (s, CH3), 56.2 (d, JCP
=
3
3
CH), 135.6 (d, JCP = 8.2 Hz, 1 C), 136.2 (d, JCP = 8.3 Hz, 1 C),
198.8 Hz, 1 C), 118.4 (s, CH), 122.0 (s, CH), 128.7 (s, CH), 138.9
2
2
138.9 (s, 1 C), 139.6 (d, JCP = 15.0 Hz, 1 C), 153.3 (s, 1 C), 168.4
(s, 1 C), 150.0 (s, 1 C), 153.1 (s, 1 C), 168.4 (d, JCP = 17.5 Hz, 1
(d, 2JCP = 5.8 Hz, 1 C) ppm. MS: m/z (%) = 592 (1) [M]+, 502 (16), C) ppm. MS: m/z (%) = 509 (100) [M]+. C25H44N5O4P (509.22):
488 (29), 441 (19), 426 (100). C32H41N4O5P (592.66): calcd. C
64.85, H 6.97, N 9.45; found C 64.91, H 6.79, N 9.55.
calcd. C 58.92, H 8.70, N 13.74; found C 58.79, H 8.78, N 13.88.
Methyl 3-[(Aminocarbonyl)hydrazono]-2-[bis(diisopropylamino)-
Ethyl 3-[(Anilinocarbonyl)hydrazono]-2-[bis(benzyloxy)(diisopropyl-
(methoxy)phosphoranylidene]pentanoate (3h): White powder; yield:
292.0 mg (65%); m.p. 124–126 °C. 1H NMR (400 MHz, [D6]-
amino)phosphoranylidene]butanoate (3d): White powder; yield:
382.3 mg (63%); m.p. 130–132 °C. 1H NMR (400 MHz, [D6]- DMSO, 25 °C): δ = 1.04–1.16 [m, 27 H, CH2CH3 and 4 CH-
DMSO, 25 °C): δ = 1.10 (t, J = 7.2 Hz, 3 H, CO2CH2CH3), 1.19
[d, J = 6.8 Hz, 12 H, 2 CH(CH3)2], 2.15 (s, 3 H, CH3), 3.83–3.89
(CH3)2], 2.31 (q, J = 7.6 Hz, 2 H, CH2CH3), 3.35 (s, 3 H, CO2CH3),
3.70–3.80 [m, 4 H, 4 CH(CH3)2], 3.74 (d, JHP = 11.6 Hz, 3 H,
3
[m, 2 H, 2 CH(CH3)2], 3.95 (q, J = 7.2 Hz, 2 H, CO2CH2CH3),
OCH3), 5.74 and 6.17 (2 br. s, 2 H, NH2), 8.71 (s, 1 H, NH) ppm.
3
5.00 and 5.08 (2 dd, J = 11.6, JHP = 7.2 Hz, 4 H, 2 OCH2Ph), 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ = 9.8 (s, CH3), 23.0 (d,
6.93 (t, J = 7.2 Hz, 1 Harom), 7.18–7.38 (m, 14 H, CHarom), 8.22 (s, 1 3JCP = 6.0 Hz, CH3), 25.9 (s, CH2), 46.5 (d, JCP = 6.8 Hz, CH3),
2
H, NH), 9.22 (s, 1 H, NH) ppm. 13C NMR (100 MHz, [D6]DMSO,
49.0 (d, JCP = 30.0 Hz, CH), 54.2 (s, CH3), 55.8 (d, JCP
=
=
2
1
3
2
25 °C): δ = 13.7 (s, CH3), 14.8 (s, CH3), 21.5 (d, JCP = 23.1 Hz, 198.8 Hz, 1 C), 151.7 (s, 1 C), 156.8 (s, 1 C), 168.4 (d, JCP
CH3), 23.6 (d, 3JCP = 19.8 Hz, CH3), 45.6 (d, 2JCP = 53.8 Hz, CH),
18.2 Hz, 1 C) ppm. MS: m/z (%) = 447 (79) [M]+, 404 (100).
2
56.7 (d, 1JCP = 119.9 Hz, 1 C), 64.6 (d, JCP = 17.4 Hz, CH2), 68.2 C20H42N5O4P (447.55): calcd. C 53.67, H 9.46, N 15.65; found C
(s, CH2), 118.3 (s, CH), 119.0 (s, CH), 121.9 (s, CH), 126.7 (s, CH), 53.66, H 9.21, N 15.58.
127.2 (s, CH), 127.8 (s, CH), 128.0 (s, CH), 128.3 (s, CH), 128.5 (s,
Ethyl 2-[Bis(diisopropylamino)(methoxy)phosphoranylidene]-3-[(tert-
3
3
CH), 135.6 (d, JCP = 8.3 Hz, 1 C), 136.2 (d, JCP = 8.4 Hz, 1 C),
butoxycarbonyl)hydrazono]butanoate (3i): White powder; yield:
444.8 mg (88%); m.p. 124–126 °C. 1H NMR (400 MHz, [D6]-
DMSO, 25 °C): δ = 1.07–1.15 [m, 27 H, CO2CH2CH3 and 4
CH(CH3)2], 1.39 [s, 9 H, C(CH3)3], 1.93 (s, 3 H, CH3), 3.69–3.81
2
138.9 (s, 1 C), 139.2 (d, JCP = 15.9 Hz, 1 C), 153.3 (s, 1 C), 168.3
2
(d, JCP = 5.8 Hz, 1 C) ppm. MS: m/z (%) = 606 (11) [M]+, 560
(8), 515 (35), 426 (100). C33H43N4O5P (606.69): calcd. C 65.33, H
7.14, N 9.23; found C 65.29, H 7.28, N 9.17.
3
[m, 4 H, 4 CH(CH3)2], 3.71 (d, JHP = 12.0 Hz, 3 H, OCH3), 3.85
Methyl 3-[(Aminocarbonyl)hydrazono]-2-[bis(diisopropylamino)(meth- (q, J = 7.2 Hz, 2 H, CO2CH2CH3), 8.90 (s, 1 H, NH) ppm. 13C
oxy)phosphoranylidene]butanoate (3e): White powder; yield:
NMR (100 MHz, [D6]DMSO, 25 °C): δ = 14.7 (s, CH3), 20.7 (s,
3
2
399.1 mg (92%); m.p. 160–162 °C. 1H NMR (400 MHz, [D6]- CH3), 23.2 (d, JCP = 5.8 Hz, CH3), 29.1 (s, CH3), 44.4 (d, JCP
=
=
2
1
DMSO, 25 °C): δ = 1.14 and 1.17 [2 d, J = 6.8 Hz, 24 H, 4 21.9 Hz, CH), 46.5 (d, JCP = 6.8 Hz, CH3), 56.6 (d, JCP
CH(CH3)2], 1.96 (s, 3 H, CH3), 3.35 (s, 3 H, CO2CH3), 3.70–3.81 196.8 Hz, 1 C), 59.2 (s, CH2), 80.1 (s, 1 C), 150.1 (s, 1 C), 153.7 (s,
3
2
[m, 4 H, 4 CH(CH3)2], 3.74 (d, JHP = 11.6 Hz, 3 H, OCH3), 5.75 1 C), 168.3 (d, JCP = 18.0 Hz, 1 C) ppm. MS: m/z (%) = 504 (58)
and 6.22 (2 br. s, 2 H, NH2), 8.71 (s, 1 H, NH) ppm. 13C NMR [M]+, 431 (100). C24H49N4O5P (504.64): calcd. C 57.12, H 9.79, N
3
(100 MHz, [D6]DMSO, 25 °C): δ = 15.0 (s, CH3), 22.8 (d, JCP
=
11.10; found C 57.21, H 9.83, N 11.13.
6.0 Hz, CH3), 46.8 (d, 2JCP = 6.8 Hz, CH3), 48.5 (d, 2JCP = 21.2 Hz,
Methyl 3-[(Aminocarbonyl)hydrazono]-2-[tris(dimethylamino)phos-
phoranylidene]butanoate (3j): Pale-pink powder; yield: 271.1 mg
(81%); m.p. 162–164 °C. H NMR (400 MHz, [D6]DMSO, 25 °C):
1
CH), 54.4 (s, CH3), 56.0 (d, JCP = 198.8 Hz, 1 C), 147.3 (s, 1 C),
2
156.2 (s, 1 C), 167.7 (d, JCP = 18.2 Hz, 1 C) ppm. MS: m/z (%) =
1
433 (85) [M]+, 390 (100). C19H40N5O4P (433.52): calcd. C 52.64, H
9.30, N 16.15; found C 52.78, H 9.27, N 15.99.
4
3
δ = 1.92 (d, JHP = 2.0 Hz, 3 H, CH3), 2.55 [d, JHP = 9.6 Hz, 18
H, 3 N(CH3)2], 3.36 (s, 3 H, CO2CH3), 6.20 (br. s, 2 H, NH2), 7.79
(s, 1 H, NH) ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ =
Ethyl 3-[(Aminocarbonyl)hydrazono]-2-[bis(diisopropylamino)(meth-
2
oxy)phosphoranylidene]butanoate (3f): Pale-pink powder; yield:
16.0 (s, CH3), 37.4 (d, 2JCP = 4.6 Hz, CH3), 38.0 (d, JCP = 4.5 Hz,
446.7 mg (100%); m.p. 168–170 °C. 1H NMR (400 MHz, [D6]- CH3), 46.1 (d, JCP = 188.1 Hz, 1 C), 50.0 (s, CH3), 146.5 (s, JCP
1
2
Eur. J. Org. Chem. 2008, 5965–5973
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5969

O. A. Attanasi, L. De Crescentini et al.
FULL PAPER
2
= 9.1 Hz, 1 C), 156.8 (s, 1 C), 166.8 (d, JCP = 16.0 Hz, 1 C) ppm. a catalytic amount in the case of 3a–i and a stoichiometric amount
MS: m/z (%) = 334 (39) [M]+, 317 (8), 303 (36), 260 (100). (1.0 mmol) in the case of 3k–n of sodium hydride was added. The
C12H27N6O3P (334.35): calcd. C 43.11, H 8.14, N 25.14; found C
43.23, H 8.24, N 25.18.
reaction mixture was magnetically stirred for 0.5–72.0 h until the
disappearance of the starting compound 3. 5-Oxo-4-phoshoranyl-
idene-4,5-dihydro-1H-pyrazoles 4a–h were obtained by column
chromatography on silica gel (elution mixtures: ethyl acetate/meth-
anol) and by subsequent crystallization from diethyl ether/light pe-
troleum ether (40–60 °C).
Ethyl
3-[(Aminocarbonyl)hydrazono]-2-[tris(dimethylamino)phos-
phoranylidene]butanoate (3k): Pale-pink powder; yield: 392.7 mg
1
(84%); m.p. 174–176 °C. H NMR (400 MHz, [D6]DMSO, 25 °C):
δ = 1.05 (t, J = 7.2 Hz, 3 H, CO2CH2CH3), 1.93 (d, 4JHP = 1.6 Hz,
3
3 H, CH3), 2.55 [d, JHP = 9.6 Hz, 18 H, 3 N(CH3)2], 3.84 (q, J =
General Procedure for the Synthesis of 5-Oxo-4-phosphoranylidene-
4,5-dihydro-1H-pyrazoles 4f–h with Silica Gel: Phosphoranylidene-
hydrazones 3j–n (1 mmol) were dissolved in a mixture of tetra-
hydrofuran (9.5 mL)/methanol (0.5 mL) at room temperature, and
silica gel (5 g) was added. The reaction mixture was magnetically
stirred for 0.1–0.2 h until the disappearance of the starting com-
pound 3. The resin was removed by filtration, and the reaction
solvents were evaporated under reduced pressure. The crude prod-
uct was purified by chromatography on a silica gel column (elution
mixtures: ethyl acetate/methanol) to give 5-oxo-4-phosphoranylid-
ene-4,5-dihydro-1H-pyrazoles 4f–h, which were crystallized from
diethyl ether/light petroleum ether (40–60 °C).
7.2 Hz, 2 H, CO2CH2CH3), 6.18 (br. s, 2 H, NH2), 7.77 (s, 1 H,
NH) ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ = 15.8 (s,
2
2
CH3), 20.7 (s, CH3), 37.4 (d, JCP = 5.8 Hz, CH3), 38.0 (d, JCP
=
1
5.3 Hz, CH3), 46.2 (d, JCP = 187.4 Hz, 1 C), 57.4 (s, CH2), 146.6
(s, 2JCP = 9.9 Hz, 1 C), 156.8 (s, 1 C), 166.4 (d, 2JCP = 15.2 Hz, 1 C)
ppm. MS: m/z (%) = 348 (1) [M]+, 302 (4), 259 (100). C13H29N6O3P
(348.38): calcd. C 44.82, H 8.39, N 24.12; found C 44.91, H 8.43,
N 24.31.
Methyl 3-[(Anilinocarbonyl)hydrazono]-2-[tris(dimethylamino)phos-
phoranylidene]butanoate (3l): Pale-pink powder; yield: 296.2 mg
1
(72%); m.p. 102–104 °C. H NMR (400 MHz, [D6]DMSO, 25 °C):
3
δ = 2.02 (s, 3 H, CH3), 2.56 [d, JHP = 9.6 Hz, 18 H, 3 N(CH3)2],
4-[Bis(benzyloxy)(diisopropylamino)phosphoranylidene]-3-methyl-5-
oxo-4,5-dihydro-1H-pyrazole-1-carboxamide (4a): Pale-pink pow-
der; yield: 324.9 mg (67%) from 3a, 309.6 mg (64%) from 3b; m.p.
3.41 (s, 3 H, CO2CH3), 6.95–7.59 (m, 5 H, CHarom), 8.39 (s, 1 H,
NH), 9.14 (s, 1 H, NH) ppm. 13C NMR (100 MHz, [D6]DMSO,
2
1
25 °C): δ = 15.3 (s, CH3), 36.9 (d, JCP = 4.6 Hz, CH3), 37.4 (d,
190–192 °C. H NMR (400 MHz, [D6]DMSO, 25 °C): δ = 1.19 [d,
2JCP = 4.5 Hz, CH3), 45.9 (d, 1JCP = 188.9 Hz, 1 C), 49.3 (s, CH3),
J = 6.8 Hz, 12 H, 2 CH(CH3)2], 2.06 (s, 3 H, CH3), 3.32–3.64 [m,
2 H, 2 CH(CH3)2], 4.85–5.09 (m, 4 H, 2 OCH2Ph), 6.29 and 9.25
118.9 (s, CH), 122.0 (s, CH), 128.5 (s, CH), 139.3 (s, 1 C), 147.6 (s,
2
2JCP = 9.9 Hz, 1 C), 152.4 (s, 1 C), 166.1 (d, JCP = 15.2 Hz, 1 C)
(2 br. s, 2 H, NH2), 7.33–7.38 (m, 10 H, CHarom) ppm. 13C NMR
=
410 (2) [M]+, 378 (10), 259 (100).
3
ppm. MS: m/z (%)
(100 MHz, [D6]DMSO, 25 °C): δ = 16.0 (s, CH3), 23.3 (d, JCP
=
=
2
2
C18H31N6O3P (410.45): calcd. C 52.67, H 7.61, N 20.48; found C
52.73, H 7.75, N 20.31.
19.0 Hz, CH3), 45.2 (d, JCP = 43.4 Hz, CH), 64.4 (d, JCP
28.1 Hz, CH2), 84.4 (d, 1JCP = 201.0 Hz, 1 C), 127.6 (s, CH), 127.8
(s, CH), 128.0 (s, CH), 128.3 (s, CH), 128.8 (s, CH), 128.9 (s, CH),
139.1 (d, 3JCP = 12.2 Hz, 1 C), 139.7 (d, 3JCP = 12.0 Hz, 1 C), 151.7
Ethyl
3-[(Anilinocarbonyl)hydrazono]-2-[tris(dimethylamino)phos-
phoranylidene]butanoate (3m): Pale-pink powder; yield: 327.2 mg
2
2
1
(s, 1 C), 153.9 (d, JCP = 5.1 Hz, 1 C), 167.4 (d, JCP = 19.6 Hz, 1
C) ppm. MS: m/z (%) = 484 (2) [M]+, 470 (6), 152 (21), 125 (48),
111 (100). C25H33N4O4P (484.52): calcd. C 61.97, H 6.86, N 11.56;
found C 61.91, H 6.71, N 11.63.
(77%); m.p. 102–104 °C. H NMR (400 MHz, [D6]DMSO, 25 °C):
δ = 1.17 (t, J = 7.2 Hz, 3 H, CO2CH2CH3), 2.13 (s, 3 H, CH3),
2.67 [d, 3JHP = 9.6 Hz, 18 H, 3 N(CH3)2], 4.01 (q, J = 7.2 Hz, 2 H,
CO2CH2CH3), 6.96–7.54 (m, 5 H, CHarom), 8.19 (s, 1 H, NH), 8.77
(s, 1 H, NH) ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ =
4-[Bis(benzyloxy)(diisopropylamino)phosphoranylidene]-3-methyl-5-
oxo-N-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide (4b): White
powder; yield: 387.2 mg (69%) from 3c, 419.8 mg (75%) from 3d;
m.p. 201–203 °C. 1H NMR (400 MHz, [D6]DMSO, 25 °C): δ = 1.19
[d, J = 6.8 Hz, 12 H, 2 CH(CH3)2], 2.12 (s, 3 H, CH3), 3.48–3.56
[m, 2 H, 2 CH(CH3)2], 4.86–4.96 (m, J = 11.6 Hz, 4 H, 2 OCH2Ph),
2
15.5 (s, CH3), 20.9 (s, CH3), 37.0 (d, JCP = 4.6 Hz, CH3), 38.0 (d,
2JCP = 4.5 Hz, CH3), 46.0 (d, 1JCP = 188.8 Hz, 1 C), 57.6 (s, CH2),
118.8 (s, CH), 121.9 (s, CH), 128.7 (s, CH), 139.5 (s, 1 C), 147.3
2
2
(d, JCP = 9.9 Hz, 1 C), 152.8 (s, 1 C), 166.4 (d, JCP = 15.2 Hz, 1
C) ppm. MS: m/z (%) = 424 (1) [M]+, 410 (81), 379 (30), 365 (11),
318 (100). C19H33N6O3P (424.47): calcd. C 53.76, H 7.84, N 19.80;
found C 53.81, H 7.91, N 19.72.
6.99–7.55 (m, 15 H, CHarom), 12.62 (s, 1 H, NH) ppm. 13C NMR
3
(100 MHz, [D6]DMSO, 25 °C): δ = 16.1 (s, CH3), 23.4 (d, JCP
=
=
2
2
15.2 Hz, CH3), 45.2 (d, JCP = 43.0 Hz, CH), 64.4 (d, JCP
Methyl 3-[(Anilinocarbonyl)hydrazono]-2-[tris(dimethylamino)phos-
28.1 Hz, CH2), 84.5 (d, 1JCP = 205.0 Hz, 1 C), 118.4 (s, CH), 119.7
(s, CH), 123.1 (s, CH), 127.6 (s, CH), 127.7 (s, CH), 128.8 (s, CH),
120.0 (s, CH), 129.3 (s, CH), 129.6 (s, CH), 138.9 (s, 1 C), 139.3
phoranylidene]pentanoate (3n): Pale-pink powder; yield: 304.9 mg
1
(72%); m.p. 110–112 °C. H NMR (400 MHz, [D6]DMSO, 25 °C):
δ = 1.01 (t, J = 7.2 Hz, 3 H, CO2CH2CH3), 2.29 (q, J = 7.2 Hz, 2
3
3
3
(d, JCP = 12.2 Hz, 1 C), 139.6 (d, JCP = 12.2 Hz, 1 C), 150.7 (s,
H, CO2CH2CH3), 2.56 [d, JHP = 9.6 Hz, 18 H, 3 N(CH3)2], 3.38
2
2
1 C), 153.5 (d, JCP = 4.8 Hz, 1 C), 167.5 (d, JCP = 19.8 Hz, 1 C)
ppm. MS: m/z (%) = 560 (1) [M]+, 546 (5), 167 (22), 152 (24), 125
(57), 111 (100). C31H37N4O4P (560.62): calcd. C 66.41, H 6.65, N
9.99; found C 66.33, H 6.78, N 9.79.
(s, 3 H, CO2CH3), 6.94–7.56 (m, 5 H, CHarom), 8.21 (s, 1 H, NH),
8.66 (s, 1 H, NH) ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C):
δ = 11.8 (s, CH3), 22.8 (s, CH2), 37.4 (d, 2JCP = 4.5 Hz, CH3), 37.6
2
1
(d, JCP = 4.6 Hz, CH3), 46.0 (d, JCP = 189.6 Hz, 1 C), 50.0 (s,
CH3), 119.7 (s, CH), 122.9 (s, CH), 129.3 (s, CH), 139.8 (s, 1 C),
4-[Bis(diisopropylamino)(methoxy)phosphoranylidene]-3-methyl-5-
oxo-4,5-dihydro-1H-pyrazole-1-carboxamide (4c): White powder;
yield: 302.1 mg (75%) from 3e, 273.8 mg (68%) from 3f; m.p. 148–
2
2
152.3 (s, JCP = 9.1 Hz, 1 C), 153.2 (s, 1 C), 167.0 (d, JCP
=
15.2 Hz, 1 C) ppm. MS: m/z (%) = 424 (50) [M]+, 393 (11), 332
(58), 274 (100). C19H33N6O3P (424.47): calcd. C 53.76, H 7.84, N
19.80; found C 53.66, H 7.94, N 19.69.
1
150 °C. H NMR (400 MHz, [D6]DMSO, 25 °C): δ = 1.20 [d, J =
6.8 Hz, 12 H, 2 CH(CH3)2], 1.27 [d, J = 6.8 Hz, 12 H, 2 CH-
(CH3)2], 2.02 (s, 3 H, CH3), 3.83–3.94 [m, 4 H, 4 CH(CH3)2], 3.89
General Procedure for the Synthesis of 5-Oxo-4-phoshoranylidene-
4,5-dihydro-1H-pyrazoles 4a–h with Sodium Hydride: α-Phosphor-
anylidene-hydrazones 3a–n (1 mmol) were dissolved in a mixture of
tetrahydrofuran (5 mL)/methanol (5 mL) at room temperature and
3
(d, JHP = 12.0 Hz, 3 H, OCH3), 6.84 and 8.70 (2 s, 2 H, NH2)
ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ = 16.1 (s, CH3),
23.1 (q, CH3), 47.9 (d, 2JCP = 6.8 Hz, CH3), 55.5 (d, 2JCP = 5.3 Hz,
5970
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 5965–5973

Practical Access to New Phosphorylated Pyrazolones
1
2
CH), 75.0 (d, JCP = 197.9 Hz, 1 C), 148.8 (d, JCP = 13.7 Hz, 1
299.1 mg (76%) using NaH, 378.1 mg (86%) using silica gel; m.p.
144–146 °C. H NMR (400 MHz, [D6]DMSO, 25 °C): δ = 1.20 (t,
2
1
C), 151.6 (s, 1 C), 167.8 (d, JCP = 25.0 Hz, 1 C) ppm. MS: m/z
(%) = 401 (1) [M]+, 358 (8), 315 (8), 258 (100). C18H36N5O3P J = 7.6 Hz, 3 H, CH2CH3), 2.37 (q, J = 7.6 Hz, 2 H, CH2CH3),
3
(401.48): calcd. C 53.85, H 9.04, N 17.44; found C 53.94, H 9.12,
N 17.54.
2.68 [d, JHP = 9.6 Hz, 18 H, 3 N(CH3)2], 7.04 (t, J = 7.6 Hz, 1 H,
CHarom), 7.32 (t, J = 7.6 Hz, 2 H, CHarom), 7.51 (d, J = 7.6 Hz, 2
H, CHarom), 12.07 (s, 1 H, NH) ppm. 13C NMR (100 MHz, [D6]-
4-[Bis(diisopropylamino)(methoxy)phosphoranylidene]-3-methyl-5-
oxo-N-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide (4d): White
powder; yield: 431.1 mg (90 %); m.p. 150–152 °C. 1H NMR
(400 MHz, [D6]DMSO, 25 °C): δ = 1.20 [d, J = 6.8 Hz, 12 H, 2
CH(CH3)2], 1.31 [d, J = 6.8 Hz, 12 H, 2 CH(CH3)2], 2.11 (s, 3 H,
2
DMSO, 25 °C): δ = 12.2 (s, CH3), 22.4 (s, CH2), 37.6 (d, JCP
=
1
5.3 Hz, CH3), 72.5 (d, JCP = 193.5 Hz, 1 C), 119.9 (s, CH), 123.5
(s, CH), 129.7 (s, CH), 139.2 (s, 1 C), 149.5 (s, 1 C), 155.6 (d, JCP
2
2
= 12.1 Hz, 1 C), 168.9 (d, JCP = 22.7 Hz, 1 C) ppm. MS: m/z (%)
= 392 (5) [M]+, 349 (1), 273 (100). C18H29N6O2P (392.43): calcd.
C 55.09, H 7.45, N 21.42; found C 55.18, H 7.67, N 21.53.
3
CH3), 3.87–3.96 [m, 4 H, 4 CH(CH3)2], 3.90 (d, JHP = 12.0 Hz, 3
H, OCH3), 6.99–7.53 (m, J = 5 H, CHarom), 11.95 (s, 1 H, NH)
ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ = 16.2 (s, CH3),
General Procedure for the Synthesis of (E)-Hydrazono-phosphonates
5a–d Starting from 1,2-Diaza-1,3-butadienes (Scheme 1, Path b):
1,2-Diaza-1,3-butadienes 1a–d (1 mmol) as a mixture of (E)/(Z)
isomers[17] and dibenzyl diisopropylphosphoramidite (2a) (4 mmol)
were magnetically stirred at room temperature for 3.0–4.5 h until
the red colour of the starting compound 1 disappeared and α-phos-
phoranylidene-hydrazones 3a–d precipitated from the reaction me-
dium. Then the temperature of the reaction mixture was raised to
40 °C, and the mixture was allowed to stand under these conditions
for 7.0–12.0 h. (E)-Hydrazono-phosphonates 5a–d were obtained
by column chromatography on silica gel (elution mixtures: ethyl
acetate/methanol). Further purification of these compounds was
achieved by crystallization from ethyl acetate/light petroleum ether
(40–60 °C).
3
2
23.1 (d, JCP = 3.8 Hz, CH3), 47.3 (d, JCP = 6.0 Hz, CH3), 55.0
(d, JCP = 6.1 Hz, CH), 76.2 (d, JCP = 196.6 Hz, 1 C), 119.2 (s,
CH), 122.9 (s, CH), 129.0 (s, CH), 138.3 (s, 1 C), 148.7 (d, JCP
13.7 Hz, 1 C), 150.4 (s, 1 C), 167.8 (d, JCP = 25.0 Hz, 1 C) ppm.
MS: m/z (%) = 477 (1) [M]+, 358 (8), 258 (100). C24H40N5O3P
(477.58): calcd. C 60.36, H 8.44, N 14.66; found C 60.31, H 8.55,
N 14.72.
2
1
2
=
2
tert-Butyl 4-[Bis(diisopropylamino)(methoxy)phosphoranylidene]-3-
methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-carboxylate (4e): White
powder; yield: 322.1 mg (70 %); m.p. 151–153 °C. 1H NMR
(400 MHz, CDCl3, 25 °C): δ = 1.30 [d, J = 6.8 Hz, 12 H, 2
CH(CH3)2], 1.34 [d, J = 6.8 Hz, 12 H, 2 CH(CH3)2], 1.61 [s, 9 H,
4
3
C(CH3)3], 2.18 (d, JHP = 0.8 Hz, 3 H, CH3), 3.88 (d, JHP
=
12.0 Hz, 3 H, OCH3), 3.90–3.98 [m, 4 H, 4 CH(CH3)2] ppm. 13C
NMR (100 MHz, [D6]DMSO, 25 °C): δ = 16.3 (s, CH3), 20.9 (s,
General Procedure for the Synthesis of (E)-Hydrazono-phosphonates
5a–d Starting from α-Phosphoranylidene-hydrazones 3a–d
(Scheme 1, Path c): A solution of α-phosphoranylidene-hydrazones
3a–d (1 mmol) in methanol (9.5 mL)/water (0.5 mL) was magneti-
cally stirred for 7.0–27.0 h until TLC revealed the disappearance of
the starting compound 3. The mixture was then dried with anhy-
drous sodium sulfate and, after evaporation of the solvent, purified
by chromatography on a silica gel column (elution mixtures: ethyl
acetate/methanol) to give hydrazono-phosphonates 5a–d in good
purity. Further purification of these compounds was achieved by
crystallization from ethyl acetate/light petroleum ether (40–60 °C).
2
2
CH3), 23.3 (s, CH3), 46.8 (d, JCP = 6.8 Hz, CH3), 54.0 (d, JCP
=
6.8 Hz, CH), 76.1 (d, 1JCP = 196.6 Hz, 1 C), 80.1 (s, 1 C), 146.6 (d,
2JCP = 13.0 Hz, 1 C), 153.6 (s, 1 C), 169.5 (d, JCP = 21.2 Hz, 1 C)
2
ppm. MS: m/z (%) = 458 (11) [M]+, 359 (6), 315 (24), 258 (100).
C22H43N4O4P (458.57): calcd. C 57.62, H 9.45, N 12.22; found C
57.58, H 9.61, N 12.03.
3-Methyl-5-oxo-4-[tris(dimethylamino)phosphoranylidene]-4,5-di-
hydro-1H-pyrazole-1-carboxamide (4f): White powder; yield:
200.1 mg (66%) from 3j and 204.9 mg (68%) from 3k using NaH,
257.1 mg (85%) from 3j and 244.5 mg (81%) from 3k using silica
gel; m.p. 174–176 °C. 1H NMR (400 MHz, [D6]DMSO, 25 °C): δ
Methyl 3-[(Aminocarbonyl)hydrazono]-2-[(benzyloxy)(diisopropyl-
amino)phosphoryl]butanoate (5a): Pale-pink powder; yield:
332.8 mg (78%) by path b, 290.1 mg (68%) by path c; m.p. 140–
3
= 1.98 (s, 3 H, CH3), 2.65 [d, JHP = 10.0 Hz, 18 H, 3 N(CH3)2],
6.88 and 8.78 (2 br. s, 2 H, NH2) ppm. 13C NMR (100 MHz, [D6]-
1
142 °C. H NMR (400 MHz, [D6]DMSO, 25 °C): δ = 1.06 [d, J =
2
DMSO, 25 °C): δ = 15.3 (s, CH3), 36.9 (d, JCP = 4.6 Hz, CH3),
6.4 Hz, 6 H, CH(CH3)2], 1.17 [d, J = 6.8 Hz, 6 H, CH(CH3)2], 2.04
71.5 (d, 1JCP = 193.5 Hz, 1 C), 149.5 (s, 2JCP = 12.1 Hz, 1 C), 151.7
4
(d, JHP = 2.8 Hz, 3 H, CH3), 3.32–3.39 [m, 2 H, 2 CH(CH3)2],
2
(s, 1 C), 168.2 (d, JCP = 22.8 Hz, 1 C) ppm. MS: m/z (%) = 302
1
3.55 (s, 3 H, CO2CH3), 4.08 (d, JHP = 20.4 Hz, 1 H, CH), 4.94 (2
(1) [M]+, 259 (100). C11H23N6O2P (302.31): calcd. C 43.70, H 7.67,
N 27.80; found C 43.81, H 7.72, N 27.66.
dd, J = 7.2, 3JHP = 12.4 Hz, 2 H, OCH2Ph), 6.29 (br. s, 2 H, NH2),
7.30–7.39 (m, 5 H, CHarom), 9.25 (s, 1 H, NH) ppm. 13C NMR
3
(100 MHz, [D6]DMSO, 25 °C): δ = 15.9 (d, JCP = 8.3 Hz, CH3),
3-Methyl-5-oxo-N-phenyl-4-[tris(dimethylamino)phosphoranylidene]-
4,5-dihydro-1H-pyrazole-1-carboxamide (4g): White powder; yield:
338.1 mg (89%) from 3l and 343.8 mg (91%) from 3m using NaH,
307.1 mg (81%) from 3l and 330.1 mg (87%) from 3m using silica
gel; m.p. 174–176 °C. 1H NMR (400 MHz, [D6]DMSO, 25 °C): δ
3
3
22.3 (d, JCP = 23.6 Hz, CH3), 23.9 (d, JCP = 19.7 Hz, CH3), 46.3
(s, CH), 52.7 (s, CH3), 56.3 (d, 1JCP = 119.1 Hz, CH), 65.3 (d, 2JCP
= 6.1 Hz, CH2), 127.9 (s, CH), 128.5 (s, CH), 129.0 (s, CH), 137.6
3
2
(d, JCP = 6.8 Hz, 1 C), 141.3 (d, JCP = 6.1 Hz, 1 C), 157.6 (s, 1
2
3
C), 167.8 (d, JCP = 5.3 Hz, 1 C) ppm. MS: m/z (%) = 426 (48)
= 2.02 (s, 3 H, CH3), 2.67 [d, JHP = 10.0 Hz, 18 H, 3 N(CH3)2],
[M]+, 411 (8), 395 (1), 383 (4), 368 (18), 351 (34), 336 (15), 326
(27), 309 (6), 294 (7), 283 (13), 272 (100). C19H31N4O5P (426.44):
calcd. C 53.51, H 7.33, N 13.14; found C 53.66, H 7.23, N 13.01.
7.04 (t, J = 7.6 Hz, 1 H, CHarom), 7.30 (t, J = 7.6 Hz, 2 H, CHarom),
7.49 (d, J = 7.6 Hz, 2 H, CHarom), 11.98 (s, 1 H, NH) ppm. 13C
NMR (100 MHz, [D6]DMSO, 25 °C): δ = 16.0 (s, CH3), 37.6 (d,
2JCP = 4.5 Hz, CH3), 73.1 (d, 1JCP = 192.7 Hz, 1 C), 119.8 (s, CH),
123.5 (s, CH), 129.7 (s, CH), 139.2 (s, 1 C), 149.4 (s, 1 C), 151.2
(d, JCP = 12.1 Hz, 1 C), 169.0 (d, JCP = 22.7 Hz, 1 C) ppm. MS:
m/z (%) = 378 (2) [M]+, 259 (100). C17H27N6O2P (378.40): calcd.
C 53.96, H 7.19, N 22.21; found C 53.88, H 7.21, N 22.12.
Ethyl 3-[(Aminocarbonyl)hydrazono]-2-[(benzyloxy)(diisopro-
pylamino)phosphoryl]butanoate (5b): Pale-pink powder; yield:
383.9 mg (87%) by path b, 274.0 mg (62%) by path c; m.p. 150–
2
2
1
152 °C. H NMR (400 MHz, [D6]DMSO, 25 °C): δ = 1.04 (t, J =
7.2 Hz, 3 H, CO2CH2CH3), 1.08 [d, J = 7.2 Hz, 6 H, CH(CH3)2],
1.19 [d, J = 6.4 Hz, 6 H, CH(CH3)2], 2.07 (s, 3 H, CH3), 3.32–3.41
[m, 2 H, 2 CH(CH3)2], 4.00–4.08 (m, 3 H, CO2CH2CH3 and CH),
3-Ethyl-5-oxo-N-phenyl-4-[tris(dimethylamino)phosphoranylidene]-
4,5-dihydro-1H-pyrazole-1-carboxamide (4h): White powder; yield:
Eur. J. Org. Chem. 2008, 5965–5973
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5971

O. A. Attanasi, L. De Crescentini et al.
FULL PAPER
4.87–4.90 and 5.02–5.05 (2 m, 2 H, OCH2Ph), 6.29 (br. s, 2 H,
Benzyl N,N-Diisopropyl-P-(5-methyl-3-oxo-2,3-dihydro-1H-pyr-
NH2), 7.30–7.39 (m, 5 H, CHarom), 9.23 (s, 1 H, NH) ppm. 13C azol-4-yl)phosphonamidate (6a): Pale-pink powder; yield: 225.1 mg
NMR (100 MHz, [D6]DMSO, 25 °C): δ = 13.7 (s, CH3), 15.3 (d, (64 %) from 5a, 234.9 mg (67 %) from 5b; m.p. 177–179 °C. 1H
3
3
3JCP = 8.1 Hz, CH3), 21.6 (d, JCP = 21.2 Hz, CH3), 23.2 (d, JCP
NMR (400 MHz, [D6]DMSO, 25 °C): δ = 1.09 [d, J = 6.0 Hz, 6 H,
CH(CH3)2], 1.15 [d, J = 6.4 Hz, 6 H, CH(CH3)2], 2.10 (s, 3 H,
CH3), 3.37–3.50 [m, 2 H, 2 CH(CH3)2], 4.81–4.85 (m, 2 H,
OCH2Ph), 6.91 (br. s, 1 H, NH), 7.25–7.43 (m, 5 H, CHarom), 9.09
(s, 1 H, NH) ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ =
1
= 18.2 Hz, CH3), 45.6 (s, CH), 55.7 (d, JCP = 119.1 Hz, CH), 60.9
(s, CH2), 64.5 (d, 2JCP = 6.1 Hz, CH2), 127.2 (s, CH), 127.8 (s, CH),
128.2 (s, CH), 136.8 (d, 3JCP = 6.8 Hz, 1 C), 140.8 (d, 2JCP = 6.1 Hz,
2
1 C), 156.9 (s, 1 C), 166.6 (d, JCP = 5.3 Hz, 1 C) ppm. MS: m/z
(%) = 440 (17) [M]+, 425 (8), 382 (18), 370 (43), 340 (39), 297 (15), 15.2 (s, CH3), 22.6 (d, 3JCP = 19.8 Hz, CH3), 44.4 (d, 2JCP = 5.3 Hz,
2
1
272 (100). C20H33N4O5P (440.47): calcd. C 54.54, H 7.55, N 12.72;
found C 54.61, H 7.58, N 12.88.
CH), 63.6 (d, JCP = 5.0 Hz, CH2), 65.8 (d, JCP = 95.1 Hz, 1 C),
3
126.98 (s, CH), 128.1 (s, CH), 128.9 (s, CH), 138.9 (d, JCP
=
=
2
2
5.9 Hz, 1 C), 152.8 (d, JCP = 12.3 Hz, 1 C), 166.1 (d, JCP
Methyl 3-[(Anilinocarbonyl)hydrazono]-2-[(benzyloxy)(diisopro-
9.2 Hz, 1 C) ppm. MS: m/z (%) = 351 (14) [M]+, 283 (11), 265 (11),
258 (100). C17H26N3O3P (351.38): calcd. C 58.11, H 7.46, N 11.96;
found C 58.23, H 7.39, N 12.03.
pylamino)phosphoryl]butanoate (5c): White powder; yield: 337.2 mg
1
(67%) by path b, 331.4 mg (66%) by path c; m.p. 198–200 °C. H
NMR (400 MHz, [D6]DMSO, 25 °C): δ = 1.09 [d, J = 6.4 Hz, 6 H,
CH(CH3)2], 1.20 [d, J = 6.0 Hz, 6 H, CH(CH3)2], 2.13 (s, 3 H, Benzyl P-[2-(Anilinocarbonyl)-5-methyl-3-oxo-2,3-dihydro-1H-pyr-
CH3), 3.30–3.40 [m, 2 H, 2 CH(CH3)2], 3.59 (s, 3 H, CO2CH3),
4.43 (d, JHP = 20.4 Hz, 1 H, CH), 4.89–4.93 and 5.04–5.07 (2 m,
2 H, OCH2Ph), 6.98 (t, J = 6.8 Hz, 1 H, CHarom), 7.25–7.39 (m, 8 204 °C. H NMR (400 MHz, [D6]DMSO, 25 °C): δ = 1.11 [d, J =
azol-4-yl]-N,N-diisopropylphosphonamidate (7a): White powder;
1
yield: 353.3 mg (75%) from 5c, 362.0 mg (77%) from 5d; m.p. 202–
1
H, CHarom), 7.57 (d, J = 7.6 Hz, 1 H, CHarom), 8.89 (s, 1 H, NH),
6.4 Hz, 6 H, CH(CH3)2], 1.19 [d, J = 6.8 Hz, 6 H, CH(CH3)2], 2.14
(s, 3 H, CH3), 3.42–3.53 [m, 2 H, 2 CH(CH3)2], 4.86–4.97 (m, 2 H,
9.82 (s, 1 H, NH) ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C):
3
3
δ = 15.5 (d, JCP = 8.3 Hz, CH3), 21.8 (d, JCP = 21.6 Hz, CH3), OCH2Ph), 7.01 (t, J = 6.8 Hz, 1 H, CHarom), 7.26–7.55 (m, 9 H,
3
23.1 (d, JCP = 19.2 Hz, CH3), 45.6 (s, CH), 52.1 (s, CH3), 55.1 (d,
CHarom), 12.63 (2 s, 2 H, 2 NH) ppm. 13C NMR (100 MHz, [D6]-
1JCP = 119.9 Hz, CH), 64.7 (d, 2JCP = 6.1 Hz, CH2), 118.9 (s, CH),
DMSO, 25 °C): δ = 15.3 (s, CH3), 22.7 (d, JCP = 15.9 Hz, CH3),
3
122.2 (s, CH), 127.2 (s, CH), 127.8 (s, CH), 127.9 (s, CH), 128.2 (s,
44.4 (d, 2JCP = 5.3 Hz, CH), 63.6 (d, 2JCP = 4.6 Hz, CH2), 65.2 (d,
1JCP = 93.3 Hz, 1 C), 117.7 (s, CH), 119.0 (s, CH), 122.4 (s, CH),
126.8 (s, CH), 128.0 (s, CH), 128.9 (s, CH), 138.9 (d, 3JCP = 5.9 Hz,
2
CH), 136.8 (d, 3JCP = 6.8 Hz, 1 C), 139.1 (s, 1 C), 141.9 (d, JCP
=
2
6.1 Hz, 1 C), 153.2 (s, 1 C), 167.2 (d, JCP = 5.3 Hz, 1 C) ppm.
MS: m/z (%) = 502 (35) [M]+, 410 (81), 247 (100). C25H35N4O5P
(502.54): calcd. C 59.75, H 7.02, N 11.15; found C 59.90, H 7.11,
N 11.29.
2
1 C), 139.3 (s, 1 C), 149.8 (s, 1 C), 152.7 (d, JCP = 12.3 Hz, 1 C),
2
166.8 (d, JCP = 9.2 Hz, 1 C) ppm. MS: m/z (%) = 470 (1) [M]+,
426 (27), 351 (100). C24H31N4O4P (470.50): calcd. C 61.27, H 6.64,
N 11.91; found C 61.34, H 6.81, N 11.88.
Ethyl 3-[(Anilinocarbonyl)hydrazono]-2-[(benzyloxy)(diisopro-
pylamino)phosphoryl]butanoate (5d): White powder; yield: 360.9 mg
(70%) by path b, 393.1 mg (76%) by path c; m.p. 208–210 °C. H
NMR (400 MHz, [D6]DMSO, 25 °C): δ = 1.06 (t, J = 7.2 Hz, 3 H,
CO2CH2CH3), 1.10 [d, J = 6.0 Hz, 6 H, CH(CH3)2], 1.20 [d, J =
X-ray Crystallography of Compound 4c: Single crystals of 4c were
obtained by dissolving a few milligrams of powder in dioxane and
allowing the solution to concentrate at room temperature. A Sie-
mens P4 four-circle diffractometer with graphite-monochromated
1
6.0 Hz, 6 H, CH(CH3)2], 2.13 (s, 3 H, CH3), 3.35–3.43 [m, 2 H, 2 Mo-Kα radiation (λ = 0.71073 Å) and the ω-scan technique were
CH(CH3)2], 4.01–4.06 (m, 2 H, CO2CH2CH3), 4.40 (d, J = 6.8 Hz,
1 H, CH), 4.87–4.90 and 5.02–5.06 (2 m, 2 H, OCH2Ph), 6.99 (t,
J = 6.8 Hz, 1 Harom), 7.27–7.39 (m, 8 H, CHarom), 7.57 (d, J =
6.8 Hz, 1 Harom), 8.89 (s, 1 H, NH), 9.80 (s, 1 H, NH) ppm. 13C
used for data collection. The structure was solved by direct meth-
ods implemented in the SHELXS-97 program.[18] Refinement was
carried out by full-matrix anisotropic least-squares methods on F2
for all reflections for non-hydrogen atoms by using the SHELXL-
NMR (100 MHz, [D6]DMSO, 25 °C): δ = 13.7 (s, CH3), 15.2 (d, 97 program.[19]
3
3
3JCP = 8.8 Hz, CH3), 21.7 (d, JCP = 21.8 Hz, CH3), 23.1 (d, JCP
1
= 19.0 Hz, CH3), 45.6 (s, CH), 55.2 (d, JCP = 119.1 Hz, CH), 61.0
Acknowledgments
(s, CH2), 64.6 (d, 2JCP = 6.1 Hz, CH2), 118.9 (s, CH), 122.3 (s, CH),
127.3 (s, CH), 127.8 (s, CH), 127.9 (s, CH), 128.3 (s, CH), 137.0 (d,
This work was supported by financial assistance from the Ministero
dell’Istruzione, dell’Università e della Ricerca (MIUR)-PRIN and
the Università degli Studi di Urbino “Carlo Bo”.
2
3JCP = 6.8 Hz, 1 C), 139.1 (s, 1 C), 142.1 (d, JCP = 6.1 Hz, 1 C),
2
153.3 (s, 1 C), 166.7 (d, JCP = 5.3 Hz, 1 C) ppm. MS: m/z (%) =
516 (39) [M]+, 424 (71), 261 (100). C26H37N4O5P (516.56): calcd.
C 60.45, H 7.22, N 10.85; found C 60.33, H 7.29, N 10.69.
[1] a) N. J. Wardle, S. W. A. Bligh, H. R. Hudson, Curr. Org.
Chem. 2005, 9, 1803–1828; b) M. L. Manier, D. L. Hachey,
B. O. Bachmann, Org. Lett. 2005, 7, 2763–2765; c) H. Seto, T.
Kuzuyama, Nat. Prod. Rep. 1999, 16, 589–596; d) S. C. Fields,
Tetrahedron 1999, 55, 12237–12273.
[2] S. Franco, E. Melendez, F. L. Merchan, J. Heterocycl. Chem.
1995, 32, 1181–1183.
[3] a) K. Y. Lee, J. M. Kim, J. N. Kim, Tetrahedron Lett. 2003,
44, 6737–6740, and references cited therein; b) J. Elguero in
Comprehensive Heterocyclic Chemistry (Eds.: A. R. Katritzky,
C. W. Rees, E. F. V. Scriven), Pergamon Press, Oxford, 1996,
vol. 3, pp. 1–75.
[4] R. Muruganantham, S. M. Mobin, I. N. N. Namboothiri, Org.
Lett. 2007, 9, 1125–1128, and references cited therein.
[5] a) A. I. Konovets, A. N. Kostyuk, A. M. Pinchuk, A. A. Tol-
machev, A. Fischer, P. G. Jones, R. Schmutzler, Heteroat.
General Procedure for the Synthesis of (3-Oxo-2,3-dihydro-1H-pyr-
azol-4-yl)phosphonamidates 6a and 7a: (E)-Hydrazono-phosphona-
tes 5a–d (1 mmol) were dissolved in a mixture of tetrahydrofuran
(5 mL)/methanol (5 mL), and a catalytic amount of sodium hydride
(0.1 mmol) was added. The reaction mixture was magnetically
stirred for 0.1–1.0 h until the disappearance of the starting com-
pound 5. Benzyl N,N-diisopropyl-P-(5-methyl-3-oxo-2,3-dihydro-
1H-pyrazol-4-yl)phosphonamidate (6a) was obtained from 5a,b,
and benzyl P-[2-(anilinocarbonyl)-5-methyl-3-oxo-2,3-dihydro-1H-
pyrazol-4-yl]-N,N-diisopropylphosphonamidate (7a) was obtained
from 5c,d. Products 6a and 7a were purified by column chromatog-
raphy on silica gel (elution mixtures: ethyl acetate/methanol) and
by subsequent crystallization from diethyl ether/light petroleum
ether (40–60 °C).
5972
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 5965–5973

Practical Access to New Phosphorylated Pyrazolones
Chem. 2003, 14, 452–458; b) A. A. Tolmachev, A. I. Konovets,
A. N. Kostyuk, A. N. Chernega, A. M. Pinchuk, Heteroat.
Chem. 1998, 9, 41–49; c) A. A. Tolmachev, A. I. Konovets,
A. N. Kostyuk, A. M. Pinchuk in Topics in Heterocyclic Sys-
tems (Eds.: O. A. Attanasi, D. Spinelli), Research Signpost, Tri-
vandrum, 1996, vol. 1, pp. 239–249, and references cited
therein; d) A. A. Tolmachev, A. I. Sviridon, A. N. Kostyuk,
A. M. Pinchuk, Heteroat. Chem. 1995, 6, 449–459.
[10] a) D. Enders, A. Saint-Dizier, M.-I. Lannou, A. Lenzen, Eur.
J. Org. Chem. 2006, 29–49.
[11] a) O. A. Attanasi, P. Filippone, D. Giovagnoli, Org. Prep. Pro-
ced. Int. 1994, 26, 321–326; b) O. A. Attanasi, P. Filippone, A.
Mei, Tetrahedron 1992, 48, 1707–1714.
[12] a) O. A. Attanasi, G. Baccolini, C. Boga, L. De Crescentini, P.
Filippone, F. Mantellini, Tetrahedron 2008, 64, 6724–6732; b)
O. A. Attanasi, G. Baccolini, C. Boga, L. De Crescentini, P.
Filippone, F. Mantellini, J. Org. Chem. 2005, 70, 4033–4037.
[13] a) W. Simons, The Sadtler Guide to Carbon-13 NMR Spectra,
Sadtler Research Laboratories, Philadelphia, PA, 1983; b) T.
Albright, W. Freeman, E. Schweizer, J. Am. Chem. Soc. 1975,
97, 940–942.
[14] CCDC-697871 contains the supplementary crystallographic
data (excluding structure factors) for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[15] a) G. Ertl, H. Knözinger, F. Schüth, J. Weitkamp (Eds.), Hand-
book of Heterogeneous Catalysis, Wiley-VCH, Weinheim, 2008,
vol. 1–8; b) K. Kaneda, Synlett 2007, 999–1015; c) J. Weit-
kamp, M. Hunger, Studies Surf. Sci. Catal. 2007, 168, 737–785;
d) M. Harmer, Q. Sun, Appl. Catal. 2001, 221, 45–62; e) L.
Caggiano, D. J. Fox, S. Warren, Chem. Commun. 2002, 2528–
2529.
[6] a) O. A. Attanasi, L. De Crescentini, P. Filippone, F. Man-
tellini, S. Santeusanio, Arkivoc 2002, 11, 274–292; b) O. A. At-
tanasi, P. Filippone, Synlett 1997, 1128–1140.
[7] a) M. Kim, H.-J. Gais, J. Org. Chem. 2006, 71, 4642–4650; b)
M. van Bergen, H.-J. Gais, J. Am. Chem. Soc. 2002, 124, 4321–
4328; c) R. K. Boeeckman Jr, J. E. Reed, P. Ge, Org. Lett. 2001,
3, 3651–3653; d) S. Polanc in Targets in Heterocyclic Systems:
Chemistry and Properties (Eds.: O. A. Attanasi, D. Spinelli),
Società Chimica Italiana, Rome, 2000, vol. 3, pp. 33–92; e) K.
Banert in Targets in Heterocyclic Systems: Chemistry and Prop-
erties (Eds.: O. A. Attanasi, D. Spinelli), Società Chimica Ital-
iana, Rome, 2000, vol. 3, pp. 1–32.
[8] a) O. A. Attanasi, L. De Crescentini, G. Favi, P. Filippone, G.
Giorgi, F. Mantellini, F. R. Perrulli, D. Spinelli, Tetrahedron
2008, 64, 3837–3858; b) O. A. Attanasi, G. Favi, P. Filippone,
G. Giorgi, F. Mantellini, G. Moscatelli, D. Spinelli, Org. Lett.
2008, 10, 1983–1986; c) O. A. Attanasi, G. Favi, P. Filippone,
S. Lillini, F. Mantellini, D. Spinelli, M. Stenta, Adv. Synth. Ca-
[16] ACD/IUPAC Name, version 3.50, Advanced Chemistry Devel-
opment Inc., Toronto, ON, 1998.
tal. 2007, 349, 907–915; d) O. A. Attanasi, P. Davoli, G. Favi, [17] a) O. A. Attanasi, P. Filippone, A. Mei, S. Santeusanio, Synthe-
P. Filippone, A. Forni, G. Moscatelli, F. Prati, Org. Lett. 2007,
9, 3461–3464; e) O. A. Attanasi, L. De Crescentini, G. Favi, P.
Filippone, S. Lillini, F. Mantellini, S. Santeusanio, Org. Lett.
2005, 7, 2469–2471.
sis 1984, 671–672; b) O. A. Attanasi, P. Filippone, A. Mei, S.
Santeusanio, Synthesis 1984, 873–874.
[18] G. Sheldrick, SHELXS-97, A program for automatic solution of
crystal structures, release 97-2, University of Göttingen, 1997.
[19] G. Sheldrick, SHELXL-97, A program for crystal structure re-
finement, release 97-2, University of Göttingen, 1997.
Received: September 4, 2008
[9] a) O. A. Attanasi, G. Favi, P. Filippone, G. Giorgi, S. Lillini,
F. Mantellini, F. R. Perrulli, Synlett 2006, 2731–2734; b) O. A.
Attanasi, L. De Crescentini, P. Filippone, F. Mantellini, L. F.
Tietze, Tetrahedron 2001, 57, 5855–5863.
Published Online: November 5, 2008
Eur. J. Org. Chem. 2008, 5965–5973
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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