Synthesis of pyridines by Diels-Alder reactions of hetero-substituted 1,2,4-triazines with enamines and an enaminone
Synthesis of pyridines by Diels-Alder reactions of hetero-substituted 1,2,4-triazines with enamines and an enaminone
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DOI：
10.1021/jo00267a007
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发表时间：
1989-03
影响因子：
3.6
通讯作者：
E. Taylor;J. Macor
中科院分区：
文献类型：
--
作者：
E. Taylor;J. Macor
H、烷基或芳基)。本文叙述了从单环酮和杂环酮衍生的(烷硫基)-和烷氧基-L，2，4-三嗪和烯胺合成取代吡啶。还详细描述了1，2，4-三氮杂环己烷与烯胺酮之间的第一个逆电子需求Diels-Alder反应。L，2，4-三嗪-6-硫酮2，2，4-三嗪-6-硫酮2，2，4-三氮-6-酮(L)3与P2S5反应制得，用三乙胺去质子化，得到的阴离子在室温下与活性卤代烷(甲基碘、溴)在硫磺上进行缓慢的烷基化反应。硫化物3与1或2当量的间氯苯甲酸氧化得到相应的6-(al-Ky-亚磺基)-或6-(烷基磺酰基)-1，2，4-三嗪4或5(方案II)。事实证明，4和5对亲核剂都非常敏感，亲核剂攻击这些化合物的未取代的3位，导致三嗪的分解。4例如，5b与1当量的吡咯烷在室温下反应生成L-(苯磺酰基)丙酮(13)，5主要是通过胺在3-位上的亲核加成(方案III)，然后进行反Diels-Alder反应并消除氮(在反应的快速过程中可以观察到)，然后在处理后再水解到13。6-烷氧基-L，2，4-三嗪因此不能通过4或5与醇类化合物反应得到，因为在(3)Taylor，EC；Macor，J.E.J.杂环上受到攻击。化学。(4)普林斯顿大学Macor，Je博士论文，1986年5月。(5)从5b和吡咯烷的反应中以43%的产率分离出(苯磺酰基)丙酮，MP 72.0-73.5C：Ir(KbR)1710,1605,1495,1410 cm“1；(CDC13)7.43-7.42(m，
H, alkyl, or aryl). We describe in this paper the synthesis of substituted pyridines from (alkylthio)-and alkoxy-l, 2, 4-triazines and enamines derivedfrom both simple and heterocyclic ke-tones. The first inverse electron demand Diels-Alder re-action between a 1, 2, 4-triazine and an enaminone is also detailed. l, 2, 4-Triazine-6-thiones 2, prepared by reaction of the corresponding l, 2, 4-triazin-6-ones (l) 3 with P2S5, were deprotonated with triethylamine; the resulting anions underwent slow alkylation on sulfur at room temperature with reactive alkyl halides (methyl iodide, benzyl bromide). Oxidation of the resulting sulfides 3 with 1 or2 equiv of m-chloroperbenzoic acid led to the corresponding 6-(al-ky lsulfinyl)-or 6-(alkylsulfonyl)-1, 2, 4-triazines 4 or 5, re-spectively (Scheme II). Both 4 and 5 proved to be ex-tremely sensitive toward nucleophiles, which attacked these compounds atthe unsubstituted 3-position leading to decomposition of the triazine. 4 Forexample, treatment of 5b with 1 equiv of pyrrolidine at room temperature led to the formation of l-(benzylsulfonyl) acetone (13), 5 ap-parently by nucleophilic addition of the amineto the 3-position (Scheme III), followed by a retro-Diels-Alder reaction with elimination of nitrogen (which could be ob-served during the rapid course of the reaction), and sub-sequent hydrolysis to 13 upon workup. 6-Alkoxy-l, 2, 4-triazines could thus not be prepared by reaction of 4 or 5 with alkoxides, since attack at position (3) Taylor, EC; Macor, J. E. J. Heterocycl. Chem. 1985, 22, 409.(4) Macor, JE Ph. D. Thesis, Princeton University, May, 1986.(5)(Benzylsulfonyl) acetone was isolated in 43% yield from the reac-tion of 5b and pyrrolidine as a white crystalline solid, mp 72.0-73.5 C: IR (KBr) 1710, 1605, 1495, 1410 cm" 1; NMR (CDC13) 7.43-7.42 (m,