ALPHA-METHOXY-ALPHA-TRIFLUOROMETHYLPHENYLACETIC ACID, A VERSATILE REAGENT FOR DETERMINATION OF ENANTIOMERIC COMPOSITION OF ALCOHOLS AND AMINES
ALPHA-METHOXY-ALPHA-TRIFLUOROMETHYLPHENYLACETIC ACID, A VERSATILE REAGENT FOR DETERMINATION OF ENANTIOMERIC COMPOSITION OF ALCOHOLS AND AMINES
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DOI：
10.1021/jo01261a013
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发表时间：
1969-01-01
影响因子：
3.6
通讯作者：
MOSHER, HS
中科院分区：
文献类型：
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作者：
DALE, JA;DULL, DL;MOSHER, HS
从甲氧基-a-三氟甲基苯基乙酰氯和各种仲醇和胺制备了非对映体酯和酰胺。R， R和S， S与R， S和S， R非对映体的核磁共振光谱显示出明显不同的化学位移：质子区为0.03-0.13 ppm，氟区为0.11-0.71 ppm。通过测量由该对映体纯试剂制备的非对映体位置的酯和酰胺基团的核磁共振信号的强度，对许多醇和胺的对映体组成进行了满意的测定。a-甲氧基-a-三氟甲基苯基乙酰基衍生物的使用与其他仅具有质子共振的试剂相比具有明显的优势，基于氟共振的对映体组成测定通常更可靠，因为氟信号简单且位于非拥挤区域。这是一种绝对方法，不依赖于光旋；可对20毫克样品进行准确测定。从而拓展了核磁共振技术的应用范围。此外，该试剂在长时间的反应条件下对外消旋反应表现出完全的稳定性。开发了一种实用的合成方法和简便的分离方法。Mislow和Raban回顾了测定对映体组成（光学纯度）方法的最新进展。2我们对这个问题的兴趣是由酮的不对称还原的持续研究决定的，并且有必要在相对较小的样品上测定所得手性醇的对映体组成。在之前的一篇论文中，我们报道了一系列单cr取代苯乙酸在核磁共振（nmr）和气液分配色谱（glpc）测定对映体组成中的应用和局限性。先前研究的试剂对于受阻的仲甲醇不能给出令人满意的结果，因为在酸部分的碳中心有外显异构。4,5此外，当核磁共振作为定量测量非对映体比例的技术时，由于质子信号的重叠，经常遇到严重的限制。在早期用glpc和核磁共振测定部分活性甲醇对映体组成的研究中，人们认识到a-甲氧基-a-三氟甲基苯基乙酸（MTPA， I）可能非常适合于这一目的。该试剂可通过其酸性氯化物发生反应
Diastereomeric esters and amides have been preparedfrom-methoxy-a-trifluoromethylphenylacetyl chloride and various secondary alcohols and amines. The nmr spectra of the R, R and S, S vs. the R, S and S, R diastereo-mers show significantly different chemical shifts: 0.03-0.13 ppm in the protonregion and 0.11-0.71 ppm in the fluorine region. By measuring the intensities of the nmr signals of the diastereomerically situated groups of esters and amides preparedfrom this enantiomerically pure reagent, satisfactory determinations of the enantiomeric composition of a number of alcohols and amines havebeen made. The use of the a-methoxy-a-trifluoro-methylphenylacetyl derivative offers the distinct advantage, over other reagents having only proton reso-nances, that determinations of enantiomeric composition based uponfluorine resonances are usually more reliable, since the fluorine signals are simple and in an uncongested region. This is a absolute method, independent of optical rotation; accurate determinations can be made on 20-mg samples. Thusthis reagentextends the ap-plication of this nmr technique. Furthermore, the reagent shows complete stability to racemization under prolonged reaction conditions. A practical synthesis and convenient resolution of the reagent have been developed.Recent developments in methods for the deter-mination of enantiomeric composition (optical purity) have been reviewed by Mislow and Raban. 2 Our interest in this problem is dictated by continuing studies on the asymmetric reduction of ketones with the necessity ofdetermining the enantiomeric composition of the resulting chiral alcohols on relatively small samples. 3 In a previous paper4 we reported on the applications and limitations of a series of mono-cr-substituted phenylacetic acids for the nuclear magnetic resonance(nmr) and gas-liquid partition chromatographic (glpc) determination of enantiomeric com-position. 5 The reagents previously studied do not give satisfactory results with hindered secondary carbinols because of epimerization at the-carbon center of the acid moiety. 4, 5 In addition, when nmr was used as the technique forquantitative measurement of diastereomer ratios, serious restrictions were often encountered owing to the overlapping of proton signals. In earlier studies on the determination of enantiomeric composition of partially active carbinols by glpc and nmr, it was recognized that a-methoxy-a-trifluoromethylphenyl-acetic acid (MTPA, I) might be ideally suited for this purpose. 5 This reagent can react via its acid chloride