Related Experiment Video
Updated: Jul 17, 2026
08:12
A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Intermolecular electrophilic O-amination of alcohols
Alfred Hassner1, Guy Patchornik, Tarun K Pradhan
1Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel. hassna@mail.biu.ac.il
The Journal of Organic Chemistry
|January 16, 2007
Summary
Researchers developed novel reagents for electrophilic O-amination of alcohols, creating new oxime ethers under mild conditions. This reaction is sensitive to steric hindrance and accelerated by aromatic or double bonds in the alcohol.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Electrophilic O-amination is a crucial transformation in organic synthesis.
- Developing new reagents for efficient O-amination of aliphatic alcohols remains a challenge.
Purpose of the Study:
- To report the first examples of intermolecular electrophilic O-amination of aliphatic alcohols.
- To introduce novel fluorenone oxime tosylate and mesylate reagents for this transformation.
Main Methods:
- Utilized fluorenone oxime tosylate (5a) or mesylate (5b) as new electrophilic aminating reagents.
- Conducted reactions with diverse aliphatic alcohols in the presence of sodium hydride (NaH) under mild conditions.
- Monitored the formation of oxime ether products (6) to analyze reaction kinetics and selectivity.
Main Results:
- Successfully achieved O-amination of various aliphatic alcohols using the novel reagents.
- Demonstrated that the reaction rate is sensitive to steric effects in the alcohol substrate.
- Observed an increased reaction rate for alcohols containing aromatic rings (benzyl) or double bonds (allyl).
Conclusions:
- Fluorenone oxime tosylate and mesylate are effective reagents for intermolecular electrophilic O-amination of alcohols.
- The developed method offers a mild and versatile route to synthetically valuable oxime ethers.
- Steric and electronic factors of the alcohol significantly influence the efficiency and rate of the O-amination reaction.
Related Concept Videos
02:15Preparation of Alcohols via Addition Reactions
Overview
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...
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...
01:19Aldehydes and Ketones with Alcohols: Hemiacetal Formation
Similar to water, alcohols can add to the carbonyl carbon of the aldehydes and ketones. The addition of one molecule of alcohol to the carbonyl compound forms the hemiacetal or half acetal. As depicted below, in a hemiacetal, the carbon is directly linked to an OH and OR group.
03:08Hydroboration-Oxidation of Alkenes
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
01:38Preparation of Alcohols via Substitution Reactions
Overview
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
01:16Amines to Alkenes: Hofmann Elimination
Alkenes can be obtained from amines via an E2 elimination. The amine is first converted into a good leaving group, such as a quaternary ammonium salt. This is accomplished by treating the amine with an excess of alkyl halide, which results in a halide salt. Next, the halide salt is transformed into a hydroxide salt that functions as a base to enable elimination.
Under thermal conditions, the hydroxide can abstract a proton from the β carbon; this generates an alkene with the simultaneous...
Under thermal conditions, the hydroxide can abstract a proton from the β carbon; this generates an alkene with the simultaneous...