布洛芬的环保合成方法

Herein, we review the recent progress in the synthesis of representative nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and naproxen. Although these drugs were discovered over 50 years ago, novel practical and asymmetric approaches are still being developed for their synthesis. In addition, this endeavor has enabled access to more potent and selective derivatives from the key frameworks of ibuprofen and naproxen. The development of a synthetic route to ibuprofen and naproxen over the last 10 years is summarized, including developing methodologies, finding novel synthetic routes, and applying continuous-flow chemistry.

Ibuprofen is a common anti-inflammatory drug (NSAID) that was first invented and patented by Boots UK back in the 1960s. Even though ibuprofen is made in huge amounts worldwide nowadays, researchers are still trying to improve how it's synthesized to make the process more efficient, sustainable, and less harmful to the environment. This paper looks at how ibuprofen synthesis methods have evolved over history, from Boots' original approach to more recent stuff like the BHC process, using electrochemistry, and continuous flow systems. It examines the mechanism, green chemistry measures, and the pros and cons of each technique. While it gave the first usable manufacturing method, Boots' synthesis wasn't so great with its atom economy. The BHC synthesis boosted yield and atom economy a lot by streamlining the process. Newer ways aim to make it even more selective and sustainable by using novel chemistries and tighter process control. Basically, ibuprofen synthesis has steadily progressed over time thanks to step-by-step innovation and a better understanding of the mechanisms. The paper suggests ways forward to produce this important drug in safer, more efficient, eco-friendly ways using modern green chemistry practices. Any pharmaceutical synthesis impacts people and the environment, so we gotta keep improving processes.

… , 4 which includes ibuprofen (1). Inspired by McQuade’s landmark continuous synthesis, 5 we sought to develop a scalable continuous synthesis of this generic pharmaceutical. …

Abstract In China, the most commonly used method for the synthesis of ibuprofen is aryl-1,2–translocation rearrangement, which comprises several main processes: the Friedel-hydrolysis reaction, ketal reaction and so on. There are some problems in the process of industrial production. The temperature control of the Friedel-hydrolysis reaction is a problem because excessive temperatures will lead to the occurrence of side reactions, and low temperatures will lead to the crystallization of raw reaction materials. The reaction time of the ketal reaction is up to 24 h, which limits the productive capacity of ibuprofen. Otherwise, the emissions of the ibuprofen synthesis processes are more than 5000 m3/h of waste gas with VOC contents of over 1000 mg/m3 and highly concentrated organic wastewater, with a COD up to 20,000 mg/L. Therefore, process intensification and waste minimization of the ibuprofen synthesis process is described in this paper. A new reactor is designed for the Friedel-hydrolysis reaction. The reaction temperature can be precisely controlled at 13–15 °C, which effectively inhibits the occurrence of side reactions. The industrial applications showed that the ketal reaction time is reduced from 24 h to less than 8 h. The VOC content is reduced to less than 100 mg/m3, and the COD value is reduced to 150 mg/L in the improved processes, which meet national emissions standards.

… ibuprofen, known as the Boots or Browns Method, is widely recognised as the conventional approach in the field. The synthesis … resemblance to that of ibuprofen. The Boots method, …

This paper makes a parallel between the original route versus the green route of Ibuprofen (non-steroidal anti-inflammatory drugs most commonly recommended) synthesis. The original route contained six steps with stoichiometric reagents (some reagents are very toxic: hydrochloric acid, ammonia), a lot of intermediate products, relatively low atom efficiency equal to 40.04% and substantial inorganic salt formation (aluminium trichloride hydrate). The green route of Ibuprofen synthesis developed only three steps, a lower amount of waste and by-products (only acetic acid that can be used for another applications) and an atom efficiency of 77.44%. The green route for Ibuprofen synthesis is an exquisite example of a simple and elegant chemical/pharmaceutical manufacturing process and the nearly complete atom utilization of this streamlined process truly makes it a wasteminimizing, environmentally friendly technology.

The ACS Green Chemistry Institute Pharmaceutical Roundtable was formed in 2005 to encourage the incorporation of green chemistry techniques into the synthetic pathways of pharmaceuticals. Through this initiative, synthetic pathways of several pharmaceuticals have been altered to adapt more environmentally friendly procedures. The amount of electricity required to complete chemical reactions have become an environmental concern due to depleting fossil fuels. A technique was recently developed in which satellite dishes were repurposed as solar reflectors capable of providing a heat source through solar irradiation. The ability to use the solar reflector as the sole heat source for synthetic reactions has been analyzed for the commercially important pharmaceutical, ibuprofen. Ibuprofen synthesis also incorporates chemicals that are not particularly friendly to the environment. The exchange of these chemicals with more environmentally friendly substitutes has been analyzed. The goal of this study is to incorporate a solar energy heat source to develop an alternative energy, more environmentally friendly pathway to ibuprofen.Graphical abstractThe synthetic route designed to synthesize ibuprofen using an alternative energy heat source and more environmentally friendly reagents.

In this study, the environmental impacts of three ibuprofen production routes, namely, the BHC, the Bogdan, and the newly developed enzymatic synthetic routes (modified Bogdan process), are assessed and compared by the application of life cycle assessment (LCA). Based on the data obtained through literature and laboratory-based experiments, a pilot-scale production with a capacity of 500 g/day of ibuprofen was simulated to generate inventory data for the LCA study, using Aspen Plus V11. The well-established BHC process was chosen as the benchmark to quantify the operational and environmental benefits of the innovative enzymatic Bogdan flow synthetic process. The comparison highlights the benefit of adopting the modified Bogdan synthesis route via an enzymatic catalyst. Results show that a general reduction of environmental impact is achievable across the whole set of impact categories of the analysis, and the magnitude of such reduction depends on the efficiency of recycling in the production system. Considering a 50% efficiency of recycling, the modified Bogdan system achieves lower environmental impacts in some impact categories like Acidification, Ecotoxicity of freshwater, Human toxicity, Particulate matter, and Resource depletion (mineral, fossils, renewables) while having higher impacts on the rest of the impact categories. Yet, the new process proposed here scores better environmental performances in all of the impact categories when the enzyme recycling is close to 100%, which is promising for future technology development.

… In this work, a simulation of (S)-ibuprofen production is carried out using ASPEN … ® process simulation software. A pilot scale production with the capacity of 500g/day of (S)-ibuprofen …

Abstract The continuous‐flow production of active pharmaceutical ingredients is a spreading applicative research field. Process simulation tools are effective means for in silico process design, but care is needed. A paradigmatic example is the synthesis of ibuprofen. First, the most appropriate thermodynamic models must be selected. The rich databases now available to collect thermodynamic properties are often insufficient because unconventional molecules are usually part of the recipe or found as intermediates or products. Furthermore, in some reaction steps ionic properties may be needed rather than those of the neutral molecules. All these points need a careful optimization of the methods for the estimation of the properties, with possible huge discrepancies of the results.

… , the scale-up of ibuprofen-loaded NP produced by three manufacturing processes – salting-out, … The equipment used for pilot-scale production was composed of three double-jacketed …

… The S-ibuprofen produced during each process was evaluated and approximately 50% increment in concentration of S-acid product was produced when dynamic kinetic resolution was …

Ibuprofen, a widely used nonsteroidal anti‐inflammatory drug (NSAID), is valued for its analgesic, antipyretic, and anti‐inflammatory properties. While batch synthesis remains dominant in industry due to its maturity, it presents drawbacks such as long reaction times, high energy consumption, and complex byproduct profiles. In response to growing demands for greener pharmaceutical manufacturing, continuous flow technology has emerged as a promising alternative. It offers enhanced efficiency, scalability, and environmental compatibility. This review highlights recent advancements in ibuprofen synthesis via batch and continuous flow approaches, with a focus on the development of catalytic systems, reactor optimization, and process intensification. The fundamental principles of flow chemistry and the current technical challenges are discussed. The study aims to provide insights into transitioning toward sustainable, high‐efficiency production of ibuprofen and to offer insights into broader applications of flow technology in pharmaceutical synthesiser.

Conventional wisdom and many published histories of “Green Chemistry” describe its start as being a result of governmental and/or regulatory actions at the US Environmental Protection Agency (“EPA”) during the early 1990’s. But there were many Real World industrial examples of environmentally friendly commercial processes in the oil and commodity chemicals industries for decades prior to the 1990s. Some early examples of commercial “Green Chemistry” are briefly described in this article. The Boots/Hoechst Celanese (“BHC”) Ibuprofen process was one of the earliest multiple-award-winning examples of industrial “Green Chemistry” in the fine chemical/pharmaceutical industry. The author, who conceived the BHC Ibuprofen synthetic strategy in 1984, reveals and documents that the BHC Ibuprofen process was not primarily a result of governmental or regulatory mandates, or environmentalist or political motivations. The BHC ibuprofen process, and probably many other early industrial “green” inventions, evolved from, and their development and commercialization motivated and guided by, a long prior industrial culture of both scientific and technical evolution. The invention and commercialization of these early industrial commercialized processes, and the BHC Ibuprofen process were also guided by both competitive and economic market needs, personal human motivations, and a low waste culture of “Quality” and “Continuous Improvement” that the commodity chemical industry internally promoted in the 1980’s. The author comments on some perceptions of the status of Green Chemistry now, and directions it should consider going in the future. The author recommends that young Green Chemists and/or Green Engineers reconsider “Quality” approaches in order to genuinely lead Society toward a Greener future.

… these conditions, and with a fixed patent lifetime, the modern pharmaceutical industry needs to make an effort in evolving toward more efficient and innovative production processes. …

… of S-ibuprofen in the reactor has been found which was equal to 3.2 wt%. The process could be improved considerably by removing the denaturing ibuprofen during hydrolysis using an …

The principles of green chemistry (GC) can be comprehensively implemented in green synthesis of pharmaceuticals by choosing no solvents or green solvents (preferably water), alternative reaction media, and consideration of one-pot synthesis, multicomponent reactions (MCRs), continuous processing, and process intensification approaches for atom economy and final waste reduction. The GC's execution in green synthesis can be performed using a holistic design of the active pharmaceutical ingredient's (API) life cycle, minimizing hazards and pollution, and capitalizing the resource efficiency in the synthesis technique. Thus, the presented review accounts for the comprehensive exploration of GC's principles and metrics, an appropriate implication of those ideas in each step of the reaction schemes, from raw material to an intermediate to the final product's synthesis, and the final execution of the synthesis into scalable industry-based production. For real-life examples, we have discussed the synthesis of a series of established generic pharmaceuticals, starting with the raw materials, and the intermediates of the corresponding pharmaceuticals. Researchers and industries have thoughtfully instigated a green synthesis process to control the atom economy and waste reduction to protect the environment. We have extensively discussed significant reactions relevant for green synthesis, one-pot cascade synthesis, MCRs, continuous processing, and process intensification, which may contribute to the future of green and sustainable synthesis of APIs.

… Two routes for the production of ibuprofen via the common … Drug Company (the discoverers of ibuprofen), entails 6 steps … The BHC ibuprofen process was commercialized in 1992 in …

… resolve enantiomers of ibuprofen (IBU) in the present study. This type of chiral resolution process involves three steps: formation of a diastereomeric salt pair of racemic ibuprofen (Rac-…

… This flow synthesis has drawbacks associated with … synthesis that provides 1 in an integrated four-step process, providing a highly practical and economical approach toward ibuprofen …

Scalable processes have been developed to convert β-pinene into 4-isopropenylcyclohexanone which is then used as a feedstock for the divergent synthesis of sustainable versions of the common painkillers, paracetamol and ibuprofen. Both synthetic routes use Pd(0) catalysed reactions to aromatise the cyclohexenyl rings of key intermediates to produce the benzenoid ring systems of both drugs. The potential of using bioderived 4-hydroxyacetophenone as a drop-in feedstock replacement to produce sustainable aromatic products is also discussed within a terpene biorefinery context.

Due to its effectiveness, ibuprofen is one of the most popular anti-inflammatory drugs worldwide. However, the poor water solubility of this active ingredient severely limits its spectrum of pharmaceutical formulations (and often results in severe adverse effects due to high administered doses). To overcome these limitations, in this work, we enzymatically synthesized more hydrophilic derivatives of ibuprofen through its covalent attachment to two biobased polyalcohols: erythritol and glycerol. Herein, we report the optimized reaction conditions to produce an IBU–erythritol ester (82% ± 4% of conversion) by using Candida antarctica lipase B (CalB). Furthermore, we also report the enantioselective solventless esterification of (S)-ibuprofen with glycerol (83% ± 5% of conversion), exploiting immobilized Rhizomucor miehei lipase as a biocatalyst. The full NMR characterizations of the prodrug esters were performed via 1H, 13C-NMR, DEPT, COSY, HSQC, and HMBC-NMR. The approach reported in this work can be extended to a large variety of poorly water-soluble active pharmaceutical ingredients (APIs).

Biocatalytic ibuprofen synthesis enhanced via in silico -guided rational enzyme design.

This work was focused on the enzymatic esterification of glycerol and ibuprofen at high concentrations in two triphasic systems composed of toluene+ibuprofene (apolar) and glycerol or glycerol–water (polar) liquid phases, and a solid phase with the industrial immobilized lipase B from Candida antarctica named Novozym®435 (N435) acting as the biocatalyst. Based on a preliminary study, the concentration of the enzyme was set at 30 g·L−1 and the stirring speed at 720 r.p.m to reduce external mass transfer limitations. To obtain more information on the reaction system, it was conducted at a wide range of temperatures (50 to 80 °C) and initial concentrations of ibuprofen (20–100 g·L−1, that is, 97 to 483 mM). Under these experimental conditions, the external mass transfer, according to the Mears criterion (Me = 1.47–3.33·10−4 << 0.15), was fast, presenting no limitation to the system productivity, regardless of the presence of water and from 50 to 80 °C. Considering that the enzyme is immobilized in a porous ion-exchange resin, limitations due to internal mass transfer can exist, depending on the values of the effectiveness factor (η). It varied from 0.14 to 0.23 at 50 to 80 °C and 0.32–1 mm particle diameter range in the absence of water, and in the same ranges, from 0.40 to 0.66 in the presence of 7.4% w/w water in the glycerol phase. Thus, it is evident that some limitation occurs due to mass transfer inside the pores, while the presence of water in the polar phase increases the productivity 3–4 fold. During the kinetic study, several kinetic models were proposed for both triphasic reacting systems, with and without first-order biocatalyst deactivation, and their fit to all relevant experimental data led to the observation that the best kinetic model was a reversible hyperbolic model with first-order deactivation in the anhydrous reaction system and a similar model, but without deactivation, for the system with added water at zero time. This fact is in sharp contrast to the use of N435 in a water-glycerol monophasic system, where progressive dissolution of ibuprofen in the reacting media, together with a notable enzyme deactivation, is observed.

… as a sustainable alternative to solvent-based synthesis, … sustainability and process efficiency of mechanochemical versus conventional solution-based routes for producing rac-ibuprofen…

This study presents a comprehensive application of integrated machine learning tools for modeling and optimizing the ibuprofen synthesis process. Initially, a database of 39,460 input combinations is created using chemical reaction theory and validated with experimental data. The CatBoost meta-model, optimized by the snow ablation optimizer, outperforms conventional algorithms in predicting reaction time, conversion rate, and production cost. Importance analyses through SHAP values identify critical input variables, notably, the concentration of the catalyst precursor (L2PdCl2), hydrogen ions (H+), and water (H2O), validating known catalytic principles and providing quantitative parameter guidance through data-driven analysis. Multiobjective optimization using NSGA-II generates a Pareto front of solutions, from which four industrial strategies are derived: balanced performance, maximum output, maximum yield, and minimum cost, each suitable for different production scenarios. The results identify optimal catalyst concentration ranges (0.002–0.01 mol/m3) that achieve high conversion rates while maintaining low costs. Uncertainty analysis conducted through Monte Carlo simulation reveals that reaction time exhibits particularly high sensitivity to parameter fluctuations, with a distinctive nonlinear response peaking at moderate perturbation levels (σ = 0.3). This study provides valuable insights for the rational design of ibuprofen synthesis conditions and demonstrates the effectiveness of integrating physics-based modeling with machine learning for chemical process optimization.

Biocatalysis is a green and sustainable process for synthesizing chiral organic building blocks and active pharmaceutical ingredients (API). United Nations' Sustainable Development Goals 2030 advocates using green, sustainable, recyclable chemicals by industries to reduce environmental pollution. Pharmaceutical companies are adopting biocatalysis technologies for manufacturing chiral active pharmaceutical ingredients. The lipase‐catalyzed kinetic and dynamic‐kinetic resolution method is a pharmaceutically accepted process for manufacturing chiral API. This review describes the reported methods for synthesizing chiral API/KSM (Key Starting Material) molecules using lipase enzymes over the last ten years.

This study investigates the enzymatic esterification of glycerol and ibuprofen in a solventless medium catalyzed by immobilized lipase B from Candida antarctica (Novozym®435). Fixing the concentration of this enzymatic solid preparation at 30 g·L−1, and operating at a constant stirring speed of 720 rpm, the temperature was changed between 50 and 80 ◦C, while the initial concentration of ibuprofen was studied from 20 to 100 g·L−1. Under these conditions, the resistance of external mass transport can be neglected, as confirmed by the Mears criterion (Me < 0.15). However, the mass transfer limitation inside the pores of the support has been evidenced. The values of the effectiveness factor (η) vary between 0.08 and 0.16 for the particle size range considered according to the Weisz–Prater criteria. Preliminary runs permit us to conclude that the enzyme was deactivated at medium to high temperatures and initial concentration values of ibuprofen. Several phenomenological kinetic models were proposed and fitted to all data available, using physical and statistical criteria to select the most adequate model. The best kinetic model was a reversible sigmoidal model with pseudo-first order with respect to dissolved ibuprofen and order 2 with respect to monoester ibuprofen, assuming the total first-order one-step deactivation of the enzyme, with partial first order for ibuprofen and enzyme activity.

In this paper, we describe the effectiveness of the combination between an organic solvent system mixture with orthoformates with different chain sizes from one to four carbon atoms. These orthoesters have been used as a “water trapper/alcohol releaser molecule” to reach a notable improvement in enantioselectivity and enantiomeric excess of our target compound, (S)-2-(4-isobutylphenyl)propanoic acid (ibuprofen eutomer), during the enzymatic kinetic resolution of rac-ibuprofen using immobilized lipase B of Candida antarctica as a biocatalyst. At the same time, one of the great problems of biocatalysis in organic media has been solved by eliminating excess water in the medium that allows the reversibility of the reaction. Following the optimization of the reaction conditions, an increase in enantiomeric excess and enantioselectivity was reached by using these acyl donors in the presence of a cosolvent.

… bonds linked to ibuprofen were synthesized and evaluated … ), a new methacrylic derivative of ibuprofen in which the drug is … , was synthesized from reaction of glycidyl methacrylate with …

The co-crystal formed from the WHO essential drug rac-Ibuprofen (IBU) and the food additive nicotinamide (NIC) exhibits enhanced physicochemical and analgesic properties compared to the pure active pharmaceutical ingredient (API),...

… ,S)-(±)-ibuprofen and their “developable” synthetic routes were … ibuprofen salt stayed dissolved even in the solvent mixture with a very low volume ratio of water to an organic anti-solvent …

… approach to synthesize glucopyranoside derivatives… synthesize the glucopyranoside ester of ibuprofen. Moreover, we went further towards an optimization of the production of ibuprofen …

Ibuprofen is a non-steroidal anti-inflammatory drug possessing analgesic and antipyretic activity. Electron paramagnetic resonance (EPR) spectroscopy could be applied to study its interaction with biological membranes and proteins if its spin-labeled analogs were synthesized. Here, a simple sequence of ibuprofen transformations—nitration, esterification, reduction, Sandmeyer reaction, Sonogashira cross-coupling, oxidation and saponification—was developed to attain this goal. The synthesis resulted in spin-labeled ibuprofen (ibuprofen-SL) in which the spin label TEMPOL is attached to the benzene ring. EPR spectra confirmed interaction of ibuprofen-SL with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. Using 2H electron spin echo envelope modulation (ESEEM) spectroscopy, ibuprofen-SL was found to be embedded into the hydrophobic bilayer interior.

… The solubility of ibuprofen was tested in various solvents, leading to the selection of toluene as the most appropriate organic medium. Preliminary runs led to fixing the concentration of …

Organic chemistry is continually evolving to improve the syntheses of value added and bioactive compounds. Through this progression, a concomitant advancement in laboratory technology has occurred. Many researchers now choose to mediate transformations in continuous-flow systems given the many benefits over round bottom flasks. Furthermore, reaction scale up is often less problematic as this is addressed at the inception of the science. Although single-step transformations in continuous-flow systems are common, multi-step transformations are more valuable. In these systems, molecular complexity is accrued through sequential transformations to a mobile scaffold, much like an in vitro version of Nature's polyketide synthases. Utilizing this methodology, multi-step continuous-flow systems have improved the syntheses of active pharmaceutical ingredients (APIs), natural products, and commodity chemicals. This Review details these advancements while highlighting the rapid progress, benefits, and diversification of this expanding field.

… In Pfizer we now carry out nitrations routinely in continuous flow with the acid resistant … At Pfizer a continuous flow process for the synthesis of pyrrolidines via [3 + 2] dipolar cycloaddition …

… Recent advances in the field of continuous flow chemistry allow the multistep preparation of … aiming to exploit flow chemistry systems for the synthesis of biologically active molecules. …

The implementation of continuous flow processing as a key enabling technology has transformed the way we conduct chemistry and has expanded our synthetic capabilities. As a result many new preparative routes have been designed towards commercially relevant drug compounds achieving more efficient and reproducible manufacture. This review article aims to illustrate the holistic systems approach and diverse applications of flow chemistry to the preparation of pharmaceutically active molecules, demonstrating the value of this strategy towards every aspect ranging from synthesis, in-line analysis and purification to final formulation and tableting. Although this review will primarily concentrate on large scale continuous processing, additional selected syntheses using micro or meso-scaled flow reactors will be exemplified for key transformations and process control. It is hoped that the reader will gain an appreciation of the innovative technology and transformational nature that flow chemistry can leverage to an overall process.

An active pharmaceutical ingredient (API) is any substance in a pharmaceutical product that is biologically active. That means the specific molecular entity is capable of achieving a defined biological effect on the target. These ingredients need to meet very strict limits; chemical and optical purity are considered to be the most important ones. A continuous-flow synthetic methodology which utilizes a continuously flowing stream of reactive fluids can be easily combined with photochemistry, which works with the chemical effects of light. These methods can be useful tools to meet these strict limits. Both of these methods are unique and powerful tools for the preparation of natural products or active pharmaceutical ingredients and their precursors with high structural complexity under mild conditions. This review shows some main directions in the field of active pharmaceutical ingredients’ preparation using continuous-flow chemistry and photochemistry with numerous examples of industry and laboratory-scale applications.

Catalytic enantioselective transformations provide well-established and direct access to stereogenic synthons that are broadly distributed among active pharmaceutical ingredients (APIs). These reactions have been demonstrated to benefit considerably from the merits of continuous processing and microreactor technology. Over the past few years, continuous flow enantioselective catalysis has grown into a mature field and has found diverse applications in asymmetric synthesis of pharmaceutically active substances. The present review therefore surveys flow chemistry-based approaches for the synthesis of chiral APIs and their advanced stereogenic intermediates, covering the utilization of biocatalysis, organometallic catalysis and metal-free organocatalysis to introduce asymmetry in continuously operated systems. Single-step processes, interrupted multistep flow syntheses, combined batch/flow processes and uninterrupted one-flow syntheses are discussed herein.

We developed a continuous, integrated production system for all reaction processes targeting ibuprofen. We succeeded in obtaining pure ibuprofen at 38% for all steps, and a production efficiency of 47...

Ibuprofen was prepared from an inactive and inexpensive p-xylene by 3-step flow functionalizations through chemoselective metalations of benzyl positions in sequence using an in-situ generated LICKOR-type superbase. The flow approach in the microreactor facilitated to comprehensively explore over 100 conditions in the first-step reaction by varying concentrations, temperatures, solvents, and equivalents of reagents, enabling to find the optimal condition with 95% yield by significantly suppressing the formation of byproducts, followed by the second C-H metalation step in 95% yield. Moreover, gram-scale synthesis of ibuprofen in the final step was achieved by biphasic flow reaction of solution-phase intermediate with CO₂, isolating 2.3 g for 10 min of operation time.

… of continuous flow organocatalysis and offer a starting point to develop new methodologies for the … of a very important generic pharmaceutical, ibuprofen 72. In 3 min only, API 72 was …

… continuous flow synthesis process for ibuprofen intermediates and proposed a solvent-free continuous … The rearrangement reaction was integrated into a continuous flow reactor, …

Summary Multi-step organic syntheses of various drugs, active pharmaceutical ingredients, and other pharmaceutically and agriculturally important compounds have already been reported using flow synthesis. Compared to batch, hazardous and reactive reagents can be handled safely in flow. This review discusses the pros and cons of flow chemistry in today’s scenario and recent developments in flow devices. The review majorly emphasizes on the recent developments in the flow synthesis of pharmaceutically important products in last five years including flibanserin, imatinib, buclizine, cinnarizine, cyclizine, meclizine, ribociclib, celecoxib, SC-560 and mavacoxib, efavirenz, fluconazole, melitracen HCl, rasagiline, tamsulosin, valsartan, and hydroxychloroquine. Critical steps and new development in the flow synthesis of selected compounds are also discussed.