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Updated: Jan 10, 2026
Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile
Published on: October 30, 2018
A Practical Solution to Achieve the Elusive Etherification of Bicyclo[1.1.1]pentyl Alcohols
Stephen J Sujansky1, Samantha A Burgess2, Xiaoshen Ma1
1Department of Discovery Chemistry, Merck & Co., Inc., 33 Ave. Louis Pasteur, Boston, Massachusetts 02215, United States.
Abstract:
Since the first synthesis of bicyclo[1.1.1]pentane (BCP) analogues in the 1960s, both the academic and industrial communities have continued to deliver novel transformations and synthetic strategies that provide access to diverse, polysubstituted BCPs. Despite these efforts, access to ether-substituted BCPs via direct etherification of a BCP alcohol remains a significant challenge. Here, we detail our approach toward overcoming this limitation by exploiting trichloroacetimidate reactivities under acidic conditions, obviating the intrinsic, base-mediated decomposition pathway that previously limited the synthetic applications of BCP alcohols. This is the first general synthesis of BCP ethers via direct alkylation of BCP alcohols.
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02:29Ethers from Alcohols: Alcohol Dehydration and Williamson Ether Synthesis
Ethers can be prepared from organic compounds by various methods. Some of them are discussed below,
Preparation of Ethers by Alcohol Dehydration
In this method, in the presence of protic acids, alcohol dehydrates to produce alkenes and ethers under different conditions. For example, in the presence of sulphuric acid, dehydration of ethanol at 413 K yields ethoxyethane, whereas it yields ethene at 443 K.
02:35Ethers from Alkenes: Alcohol Addition and Alkoxymercuration-Demercuration
Ethers can also be prepared from alkenes through acid-catalyzed addition of alcohols and alkoxymercuration–demercuration.
Preparation of Ethers by Acid-Catalyzed Addition of Alcohol to Alkenes
The acid-catalyzed addition of alcohol to an alkene involves treating the alkene with an excess of alcohol in the presence of an acid catalyst to form an ether under suitable conditions. The hydrogen will add to the less substituted carbon so that the nucleophile can attack the more substituted...
02:15Preparation of Alcohols via Addition Reactions
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...
02:17Physical Properties of Ethers
An ether molecule has a net dipole moment due to the polarity of C–O bonds. Subsequently, boiling points of ethers are lower than those of alcohols of comparable molecular weight and slightly higher than those of hydrocarbons of comparable molecular weight (Table 1).
Ethers can act as hydrogen bond acceptors, making them more water-soluble than hydrocarbons, but since ethers cannot act as hydrogen bond donors, they are much less soluble in water than alcohols. Ethers are considered...
03:08Hydroboration-Oxidation of Alkenes
02:23Autoxidation of Ethers to Peroxides and Hydroperoxides