Sunday, September 8, 2019

M(alpha)NP Acid: An Alternative To Separate Alcohol Enantiomers

How do you usually handle alcohol racemic? Do you separate the enantiomers? How to do it? Column Chromatograph? 

Sometimes, using column chromatograph equipped with a chiral column can be helpful in separating the enantiomers. However, sometimes it doesn't work. Introducing M(alpha)NP Acid is one of the alternatives to separate the alcohol enantiomers. This method was developed by Kasai et al (2004). This powerful chiral molecular tool is able to determine their absolute configurations in an unambiguous way through 1H NMR anisotropy Method.  


How to introduce the M(alpha)NP Acid into the molecule? Here is the way:

The racemic of alcohol compound is added with 1,4-dimethylaminopyridine (DMAP), 10-camphorsulfonic acid (CSA), and 1,3-dicyclohexylcarbodiimide (DCC), then dissolved them with dichloromethane (DCM). Stir them at room temperature overnight. After working up the reaction solution, try to purify with column chromatograph, then measure the 1HNMR of first and second eluted sample because we need the chemical shift data from both to do the calculation through 1HNMR anisotrophy method. 

To know whether the 1st eluted sample is  S or R configuration, firstly, assign the proton from the NMR spectrum. Put the chemical shift data like the picture below. Left side for the 1st eluted sample and the right side for the 2nd eluted sample. Then, subtract the value of chemical shift data of 2nd eluted sample with 1st eluted sample. Then put the result on each proton location in the structure and always arrange it based on the sector rule. 


The M(alpha)NP Acid with thick black arrow, H proton with a dashed arrow, and left side for the proton which the result of the subtraction less than 0 (negative), and right side for proton which the result of the subtratction more than 0 (positive). By arranging like that, now we can see the configuration of the 1st eluted sample. The direction is counterclockwise, so the 1st eluted sample is S-configuration. This determination also means that the 2nd sample is in the opposite configuration which is R-configuration.


All the data and explanation is referred to this reference:
Kasai, Y., Ji, H. T. A., Fujita, T., Yamamoto, Y., Akagi, M., Sugio, A., … Harada, N. (2004). M A NP Acid , a Powerful Chiral Molecular Tool for Preparation of Enantiopure Alcohols by Resolution and Determination of Their Absolute Configurations by the 1 H NMR Anisotropy Method, 585(10045022), 569–585. https://doi.org/10.1002/chir.20077

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