A field guide to flow chemistry for synthetic organic chemists

Chemical Science, Год журнала: 2023, Номер 14(16), С. 4230 - 4247

Опубликована: Янв. 1, 2023

This review explores the benefits of flow chemistry and dispels notion that it is a mysterious “black box”, demonstrating how can push boundaries organic synthesis through understanding its governing principles.

Язык: Английский

---

Efficient C(sp³)−H Carbonylation of Light and Heavy Hydrocarbons with Carbon Monoxide via Hydrogen Atom Transfer Photocatalysis in Flow**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(36)

Опубликована: Июль 17, 2023

Abstract Despite their abundance in organic molecules, considerable limitations still exist synthetic methods that target the direct C−H functionalization at sp 3 ‐hybridized carbon atoms. This is even more case for light alkanes, which bear some of strongest bonds known Nature, requiring extreme activation conditions are not tolerant to most molecules. To bypass these issues, chemists rely on prefunctionalized alkyl halides or organometallic coupling partners. However, new regioselectively a variety different scaffolds would be great added value, only late‐stage biologically active molecules but also catalytic upgrading cheap and abundant hydrocarbon feedstocks. Here, we describe general, mild scalable protocol enables C(sp )−H carbonylation saturated hydrocarbons, including natural products using photocatalytic hydrogen atom transfer (HAT) gaseous monoxide (CO). Flow technology was deemed crucial enable high gas‐liquid mass rates fast reaction kinetics, needed outpace deleterious pathways, leverage safe process.

Язык: Английский

---

Carbonylative transformation of aryl halides and strong bonds via cheap metal catalysts and sustainable technologies

Green Synthesis and Catalysis, Год журнала: 2024, Номер 5(4), С. 211 - 269

Опубликована: Май 6, 2024

The development of catalytic carbonylation reactions has increased considerably. Although many reviews/chapters/books on have been published, summaries cheap metal-catalyzed aryl halides and other chemical bonds with high dissociation energy C-Y (Y = O, N, H) are still very rare. Focusing green sustainable chemistry, this review summarizes discusses the achievements carbonylative transformations (C(sp2)-X) strong based non-expensive metal catalysts (Co, Mn, Mo, Ni, Fe, Cu), photochemical electrochemical systems developed in recent decades.

Язык: Английский

---

Recent Advances in Continuous Flow Synthesis of Metal-Organic Frameworks and Their Composites

Chemical Communications, Год журнала: 2024, Номер 60(65), С. 8497 - 8515

Опубликована: Янв. 1, 2024

Continuous flow synthesis offers a powerful approach for MOF & composite creation. This review explores its recent advancements, advantages over batch methods, impact on properties.

Язык: Английский

---

Continuous Microfluidic Antisolvent Crystallization as a Bottom-Up Solution for the Development of Long-Acting Injectable Formulations

Pharmaceutics, Год журнала: 2024, Номер 16(3), С. 376 - 376

Опубликована: Март 8, 2024

A bottom-up approach was investigated to produce long-acting injectable (LAI) suspension-based formulations overcome specific limitations of top-down manufacturing methods by tailoring drug characteristics while making the more sustainable and cost-efficient. Secoya microfluidic crystallization technology-based continuous liquid antisolvent (SCT-CLASC) process optimized afterward compared an earlier developed microchannel reactor-based (MCR-CLASC) setup, using itraconazole (ITZ) as model drug. After operating parameter optimization downstream processing (i.e., concentrating suspensions), stable microsuspensions were generated with a final solid loading 300 mg ITZ/g suspension. The post-precipitation feed suspension consisted 40 drug-to-excipient ratio 53:1. Compared MCR-CLASC where suspensions contained 10 had 2:1, higher concentration lower excipient use successfully achieved LAI SCT-CLASC setup. To ensure stability during storage, suspensions' quality monitored for particle size distribution (PSD), solid-state form, morphology. PSD ITZ crystals in maintained within target range 1-10 µm, displayed elongated plate-shaped morphology state confirmed be form I, which is most thermodynamically ITZ. In conclusion, this work lays foundation energy-efficient, robust, reproducible manufacture at industrial scale.

Язык: Английский

---

Advances in the Continuous Flow Synthesis of 3‐ and 4‐Membered Ring Systems

Chemistry - A European Journal, Год журнала: 2024, Номер 30(32)

Опубликована: Апрель 2, 2024

Abstract Small carbo‐ and heterocyclic ring systems have experienced a significant increase in importance recent years due to their relevance modern pharmaceuticals, as building blocks for designer materials or synthetic intermediates. This necessitated the development of new methods preparation these strained focusing on effectiveness scalability. The high strain entities well use high‐energy reagents intermediates has often challenged synthesis. Continuous flow approaches thus emerged highly effective means safely reliably access scaffolds. In this short review, key developments field are summarised showcasing power continuous accessing 3‐ 4‐membered via thermal, photo‐ electrochemical processes.

Язык: Английский

---

Combining computational fluid dynamics, photon fate simulation and machine learning to optimize continuous-flow photocatalytic systems

Reaction Chemistry & Engineering, Год журнала: 2023, Номер 8(9), С. 2119 - 2133

Опубликована: Янв. 1, 2023

Photoredox catalysis is a thriving field in chemistry. Microfluidics bring advantages for light-mediated reactions. CFD, ray-tracing, and machine learning hold promise advancing microflow techniques.

Язык: Английский

---

Modular Photochemical Flow Synthesis of Structurally Diverse Benzyne and Triazine Precursors

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(15), С. 2628 - 2635

Опубликована: Июль 3, 2023

Abstract Benzyne and related arynes are classical high‐energy species with a rich history of widespread applications in synthesis. However, despite several synthetic routes being available to generate their precursors, none represents an ideal entry benzyne chemistry view safety, scalability, sustainability. Here we report new photochemical flow process allowing for the generation precursors high yields, throughput, easy isolation multigram quantities products. This leverages catalyst‐free rearrangement via photoexcited nitro arene which involves cyclic hydroxylamine intermediate that has been fully characterized. The resulting were converted benzynes second generating heterocyclic targets upon trapping azide sydnone partners. Remarkably, when reacting secondary amines, wide range aryl triazines is obtained good yields third photo‐flow transformation. modular approach synthesize these species, avoids use potentially explosive diazonium salts. Ultimately, three processes using single high‐power LED light source (365 nm, adjustable in‐put power) presented manifest benefits compared batch processing. Moreover, functionalization pendent carboxyl group form sets biologically relevant triazine‐based amides highlights further unique industrially triazine entities.

Язык: Английский

---

Controlling the Crystallisation and Hydration State of Crystalline Porous Organic Salts

Chemistry - A European Journal, Год журнала: 2023, Номер 29(64)

Опубликована: Авг. 24, 2023

Crystalline porous organic salts (CPOS) are a subclass of molecular crystals. The low solubility CPOS and their building blocks limits the choice crystallisation solvents to water or polar alcohols, hindering isolation, scale-up, scope material. In this work, high throughput screening was used expand solvent scope, resulting in identification new salt, CPOS-7, formed from tetrakis(4-sulfophenyl)methane (TSPM) tetrakis(4-aminophenyl)methane (TAPM). CPOS-7 does not form with standard for CPOS, rather hydrated phase (Hydrate2920) previously reported is isolated. Initial attempts translate batch led challenges loss crystallinity Hydrate2920 forming favorably presence excess water. Using acetic acid as dehydrating agent hindered formation furthermore allowed direct conversion CPOS-7. To allow flow chemistry first time circumvent issues found batch. were shown have promise CO

Язык: Английский

---

Continuous Flow Oxidation of Alcohols Using TEMPO/NaOCl for the Selective and Scalable Synthesis of Aldehydes

Organic Process Research & Development, Год журнала: 2023, Номер 28(5), С. 1587 - 1596

Опубликована: Сен. 7, 2023

A simple and benign continuous flow oxidation protocol for the selective conversion of primary secondary alcohols into their respective aldehyde ketone products is reported. This approach makes use catalytic amounts TEMPO in combination with sodium bromide hypochlorite a biphasic solvent system. variety substrates are tolerated including those containing heterocycles based on potentially sensitive nitrogen sulfur moieties. The can be coupled inline reactive extraction by formation carbonyl-bisulfite adduct which aids separation remaining substrate or other impurities. Process robustness evaluated preparation phenylpropanal at decagram scale, trifluoromethylated oxazole building block as well late-stage intermediate anti-HIV drug maraviroc demonstrates potential value this method.

Язык: Английский

---