Solvent-free Ball-milling Conditions Research Articles

Convenient and efficient N-methylation of secondary amines under solvent-free ball milling conditions

In the present work, we report the development of a rapid, efficient, and solvent-free procedure for the N-methylation of secondary amines under mechanochemical conditions. After optimization of the milling parameters, a vibrational ball mill was used to synthesize 26 tertiary N-methylated amine derivatives in a short time of 20 min (30 Hz frequency) and high yields ranging from 78 to 95%. An exception was compounds having a hydroxyl group in their structure, for which a decrease in reaction efficiency was observed. During our research, we investigated alternate reaction selectivity occurring in compounds able to form ring closure products that are 3,4-dihydro-2H-1,3-benzoxazine derivatives instead of N-methylated products. The liquid-assisted grinding technique has been applied using formalin as a methylating agent and sodium triacetoxyborohydride as a reducing agent in a reductive amination reaction.

Unexpected and divergent mechanosynthesis of furanoid-bridged fullerene dimers C120O and C120O2.

An unexpected, divergent and efficient approach toward furanoid-bridged fullerene dimers C120O and C120O2 was established under different solvent-free ball-milling conditions by simply using pristine C60 as the starting material, water as the oxygen source and FeCl3 as the mediator. The structures of C120O and C120O2 were unambiguously established by single-crystal X-ray crystallography. A plausible reaction mechanism is proposed on the basis of control experiments. Furthermore, C120O2 has been applied in organic solar cells as the third component and exhibits good performance.

Solvent-Free Mechanosynthesis of Polysubstituted 1,2-Dihydroquinolines from Anilines and Alkyne Esters.

A novel one-pot reaction of anilines with acetylenedicarboxylate diesters in the presence of boron trifluoride, iodine, and trifluoroacetic acid or methylsulfonic acid has been developed under solvent-free ball-milling conditions, affording a variety of polysubstituted 1,2-dihydroquinolines bearing multiple ester groups in moderate to excellent yields. The present protocol features mild reaction conditions, short reaction time, and feasibility of large-scale synthesis, providing a facile and practical alternative to 1,2-dihydroquinoline synthesis. Intriguingly, the generated 1,2-dihydroquinolines can be further transformed into quinoline derivatives.

Regiodivergent Synthesis of 4,5'- and 4,4'-Imidazolinyl Spiropyrazolones from 4-Alkylidene Pyrazolones and Amidines.

The solvent-free reaction of 4-alkylidene pyrazolones with amidines can furnish 4,5'-imidazolinyl spiropyrazolones in good to excellent yields when promoted by N-iodosuccinimide under solvent-free ball-milling conditions, whereas it almost exclusively affords 4,4'-imidazolinyl spiropyrazolones if mediated by N-bromosuccinimide in heated toluene. On the basis of this switchable cyclization strategy, a powerful metal-free method for regioselective and diastereoselective synthesis of structurally diverse 4,5'- and 4,4'-imidazolinyl spiropyrazolones has been successfully developed.

Sulfamic acid catalyzed oxonium-ene reactions under ball milling conditions: Straightforward access to highly functionalized Oxabicyclo[3.2.1]octenes

Herein, we report a facile green procedure for the synthesis of oxabicyclo[3.2.1]octenes using sulfamic acid as catalyst under solvent-free ball milling conditions. A series of aldehydes or epoxides underwent oxonium-ene reaction with (−)-terpinen-4-ol under optimized conditions to produce a variety of oxabicyclo[3.2.1]octene derivatives. The excellent selectivity, higher isolated yields of the products, use of mild catalyst and solvent-free ball milling conditions, and recyclability are the major advantages of the present procedure.

Mechanochemically Activated Asymmetric Organocatalytic Domino Mannich Reaction-Fluorination

Mechanochemical activation effectively mediated asymmetric organocatalytic domino Mannich addition followed by diastereoselective fluorination. The Mannich reactions of pyrazolones and to a lesser extent those of isoxazolones were effective under solvent-free ball-milling conditions. This reaction in combination with a chiral squaramide catalyst provided corresponding products in high yields and enantiomeric purities up to 99:1 e.r. and as a single diastereomer. DFT calculations revealed reasons for high diastereoselectivity.

One-Pot Multicomponent Mechanosynthesis of Polysubstituted trans-2,3-Dihydropyrroles and Pyrroles from Amines, Alkyne Esters, and Chalcones.

An efficient and practical one-pot multicomponent reaction of amines with alkyne esters and chalcones promoted by I2/PhI(OAc)2 has been developed under solvent-free ball-milling conditions to afford a variety of polysubstituted trans-2,3-dihydropyrroles in moderate to good yields. The present method features a short reaction time, mild reaction conditions, broad substrate scope, and feasibility of large-scale synthesis. Intriguingly, this protocol can also furnish the corresponding synthetically more attractive pyrroles with the addition of an oxidant in a one-pot way.

Solvent-free N-iodosuccinimide-promoted synthesis of spiroimidazolines from alkenes and amidines under ball-milling conditions

An environmentally benign and N-iodosuccinimide-promoted intermolecular cyclization between alkenes and amidines has been demonstrated under solvent-free ball-milling conditions, affording a variety of spiroimidazolines with remarkable functional group tolerance and good to excellent yields.

Manganese (III) acetate mediated synthesis of polysubstituted pyrroles under solvent-free ball milling

Under solvent-free ball milling conditions, a simple and mild method was developed for efficient synthesis of 2,5-dimethyl-3,4-dicarboxylate-pyrroles and N-substituted 3,4-diphenylpyrroles via condensation-annulation of amines with acetoacetate and 2-phenylacetaldehyde, respectively. The use of cheap and safe Mn(OAc)3 as a mediator, no use of commonly employed acetic acid as solvent, short reaction time and readily available starting materials make this protocol a good alternative to traditional synthesis of polysubstituted pyrroles.

Green High-Yielding One-Pot Approach to Biginelli Reaction under Catalyst-Free and Solvent-Free Ball Milling Conditions

A simple, green, and efficient approach was used to synthesize 3,4-dihydropyrimidines derivatives. We showed that the application of the planetary ball milling method with a ball-to-reagent weight ratio of 8 for the Biginelli reaction provides 3,4-dihydropyrimidines derivatives with excellent yields (>98%) in a short reaction time from the one-pot, three-component condensation of aldehydes, ethyl acetoacetate, and urea (or thiourea).

Eco-friendly one-pot, three-component synthesis of novel derivatives of kojic acid by the Mannich-type reaction under solvent-free ball-milling conditions

A novel series of aminokojic acid derivatives were efficiently synthesized by one-pot condensation of kojic acid, aromatic aldehydes and heteroaromatic amines in the presence of cerium(III) sulphate as an efficient and recyclable catalyst in ball-milling under solvent-free conditions at room temperature. This synthesis method offers several advantages, including a green and eco-friendly protocol, operational simplicity, mild reaction conditions, short reaction time, higher yields and easy workup procedures. The workup of these very clean reactions involves only a simple washing with acetone/cold water. The catalytic system can be reused several times with no loss of activity.

Solvent-free synthesis of naphthopyrans under ball-milling conditions

Under solvent-free ball-milling conditions, the nucleophilic addition reactions of terminal alkynes to carbonyl compounds promoted by KOH proceeded efficiently at ambient temperature. Subsequent cyclization reactions of the synthesized propargylic alcohols with 2-naphthol catalyzed by indium trichloride tetrahydrate, leading to the formation of naphthopyrans, were then investigated. In most cases, side reactions were avoided and thus high yields were achieved.

Unexpected Solvent-Free Cycloadditions of 1,3-Cyclohexanediones to 1-(Pyridin-2-yl)-enones Mediated by Manganese(III) Acetate in a Ball Mill

Under solvent-free ball-milling conditions, manganese(III) acetate dihydrate-mediated cycloadditions of 5,5-dimethyl-1,3-cyclohexanedione and 1,3-cyclohexanedione to various 1-(pyridin-2-yl)-enones proceeded efficiently to afford trans-2-acyl-3-aryl/alkyl-2,3,6,7-tetrahydro-4(5H)-benzofuranone derivatives. The cyclization reactions exhibited good to excellent yields, as well as extremely high diastereoselectivity and unexpected regioselectivity. Manganese(III) acetate behaved both as an oxidant and as a Lewis acid.