72046-73-2

Upstream product

• 50-00-0 formaldehyd 
• 621-23-8 1,2,3-trimethoxybenzene 
• 64-17-5 ethanol 
• 4540-33-4 piperdinium acetate 
• 77648-20-5 2,4,6-trimethoxybenzylamine 
• 21988-87-4 1,3,5-tris(bromomethyl)-2,4,6-trimethylbenzene 
• 133349-87-8 2-(1H-Benzotriazol-1-ylmethyl)-1,3,5-trimethoxybenzene 
• 101864-26-0 bis(2,4,6-trimethoxyphenyl)methanol 
• 51903-38-9 2,4,6-trimethoxybenzaldehyde oxime 
• 845281-85-8 N-(2,4,6-trimethoxybenzyl)aniline 
• 622-79-7 benzyl azide 
• 67-68-5 dimethyl sulfoxide 
• 124-38-9 carbon dioxide 
• 576-26-1 2.6-dimethylphenol 

Relevant academic research and scientific papers

Development of Transition-Metal-Free Lewis Acid-Initiated Double Arylation of Aldehyde: A Facile Approach Towards the Total Synthesis of Anti-Breast-Cancer Agent

This work describes a mild and robust double hydroarylation strategy for the synthesis of symmetrical /unsymmetrical diaryl- and triarylmethanes in excellent yields using Lambert salt (0.2–1.0 mol%). Despite the anticipated challenges associated with controlling selective product formation, unsymmetrical diaryl- and triarylmethanes products are obtained unprecedentedly. A highly efficient gram scale reaction has also been reported (TON for symmetrical product=475 and for unsymmetrical product=390). The synthetic utility of the methodology is demonstrated by the preparation of several unexplored diaryl- and triarylmethane-based biologically relevant molecules, such as arundine, vibrindole A, turbomycin B, and certain anti-inflammatory agents. A total synthesis of an anti-breast-cancer agent is also demonstrated. Control experiments, Hammett analysis, HRMS and GC-MS studies reveal the reaction intermediates and reaction mechanism.

Polyethylene Glycol (PEG-400) as Methylene Spacer and Green Solvent for the Synthesis of Heterodiarylmethanes under Metal-Free Conditions

Polyethylene glycol 400 (PEG-400) has been employed as a green, biodegradable solvent as well as methylene spacer for the one-pot synthesis of heterodiarylmethanes under metal-free conditions. PEG-400 is used for the dimerization of both symmetrical and unsymmetrical fused heterocycles and arenes as methylene spacer. The reaction was facilitated by (diacetoxyiodo)benzene (PIDA) as an oxidant. This reaction proceeds without transition metal, base, ligand, and under additive-free conditions involving the coupling of sp3 and sp2-hybridized carbon atoms. The method is applicable for variety of heterocycles such as imidazopyridines, imidazothioazoles, imidazobenzothiozoles, indolizines, indole, 1-methyl-1H-indole, N,N-dimethylaniline and trimethoxybenzene. Good to excellent yields and applicability to gram-scale synthesis demonstrate the potential scope of the process for commercial/industrial applications.

Sc(OTf)3-Catalyzed Synthesis of Symmetrical Dithioacetals and Bisarylmethanes Using Nitromethane as a Methylene Source

Use of nitromethane as an electrophilic methylene source for the synthesis of symmetrical dithioacetals and bisarylmethanes has been showcased using Sc(OTf)3 as a catalyst. The procedure allows straightforward access to the densely functionalized dithioacetals and bisarylmethanes under mild conditions. Additionally, the method has been applied for the synthesis of antimalarial tetramethyl mellotojaponin C and anticancer dimeric phloroglucinol derivative.

One-pot solvent-free synthesis of triaryl- and triheteroarylmethanes by Bi(OTf)3-catalyzed Friedel-Crafts reaction of arenes/heteroarenes with trialkyl orthoformates

A convenient, practical and highly efficient one-pot method has been developed for the synthesis of triaryl- and triheteroarylmethane derivatives by Bi(OTf)3-catalyzed Friedel-Crafts alkylation of trialkyl orthoformates in combination with a wide variety of arenes/heteroarenes at room temperature under solvent-free conditions and in an air atmosphere. The methodology offers an operational simplicity, high atom economy and environmentally benign procedure. Furthermore, selected compound 3k showed promising anti-inflammatory activity with inhibition nitric oxide and did not exhibit significant cytotoxic effects on macrophage cells.

Ammonium persulfate activated DMSO as a one-carbon synthon for the synthesis of methylenebisamides and other applications

Activation of DMSO to work as an economical and environmentally benign one-carbon synthon has been achieved by using a bench-top reagent ammonium persulfate for general and efficient access to symmetrical methylenebisamides from primary amides. This methodology was used to achieve a three-component Mannich reaction using acetophenone, saccharin and DMSO to furnish a β-amino ketone. It also provided a metal-free synthesis of thiadiazole and bis(phenyl)methane. Effectively, this method uses DMSO as a safer surrogate to formaldehyde. A mechanism for methylenebisamide formation involving radical intermediates has been proposed based on mechanistic studies.

Catalytic methylation of C-H bonds using CO2 and H2

Formation of C-C bonds from CO2 is a much sought after reaction in organic synthesis. To date, other than C-H carboxylations using stoichiometric amounts of metals, base, or organometallic reagents, little is known about C-C bond formation. In fact, to the best of our knowledge no catalytic methylation of C-H bonds using CO2 and H2 has been reported. Described herein is the combination of CO2 and H2 for efficient methylation of carbon nucleophiles such as indoles, pyrroles, and electron-rich arenes. Comparison experiments which employ paraformaldehyde show similar reactivity for the CO2/H2 system. Capturing: Carbon dioxide in the presence of H2 is shown to be an efficient methylating reagent for carbon nucleophiles such as 2-substituted indoles, pyrroles, and electron-rich arenes. Experimental data support the formal capture of formaldehyde. acac=acetylacetonate, triphos=1,1,1-tris(diphenylphosphinomethyl)ethane.

Acid-promoted rearrangement of arylmethyl azides: Applications toward the synthesis of N-arylmethyl arenes and polycyclic heteroaromatic compounds

An acid-promoted Aubé-Schmidt's rearrangement of arylmethyl azides provides a useful in situ iminium ion intermediate, which can be efficiently trapped by various nucleophiles. We report here the reaction of this iminium ion with aromatic nucleophiles to

Unusual Stabilities and Reactivities of Tris- and Bis(2,4,6-trimethoxyphenyl)carbenium Salts

2,4,6-Trimethoxyphenyllithium, Φ + ′Li[Φ + ′=2,4,6-(MeO)3C6H2], reacted with diphenyl carbonate and with ethyl formate to give tris(2,4,6-trimethoxyphenyl)methanol, Φ + ′3COH (1), and bis(2,4,6-trimethoxyphenyl)methanol, Φ + ′2CHOH (2), respectively. Compound 1 reacted with a slight excess of perchloric acid in 2-propanol to give very dark-purple crystals of the triarylcarbenium salt, [Φ + ′3C]X (3, X=ClO4), which were inert even in hot ethanol. However, a treatment of 3 (X=Cl), prepared in situ in 1 M (1 M=1 moldm-3) hydrochloric acid, with 1 M sodium hydroxide resulted to give 4-bis(2,4,6-trimethoxyphenyl)methylene-3,5-dimethoxy-2,5-cyclohexadienone. Compound 2 also reacted with a slight excess of perchloric acid in methanol to give dark-red crystals of the diarylcarbenium salt, [Φ + ′2CH]X (5, X=ClO4). Compound 5 was considerably inert even in hot methanol, but was easily reduced in primary and secondary alcohols to give bis(2,4,6-trimethoxyphenyl)methane, Φ + ′2CH2. Measurements of the half-lives of 5 in these alcohols showed that 5 was more labile in secondary alcohols, such as 2-propanol and 2-butanol, than in primary alcohols. When a suspension of 5 (X=Cl), prepared in situ in 1 M hydrochloric acid, was heated, tris(2,4,6-trimetrioxyphenyl)methane, Φ + ′3CH (7), was obtained. Analogous reactions to give 7 were observed in methanol containing a slight excess of hydrochloric acid or nitric acid in place of perchloric acid. The possible paths of these reactions are discussed.

N-benzotriazoles: Preparation and Use in Synthesis

Methoxybenzenes and -naphthalenes are benzotriazolylmethylated in the para-position or if this is blocked in an ortho-position.The methylene groups in the products are readily substituted by electrophiles via the lithiated derivatives.Displacement ot the benzotriazole group can be effected by organometallic reagents or by electron-rich benzoid compounds to afford a versatile method for the synthesis of substituted aryl ethers.Key Words: Lithiation/ Grignard reaction/ Condensation/ Aryl ethers/ Diarylmethanes