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Comparison of three methods for the methylation of aliphatic and aromatic compounds

Lee, Hyejung and Feakins, Sarah J. and Lu, Zhiyao and Schimmelmann, Arndt and Sessions, Alex L. and Tierney, Jessica E. and Williams, Travis J. (2017) Comparison of three methods for the methylation of aliphatic and aromatic compounds. Rapid Communications in Mass Spectrometry, 31 (19). pp. 1633-1640. ISSN 0951-4198. http://resolver.caltech.edu/CaltechAUTHORS:20170807-134931467

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Abstract

Rationale: Methylation protocols commonly call for acidic, hot conditions that are known to promote organic ^1H/^2H exchange in aromatic and aliphatic C—H bonds. Here we tested two such commonly-used methods and compared a third that avoids these acidic conditions, to quantify isotope effects with each method and to directly determine acidic-exchange rates relevant to experimental conditions. Methods: We compared acidic and non-acidic methylation approaches catalyzed by hydrochloric acid, acetyl chloride and EDCI (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) / DMAP (4-dimethylaminopyridine) respectively. These were applied to two analytes: phthalic acid (an aromatic) and octacosanoic acid (an aliphatic). We analyzed yield by gas chromatography flame ionization (GC/FID) and hydrogen and carbon isotopic composition by isotope ratio mass spectrometry (GC/IRMS). We quantified the ^1H/^2H exchange rate on dimethyl phthalate under acidic conditions with proton nuclear magnetic resonance (^1H-NMR) measurements. Results: The δ^2H and δ^(13)C values and yield were equivalent among the three methods for methyl octacosanoate. The two acidic methods resulted in comparable yield and isotopic composition of dimethyl phthalate; however, the non-acidic method resulted in lower δ^2H and δ^(13)C values perhaps due to low yields. Concerns over acid-catalyzed ^1H/^2H exchange are unwarranted as the effect was trivial over a 12-hour reaction time. Conclusions: We find product isolation yield and evaporation to be the main concerns in the accurate determination of isotopic composition. ^1H/^2H exchange reactions are too slow to cause measurable isotope fractionation over the typical duration and reaction conditions used in methylation. Thus, we are able to recommend continued use of acidic catalysts in such methylation reactions for both aliphatic and aromatic compounds.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/rcm.7947DOIArticle
http://onlinelibrary.wiley.com/doi/10.1002/rcm.7947/abstractPublisherArticle
ORCID:
AuthorORCID
Feakins, Sarah J.0000-0003-3434-2423
Sessions, Alex L.0000-0001-6120-2763
Additional Information:© 2017 Wiley. Accepted manuscript online: 1 August 2017; Manuscript Accepted: 26 July 2017; Manuscript Revised: 25 July 2017; Manuscript Received: 2 March 2017. This work was supported by funding from the US American Chemical Society Award #PRF-53747-ND2 to SF, from the US National Science Foundation Award CHE-1566167 to TW, and from the USC Provost fellowship to HJL. Federal support of NMR spectrometers (NSF DBI-0821671, CHE-0840366; NIH S10 RR25432) is gratefully acknowledged. We thank Elias Karkabi for discussions. This manuscript was improved with the comments from three reviewers.
Funders:
Funding AgencyGrant Number
American Chemical Society Petroleum Research FundPRF-53747-ND2
NSFCHE-1566167
University of Southern CaliforniaUNSPECIFIED
NSFDBI-0821671
NSFCHE-0840366
NIHS10 RR25432
Record Number:CaltechAUTHORS:20170807-134931467
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20170807-134931467
Official Citation:Lee H, Feakins SJ, Lu Z, et al. Comparison of three methods for the methylation of aliphatic and aromatic compounds. Rapid Commun Mass Spectrom. 2017;31:1633-1640. https://doi.org/10.1002/rcm.7947
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:79854
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:07 Aug 2017 21:22
Last Modified:05 Sep 2017 20:41

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