478059-14-2

Upstream product

• 108-88-3 toluene 
• 445-29-4 o-fluoro-benzoic acid 
• 393-52-2 2-Fluorobenzoyl chloride 
• 30148-19-7 (2-fluoro-phenyl)-(1-methyl-1H-imidazol-2-yl)-methanone 
• 100-51-6 benzyl alcohol 
• 446-52-6 2-Fluorobenzaldehyde 
• 100-52-7 benzaldehyde 
• 908094-04-2 phenyldiazomethane 
• 5281-18-5 benzaldehyde, hydrazone 
• 24424-99-5 di-tert-butyl dicarbonate 
• 124-38-9 carbon dioxide 
• 348-52-7 1-Fluoro-2-iodobenzene 
• 100-39-0 benzyl bromide 

Downstream Products

• 849048-64-2 ethyl N-(2-benzyloxycarbonylphenoxy)acetimidate 
• 445-29-4 o-fluoro-benzoic acid 

Relevant academic research and scientific papers

Base-Promoted Amidation and Esterification of Imidazolium Salts via Acyl C-C bond Cleavage: Access to Aromatic Amides and Esters

Imidazolium salts have been effectively employed as suitable acyl transfer agents in amidation and esterification in organic synthesis. The weak acyl C(O)-C imidazolium bond was exploited to generate acyl electrophiles, which further react with amines and alcohols to afford amides and esters. The broad substrate scope of anilines and benzylic amines and base-promoted conditions are the benefits of this route. Interestingly, phenol, benzylic alcohols, and a biologically active alcohol can also be subjected to esterification under the optimized conditions.

METHOD OF CONVERTING ALCOHOL TO HALIDE

The present invention relates to a method of converting an alcohol into a corresponding halide. This method comprises reacting the alcohol with an optionally substituted aromatic carboxylic acid halide in presence of an N-substituted formamide to replace a hydroxyl group of the alcohol by a halogen atom. The present invention also relates to a method of converting an alcohol into a corresponding substitution product. The second method comprises: (a) performing the method of the invention of converting an alcohol into the corresponding halide; and (b) reacting the corresponding halide with a nucleophile to convert the halide into the nucleophilic substitution product.

N-Heterocyclic Carbene-Mediated Oxidative Electrosynthesis of Esters in a Microflow Cell

An efficient N-heterocyclic carbene (NHC)-mediated oxidative esterification of aldehydes has been achieved in an undivided microfluidic electrolysis cell at ambient temperature. Productivities of up to 4.3 g h-1 in a single pass are demonstrated, with excellent yields and conversions for 19 examples presented. Notably, the oxidative acylation reactions were shown to proceed with a 1:1 stoichiometry of aldehyde and alcohol (for primary alcohols), with remarkably short residence times in the electrolysis cell (13 s), and without added electrolyte. (Chemical Equation Presented).

Palladium-catalyzed benzylation of carboxylic acids with toluene via benzylic C-H activation

Direct benzylation of carboxylic acids with toluene has been developed via palladium-catalyzed C-H acyloxylation under 1 atm of oxygen. This reaction demonstrates good functional group tolerance and high yields, providing a facile, atom-economic, and efficient method for the synthesis of benzyl esters.

Titration of nonstabilized diazoalkane solutions by fluorine NMR

A new protocol for titrating nonstabilized diazoalkane solutions by quantitative 19F NMR is reported. An excess of 2-fluorobenzoic acid dissolved in CDCl3 is treated with the diazoalkane solution at a low temperature, immediately forming the corresponding 2-fluorobenzoate ester upon warming. A significant difference in the 19F chemical shift between the ester and acid is seen, allowing facile and accurate integration to determine titer. The procedure is safe, rapid, and indicates the active diazoalkane concentration with high precision.

An enantioselective synthesis of 2-aryl cycloalkanones by sc-catalyzed carbon insertion

Current methods for asymmetric α-arylation require blocking groups to prevent reaction at the R0-carbon, basic conditions that promote racemization, or multistep synthesis. This work records the first catalytic enantioselective examples of the diazoalkane-carbonyl homologation reaction. Medium ring 2-aryl ketones are prepared in one step in up to 98:2 er and 99% yield from the unsubstituted lower homologue by Sc-catalyzed aryldiazomethyl insertion with simple bis- and tris(oxazoline) ligands.

Domino catalysis in the direct conversion of carboxylic acids to esters

The combined use of high concentration conditions, auxiliary bases, and new catalysts allows for the rapid synthesis of sterically hindered carboxylic acid esters at room temperature. Mechanistic analysis indicates the intermediate formation of acid anhydrides and subsequent rate-limiting transformation to the ester products.

Inhibitors of transthyretin amyloid fibril formation

Bisaryloxime ethers and bisarylhydroazones are shown to be effective for inhibiting formation of amyloid fibrils of transthyretin.

Bisaryloxime ethers as potent inhibitors of transthyretin amyloid fibril formation

Amyloid fibril formation by the plasma protein transthyretin (TTR), requiring rate-limiting tetramer dissociation and monomer misfolding, is implicated in several human diseases. Amyloidogenesis can be inhibited through native state stabilization, mediated by small molecule binding to TTR's primarily unoccupied thyroid hormone binding sites. New native state stabilizers have been discovered herein by the facile condensation of arylaldehydes with aryloxyamines affording a bisarylaldoxime ether library. Of the library's 95 compounds, 31 were active inhibitors of TTR amyloid formation in vitro. The bisaryloxime ethers selectively stabilize the native tetrameric state of TTR over the dissociative transition state under amyloidogenic conditions, leading to an increase in the dissociation activation barrier. Several bisaryloxime ethers bind selectively to TTR in human blood plasma over the plethora of other plasma proteins, a necessary attribute for efficacy in vivo. While bisarylaldoxime ethers are susceptible to degradation by N-O bond cleavage, this process is slowed by their binding to TTR. Furthermore, the degradation rate of many of the bisarylaldoxime ethers is slow relative to the half-life of plasma TTR. The bisaryloxime ether library provides valuable structure-activity relationship insight for the development of structurally analogous inhibitors with superior stability profiles, should that prove necessary.

Carboxylation and esterification of functionalized arylcopper reagents

Functionalized arylcopper reagents have been produced in good yields at 25 °C from activated copper and the corresponding functionalized aryl iodides without the need of traditional organolithium or Grignard precursors. These organocopper compounds will undergo carboxylation with CO2 to form the corresponding copper benzoates. In turn, these salts can be acidified to produce the functionalized aryl acids or treated with appropriate alkyl halides in the presence of a dipolar aprotic solvent to generate the corresponding aryl esters. This methodology permits the formation of functionalized organic acids and esters that could not be generated by the carboxylation of organomagnesium compounds.