Arylmethyl Halides Research Articles

G-C3N4 catalysed sustainable synthesis of (hetero)aryl acids and regioselective α-bromo ketones in one pot under visible light catalysis

Visible light-induced graphitic carbon nitride (g-C3N4) catalysed direct oxidation of (hetero)aryl methyl halides to (hetero)aryl carboxylic acids using O2 as a green oxidant and subsequent formation of α-bromo ketones in one vessel.

Triton-X-100 as an Organic Catalyst for One-Pot Synthesis of Arylmethyl-H-phosphinic Acids from Red Phosphorus and Arylmethyl Halides in the KOH/H2O/Toluene Multiphase Superbase System

Triton-X-100, a polyethylene glycol 4-(tert-octyl)phenyl ether, has been found to be an active micellar organic catalyst for the one-pot selective synthesis of arylmethyl-H-phosphinic acids in up to 65% yields by the direct phosphinylation of arylmethyl halides with red phosphorus in the KOH/H2O/toluene multiphase superbase system. The catalyst demonstrates a good recyclability. As a result, an expeditious method for the chemoselective synthesis of arylmethyl-H-phosphinic acids—versatile sought-after organophosphorus compounds—has been developed. The synthesis is implemented via direct alkylation/oxidation of red phosphorus with arylmethyl halides, promoted by superbase hydroxide anions using Triton-X-100 (a commercial off-the-shelf organic recyclable micellar catalyst). The reaction comprises the hydroxide anions-assisted disassembly of Pred 3D polymer molecules triggered by the separation from the potassium cation in ordinary crown-like micelles to produce polyphosphide anions in aqueous phase. Further, polyphosphide anions are alkylated with arylmethyl halides in organic phase in the presence of the catalytic Triton-X-100 reverse micelles and alkylated polyphosphide species undergo the double hydroxylation. The advantages of the strategy developed include chemoselectivity, benign and accessible starting reagents, catalyst recyclability, and facile one-pot implementation.

Pd-Catalyzed Cross-Coupling of Sb-Aryl Stibines with Halogenomethyl Arenes to Give Unsymmetirc Diarylmethanes.

Herein, we describe a general method for the synthesis of unsymmetric diarylmethanes from (hetero)aryl methyl halides and Sb-aryl stibines. This protocol shows a broad substrate scope and a good functional group tolerance. Drug molecules, including beclobrate 3al and bifemelane 3as, and drug derivatives, including celecoxib 3p, ibuprofen 3ao, and probenecid 3ap, were efficiently synthesized on a gram scale. The possible mechanism is proposed on the basis of the results of control experiments.

Nitrosoarene-Catalyzed HFIP-Assisted Transformation of Arylmethyl Halides to Aromatic Carbonyls under Aerobic Conditions.

A rare metal-free nucleophilic nitrosoarene catalysis accompanied by highly hydrogen-bond-donor (HBD) solvent, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), organocatalytically converts arylmethyl halides to aromatic carbonyls. This protocol offers an effective means to access a diverse array of aromatic carbonyls with good chemoselectivity under mild reaction conditions. The activation of arylmethyl halides by HFIP to generate stable carbocation and autoxidation of in situ generated hydroxylamine to nitrosoarene in the presence of atmospheric O2 are the keys to success.

One-Pot Synthesis of Deuterated Aldehydes from Arylmethyl Halides.

A facile, one-pot approach for synthesizing deuterated aldehydes from arylmethyl halides was developed using D2O as the deuterium source. The efficient process is realized by a sequence of formation, H/D exchange, and oxidation of pyridinium salt intermediates. The mild and air-compatible reaction conditions enable efficient synthesis of diverse deuterated aldehydes with high deuterium incorporation.

ChemInform Abstract: Synthesis of Benzimidazoles by Copper‐Catalyzed Aerobic Oxidative Domino Reaction of 1,2‐Diaminoarenes and Arylmethyl Halides.

AbstractThe title compounds are synthesized by a simple, practical, and cost‐saving method tolerating wide range of functional groups.

ChemInform Abstract: Copper‐Catalyzed Domino Synthesis of Quinazolin‐4(3H)‐ones from (Hetero)arylmethyl Halides, Bromoacetate, and Cinnamyl Bromide.

Alkyl halides, including heteroarylmethyl and arylmethyl halides, bromoacetate, and cinnamyl bromide, are readily prepared via halogenation from basic raw materials, even using green processes. It is essential to replace their downstream products with them to prepare medicinally important heterocycles quinazolin-4(3H)-ones. Copper(I) bromide catalyzed domino reaction of alkyl halides and anthranilamides under air affords 2-substituted quinazolin-4(3H)-ones in good to excellent yields and with wide functional group tolerance. A mechanism for a copper(I) bromide involved organometal-catalyzed reaction via a four-step domino reaction is proposed.

Synthesis, antimicrobial, and anti-inflammatory activity, of novel S-substituted and N-substituted 5-(1-adamantyl)-1,2,4-triazole-3-thiols.

The reaction of 5-(1-adamantyl)-4-phenyl-1,2,4-triazoline-3-thione (compound 5) with formaldehyde and 1-substituted piperazines yielded the corresponding N-Mannich bases 6a–f. The reaction of 5-(1-adamantyl)-4-methyl-1,2,4-triazoline-3-thione 8 with various 2-aminoethyl chloride yielded separable mixtures of the S-(2-aminoethyl) 9a–d and the N-(2-aminoethyl) 10a–d derivatives. The reaction of compound 5 with 1-bromo-2-methoxyethane, various aryl methyl halides, and ethyl bromoacetate solely yielded the S-substituted products 11, 12a–d, and 13. The new compounds were tested for activity against a panel of Gram-positive and Gram-negative bacteria and the pathogenic fungus Candida albicans. Compounds 6b, 6c, 6d, 6e, 6f, 10b, 10c, 10d, 12c, 12d, 12e, 13, and 14 displayed potent antibacterial activity. Meanwhile, compounds 13 and 14 produced good dose-dependent anti-inflammatory activity against carrageenan-induced paw edema in rats.

Synthesis of benzimidazoles by copper‐catalyzed aerobic oxidative domino reaction of 1,2‐diaminoarenes and arylmethyl halides

Arylmethyl halides are readily synthesized via halogenation from the basic raw materials, even in green processes. They are used to replace their downstream products to prepare medicinally important 2‐aryl benzimidazoles. CuBr‐catalyzed synthesis of 2‐aryl benzimidazoles from arylmethyl halides and 1,2‐diaminoarenes via a one‐pot domino reaction is developed. This new synthetic method is simple, practical and cost saving, and tolerates wide functional groups. A mechanism of CuBr‐catalyzed aerobic oxidative domino reaction via a one‐pot four‐step process is proposed. Copyright © 2013 John Wiley & Sons, Ltd.

Pyrimidine-5-carbonitriles – part III: synthesis and antimicrobial activity of novel 6-(2-substituted propyl)-2,4-disubstituted pyrimidine-5-carbonitriles

Abstract The reaction of 6-(2-methylpropyl or 2-phenylpropyl)-2-thiouracil-5-carbonitriles (4a,b) with various arylmethyl halides, 2-bromoethyl methyl ether, benzyl chloromethyl ether, and 2-bromomethyl-5-nitrofuran in N,N-dimethylformamide or acetone yielded the corresponding substituted thio-3,4-dihydro-4-oxopyrimidine-5-carbonitrile analogues 5a–h, 6a,b, 7, and 8a,b, respectively. Treatment of 5c with phosphorus oxychloride and N,N-dimethylaniline yielded the 4-chloropyrimidine derivative 9, which was allowed to react with various arylthiols, arylamines, and 1-substituted piperazines to yield the respective 4-arylthio 10a–d, 4-arylamino 11a–d, and 4-piperazino 12a,b derivatives. The newly synthesized compounds were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 5e, 5f, 5g,h, 7, 8a,b, and 12a display marked antibacterial activity, particularly against the Gram-positive bacteria. None of these compounds are active against C. albicans.

Copper-Catalyzed Domino Synthesis of Quinazolin-4(3H)-ones from (Hetero)arylmethyl Halides, Bromoacetate, and Cinnamyl Bromide

Alkyl halides, including heteroarylmethyl and arylmethyl halides, bromoacetate, and cinnamyl bromide, are readily prepared via halogenation from basic raw materials, even using green processes. It is essential to replace their downstream products with them to prepare medicinally important heterocycles quinazolin-4(3H)-ones. Copper(I) bromide catalyzed domino reaction of alkyl halides and anthranilamides under air affords 2-substituted quinazolin-4(3H)-ones in good to excellent yields and with wide functional group tolerance. A mechanism for a copper(I) bromide involved organometal-catalyzed reaction via a four-step domino reaction is proposed.

ChemInform Abstract: Synthesis of Aryl and Arylmethyl Phosphonates by Cross‐Coupling of Aryl or Arylmethyl Halides (X: I, Br and Cl) with Diisopropyl H‐Phosphonate.

AbstractThe new method for the palladacycle‐catalyzed arylation reaction is applicable to a wide range of substrates as aryl iodides, bromides and chlorides tolerating diverse substitution pattern including several ortho‐substituents.

Synthesis of Aryl and Arylmethyl Phosphonates by Cross‐Coupling of Aryl or Arylmethyl Halides (X = I, Br and Cl) with Diisopropyl H‐Phosphonate

AbstractAn efficient and generally applicable protocol for the palladacycle‐catalysed arylation or K2CO3‐promoted arylmethylation of diisopropyl H‐phosphonate has been developed. The remarkable features of the palladacycle‐catalysed arylation reaction include wide substrate scope (aryl iodides, bromides and chlorides), significant shortening of the reaction time (2 or 3 h) and a low catalyst loading of 1 mol‐%. Note that with the base K2CO3 as promoter, arylmethylation could be achieved without any palladium catalyst. Moreover, the first example of a palladium‐catalysed phosphonation of inactive electron‐rich aryl chlorides with tBuOK as the base has been realized. This result could be considered an important improvement and complement to earlier work of Montchamp and Han, whose catalytic systems are typically compatible with electron‐deficient and electron‐neutral aryl chlorides.

Cu(acac)2-Catalyzed Synthesis of Functionalized Bis(arylmethyl)zinc Reagents and Their Olefination Reaction with Aromatic Aldehydes

An efficient and facile copper(II) acetylacetonate catalyzed synthesis of functionalized bis(arylmethyl)zinc reagents from arylmethyl halides and their olefination reaction with aromatic aldehydes is reported. Aluminum trichloride was found to be the key ingredient in these reactions and (E)-stilbenes were obtained in high yields.

N4-(3-Bromophenyl)-7-(substituted benzyl) pyrrolo[2,3-d]pyrimidines as potent multiple receptor tyrosine kinase inhibitors: Design, synthesis, and in vivo evaluation

With the goal of developing multitargeted receptor tyrosine kinase inhibitors that display potent inhibition against PDGFRβ and VEGFR-2 we designed and synthesized eleven N4-(3-bromophenyl)-7-(substitutedbenzyl) pyrrolo[2,3-d]pyrimidines 9a–19a. These compounds were obtained from the key intermediate N4-(3-bromophenyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine 29. Various arylmethyl groups were regiospecifically attached at the N7 of 29 via sodium hydride induced alkylation with substituted arylmethyl halides. Compounds 11a and 19a were potent dual inhibitors of PDGFRβ and VEGFR-2. In a COLO-205, in vivo tumor mouse model 11a demonstrated inhibition of tumor growth, metastasis, and tumor angiogenesis that was better than or comparable to the standard compound TSU-68 (SU6668, 8).

Iron Nanoparticle-Promoted Cu (I)-Catalysed Homocoupling of Arylmethyl Halides for the Synthesis of 1,2-diarylethanes

Carbon–carbon bond formation is important in organic synthesis for the preparation of natural products, organic materials and polymers and so on. An efficient and mild reductive homocoupling of arylmethyl halides is now described. Treatment of various benzylic halides in the presence of zero valent iron nanoparticles (nZVI) and a catalytic amount of CuBr in air and water at room temperature afforded 1,2-diarylethanes in excellent yields.

ChemInform Abstract: Single-Electron-Transfer-Initiated Thermal Reactions of Arylmethyl Halides. Part 15. The Reaction of Triphenylmethyl Bromide with Potassium O-Ethyl Dithiocarbonate (Potassium Xanthate) in Benzene and Cumene. A Note of Caution on the A

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Palladium‐Catalyzed Carbonylation of Arylmethyl Halides: Efficient Synthesis of Arylacetic Acid and Esters.

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Palladium-catalyzed carbonylation of arylmethyl halides: efficient synthesis of arylacetic acid and esters

Organopalladium complexes derived from 2-(bromomethyl)benzenemethanol, 2- bromo- and iodobenzenemethanols and 2-iodobenzeneethanol are efficient catalysts for the reaction of carbon monoxide and arylmethyl halides leading to arylacetic acids and esters.

Regioselective Synthesis of 1‐Allyl‐ and 1‐Arylmethyl Uracil and Thymine Derivatives.

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