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21 pages, 960 KiB

Open AccessArticle

Reshuffle Bonds by Ball Milling: A Mechanochemical Protocol for Charge-Accelerated Aza-Claisen Rearrangements

by Christian Schumacher, Lieselotte Fritz, Lena M. Hanek, Vitali Sidorin, Daniel Brüx and Carsten Bolm

Molecules 2023, 28(2), 807; https://doi.org/10.3390/molecules28020807 - 13 Jan 2023

Viewed by 2366

Abstract

This study presents the development of a mechanochemical protocol for a charge-accelerated aza-Claisen rearrangement. The protocol waives the use of commonly applied transition metals, ligands, or pyrophoric Lewis acids, e.g., AlMe₃. Based on (heterocyclic) tertiary allylamines and acyl chlorides, the desired [...] Read more.

This study presents the development of a mechanochemical protocol for a charge-accelerated aza-Claisen rearrangement. The protocol waives the use of commonly applied transition metals, ligands, or pyrophoric Lewis acids, e.g., AlMe₃. Based on (heterocyclic) tertiary allylamines and acyl chlorides, the desired tertiary amides were prepared in yields ranging from 17% to 84%. Moreover, the same protocol was applied for a Belluš–Claisen-type rearrangement resulting in the synthesis of a 9-membered lactam without further optimization. Full article

(This article belongs to the Special Issue Mechanochemical Synthesis of Organic Compounds)

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11 pages, 1792 KiB

Open AccessArticle

N-Formylsaccharin: A Sweet(able) Formylating Agent in Mechanochemistry

by Federico Cuccu, Francesco Basoccu, Claudia Fattuoni and Andrea Porcheddu

Molecules 2022, 27(17), 5450; https://doi.org/10.3390/molecules27175450 - 25 Aug 2022

Cited by 3 | Viewed by 2220

Abstract

The acylation of amines has always attracted a deep interest as a synthetic route due to its high versatility in organic chemistry and biochemical processes. The purpose of this article is to present a mechanochemical acylation procedure based on the use of acyl-saccharin [...] Read more.

The acylation of amines has always attracted a deep interest as a synthetic route due to its high versatility in organic chemistry and biochemical processes. The purpose of this article is to present a mechanochemical acylation procedure based on the use of acyl-saccharin derivatives, namely N-formylsaccharin, N-acetylsaccharin, and N-propionylsaccharin. This protocol furnishes a valuable solvent-free alternative to the existing processes and aims to be highly beneficial in multi-step procedures due to its rapid and user-friendly workup. Full article

(This article belongs to the Special Issue Mechanochemical Synthesis of Organic Compounds)

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23 pages, 3227 KiB

Open AccessFeature PaperArticle

Synthesis of Mixed Dinucleotides by Mechanochemistry

by Faisal Hayat, Mikhail V. Makarov, Luxene Belfleur and Marie E. Migaud

Molecules 2022, 27(10), 3229; https://doi.org/10.3390/molecules27103229 - 18 May 2022

Cited by 4 | Viewed by 2262

Abstract

We report the synthesis of vitamin B1, B2, and B3 derived nucleotides and dinucleotides generated either through mechanochemical or solution phase chemistry. Under the explored conditions, adenosine and thiamine proved to be particularly amenable to milling conditions. Following optimization of the chemistry related [...] Read more.

We report the synthesis of vitamin B1, B2, and B3 derived nucleotides and dinucleotides generated either through mechanochemical or solution phase chemistry. Under the explored conditions, adenosine and thiamine proved to be particularly amenable to milling conditions. Following optimization of the chemistry related to the formation pyrophosphate bonds, mixed dinucleotides of adenine and thiamine (vitamin B1), riboflavin (vitamin B2), nicotinamide riboside and 3-carboxamide 4-pyridone riboside (both vitamin B3 derivatives) were generated in good yields. Furthermore, we report an efficient synthesis of the MW+4 isotopologue of NAD⁺ for which deuterium incorporation is present on either side of the dinucleotidic linkage, poised for isotopic tracing experiments by mass spectrometry. Many of these mixed species are novel and present unexplored possibilities to simultaneously enhance or modulate cofactor transporters and enzymes of independent biosynthetic pathways. Full article

(This article belongs to the Special Issue Mechanochemical Synthesis of Organic Compounds)

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14 pages, 1484 KiB

Open AccessArticle

Mechanochemical Dimerization of Aldoximes to Furoxans

by Run-Kai Fang, Kuan Chen, Chuang Niu and Guan-Wu Wang

Molecules 2022, 27(8), 2604; https://doi.org/10.3390/molecules27082604 - 18 Apr 2022

Cited by 2 | Viewed by 2039

Abstract

Solvent-free mechanical milling is a new, environmentally friendly and cost-effective technology that is now widely used in the field of organic synthesis. The mechanochemical solvent-free synthesis of furoxans from aldoximes was achieved through dimerization of the in situ generated nitrile oxides in the [...] Read more.

Solvent-free mechanical milling is a new, environmentally friendly and cost-effective technology that is now widely used in the field of organic synthesis. The mechanochemical solvent-free synthesis of furoxans from aldoximes was achieved through dimerization of the in situ generated nitrile oxides in the presence of sodium chloride, Oxone and a base. A variety of furoxans was obtained with up to a 92% yield. The present protocol has the advantages of high reaction efficiency and mild reaction conditions. Full article

(This article belongs to the Special Issue Mechanochemical Synthesis of Organic Compounds)

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16 pages, 1835 KiB

Open AccessArticle

Manipulating Reaction Energy Coordinate Landscape of Mechanochemical Diaza-Cope Rearrangement

by Tingting Cheng, Wenxian Ma, Hao Luo, Yangzhi Ye and KaKing Yan

Molecules 2022, 27(8), 2570; https://doi.org/10.3390/molecules27082570 - 15 Apr 2022

Cited by 2 | Viewed by 2224

Abstract

Chiral vicinal diamines, a unique class of optically-active building blocks, play a crucial role in material design, pharmaceutical, and catalysis. Traditionally, their syntheses are all solvent-based approaches, which make organic solvent an indispensable part of their production. As part of our program aiming [...] Read more.

Chiral vicinal diamines, a unique class of optically-active building blocks, play a crucial role in material design, pharmaceutical, and catalysis. Traditionally, their syntheses are all solvent-based approaches, which make organic solvent an indispensable part of their production. As part of our program aiming to develop chemical processes with reduced carbon footprints, we recently reported a highly practical and environmentally-friendly synthetic route to chiral vicinal diamines by solvent-free mechanochemical diaza-Cope rearrangement. We herein showed that a new protocol by co-milling with common laboratory solid additives, such as silica gel, can significantly enhance the efficiency of the reaction, compared to reactions in the absence of additives. One possible explanation is the Lewis acidic nature of additives that accelerates a key Schiff base formation step. Reaction monitoring experiments tracing all the reaction species, including reactants, intermediates, and product, suggested that the reaction profile is distinctly different from ball-milling reactions without additives. Collectively, this work demonstrated that additive effect is a powerful tool to manipulate a reaction pathway in mechanochemical diazo-Cope rearrangement pathway, and this is expected to find broad interest in organic synthesis using mechanical force as an energy input. Full article

(This article belongs to the Special Issue Mechanochemical Synthesis of Organic Compounds)

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18 pages, 5520 KiB

Open AccessArticle

Mechanochemical Applications of Reactive Extrusion from Organic Synthesis to Catalytic and Active Materials

by Emanuela Calcio Gaudino, Giorgio Grillo, Maela Manzoli, Silvia Tabasso, Simone Maccagnan and Giancarlo Cravotto

Molecules 2022, 27(2), 449; https://doi.org/10.3390/molecules27020449 - 10 Jan 2022

Cited by 18 | Viewed by 3928

Abstract

In the past, the use of mechanochemical methods in organic synthesis was reported as somewhat of a curiosity. However, perceptions have changed over the last two decades, and this technology is now being appreciated as a greener and more efficient synthetic method. The [...] Read more.

In the past, the use of mechanochemical methods in organic synthesis was reported as somewhat of a curiosity. However, perceptions have changed over the last two decades, and this technology is now being appreciated as a greener and more efficient synthetic method. The qualified “offer” of ball mills that make use of different set-ups, materials, and dimensions has allowed this technology to mature. Nevertheless, the intrinsic batch nature of mechanochemical methods hinders industrial scale-ups. New studies have found, in reactive extrusion, a powerful technique with which to activate chemical reactions with mechanical forces in a continuous flow. This new environmentally friendly mechanochemical synthetic method may be able to miniaturize production plants with outstanding process intensifications by removing organic solvents and working in a flow mode. Compared to conventional processes, reactive extrusions display high simplicity, safety, and cleanliness, which can be exploited in a variety of applications. This paper presents perspective examples in the better-known areas of reactive extrusions, including oxidation reactions, polymer processing, and biomass conversion. This work should stimulate further developments, as it highlights the versatility of reactive extrusion and the huge potential of solid-phase flow chemistry. Full article

(This article belongs to the Special Issue Mechanochemical Synthesis of Organic Compounds)

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10 pages, 9964 KiB

Open AccessArticle

Ionic Liquid-Assisted Grinding: An Electrophilic Fluorination Benchmark

by Pavel A. Zaikin, Ok Ton Dyan, Innokenty R. Elanov and Gennady I. Borodkin

Molecules 2021, 26(19), 5756; https://doi.org/10.3390/molecules26195756 - 23 Sep 2021

Cited by 13 | Viewed by 2098

Abstract

We demonstrated the influence of liquid additives on the rate and selectivity of mechanochemical fluorination of aromatic and 1,3-dicarbonyl compounds with F-TEDA-BF₄. Substoichiometric catalytic quantities of ionic liquids speed up the reaction. We proposed an improved protocol for ionic liquids-assisted fluorination [...] Read more.

We demonstrated the influence of liquid additives on the rate and selectivity of mechanochemical fluorination of aromatic and 1,3-dicarbonyl compounds with F-TEDA-BF₄. Substoichiometric catalytic quantities of ionic liquids speed up the reaction. We proposed an improved protocol for ionic liquids-assisted fluorination that allows easy and efficient isolation of fluorinated products by vacuum sublimation. A careful choice of additive results in high yields of fluorinated products and low E-factor for the overall process. Here, we report a benchmarking study of various ionic liquids in comparison with representative molecular solvents. A lower viscosity of ionic liquid additive is typically associated with higher yields and a higher degree of difluorination. Ionic liquids with fluorous anions (triflate and triflimide) are shown to be the most efficient catalysts for ionic liquid-assisted grinding. Full article

(This article belongs to the Special Issue Mechanochemical Synthesis of Organic Compounds)

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14 pages, 2190 KiB

Open AccessArticle

Solvent-Free Mechanochemical Synthesis of High Transition Biphenyltetracarboxydiimide Liquid Crystals

by Jehan Y. Al-Humaidi, Siham A. Alissa, Kanubhai D. Katariya, Khulood A. Abu Al-Ola, Mohamed Hagar and Khaled D. Khalil

Molecules 2021, 26(10), 3035; https://doi.org/10.3390/molecules26103035 - 19 May 2021

Cited by 7 | Viewed by 1829

Abstract

A series of high temperature alkyl and alkoxy biphenyltetracarboxydiimide liquid crystals have been prepared under ball mill method using solvent-free mechanochemical approach. The thermal properties of the prepared compounds were investigated by deferential scanning calorimetry (DSC) measurements and the textures were identified by [...] Read more.

A series of high temperature alkyl and alkoxy biphenyltetracarboxydiimide liquid crystals have been prepared under ball mill method using solvent-free mechanochemical approach. The thermal properties of the prepared compounds were investigated by deferential scanning calorimetry (DSC) measurements and the textures were identified by polarized optical microscope (POM). The compounds showed smectic mesomorphic behaviour. The results showed the increasing nature of transition temperature Cr-SmC with chain length with increments of the SmC mesophase range. However, the mesophase range of the SmA was decreased with the terminal chain length either for the alkyl or alkoxy terminal groups. Moreover, the DFT theoretical calculations have been conducted give a detailed projection of the structure of the prepared compounds. A conformational investigation of the biphenyl part has been studied. A deep illustration of the experimental mesomorphic behaviour has been discussed in terms of the calculated aspect ratio. A projection of the frontier molecular orbitals as well as molecular electrostatic potential has been studied to show the effect of the polarity of the terminal chains on the level and the gab of the FMOs and the distribution of electrostatic charges on the prepared molecules. Full article

(This article belongs to the Special Issue Mechanochemical Synthesis of Organic Compounds)

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Review

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27 pages, 8964 KiB

Open AccessReview

Synthesis of Biologically Relevant 1,2,3- and 1,3,4-Triazoles: From Classical Pathway to Green Chemistry

by Lori Gonnet, Michel Baron and Michel Baltas

Molecules 2021, 26(18), 5667; https://doi.org/10.3390/molecules26185667 - 18 Sep 2021

Cited by 17 | Viewed by 4023

Abstract

Green Chemistry has become in the last two decades an increasing part of research interest. Nonconventional «green» sources for chemical reactions include micro-wave, mechanical mixing, visible light and ultrasound. 1,2,3-triazoles have important applications in pharmaceutical chemistry while their 1,2,4 counterparts are developed to [...] Read more.

Green Chemistry has become in the last two decades an increasing part of research interest. Nonconventional «green» sources for chemical reactions include micro-wave, mechanical mixing, visible light and ultrasound. 1,2,3-triazoles have important applications in pharmaceutical chemistry while their 1,2,4 counterparts are developed to a lesser extent. In the review presented here we will focus on synthesis of 1,2,3 and 1,2,4-triazole systems by means of classical and « green chemistry » conditions involving ultrasound chemistry and mechanochemistry. The focus will be on compounds/scaffolds that possess biological/pharmacophoric properties. Finally, we will also present the formal cycloreversion of 1,2,3-triazole compounds under mechanical forces and its potential use in biological systems. Full article

(This article belongs to the Special Issue Mechanochemical Synthesis of Organic Compounds)

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