3469-00-9

Usage

Uses

Used in Chemical Industry:
Methyl diphenylacetate is used as a chemical intermediate for the synthesis of various organic compounds and pharmaceuticals. Its unique structure allows it to be a versatile building block in the development of new molecules and materials.
Used in Research and Development:
As a research chemical, methyl diphenylacetate is utilized in academic and industrial laboratories for the investigation of its properties and potential applications. It can be employed in the study of organic reactions, synthesis methods, and the development of new chemical processes.
Used in Pharmaceutical Industry:
Methyl diphenylacetate may also be used in the pharmaceutical industry as a starting material or intermediate in the production of various drugs and medications. Its unique structure can contribute to the development of new therapeutic agents with improved efficacy and safety profiles.

Synthesis Reference(s)

Tetrahedron, 46, p. 1839, 1990 DOI: 10.1016/S0040-4020(01)89753-2Tetrahedron Letters, 25, p. 4943, 1984 DOI: 10.1016/S0040-4039(01)91265-1

InChI:InChI=1/C15H14O2/c1-17-15(16)14(12-8-4-2-5-9-12)13-10-6-3-7-11-13/h2-11,14H,1H3

Upstream product

• 186581-53-3 diazomethane 
• 117-34-0 2,2-diphenylacetic acid 
• 67-56-1 methanol 
• 384-94-1 1,1'-(2,2,2-trifluoro-1,1-ethanediyl)dibenzene 
• 124-41-4 sodium methylate 
• 6632-43-5 methyl α-acetoxy-α-phenylbenzeneacetate 
• 501-65-5 diphenyl acetylene 
• 3469-17-8 2-diazo-1,2-diphenylethan-1-one 
• 37167-62-7 bromo-phenyl-acetic acid methyl ester 
• 71-43-2 benzene 
• 15745-93-4 triphenyl-azetidine-2,4-dione 
• 54311-64-7 methyl α-chloro-α-phenylbenzeneacetate 
• 25327-58-6 Benzoic diphenylacetic anhydride 
• 40195-27-5 (1-methoxy-2-phenylvinyloxy)trimethylsilane 

Downstream Products

• 7476-11-1 1,1,3,3-tetraphenylpropane-2-one 
• 72727-35-6 2,2,N-triphenyl-3-thio-malonamic acid methyl ester 
• 13027-73-1 methyl 2-cyclohexyl-2-phenylacetate 
• 83004-43-7 methyl 2,2-bis(4-nitrophenyl)ethanoate 
• 104488-36-0 Bromdiphenylessigsaeure-methylester 
• 7770-42-5 diphenyl-malonic acid dimethyl ester 
• 93008-37-8 N-(2-Hydroxyethyl)-2,2-diphenylacetamid 
• 57272-44-3 methyl α-hydroperoxy-α,α-diphenylacetate 
• 123172-65-6 4-Hydroxy-3,3-diphenyl-dihydro-furan-2-one 
• 84960-26-9 2,6-bis(α-phenyl-α-carbomethoxybenzyl)pyridine 
• 91614-23-2 Diphenyl-acetic acid 1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-piperidin-4-yl ester 
• 51552-62-6 methoxy-diphenyl-acetic acid methyl ester 
• 4406-93-3 α-ethoxydiphenylacetic acid ethyl ester 
• 76-93-7 Benzilic acid 

Relevant academic research and scientific papers

Green Esterification of Carboxylic Acids Promoted by tert-Butyl Nitrite

In this work, the green esterification of carboxylic acids promoted by tert-butyl nitrite has been well developed. This transformation is compatible with a broad range of substrates and exhibits excellent functional group tolerance. Various drugs and substituted amino acids are applicable to this reaction under near neutral conditions, with good to excellent yields.

Iodoarene-Catalyzed Oxyamination of Unactivated Alkenes to Synthesize 5-Imino-2-Tetrahydrofuranyl Methanamine Derivatives

Reported here is the room-temperature metal-free iodoarene-catalyzed oxyamination of unactivated alkenes. In this process, the alkenes are difunctionalized by the oxygen atom of the amide group and the nitrogen in an exogenous HNTs2 molecule. This mild and open-air reaction provided an efficient synthesis to N-bistosyl-substituted 5-imino-2-tetrahydrofuranyl methanamine derivatives, which are important motifs in drug development and biological studies. Mechanistic study based on experiments and density functional theory calculations showed that this transformation proceeds via activation of the substrate alkene by an in situ generated cationic iodonium(III) intermediate, which is subsequently attacked by an oxygen atom (instead of nitrogen) of amides to form a five-membered ring intermediate. Finally, this intermediate undergoes an SN2 reaction by NTs2 as the nucleophile to give the oxygen and nitrogen difunctionalized 5-imino-2-tetrahydrofuranyl methanamine product. An asymmetric variant of the present alkene oxyamination using chiral iodoarenes as catalysts also gave promising results for some of the substrates.

Boryl Radical Activation of Benzylic C-OH Bond: Cross-Electrophile Coupling of Free Alcohols and CO2via Photoredox Catalysis

A new strategy for the direct cleavage of the C(sp3)-OH bond has been developed via activation of free alcohols with neutral diphenyl boryl radical generated from sodium tetraphenylborate under mild visible light photoredox conditions. This strategy has been verified by cross-electrophile coupling of free alcohols and carbon dioxide for the synthesis of carboxylic acids. Direct transformation of a range of primary, secondary, and tertiary benzyl alcohols to acids has been achieved. Control experiments and computational studies indicate that activation of alcohols with neutral boryl radical undergoes homolysis of the C(sp3)-OH bond, generating alkyl radicals. After reducing the alkyl radical into carbon anion under photoredox conditions, the following carboxylation with CO2 affords the coupling product.

Visible-light photoredox-catalyzed selective carboxylation of C(sp3)?F bonds with CO2

It is highly attractive and challenging to utilize carbon dioxide (CO2), because of its inertness, as a nontoxic and sustainable C1 source in the synthesis of valuable compounds. Here, we report a novel selective carboxylation of C(sp3)?F bonds with CO2 via visible-light photoredox catalysis. A variety of mono-, di-, and trifluoroalkylarenes as well as α,α-difluorocarboxylic esters and amides undergo such reactions to give important aryl acetic acids and α-fluorocarboxylic acids, including several drugs and analogs, under mild conditions. Notably, mechanistic studies and DFT calculations demonstrate the dual role of CO2 as an electron carrier and electrophile during this transformation. The fluorinated substrates would undergo single-electron reduction by electron-rich CO2 radical anions, which are generated in situ from CO2 via sequential hydride-transfer reduction and hydrogen-atom-transfer processes. We anticipate our finding to be a starting point for more challenging CO2 utilization with inert substrates, including lignin and other biomass.

Photoredox Catalytic Phosphite-Mediated Deoxygenation of α-Diketones Enables Wolff Rearrangement and Staudinger Synthesis of β-Lactams

A novel visible-light-driven catalytic activation of C=O bonds by exploiting the photoredox chemistry of 1,3,2-dioxaphospholes, readily accessible from α-diketones and trialkyl phosphites, is reported. This mild and environmentally friendly strategy provides an unprecedented and efficient access to the Wolff rearrangement reaction which traditionally entails α-diazoketones as precursors. The resulting ketenes could be precisely trapped by alcohols/thiols to give α-aryl (thio)acetates and by imines to afford the valuable β-lactams in up to 99 % yields.

Time-Economical Synthesis of Diarylacetates Enabled by TfOH-Catalyzed Arylation of α-Aryl-α-Diazoesters with Arenes

Diarylacetates are privileged structures of many bioactive natural products and pharmaceutical compounds. A time-economical synthesis of diarylacetates by TfOH-catalyzed arylation of α-aryl-α-diazoesters with arenes is described. This protocol provides a variety of diarylacetates in good yields with broad substrate scope, excellent functional group compatibility, and mild reaction conditions. Also, a new mechanism for the arylation reaction of α-aryl-α-diazoesters with arenes under TfOH catalysis is presented.

Asymmetric Intramolecular Hydroalkoxylation of Unactivated Alkenes Catalyzed by Chiral N-Triflyl Phosphoramide and TiCl4?

By using a combination of a chiral N-triflyl phosphoramide and TiCl4 as the catalyst, a new process for asymmetric intramolecular hydroalkoxylation of unactivated alkenes was developed, producing various chiral tetrahydrofuran derivatives in 51%—99% yields with 30%—71% ee's.

mCPBA-mediated dioxygenation of unactivated alkenes for the synthesis of 5-imino-2-tetrahydrofuranyl methanol derivatives

A mCPBA-mediated, metal-free, intramolecular dioxygenation reaction of unactivated alkenes is reported. In the presence of m-chlorobenzoic peracid, different unsaturated amide substrates could be cyclized via epoxide intermediates, producing the corresponding 5-imino-2-tetrahydrofuranyl methanol products in up to 94% yield at room temperature.

Room Temperature Coupling of Aryldiazoacetates with Boronic Acids Enhanced by Blue Light Irradiation

A visible-light-promoted photochemical protocol is reported for the coupling of aryldiazoacetates with boronic acids. This photochemical reaction shows great enhancement compared to the same protocol performed in the absence of light. Except for a few cases, the room temperature coupling in the dark (thermal process) generally does not work. When it does, it is likely to also involve free carbenes as key intermediates. Alternatively, photochemical reactions show a broad scope, can be performed under air and tolerate a wide variety of functional groups. Reaction-evolution monitoring, DFT calculations and control experiments have been used to evaluate the main aspects of this intricate mechanistic scenario. Biologically active molecules Adiphenine, Benactyzine and Aprophen have been prepared as examples of synthetic applications.

Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation

AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.