Selective ipso-substitution in pyridine ring and its application for the synthesis of macrocylces containing both oxa- and thia-bridges
✍ Scribed by Naomichi Furukawa; Satoshi Ogawa; Tsutomu Kawai; Shigeru Oae
- Publisher
- Elsevier Science
- Year
- 1983
- Tongue
- French
- Weight
- 244 KB
- Volume
- 24
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
Both the sulfinyl and sulfonyl groups directly bound to 2 or 4 position in pyridine were readily displaced by several nucleophiles such as RO-and RS-. The facility of the leaving groups is RS022RSO>BrzC1))RS (R:alkyl or benzyl). The ipso-substitution could be applied for the synthesis of new type of 2,6-disubstituted macrocycles containg both carbonoxygen and carbon-sulfur bridges in moderate yields. The nucleophilic substitution on pyridine ring takes place more readily than that of simple benzene system, since the halogen atom in 2 or 4-halopyridines can be substituted readily with several nucleophiles such as thiolates while the corresponding substitution of simple halobenzenes does not take place under the same conditions. Recently, we have prepared several new sulfur compounds containing pyridine ring and shown that these alkyl 2-pyridyl sulfoxides or 2,6_disulfinylated pyridine derivatives can be used as phase transfer catalysts. 11 However, the general reactivities of these sulfur compounds bound to pyridine ring have not been well investigated at all. In this communication, we report that the new type of ipso-substitution in pyridine ring and its application for the synthesis of macrocyclic compounds containing pyridine ring. Generally, the preparation of sulfur compounds bound to pyridine ring was carried out by employing the displacement reactions of 2-halo-or 2,6_dihalopyridines with thiolate anions in alcohol. 2) However, when 2,6_dihalopyridines were treated with several thiolates under the phase transfer conditions using quaternary ammonium salts, e.g., tetra-n-butylammonium bromide, and sodium hydroxide as a base in two phase system, the reaction stopped at the mono-substitution stage affording the 2-halo-6-alkylthiopyridines in quantitative yields as shown in Table 1. Furthermore, when one of these products, 2-chloro-6-methylthiopyridine was treated with several nucleophiles such as alkoxides and thiolates in refluxing alcohol, pyridine derivatives bearing two different substituents on 2 or 6 positions, e.g., 2-alkoxy-6-methylthiopyridines were obtained in good yields as shown in Table 2. Moreover, the reaction of 2-chloro-6-methylthiopyridine with several oligoethylene glycols in the presence of sodium hydride as a base in refluxing xylene afforded oligoether bridged methylthiopyridines in good yields as shown in Table 3. These bridged products were readily oxidized to the corresponding sulfone upon treatment with m-chloroperoxybenzoic acid or hydrogen peroxide in quantitative yields as also shown in Table 3. Oxidation of these 2-halo-6-alkylthiopyridine derivatives with m-chloro-C2H50Na reflux 5 no reaction Q-2CH,
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