Reactions of perhaloacetones with dihydropyridines and other electron donors
Reactions of perhaloacetones with dihydropyridines and other electron donors
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全卤丙酮与二氢吡啶和其他电子给体的反应
DOI：
10.1021/jo00880a011
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发表时间：
1976
期刊：
影响因子：
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通讯作者：
C. S. Greene
中科院分区：
文献类型：
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作者：
D. Dittmer;A. Lombardo;F. Batzold;C. S. Greene
3-取代的1-苄基-1,4-二氢吡啶还原六氯丙酮的动力学在每种反应物中都是一级的。还原速率对3个取代基的吸电子能力敏感。在二氢吡啶环的3或1位上连接吲哚部分至多导致速率的小幅下降。 3-氨基甲酰基-和3-氰基二氢吡啶还原的活化能很低（5-7 kcal mol-1），并且活化熵非常负（-46，-47 eu）。 3-氨基甲酰基衍生物的还原反应在乙腈中比在苯中快 33 倍。六氯丙酮、五氯丙酮和对四氯丙酮与1-苄基-3-氨基甲酰基-1,4-二氢吡啶-4-d反应中产物形成步骤中的同位素效应(ku/ko)基本上与卤代酮的性质无关。当二氢吡啶和卤代酮混合时，观察到紫外-可见光谱的变化，表明中间配合物可能干预还原反应。尽管电子自旋共振研究表明这些反应中缺乏可检测到的自由基，但从N,N,N',N'-四甲基对苯二胺到六氟丙酮发生单电子转移，产生胺的阳离子自由基。五氯丙酮是六氯丙酮和二胺的产物。乙腈中的 1, 4, 4-三甲基-1, 4-二氢吡啶与六氯丙酮或四氯苯醌混合时会产生高度着色的溶液。无法从这些反应中鉴定产物。1-取代的 1, 4-二氢烟酰胺对硫代二苯甲酮 1 和卤代酮 2 的有效非酶还原类似于辅酶 NADH 对简单羰基的生物还原。电负性卤素原子增强了卤代酮中羰基还原的容易性，这一发现与当存在吸电子取代基时硫代二苯甲酮中硫代羰基还原速率的增加以及NADH模型中缺电子硝基和亚硝基还原速率的增加一致。 3·4 最近，Creighton 和 Sigman 发现，1,10-菲咯啉-2-甲醛的羰基与锌离子络合，可以使其被 1,4-二氢烟酰胺有效还原。 6 金属离子还有助于通过 NADH 模型还原磷酸吡哆醛、6 羟基酮的还原以及丙酮酸和苯甲酰甲酸 7 的酯的立体选择性还原。在通过二氢烟酰胺生物还原羰基的模型系统中，没有一个简单的、未活化的羰基被有效地还原；需要金属离子或高负电性羰基化合物。上述这些例子涉及氢从 NADH 模型转移到底物。 NADH 模型还能够进行电子捐赠、8 和 1 电子转移至四氰乙烯、9 醌、10 N-甲基吩嗪鎓
The kinetics of the reduction of hexachloroacetone by 3-substituted l-benzyl-l, 4-dihydropyridines is first order in each reactant. The rate of reduction is sensitive to the electron-withdrawing power of the 3 substituent. Attach-ment of an indole moiety at either the 3 or the 1 position of the dihydropyridine ring resulted at most in a small de-crease in the rate. Activation energies for reduction by the 3-carbamoyl-and 3-cyanodihydropyridines are low (5-7 kcal mol-1) and the entropies of activation are very negative (-46,-47 eu). Reduction by the 3-carbamoyl deriva-tive proceeds 33 times more rapidly in acetonitrile than in benzene. The isotope effect (ku/ko) in the product-form-ing step in reactions of hexachloroacetone, pentachloroacetone, and sym-tetrachloroacetone with l-benzyl-3-carbamoyl-l, 4-dihydropyridine-4-d is essentially invariant with the nature of the halo ketone. Changes in the ultraviolet-visible spectra are observed when dihydropyridines and haloketones are mixed, suggesting the possible intervention of intermediate complexes in the reduction. Although electron spin resonance studies indicated the lack of detectable radicals in these reactions, one-electron transfer occurs from N, N, N', N'-tetramethyl-p-phenylenedi-amine to hexafluoroacetone to yield the cation radicalof the amine. Pentachloroacetone is the product from hexachloroacetone and the diamine. 1, 4, 4-Trimethyl-1, 4-dihydropyridine in acetonitrile gives highly colored solutions when mixed eitherwith hexachloroacetone or chloranil. It was not possible to identify products from these reac-tions.The efficient, nonenzymic reductions of thiobenzophe-nones1 and halo ketones2 by 1-substituted 1, 4-dihydronicotinamides are approximations to the biological reductions of simple carbonyl groups by the coenzyme, NADH. Electronegative halogen atoms enhance the ease of reduction of the carbonyl group in the halo ketones, a finding consistent with the increase in the rate of reduction of the thiocarbonyl groups in thiobenzophenones when electron-withdrawing substitu-ents are present1 and in the reduction of electron-deficient nitro and nitroso groups by NADH models. 3· 4 Recently, Creighton and Sigman found that complexation of the car-bonyl group of l, 10-phenanthroline-2-carboxaldehyde by zinc ions allows its efficient reduction by ln-propyl-l, 4-dihy-dronicotinamide. 6 Metal ionsalso facilitate the reduction of pyridoxal phosphate, 6 thereduction of-hydroxy ketones, and the stereoselective reduction of esters of pyruvic and benzoylformic acids7 by NADH models. In none of the model systems for the biological reduction of a carbonyl group by dihydronicotinamides has a simple, unactivated carbonyl group been reduced efficiently; metal ions or highly electronegative carbonyl compounds are required. These above examples involve hydrogen transfers from NADH models to a substrate. The NADH models are capable also of electron donation, 8 and one-electron transfers to tetracyanoethylene, 9 quiñones, 10 N-methylphenazinium