NMR Determination of Enantiomeric Composition of Chiral Alcohols Using Camphorsulfonate Esters

Masthead Logo The Fordham Undergraduate Research Journal Volume 1 | Issue 1 Article 10 December 2013 NMR Determination of Enantiomeric Composition of Chiral Alcohols Using Camphorsulfonate Esters Steven Bondi FCRH '11 Fordham University, Thomas Lobasso FCRH '09 Fordham University, Christa Iwanoski FCRH '09 Fordham University, Shahrokh Saba Fordham University, Donald Clarke Fordham University, Follow this and additional works at: https://fordham.bepress.com/furj Part of the Materials Chemistry Commons Recommended Citation Bondi, Steven FCRH '11; Lobasso, Thomas FCRH '09; Iwanoski, Christa FCRH '09; Saba, Shahrokh; and Clarke, Donald (2013) "NMR Determination of Enantiomeric Composition of Chiral Alcohols Using Camphorsulfonate Esters," The Fordham Undergraduate Research Journal: Vol. 1 : Iss. 1 , Article 10. Available at: https://fordham.bepress.com/furj/vol1/iss1/10 This Article is brought to you for free and open access by DigitalResearch@Fordham. It has been accepted for inclusion in The Fordham Undergraduate Research Journal by an authorized editor of DigitalResearch@Fordham. For more information, please contact . NMR Determination of Enantiomeric Composition of Chiral Alcohols Using Camphorsulfonate Esters Cover Page Footnote Steven P. Bondi, FCRH 2011, is from New Hyde Park, New York. He is a mathematics major and a chemistry minor. Steven is currently conducting organic chemistry research in Dr. Shahrokh Saba’s lab on amine synthesis and alcohol enantiomeric ratio determination. After graduating, Steven will be attending medical school and pursuing a career in medicine. This article is available in The Fordham Undergraduate Research Journal: https://fordham.bepress.com/furj/vol1/iss1/10 FURJ | Volume 1 | Spring 2011 C ommunication s Bondi et al.: Enantiomeric Composition of Chiral Alcohols NMR Determination of Enantiomeric Composition of Chiral Alcohols Using Camphorsulfonate Esters CHEMISTRY Steven Bondi, FCRH ’11 Thomas Lobasso, FCRH ’09 Christa Iwanoski, FCRH ’09 Dr. Shahrokh Saba Dr. Donald Clarke Introduction Most biologically active compounds, including pharmaceuticals, have chiral molecular structures. With increased recognition that enantiomers of chiral drugs are metabolized differently, there has been enormous interest in the development of enantioselective methodologies for the synthesis of chiral compounds. NMR spectroscopy has emerged as a powerful method for discrimination of enantiomers of chiral compounds.1 One strategy by which the NMR method is exploited is based on converting the enantiomers of a chiral compound to diastereomers using a chiral derivatizing agent. These diastereomers often display anisochronous NMR signals, which can be identified and integrated affording quantitative measurements of the optical purity of a sample. The hydroxyl group is a highly prevalent functionality found in naturally occurring compounds and pharmaceuticals. The chiral auxiliaries used in common practice to identify enantiomeric alcohols are usually chiral carboxylic acids, or their chlorides, which readily form diastereomeric esters and show appreciable diastereomeric differences at certain positions in the molecule. The most widely used carboxylic acid for such studies is that developed by Mosher, namely α-methoxyα-trifluoromethylphenylacetic acid.2 However, while commercially available, this compound is 173 times more expensive than (S)-camphorsulfonyl chloride [(S)-CSCl] (Figure 1). A much older chiral auxiliary is camphorsulfonic acid, which has been used extensively to derivatize chiral amines, but not to make derivatives of chiral alcohols. It has not been extensively used to make derivatives of chiral alcohols. This is because sulfonate esters are more difficult to prepare than carboxylate esters. On the other hand, the poor reactivity of sulfonyl chlorides, as compared to carboxylic acid chlorides, makes this reagent more easily stored without decomposition by hydrolysis. We have recently expanded the protocol for the hydration of 1-hexene, which affords 2- and 3-hexanols, by treating the reaction product with (S)-CSCl and triethylamine to produce diastereomeric esters of these chiral alcohols. ¹H and ¹³C NMR spectroscopy were used to determine the enantiomeric composition of alcohols obtained.3 Figure 1 We have now extended our studies to other chiral alcohols and herein report on the synthesis and ¹H and ¹³C NMR spectra of camphorsulfonate esters of (+/-)-ethyl-3-hydroxybutyrate, (+/-)-2-butanol, (+/-)-1-phenylethanol, (+/-)-2-hydroxymethyloxirane, and (+/-)-1-phenyl-2-propyn-1-ol. SB would like to thank the Fordham College at Rose Hill Dean’s Office and Dr. Moses K. Kaloustian for their financial support during the summers of 2009 and 2010. Direct all correspondence to Steven Bondi at . Published by DigitalResearch@Fordham, 2011 642 1 C ommunication s FURJ | Volume 1 | Spring 2011 The Fordham Undergraduate Research Journal, Vol. 1 [2011], Iss. 1, Art. 10 Experimental Procedure CHEMISTRY A 50 mL Erlenmeyer flask was charged with an alcohol (5 mmol). To this, a solution of triethylamine (7.5 mmol) and methylene chloride (25 mL) was added. The mixture was swirled and cooled in an ice H2O bath for 15 minutes. (1S)-(+)-Camphorsulfonyl chloride (5.5 mmol) was then added over a period of 5 minutes. The flask was then ice cooled for an additional 45 minutes. The product was then purified by sequential extractions of the reaction mixture with ice-cold H2O (10 mL), 10% HCl (8 mL), a saturated NaHCO3 solution (10 mL), and finally with H2O (10 mL). The organic layer was then dried over anhydrous sodium sulfate, followed by rotary evaporation of the solvent affording the sulfonate esters in 75-86 percent yield. www.fordham.edu/fcrh/furj CS ester derived from the R enantiomer of ethyl-3-hydroxybutyrate. The ¹H NMR spectrum of the CS ester derived from authentic (R)-2-butanol similarly shows two separate doublets centered at 3.0 and 3.6 ppm for the SCH2 moiety. For the CS diastereomers obtained from racemic 2-butanol, four doublets representing the same hydrogens are observed. Assignment of the signals was made by adding a small sample of CS ester of (R)-2-butanol (Figure 3). The ¹³C NMR spectrum of CS diastereomers obtained from racemic 2-butanol, shows partially resolved signals for the carbon attached to the oxygen in the 2-butyl moiety. Assignment of the signals was made by adding a small sample of CS ester of (R)-2-butanol. Results and Discussion The ¹H NMR spectrum of the camphorsulfonate (CS) ester derived from (R)-ethyl-3-hydroxybutyrate shows two doublets centered at 3.0 and 3.7 ppm, representing the diastereotopic hydrogens of the SCH2 moiety. The diastereomeric CS esters derived from (+/-)-ethyl3-hydroxybutyrate display four well-resolved doublets representing the same hydrogens in the two separate diastereomers (Figure 2). Addition of a small sample of the CS ester derived from authentic (R)-ethyl-3-hydrox (...truncated)