Carbon-phosphorus bond formation and transformation in the reaction of 1,2-diaza-1,3-butadienes with alkyl phenylphosphonites

Article abstract of DOI:10.1016/j.tet.2008.05.007

The reaction of 1,2-diaza-1,3-butadienes with dialkyl phenylphosphonites under solvent-free conditions proceeds via zwitterionic intermediate and gives, by precipitation, the stable ylidic α-phosphanylidene-hydrazones that, in turn, can be transformed int

Full text of DOI:10.1016/j.tet.2008.05.007

Tetrahedron 64 (2008) 6724–6732
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Carbon–phosphorus bond formation and transformation in the reaction of
1,2-diaza-1,3-butadienes with alkyl phenylphosphonites
,
b
b
a
,
a
Orazio A. Attanasi a , Graziano Baccolini , Carla Boga , Lucia De Crescentini , Paolino Filippone ,
*
*
Fabio Mantellini a
a
`
Istituto di Chimica Organica, Universita degli Studi di Urbino ‘Carlo Bo’, Via I Maggetti 24, 61029 Urbino, Italy
Dipartimento di Chimica Organica ‘A. Mangini’, Universita degli Studi di Bologna, Viale Risorgimento 4, 40136 Bologna, Italy
b
`
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of 1,2-diaza-1,3-butadienes with dialkyl phenylphosphonites under solvent-free conditions
Received 18 February 2008
Received in revised form 10 April 2008
Accepted 1 May 2008
proceeds via zwitterionic intermediate and gives, by precipitation, the stable ylidic
hydrazones that, in turn, can be transformed into the corresponding 3-phenyl-2H-1,2,3
holes. The latter compounds are converted by hydrolytic cleavage in methanol–water (95:5) into
E-hydrazonophosphonates that are useful for the preparation of the corresponding -ketophosphonates
a
-phosphanylidene-
l
5-diazaphosp-
Available online 3 May 2008
b
and 4-[alkoxy(phenyl)phosphoryl]-1,2-diaza-1,3-butadienes. These peculiar 1,2-diaza-1,3-butadienes,
bearing an alkoxy(phenyl)phosphoryl group on the carbon atom in position 4 are also able to add dif-
ferent nucleophiles, such as methanol or thiourea, giving 2-[alkoxy(phenyl)phosphoryl]-2-methoxyhy-
drazones and 5-phosphinate-substituted thiazol-4-ones, respectively.
Keywords:
1,2-Diaza-1,3-butadienes
Diazaphospholes
Ylides
Ó 2008 Elsevier Ltd. All rights reserved.
Hydrazones
Phospha-Michael addition
1. Introduction
In the past years, all these considerations suggested us to
examine the reaction between 1,2-diaza-1,3-butadienes and tri-
Since the 1960s, investigations regarding 1,2-diaza-1,3-butadi-
enes have drastically increased, showing the usefulness of these
compounds in organic chemistry.1,2 Our group has a 30-year ex-
perience in this field. In particular, we have studied the reactivity of
these substrates, both in solution and solid phase,3 toward a large
variety of nucleophiles.1 The 1,4-conjugate addition (Michael-type)
of the latter on the terminal carbon atom of the heterodiene system
and the subsequent internal ring closure of the 1,4-adduct hydra-
zonic intermediates form polyfunctionalized five- or six-membered
heterocycles, such as pyrroles,3a,4 thiazoles,5 thiazolinones,3a,c
pyrazoles,3a,6 thiadiazoles,7 selenadiazoles,7 indoles,8,4b,c imidaz-
oles,9 1,2,4-triazines,1c pyrazines,10 and pyridazines.11
On the other hand, the phospha-Michael (P-Michael) addition,
i.e., the addition of a phosphorus nucleophile to an appropriate
acceptor, is probably one of the most versatile tools for the for-
mation of the P–C bond.12 This occurrence is important because it
offers an entry to many diversely functionalised derivatives. In
addition, natural products containing a P–C bond exhibit important
biological activity.13
phenyl-14a or trialkyl-phosphines14b to obtain pyrazoles or 4-
phosphoranylidene-4,5-dihydropyrazol-5-ones. More recently, we
have investigated the reaction of the same 1,2-diaza-1,3-butadienes
with trialkyl phosphites that represented a facile access to new
1,2,3-diazaphospholes, if the reaction was carried out under a ni-
trogen atmosphere, or to E-hydrazonophosphonates, in the pres-
ence of atmospheric moisture.15
With the aim to study the behavior of other trivalent phosphorus
nucleophiles towards 1,2-diaza-1,3-butadiene systems and consid-
ering the different electron-donating effects of the phenyl group
with respect to the alkoxy one, in this paper we consider the reaction
of these compounds with dimethyl or diethyl phenylphosphonites.
It turned out to be very interesting because, in some cases, the 1,4-
addition products directly precipitate from the reaction medium,
permitting us to define the mechanistic aspects of the reaction.
On the other hand, with the same reaction pathway, we can
obtain 3-phenyl-2H-1,2,3l
5-diazaphospholes, also in the presence
of air. Furthermore, the procedure here described represents an
easy alternative route to the synthesis of 1,2,3-diazaphospholes. In
fact, the classical method for their preparation implicates the PCl3
condensation of the alkylketone hydrazones16 while 2,4,5-tri-
phenyl-1,2,3-diazaphosphole is best prepared from the respective
1,2-diaza-1,3-butadiene and a fused benzothiadiphosphole as the
phosphorus donating reagent.17
* Corresponding authors. Fax: þ39 0722303441.
E-mail addresses: orazio.attanasi@uniurb.it (O.A. Attanasi), lucia.decrescentini@
uniurb.it (L. De Crescentini).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.007

O.A. Attanasi et al. / Tetrahedron 64 (2008) 6724–6732
6725
Here, we also report the hydrolytic cleavage of 1,2,3-di-
azaphospholes to give the corresponding E-hydrazonophospho-
nates thatcanbeconvenientlyusedforthepreparationof interesting
-ketophosphonates and 4-[alkoxy(phenyl)phosphoryl]-1,2-diaza-
The ylidic nature of compounds 3a–d is clearly supported by 13
C
chemical shifts of the P–C signals (55.3–56.6 ppm) and by their P–C
coupling constants (167–168 Hz), which are in good agreement
with the values found in the literature.15,18
b
1,3-butadienes. Besides, we have tested the ability of these partic-
ular 1,2-diaza-1,3-butadienes to add some nucleophiles such as
methanol and thiourea to give 2-[alkoxy(phenyl)phosphoryl]-2-
methoxyhydrazonesand5-phosphinate-substitutedthiazol-4-ones,
respectively.
The possibility to obtain in some cases intermediates 3 simply
by precipitation and subsequent filtration can suggest that the
presence of a phenyl group directly bound to the phosphorus atom
enhances their stability.
The isolation and the characterization of the intermediates 3a–
d have represented the key to determine the exact mechanism for
the formation of the 1,2,3-diazaphospholes 4. The nucleophilic 1,4-
addition of the phosphorus at the terminal carbon atom of the
heterodiene system induces the formation of a zwitterionic in-
termediate (I) that exists in equilibrium with its ylidic form 3, de-
rived from the 1,4-shift of a proton. 1,2,3-Diazaphospholes 4 are
obtained by means of an intramolecular attack of the NH hydra-
zonic nitrogen of 3 at the phosphorus atom, with loss of an alcohol
molecule (Scheme 2).
2. Results and discussion
1-Aminocarbonyl-1,2-diaza-1,3-butadiene-4-carboxylates 1a,b
easily reacted with dimethyl or diethyl phenylphosphonites 2a,b in
the presence of atmospheric moisture and in solvent-free condi-
tions in 0.5 h to give a mixture of
a-phosphanylidene-hydrazones
3a–d and 3-phenyl-2H-1,2,3
l
5-diazaphospholes 4a,b,e,f (Scheme 1,
path a, Table 1). Products 3 directly precipitated from the reaction
medium, while the corresponding 4a,b,e,f were obtained by chro-
matographic purification of the mother liquor. If the same reaction
was carried out starting from 1c,d with 2a,b, the isolation of
hydrazones 3 was not possible, either by precipitation or by chro-
matographic methods.
Ylidic intermediates 3a–d can be easily converted into the cor-
responding 1,2,3-diazaphospholes 4a,b,e,f in tetrahydrofuran at
room temperature (Scheme 1, path b, Table 1). This represents
further support for the described mechanism.
3-Phenyl-2H-1,2,3l
5-diazaphospholes 4a–h can also be
obtained in a one-pot procedure. In fact, 1-aminocarbonyl-1,2-
diaza-1,3-butadiene-4-carboxylates 1a,b,d and 1-aminocarbonyl-
1-2-diaza-1,3-butadiene-4-carboxamide 1c easily reacted with
dimethyl or diethyl phenylphosphonites 2a,b in solvent-free con-
ditions and in the presence of atmospheric moisture. After com-
pletion of the reaction, revealed by the disappearance of the red
color of 1,2-diaza-1,3-butadiene, THF was directly added to the
O
R2
OR3
P
N
NH2
R1
N
R3O
Ph
+
O
1a-d
2a,b
path a
path c
reaction medium giving 3-phenyl-2H-1,2,3l
5-diazaphospholes 4a–
1) solvent-free, rt
2) THF, rt
solvent-free, rt
h in very good yields (Scheme 1, path c, Table 1). Probably, the
presence of a phenyl moiety bound to the phosphorus atom confers
a particular stability to compounds 4a–h, which, if stored for one
year at 4 ꢀC, showed no decomposition nor any loss in purity.
The treatment of 1,2,3-diazaphospholes 4a–h with THF–water
(95:5) produced the corresponding E-hydrazonophosphonates 5a–
h in 6.0–10.0 h, in good yields (Scheme 1, Table 1). Their formation
is due to the hydrolytic ring opening of diazaphosphole that occurs
with the cleavage of the P–N bond of the intermediate II (Scheme
2). The E-configuration of the C]N was assigned by means of NOE
experiments.15
O
R2
R1
R3O
Ph
H
O
R2
N
NH2
P
N
R1
N
Ph
OR3
+
N
R3O
P
O
O
NH2
3a-d
path b
4a-h
THF, rt
MeOH/H2O, rt
H
These hydrazonic derivatives featured an interesting synthetic
utility for a series of chemical transformations. In fact, when
compounds 5a,b,d,f,g, chosen as examples, were treated with
4 equiv of Amberlyst 15H in a mixture of acetone–water (9:1), they
O
O
R2
N
NH2
R1
N
P
Ph
O
OR3
were converted into b-ketophosphonates 6a–e in 3.0–5.0 h with
5a-h
good yields (59–72%) (Scheme 3, Table 2), by means of the hydro-
lytic cleavage of the C]N hydrazonic bond.19
Scheme 1.
Table 1
Yields and reaction times of
a
-phosphanylidene-hydrazones 3a–d, 3-phenyl-2H-1,2,3
l
5-diazaphospholes 4a–h, and E-hydrazonophosphonates 5a–h
1
R1
R2
2
R3
3
Yielda (%)
4
Yielda (%)
Yieldb (%)
Yieldc (%)
Timed (h)
5
Yielde (%)
Timef (h)
1a
1b
1c
1d
1a
1b
1c
1d
OMe
OEt
NMe2
OMe
OMe
OEt
Me
Me
Me
Et
Me
Me
Me
Et
2a
2a
2a
2a
2b
2b
2b
2b
Me
Me
Me
Me
Et
Et
Et
Et
3a
3b
45
47
4a
4b
4c
4d
4e
4f
45
47
65
68
77
78
84
87
78
69
88
93
1.0
2.0
1.0
2.0
2.0
2.0
1.0
2.0
5a
5b
5c
5d
5e
5f
79
81
74
62
65
63
73
60
9.0
10.0
8.0
6.0
8.0
10.0
6.0
6.0
3c
3d
52
51
22
26
63
68
NMe2
OMe
4g
4h
5g
5h
a
b
c
d
e
f
Yield of pure isolated products, referred to the path a of Scheme 1, based on starting compounds 1a,b.
Yield of pure isolated products, referred to the path b of Scheme 1, based on starting compounds 3a–d.
Yield of pure isolated products referred to the path c of Scheme 1, based on starting compounds 1a–d.
Time for the formation of compounds 4a–h.
Yield of pure isolated products 5a–h, based on starting compounds 4a–h.
Time of disappearance of the starting compounds 4a–h.

6726
O.A. Attanasi et al. / Tetrahedron 64 (2008) 6724–6732
O
b-ketophosphonates starting from b-ketophosphonate-hydra-
R1
R2
zones, using paraformaldehyde and acetone in the presence of
boron trifluoride, that occurred in 48 h with 47–62% yields.23 The
methodology described here for their preparation represents an
improvement with respect to the previously reported procedures.
E-Hydrazonophosphonates 5a–f, chosen as examples, can also
be conveniently used for the preparation of 4-[alkoxy-
(phenyl)phosphoryl]-1,2-diaza-1,3-butadienes 9a–e. In fact, when
they were treated with 2,4,4,6-tetrabromo-3-n-pentadecyl-2,5-
cyclohexadienone 7 (TBPCO), they furnished the non-isolable 4-
bromo-hydrazonophosphonate intermediates 8 that, in turn, were
converted into pertinent azoalkenes 9a–e, by treatment with an
aqueous saturated solution of sodium carbonate to induce a dehy-
drobromination (Scheme 3, Table 2).24
OR3
P
O
R2
R3O
+
P
N
N
NH2
R3O
Ph
R1
N
R3O
-
N
+
Ph
NH2
2
O
1
O
I
O
O
R1
R3O
R3O
R2
R2
R1
R3O
Ph
-R3OH
P
N
N
P
N
Ph
NH2
N
H
O
NH2
O
4
3
TBPCO, a brominating agent easily synthesized starting from 3-
n-pentadecylphenol,25 proved to be more effective than other
+H2O
commonly used reagents for such
a reaction, like phenyl-
trimethylammonium tribromide (PTAB) or N-bromosuccinimide
(NBS), furnishing higher overall yields (42–56%) of the final com-
pounds 9a–e. These latter compounds are peculiar 1,2-diaza-1,3-
butadienes, bearing an [alkoxy(phenyl)phosphoryl] group on the
carbon atom in position 4 and they maintain the ability to add
different nucleophiles.
O
O
R2
H
N
R2
H
N
R1
NH2
R1
N
Ph
R3O
P
N
O
P
Ph
O
O
OR3
5
H
O
NH2
In fact, compounds 9b,e reacted with methanol in the presence
of sodium methoxide to give 2-[alkoxy(phenyl)phosphoryl]-2-
methoxyhydrazones 10a,b,26 by 1,4-addition of methanol to the
heterodiene system (Michael-type) (Scheme 3, Table 2). Com-
pounds 9a,c,d, treated with thiourea 11 in methanol, furnished 5-
phosphinate-substituted thiazol-4-ones 12a–c (Scheme 3, Table
2).3c,27 The mechanism for the formation of compounds 12 impli-
cates SH nucleophilic attack of the thioloimido form to the terminal
carbon atom of the azoene system and subsequent ring closure to
the thiazolinone ring due to an intramolecular NH nucleophilic
attack at the ester group bound to the same terminal carbon atom.
II
Scheme 2.
b
-Ketophosphonates owe their importance to the fact that they
are valuable intermediates in organic synthesis, i.e., the Horner–
Wadsworth–Emmons condensation, used for the preparation of
a,b
-unsaturated carbonyl compounds.20 The classical methods for
their preparation are the Arbuzov reaction21 and the acylation of
alkylphosphonate anions,22 but both these synthetic approaches
present some restrictions, due to the difficult nucleophilic sub-
stitution or poor nucleophilic power of the phosphorus reagents.
In the past years, one of us described the synthesis of
3. Conclusions
In conclusion, this work contributes to the chemistry of phos-
phorus derivatives from both synthetic and mechanistic points of
view. The synthetic importance of the reaction between 1,2-diaza-
1,3-butadienes and dialkyl phenylphosphonites is due to the de-
velopment of simple and environmentally friendly procedures for
the preparation of 1,2,3-diazaphospholes and E-hydrazono-
phosphonates, not easily accessible by other methods. Moreover,
the latter compounds have been demonstrated to be useful starting
O
O
O
O
O
R2
H
N
COMe2-H2O (9:1)
Amberlyst 15H
R1O
R2
NH2
R1
N
P
Ph
reflux
P
Ph
O
OR3
6a-e
OR3
5a-h
O
Br
Br
C15H31
CH2Cl2, rt
materials to obtain
b-ketophosphonates and unknown 4-
[alkoxy(phenyl)phosphoryl]-1,2-diaza-1,3-butadienes that, in turn,
can be used for the preparation of 2-[alkoxy(phenyl)phosphoryl]-2-
methoxyhydrazones and 5-phosphinate-substituted thiazol-4-
Br Br
7
ones. Furthermore, the isolation of a-phosphanylidene-hydrazone
O
R2
H
N
O
O
R2
Br
P
intermediates by the reaction of 1,2-diaza-1,3-butadienes and
dialkyl phenylphosphonites permitted us to throw light on mech-
anistic aspects involved in the formation of 1,2,3-diazaphospholes.
NH2
Na2CO3(aq)
N
O
NH2
R1
N
R1
N
-HBr
O
Ph
O
P
Ph
OR3
OR3
8
9a-e
4. Experimental
4.1. General
S
MeOH/MeONa, rt
H
H2N
11
NH2
MeOH, rt
O
R2
R1=OMe, OEt
O
Methyl or ethyl 2-chloroacetoacetate, methyl 2-chloro-3-oxo-
pentanoate, semicarbazide hydrochloride, sodium acetate, di-
methyl or diethyl phenylphosphonite, Amberlyst 15H, sodium
methoxide, and thiourea 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 over sodium hydroxide. Melting points were determined
on open capillary tubes. FTIR spectra were obtained as Nujol mulls.
N
NH2
R1
N
Ph
P
O
O
OR3
O
O
P Ph
O
OR3
N
10a,b
N
H
NH2
N
S
H
R2
NH
12a-c
Scheme 3.

O.A. Attanasi et al. / Tetrahedron 64 (2008) 6724–6732
6727
Table 2
Yields and reaction times of b-ketophosphonates 6a–e, 4-[alkoxy(phenyl)phosphoryl]-1,2-diaza-1,3-butadienes 9a–e, 2-[alkoxy(phenyl)phosphoryl]-2-methoxyhydrazones
10a,b, and 5-phosphinate-substituted thiazol-4-ones 12a–c
5
6
Yielda (%)
Time (h)
9
Yielda (%)
10
Yieldb (%)
65
Time (h)
0.5
12
Yieldb (%)
61
Time (h)
2.0
5a
5b
5d
5e
5f
6a
6b
6c
66
72
58
3.0
4.5
5.0
9a
9b
9c
9d
9e
43
48
42
56
41
12a
10a
12b
12c
60
63
1.0
1.5
6d
6e
66
59
4.0
4.0
10b
78
1.0
5g
a
Yield of pure isolated products based on compounds 5.
Yield of pure isolated products based on compounds 9.
b
Mass spectra EI were recorded at an ionizing voltage of 70 eV. 1H
NMR, 13C NMR, and 31P NMR spectra were recorded at 400, 100.32,
161.9 MHz, respectively. All NMR spectra were recorded in CDCl3 or
in DMSO-d6, as specified below. Chemical shifts (dH) are reported in
parts per million (ppm), relative to TMS as internal standard. All
presence of
a-phosphanylidene-hydrazones 3 and 3-phenyl-2H-
1,2,3l
5-diazaphospholes 4. In order to completely convert 3 into the
relevant products 4, THF (10 mL) was added to the reaction me-
dium, that was magnetically stirred for an additional time of 1.0–
2.0 h. 3-Phenyl-2H-1,2,3l
5-diazaphospholes 4a–h were obtained by
coupling constants (J) values are given in hertz. Chemical shifts (dC
)
chromatography on silica gel column (elution mixture: ethyl ace-
tate–cyclohexane). Further purification of compounds 4 can be
obtained by crystallization from diethyl ether–light petroleum (bp
40–60 ꢀC).
are reported in parts per million (ppm), relative to CDCl3 or DMSO-
d6 as internal standard in a broad band decoupled mode; the
multiplicities were obtained using 135ꢀ and 90ꢀ DEPT experiments
to aid in assignment. Chemical shifts (dP) are reported in parts per
million (ppm), relative to external standard 85% H3PO4. The ab-
breviations used are as follows: s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet; br, broad. All the NH, NH2, and OH exchanged
with D2O. Precoated silica gel plates (0.25 mm) were employed for
4.4.1. Methyl 3-[2-(aminocarbonyl)hydrazono]-2-(1,1-dimethoxy-
1-phenyl-l
5-phosphanylidene)butanoate (3a)
White powder; mp 91–95 ꢀC; IR (Nujol) nmax 3445, 3314, 3192,
1686, 1634 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d
2.00 (s, 3H, CH3),
3
analytical thin layer chromatography and silica gel 35–70
m
for
3.39 (s, 3H, CO2CH3), 3.70 (d, 6H, JHP¼12.4 Hz, 2OCH3), 5.67 (br s,
column chromatography. All new compounds shown satisfactory
elemental analysis (Cꢁ0.35; Hꢁ0.30; Nꢁ0.30). The nomenclature
was generated using ACD/IUPAC Name (version 3.50, 5 Apr. 1998),
Advanced Chemistry Development Inc., Toronto, ON (Canada).
2H, NH2), 7.48–7.71 (m, 5H, CHarom), 8.56 (s, 1H, NH); 13C NMR
(100 MHz, DMSO-d6)
d
18.7 (d, 3JCP¼6.8 Hz, CH3), 49.2 (s, CH3), 54.1
2
1
(d, JCP¼5.6 Hz, CH3), 55.3 (d, JCP¼167.0 Hz, C), 127.9 (d,
1JCP¼189.6 Hz, C), 128.7 (d, 2JCP¼14.4 Hz, CH), 131.1 (d, 3JCP¼10.6 Hz,
2
CH), 132.6 (s, CH), 148.2 (d, JCP¼7.6 Hz, C), 157.2 (s, C), 168.3 (d,
4.2. General procedure for the synthesis of
2JCP¼18.2 Hz, C); MS m/z 341 (1) [Mþ], 309 (33), 266 (100). Anal.
Calcd for C14H20N3O5P: C, 49.27; H, 5.91; N, 12.31. Found: C, 49.39;
H, 5.67; N, 11.29.
a
-phosphanylidene-hydrazones 3a–d and of 3-phenyl-2H-
1,2,3
l
5-diazaphospholes 4a,b,e,f (path a)
1,2-Diaza-1,3-butadienes 1a,b (1 mmol) as a mixture of E/Z
isomers24 and dialkyl phenylphosphonites 2a,b (4 mmol) were
magnetically stirred for 0.5 h, until the red color of the starting
4.4.2. Ethyl 3-[2-(aminocarbonyl)hydrazono]-2-(1,1-dimethoxy-1-
phenyl-
White powder; mp 90–95 ꢀC; IR (Nujol) nmax 3474, 3380, 3303,
3187, 1682, 1639, 1630 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
0.95
l
5-phosphanylidene)butanoate (3b)
product disappeared. The
a
-phosphanylidene-hydrazones 3a–d di-
;
d
3
rectly precipitate from the reaction medium as white solid. The
mother liquor was then chromatographed on silica gel column
(elution mixture: ethyl acetate–cyclohexane) to give 3-phenyl-2H-
(t, 3H, J¼7.2 Hz, CO2CH2CH3), 2.01 (s, 3H, CH3), 3.70 (d, 6H, JHP¼
12.0 Hz, 2OCH3), 3.83 (q, 2H, J¼7.2 Hz, CO2CH2CH3), 5.70 (br s, 2H,
NH2), 7.50–7.72 (m, 5H, CHarom), 8.54 (s,1H, NH); 13C NMR (100 MHz,
3
1,2,3
l
5-diazaphospholes 4a,b,e,f. Further purification of these latter
DMSO-d6)
d
14.4 (s, CH3), 18.7 (d, JCP¼6.8 Hz, CH3), 54.1 (d,
compounds can be obtained by crystallization from diethyl ether–
light petroleum (bp 40–60 ꢀC).
2JCP¼5.8 Hz, CH3), 55.5 (d, 1JCP¼168.0 Hz, C), 57.6 (s, CH2), 128.0 (d,
1JCP¼152.5 Hz, C), 128.5 (d, 2JCP¼15.2 Hz, CH), 131.1 (d, 3JCP¼10.6 Hz,
2
CH), 132.6 (s, CH), 148.3 (d, JCP¼7.6 Hz, C), 157.2 (s, C), 167.9 (d,
4.3. General procedure for the synthesis of 3-phenyl-2H-
2JCP¼18.2 Hz, C); 31P NMR (162 MHz, DMSO-d6)
d 67.07; MS m/z 355
1,2,3l
5-diazaphospholes 4a,b,e,f starting from
(37) [Mþ], 324 (20), 310 (25), 280 (62), 266 (100). Anal. Calcd
for C15H22N3O5P: C, 50.70; H, 6.24; N,11.83. Found: C, 50.57; H, 6.17;
N, 11.70.
a
-phosphanylidene-hydrazones 3a–d (path b)
a
-Phosphanylidene-hydrazones 3a–d (1 mmol) were dissolved
in tetrahydrofuran (10 mL) and magnetically stirred for 2.0 h, until
4.4.3. Methyl 3-[2-(aminocarbonyl)hydrazono]-2-(1,1-diethoxy-1-
the disappearance of the starting compound 3. 3-Phenyl-2H-
phenyl-
White powder; mp 82–86 ꢀC; IR (Nujol) nmax 3462, 3189, 1699,
1650 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
l
5-phosphanylidene)butanoate (3c)
1,2,3l
5-diazaphospholes 4a,b,e,f were obtained by chromatography
on silica gel column (elution mixture: ethyl acetate–cyclohexane)
and by subsequent crystallization from diethyl ether–light petro-
leum (bp 40–60 ꢀC).
;
d
1.20 (t, 6H, J¼7.0 Hz,
2OCH2CH3), 1.99 (s, 3H, CH3), 3.35 (s, 3H, CO2CH3), 4.02–4.08 (m,
4H, 2OCH2CH3), 5.67 (br s, 2H, NH2), 7.49–7.72 (m, 5H, CHarom), 8.55
3
(s, 1H, NH); 13C NMR (100 MHz, DMSO-d6)
d
16.5 (d, JCP¼6.0 Hz,
4.4. General procedure for the one-pot synthesis of
CH3), 19.3 (d, 3JCP¼6.8 Hz, CH3), 49.7 (s, CH3), 56.6 (d, 1JCP¼167.0 Hz,
2
2
3-phenyl-2H-1,2,3
l
5-diazaphospholes 4a–h (path c)
C), 64.2 (d, JCP¼6.1 Hz, CH2), 129.3 (d, JCP¼14.4 Hz, CH), 129.4 (d,
1JCP¼154.0 Hz, C), 131.6 (d, 3JCP¼10.6 Hz, CH), 132.5 (s, CH), 149.0 (d,
2
1,2-Diaza-1,3-butadienes 1a–d (1 mmol) as a mixture of E/Z
isomers24 and dialkyl phenylphosphonites 2a,b (4 mmol) were
magnetically stirred for 0.5 h, until the red color of the reaction
mixture disappeared. At this moment, a TLC check revealed the
2JCP¼7.6 Hz, C), 157.9 (s, C), 169.0 (d, JCP¼18.2 Hz, C); MS m/z 369
(6) [Mþ], 326 (47), 323 (59), 295 (11), 280 (100). Anal. Calcd for
C16H24N3O5P: C, 52.03; H, 6.55; N, 11.38. Found: C, 52.07; H, 6.47; N,
11.42.

6728
O.A. Attanasi et al. / Tetrahedron 64 (2008) 6724–6732
2
4.4.4. Ethyl 3-[2-(aminocarbonyl)hydrazono]-2-(1,1-diethoxy-1-
phenyl-
5-phosphanylidene)butanoate (3d)
White powder; mp 89–93 ꢀC; IR (Nujol) nmax 3462, 3198, 1699,
1641 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
(s, CH2), 49.7 (s, CH3), 52.3 (d, JCP¼8.1 Hz, CH3), 61.6 (d,
l
1JCP¼154.8 Hz, C), 124.4 (d, 1JCP¼159.4 Hz, C), 128.5 (d, 2JCP¼16.0 Hz,
CH), 132.7 (d, 3JCP¼12.1 Hz, CH), 133.2 (s, CH), 153.7 (d, 2JCP¼8.4 Hz,
C), 159.9 (d, 2JCP¼22.7 Hz, C), 163.7 (d, 2JCP¼19.7 Hz, C); MS m/z 323
(31) [Mþ], 292 (5), 280 (100). Anal. Calcd for C14H18N3O4P: C, 52.01;
H, 5.61; N, 13.00. Found: C, 52.14; H, 5.71; N, 12.89.
;
d
0.93 (t, 3H, J¼7.2 Hz,
CO2CH2CH3), 1.20 (t, 6H, J¼7.0 Hz, 2OCH2CH3), 2.00 (s, 3H, CH3),
3.80 (q, 2H, J¼7.2 Hz, CO2CH2CH3), 4.02–4.08 (m, 4H, 2 OCH2CH3),
5.69 (br s, 2H, NH2), 7.49–7.73 (m, 5H, CHarom), 8.56 (s, 1H, NH); 13
C
NMR (100 MHz, DMSO-d6)
d
14.5 (s, CH3), 15.8 (d, 3JCP¼6.8 Hz, CH3),
4.4.9. Methyl 2-(aminocarbonyl)-3-ethoxy-5-methyl-3-phenyl-2H-
3
18.7 (d, JCP¼6.8 Hz, CH3), 56.0 (d, 1JCP¼167.0 Hz, C), 57.6 (s, CH2),
1,2,3
Colorless crystals; mp 112–115 ꢀC; IR (Nujol) nmax 3398, 3299,
3218, 1696, 1657 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
1.24 (t, 3H,
l
5-diazaphosphole-4-carboxylate (4e)
2
2
63.4 (d, JCP¼6.8 Hz, CH2), 63.5 (d, JCP¼6.8 Hz, CH2), 128.6 (d,
2JCP¼13.6 Hz, CH), 128.9 (d, 1JCP¼150.9 Hz, C), 131.0 (d, 3JCP¼10.7 Hz,
d
2
CH), 132.4 (s, CH), 148.4 (d, JCP¼7.6 Hz, C), 157.2 (s, C), 167.9 (d,
J¼7.2 Hz, OCH2CH3), 2.22 (s, 3H, CH3), 3.36 (s, 3H, CO2CH3), 3.88–
2JCP¼17.5 Hz, C); MS m/z 383 (1) [Mþ], 337 (35), 294 (62), 240 (67),
220 (100). Anal. Calcd for C17H26N3O5P: C, 53.26; H, 6.84; N, 10.96.
Found: C, 53.37; H, 6.78; N, 10.62.
4.04 (m, 2H, OCH2CH3), 6.87 and 7.15 (2br s, 2H, NH2), 7.54–7.75
(m, 5H, CHarom); 13C NMR (100 MHz, DMSO-d6)
d 14.1 (s, CH3), 17.0
3
2
(d, JCP¼6.1 Hz, CH3), 49.8 (s, CH3), 63.3 (d, JCP¼7.1 Hz, CH2), 65.1
1
1
(d, JCP¼157.6 Hz, C), 124.9 (d, JCP¼160.1 Hz, C), 129.0 (d,
3
4.4.5. Methyl 2-(aminocarbonyl)-3-methoxy-5-methyl-3-phenyl-
2JCP¼16.0 Hz, CH), 132.2 (d, JCP¼12.0 Hz, CH), 133.3 (s, CH), 154.1
2H-1,2,3
l
5-diazaphosphole-4-carboxylate (4a)
(d, 2JCP¼8.3 Hz, C), 155.6 (d, 2JCP¼25.0 Hz, C), 164.2 (d, 2JCP¼19.5 Hz,
Colorless crystals; mp 125–127 ꢀC; IR (Nujol) nmax 3415, 3212,
C); MS m/z 323 (53) [Mþ], 292 (6), 280 (100). Anal. Calcd for
1704, 1657 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d
2.24 (s, 3H, CH3),
C14H18N3O4P: C, 52.01; H, 5.61; N, 13.00. Found: C, 52.09; H, 5.49;
3.36 (s, 3H, CO2CH3), 3.61 (d, 3H, 3JHP¼14.4 Hz, OCH3), 6.90 and 7.18
N, 13.29.
(2br s, 2H, NH2), 7.54–7.76 (m, 5H, CHarom); 13C NMR (100 MHz,
2
DMSO-d61)
d
17.1 (s, CH3), 49.7 (s, CH3), 52.4 (d, JCP¼13.7 Hz, CH3),
4.4.10. Ethyl 2-(aminocarbonyl)-3-ethoxy-5-methyl-3-phenyl-2H-
1
63.0 (d, JCP¼158.0 Hz, C), 124.3 (d, JCP¼160.1 Hz, C), 128.5 (d,
2JCP¼16.0 Hz, CH), 132.8 (d, 3JCP¼12.2 Hz, CH),133.3 (s, CH), 153.7 (d,
2JCP¼8.4 Hz, C), 155.2 (d, 2JCP¼25.0 Hz, C), 164.2 (d, 2JCP¼19.7 Hz, C);
MS m/z 309 (31) [Mþ], 278 (7), 266 (100). Anal. Calcd for
1,2,3
Colorless crystals; mp 119–121 ꢀC; IR (Nujol) nmax 3372, 3291,
3205, 1704, 1687 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
0.86 (t, 3H,
l
5-diazaphosphole-4-carboxylate (4f)
d
J¼6.8 Hz, CO2CH2CH3), 1.25 (t, 3H, J¼7.2 Hz, OCH2CH3), 2.21 (s, 3H,
CH3), 3.82 (q, 2H, J¼6.8 Hz, CO2CH2CH3), 3.96–4.01 (m, 2H,
OCH2CH3), 6.92 and 7.16 (2br s, 2H, NH2), 7.52–7.74 (m, 5H,
C
13H16N3O5P: C, 50.49; H, 5.21; N, 13.59. Found: C, 50.29; H, 5.08; N,
13.66.
CHarom); 13C NMR (100 MHz, DMSO-d6)
d 14.4 (s, CH3), 16.8 (d,
3
4.4.6. Ethyl 2-(aminocarbonyl)-3-methoxy-5-methyl-3-phenyl-2H-
3JCP¼6.0 Hz, CH3), 17.7 (d, JCP¼5.3 Hz, CH3), 58.3 (s, CH3), 63.1 (d,
2JCP¼6.9 Hz, CH2), 65.2 (d, 1JCP¼157.0 Hz, C), 125.8 (d, 1JCP¼160.1 Hz,
C), 129.2 (d, 2JCP¼16.0 Hz, CH), 131.9 (d, 3JCP¼10.0 Hz, CH), 133.3 (s,
1,2,3
Colorless crystals; mp 127–130 ꢀC; IR (Nujol) nmax 3467, 3313,
3275, 1713, 1662 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
0.84 (t, 3H,
l
5-diazaphosphole-4-carboxylate (4b)
2
2
d
3
CH), 154.5 (d, JCP¼8.3 Hz, C), 155.8 (d, JCP¼25.1 Hz, C), 164.3 (d,
J¼7.2 Hz, CO2CH2CH3), 2.23 (s, 3H, CH3), 3.61 (d, 3H, JHP¼14.4 Hz,
OCH3), 3.75–3.91 (m, 2H, CO2CH2CH3), 6.90 and 7.18 (2br s, 2H,
NH2), 7.53–7.75 (m, 5H, CHarom); 13C NMR (100 MHz, DMSO-d6)
2JCP¼19.0 Hz, C); MS m/z 337 (58) [Mþ], 294 (100). Anal. Calcd for
C
15H20N3O4P: C, 53.41; H, 5.98; N, 12.46. Found: C, 53.47; H, 5.79;
N, 12.61.
d
14.1 (s, CH3), 16.9 (d, 3JCP¼5.3 Hz, CH3), 52.3 (d, 2JCP¼6.8 Hz, CH3),
57.6 (s, CH2), 63.1 (d, 1JCP¼157.0 Hz, C), 124.6 (d, 1JCP¼160.1 Hz, C),
128.4 (d, 2JCP¼15.9 Hz, CH),132.7 (d, 3JCP¼12.1 Hz, CH),133.2 (s, CH),
4.4.11. N4,N4,5-Trimethyl-3-ethoxy-3-phenyl-2H-1,2,3l5
diazaphosphole-2,4-dicarboxamide (4g)
-
2
2
153.7 (d, JCP¼8.4 Hz, C), 155.1 (d, JCP¼25.1 Hz, C), 163.6 (d,
White solid; mp 138–141 ꢀC; IR (Nujol) nmax 3361, 3218, 1741,
2JCP¼18.8 Hz, C); 31P NMR (162 MHz, DMSO-d6)
d
58.51; MS m/z 323
1680 cmꢂ1
;
1H NMR (400 MHz, DMSO-d6)
d
1.24 (t, 3H, J¼6.8 Hz,
(33) [Mþ], 280 (100). Anal. Calcd for C14H18N3O4P: C, 52.01; H, 5.61;
N, 13.00. Found: C, 51.97; H, 5.57; N, 13.58.
OCH2CH3), 2.11 (s, 3H, CH3), 2.79 (s, 6H, N(CH3)2), 3.82–4.06 (m, 2H,
OCH2CH3), 6.79 and 7.07 (2br s, 2H, NH2), 7.52–7.76 (m, 5H, CHarom);
3
13C NMR (100 MHz, DMSO-d6)
d
15.3 (d, JCP¼6.8 Hz, CH3), 17.1 (d,
4.4.7. N4,N4,5-Trimethyl-3-methoxy-3-phenyl-2H-1,2,3l5
diazaphosphole-2,4-dicarboxamide (4c)
-
3JCP¼6.0 Hz, CH3), 38.2 (s, CH3), 61.9 (d, JCP¼6.1 Hz, CH2), 66.0 (d,
1JCP¼155.6 Hz, C), 125.3 (d, 1JCP¼159.3 Hz, C), 128.5 (d, 2JCP¼16.0 Hz,
CH), 133.1 (d, 3JCP¼11.3 Hz, CH), 133.3 (s, CH), 153.7 (d, 2JCP¼9.1 Hz,
C), 153.8 (d, 2JCP¼21.3 Hz, C), 167.8 (d, 2JCP¼19.7 Hz, C); MS m/z 337
(7) [Mþ], 310 (40), 267 (100). Anal. Calcd for C15H21N4O3P: C, 53.57;
H, 6.29; N, 16.66. Found: C, 53.39; H, 6.41; N, 16.38.
2
White solid; mp 125–127 ꢀC; IR (Nujol) nmax 3354, 3221, 1713,
1698 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d 2.12 (s, 3H, CH3), 2.79
(s, 6H, N(CH3)2), 3.58 (d, 3H, 3JHP¼14.0 Hz, OCH3), 6.85 and 7.17 (2br
s, 2H, NH2), 7.52–7.76 (m, 5H, CHarom); 13C NMR (100 MHz, DMSO-
3
2
d6)
d
17.1 (d, JCP¼6.1 Hz, CH3), 37.5 (s, CH3), 52.4 (d, JCP¼6.8 Hz,
CH3), 65.2 (d, 1JCP¼154.7 Hz, C), 124.7 (d, 1JCP¼160.0 Hz, C), 128.6 (d,
2JCP¼15.0 Hz, CH), 133.2 (d, 3JCP¼11.3 Hz, CH), 133.3 (s, CH), 153.8 (d,
2JCP¼8.3 Hz, C), 154.0 (d, 2JCP¼23.5 Hz, C), 167.7 (d, 2JCP¼19.0 Hz, C);
MS m/z 322 (5) [Mþ], 252 (5), 220 (26), 205 (100). Anal. Calcd for
4.4.12. Ethyl 2-(aminocarbonyl)-3-ethoxy-5-methyl-3-phenyl-2H-
1,2,3
White solid; mp 126–127 ꢀC; IR (Nujol) nmax 3457, 3195, 1696,
1687 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
l
5-diazaphosphole-4-carboxylate (4h)
;
d
1.18 (t, 3H, J¼7.2 Hz,
C
14H19N4O3P: C, 52.17; H, 5.94; N, 17.38. Found: C, 52.31; H, 6.01; N,
CH2CH3), 1.26 (t, 3H, J¼6.8 Hz, OCH2CH3), 2.58–2.76 (m, 2H,
CH2CH3), 3.37 (s, 3H, CH3), 3.88–4.03 (m, 2H, OCH2CH3), 6.86 and
17.33.
7.18 (2br s, 2H, NH2), 7.53–7.74 (m, 5H, CHarom); 13C NMR (100 MHz,
3
4.4.8. Methyl 2-(aminocarbonyl)-5-ethyl-5-methoxy-3-phenyl-2H-
DMSO-d6)
d
12.3 (s, CH3), 15.4 (d, JCP¼5.6 Hz, CH3), 23.8 (s, CH2),
2
1,2,3
White solid; mp 124–125 ꢀC; IR (Nujol) nmax 3430, 3210, 1691,
1654 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
l
5-diazaphosphole-4-carboxylate (4d)
49.6 (s, CH3), 62.4 (d, 1JCP¼156.3 Hz, C), 62.5 (d, JCP¼6.1 Hz, CH2),
1
2
124.9 (d, JCP¼160.1 Hz, CH), 128.5 (d, JCP¼15.9 Hz, CH), 132.6 (d,
2
;
d
1.84 (t, 3H, J¼7.2 Hz,
3JCP¼12.2 Hz, CH), 133.1 (s, CH), 153.8 (d, JCP¼8.3 Hz, C), 159.9 (d,
2
CH2CH3), 2.59–2.77 (m, 2H, CH2CH3), 3.36 (s, 3H, CO2CH3), 3.61 (d,
2JCP¼24.3 Hz, C), 163.8 (d, JCP¼19.7 Hz, C); MS m/z 337 (58) [Mþ],
3
3H, JHP¼10.4 Hz, OCH3), 6.88 and 7.21 (2br s, 2H, NH2), 7.55–7.76
306 (7), 294 (100). Anal. Calcd for C15H20N3O4P: C, 53.41; H, 5.98; N,
12.46. Found: C, 53.55; H, 5.74; N, 12.58.
(m, 5H, CHarom); 13C NMR (100 MHz, DMSO-d6)
d 12.2 (s, CH3), 23.8

O.A. Attanasi et al. / Tetrahedron 64 (2008) 6724–6732
6729
4.5. General procedure for the synthesis of
E-hydrazonophosphonates 5a–h
2JCP¼6.8 Hz, CH3), 55.8 (d, 1JCP¼91.8 Hz, CH), 128.5 (d, 2JCP¼13.7 Hz,
CH), 131.0 (d, 3JCP¼11.3 Hz, CH), 131.4 (d, 1JCP¼111.6 Hz, C), 133.1 (s,
2
2
CH), 145.1 (d, JCP¼6.8 Hz, C), 158.1 (s, C), 166.8 (d, JCP¼5.7 Hz, C);
A
solution of 3-phenyl-2H-1,2,3l
5-diazaphospholes 4a–h
MS m/z 341 (11) [Mþ], 310 (28), 266 (100). Anal. Calcd for
(1 mmol) in methanol–water (9.5:0.5 mL) was magnetically stirred
for 6.0–10.0 h, until a TLC check revealed the disappearance of the
starting compound 4. The mixture was then dried over anhydrous
sodium sulfate and, after evaporation of the solvent, it was chro-
matographed on a silica gel column (elution mixture: ethyl ace-
tate–methanol) to give hydrazonophosphonates 5a–h in good
purity. Further purification of these compounds can be obtained by
crystallization from ethyl acetate–light petroleum (bp 40–60 ꢀC).
C14H20N3O5P: C, 49.27; H, 5.91; N, 12.31. Found: C, 49.44; H, 5.96; N,
12.03.
4.5.5. Methyl 3-[2-(aminocarbonyl)hydrazono]-2-[ethoxy-
(phenyl)phosphoryl]butanoate (5e)
White solid; mp 126–128 ꢀC; IR (Nujol) nmax 3469, 3296, 1750,
1705, 1684 cmꢂ1
;
1H NMR (400 MHz, DMSO-d6)
d
1.18 (t, 3H,
4
J¼7.2 Hz, OCH2CH3), 1.92 (d, 3H, JHP¼1.6 Hz, CH3), 3.65 (s, 3H,
2
CO2CH3), 3.89–3.91 (m, 2H, OCH2CH3), 4.40 (d, 1H, JHP¼19.2 Hz,
4.5.1. Methyl 3-[2-(aminocarbonyl)hydrazono]-2-[methoxy-
(phenyl)phosphoryl]butanoate (5a)
CH), 6.23 (br s, 2H, NH2), 7.51–7.74 (m, 5H, CHarom), 9.30 (s, 1H, NH);
13C NMR (100 MHz, DMSO-d6)
d
15.8 (s, CH3), 16.2 (d, JCP¼6.0 Hz,
2
2
White solid; mp 148–150 ꢀC; IR (Nujol) nmax 3469, 3310, 1740,
CH3), 52.3 (s, CH3), 57.1 (d, 1JCP¼88.0 Hz, CH), 61.1 (d, JCP¼6.3 Hz,
1692 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.95 (s, 3H, CH3), 3.57 (s,
CH2), 128.4 (d, JCP¼12.9 Hz, CH), 129.8 (d, 1JCP¼132.0 Hz, C), 131.7
2
2
3H, CO2CH3), 3.66–3.72 (m, 3H, OCH3), 4.16 (d, 1H, JHP¼18.8 Hz,
(d, 3JCP¼9.9 Hz, CH), 132.6 (s, CH), 139.4 (d, 2JCP¼6.9 Hz, C), 156.8 (s,
C),166.7 (d, 2JCP¼5.3 Hz, C); MS m/z 341 (1) [Mþ], 325 (31), 296 (44),
266 (100). Anal. Calcd for C14H20N3O5P: C, 49.27; H, 5.91; N, 12.31.
Found: C, 49.38; H, 5.65; N, 12.37.
CH), 5.77 (br s, 2H, NH2), 7.40–7.76 (m, 5H, CHarom), 8.95 (s, 1H, NH);
13C NMR (100 MHz, CDCl3)
d 14.2 (s, CH3), 52.6 (s, CH3), 53.6 (d,
2JCP¼6.8 Hz, CH3), 53.9 (d, JCP¼136.0 Hz, CH), 129.4 (d,
1
2JCP¼14.4 Hz, CH), 130.0 (d, 1JCP¼107.0 Hz, C), 132.2 (d, 3JCP¼11.4 Hz,
2
CH), 132.6 (d, JCP¼10.6 Hz, C), 133.6 (s, C), 162.5 (s, C), 165.8 (d,
4.5.6. Ethyl 3-[2-(aminocarbonyl)hydrazono]-2-[ethoxy-
(phenyl)phosphoryl]butanoate (5f)
2JCP¼5.2 Hz, C); MS m/z 327 (11) [Mþ], 296 (100). Anal. Calcd for
C
13H18N3O5P: C, 47.71; H, 5.54; N, 12.84. Found: C, 47.68; H, 5.44; N,
White solid; mp 129–130 ꢀC; IR (Nujol) nmax 3471, 3306, 1747,
12.65.
1692, 1684 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d 0.94 (t, 3H,
J¼7.2 Hz, CO2CH2CH3), 1.17 (t, 3H, J¼6.8 Hz, OCH2CH3), 1.94 (s, 3H,
CH3), 3.88–3.97 (m, 4H, CO2CH2CH3 and OCH2CH3), 4.37 (d, 1H,
2JHP¼19.2 Hz, CH), 6.26 (br s, 2H, NH2), 7.51–7.75 (m, 5H, CHarom),
4.5.2. Ethyl 3-[2-(aminocarbonyl)hydrazono]-2-[methoxy-
(phenyl)phosphoryl]butanoate (5b)
White solid; mp 146–147 ꢀC; IR (Nujol) nmax 3478, 3300, 1744,
9.31 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6)
d 13.5 (s, CH3), 15.8
1700, 1687 cmꢂ1
;
1H NMR (400 MHz, DMSO-d6)
d
0.93 (t, 3H,
(s, CH3), 16.2 (d, 3JCP¼5.3 Hz, CH3), 57.2 (d, 1JCP¼88.0 Hz, CH), 61.1 (d,
4
2
J¼6.8 Hz, CO2CH2CH3), 1.95 (d, 3H, JHP¼1.6 Hz, CH3), 3.56 (d, 3H,
3JHP¼11.2 Hz, OCH3), 3.90–3.93 (m, 2H, CO2CH2CH3), 4.41 (d, 1H,
2JHP¼18.8 Hz, CH), 6.26 (br s, 2H, NH2), 7.52–7.75 (m, 5H, CHarom),
2JCP¼13.6 Hz, CH2), 61.2 (s, CH2), 128.4 (d, JCP¼12.9 Hz, CH), 130.1
3
(d, 1JCP¼131.3 Hz, C), 131.7 (d, JCP¼9.8 Hz, CH), 132.5 (s, CH), 139.9
(d, 2JCP¼6.8 Hz, C), 156.9 (s, C), 166.2 (d, 2JCP¼7.6 Hz, C); MS m/z 355
9.33 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6)
d
13.5 (s, CH3), 15.8
(7) [Mþ], 338 (12), 309 (10), 292 (13), 266 (100). Anal. Calcd for
(s, CH3), 51.7 (d, 2JCP¼6.8 Hz, CH3), 56.9 (d, 1JCP¼88.0 Hz, CH), 61.1 (s,
C15H22N3O5P: C, 50.70; H, 6.24; N, 11.83. Found: C, 50.53; H, 6.33; N,
11.71.
2
CH2), 128.5 (d, JCP¼12.9 Hz, CH), 129.2 (d, 1JCP¼162.0 Hz, C), 131.9
(d, 3JCP¼9.9 Hz, CH), 132.8 (s, CH), 139.8 (d, 2JCP¼6.9 Hz, C), 156.8 (s,
C), 166.2 (d, 2JCP¼5.3 Hz, C); 31P NMR (162 MHz, DMSO-d6)
d
36.40;
4.5.7. Ethyl {2-[2-(aminocarbonyl)hydrazono]-1-
MS m/z 341 (7) [Mþ], 278 (15), 266 (18), 252 (100). Anal. Calcd for
[(dimethylamino)carbonyl]propyl}phenylphosphinate (5g)
White solid; mp 165–168 ꢀC; IR (Nujol) nmax 3470, 3305, 1718,
C
14H20N3O5P: C, 49.27; H, 5.91; N, 12.31. Found: C, 49.33; H, 5.88; N,
12.43.
1685 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d 1.17 and 1.18 (dt, 3H,
4
4
J¼6.8 Hz, JHP¼2.0 Hz, OCH2CH3), 1.86 (d, 3H, JHP¼2.0 Hz, CH3),
4.5.3. Methyl {2-[2-(aminocarbonyl)hydrazono]-1-
2.79 and 2.94 (2s, 6H, N(CH3)2), 3.82–4.03 (m, 2H, OCH2CH3), 4.67
2
[(dimethylamino)carbonyl]propyl}phenylphosphinate (5c)
White solid; mp 173–177 ꢀC; IR (Nujol) nmax 3472, 3298, 1725,
(d, 1H, JHP¼18.8 Hz, CH), 6.17 (br s, 2H, NH2), 7.46–7.72 (m, 5H,
CHarom), 9.22 (2s, 1H, NH); 13C NMR (100 MHz, DMSO-d6)
d 14.0 (s,
1692 cmꢂ1
;
1H NMR (400 MHz, DMSO-d6)
d
1.87 (d, 3H,
CH3), 15.3 (s, CH3), 35.3 (s, CH3), 37.5 (s, CH3), 55.0 (d, 2JCP¼94.1 Hz,
4JHP¼2.0 Hz, CH3), 2.79 and 2.94 (2s, 6H, N(CH3)2), 3.56 (d, 3H,
CH), 60.7 (d, 2JCP¼6.8 Hz, CH2), 128.0 (d, 2JCP¼12.2 Hz, CH), 130.4 (d,
3JHP¼10.8 Hz, OCH3), 4.69 (d, 1H, JHP¼18.8 Hz, CH), 6.18 (br s, 2H,
1JCP¼132.2 Hz, C), 131.6 (d, JCP¼9.9 Hz, CH), 132.1 (s, CH), 141.0 (d,
2
3
NH2), 7.48–7.71 (m, 5H, CHarom), 9.25 (s, 1H, NH); 13C NMR
2JCP¼7.5 Hz, C), 156.9 (s, C), 165.2 (d, 2JCP¼3.8 Hz, C); MS m/z 354 (2)
[Mþ], 337 (13), 310 (51), 266 (100). Anal. Calcd for C15H23N4O4P: C,
50.84; H, 6.54; N, 15.51. Found: C, 50.77; H, 6.39; N, 15.48.
(100 MHz, DMSO-d6) d 15.9 (s, CH3), 35.9 (s, CH3), 38.1 (s, CH3), 52.1
2
1
(d, JCP¼6.0 Hz, CH3), 54.8 (d, JCP¼78.9 Hz, CH), 128.8 (d,
2JCP¼12.2 Hz, CH), 130.8 (d, 1JCP¼132.0 Hz, C), 132.5 (d, 3JCP¼9.9 Hz,
2
CH), 132.8 (s, CH), 141.6 (d, JCP¼6.8 Hz, C), 157.6 (s, C), 165.9 (d,
4.5.8. Methyl 3-[2-(aminocarbonyl)hydrazono]-2-[ethoxy-
(phenyl)phosphoryl]pentanoate (5h)
2JCP¼4.5 Hz, C); MS m/z 340 (1) [Mþ], 296 (41), 266 (100). Anal.
Calcd for C14H21N4O4P: C, 49.41; H, 6.22; N, 16.46. Found: C, 49.67;
H, 6.18; N, 16.59.
White solid; mp 128–132 ꢀC; IR (Nujol) nmax 3480, 3270, 1752,
1695 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.08 (t, 3H, J¼7.6 Hz,
CH2CH3), 1.16 (t, 3H, J¼7.2 Hz, OCH2CH3), 2.30–2.48 (m, 2H,
4.5.4. Methyl 3-[2-(aminocarbonyl)hydrazono]-2-[methoxy-
(phenyl)phosphoryl]pentanoate (5d)
CH2CH3), 3.62 (s, 3H, CO2CH3), 3.69–3.74 (m, 2H, OCH2CH3), 4.14 (d,
2
1H, JHP¼18.6 Hz, CH), 6.15 (br s, 2H, NH2), 7.42–7.79 (m, 5H,
White solid; mp 120–123 ꢀC; IR (Nujol) nmax 3465, 3290, 1748,
CHarom), 8.93 (s, 1H, NH); 13C NMR (100 MHz, CDCl3)
d
9.1 (s, CH3),
3
1700, 1684 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.06 (t, 3H, J¼7.6 Hz,
16.0 (d, JCP¼6.1 Hz, CH3), 23.3 (s, CH2), 52.3 (s, CH3), 61.0 (d,
2JCP¼6.3 Hz, CH2), 53.9 (d, 1JCP¼91.6 Hz, CH), 129.1 (d, 2JCP¼13.7 Hz,
CH), 131.2 (d, 3JCP¼11.3 Hz, CH), 131.6 (d, 1JCP¼111.0 Hz, C), 132.9 (s,
CH2CH3), 2.32–2.50 (m, 2H, CH2CH3), 3.62 (s, 3H, CO2CH3), 3.70–
2
3.72 (m, 3H, OCH3), 4.14 (d, 1H, JHP¼18.6 Hz, CH), 6.21 (br s, 2H,
2
2
NH2), 7.44–7.80 (m, 5H, CHarom), 8.82 (s, 1H, NH); 13C NMR
CH), 144.7 (d, JCP¼7.2 Hz, C), 158.7 (s, C), 166.9 (d, JCP¼6.2 Hz, C);
MS m/z 355 (6) [Mþ], 338 (15), 280 (100). Anal. Calcd for
(100 MHz, CDCl3)
d 9.0 (s, CH3), 23.1 (s, CH2), 52.1 (s, CH3), 52.9 (d,

6730
O.A. Attanasi et al. / Tetrahedron 64 (2008) 6724–6732
C15H22N3O5P: C, 49.27; H, 5.91; N, 12.31. Found: C, 49.12; H, 5.87; N,
12.37.
tautomer), 1.09 (t, 0.15H, J¼7.2 Hz, CO2CH2CH3 keto tautomer), 1.39
(t, 3H, J¼7.2 Hz, OCH2CH3 keto and enol tautomers), 2.38 (s, 0.15H,
CH3 keto tautomer), 2.49 (s, 2.85H, CH3 enol tautomer), 3.89–4.22
(m, 4H, CO2CH2CH3 and OCH2CH3 keto and enol tautomers), 5.56–
5.58 (m, 0.05H, CH keto tautomer), 7.40–7.84 (m, 5H, CHarom keto
4.6. General procedure for the synthesis of
b-ketophosphonates 6a–e
and enol tautomers), 14.46 (s, 0.95H, OH enol tautomer); 13C NMR
3
To a solution of E-hydrazonophosphonates 5a,b,d,f,g (1 mmol)
(100 MHz, CDCl3)
d
14.0 (s, CH3), 14.1 (s, CH3), 16.5 (d, JCP¼6.8 Hz,
3
2
in acetone–water (9:1, 15 mL), 4 equiv of Amberlyst 15H was added
and the reaction was refluxed for 3.0–5.0 h, until the disappearance
of the starting compound 5 (monitored by TLC). The resin was re-
moved by filtration and the reaction solvent was evaporated under
reduced pressure. Then the crude was chromatographed on silica
gel column (elution mixture: ethyl acetate–cyclohexane) to give
products 6a–d as oils, while 6e was crystallized from ethyl acetate–
cyclohexane.
CH3), 23.9 (d, JCP¼9.1 Hz, CH3), 60.0 (s, CH2), 61.6 (d, JCP¼9.1 Hz,
CH2), 89.8 (d, 1JCP¼127.5 Hz, C), 108.1 (d, 1JCP¼119.0 Hz, CH), 128.2
2
1
(d, JCP¼13.6 Hz, CH), 131.4 (d, JCP¼155.0 Hz, C), 131.7 (d,
3JCP¼10.6 Hz, CH), 132.6 (s, CH), 166.1 (d, JCP¼11.3 Hz, C), 190.0 (s,
2
C), 197.0 (s, C); MS m/z 298 (64) [Mþ], 283 (45), 252 (24), 225 (37),
211 (30), 183 (32), 169 (100). Anal. Calcd for C14H19O5P: C, 53.34; H,
5.59. Found: C, 53.39; H, 5.54.
4.6.5. Ethyl {1-[(dimethylamino)carbonyl]-2-hydroxy-1-propenyl}-
phenylphosphinate (enol tautomer: 100%) (6e)
4.6.1. Methyl 2-[methoxy(phenyl)phosphoryl]-3-oxobutanoate
(keto tautomer: 3%)/methyl 3-hydroxy-2-[methoxy(phenyl)-
phosphoryl]-2-butenoate (enol tautomer: 97%) (6a)
White solid; mp 88–91 ꢀC; IR (Nujol) nmax 3300 (br), 1742,
1712 cmꢂ1
;
1H NMR (400 MHz, DMSO-d6)
d
1.19 (t, 3H, J¼7.6 Hz,
Colorless oil; IR (Nujol) nmax 3279 (br), 1741, 1715 cmꢂ1; 1H NMR
OCH2CH3), 2.24 (s, 3H, CH3), 2.70 and 2.89 (2s, 6H, N(CH3)2), 3.89–
4.21 (m, 2H, OCH2CH3), 7.44–7.76 (m, 5H, CHarom), 12.22 (s, 1H, OH);
(400 MHz, CDCl3)
d 2.38 (s, 0.09H, CH3 keto tautomer), 2.49 (s,
2.91H, CH3 enol tautomer), 3.51 (s, 2.91H, CO2CH3 enol tautomer),
13C NMR (100 MHz, DMSO-d6)
d
15.3 (s, CH3), 15.4 (s, CH3), 24.7 (d,
2
3
2
3.62 (s, 0.09H, CO2CH3 keto tautomer), 3.82 (d, 3H, JHP¼12.4 Hz,
3JCP¼9.1 Hz, CH3), 16.8 (d, JCP¼6.8 Hz, CH3), 61.6 (d, JCP¼9.1 Hz,
CH2), 89.1 (d, 1JCP¼129.1 Hz, C), 128.2 (d, 2JCP¼13.6 Hz, CH), 131.1 (d,
1JCP¼155.1 Hz, C), 131.6 (d, 3JCP¼10.6 Hz, CH), 132.5 (s, CH), 166.7 (d,
2JCP¼11.1 Hz, C), 190.0 (s, C); MS m/z 297 (20) [Mþ], 279 (58), 253
(100). Anal. Calcd for C14H20NO4P: C, 56.56; H, 6.78. Found: C,
56.47; H, 6.79.
OCH3 keto and enol tautomers), 5.56–5.58 (m, 0.03H, CH keto
tautomer), 7.44–7.84 (m, 5H, CHarom keto and enol tautomers),
14.69 (s, 0.97H, OH enol tautomer); 13C NMR (100 MHz, CDCl3)
d
24.0 (d, 3JCP¼9.1 Hz, CH3), 24.1 (d, 3JCP¼9.1 Hz, CH3), 51.0 (s, CH3),
2
1
51.9 (d, JCP¼6.8 Hz, CH3), 89.1 (d, JCP¼129.0 Hz, C), 108.1 (d,
1JCP¼129.0 Hz, CH), 128.4 (d, JCP¼14.4 Hz, CH), 131.2 (d,
2
1JCP¼154.8 Hz, C), 131.7 (d, 3JCP¼10.6 Hz, CH), 132.5 (d, 4JCP¼3.0 Hz,
4.7. General procedure for the synthesis of 4-[alkoxy(phenyl)-
phosphoryl]-1,2-diaza-1,3-butadienes 9a–e
CH), 165.5 (d, JCP¼11.3 Hz, C), 190.3 (s, C), 197.0 (s, C); 31P NMR
2
(162 MHz, DMSO-d6)
d
33.45, 46.60; MS m/z 270 (60) [Mþ], 255
(60), 238 (20), 223 (14), 197 (18), 173 (25), 155 (100). Anal. Calcd for
12H15O5P: C, 53.34; H, 5.59. Found: C, 53.39; H, 5.54.
To a magnetically stirred solution of E-hydrazonophosphonates
5a,b,d,f,g (1 mmol) in dichloromethane (150 mL), 2,4,4,6-tetra-
bromo-3-n-pentadecyl-2,5-cyclohexadienone (TBPCO)25 (1.1 mmol)
was added portion-wise at room temperature obtaining the
C
4.6.2. Ethyl 3-hydroxy-2-[methoxy(phenyl)phosphoryl]-2-
butenoate (enol tautomer: 100%) (6b)
corresponding a-bromohydrazones 8 (check by TLC), in 2.0 h. The
Colorless oil; IR (Nujol) nmax 3300 (br), 1740, 1710 cmꢂ1; 1H NMR
mixture was then treated with an aqueous solution of sodium
acetate (20 mLꢃ2) and the organic layer was dried on sodium
sulfate. Dichloromethane was evaporated under reduced pressure
and the final 4-[alkoxy(phenyl)phosphoryl]-1,2-diaza-1,3-butadi-
enes 9a–e were purified by chromatography on silica gel column
(elution mixture: ethyl acetate–cyclohexane) and were obtained as
red oils.
(400 MHz, CDCl3)
d
1.01 (t, 3H, J¼7.2 Hz, CO2CH2CH3), 2.50 (3H, s,
3
CH3), 3.82 (d, 3H, JHP¼11.6 Hz, OCH3), 3.94–4.00 (m, 2H,
CO2CH2CH3), 7.42–7.83 (m, 5H, CHarom), 14.67 (s, 1H, OH); 13C NMR
(100 MHz, CDCl3)
d
14.2 (s, CH3), 23.9 (d, 3JCP¼9.1 Hz, CH3), 51.8 (d,
2JCP¼6.8 Hz, CH3), 60.0 (s, CH2), 89.0 (d, 1JCP¼129.0 Hz, C), 128.3 (d,
2JCP¼13.6 Hz, CH), 131.5 (d, 1JCP¼155.5 Hz, C), 131.6 (d, 3JCP¼10.6 Hz,
CH), 132.5 (s, CH), 166.0 (d, 2JCP¼10.6 Hz, C), 190.3 (s, C); MS m/z 284
(61) [Mþ], 269 (58), 239 (20), 311 (38), 155 (100). Anal. Calcd for
4.7.1. Methyl 3-[2-(aminocarbonyl)-1-diazenyl]-2-[methoxy-
C
13H17O5P: C, 54.93; H, 6.03. Found: C, 54.81; H, 5.99.
(phenyl)phosphoryl]-2-butenoate (9a)
Red oil; IR (Nujol) nmax 3291, 3170, 1734, 1615 cmꢂ1
;
1H NMR
4
4.6.3. Methyl 3-hydroxy-2-[methoxy(phenyl)phosphoryl]-2-
pentenoate (enol tautomer: 100%) (6c)
(400 MHz, CDCl3)
d
2.03 (d, 3H, JHP¼2.4 Hz, CH3), 3.69 (d, 3H,
3JHP¼11.6 Hz, OCH3), 3.89 (s, 3H, CO2CH3), 5.17 and 7.10 (2br s, 2H,
Pale yellow oil; IR (Nujol) nmax 3305 (br), 1738, 1710 cmꢂ1
;
1H
NH2), 7.45–7.84 (m, 5H, CHarom); 13C NMR (100 MHz, CDCl3)
d 13.5
NMR (400 MHz, CDCl3)
d
1.20 (t, 3H, J¼7.2 Hz, OCH2CH3), 2.85 (q,
(d, 3JCP¼9.8 Hz, CH3), 51.4 (s, CH3), 52.7 (d, 2JCP¼28.8 Hz, CH3), 128.8
2
1
2H, J¼7.2 Hz, CO2CH2CH3), 3.48 (s, 3H, CO2CH3), 3.80 (d, 3H,
(d, JCP¼13.6 Hz, CH), 130.7 (d, JCP¼146.4 Hz, C), 131.5 (d,
3JCP¼12.0 Hz, CH), 133.2 (s, CH), 136.4 (d, 1JCP¼123.0 Hz, C), 159.4 (s,
3JHP¼12.4 Hz, OCH3), 7.40–7.81 (m, 5H, CHarom), 14.81 (s, 1H, OH);
13C NMR (100 MHz, CDCl3)
d
11.6 (s, CH3), 51.1 (s, CH3), 63.2 (d,
C), 163.3 (d, JCP¼21.0 Hz, C), 165.4 (d, JCP¼7.6 Hz, C); 31P NMR
2
2
3JCP¼6.8 Hz, CH2), 51.9 (d, 2JCP¼6.8 Hz, CH3), 88.9 (d, 1JCP¼127.5 Hz,
(162 MHz, DMSO-d6)
d
26.78; MS m/z 326 (3) [Mþþ1], 308 (11), 267
C), 128.2 (d, JCP¼13.6 Hz, CH), 131.4 (d, 1JCP¼155.0 Hz, C), 131.7 (d,
(15), 253 (63), 221 (45), 207 (81), 195 (100). Anal. Calcd for
2
3JCP¼10.6 Hz, CH), 132.6 (s, CH), 166.4 (d, JCP¼11.3 Hz, C), 190.1 (s,
C13H16N3O5P: C, 48.01; H, 4.96; N, 12.92. Found: C, 47.99; H, 4.94; N,
12.97.
2
C); MS m/z 284 (37) [Mþ], 255 (100). Anal. Calcd for C13H17O5P: C,
54.93; H, 6.03. Found: C, 54.81; H, 5.99.
4.7.2. Ethyl 3-[2-(aminocarbonyl)-1-diazenyl]-2-[methoxy-
(phenyl)phosphoryl]-2-butenoate (9b)
4.6.4. Ethyl 2-[ethoxy(phenyl)phosphoryl]-3-oxobutanoate (keto
tautomer: 5%)/ethyl 2-[ethoxy(phenyl)phosphoryl]-3-hydroxy-2-
butenoate (enol tautomer: 95%) (6d)
Red oil; mixture of isomers; IR (Nujol) nmax 3284, 3168, 1731,
1616 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 1.25 and 1.35 (2t, 3H,
Pale yellow oil; IR (Nujol) nmax 3305 (br), 1742, 1710 cmꢂ1
;
1H
J¼7.2 Hz, CO2CH2CH3), 2.03 and 2.14 (2d, 3H, 4JHP¼1.2 Hz, CH3), 3.69
3
NMR (400 MHz, CDCl3)
d
1.02 (t, 2.85H, J¼7.2 Hz, CO2CH2CH3 enol
and 3.82 (2d, 3H, JHP¼11.6 Hz, OCH3), 4.22–4.39 (m, 2H,

O.A. Attanasi et al. / Tetrahedron 64 (2008) 6724–6732
6731
CO2CH2CH3), 5.56, 5.97, 6.02, and 7.01 (4br s, 2H, NH2), 7.45–7.95
(10 mL) at room temperature, a catalytic amount of sodium
methoxide (0.1 mmol) was added. The reaction was allowed to
stand in these conditions for 0.5–1.0 h, until the disappearance of
the red color of the starting compound 6. After evaporation of the
solvent under reduced pressure, the products 10a,b were obtained
by chromatography on a silica gel column (elution mixture: ethyl
acetate–cyclohexane) and were crystallized from ethyl acetate–
light petroleum (bp 40–60 ꢀC).
(m, 5H, CHarom); 13C NMR (100 MHz, CDCl3)
d 12.0 (s, CH3), 13.5 (d,
3
2
3JCP¼9.8 Hz, CH3), 14.3 (d, JCP¼9.8 Hz, CH3), 52.2 (d, JCP¼28.8 Hz,
2
CH3), 62.4 (s, CH2), 62.6 (s, CH2), 128.9 (d, JCP¼14.0 Hz, CH), 129.0
2
1
(d, JCP¼13.7 Hz, CH), 129.6 (d, JCP¼135.0 Hz, C), 131.7 (d,
3JCP¼11.4 Hz, CH), 132.1 (d, JCP¼10.6 Hz, CH), 133.0 (s, CH), 137.1
3
(d, 1JCP¼123.7 Hz, C),140.4 (d, 1JCP¼122.9 Hz, C),159.0 (s, C),162.1 (d,
2JCP¼21.2 Hz, C), 162.4 (d, 2JCP¼24.3 Hz, C), 165.2 (d, 2JCP¼8.3 Hz, C),
165.7 (d, 2JCP¼9.1 Hz, C); MS m/z 340 (2) [Mþþ1], 322 (13), 267 (12),
253 (60), 221 (33), 207 (83), 195 (100). Anal. Calcd for C14H18N3O5P:
C, 49.56; H, 5.35; N, 12.38. Found: C, 49.63; H, 5.46; N, 12.01.
4.8.1. Ethyl 3-[2-(aminocarbonyl)hydrazono]-2-methoxy-2-
[methoxy(phenyl)phosphoryl]butanoate (10a)
White powder; mp 111–113 ꢀC; IR (Nujol) nmax 3358, 3100, 1705,
4.7.3. Methyl 3-[2-(aminocarbonyl)-1-diazenyl]-2-[methoxy-
1620 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 0.88–0.93 (m, 3H,
(phenyl)phosphoryl]-2-pentenoate (9c)
CO2CH2CH3), 2.45 and 2.54 (2s, 3H, CH3), 3.66 and 3.69 (2s, 3H,
3
Red oil; IR (Nujol) nmax 3290, 3150, 1725, 1623 cmꢂ1
;
1H NMR
OCH3), 3.74 and 3.76 (2d, 3H, JHP¼2.1 Hz, POCH3), 3.81–3.93 (m,
(400 MHz, DMSO-d6)
d
1.06 (t, 3H, J¼7.2 Hz, CH2CH3), 2.43–2.55 (m,
2H, CO2CH2CH3), 5.64 and 6.12 (2br s, 2H, NH2), 7.38–7.43 (m, 3H,
2H, CH2CH3), 3.70 (d, 3H, 3JHP¼11.6 Hz, OCH3), 3.87 (s, 3H, CO2CH3),
CHarom), 7.75–7.79 (m, 2H, CHarom), 9.81 and 10.61 (2s, 1H, NH); 13
C
5.17 and 7.10 (2br s, 2H, NH2), 7.45–7.85 (m, 5H, CHarom); 13C NMR
NMR (100 MHz, DMSO-d6) d 14.2 (s, CH3), 14.3 (s, CH3), 25.3 (d,
(100 MHz, DMSO-d6)
d
12.3 (s, CH3), 13.1 (d, 3JCP¼7.3 Hz, CH2), 52.0
3JCP¼10.6 Hz, CH3), 29.9 (s, CH3), 54.0 (d, 2JCP¼13.9 Hz, CH3), 59.2 (s,
2
2
(s, CH3), 53.1 (d, JCP¼28.6 Hz, CH3), 128.7 (d, JCP¼14.4 Hz, CH),
CH2), 59.6 (s, CH2), 80.6 (d, 1JCP¼135.8 Hz, C), 128.0 (d, 2JCP¼13.7 Hz,
130.8 (d, 1JCP¼135.1 Hz, C), 131.4 (d, 3JCP¼11.4 Hz, CH), 133.0 (s, CH),
CH), 130.7 (d, JCP¼6.1 Hz, CH), 130.8 (d, JCP¼6.1 Hz, CH), 131.3 (d,
4JCP¼2.5 Hz, CH), 134.6 (d, 1JCP¼147.4 Hz, C), 135.6 (d, 1JCP¼149.5 Hz,
C), 167.5 (d, 2JCP¼12.2 Hz, C), 169.7 (d, 2JCP¼12.2 Hz, C), 172.6 (s, C),
174.1 (d, 2JCP¼6.1 Hz, C); MS m/z 371 (1) [Mþ], 283 (100). Anal. Calcd
for C15H22N3O6P: C, 48.52; H, 5.97; N, 11.32. Found: C, 48.57; H,
6.01; N, 11.44.
3
3
1
2
136.3 (d, JCP¼123.0 Hz, C), 159.3 (s, C), 162.5 (d, JCP¼32.0 Hz, C),
165.2 (d, 2JCP¼8.3 Hz, C); MS m/z 340 (1) [Mþþ1], 267 (10), 253 (45),
239 (33), 222 (23), 207 (100). Anal. Calcd for C14H18N3O5P: C, 49.56;
H, 5.35; N, 12.38. Found: C, 49.63; H, 5.68; N, 12.55.
4.7.4. Methyl 3-[2-(aminocarbonyl)-1-diazenyl]-2-[ethoxy-
(phenyl)phosphoryl]-2-butenoate (9d)
4.8.2. Methyl 3-[2-(aminocarbonyl)hydrazono]-2-[ethoxy-
(phenyl)phosphoryl]-2-methoxybutanoate (10b)
Red oil; IR (Nujol) nmax 3288, 3162, 1730, 1628 cmꢂ1 1H NMR
;
(400 MHz, CDCl3)
d
1.29 (t, 3H, J¼7.2 Hz, CO2CH2CH3), 2.03 (d, 3H,
White powder; mp 117–119 ꢀC; IR (Nujol) nmax 3360, 3090, 1698,
4JHP¼2.4 Hz, CH3), 3.89 (s, 3H, CO2CH3), 3.96–4.00 and 4.09–4.15
1622 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 1.20–1.40 (m, 3H,
(2m, 2H, CO2CH2CH3), 5.41 and 7.03 (2br s, 2H, NH2), 7.26–7.48 (m,
OCH2CH3), 2.46 and 2.58 (2s, 3H, CH3), 3.42 and 3.44 (2s, 3H,
CO2CH3), 3.64 and 3.88 (2s, 3H, OCH3), 4.06–4.16 (m, 2H, OCH2CH3),
5.17 and 5.58 (2br s, 2H, NH2), 7.38–7.44 (m, 3H, CHarom), 7.78–7.82
(m, 2H, CHarom), 9.75 and 10.15 (2s, 1H, NH); 13C NMR (100 MHz,
2H, CHarom), 7.52–7.54 (m, 1H, CHarom), 7.81–7.87 (m, 2H, CHarom);
13C NMR (100 MHz, CDCl3)
d
13.7 (d, JCP¼9.8 Hz, CH3), 16.3
3
(d, 3JCP¼6.8 Hz, CH3), 52.2 (s, CH3), 61.8 (d, 2JCP¼6.0 Hz, CH2), 128.7
2
3
3
3
(d, JCP¼13.6 Hz, CH), 131.4 (d, JCP¼10.7 Hz, CH), 131.5 (d,
DMSO-d6)
d
18.2 (d, JCP¼6.0 Hz, CH3), 25.5 (d, JCP¼10.6 Hz, CH3),
1JCP¼144.1 Hz, C), 132.7 (s, CH), 137.0 (d, 1JCP¼123.0 Hz, C), 159.3 (s,
29.8 (s, CH3), 49.6 (s, CH3), 64.8 (d, JCP¼7.1 Hz, CH2), 80.8 (d,
1JCP¼137.4 Hz, C), 128.1 (d, 2JCP¼13.6 Hz, CH), 130.8 (d, 3JCP¼6.1 Hz,
CH), 131.1 (s, CH), 134.8 (d, 1JCP¼147.4 Hz, C), 167.8 (d, 2JCP¼12.0 Hz,
2
2
2
C), 162.2 (d, JCP¼31.8 Hz, C), 165.8 (d, JCP¼8.3 Hz, C); MS m/z 340
(2) [Mþþ1], 322 (15), 281 (17), 266 (58), 207 (100). Anal. Calcd for
2
C
14H18N3O5P: C, 49.56; H, 5.35; N,12.38. Found: C, 49.68; H, 5.26; N,
C), 172.8 (s, C), 174.0 (d, JCP¼6.1 Hz, C); MS m/z 371 (2) [Mþ], 339
12.60.
(15), 283 (100). Anal. Calcd for C15H22N3O6P: C, 48.52; H, 5.97; N,
11.32. Found: C, 48.52; H, 5.97; N, 11.12.
4.7.5. Ethyl 3-[2-(aminocarbonyl)-1-diazenyl]-2-[ethoxy(phenyl)-
phosphoryl]-2-butenoate (9e)
4.9. General procedure for the synthesis of 5-phosphinate-
substituted thiazol-4-ones 12a–c
Red oil; mixture of isomers; IR (Nujol) nmax 3284, 3160, 1730,
1625 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d 1.14 and 1.18 (2t, 3H,
J¼6.8 Hz, OCH2CH3), 1.26 and 1.27 (2t, 3H, J¼7.2 Hz, CO2CH2CH3),
A solution of 4-[alkoxy(phenyl)phosphoryl]-1,2-diaza-1,3-bu-
tadienes 9a,c,d (1 mmol) and thiourea 11 (1 mmol) in methanol
(10 mL) was magnetically stirred at room temperature for 1.0–2.0 h,
until the disappearance of the reagents (monitored by TLC). The
compounds 12a–c were directly crystallized from the reaction
medium and collected as pure products by filtration.
4
1.83 and 1.98 (2d, 3H, JHP¼0.8 Hz, CH3), 3.85–4.11 (m, 2H,
OCH2CH3), 4.15 and 4.29 (2q, 2H, J¼7.2 Hz, CO2CH2CH3), 5.19, 5.65,
5.96, and 7.10 (4br s, 2H, NH2), 7.46–7.85 (m, 5H, CHarom); 13C NMR
(100 MHz, DMSO-d6)
d
11.8 (s, CH3), 13.5 (d, 3JCP¼9.1 Hz, CH3), 14.5
(d, 3JCP¼9.1 Hz, CH3), 16.7 (d, 3JCP¼6.9 Hz, CH3), 61.8 (d, 2JCP¼6.0 Hz,
CH2), 62.1 (s, CH2), 62.5 (d, 2JCP¼6.0 Hz, CH2), 129.0 (d, 2JCP¼13.7 Hz,
CH), 129.7 (d, 2JCP¼13.6 Hz, CH), 130.3 (d, 1JCP¼144.0 Hz, C), 132.1 (d,
4.9.1. Methyl (5-{1-[2-(aminocarbonyl)hydrazono]ethyl}-2-imino-
4-oxo-1,3-thiazolan-5-yl)phenylphosphinate (12a)
3JCP¼10.6 Hz, CH), 132.3 (d, JCP¼11.3 Hz, CH), 133.9 (s, CH), 136.0
3
(d, 1JCP¼123.0 Hz, C), 138.2 (d, 1JCP¼123.0 Hz, C), 159.7 (s, C), 164.3
White powder; mp 172–175 ꢀC; IR (Nujol) nmax 3315, 3280, 3110,
2
2
2
(d, JCP¼20.0 Hz, C), 165.5 (d, JCP¼8.3 Hz, C), 165.8 (d, JCP¼8.4 Hz,
C); MS m/z 354 (3) [Mþþ1], 336 (12), 281 (21), 266 (61), 221 (100).
Anal. Calcd for C15H20N3O5P: C, 50.99; H, 5.71; N, 11.89. Found: C,
51.03; H, 5.88; N, 11.73.
1715 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d 1.72 (s, 3H, CH3), 3.58
(d, 3H, 3JHP¼10.8 Hz, OCH3), 6.26 (br s, 2H, NH2), 7.43–7.79 (m, 5H,
CHarom), 9.07 (s, 1H, NH), 9.30 (s, 1H, NH), 9.58 (s, 1H, NH); 13C NMR
(100 MHz, DMSO-d6)
d 13.2 (s, CH3), 52.4 (s, CH3), 75.9 (d,
1JCP¼93.3 Hz, C),127.8 (d, 2JCP¼12.2 Hz, CH),129.8 (d, 1JCP¼139.8 Hz,
3
4.8. General procedure for the synthesis of 2-[alkoxy(phenyl)-
phosphoryl]-2-methoxyhydrazones 10a,b
C), 132.5 (s, CH), 133.4 (d, JCP¼9.1 Hz, CH), 141.3 (s, C), 157.0 (d,
2JCP¼22.0 Hz, C),179.7 (s, C),182.0 (s, C); 31P NMR (162 MHz, DMSO-
d6)
d
34.88; MS m/z 369 (1) [Mþ], 294 (7), 266 (14), 212 (43), 185
To
a
magnetically stirred solution of 4-[alkoxy(phenyl)-
(23), 171 (42), 155 (100). Anal. Calcd for C13H16N5O4PS: C, 42.28; H,
4.37; N, 18.96. Found: C, 42.49; H, 4.22; N, 19.02.
phosphoryl]-1,2-diaza-1,3-butadienes 9b,e (1 mmol) in methanol

6732
O.A. Attanasi et al. / Tetrahedron 64 (2008) 6724–6732
3. (a) Attanasi, O. A.; De Crescentini, L.; Filippone, P.; Mantellini, F.; Tietze, L. F.
Tetrahedron 2001, 57, 5855; (b) Attanasi, O. A.; De Crescentini, L.; Filippone, P.;
Mantellini, F.; Santeusanio, S. Synlett 2003, 1183; (c) Attanasi, O. A.; De Cres-
centini, L.; Favi, G.; Filippone, P.; Lillini, S.; Mantellini, F.; Santeusanio, S. Org.
Lett. 2005, 7, 2469.
4. (a) Attanasi, O. A.; De Crescentini, L.; Favi, G.; Filippone, P.; Mantellini, F.;
Santeusanio, S. J. Org. Chem. 2004, 69, 2686; (b) Attanasi, O. A.; Favi, G.; Fili-
ppone, P.; Lillini, S.; Mantellini, F.; Spinelli, D.; Stenta, M. Adv. Synth. Catal. 2007,
349, 907; (c) Schmidt, A.; Karapetyan, V.; Attanasi, O. A.; Favi, G.; Go¨rls, H.;
Mantellini, F.; Langer, P. Synlett 2007, 2965.
5. Attanasi, O. A.; Berretta, S.; De Crescentini, L.; Favi, G.; Filippone, P.; Giorgi, G.;
Lillini, S.; Mantellini, F. Tetrahedron Lett. 2007, 48, 2449.
6. Attanasi, O. A.; Favi, G.; Filippone, P.; Giorgi, G.; Lillini, S.; Mantellini, F.; Perrulli,
F. R. Synlett 2006, 2731.
7. Attanasi, O. A.; De Crescentini, L.; Favi, G.; Filippone, P.; Giorgi, G.; Mantellini, F.;
Santeusanio, S. J. Org. Chem. 2003, 68, 1947.
4.9.2. Methyl (5-{1-[2-(aminocarbonyl)hydrazono]propyl}-2-
imino-4-oxo-1,3-thiazolan-5-yl)phenylphosphinate (12b)
White powder; mp 142–145 ꢀC with decomposition; IR (Nujol)
nmax 3325, 3280, 3105, 1720 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
;
d
0.87 (t, 3H, J¼7.2 Hz, CH2CH3), 2.44 (t, 2H, J¼7.2 Hz, CH2CH3), 3.61
3
(d, 3H, JCP¼10.8 Hz, OCH3), 6.19 (br s, 2H, NH2), 7.45–7.81 (m, 5H,
CHarom), 9.05 (s, 1H, NH), 9.27 (s, 1H, NH), 9.67 (s, 1H, NH); 13C NMR
(100 MHz, DMSO-d6) d 9.8 (s, CH3), 20.4 (s, CH2), 52.5 (s, CH3), 76.0 (d,
1JCP¼93.8 Hz, C), 127.8 (d, 2JCP¼12.9 Hz, CH),129.3 (d, 1JCP¼136.5 Hz,
3
C), 132.5 (s, CH), 133.4 (d, JCP¼9.1 Hz, CH), 144.9 (s, C), 156.9 (d,
2JCP¼22.0 Hz, C), 179.7 (s, C), 182.0 (s, C); MS m/z 383 (1) [Mþ], 368
(20), 340 (8), 266 (59), 172 (100). Anal. Calcd for C14H18N5O4PS: C,
43.86; H, 4.73; N, 18.27. Found: C, 43.93; H, 4.84; N, 18.16.
ˇ
8. Attanasi, O. A.; De Crescentini, L.; Favi, G.; Filippone, P.; Golobic, A.; Lillini, S.;
Mantellini, F. Synlett 2006, 2735.
9. (a) Attanasi, O. A.; De Crescentini, L.; Favi, G.; Filippone, P.; Mantellini, F.;
Santeusanio, S. Synlett 2004, 549; (b) Attanasi, O. A.; Davoli, P.; Favi, G.; Fili-
ppone, P.; Forni, A.; Moscatelli, G.; Prati, F. Org. Lett. 2007, 9, 3461.
10. Aparicio, D.; Attanasi, O. A.; Filippone, P.; Ignacio, R.; Lillini, S.; Mantellini, F.;
Palacios, F.; de los Santos, J. M. J. Org. Chem. 2006, 71, 5897.
4.9.3. Ethyl (5-{1-[2-(aminocarbonyl)hydrazono]ethyl}-2-imino-4-
oxo-1,3-thiazolan-5-yl)phenylphosphinate (12c)
White powder; mp 176–179 ꢀC; IR (Nujol) nmax 3330, 3275, 3108,
1710 cmꢂ1 1H NMR (400 MHz, DMSO-d6)
; d 1.14–1.27 (m, 3H,
OCH2CH3), 1.74 (s, 3H, CH3), 3.92–4.02 (m, 2H, OCH2CH3), 6.41 (br s,
ˇ
11. Attanasi, O. A.; Favi, G.; Filippone, P.; Golobic, A.; Perrulli, F. R.; Stanovnik, B.;
Svete, J. Synlett 2007, 2971.
12. Enders, D.; Saint-Dizier, A.; Lannou, M.-I.; Lenzen, A. Eur. J. Org. Chem. 2006, 29.
13. (a) Seto, H.; Kuzuyama, T. Nat. Prod. Rep. 1999, 16, 589; (b) Fields, S. C. Tetra-
hedron 1999, 55, 12237.
14. (a) Attanasi, O. A.; Filippone, P.; Mei, A. Tetrahedron 1992, 48, 1707; (b) Attanasi,
O. A.; Filippone, P.; Giovagnoli, D. Org. Prep. Proced. Int. 1994, 26, 321.
15. Attanasi, O. A.; Baccolini, G.; Boga, C.; De Crescentini, L.; Filippone, P.; Man-
tellini, F. J. Org. Chem. 2005, 70, 4033.
16. Schmidpeter, A. Comprehensive Heterocyclic Chemistry-II; Katritzky, A. R., Rees,
C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, UK, 1996; Vol. 4, p 771 and
references cited therein.
17. Baccolini, G.; Orsolan, G.; Mezzina, E. Tetrahedron Lett. 1995, 36, 447.
18. (a) Albrigt, T.; Freeman, W.; Schweizer, E. J. Am. Chem. Soc. 1975, 97, 940; (b)
Simons, W. The Sadtler Guide to Carbon-13 NMR Spectra; Sadtler Research
Laboratories: Philadelphia, PA, 1983.
2H, NH2), 7.47–7.81 (m, 5H, CHarom), 9.07 (s, 1H, NH), 9.30 (s, 1H,
NH), 9.60 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6)
d 13.1 (s, CH3),
2
1
16.2 (s, CH3), 61.7 (d, JCP¼6.0 Hz, CH2), 76.0 (d, JCP¼93.3 Hz, C),
127.8 (d, 2JCP¼12.9 Hz, CH), 129.9 (d, 1JCP¼142.2 Hz, C), 132.4 (s, CH),
3
2
133.4 (d, JCP¼9.1 Hz, CH), 141.3 (s, C), 156.9 (d, JCP¼22.0 Hz, C),
179.9 (s, C), 182.3 (s, C); MS m/z 383 (1) [Mþ], 368 (21), 340 (18), 283
(31), 214 (100). Anal. Calcd for C14H18N5O4PS: C, 43.86; H, 4.73; N,
18.27. Found: C, 43.78; H, 4.59; N, 18.31.
Acknowledgements
19. Ballini, R.; Petrini, M. J. Chem. Soc., Perkin Trans. 1 1988, 2563.
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(b) Wadsworth, W. S., Jr.; Emmons, W. D. J. Am. Chem. Soc. 1961, 83, 1733; (c)
Wadsworth, W. S., Jr. Org. React. (N.Y.) 1977, 25, 73.
This work was supported by the financial assistance from the
`
Ministero dell’Universita, dell’Istruzione e della Ricerca (MIUR)-
`
PRIN and the Universita degli Studi di Urbino ‘Carlo Bo’.
21. Maryanoff, B.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
22. (a) Aboujaoude, E. E.; Colligan, N.; Savignac, P. J. Organomet. Chem. 1984, 264, 9;
(b) Mikolajczyk, M.; Balezewski, P. Synthesis 1984, 691.
References and notes
23. Baccolini, G.; Todesco, P. E.; Dalpozzo, R.; De Nino, A. Gazz. Chim. Ital. 1996,
126, 271.
24. (a) Attanasi, O. A.; Filippone, P.; Mei, A.; Santeusanio, S. Synthesis 1984,
671; (b) Attanasi, O. A.; Filippone, P.; Mei, A.; Santeusanio, S. Synthesis 1984,
873.
25. Attanasi, O. A.; Berretta, S.; Favi, G.; Filippone, P.; Mele, G.; Moscatelli, G.;
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26. Attanasi, O. A.; De Crescentini, L.; Filippone, P.; Foresti, E.; Galeazzi, R.;
Ghiviriga, I.; Katritzky, A. R. Tetrahedron 1997, 53, 5617.
1. (a) Attanasi, O. A.; Caglioti, L. Org. Prep. Proced. Int. 1986, 18, 299; (b) Attanasi,
O. A.; Filippone, P. Synlett 1997, 1128; (c) Attanasi, O. A.; De Crescentini, L.;
Filippone, P.; Mantellini, F.; Santeusanio, S. ARKIVOC 2002, xi, 274.
2. (a) Banert, K. Targets in Heterocyclic Systems: Chemistry and Properties; Attanasi,
O. A., Spinelli, D., Eds.; Societa` Chimica Italiana: Rome, 2000; Vol. 3, p 1; (b)
Polanc, S. Targets in Heterocyclic Systems: Chemistry and Properties; Attanasi,
O. A., Spinelli, D., Eds.; Societa` Chimica Italiana: Rome, 2000; Vol. 3, p 33; (c)
Boeckman, R. K., Jr.; Reed, J. E.; Ge, P. Org. Lett. 2001, 3, 3651; (d) van Bergen, M.;
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27. Attanasi, O. A.; De Crescentini, L.; Foresti, E.; Galarini, R.; Santeusanio, S.; Serra-
Zanetti, F. Synthesis 1995, 1397.