Synthesis and Reactions of 2-Aminotropone-imines Directed toward Synthesis of Tropones Having a Carbon Side-chain

Friedel-Craft反应是在苯基芳环上引入碳侧链的一种很好的方法。然而，该反应不适用于托普隆衍生物，因为托普罗酮与催化剂如三氯化铝形成金属络合物。为了克服这一缺陷，我们研究了N，N‘-二烷基和N，N’-二芳基-2-氨基-2-激动酮亚胺的合成和反应：(1)2-氨基-促性腺激素亚胺的合成：环七[b]-[1，4]苯并恶嗪与脂肪胺反应合成了7个N，N‘-二烷基-2-氨基-2-氨基促性腺激素亚胺，而与芳香胺的反应没有得到相应的2-氨基-促性腺激素亚胺。以1，7，7-三氯三甲基苯二胺为原料合成了N，N‘-二芳基-2-氨基-促性腺激素亚胺类化合物。(2)N，N‘-二烷基-2-氨基-2-甲酰亚胺分别与溴和硝酸反应生成5-溴和5-硝基-N，N’-二烷基-2-氨基-2-甲酰亚胺，但未发生Friedel-Craft酰化反应。2-氨基-激动酮亚胺的环状类似物2，3-二氢-1H-环庚烷[b]吡嗪与酰氯反应，得到N-酰化产物和吡嗪开环产物。另一方面，5-溴-N，N‘-二苄基-2-氨基-促性腺激素亚胺在丁基锂存在下与乙酸乙酯和甲酸甲酯反应，分别得到5-乙酰基和5-甲酰基-2-氨基-促性腺激素亚胺。前者经5-乙酰基-2-苄基氨基-托洛酮水解得到5-乙酰基托波酮。

Friedel-Crafts reaction is an excellent method for introducing a carbon side chain onto an benzenoid aromatic ring. However, the reaction is not applicable to tropolone derivatives because tropolones form metal complexes with catalyst such as aluminum chloride. In order to overcome this defect, we studied the synthesis and reactions of N,N'-dialkyl- and N,N'-diaryl-2-aminotroponeimines.(1) Synthesis of 2-Aminotroponeimines : Seven N,N'-dialkyl-2-aminotroponeimines were obtained by the reactions of cyclohepta[b]-[1,4]benzoxazine with aliphatic amines, while the reactions with aromatic amines did not give the corresponding 2-aminotroponeimines. The N,N'-diaryl-2-aminotroponeimines were prepared by the reactions of 1,7,7-trichlorotropilidene with anilines. A new synthon, 1,2-di-chlorotropylium salt, was also obtained.(2) Reactions of 2-Aminotroponeimines : N,N'-Dialkyl-2-aminotroponeimines reacted with bromine and nitric acid to yield 5-bromo-and 5-nitro-N,N'-dialkyl-2-aminotroponeimines, respectively, but Friedel-Crafts acylation was not achieved. The reactions of 2,3-di-hydro-1H-cyclohepta[b]pyrazine, which is cyclic analog of 2-aminotroponeimines, with acyl chloride gave N-acylated products and pyrazine ring-opened ones. On the other hand, 5-bromo-N,N'-dibenzyl-2-amino-troponeimine reacted with ethyl acetate and methyl formate in the presence of buthyllithium to afford 5-acetyl- and 5-formyl-2-aminotroponeimine, respectively. The former was hydrolyzed to yield 5-acetyl-tropolone via 5-acetyl-2-benzylaminotropone.