Novel Methodologies for Chemical Activation in Organic Synthesis under Solvent-Free Reaction Conditions DOI Creative Commons
C.G. Ávila-Ortíz, Eusebio Juaristi

Molecules, Journal Year: 2020, Volume and Issue: 25(16), P. 3579 - 3579

Published: Aug. 6, 2020

One central challenge for XXI century chemists is the development of sustainable processes that do not represent a risk either to humanity or environment. In this regard, search more efficient and clean alternatives achieve chemical activation molecules involved in transformations has played prominent role recent years. The use microwave UV-Vis light irradiation, mechanochemical already widespread many laboratories. Nevertheless, an additional condition “green” comes from point view so-called atom economy. removal solvents reactions generally leads cleaner, economical processes. This review presents several illustrative applications protocols synthesis organic compounds under solvent-free reaction conditions.

Language: Английский

Salient Achievements in Synthetic Organic Chemistry Enabled by Mechanochemical Activation DOI
Eusebio Juaristi, C.G. Ávila-Ortíz

Synthesis, Journal Year: 2023, Volume and Issue: 55(16), P. 2439 - 2459

Published: May 3, 2023

Abstract Although known for millennia, it is only recently that mechanochemistry has received serious attention by chemists. Indeed, during the past 15 years an extraordinary number of reports concerning solid-state chemical transformations through grinding and milling techniques have been recorded. This short review discusses circumstances led this renaissance, highlighting present intense interest in so-called green chemistry, enabling capacity to handle insoluble substrates, identification profound influence additives can on mechanochemically activated reactions. The core account focuses salient developments synthetic organic especially amino acid peptide­ mechanosynthesis, successful employment mechanochemical activation combination with asymmetric organocatalysis, promising enzymatic whole cell biocatalysis, remarkable achievement multicomponent selective reactions via complex, multistep reaction pathways, mechanosynthesis representative heterocycles. final section comments some pending tasks area, such as scaling-up processes be practical use industry, requirement easier more efficient control parameters monitoring devices, consequently careful analysis additional procedures a proper understanding phenomena. 1 Introduction 2 Brief History Mechanochemistry 3 Milling Equipment Reaction Parameters 4 Attributes That Propelled Its Present Renaissance 4.1 Enormous Attention Being Presently Paid Sustainable Chemistry 4.2 Reduced Energy Consumption 4.3 Additive-Based 4.4 Handling Insoluble Reactants 4.5 ‘Impossible’ Reactions Are Successful 4.6 Air- Water-Sensitive Reagents Ball 5 Salient Developments Mechanochemical Activation Synthetic Organic 5.1 Amino Acid Peptide Mechanosynthesis 5.2 Asymmetric Synthesis Organocatalysis under Ball-Milling Conditions 5.3 Mechanoenzymology 5.4 Multicomponent Activated 5.5 Heterocycles Modification 6 Future Directions 6.1 Scaling-Up Protocols 6.2 Temperature-Controlled 6.3 Understanding Transformations 6.4 Emerging Techniques 7 Conclusions

Language: Английский

Citations

52
Process Mass Intensity (PMI): A Holistic Analysis of Current Peptide Manufacturing Processes Informs Sustainability in Peptide Synthesis DOI Creative Commons
Ivy Kekessie, Katarzyna Wegner,

Isamir Martinez

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(7), P. 4261 - 4282

Published: March 20, 2024

Small molecule therapeutics represent the majority of FDA-approved drugs. Yet, many attractive targets are poorly tractable by small molecules, generating a need for new therapeutic modalities. Due to their biocompatibility profile and structural versatility, peptide-based possible solution. Additionally, in past two decades, advances peptide design, delivery, formulation, devices have occurred, making peptides an modality. However, manufacturing is often limited solid-phase synthesis (SPPS), liquid phase (LPPS), lesser extent hybrid SPPS/LPPS, with SPPS emerging as predominant platform technology synthesis. involves use excess solvents reagents which negatively impact environment, thus highlighting newer technologies reduce environmental footprint. Herein, fourteen American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR) member companies portfolio compiled Process Mass Intensity (PMI) metrics help inform sustainability efforts This includes PMI assessment on 40 synthetic processes at various development stages pharma, classified according phase. most comprehensive date. The process was divided into (synthesis, purification, isolation) determine respective PMI. On average, (SPPS) (PMI ≈ 13,000) does not compare favorably other modalities such molecules median 168–308) biopharmaceuticals 8300). Thus, high warrants more environmentally friendly manufacturing.

Language: Английский

Citations

28
Biomass-Derived Solvents for Sustainable Transition Metal-Catalyzed C–H Activation DOI
Parthasarathy Gandeepan, Nikolaos Kaplaneris, Stefano Santoro

et al.

ACS Sustainable Chemistry & Engineering, Journal Year: 2019, Volume and Issue: 7(9), P. 8023 - 8040

Published: March 29, 2019

Transition metal-catalyzed C–H activation has emerged as an increasingly powerful strategy in molecular syntheses and a particularly attractive alternative to classical methods of cross-couplings. During the recent years, significant focus been dedicated further improve sustainable nature approach. As solvents represent major portion organic pollution caused by chemical syntheses, range nontoxic, biobased, have developed substitute for common reaction media. In this review, we present general perspective biomass-derived transition reactions their unique potential up January 2019.

Language: Английский

Citations

100
Solvent-Free, Continuous Synthesis of Hydrazone-Based Active Pharmaceutical Ingredients by Twin-Screw Extrusion DOI Creative Commons
Deborah E. Crawford, Andrea Porcheddu,

Aaron S. McCalmont

et al.

ACS Sustainable Chemistry & Engineering, Journal Year: 2020, Volume and Issue: 8(32), P. 12230 - 12238

Published: Aug. 5, 2020

Twin-screw extrusion (TSE) was used to synthesize hydantoin-based active pharmaceutical ingredients (APIs) such as nitrofurantoin and dantrolene, employing minimal or no solvent. Postsynthetic workup not required. This work demonstrates that solvent-free synthesis can be conducted in a continuous manner for products.

Language: Английский

Citations

94
Greening the synthesis of peptide therapeutics: an industrial perspective DOI Creative Commons
Vincent Martin, Peter H. G. Egelund, Henrik Johansson

et al.

RSC Advances, Journal Year: 2020, Volume and Issue: 10(69), P. 42457 - 42492

Published: Jan. 1, 2020

This review highlights the efforts made to date promote greener peptide synthesis, from an industrial perspective.

Language: Английский

Citations

94
Green strategies for transition metal-catalyzed C–H activation in molecular syntheses DOI Creative Commons
Uttam Dhawa, Nikolaos Kaplaneris, Lutz Ackermann

et al.

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(17), P. 4886 - 4913

Published: Jan. 1, 2021

Sustainable strategies for the activation of inert C–H bonds towards improved resource-economy.

Language: Английский

Citations

81
Mechanochemical Grignard Reactions with Gaseous CO2 and Sodium Methyl Carbonate** DOI Creative Commons
Victoria S. Pfennig, Romina C. Villella, Julia Nikodemus

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(9)

Published: Dec. 23, 2021

Abstract A one‐pot, three‐step protocol for the preparation of Grignard reagents from organobromides in a ball mill and their subsequent reactions with gaseous carbon dioxide (CO 2 ) or sodium methyl carbonate providing aryl alkyl carboxylic acids up to 82 % yield is reported. Noteworthy are short reaction times significantly reduced solvent amounts [2.0 equiv. liquid assisted grinding (LAG) conditions]. Unexpectedly, bromides methoxy substituents lead symmetric ketones as major products.

Language: Английский

Citations

63
Mechanochemical C−X/C−H Functionalization: An Alternative Strategic Access to Pharmaceuticals DOI
Xinjie Yang, Chongyang Wu, Weike Su

et al.

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 2022(8)

Published: Jan. 11, 2022

Abstract In the pursuit of clean pharmaceutical production, chemists in medicinal industry require access to new sustainable methodologies reduce and even eliminate pollution, which is mainly produced by overuse organic solvents during chemical synthesis active ingredients (APIs). this context, solvent‐free/less mechanochemical functionalization small molecules has gradually emerged as a powerful strategy for green modification APIs, bioactive compounds, functional materials. review, we present an overview C−X/C−H applications chemistry, involving cross‐coupling, cross‐dehydrogenative coupling, oxidative coupling (via C−H activation pathway), direct radical pathway) key steps preparation APIs compounds.

Language: Английский

Citations

45
Solid‐State Enzymatic Hydrolysis of Mixed PET/Cotton Textiles** DOI
Sandra Kaabel,

Jane Arciszewski,

Tristan H. Borchers

et al.

ChemSusChem, Journal Year: 2022, Volume and Issue: 16(1)

Published: Sept. 27, 2022

Waste polyester textiles are not recycled due to separation challenges and partial structural degradation during use recycling. Chemical recycling of polyethylene terephthalate (PET) through depolymerization can provide a feedstock monomers make "as-new" polymers. While enzymatic PET is more selective sustainable approach, methods in development, however, have thus far been limited clean, high-quality feedstocks, require an energy-intensive melt-amorphization step ahead treatment. Here, high-crystallinity mixed PET/cotton could be directly selectively depolymerized terephthalic acid (TPA) by using commercial cutinase from Humicola insolens under moist-solid reaction conditions, affording up 30±2 % yield TPA. The process was readily combined with cotton simultaneous or sequential application the cellulase enzymes CTec2®, providing 83±4 glucose without any negative influence on TPA yield.

Language: Английский

Citations

39
Mechanochemical Synthesis of Aryl Fluorides by Using Ball Milling and a Piezoelectric Material as the Redox Catalyst DOI
Xiaohong Wang, Xuemei Zhang, Xue Li

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(39)

Published: July 31, 2023

Abstract Aryl fluorides are important structural motifs in many pharmaceuticals. Although the Balz–Schiemann reaction provides an entry to aryl from aryldiazonium tetrafluoroborates, it suffers drawbacks such as long time, high temperature, toxic solvent, gas release, and low functional group tolerance. Here, we describe a general method for synthesis of tetrafluoroborates using piezoelectric material redox catalyst under ball milling conditions presence Selectfluor. This approach effectively addresses aforementioned limitations. Furthermore, can be recycled multiple times. Mechanistic investigations indicate that this fluorination may proceed via radical pathway, Selectfluor plays dual role both source fluorine terminal reductant.

Language: Английский

Citations

27