Solvent-free reaction of some 1,2-diaza-1,3-butadienes with phosphites: Environmentally friendly access to new diazaphospholes and E- hydrazonophosphonates

Article abstract of DOI:10.1021/jo050242n

The present article describes the reaction between 1,2-diaza-1,3-butadienes and trialkyl phosphites, under an atmosphere of nitrogen and under solvent-free conditions, to give alkyl 3,3-dialkoxy-2H-1,2,3λ⁵- diazaphosphole-4-carboxylates that, i

Full text of DOI:10.1021/jo050242n

Solvent-Free Reaction of Some 1,2-Diaza-1,3-butadienes with
Phosphites: Environmentally Friendly Access to New
Diazaphospholes and E-Hydrazonophosphonates
Orazio A. Attanasi,† Graziano Baccolini,‡ Carla Boga,‡ Lucia De Crescentini,†
Paolino Filippone,*,† and Fabio Mantellini*,†
Istituto di Chimica Organica, Universita` degli Studi di Urbino “Carlo Bo”, Via Sasso 75,
61029 Urbino, Italy, and Dipartimento di Chimica Organica “A. Mangini”, Universita` degli Studi di
Bologna, Viale Risorgimento 4, 40136 Bologna, Italy
filippone@uniurb.it
Received February 7, 2005
The present article describes the reaction between 1,2-diaza-1,3-butadienes and trialkyl phosphites,
under an atmosphere of nitrogen and under solvent-free conditions, to give alkyl 3,3-dialkoxy-2H-
1,2,3λ5-diazaphosphole-4-carboxylates that, in turn, are converted into corresponding E-hydra-
zonophosphonates by treatment with THF:water (95:5). These latter compounds are obtained directly
by the reaction of 1,2-diaza-1,3-butadienes with trialkyl phosphites in the presence of air. These
compounds are useful for the further preparation of dialkyl (5-methyl-3-oxo-2,3-dihydro-1H-4-
pyrazolyl)phosphonates and 2-dialkoxyphosphoryl-1,2,3-thiadiazoles.
Introduction
Recently, 1,2-diaza-1,3-butadienes have been inten-
sively studied by several authors and have been demon-
strated to be interesting products and powerful interme-
diates in organic synthesis.1,2 In our investigations, these
compounds have manifested the aptitude to give rise to
polyfunctionalized five-membered heterocycles, in par-
ticular, pyrazoles,3 thiadiazoles,4 and selenadiazoles4
(Figure 1) by means of preliminary carbon-carbon or
carbon-heteroatom bond formation and subsequent in-
ternal ring closure.
FIGURE 1. Five-membered heterocycles obtained from 1,2-
diaza-1,3-butadienes.
Generally, these compounds are prepared by the reaction
of hydrazones with PCl3. However, this procedure pre-
sents an important limitation: the large amount of HCl
formed during the process may cause an easy P-N
cleavage and consequent formation of related open-ring
products6 and may induce the acidic hydrolysis of the
hydrazone bond, producing the parent carbonyl deriva-
tive.7,8 The same behaviors have not been observed in the
case of 1,2-diaza-1,3-butadienes. Considering these facts,
we hypothesized that diazaphosphole derivatives could
be useful intermediates for the ready formation of in-
doles,9 pyrroles,10 and other azaheterocycles.11
Previously, some of us used conjugated phenylazo-
alkenes to obtain 2H-1,2,3-diazaphosphole derivatives.5
† Universita` degli Studi di Urbino.
‡ Universita` degli Studi di Bologna.
(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. (d) Attanasi, O. A.; De Crescentini, L.;
Filippone, P.; Mantellini, F.; Santeusanio, S. Synlett 2003, 8, 1183. (e)
Attanasi, O. A.; De Crescentini, L.; Favi, G.; Filippone, P.; Mantellini,
F.; Santeusanio, S. J. Org. Chem. 2004, 69, 2686.
Some of us have preliminarily reported the reaction of
phenylazostilbene (PAS) with some phosphites in hexane
10.1021/jo050242n CCC: $30.25 © 2005 American Chemical Society
Published on Web 04/09/2005
J. Org. Chem. 2005, 70, 4033-4037
4033

Attanasi et al.
SCHEME 1a
at room temperature which required nearly 1 month for
completion.12 The reaction of PAS with trialkyl phosphi-
tes (1a-b) afforded a mixture of 3-alkoxy-2,4,5-triphenyl-
3,4-dihydro-2H-1,2,3λ5-diazaphosphol-3-ones (2a-b) and
dialkyl {1,2-diphenyl-2-[(Z)-2-phenylhydrazono]-ethyl}-
phosphonates (3a-b), derived by hydrolytic ring opening.
The reaction of PAS with triphenyl phosphite (1c)
produced 3,3-diphenoxy-2,4,5-triphenyl-3,4-2H-1,2,3λ5-
diazaphosphole (4c), together with the expected di-
phenyl {1,2-diphenyl-2-[(Z)-2-phenylhydrazono]ethyl}-
phosphonate (3c) (Scheme 1). Product 4c represents one
of the rare examples in the literature13-15 of such a
(2) (a) Figuereido, J. O.; Kascheres C. J. Org. Chem. 1997, 62, 1164.
(b) Caposcialli, N.; Novi, M.; Petrillo, G.; Tavani, C. Tetrahedron 1998,
54, 5315. (c) Schantl, J. R.; Na`denik, P. Synlett 1998, 786. (d) South,
M. S. J. Heterocycl. Chem. 1999, 36, 301. (e) Banert, K. In Targets in
Heterocyclic Systems-Chemistry and Properties; Attanasi, O. A., Spinel-
li, D., Eds.; Societa` Chimica Italiana: Rome, 2000; Vol. 3, p 1. (f)
Polanc, S. In Targets in Heterocyclic Systems-Chemistry and Properties;
Attanasi, O. A., Spinelli, D., Eds.; Societa` Chimica Italiana: Rome,
2000; Vol. 3, p 33. (g) Kuznetsov, M. A.; Kuznetsova L. M.; Schantl, J.
Russ. J. Org. Chem. 2000, 36, 836. (h) Boeckman, R. K., Jr.; Reed, J.
E.; Ge, P. Org. Lett. 2001, 3, 3651. (i) Boeckman, R. K., Jr.; Ge, P.;
Reed, J. E. Org. Lett. 2001, 3, 3647. (j) Avalos, M.; Babiano, R.; Cintas,
P.; Clemente, F. R.; Gordillo, R.; Hursthouse, M. B.; Jime´nez, J. L.;
Light, M. E.; Palacios, J. C. Tetrahedron: Asymmetry 2001, 12, 2261.
(k) Alonso, C.; Palacios, F.; Rubiales, G.; Villegas, M. Tetrahedron Lett.
2004, 45, 4031.
a a: R ) Me; b: R ) Et; c: R ) Ph.
compound with an ylide structure, which is likely favored
by its aromatic character.
By continuing our investigations of 1,2-diaza-1,3-
butadienes as building blocks for the constructions of five-
membered diazaheterorings, we decided to explore more
extensively the reactions of dimethyl or diethyl phos-
phites with 1-alkoxycarbonyl or 1-aminocarbonyl-1,2-
diaza-1,3-butadiene-4-carboxylates under solvent-free
conditions, in an attempt to obtain faster reaction times
by means of simple and environmentally friendly pro-
cedures.4,16-18 We also planned to perform the reactions
under a nitrogen atmosphere, to tentatively avoid the
concomitant formation of hydrazonic derivatives 3. Fur-
thermore, we tried successfully to selectively obtain these
hydrazonic derivatives in the presence of atmospheric
moisture. In fact, these latter products have been shown
to derive by the hydrolytic opening of diazaphospholes.
(3) (a) Attanasi, O. A.; Filippone, P.; Mei, A. Tetrahedron 1992, 48,
1707. (b) Attanasi, O. A., Filippone, P.; Fiorucci, C.; Mantellini, F.
Tetrahedron Lett. 1999, 40, 3891.
(4) (a) Attanasi, O. A.; De Crescentini, L.; Filippone, P.; Mantellini,
F. Synlett 2001, 4, 557. (b) Attanasi, O. A.; De Crescentini, L.; Favi,
G.; Filippone, P.; Giorgi, G.; Mantellini, F.; Santeusanio, S. J. Org.
Chem. 2003, 68, 1947.
(5) Baccolini, G.; Todesco, P. E. J. Org. Chem. 1974, 39, 2650.
(6) For reviews about diazaphospholes see (a) Schmidpeter, A.;
Karaghiosoff, K. Azaphospholes. In Rings, Clusters and Polymers in
Main Group and Transition Element; Roesky, H. W., Ed.; Elsevier:
Amsterdam, 1989; p 308. (b) Schmidpeter, A.; Karaghiosoff, K. Het-
erophospholes. In Multiple Bonds and Low Coordination in Phosphorus
Chemistry; Regitz, M., Scherer, O. J., Eds.; Thieme G.: Stuttgart,
Germany, 1990; p 258. (c) Majoral, J. P. Synthesis 1978, 557. (d)
Schmidpeter, A. In Comprehensive Heterocyclic Chemistry-II; Katrizky,
A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K.;
1996; Vol. 4, p 771.
Results and Discussion
1-Aminocarbonyl-1,2-diaza-1,3-butadiene-4-carboxy-
lates 5a-f or 1-tert-butoxycarbonyl-1,2-diaza-1,3-buta-
diene-4-carboxylate 5g reacted with four equivalents of
trimethyl or triethyl phosphites 1a-b under a nitrogen
atmosphere in 4.0-7.5 h to give alkyl 3,3-dialkoxy-2H-
1,2,3λ5-diazaphosphole-4-carboxylates 6a-h in nearly
quantitative yields (Scheme 2, Route A; Table 1).
(7) (a) Attanasi, O. A.; Gasperoni, S. Gazz. Chim. Ital. 1978, 108,
137. (b) Attanasi, O. A.; Gasperoni, S.; Carletti, C. J. Prakt. Chem.
1980, 322, 1063. (c) Attanasi, O. A.; Grossi, M.; Serra-Zanetti, F. J.
Chem. Res. (S) 1983, 322.
(8) (a) McOmie, J. F. W. Protective Groups in Organic Chemistry;
Plenum Press: London, 1973. (b) Kocienski, P. J. Protecting Groups;
Thieme G.: Stuttgart, Germany; 1994. (c) Schelhaas, M.; Waldmann,
H. Angew. Chem., Int. Ed. Engl. 1996, 35, 2056. (d) Greene, T. W.;
Wuts, P. G. M. Protective Groups in Organic Synthesis; John Wiley &
Sons: New York, 1999. (e) Hanson, J. R. Protecting Groups in Organic
Synthesis; Sheffield Academic Press: Sheffield, U.K.; 1999.
(9) Baccolini, G.; Todesco, P. E. J. Chem. Soc., Chem. Commun.
1981, 563.
The reaction of 1,2-diaza-1,3-butadienes 5a-g with
four equivalents of trimethyl or triethyl phosphites 1a-
b, in the presence of atmospheric moisture, provided
hydrazonophosphonates 7a-h in E isomeric form within
2-4 days (Scheme 2, Route B; Table 1). The configuration
of the CdN bond was determined by NOE experiments
(DPFGSE-NOE sequence).19 The irradiation of the meth-
(10) Baccolini, G.; Sandali. C. J. Chem. Soc., Chem. Commun. 1987,
788.
(11) Baccolini, G. In Topics in Heterocyclic Systems-Synthesis,
Reactions and Properties; Attanasi, O. A., Spinelli, D., Eds.; Research
Signpost: Trivandrum, India; 1996; Vol. 1, p 103.
(12) (a) Baccolini, G.; Todesco, P. E. Tetrahedron Lett. 1978, 26,
2313. (b) Baccolini, G.; Todesco, P. E.; Bartoli, G. Phosphorus Sulfur
1980, 9, 203.
(13) (a) Baccolini, G.; Dalpozzo, R.; Mele, V.; Mezzina, E. Phosphorus
Sulfur 1988, 39, 179. (b) Baccolini, G.; Orsolan, G.; Mezzina, E.
Tetrahedron Lett. 1995, 36, 447.
(16) (a) Varma, R. S. Green Chem. 1999, 43. (b) Metzger, J. O.
Angew. Chem., Int. Ed. 1998, 37, 2975. (c) Tanaka, K.; Toda, F. Chem.
Rev. 2000, 100, 1025. (d) Varma, R. S. Pure Appl. Chem. 2001, 73,
193. (e) Cave, G. W. V.; Raston, C. L.; Scott, J. L. Chem. Commun.
2001, 2159. (f) Tanaka, K.; Toda, F. In Solvent-free Organic Synthesis;
Wiley-VCH: Weinheim, Germany; 2003.
(17) (a) Loh, T.-P.; Huang, J.-M.; Goh, S.-H.; Vittal, J. Org. Lett.
2000, 2, 1291. (b) Hajipour, A. R.; Arbabian, M.; Ruoho, A. E. J. Org.
Chem. 2002, 67, 8622. (c) Xu, Z.-B.; Lu, Y.; Guo, Z.-R. Synlett 2003, 4,
564. (d) Lee, J. C.; Bae, Y. H. Synlett 2003, 4, 507. (e) Yadav, L. D. S.;
Singh, S. Synthesis 2003, 1, 63.
(18) Attanasi, O. A.; De Crescentini, L.; Favi, G.; Filippone, P.;
Mantellini, F.; Santeusanio, S. Synlett 2004, 3, 549.
(19) (a) Stonehouse, J.; Adell, P.; Keeler, J.; Shaka, A. J. J. Am.
Chem. Soc. 1994, 116, 6037. (b) Stott, K.; Stonehouse, J.; Keeler, J.;
Hwang, T. L.; Shaka, A. J. J. Am. Chem. Soc. 1995, 117, 4199. (c) Stott,
K.; Keeler, J.; Van, Q. N.; Shaka, A. J. J. Magn. Reson. 1997, 125,
302. (d) Van, Q. N.; Smith, E. M.; Shaka, A. J. J. Magn. Reson. 1999,
141, 191.
(14) (a) Arbuzov, B. A.; Dianova, E. N.; Zabotina, E. Ya. Izv. Akad.
Nauk, Ser. Khim. 1981, 2635. (b) Diallo, O.; Boisdon, M. T.; Lopez, L.;
Malavaud, C.; Barrans, J. Tetrahedron Lett. 1986, 27, 2971. (c)
Arbuzov, B. A.; Dianova, E. N. Dokl. Akad. Nauk SSSR 1980, 255,
1117. (d) Arbuzov, B. A.; Dianova, E. N.; Sharipova, S. M. Izv. Akad.
Nauk, Ser. Khim. 1981, 1600. (e) Litvinov, I. A.; Struchkov, Yu. T.;
Arbuzov, B. A.; Dianova, E. N.; Galeeva, I. Z. Izv. Akad. Nauk, Ser.
Khim. 1983, 2280.
(15) SciFinder Scholar, CAS, American Chemical Society: Colum-
bus, Ohio; 2004.
4034 J. Org. Chem., Vol. 70, No. 10, 2005

Reaction of 1,2-Diaza-1,3-butadienes with Phosphites
according to a typical Hurd-Mori reaction.4 Yields and
reaction times of compounds 8a-b and 9a-c are shown
in Table 2.
SCHEME 2a
Conclusion
The present article describes the general protocol for
the selective preparation of alkyl 3,3-dialkoxy-2H-1,2,3λ5-
diazaphosphole-4-carboxylates in high yields under a
nitrogen atmosphere. To the best of our knowledge, this
represents one of the rare examples reported in the
literature for the synthesis of such products.13-15 Because
the procedure does not require the use of solvent or
additional catalyst, this process is economical, environ-
mentally friendly, and particularly adequate for large-
scale production.16-18
a Reagents and conditions: i, rt, nitrogen atmosphere; ii, rt; iii,
rt, THF + H2O.
In addition, a similar procedure in the presence of
atmospheric moisture permits the selective production
of hydrazonophosphonate derivatives that can be conve-
niently used for the preparation of interesting dimethyl
or diethyl (5-methyl-3-oxo-2,3-dihydro-1H-4-pyrazolyl)-
phosphonates20 and 2-dialkoxyphosphoryl-1,2,3-thiadia-
zoles.4
yl signal at about 1.9 ppm enhances the NH signal at
∼9 ppm and vice versa: this evidence suggests the
proximity of these two groups, which is in good agree-
ment with the E configuration of the CdN center. Yields
and reaction times of compounds 6a-h and 7a-h are
shown in Table 1.
The formation of alkyl 3,3-dialkoxy-2H-1,2,3λ5-diaza-
phosphole-4-carboxylates 6 likely occurs because of the
preliminary nucleophilic attack of the phosphorus at the
terminal carbon atom of the azo-ene system with the
formation of a zwitterionic intermediate (I). The subse-
quent intramolecular attack of the negative nitrogen at
the positive phosphorus atom gives rise to dihydro-
diazaphosphole intermediate II. The conversion of II into
the corresponding diazaphospholes 6 by the loss of an
alcohol molecule is favored by the aromatic character of
these latter compounds (Scheme 3).
Experimental Section
General Methods. Reagents and solvents, workup proce-
dures, and analyses were performed in general as described
in the Supporting Information.
General Procedure for the Synthesis of Alkyl 3,3-
Dialkoxy-2H-1,2,3λ5-diazaphosphole-4-carboxylates 6a-h
(Route A). 1,2-Diaza-1,3-butadienes 5a-g (1 mmol) as a
mixture of E/Z isomers21 and dialkyl phosphites 1a-b (4
mmol) were magnetically stirred for 4.0-7.5 h under nitrogen
atmosphere. The residual trialkyl phosphite was removed
under reduced pressure to give the crude alkyl 3,3-dialkoxy-
2H-1,2,3λ5-diazaphosphole-4-carboxylates 6a-h in good purity.
Further purification can be obtained by crystallization from
ethyl acetate-cyclohexane.
Indeed, hydrazonophosphonates 7 were derived by
hydrolytic ring opening of diazaphosphole 6 through the
intermediate III and the subsequent cleavage of the P-N
bond.
Methyl 2-(Aminocarbonyl)-3,3-dimethoxy-5-methyl-
2H-1,2,3λ5-diazaphosphole-4-carboxylate (6a). White solid;
mp 118-120 °C; IR (Nujol) νmax 3382, 3241, 3195, 1710, 1671
cm-1; 1H NMR (400 MHz, DMSO-d6) δ 2.26 (d, 3Η, 4JHP ) 0.8
This pathway was confirmed by the treatment of
diazaphospholes 6a-h with THF:water (95:5) (Scheme
2, Route C; Table 1), which produced the corresponding
hydrazonophosphonates 7a-h in 24-36 h in quantitative
yields. This behavior was checked by monitoring the
reaction between trimethyl phosphite (1a) and 1,2-diaza-
1,3-butadiene 5a directly in an NMR tube by 31P NMR
spectroscopy. The spectra (in CDCl3) showed a gradual
disappearance of the signal at 57.13 ppm that was
ascribable to compound 6a and the concomitant appear-
ance of that at 20.25 ppm related to 7a.
In turn, the compounds 7a and e can be conveniently
used for the construction of dimethyl or diethyl (5-methyl-
3-oxo-2,3-dihydro-1H-4-pyrazolyl)phosphonates 8a-b by
treatment with sodium hydride in THF at room temper-
ature. The closure to the pyrazolone ring is due to the
intramolecular nucleophilic attack of the NH hydrazonic
nitrogen atom at the ester group with loss of an alcohol
molecule. The concomitant base-promoted hydrolytic
cleavage of the aminocarbonyl group linked to the
nitrogen in position 1 of the pyrazolone also takes place
(Scheme 4).3
3
Hz), 3.68 (s, 3H), 3.84 (d, 6H, JHP ) 13.6 Hz), 5.58 and 6.53
(2 br s, 2H); 13C NMR (100 MHz, DMSO-d6) δ 18.1 (q, JCP
)
3
2
1
6.1 Hz), 50.4 (q), 56.2 (q, JCP ) 6.8 Hz), 59.7 (s, JCP ) 206.7
3
2
Hz), 154.3 (s, JCP ) 8.4 Hz), 156.5 (s, JCP ) 34.9 Hz), 164.9
2
(s, JCP ) 19.0 Hz); 31P NMR (162 MHz, DMSO-d6) δ 57.13;
MS (ESI+) m/z 264 (M+H), 286 (M+Na), 304 (M+K). Anal.
Calcd for C8H14N3O5P: C, 36.51; H, 5.36; N, 15.97. Found: C,
36.39; H, 5.47; N, 16.09.
General Procedure for the Synthesis of E-Hydrazono-
phosphonates 7a-h (Route B). 1,2-Diaza-1,3-butadienes
5a-g (1 mmol) as a mixture of E/Z isomers21 and dialkyl
phosphites 1a-b (4 mmol) were magnetically stirred for 24.0-
96.0 h in the presence of air moisture. The residual trialkyl
phosphite was removed under reduced pressure to give E-
hydrazonophosphonates 7a-h in good purity. Further puri-
fication can be obtained by crystallization from ethyl acetate-
cyclohexane.
General Procedure for the Synthesis of E-Hydrazono-
phosphonates 7a-h (Route C). A solution of alkyl 3,3-
dialkoxy-2H-1,2,3λ5-diazaphosphole-4-carboxylates 6a-h (1
mmol) in tetrahydrofuran:water (9.5:0.5 mL) was magnetically
(20) Khotinen, A. V.; Polozov, A. M.; Alexander, M. Phosphorus,
Sulfur Silicon Relat. Elem. 1993, 83, 53.
(21) (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.
Moreover, the compounds 7a, b, and f readily produced
2-dialkoxyphosphoryl-1,2,3-thiadiazoles 9a-c by treat-
ment with thionyl chloride under solvent-free conditions,
J. Org. Chem, Vol. 70, No. 10, 2005 4035

Attanasi et al.
TABLE 1. Yields and Reaction Times of Alkyl 3,3-Dialkoxy-2H-1,2,3λ5-diazaphosphole-4-carboxylates 6a-h and
E-Hydrazonophosphonates 7a-h
1
R1
5
R2
R3
6
yield (%)
7
yield (%)
time (h)
1a
1a
1a
1a
1b
1b
1b
1b
Me
Me
Me
Me
Et
5a
5b
5c
5d
5b
5e
5f
Me
Et
NH2
6a
6b
6c
6d
6e
6f
98a,b
97a,b
96a,b
96a,b
91a,b
87a,b
88a,b
91a,b
7a
7b
7c
7d
7e
7f
95c
98d
97d
97d
95d
97d
95d
94d
98d
4.0b
6.5b
5.5b
7.5b
6.0b
5.5b
4.5b
7.0b
24.0c
28.0c
72.0c
58.0c
96.0c
60.0c
30.0c
28.0c
24.0d
32.0d
34.0d
28.0d
36.0d
24.0d
26.0d
30.0d
NH2
94a,c
95a,c
93a,c
89a,c
89a,c
91a,c
88a,c
C(CH3)3
NH2
CH2CHdCH2
Et
Bn
Et
Me
NH2
NH2
Et
NH2
Et
Et
NHPh
OC(CH3)3
6g
6h
7g
7h
5g
a Yields of pure isolated products are based on reagents 5a-g. b Route A (Scheme 2). c Route B (Scheme 2). d Route C (Scheme 2);
yields of pure isolated products are based on reagents 6a-h.
SCHEME 3
TABLE 2. Yields and Reaction Times of Dialkyl
(5-Methyl-3-oxo-2,3-dihydro-1H-4-pyrazolyl)phosphonates
8a-b and 2-Dialkoxyphosphoryl-1,2,3-thiadiazoles 9a-c
SCHEME 4
yield time
yield time
7
R1
R2
R3
8
(%)a
89
(h)
9
(%)a
(h)
7a Me Me NH2 8a
1.5
9a
9b
72
77
0.8
1.2
7b Me Et
7e Et Et
7f Et
NH2
NH2 8b
95
2.5
Bn NH2
9c
71
1.0
a Yields of pure isolated products.
General Procedure for the Synthesis of Dialkyl (5-
Methyl-3-oxo-2,3-dihydro-1H-4-pyrazolyl)phospho-
nates 8a-b. To a magnetically stirred solution of hydrazono-
phosphonates 7a and e (1 mmol) in tetrahydrofuran (10 mL),
a stoichiometric amount of sodium hydride (1 mmol) was
added. The conversion into pertinent dialkyl (5-methyl-3-oxo-
2,3-dihydro-1H-4-pyrazolyl)phosphonates 8a-b occurred in
1.5-2.5 h. The reaction mixture was neutralized with Am-
berlyst 15H (2.5 mmol) and left under magnetic stirring for
about 1.0 h. After filtration of the resin and evaporation of
the reaction solvent, products 8a-b were purified by flash
chromatography on a silica gel column and crystallized from
ethyl acetate-cyclohexane.
stirred for 24-36 h. The mixture was dried over anhydrous
sodium sulfate and then the solvent was evaporated under
reduced pressure to give crude hydrazonophosphonates 7a-h
in good purity. Further purification can be obtained by
crystallization from ethyl acetate-cyclohexane.
Methyl 3-[(E)-2-(Aminocarbonyl)hydrazono]-2-(dimeth-
oxyphosphoryl)butanoate (7a). White solid; mp 101-105
°C; IR (Nujol) νmax 3460, 3205, 1744, 1719 cm-1; 1H NMR (400
MHz, CDCl3) δ 2.04 (d, 3Η, 4JHP ) 1.6 Hz), 3.73-3.85 (m, 9H),
Dimethyl (5-Methyl-3-oxo-2,3-dihydro-1H-4-pyrazolyl)-
phosphonate (8a). White solid; mp 200-203 °C; IR (Nujol)
2
1
4.06 (d, 1H, JHP ) 24.4 Hz), 5.47 and 6.09 (2 br s, 2H), 8.91
νmax 3292, 3165, 1730, 1683, 1642 cm-1; H NMR (400 MHz,
(br s, 1H); 13C NMR (100 MHz, CDCl3) δ 15.0 (q), 53.0 (q), 53.6
CDCl3) δ 1.99 (d, 3Η, 4JHP ) 0.4 Hz), 3.48 (d, 6H, 3JHP ) 11.2
2
1
2
(q, JCP ) 7.8 Hz), 54.4 (d, JCP ) 144.2 Hz), 141.3 (s, JCP
)
Hz), 6.78 (br s, 1H), 8.99 (br s, 1H); 13C NMR (100 MHz, CDCl3)
7.6 Hz), 157.7 (s), 166.5 (s, 2JCP ) 4.2 Hz); 31P NMR (162 MHz,
CDCl3) δ 20.25; MS (ESI+) m/z 282 (M+H), 304 (M+Na), 322
(M+K). Anal. Calcd for C8H16N3O6P: C, 34.17; H, 5.74; N,
14.94. Found: C, 33.94; H, 6.02; N, 15.07.
δ 15.8 (q), 51.8 (q, JCP ) 4.6 Hz), 152.6 (s, JCP ) 15.2 Hz),
153.7 (s), 168.5 (s, 2JCP ) 22.7 Hz); MS (ESI+) m/z 207 (M+H),
229 (M+Na), 247 (M+K). Anal. Calcd for C6H11N2O4P: C,
34.96; H, 5.38; N, 13.59. Found: C, 34.84; H, 5.45; N, 13.43.
2
2
4036 J. Org. Chem., Vol. 70, No. 10, 2005

Reaction of 1,2-Diaza-1,3-butadienes with Phosphites
General Procedure for the Synthesis of Alkyl 2-(Di-
alkoxyphosphoryl)-2-(1,2,3-thiadiazol-4-yl)acetates 9a-
c. Hydrazonophosphonates 7a, b, and f (1 mmol) were mag-
netically stirred in thionyl chloride (10 mL) at room temperature
for 0.8-1.2 h. The crude was neutralized with a saturated
aqueous solution of sodium hydrogen carbonate until pH ∼ 7
and then was extracted with ethyl acetate. The organic layer
was washed with water and dried with sodium sulfate.
2-Dialkoxyphosphoryl-1,2,3-thiadiazoles 9a-c were crystal-
lized from diethyl ether-light petroleum ether (40-60 °C).
Methyl 2-(Dimethoxyphosphoryl)-2-(1,2,3-thiadiazol-
4-yl)acetate (9a). Yellow solid; mp 101-103 °C; IR (Nujol)
νmax 3108, 1745, 1720 cm-1; 1H NMR (400 MHz, CDCl3) δ 3.67
[M+], 252 (60), 206 (47), 192 (67), 179 (100). Anal. Calcd for
C7H11N2O5PS: C, 31.58; H, 4.16; N, 10.52. Found: C, 31.61;
H, 4.25; N, 10.23.
Acknowledgment. This work was supported by the
financial assistance from the Ministero dell’Universita`,
dell’Istruzione e della Ricerca (MIUR)-Roma and Uni-
versita` degli Studi di Urbino.
Supporting Information Available: General procedures
for the preparation of compounds 6a-h, 7a-h, 8a-b, and 9a-
c; product characterization data and 1H, 13C, and 31P peak
listing for 6a-h, 7a-h, 8a-b, and 9a-c; 31P spectra from the
reaction between 5a and 1b directly done in NMR tube. This
material is available free of charge via the Internet at
http://pubs.acs.org.
3
3
(d, 3H, JHP ) 11.2 Hz), 3.80 (s, 3H), 3.81 (d, 3H, JHP ) 11.2
Hz), 5.32 (d, 1H, 2JHP ) 24.4 Hz), 8.93 (d, 1H, 4JHP ) 2.4 Hz);
1
13C NMR (100 MHz, CDCl3) δ 45.1 (d, JCP ) 132.0 Hz), 53.4
2
3
(q), 54.0 (q, JCP ) 6.8 Hz), 136.3 (d, JCP ) 3.8 Hz), 153.2 (s,
2JCP ) 6.9 Hz), 166.3 (s, JCP ) 4.5 Hz); MS (EI) m/z 266 (1)
JO050242N
2
J. Org. Chem, Vol. 70, No. 10, 2005 4037