Reaction of 2-alkylidene-3,1-benzoxathiin-4-ones with nitrones

Full text of DOI:10.1080/10426507.2016.1255620

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Reaction of 2-alkylidene-3,1-benzoxathiin-4-ones with nitrones
Masao Shimizu1,*, Masaki Yamanaka2, Koujiro Kurita2, Shinji Tanaka1, Wataru Ando1, and
Norio Sakai2
1National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi,
Tsukuba, Ibaraki 305-8565, Japan
2Department of Pure and Applied Chemistry, Tokyo, Faculty of Science and Technology,
University of Science (RIKADAI), 2641 Noda, Chiba 278-8510, Japan
*Address correspondence to Masao Shimizu, National Institute of Advanced Industrial Science
and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan. Email:
m.shimizu@aist.go.jp
GRAPHICAL ABSTRACT
Abstract
2-Methylene-3,1-benzoxathiin-4-ones reacted with nitrones at methylene moieties of 3,1-
benzoxathiine rings to yield spiro 1,3-dipolar cycloadducts. The benzoxathiin-4-one rings easily
occurred ring opening reaction with NaOSiMe3 and isoxazolidin-5-one derivatives were obtained
in good yields. As a result, 2-methylene-3,1-benzoxathiin-4-ones can be used as a ketene
equivalent.
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Keywords
1,3-Dipolar addition; spiro cycloadduct; isoxazolidin-5-one; ketene equivalent
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INTRODUCTION
3,1-Benzoxathiin-4-ones can be used as starting materials for other heterocycles. We have
reported that 3,1-benzoxathiin-4-one 1-oxides were synthetic intermediates of 1,2-
benzisothiazol-3-ones.1 When 3,1-benzoxathiin-4-ones were treated with nucleophiles, ring
opening reaction occurred and carbonyl compounds derived from the C-2 carbons of the rings
are formed. During our study of synthesis of 3,1-benzoxathiin-4-ones which have a variety kind
of substituents on the C-2 carbons, we have recently succeeded in two synthetic methods of 2-
alkylidene-3,1-benzoxathiin-4-one derivatives: synthesis from the reaction of S-acylthiosalicylic
acids with dehydrate reagents,2 and from the Pummerer type reaction of 2-alkyl-3,1-
benzoxatuiin-4-ones with trifluoroacetic anhydride.3 Because the 2-alkylidene-3,1-benzoxathiin-
4-ones were regarded as masked ketenes with thiosalicylic acid, it is expected that they operate
as ketene equivalents. Therefore, we carried out 1,3-dipolar cycloaddition of 2-alkylidene-3,1-
benzoxathiin-4-ones with nitrones, and following nucleophilic ring opening reaction.
RESULTS AND DISCUSSION
Reaction of 2-Methylene-3,1-benzoxathiin-4-one with Nitrones
When
2-methylene-3,1-benzoxathiin-4-one
(1a)
was
treated
with
N-(4-chloro-
benzylidene)methylamine oxide (2a) in 1,2-dichloromethane at 140 ºC for 20 min, imide
derivative (3) was obtained in 75% yield. This product was formed by nucleophilic ring-opening
reaction of the 1,3-oxathiine ring with the nitrone oxygen atom instead of 1,3-dipolar
cycloaddition, and successive rearrangement occurred to give 3. It was reported that the similar
product was obtained from the reaction of nitrones with acid chlorides.4
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On the contrary, when the reaction was carried out in toluene, cycloadduct 4a was obtained in
52% yield. Cyclization occurred by attack of the nitrone oxygen atom to the C-2 carbon of 3,1-
benzoxathiine ring. The product which the nitrone oxygen atom attacked to the terminal
methylene group did not obtained. For various kinds of nitrones, similar cycloadducts 4 were
obtained (Table 1). Reactivity of an E-form cyclic nitrone was high and the reaction proceeded
lower reaction temperature (Entry 3) than that of Z-form nitrones. The same type of
cycloaddition also occurred for 2-methylene-3,1-benzoxathiin-4-one 1,1-dioxide (1b) (Entry 4).
Carbonyl Group Formation from Cycloadducts
When 3,1-benzoxathiin-4-ones were treated with some nucleophiles, the reaction
occurred at their carbonyl groups and the following ring-opening reaction produce carbonyl
groups derived from the C-2 carbons of 3,1-benzoxathiin-4-ones. Therefore, we carried out the
reaction of the cyclization products 4 with nucleophiles. Although amines, thiols, and alkoxides
were used as nucleophiles, the aimed product was not obtained. It was reported that sodium
timethylsilanolate was used for hydrolysis of lactone rings.5 This reagent was applied for
cycloadduct 4. As a result, the nucleophile attacked to the benzoxathiine carbonyl group and not
to the carbonyl groups of a product; deprotected products, isoxazolidin-5-one derivatives 5, were
obtained in a good yield. In the case of sulfone derivatives 4d, product purification was easier
than 4a-c because of formation of sulfinic acid derivatives, which was able to be soluble in water,
instead of thiosalicylic acid; purification was possible by extraction for aqueous reaction mixture.
CONCLUSIONS
2-Methylene-3,1-benzoxathiin-4-ones reacted with nitrones to yield 1,3-dipolar
cycloadducts, spiro-isoxazolidines, and the products hydrolyzed to isoxazolidin-5-ones.
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Therefore, 2-methylene-3,1-benzoxathiin-4-ones were regarded as one of the ketene equivalents
in the 1,3-dipolar cycloaddition with nitrones.
Graphic for Table of Contents
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REFERENCES
1. Shimizu, M.; Shimazaki, T.; Yoshida, T.; Ando, W.; Konakahara, T. Tetrahedron, 2012, 68,
3932-3936.
2. Shimizu, M.; Yamanaka, M.; Ando, W.; Shimada, S.; Konakahara, T.; Sakai, N. Heterocycles,
2014, 89, 981-993 (2014).
3. Yamanaka, M.; Shimada, S.; Ando, W.; Konakahara, T.; Sakai, N,; Shimizu, M. Phosphorus,
Sulfur, and Silicon and the Related Elements, 2015, 190, 1307-1308.
4. Heine, H.; Zibuck, K.; VandenHeuvel, W. J. A. J. Am. Chem. Soc., 1982, 104, 3691-3694.
5. Lemoine, H.; Markovic, D.; Deguin, B. J. Org. Chem., 2014, 79, 4358-4366.
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Table 1 Reaction of 1 with nitrones in toluene
:
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Table 2 Deprotection reaction of 4 with NaOSiMe3
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Scheme 1 Reaction of 1 with a nitrone in 1,2-dichloroethane
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