A. Hameurlaine et al. / Tetrahedron Letters 43 (2002) 1015–1017
1017
S
equivalent of methyl iodide, the dialkylated pyrazoles
S
8a,b and 9a. 13C NMR spectroscopic analysis showed
that O-alkylation occurred in the case of benzoyl
derivative 3. The 13C NMR signals for methyl or meth-
ylene groups of 8a and 8b are at 56 and 65 ppm,
respectively. However, we were surprised to see that the
tosyl derivative 9a was N-alkylated (13C NMR signal
for methyl at 36 ppm).
O
S
O
N
O
H+
N
S
Ph
O
NH
Ph
N
N
S
Ph
N
O
O
S
16
17
18
When the ring cleavage of hydrazides 3–5 was carried
out in the presence of 2 equiv. or more of t-BuOK, the
cyclization takes another course. Thus, the decomposi-
tion of benzoyl hydrazide 3 followed by alkylation
results in 1,3,4-oxadiazin-5-one derivatives 11a,b. On
the other hand, the tosylhydrazide 4 under the same
conditions yields benzyltolylsulfinate7 as the only iden-
tifiable decomposition product (Table 2).
Scheme 4.
Acknowledgements
We thank the University, the Ministerie voor Weten-
schapsbeleid and the FWO Vlaanderen for their contin-
uing support.
In the case of the benzoyl hydrazide 3, we can rational-
ize the product obtained by the intermediacy of the
alkynethiolate dianion 12, which does not cyclize, but
rather is monoalkylated to the alkynesulfide 13, which
undergoes cyclization to the six-membered ring by
attack of the imidate anion on the alkynesulfide, rather
than the formation of the alternative seven-membered
ring (Scheme 3). The resulting anion 14 is then alky-
lated on nitrogen (13C NMR methyl or methylene
signals for 11a,b at 36 and 52 ppm). We were not able
to isolate monoalkylated oxadiazine derivatives from
this reaction.
References
1. Raap, R.; Micetich, R. G. Can. J. Chem. 1968, 46, 1057.
2. Laishev, V. Z.; Petrov, M. L.; Petrov, A. A. Zh. Org.
Khim. 1982, 18, 281 and 514.
3. (a) Zmitrovich, N. I.; Petrov, M. L. Zh. Obsch. Khim.
1999, 35, 781; (b) Murai, T.; Esaka, T.; Kato, S. Bull.
Chem. Soc. Jpn. 1998, 71, 1193; (c) Murai, T.; Kakami, T.;
Hayashi, A.; Komuro, T.; Takada, H.; Fujii, M.; Kanda,
K.; Kato, S. J. Am. Chem. Soc. 1997, 119, 8592; (d)
L’abbe´, G.; Dehaen, W.; Haelterman, B. J. Chem. Soc.,
Perkin Trans. 1 1994, 2203; (e) Ishihara, H.; Yoshimi, M.;
Kato, S. Angew. Chem. 1990, 102, 572.
4. (a) D’hooge, B.; Smeets, S.; Toppet, S.; Dehaen, W. J.
Chem. Soc., Chem. Commun. 1997, 1753; (b) Abramov, M.
A.; Dehaen, W. Synthesis 2000, 1529.
5. Abramov, M. A.; Dehaen, W.; D’hooge, B.; Petrov, M. L.;
Smeets, S.; Toppet, S.; Voets, M. Tetrahedron 2000, 56,
3933.
Finally, 1,2,3-thiadiazole-4-carbohydrazide 5, after
cleavage of two 1,2,3-thiadiazole rings, recyclization
and alkylation gives the novel fused 7H-pyrazolo[5,1-
b][1,3]thiazine-2,7-diones 15a–c (Table 2). Here we can
assume that the bis(alkynethiolate) 16 is formed first,
which then cyclizes, similar to Scheme 2, to the pyra-
zole-5-thiolate 17. This can undergo a second cycliza-
tion with the formation of a thiazine-6-thiolate 18,
which finally is alkylated to give the products 15a–c
(Scheme 4).
6. Petrov, M. L.; Abramov, M. A.; Dehaen, W.; Toppet, S.
Tetrahedron Lett. 1999, 40, 3903.
7. Maiti, A. K.; Bhattacharyya, P. Tetrahedron 1994, 50, 3.
8. Pain, D. L.; Slack, R. J. Chem. Soc. 1965, 5166.
9. 1-Tosyl-5-(1-hexadecylthio)pyrazol-3-one 7b. To a solu-
tion of hydrazide 4 (1 mmol) in DMSO (5 mL) a solution
of t-BuOK (1 mmol) in DMSO (5 mL) was added and the
reaction mixture was stirred at room temperature for 18 h.
1-Bromohexadecane (1 mmol) was added and after stirring
for 6 h, the solvent was evaporated under reduced pressure
at 40°C. Dichloromethane was added to the residue, the
organic layer was washed twice with water, dried, evapo-
rated, and the reaction product was purified by silica gel
column chromatograpy. Yield of 7b: 30%, mp 116–118°C.
1H NMR (CDCl3, l, ppm): 0.88 (t, 3H, CH3), 1.26 (s,
24H, (CH2)12), 1.40 (txd, 2H, SCH2CH2CH2), 1.68 (txd,
2H, SCH2CH2), 2.42 (s, 3H, CH3), 2.87 (t, 2H, SCH2),
5.65 (s, 1H, CHhet), 7.26 (d, 2H m-CHarom.), 7.85 (d, 2H,
o-CHarom.), and 11.31 (br s, 1H, NHhet). 13C NMR
(CDCl3, l, ppm): 14.5, 22.1 (CH3 tosyl), 23.0, 28.5, 29.2,
29.4, 29.5, 29.8, 30.0, 32.3, 34.4 (CH2S), 99.3 (C4het), 128.5,
130.2, 133.7, 146.0, 148.7 and 166.1 (C5het and Ch3et). MS
495. Found: C, 62.9; H, 8.3; N, 6.0. C26H42N2O3S2. M 495.
Calcd: C, 63.1; H, 8.6; N, 5.7%.
O
O
S
S
HN
N
HN
N
R'X
R'
O
O
Ph
Ph
13
12
O
R'
N
S
11a,b
N
O
Ph
14
Scheme 3.