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Publication Date
2020
First Advisor
David Gorin
Document Type
Honors Project
Degree Name
Bachelor of Arts
Department
Chemistry
Keywords
Chemistry, Organic chemistry, Catalysis, Green chemistry, Methylation
Abstract
O-methylation is an important chemical reaction for synthesizing a variety of
biological products and pharmaceuticals. One important class of methylated product is N- heterocycle-fused aryl methyl ethers. The typical methyl sources for methylating phenols are
electrophiles such as diazomethane, TMSD, dimethyl sulfate, and iodomethane, all of which are either unstable or highly toxic. One alternative to these hazardous reagents is to use a nucleophilic methyl source. The Chan-Lam reaction couples a nucleophile with nucleophilic boronic acid in an oxidative cross-coupling reaction catalyzed by copper. Although the reaction most commonly uses an arylboronic acid, several N- and O-methylations have been published using methylboronic acid, including one by the Gorin lab using carboxylic acids as a substrate. The Gorin lab has also developed conditions for methylating phenols, but previously had only successfully methylated one nitrogen-containing phenol. After screening seven N-heterocyclic phenols, one successfully methylated product was isolated at 54% yield. Three other substrates showed evidence on 1HNMR of methylated product, but it could not be isolated.
Another class of methylated product is an aliphatic methyl ether. These are commonly made by methylating aliphatic alcohols with iodomethane or dimethyl sulfate. A few Chan-Lam arylations of aliphatic alcohols have been published, but no alkylations. We developed an assay using fluorinated aliphatic alcohol substrates so that conditions could be screened and yields quantified using 19FNMR. Several conditions were adapted from O-methylations, N- methylations, and aliphatic alcohol arylations and screened on these substrates. One set of conditions showed potential success, although product was not isolated and confirmed. Further tests can isolate the product and determine whether it is the desired ether. If so, these conditions can be optimized and applied to a wider range of substrates.
Rights
2020 Uma Bhagwat Gaffney. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.
Language
English
Recommended Citation
Gaffney, Uma Bhagwat, "Chan-Lam O-methylation of aliphatic alcohols and phenolic n-heterocycles" (2020). Honors Project, Smith College, Northampton, MA.
https://scholarworks.smith.edu/theses/2213
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Comments
55 pages : illustrations (some color) Includes bibliographical references (pages 52-55)