DERIVATIVES OF α,β-DIAMINO KETONES
DERIVATIVES OF α,β-DIAMINO KETONES
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α,β-二氨基酮衍生物
DOI：
10.1021/jo01152a015
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发表时间：
1950
期刊：
影响因子：
--
通讯作者：
K. Tsou
中科院分区：
文献类型：
--
作者：
N. Cromwell;K. Tsou
已发现某些α，β-二氨基酮具有温和的禽抗疟活性。将这些α，β-二氨基酮转化为更可溶的衍生物似乎可能增加对它们用于各种类型的药理学筛选测试的兴趣。本实验室的先前研究表明，α，β-二氨基酮中的羰基不容易还原为仲醇官能团2（1）。其他研究表明，将格氏试剂添加到此类酮中会导致叔醇的生成，产率较低（2，3，4）。据推测（3），α，β-二氨基酮中羰基的低反应性由α和β氨基的立体效应引起。因此，似乎合理的是，新的和多功能的还原剂（5），氢化铝锂，可能特别适合于这些空间位阻酮的还原。这些化合物容易被该试剂还原的事实表明，氢化铝锂在这种氢化中的空间需求远小于表面活性催化剂，并且小于异丙醇铝。Trelett和Brown（6）曾研究和讨论过这类氢化反应的机理。由α，S-二溴苄基丙酮与二甲胺反应，以较好的产率合成了α，S-双二甲氨基苄基丙酮。这些研究中使用的其他α，β-二氨基酮是从先前报道的此类化合物列表中选择的代表性类型（7）。所制备的α，β-二氨基醇描述于表I中。在几种情况下，从这些反应混合物中分离出两种异构体产物，可能是不同的外消旋混合物。这些醇中的一些的苯甲酰基和乙酰基衍生物列于表II中。
Certain a,/3-diamino ketones had been found to possess mild avian antimalarial activity. 1 It seemed possible that conversion of these a,/3-diamino ketones to more soluble derivatives might increase the interest in them for various types of pharmacological screen testing. Previous investigations in this laboratory have indicated that the carbonyl group in the a,/3-diamino ketones is not readily re-duced to a secondary alcohol function2 (1). Other studies have shown the addi-tion of Grignard reagents to such ketones resultsin the formation of the tertiary alcohols in low yields (2, 3, 4). It has been postulated (3) that the low reactivity of the carbonyl group in the a,/3-diamino ketones results from thesteric effects of the alpha and beta amino groups. It thus seemed reasonable that the new and versatile reducing agent (5), lithium aluminum hydride, might be especially well suited for the reduction ofthese sterically hindered ketones. The fact that these compounds are readily reduced by this reagent indicates that the steric re-quirement of lithium aluminum hydride in such hydrogenations is considerably less than that of the surface active catalysts, and less than that of aluminum isopropoxide. The mechanism of such related hydrogenations has been investi-gated and discussed byTrevoy and Brown (6). a,/3-Bis-dimethylaminobenzylacetone was prepared in fair yield by the re-action of a,/S-dibromobenzylacetone with dimethylamine. The other a,/3-diamino ketones used in these studies were selected as representative types from the lists of such compounds which have been reported previously (7). The, ß-diamino alcohols which were prepared are described in Table I. In several cases two isomeric products, presumably different racemic mixtures, were isolated from these reaction mixtures. The benzoyl and acetyl derivatives of some of these alcohols are listed in Table II.