Expeditious synthesis of new 1,2,3-thiadiazoles and 1,2,3-selenadiazoles from 1,2-diaza-1,3-butadienes via Hurd-Morio-type reactions

Article abstract of DOI:10.1021/jo0264832

α-Substituted hydrazones obtained from 1,2-diaza-1,3-butadienes and methylenic or methinic activated substrates gave rise to a wide range of cyclic compounds. In particular, in the presence of thionyl chloride as solvent-reagent, they were transformed int

Full text of DOI:10.1021/jo0264832

Exp ed itiou s Syn th esis of New 1,2,3-Th ia d ia zoles a n d
1,2,3-Selen a d ia zoles fr om 1,2-Dia za -1,3-bu ta d ien es via
Hu r d -Mor i-Typ e Rea ction s
Orazio A. Attanasi,† Lucia De Crescentini,† Gianfranco Favi,† Paolino Filippone,*,†
Gianluca Giorgi,‡ Fabio Mantellini,† and Stefania Santeusanio†
Istituto di Chimica Organica, Universita` degli Studi di Urbino, Piazza della Repubblica 13,
61029 Urbino, Italy, and Centro Interdipartimentale di Analisi e Determinazioni Strutturali,
Universita` degli Studi di Siena, Via Aldo Moro, 53100 Siena, Italy
filippone@uniurb.it
Received September 26, 2002
R-Substituted hydrazones obtained from 1,2-diaza-1,3-butadienes and methylenic or methinic
activated substrates gave rise to a wide range of cyclic compounds. In particular, in the presence
of thionyl chloride as solvent-reagent, they were transformed into 1,2,3-thiadiazoles,1 with selenium
oxychloride in new 4-substituted 2,3-dihydro-1,2,3-selenadiazoles, while with selenium dioxide, they
were transformed into 4-substituted 1,2,3-selenadiazoles. We have also examined the nucleophilic
behavior of 1,2,3-thiadiazole 4a in the reaction with 1,2-diaza-1,3-butadienes that produced, under
basic conditions, 4-hydrazono-1-(1,2,3-thiadiazolyl)pentane derivatives. This event represents an
interesting example of stereoselective synthesis because it leads exclusively to the formation of
the RR/SS racemic mixture. These latter compounds, treated with thionyl chloride, gave the
corresponding 1,3-di-1,2,3-thiadiazolylpropane derivatives, while with sodium methoxide they
afforded 1,2,3-thiadiazolyl-2-oxo-2,3-dihydro-1H-pyrrole systems.
In tr od u ction
that is also able to determine the regioselectivity of such
attack on the terminal carbon atom. Hence, the synthesis
of R-substituted hydrazone derivatives is obtained as a
consequence of 1,4-conjugated addition (Michael-type) of
nucleophiles to the heterodiene system of 1,2-diaza-1,3-
butadienes. In continuation of our ongoing interest in the
chemistry of 1,2-diaza-1,3-butadienes, we have recently
reported the synthesis of 4-substituted 1,2,3-thiadiazoles
via Hurd-Mori reaction5 from R-substituted hydra-
zones.6-8 Based on this experience and considering the
increased interest in the chemical and bioactive nature
of several organosulfur9-,14 or organoselenium3,15,16 com-
In our 25 years of experience in the field of the
heterocyclic chemistry,2 1,2-diaza-1,3-butadienes were
demonstrated to have considerable potential toward a
wide range of nucleophiles.3,4 This behavior is ascribable
to the presence of the azo group in conjugated azoalkenes
* To whom correspondence should be addressed. Fax: +39-0722-
2907. E-mail: (O.A.A.) attanasi@uniurb.it.
† Universita` degli Studi di Urbino.
‡ Universita` degli Studi di Siena.
(1) Stanetty, P.; Turner, M.; Mihovilovic, M. D. In Targets in
Heterocyclic SystemssChemistry and Properties; Attanasi, O. A.,
Spinelli, D., Eds.; Societa` Chimica Italiana: Rome, 1999; Vol. 3, p 265.
Meier, H.; Hanold, N. In Methoden der Organischen Chemie; Houben-
Weyl, Thieme, G.: Stuttgart, New York, 1994; Vol. E8D, p 60. Thomas,
E. W. In Comprehensive Heterocyclic Chemistry II; Storr, R. C.,
Katritzky, A. R., Rees, C. W., Sriven, E. F. V., Series Eds.; Pergamon:
London, 1996; Vol. 4, p 289.
(4) Clarke, S. J .; Gilchrist, T. L.; Lemos, A.; Roberts, T. G. Tetra-
hedron 1991, 47, 5615. Gilchrist, T. L.; Lemos, A. J . Chem. Soc., Perkin
Trans. 1 1993, 1391.
(5) Attanasi, O. A.; De Crescentini, L.; Filippone, P.; Mantellini, F.
Synlett 2001, 557.
(2) Attanasi, O. A.; Filippone, P. In Topics in Heterocyclic Systems,
Synthesis, Reactions and Properties; Attanasi, O. A., Spinelli, D., Eds.;
Societa` Chimica Italiana: Rome, 1996; Vol. 1, p 157. Attanasi, O. A.;
Filippone, P. Synlett 1997, 1128. Attanasi, O. A.; De Crescentini, L.;
Filippone, P.; Foresti, E.; Mantellini, F. J . Org. Chem. 2000, 65, 2820.
Attanasi, O. A.; De Crescentini, L.; Filippone, P.; Mantellini, F.; Tietze,
L. F. Tetrahedron 2001, 57, 5855. Attanasi, O. A.; De Crescentini, L.;
Filippone, P.; Mantellini, F.; Santeusanio, S. Helv. Chim. Acta 2001,
84, 2379. Rossi, E.; Arcadi, A.; Abbiati, G.; Attanasi, O. A.; De
Crescentini, L. Angew. Chem., Int. Ed. 2002, 41, 1400. Attanasi, O.
A.; De Crescentini, L.; Favi, G.; Filippone, P.; Mantellini, F.; Santeu-
sanio, S. Synthesis 2002, 1546. Attanasi, O. A.; De Crescentini, L.; Favi,
G.; Filippone, P.; Mantellini, F.; Santeusanio, S. J . Org. Chem. 2002,
67, 8178.
(3) Banert, K. In Targets in Heterocyclic SystemssChemistry and
Properties; Attanasi, O. A., Spinelli, D., Eds.; Societa` Chimica Ital-
iana: Rome, 2000; Vol. 3, p 1. Polanc, S. In Targets in Heterocyclic
SystemssChemistry and Properties; Attanasi, O. A., Spinelli, D., Eds.;
Societa` Chimica Italiana: Rome, 2000; Vol. 3, p 33 and references
therein.
(6) Attanasi, O. A.; De Crescentini, L.; Serra-Zanetti, F. Can. J .
Chem. 1994, 72, 2305.
(7) Arcadi, A.; Attanasi, O. A.; Liao, Z.; Serra-Zanetti, F. Synthesis
1994, 605.
(8) Attanasi, O. A.; Filippone, P.; Fiorucci, C.; Foresti, E.; Mantellini,
F. J . Org. Chem. 1998, 63, 9880.
(9) Thomas, E. W.; Nishizawa, E. E.; Zimmermann, D. C.; Williams,
D. J . J . Med. Chem. 1985, 28, 442.
(10) Pain, D. L.; Slack, R. J . Chem. Soc. 1965, 5166. Lewis, G. S.;
Nelson, P. H. J . Med. Chem. 1979, 22, 1214. Lalezari, I.; Shafiee, A.;
Yazdany, S. J . Pharm. Sci. 1974, 63, 628.
(11) Ramsden, S. I.; O¨ gren, S. O.; Ross, S. S.; Stjernstrom, N. E.
Acta Pharm. Suec. 1973, 10, 285.
(12) FMC Corp. U. S. Pat. 3 874 873, 1975; Chem. Abstr. 1973, 78,
97663.
(13) Schurter, R.; Kunz, W.; Nyfeler, R. European Patent Appl. EP
0, 313, 512 A2, 1990; Chem. Abstr. 1990, 112, 17750a. Kunz, W.;
Schurter, R.; Maetzke, T. Pestic. Sci. 1997, 50, 275. Stanetty, P.; Kunz,
W. European Patent Appl. EP 780394A1, 1997; Chem. Abstr. 1997,
127, 121735.
10.1021/jo0264832 CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/07/2003
J . Org. Chem. 2003, 68, 1947-1953
1947

Attanasi et al.
SCHEME 1a
pounds, we have developed a procedure to prepare new
4-substituted 2,3-dihydro-1,2,3-selenadiazoles and 4-sub-
stituted 1,2,3-selenadiazoles following a Hurd-Mori-type
reaction. We have also corrected a methodology for the
preparation of di-1,2,3-thiadiazole and 1,2,3-thiadiazole-
2-oxo-2,3-dihydro-1H-pyrrole systems, thanks to a further
addition of another molecule of 1,2-diaza-1,3-butadiene
onto some 1,2,3-thiadiazoles and a subsequent cyclization
process.
Resu lts a n d Discu ssion
1,2-Diaza-1,3-butadienes 1a -d reacted with activated
methylenic and methinic compounds 2a -h to give R-sub-
stituted hydrazones 3a -m in good to excellent yields
(Scheme 1) by means of 1,4-conjugated addition (Michael
type).6-8
This reaction easily occurred in tetrahydrofuran in the
presence of a catalytic amount of sodium methoxide (for
3a -j) or sodium hydride (for 3k -m ).
In a previous work,5 we described the formation of
1,2,3-thiadiazoles via the Hurd-Mori reaction, starting
from these latter substrates. In fact, at room tempera-
ture, R-substituted hydrazones 3a ,b,d ,e,g,h ,j-l, derived
from 1-tert-butoxycarbonyl-1,2-diaza-1,3-butadienes, read-
ily reacted under solvent-free conditions with thionyl
chloride, both as solvent and reagent, producing 1,2,3-
thiadiazoles 4a -i in good yields (Scheme 1, path A).
Starting from the same compounds 3b,e, new 4-sub-
stituted 2,3-dihydro-1,2,3-selenadiazoles 5a ,b were ob-
tained. The reaction happened in the presence of 2 equiv
of selenium oxychloride,17 in dichloromethane, from -20
°C to room temperature (Scheme 1, path B, Table 1).
Under these mild conditions, the aromatization process
did not occur, and only 2,3-dihydro compounds were
observed. The advantage of this synthetic approach is the
ease of workup: in fact, compounds 5a ,b were achieved
pure solely by addition to the reaction mixture of aqueous
saturated solution of sodium hydrogen carbonate and
subsequent evaporation of the organic solvent.
Instead, semicarbazones 3f,i,m , obtained from 1-ami-
nocarbonyl-1,2-diaza-1,3-butadiene 1d and methinic de-
rivatives such as diethyl phenylmalonate 2c, trimethyl
methanetricarboxylate 2e, and 2,2-dimethyl-5-phenyl-
1,3-dioxane-4,6-dione 2h , produced the pertinent 4-sub-
stituted 1,2,3-selenadiazoles 6a -c by treatment with 3
equiv of selenium dioxide18 in acetic acid at 90 °C. Under
a
Reagents and conditions: (i) THF/rt, MeONa or NaH; (ii)
SOCl2/rt; (iii) SeOCl2 (2 equiv), CH2Cl2/from -20 °C to rt; (iv) SeO2
(3 equiv), AcOH/90 °C.
TABLE 1. Yield s a n d Rea ction Tim es of 4-Su bstitu ted
2,3-Dih yd r o-1,2,3-selen a d ia zoles (5a ,b)
3
R1
R2
R3 R4
R5
5
yielda (%) time (h)
3b Et
3e Me O-t-Bu Ph Et
O-t-Bu
H
Me CO2Me 5a
77
71
12.0
10.0
CO2Et
5b
a
Yield of pure isolated products.
TABLE 2. Yield s a n d Rea ction Tim es of 4-Su bstitu ted
1,2,3-Selen a d ia zoles (6a -c)
3
R1
Me NH2 Ph
Me NH2 CO2Et Et CO2Et 6b
R2
R3
R4
R5
6
yielda (%) time (h)
3f
3i
Et CO2Et 6a
87
75
88
5.0
7.0
8.0
(14) Stanetty, P.; Turner, M.; Mihovilovic, M. D. In Targets in
Heterocyclic SystemssChemistry and Properties; Attanasi, O. A.,
Spinelli, D., Eds.; Societa` Chimica Italiana: Rome, 2000; Vol. 3, p 265.
(15) Mandour, A. H.; El-Shihi, T. H.; Nehad, A. L.; El-Bazza, Z. E.
Phosphorus, Sulfur Silicon Relat. Elem. 1996, 113, 155. Litvinov, V.
P.; Dyachenko, V. D. Russian Chem. Rev. 1997, 66, 923. Bradley, P.
A.; Wilkins, D. J . Prog. Heterocycl. Chem. 1998, 10, 172 and references
therein. Reddy, D. B.; Reddy, M. V. R.; Padmaja, A.; Padmavathi, V.
Phosphorus, Sulfur Silicon Relat. Elem. 1998, 141, 191. Shafiee, A.;
J ialilian, A. R., Rezaei, M. J . J . Heterocycl. Chem. 2000, 37, 1325.
(16) Selenium in Biology and Human Health; Burk, R. F., Ed.;
Springer-Verlag: New York, 1989. Nishihara, T.; Nishikawa, J .;
Kanajama, T.; Dakejama, F.; Saito, K.; Imagawa, M.; Takatori, S.;
Kitagawa, Y.; Hori, S.; Utsumi, H. J . Health Sci 2000, 46, 282. Kim,
Y. Y. J . Anim. Sci. Technol. 2000, 42, 835. Bushnell, D. A.; Cramer,
P.; Kornberg, R. D. Structure 2001, 9, 11. Block, E.; Birringer, M.;
J iang, V.; Nakahodo, T.; Thompson, H. J .; Toscano, P. J .; Vzar, H.;
Zhang, X.; Zhu, Z. J . Agric. Food Chem. 2001, 49, 458. Burling, F. T.;
Goldenstein, B. M. J . Am. Chem. Soc. 1992, 114, 2313.
3m Me NH2 Ph
6c
a
Yield of pure isolated products.
these more drastic conditions, the aromatization process
took place (Scheme 1, path C, Table 2).
Under the same reaction conditions used for 6a -c, the
semicarbazone 3c, obtained from 1-aminocarbonyl-1,2-
diaza-1,3-butadiene 1c and dimethyl malonate 2a , gave
(18) Lalezari, I.; Shafiee, A.; Yalpani, M. Tetrahedron Lett. 1969,
58, 5105. Lalezari, I.; Shafiee, A.; Yalpani, M. Angew. Chem. 1970, 9,
464.
(17) Grandi, R.; Vivarelli, P. J . Chem. Res. 1989, 186.
1948 J . Org. Chem., Vol. 68, No. 5, 2003

Synthesis of New 1,2,3-Thiadiazoles and 1,2,3-Selenadiazoles
SCHEME 2
SCHEME 3a
TABLE 3. Yield s of 2-Eth yl-1,1-d im eth yl-2-
(1,2,3-selen a d ia zol-4-yl)eth a n e-1,1,2-tr ica r boxyla te (6d )
a n d 2-Eth yl-1,1-d im eth yl-2-(1,2,3-selen a d ia zol-4-yl)-
eth ylen e-1,1,2-tr ica r boxyla te (7a )
3 or 9
6
yielda (%)
7
yielda (%)
3c
3c
6d
6d
18b
43c
7a
7a
58b
25c
Yield of pure isolated products. b Yield refers to use of 3.0 equiv
of selenium dioxide. c Yield refers to use of 1.5 equiv of selenium
dioxide.
a
a
Reagents and conditions: (i) THF, MeONa or NaH; (ii) SeO2
(3 equiv), AcOH/90 °C.
TABLE 4. Yield s a n d Rea ction Tim es of r,â-Olefin a ted
Hyd r a zon es (10a -c)
a mixture of two products: the expected 4-ethane-1,2,3-
selenadiazole 6d and 4-ethylene-1,2,3-selenadiazole 7a
produced by means of the carbon-carbon single-bond
oxidation. Products 6d and 7a were separated by chro-
matographic methods, and 7a was found to be the main
component (6d , 18%; 7a , 58%). The best conditions to
enhance the formation of 6d required the use of 1.5 equiv
of selenium dioxide in acetic acid at 90 °C (6d , 43%; 7a ,
25%) (Scheme 2, Table 3).
To obtain pure compound 7a , we planned to start from
R,â-olefinated hydrazones. These latter compounds were
prepared starting from 1,2-diaza-1,3-butadienes 1b-d
with dimethyl or diethyl nitromalonates 8a ,b in tetrahy-
drofuran, using a catalytic amount of sodium hydride
(Scheme 3, Table 4).19
1
R1
R2
8
R3
X
10
yielda (%) time (h)
1c Et
1b Et
1d Me NH2
NH2
O-t-Bu 8b Et
8a Me NO2 10a
68
64
85
7.0
48.0
8.0
NO2 10b
NO2 10c
8b Et
a
Yield of pure isolated products.
SCHEME 4
The reaction proceeded via preliminary formation of
1,4-adduct intermediates 9, and the subsequent elimina-
tion of a nitrous acid molecule produced the expected R,â-
olefinated hydrazones 10a -c. The use of nitromalonate
derivatives furnishes a further contribution to the exis-
tent literature19 for the synthesis of similar compounds.
TABLE 5. Yield s a n d Rea ction Tim es of
2-(1,2,3-Th ia d ia zol-4-yl)eth ylen e-1,1,2-tr ica r boxyla tes
(11a ,b)
10
R1
R2
R3
11
yielda (%)
time (h)
As formerly supposed, R,â-olefinated hydrazone 10a ,
treated with 3 equiv of selenium dioxide in acetic acid at
90 °C, gave only product 7a in 7 h in satisfactory purity
(yield 79%) (Scheme 3).
10b
10c
Et
Me
O-t-Bu
NH2
Et
Et
11a
11b
61
58
1.2
168.0
a
Yield of pure isolated products.
The structure of 1,2,3-selenadiazoles 5a ,b, 6a -d , and
By analogy, R,â-olefinated hydrazones 10b,c, treated
with thionyl chloride as solvent-reagent, at room tem-
perature afforded the relevant 4-ethylene-1,2,3-thiadia-
zole derivatives 11a ,b (Scheme 4, Table 5).
In these types of reactions, the importance of the
leaving group in the Hurd-Mori process was remark-
able: we observed that, in the case of 10b, where the
hydrazino moiety was tert-butyl carbazate, its transfor-
1
7a was confirmed using H and 13C NMR techniques by
the presence of two satellite peaks, due to the coupling
77Se-C-H. In particular, the proton bound to C5 gives
a strong singlet at 9.00-9.50 ppm with a weak doublet
1
(J ) 43-45 Hz) in H NMR, while C5 shows a signal at
135.0-146.0 ppm with a satellite doublet (J ) 134-137
Hz) in 13C NMR, in good agreement with the data
reported in the literature.20
(20) Lalezari, I.; Shafiee, A.; Yalpani, M. J . Org. Chem. 1971, 36,
2836. Petrov, M. L.; Abramov, M. A.; Dehaen, W.; Toppet, S. Tetra-
hedron Lett. 1999, 40, 3903.
(19) Attanasi, O. A.; Ballini, R.; De Crescentini, L.; Filippone, P.;
Mantellini, F. J . Org. Chem. 1999, 64, 9653.
J . Org. Chem, Vol. 68, No. 5, 2003 1949

Attanasi et al.
SCHEME 5a
cess two crystal lattices, i.e., triclinic (12a 1) and ortho-
rhombic (12a 2), are energetically accessible. Both the
polymorphs crystallizes as racemic forms RR/SS. In 12a 1
and 12a 2, geometric parameters are quite close each
other, while significant differences are in the molecular
conformations, mainly due to the orientation of the
carboxymethyl groups and to the hydrazone side chain.
For example, the torsion angle C(5)-C(8)-C(11)-O(12)
is 159.84(14)° in 12a 1, while it is rotated about 184° in
12a 2. The crystal lattices of the two structures are
stabilized by van der Waals interactions.
Indeed, it is noteworthy that the formation of 12a -d
is highly stereoselective, since the reaction produced
exclusively a racemic form of RR/SS enantiomers.
Compounds 12a ,b were then treated with thionyl
chloride both as solvent and reagent, and the 1,3-di-1,2,3-
thiadiazolylpropane derivatives 13a ,b were formed in
good yields (Scheme 5, path B, Table 6).
If compounds 12c,d were worked up with sodium
methoxide in a tetrahydrofuran-methanol mixture, 1,2,3-
thiadiazolyl-2-oxo-2,3-dihydro-1H-pyrrole systems 14a ,b
were obtained, as a 50:50 diastereoisomeric mixture, in
good yields (Scheme 5, path C, Table 6). The reaction
proceeds by means of an intramolecular nucleophilic
attack of the -CdN- nitrogen atom to the ester group
derived from the starting malonate, with consequential
loss of an alcohol molecule.6,21
The NMR spectroscopy and the X-ray evidence un-
equivocally confirmed that the attack of 4a onto the azo-
ene system happened by the carbon in position 1 of the
exo chain because of its major acidity due to the activa-
tion for the presence of two carbonyl groups on this atom.
a
Reagents and conditions: (i) THF/rt, MeONa (0.2 equiv); (ii)
SOCl2/rt; (iii) THF-MeOH/rt; CH3ONa (0.4 equiv).
1
In fact, the H and 13C NMR spectra of compound 13a
TABLE 6. Yield s a n d Rea ction Tim es of
4-Hyd r a zon o-1-(1,2,3-th ia d ia zolyl)p en ta n e Der iva tives
(12a -d ), 1,3-Di-1,2,3-th ia d ia zolylp r op a n e Der iva tives
(13a ,b), a n d 1,2,3-Th ia d ia zolyl-2-oxo-2,3-d ih yd r o-1H-
p yr r ole System s (14a ,b)
(where R1 ) Me) showed a perfect symmetry of the
molecule, in accordance with the suggested structure for
this compound. If the attack of substrate 4a onto 1,2-
diaza-1,3-butadiene had occurred by means of the carbon
atom in position 2 of the exo chain, the structure
resulting from the cyclization in the presence of SOCl2
would not have exhibited the above-mentioned symmetry.
yielda time
yielda time
4
R1
R2
12
(%)
(h)
13, 14
(%)
(h)
4a Me O-t-Bu 12a
4b Et
4d Et
93
94
87
64
0.2
0.2
2.0
2.7
13a
13b
14a
14b
82
60
61
78
4.0
O-t-Bu 12b
2.712
2.0
NH2
12c
12d
Con clu sion
4e Me NH2
1.5
a
Yield of pure isolated products.
In conclusion, this paper reports the elegant and facile
synthesis of new 4-substituted 2,3-dihydroselenadiazoles
and 4-substituted 1,2,3-selenadiazoles as well as of
4-substituted 1,2,3-thiadiazoles. These compounds have
been found to undergo subsequent synthetic transforma-
tions and represent in turn useful entries to di-1,2,3-
thiadiazole and 1,2,3-thiadiazolyl-2-oxo-2,3-dihydro-1H-
pyrrole systems. Organosulfur compounds are interesting
because of their use in medicinal chemistry for the
treatment of thrombosis,9 as antibacterials10 or seda-
tives,11 and in agricultural chemistry as herbicides,12
plant activators, or inducers of systemic acquired resis-
tance (SAR) in plants.13 Otherwise, organoselenium
compounds are the object of interest in connection with
the role of selenium in a second-line antioxidant defense
against lipid autoxidation22 as well as the bioactive
nature of selenium compounds.3,15,16,23
mation into the corresponding 11a occurred in 1.2 h,
while, in the case of 10c, where the hydrazino moiety
was semicarbazide, the reaction to give 11b happened
very slowly (168.0 h).
The presence of two carbonyl groups bound at the
carbon in position 1 of the side chain makes compound
4a able to behave as nucleophile. In fact, under basic
conditions, the 1,4-addition of this substrate to another
molecule of 1,2-diaza-1,3-butadiene 1a -d resulted in the
formation of the corresponding 4-hydrazono-1-(1,2,3-
thiadiazolyl)pentane derivatives 12a -d (Scheme 5, path
A, Table 6).
The 1H and 13C NMR analysis surprisingly revealed
that compounds 12a -d were obtained exclusively as a
sole couple of enantiomers. To determine the exact
configuration, an X-ray crystallographic study was car-
ried out on 12a . It crystallizes as two different poly-
morphs, suggesting that during the crystallization pro-
(21) Attanasi, O. A.; De Crescentini, L.; Filippone, P.; Mantellini,
F. New J . Chem. 2001, 25, 534.
1950 J . Org. Chem., Vol. 68, No. 5, 2003

Synthesis of New 1,2,3-Thiadiazoles and 1,2,3-Selenadiazoles
Gen er a l P r oced u r e for th e Syn th esis of 1,2,3-Th ia d ia -
zoles 4a -i. R-Substituted hydrazones 3a ,b,d ,e,g,h ,j-l (1
mmol) were magnetically stirred in thionyl chloride (10 mL).
The reaction mixture was allowed to stand at room tempera-
ture until the disappearance of 3 (0.1-4.5 h, monitored by
TLC). At the end of the reaction, the crude was neutralized
by adding a saturated aqueous solution of sodium hydrogen
carbonate until pH ∼7 and then extracted with ethyl acetate.
The organic layer was washed with water and dried on sodium
sulfate. Products 4a -i were purified by chromatography on a
silica gel column and then crystallized as follows: 4a from
ethyl acetate-diethyl ether, 4b from ethyl acetate-petroleum
ether (40-60 °C), 4c,d ,g-i from diethyl ether-light petroleum
(40-60 °C), while 4e,f are oils.
Exp er im en ta l Section
Gen er a l Meth od s. Dimethyl malonate (2a ), dibenzyl malo-
nate (2b), diethyl phenylmalonate (2c), diethyl methylmalo-
nate (2d ), triethyl methanetricarboxylate (2e), ethyl 4-nitro-
phenylacetate (2f), 2,2-dimethyl-5-phenyl-1,3-dioxane-4,6-
dione (2h ), dimethyl nitromalonate (7a ), and diethyl nitro-
malonate (7b) were commercial materials and were used
without further purification. 5-Isopropyl Meldrum’s acid de-
rivative (2g) was obtained according to literature procedure.24
Solvents and reagents were purchased and were used without
further purification with the exception of THF, which was
distilled from sodium hydroxide. Light petroleum refers to the
fraction with bp 40-60 °C. 1,2-Diaza-1,3-butadienes 1a -d
were synthesized as standard E/ Z isomeric mixture according
to previously reported procedure.25,26 Melting points were
determined in open capillary tubes and are uncorrected. IR-
FT spectra were obtained as Nujol mulls. Mass spectra were
made at an ionizing voltage of 70 eV. All 1H NMR and 13C
NMR spectra were recorded at 200 or 400 MHz and at 50.32
or 100.65 MHz, respectively, in DMSO-d6 solutions unless
specified otherwise. Chemical shifts (δH) are reported relative
to TMS as internal standard. All coupling constants (J ) values
are given in Hz. Chemical shifts (δC) are reported relative to
DMSO-d6 as internal standard, unless otherwise stated, in a
broad band decoupled mode; the multiplicities were obtained
using 135 and 90° DEPT experiments to aid in assignment
(q ) methyl, t ) methylene, d ) methine, s ) quaternary).
The abbreviations used are as follows: s, singlet; d, doublet;
t, triplet; q, quartet; ept, eptet; m, multiplet; br, broad. All the
NH and NH2 exchanged with D2O. Precoated silica gel plates
0.25 mm were employed for analytical thin-layer chromatog-
raphy and silica gel 60 Å (35-70 µ) for column chromatogra-
phy. All new compounds showed satisfactory elemental analy-
sis (C ( 0.35; H ( 0.30, N ( 0.30). The nomenclature was
generated using ADC/IUPAC Name (version 3.50, 5 Apr 1998),
Advanced Chemistry Development Inc., Toronto, ON (Canada).
Gen er a l P r oced u r e for th e Syn th esis of r-Su bstitu ted
Hyd r a zon es 3a -m . Products 3b,c,f 6 and 3m 7 were obtained
according to the procedures reported in the literature, while
3a ,d -l were synthesized as follows: to a magnetically stirred
solution of 1,2-diaza-1,3-butadienes 1a -d and activated meth-
ylenic and methinic compounds 2a -h (1 mmol) in THF (8 mL)
was added a catalytic amount of sodium methoxide (5.4 mg,
0.1 mmol) or sodium hydride (2.4 mg, 0.1 mmol). The mixture
was allowed to stand at room temperature until the disap-
pearance of the reagents (0.1-24.0 h, monitored by TLC). The
major products 3 were purified by chromatography on a silica
gel column and then crystallized as follows: 3a ,e,g,i-l from
ethyl acetate-light petroleum (40-60 °C), 3b,c,f,m from THF-
n-pentane, and 3d from ethyl ether-light petroleum (40-60
°C), while 3h is an oil.
Tr im eth yl 2-(1,2,3-th ia d ia zol-4-yl)eth a n e-1,1,2-tr ica r -
boxyla te (4a ): mp 119-121 °C; IR νmax 3099, 1740, 1731 cm-1
;
1H NMR δ 3.48 (s, 3 H), 3.62 (s, 3 H), 3.71 (s, 3 H), 4.45 (d, 1
H, J ) 10.5), 5.03 (d, 1 H, J ) 10.5), 9.24 (s, 1 H); 13C NMR δ
44.01 (d), 52.71 (q), 52.77 (q), 52.91 (q), 53.23 (d), 136.41 (d),
156.11 (s), 166.49 (s), 167.14 (s), 169.40 (s); MS m/z 228 (1)
[M+], 257 (24), 225 (100). Anal. Calcd for C10H12N2O6S: C,
41.67; H, 4.20; N, 9.72. Found: C, 41.85; H, 4.41; N, 9.78.
Gen er a l P r oced u r e for th e Syn th esis of 4-Su bstitu ted
2-(t er t -b u t oxyca r b on yl)-2,3-d ih yd r o-1,2,3-se le n a d ia -
zoles 5a ,b. To a magnetically stirred solution of R-substituted
hydrazones 3b,e (1.0 mmol) in dichloromethane (20 mL) was
added selenium oxychloride (2.0 equiv) at -20 °C. The reaction
mixture was allowed to stand at -20 °C for 4.0 h and then
was slowly warmed at room temperature (6.0 h). The formation
of compounds 5a ,b were detected by TLC. The reaction
mixture was washed with an aqueous saturated solution of
sodium carbonate (2 × 20 mL) and dried with sodium sulfate.
This workup procedure gave pure 5a ,b as oils.
2-Eth yl 1,1-d im eth yl-2-[2-(ter t-bu toxyca r bon yl)-2,3-d i-
h yd r o-1,2,3-selen a d ia zol-4-yl]et h a n e-1,1,2-t r ica r b oxyl-
1
a te (5a ): IR νmax 3105, 1745, 1725 cm-1; H NMR (CDCl3) δ
1.19 (t, 3 H, J ) 7.2), 1.56 (s, 9 H), 3.66 (s, 3 H), 3.80 (s, 3 H),
4.03-4.17 (m, 3 H), 4.36 (d, 1 H, J ) 7.2), 9.40 (s, 1 H), 9.63
(brs, 1 H); 13C NMR (CDCl3) δ ) 14.11 (q), 28.34 (q), 40.87 (d),
50.22 (d), 53.63 (q), 53.81 (q), 62.86 (q), 83.84 (s), 143.02 (s),
151.59 (s), 167.84 (s), 168.15 (s), 168.34 (s), 190.95 (s); MS m/z
454 (1) [M+ + 3], 452 (3) [M+ + 1], 450 (2), 449 (1), 448 (1),
423 (4), 421 (18), 419 (8), 418 (3), 364 (23), 362 (100). Anal.
Calcd for C16H24N2O8Se: C, 42.58; H, 5.36; N, 6.21. Found:
C, 42.71; H, 5.49; N, 6.15.
Gen er a l P r oced u r e for th e Syn th esis of 4-Su bstitu ted
1,2,3-Selen a d ia zoles 6a-d a n d 7a . To a magnetically stirred
solution of R-substituted hydrazones 3f,i,m (1.0 mmol) in acetic
acid (15 mL) was added selenium dioxide (3.0 equiv) at 90 °C.
The reaction mixture was allowed to stand at 90 °C until the
disappearance of R-substituted hydrazones 3f,i,m (5 h, moni-
tored by TLC). When selenium dioxide (1.5 or 3.0 equiv) was
added to a solution of 3c (1 mmol) in acetic acid (15 mL), we
observed the concomitant formation of compounds 6d and 7a
(the synthesis of pure 7a is described below). The reaction
solvent was removed under reduced pressure, and products
6a -d were purified by chromatography on a silica gel column
and obtained as brown oils.
Tr im eth yl 3-[2-(ter t-bu toxycar bon yl)h ydr azon o]bu tan e-
1,1,2-tr ica r boxyla te (3a ): mp 133-135 °C; IR νmax 3236,
3160, 1754, 1742, 1727, 1700 cm-1; H NMR δ 1.41 (s, 9 H),
1
1.84 (s, 3 H), 3.60 (s, 3 H), 3.62 (s, 3 H), 3.64 (s, 3 H), 3.86 (d,
1 H, J ) 10.8), 4.07 (d, 1 H, J ) 10.8), 9.67 (s, 1 H); 13C NMR
δ 16.61 (q), 28.71 (q), 51.87 (d), 53.22 (q), 53.33 (q), 53.41 (d),
53.46 (q), 80.04 (s), 153.42 (s), 167.99 (s), 168.54 (s), 170.51
(s); MS m/z 360 (6) [M+], 358 (22), 304 (17), 287 (18), 273 (36),
241 (100). Anal. Calcd for C15H24N2O8: C, 50.00; H, 6.71; N,
7.77. Found: C, 49.89; H, 6.59; N, 7.85.
1,1-Dieth yl 2-m eth yl 2-(1,2,3-selen a d ia zol-4yl)-1-p h en -
yleth a n e-1,1,2-tr ica r boxyla te (6a ): IR νmax 3077, 1762, 1749,
1736, 1469, 1460 cm-1 1H NMR (CDCl3) δ 1.22-1.34 (m, 6
;
(22) Coultate, T. P. Food, The Chemistry of the Components; Royal
Society of Chemistry: London, 1984; p 174.
(23) Shafiee, A.; Lalezari, I.; Yazdani, S.; Pournorouz, A. J . Pharm.
Sci. 1973, 62, 839. Lalezari, I.; Shafiee, A.; Yazdani, S. J . Pharm. Sci.
1974, 63, 628.
(24) Chan, C. C.; Huang, X. Synthesis 1984, 224. Hrubowchak, D.
M.; Smith, F. X. Tetrahedron Lett. 1983, 24, 4951.
(25) Sommer, S. Tetrahedron Lett. 1977, 117. Attanasi, O. A.;
Filippone, P.; Mei, A.; Santeusanio, S. Synthesis 1984, 671. Attanasi,
O. A.; Filippone, P.; Mei, A.; Santeusanio, S. Synthesis 1984, 873.
(26) Sheldrick, G. M. SHELXL-97; Rel. 97-2, Universita¨t Go¨ttingen,
1997.
H), 3.73 (s, 3 H), 4.28-4.38 (m, 4 H), 5.70 (s, 1 H), 7.07-7.20
(m, 5 H), 8.94 (s, 1 H); 13C NMR (CDCl3) δ 13.73 (q), 13.88 (q),
52.06 (d), 52.65 (q), 62.19 (t), 62.43 (t), 65.97 (s), 127.68 (d),
128.70 (d), 134.57 (s), 143.32 (d), 155.63 (s), 166.72 (s), 169.72
(s), 170.54 (s); MS m/z 442 (1) [M+ + 2], 440 (10) [M+] 438 (4),
437 (1), 436 (1), 413 (1), 411 (13), 409 (5), 407 (1), 397 (5), 395
(27), 393 (15), 391 (4), 354 (13), 352 (100). Anal. Calcd for
C
18H20N2O6Se: C, 49.09; H, 4.58; N, 6.36. Found: C, 49.15;
H, 4.61; N, 6.31.
J . Org. Chem, Vol. 68, No. 5, 2003 1951

Attanasi et al.
2-Eth yl 1,1-d im eth yl 2-(1,2,3-selen a d ia zol-4yl)eth yl-
3.55 (s, 3 H), 3.59 (s, 3 H), 3.67 (s, 3 H), 3.71 (s, 3 H), 5.48 (s,
1 H), 8.95 (s, 1 H), 9.68 (brs, 1 H); 13C NMR δ 18.97 (q), 29.00
(q), 47.72 (d), 53.08 (q), 53.19 (q), 53.64 (q), 56.41 (d), 60.27
(s), 80.10 (s), 139.82 (d), 146.05 (s), 153.48 (s), 156.33 (s), 169.06
(s), 169.49 (s), 169.75 (s), 170.83 (s); MS m/z 516 (4) [M+], 485
(4), 429 (18), 398 (100). Anal. Calcd for C20H28N4O10S: C, 46.51;
H, 5.46; N, 10.85. Found: C, 46.65; H, 5.41; N, 10.77.
X-r a y Cr ysta l Str u ctu r e Deter m in a tion of 12a . Single
crystals of 12a were obtained by dissolving a few milligrams
in methanol and allowing the solution to concentrate at room
temperature. Two set of crystals were obtained: needles
(approximate dimensions 0.5 × 0.2 × 0.2 mm) and prisms
(approximate dimensions 0.5 × 0.4 × 0.4 mm). A Siemens P4
four-circle diffractometer with graphite-monochromated Mo
KR radiation (λ ) 0.710 73 Å) and the ω/2θ scan technique
were used for data collections.
The two structures were solved by direct methods imple-
mented in the SHELXS-97 program. [Sheldrick, G. M.
SHELXL-97, Rel. 97-2, Universita¨t Go¨ttingen, 1997] The
refinements were carried out by full-matrix anisotropic least-
squares methods on F2 for all reflections for non-H atoms by
using the SHELXL-97 program.26 The two sets of crystals were
revealed to be two different polymorphs (12a 1 and 12a 2) of
the same molecule. In the structure of polymorph 2, disorder
at the tert-butyl group has been treated by refining two
different positions for atoms C(22) and C(23). The refined site
occupation factors are 0.55(6) for one position and 0.45(6) for
the other.
en e-1,1,2 tr ica r boxyla te (7a ): IR νmax 3071, 1742, 1729, 1700
1
cm-1; H NMR (CDCl3) δ 1.39 (t, 3 H, J ) 7.2), 3.86 (s, 3 H),
3.88 (s, 3 H), 4.45 (q, 2 H, J ) 7.2), 9.44 (s, 1 H); 13C NMR
(CDCl3) δ 14.22 (q), 53.21 (d), 53.52 (q), 63.01 (t), 127.58 (s),
136.07 (s), 146.31 (d), 163.31 (s), 165.24 (s), 166.01 (s), 169.29
(s); MS m/z 348 (1) [M+], 319 (1), 317 (20), 315 (12), 314 (2),
313 (2), 262 (17), 260 (100). Anal. Calcd for C11H12N2O6Se: C,
37.93; H, 3.48; N, 8.05. Found: C, 37.81; H, 3.52; N, 8.19.
Gen er a l P r oced u r e for th e Syn th esis of r,â-Olefin a ted
Hyd r a zon es 10a -c. To a magnetically stirred solution of 1,2-
diaza-1,3-butadienes 1b,d and dimethyl or diethyl nitromalo-
nate (8a ,b) in THF (8 mL) was added a catalytic amount of
sodium hydride (2.4 mg, 0.1 mmol). The stirring was main-
tained until the disappearance of the reagents (7.0-48.0 h,
monitored by TLC). The products 10a -c were purified by
chromatography on a silica gel column and then crystallized
from ethyl acetate-light petroleum.
1,1-Dim eth yl 2-eth yl 3-[2-(a m in oca r bon yl)h yd r a zon o]-
bu t-1-en e-1,1,2-tr ica r boxyla te (10a ): mp 170-173 °C; IR
1
νmax 3476, 3234, 1742, 1729, 1698 cm-1; H NMR δ 1.24 (t, 3
H, J ) 7.0), 1.86 (s, 3 H), 3.71 (s, 3 H), 3.72 (s, 3 H), 4.25 (q,
2 H, J ) 7.0), 6.01 and 6.52 (2 brs, 2 H), 10.07 (s, 1 H); 13C
NMR δ 19.51 (q), 19.82 (q), 58.59 (q), 58.88 (q), 67.81 (t), 143.73
(s), 150.01 (s), 156.04 (s), 161.79 (s), 168.71 (s), 170.93 (s),
171.01 (s); MS m/z 315 (1) [M+], 213 (32), 181 (24), 167 (100).
Anal. Calcd for C12H17N3O7: C, 45.72; H, 5.43; N, 13.33.
Found: C, 45.61; H, 5.51; N, 13.28.
Gen er a l P r oced u r e for th e Syn th esis of P u r e 4-Su b-
stitu ted 1,2,3-Selen a d ia zole 7a . To a magnetically stirred
solution of R,â-olefinated hydrazone 10a (1.0 mmol) in acetic
acid (15 mL) was added selenium dioxide (3.0 equiv) at 90 °C.
The reaction mixture was allowed to stand at 90 °C for 7.0 h,
until the disappearance of 10a (monitored by TLC). The
reaction solvent was removed under reduced pressure, and
product 7a was purified by chromatography on a silica gel
column.
Gen er a l P r oced u r e for th e Syn th esis of 4-Eth ylen e-
1,2,3-Th ia d ia zoles 11a ,b. R,â-Olefinated hydrazones 10b,c
(1 mmol) were magnetically stirred in thionyl chloride (10 mL).
The reaction mixture was allowed to stand at room tempera-
ture until the disappearance of 10 (1.2-168.0 h, monitored
by TLC). At the end of the reaction, the crude was neutralyzed
by adding a saturated aqueous solution of sodium hydrogen
carbonate until pH ∼7 and then extracted with ethyl acetate.
The organic layer was washed with water and dried on sodium
sulfate. Products 11a ,b were purified by chromatography on
a silica gel column and obtained as yellow oils.
Tet r a m et h yl (3RS,5RS)-4-[2-(a m in oca r b on yl)h yd r a -
zon o]-1-(1,2,3-t h ia d ia zol-4-yl)p en t a n e-1,2,2,3-t et r a ca r -
boxyla te (12c): mp 173-177 °C; IR νmax 3471, 3450, 3221,
1749, 1734, 1703, 1607 cm-1; 1H NMR δ 1.65 (s, 3 H), 3.23 (s,
1 H), 3.56 (s, 3 H), 3.59 (s, 3 H), 3.64 (s, 3 H), 3.71 (s, 3 H),
5.32 (s, 1 H), 6.27 and 6.58 (2 brs, 2 H), 8.91 (s, 1 H), 9.47 (s,
1 H); 13C NMR δ 18.80 (q), 47.88 (d), 53.33 (q), 53.47 (q), 53.52
(q), 53.64 (q), 56.05 (d), 60.21 (s), 140.08 (d), 142.95 (s), 155.89
(s), 157.57 (s), 168.81 (s), 169.52 (s), 170.64 (s), 171.60 (s); MS
m/z 459 (6) [M+], 428 (8), 414 (31), 400 (61), 354 (28), 327 (63),
316 (100). Anal. Calcd for C16H21N5O9S: C, 41.83; H, 4.61; N,
15.24. Found: C, 41.68; H, 4.63; N, 15.17.
Gen er a l P r oced u r e for th e Syn th esis of 1,3-Di-1,2,3-
th ia d ia zolylp r op a n e Der iva tives 13a ,b. 4-Hydrazono-1-
(1,2,3-thiadiazolyl)pentane derivatives 12a ,b (1 mmol) were
magnetically stirred in thionyl chloride (10 mL). The reaction
mixture was allowed to stand at room temperature until the
disappearance of 12a ,b (2.7-4.0 h, monitored by TLC). At the
end of the reaction, the crude was neutralized by adding
saturated aqueous solution of sodium hydrogen carbonate until
pH ∼7 and then extracted with ethyl acetate. The organic layer
was washed with water and dried on sodium sulfate. Products
13a ,b were purified by chromatography on a silica gel column
and then crystallized from diethyl ether-light petroleum (40-
60 °C).
1,1,2-Tr ieth yl 2-(1,2,3-th ia d ia zol-4-yl)eth ylen e-1,1,2-tr i-
1
ca r boxyla te (11a ): IR νmax 3108, 1740, 1725, 1640 cm-1; H
NMR (CDCl3) δ 1.22-1.39 (m, 9 H), 4.28-4.48 (m, 6 H), 8.65
(s, 1 H); 13C NMR (CDCl3) δ 14.36 (q), 14.39 (q), 14.48 (q), 63.13
(t), 63.30 (t), 63.57 (t), 130.41 (s), 134.76 (s), 138.39 (d), 155.68
(s), 163.74 (s), 165.42 (s), 166.86 (s); MS m/z 328 (1) [M+], 283
(25), 252 (12), 212 (100). Anal. Calcd for C13H16N2O6S: C,
47.56; H, 4.91; N, 8.53. Found: C, 47.45; H, 4.99; N, 8.65.
Gen er a l P r oced u r e for th e Syn th esis of 4-Hyd r a zon o-
1-(1,2,3-th ia d ia zolyl)p en ta n e Der iva tives 12a -d . To a
magnetically stirred solution of 1,2,3-thiadiazole 4a and
sodium methoxide (0.2 mmol) in tetrahydrofuran (6 mL) was
added dropwise a solution of 1,2-diaza-1,3-butadienes 1a -d
in THF (6 mL). The reaction mixture was allowed to stand at
room temperature until the disappearance of the reagents
(0.2-2.7 h, monitored by TLC). Products 12a -d were purified
by chromatography on a silica gel column and then crystallized
as follows: 12a ,d from diethyl ether-light petroleum (40-60
°C), 12b from ethyl acetate-cyclohexane, and 12c from
tetrahydrofuran.
Tet r a m et h yl (1RS,3RS)-1,3-d i(1,2,3-t h ia d ia zol-4-yl)-
p r op a n e-1,2,2,3-tetr a ca r boxyla te (13a ): mp 153-155 °C;
1
IR νmax 3114, 3098, 1742 cm-1; H NMR δ 3.52 (s, 6 H), 3.77
(s, 6 H), 4.73 (s, 2 H), 8.88 (s, 2 H); 13C NMR δ 47.79 (d), 52.65
(q), 53.12 (q), 60.28 (s), 139.63 (d), 154.69 (s), 168.69 (s), 169.13
(s); MS m/z 412 (31) [M+], 383 (100). Anal. Calcd for
C
15H16N4O8S2: C, 40.54; H, 3.63; N, 12.61. Found: C, 40.66;
H, 3.48; N, 12.78.
Gen er a l P r oced u r e for th e Syn th esis of 1,2,3-Th ia d ia -
zolyl-2-oxo-2,3-d ih yd r o-1H-p yr r ole System s 14a ,b. To a
magnetically stirred solution of 4-hydrazono-1-(1,2,3-thiadia-
zolyl)pentane derivatives 12c,d (1 mmol) in THF/MeOH
mixture (5:5 mL) was added sodium methoxide (9.6 mg, 0.4
mmol). The stirring was allowed to stand at room temperature
until disappearance of the reagents (1.5-2.0 h, monitored by
TLC). Products 14a ,b were purified by chromatography on a
silica gel column and then crystallized from ethyl acetate-
light petroleum (40-60 °C) as 50:50 diastereoisomeric mix-
tures.
Tetr a m eth yl (3RS,5RS)-4-[2-(ter t-bu toxyca r bon yl)h y-
d r a zon o]-1-(1,2,3-t h ia d ia zol-4-yl)p en t a n e-1,2,2,3-t et r a -
ca r boxyla te (12a ): mp 175-177 °C; IR νmax 3289, 3156, 1759,
1733 cm-1; 1H NMR δ 1.47 (s, 9 H), 1.60 (s, 3 H), 3.16 (s, 1 H),
1952 J . Org. Chem., Vol. 68, No. 5, 2003

Synthesis of New 1,2,3-Thiadiazoles and 1,2,3-Selenadiazoles
Dim eth yl 1-[(am in ocar bon yl)am in o]-5-m eth yl-3-[m eth -
yl (1,2,3-th ia d ia zol-4-yl)m eth yl-1-ca r boxyla te]-2-oxo-2,3-
d ih yd r o-1H-p yr r ole-3,4-d ica r boxyla te (14a ): mp 202-204
°C; IR νmax 3297, 3156, 1745, 1717, 1675, 1609 cm-1; 1H NMR
δ 1.97 and 2.12 (2 s, 3 H), 3.29, 3.42, 3.57, 3.62, 3.64 and 3.69
(6 s, 9 H), 5.59 and 5.62 (2 s, 1 H), 5.88, 6.17 and 6.52 (3 brs,
2 H), 8.99 and 9.03 (2 s, 1 H), 9.08 and 9.24 (2 brs, 1 H); 13C
NMR δ 14.70 (q), 14.96 (q), 46.78 (d), 47.43 (d), 51.83 (q), 52.03
(q), 53.26 (q), 53.43 (q), 54.13 (s), 54.26 (q), 59.13 (s), 59.64 (s),
103.17 (s), 103.29 (s), 138.83 (d), 139.12 (d), 155.97 (s), 156.08
(s), 157.39 (s), 157.84 (s), 159.33 (s), 159.46 (s), 162.52 (s),
162.94 (s), 166.79 (s), 167.07 (s), 169.40 (s), 169.57 (s), 170.85
(s), 171.79 (s); MS m/z 427 (9) [M+], 411 (10), 383 (51), 368
(20), 353 (35), 338 (18), 278 (38), 251 (100). Anal. Calcd for
Ack n ow led gm en t. This work was supported by
financial assistance from the Ministero dell’Universita`
e della Ricerca Scientifica e Tecnologica-MURST-Roma
(National Project “Building-blocks da e/o per sistemi
eterociclici. Processi innovativi e sintesi di molecole di
potenziale attivita` biologica”), the Consiglio Nazionale
delle Ricerche-CNR-Roma, and the Universita` degli
Studi di Urbino.
Su p p or tin g In for m a tion Ava ila ble: Yields and reaction
times for compounds 3a -m and 4a -i. Product characteriza-
tion data, 1H and 13C NMR peak listings for 3b-m , 4b-i, 5b,
6b-d , 10b,c, 11b, 12b,d , 13b, and 14b. ORTEPS and X-ray
data for 12a . This material is available free of charge via the
Internet at http://pubs.acs.org.
C
15H17N5O8S: C, 42.15; H, 4.01; N, 16.39. Found: C, 42.19;
H, 4.13; N, 16.27.
J O0264832
J . Org. Chem, Vol. 68, No. 5, 2003 1953