01313nas a2200193 4500008004100000022001400041245004800055210004800103260007100151300001300222490000700235520067400242100002300916700002600939700002800965700002200993700002201015856008201037 2008 eng d a1083-616000aContinuous flow nitration of salicylic acid0 aContinuous flow nitration of salicylic acid a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcSEP a995-10000 v123 a

Continuous flow nitration of salicylic acid using HNO3/AcOH was studied in the SS316 tubular microreactor. At specific reaction conditions, complete conversion of the reactant was achieved in less than 7 min. It yielded only mononitro derivatives with a higher selectivity of 5-nitrosalicylic acid. Presence of the lower amount of acetic acid in the reaction mixture was seen to be detrimental, leading to precipitation of the desired product (5-nitrosalicylic acid). Reaction at higher temperatures yielded byproducts. The continuous mode operation using the system comprising the microdevices was demonstrated for 2 h with consistent composition at the outlet.

1 aKulkarni, Amol, A.1 aNivangune, Nayana, T.1 aKalyani, Vishwanath, S.1 aJoshi, Ramesh, A.1 aJoshi, Rohini, R. uhttps://library.ncl.res.in/content/continuous-flow-nitration-salicylic-acid-001101nas a2200181 4500008004100000022001400041245004600055210004600101260007100147300001300218490000700231520050600238100002300744700002800767700002200795700002200817856008000839 2009 eng d a1083-616000aContinuous flow nitration of benzaldehyde0 aContinuous flow nitration of benzaldehyde a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcOCT a999-10020 v133 a

The nitration of benzaldebyde can be carried out in a safe manner in continuous mode using a microreactor system. Choice of a micromixer was seen to affect the performance of this two-phase reaction significantly The reaction time could he brought down to 2 min by increasing the reaction temperature and thereby taking advantage of higher heat transfer area. The simple T-micromixer is seen to be inefficient for two-phase reactions. Further scope of process intensification is also discussed.

1 aKulkarni, Amol, A.1 aKalyani, Vishwanath, S.1 aJoshi, Ramesh, A.1 aJoshi, Rohini, R. uhttps://library.ncl.res.in/content/continuous-flow-nitration-benzaldehyde-001398nas a2200217 4500008004100000022001400041245005400055210005400109260008600163300001200249490000700261520069400268653002000962653001900982653001801001653001401019653001601033653002001049100002301069856008801092 2014 eng d a1860-539700aContinuous flow nitration in miniaturized devices0 aContinuous flow nitration in miniaturized devices aTRAKEHNER STRASSE 7-9, FRANKFURT AM MAIN, 60487, GERMANYbBEILSTEIN-INSTITUTcFEB a405-4240 v103 a

This review highlights the state of the art in the field of continuous flow nitration with miniaturized devices. Although nitration has been one of the oldest and most important unit reactions, the advent of miniaturized devices has paved the way for new opportunities to reconsider the conventional approach for exothermic and selectivity sensitive nitration reactions. Four different approaches to flow nitration with microreactors are presented herein and discussed in view of their advantages, limitations and applicability of the information towards scale-up. Selected recent patents that disclose scale-up methodologies for continuous flow nitration are also briefly reviewed.

10acontinuous flow10aflow chemistry10amicroreactors10anitration10anitric acid10aTubular reactor1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-flow-nitration-miniaturized-devices-001699nas a2200241 4500008004100000022001400041245003900055210003800094260008300132300001200215490000600227520095700233653001901190653001901209653002501228653002301253653001501276653002401291100002101315700002201336700002301358856007601381 2014 eng d a2062-249X00aContinuous-flow meerwein arylation0 aContinuousflow meerwein arylation aPRIELLE K U 19, PO BOX 245,, H-1117 BUDAPEST, HUNGARYbAKADEMIAI KIADO RTcDEC a211-2160 v43 a

The continuous-flow Meerwein arylation is demonstrated for a set of few aryl donors (anilines and m-aminoacetophenone) and specific radical acceptors. Homogeneous catalyst (CuBr in HBr and CuCl in HCl) was used to facilitate the reaction. The effect of parameters, viz., temperature, catalyst concentration, residence time, and concentration of the radical acceptor on the yield of the arylated product, was studied. The yield of the aryl derivative obtained by continuous-flow syntheses was always better than the respective experiments in batch mode. Flow synthesis allows easy variation in these parameters and thus allows going close to the maximum possible yields in a system where the relative rates of different reactions create a complex situation. Temperature plays a crucial role by affecting the rates as well as by governing the system homogeneity. The nitrogen bubbles generated in the reaction helped to avoid any channel blockage.

10adiazonium salt10aflow chemistry10ahomogeneous catalyst10aMeerwein arylation10amicromixer10amultistep synthesis1 aBhaya, Vinay, G.1 aJoshi, Ramesh, A.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-flow-meerwein-arylation-001612nas a2200229 4500008004100000022001400041245007000055210006400125260006900189300001200258490000800270520087300278653001001151653001501161653000801176653001601184653001201200100002201212700002701234700002301261856009801284 2015 eng d a1385-894700aCRE for magic(modular, agile, intensified & continuous) processes0 aCRE for magicmodular agile intensified continuous processes aPO BOX 564, 1001 LAUSANNE, SWITZERLANDbELSEVIER SCIENCE SAcOCT a454-4680 v2783 a

Fine and specialty chemical industry caters to several key applications required for maintaining and enhancing quality of life. Most of these fine and specialty chemicals are still manufactured in stirred tank reactors operated in batch or semi-batch modes. A paradigm shift is necessary to transform these into new age, efficient and continuous processes and plants. In this paper, recent attempts of our group on developing MAGIC (modular, agile, intensified and continuous) devices, processes and plants for fine and specialty chemicals industry are discussed. The focus is on key chemical reaction engineering aspects of developing MAGIC processes. An attempt is made to evolve guidelines for designing MAGIC devices and reactors. The discussion will be useful to researchers as well as to industry practitioners. (C) 2014 Elsevier B.V. All rights reserved.

10aAgile10aContinuous10aCRE10aIntensified10aModular1 aRanade, Vivek, V.1 aSharma, Mrityunjay, K.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/cre-magic-modular-agile-intensified-continuous-processes-001491nas a2200169 4500008004100000245009900041210007100140260000800211300001600219490000700235520085000242100002201092700002201114700002201136700002301158856014001181 2016 eng d00aContinuous flow doebner–miller reaction and isolation using continuous stirred tank reactors0 aContinuous flow doebner–miller reaction and isolation using cont cAUG a1621–16250 v203 a

Continuous flow Doebner–Miller synthesis of different quinaldines from respective anilines is demonstrated using sulfuric acid as a homogeneous catalyst. The extent of reaction was monitored for various parameters, namely, temperature, residence time, mole ratio of sulfuric acid to substrate, mole ratio of crotonaldehyde to substrate, and so forth. Continuous stirred reactors in series were used as a preferred configuration for this rection that generates byproduct in the form of sticky solid material. The approach has been extended for six different anilines, and the results are compared with batch reactions. Continuous stirred reactors in series with distributed dosing of crotonaldehyde facilitated a continuous flow reaction with lower byproduct formation, increased yields, and continuous workup and is a scalable approach.

1 aYadav, Maruti, B.1 aKulkarni, Sourabh1 aJoshi, Ramesh, A.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-flow-doebner%E2%80%93miller-reaction-and-isolation-using-continuous-stirred-tank-reactors01160nas a2200145 4500008004100000245009700041210006900138260000800207520060200215100001500817700001500832700002200847700002300869856012200892 2017 eng d00aContinuous flow telescopic oxidation of alcohols via generation of chlorine and hypochlorite0 aContinuous flow telescopic oxidation of alcohols via generation  cMAR3 aA 3-step continuous flow oxidation of alcohols is demonstrated with continuous generation of chlorine as the first step followed by its use for the flow synthesis of high strength sodium hypochlorite. The solution is subsequently used for oxidation of alcohols in the presence of a catalytic amount of the nitroxyl radical “TEMPO”, which inhibits oxidation at the aldehyde stage. Selective oxidations of eight different alcohols were demonstrated. To achieve identical yields, the aromatic alcohols containing electron withdrawing groups needed a longer residence time than aliphatic alcohols.1 aSharma, Y.1 aMoolya, S.1 aJoshi, Ramesh, A.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-flow-telescopic-oxidation-alcohols-generation-chlorine-and-hypochlorite01399nas a2200169 4500008004100000022001400041245011100055210006900166260000900235300001400244490000700258520076400265100002401029700002601053700002301079856012701102 2019 eng d a1463-926200aContinuous flow solvent free organic synthesis involving solids (reactants/products) using a screw reactor0 aContinuous flow solvent free organic synthesis involving solids  cOCT  a5639-56460 v213 a

Here we report for the first-time various organic transformations such as aldol condensation, oxidation, nucleophilic substitutions, protection, acylations and coupling reactions using a mechanochemical approach at a controlled temperature using a single synthesis platform. Almost minimal solvents or solvent-free conditions are used, making it a very efficient and clean synthesis of various products. A jacketed screw reactor when operated at different temperatures (0 degrees C to 160 degrees C) and over a range of rotation speeds for changing the residence time (15 s-300 s) helped to achieve maximum conversion. This approach is also extended to the synthesis using substrates having different substitutions, heterocycles and steric hindrance.

1 aSharma, Brijesh, M.1 aAtapalkar, Ranjit, S.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-flow-solvent-free-organic-synthesis-involving-solids-reactantsproducts-using01188nas a2200133 4500008004100000245005800041210005700099260000800156300001200164520074000176100002300916700002600939856008900965 2020 eng d00aChapter 9. continuous flow synthesis of nanomaterials0 aChapter 9 continuous flow synthesis of nanomaterials bRSC a316-3393 a

Continuous flow synthesis of nanoparticles is now a well-accepted and reliable synthesis approach that gives consistent product properties. This chapter aims to do a critical analysis of the recent work in some of the relevant areas and gives specific recommendations where flow synthesis of nanomaterials can be realized as a reliable manufacturing process. The chapter also highlights the typical engineering issues that one needs to consider while transforming a batch synthesis protocol into continuous mode and its scale-up.

1 aKulkarni, Amol, A.1 aJundale, Rajashri, B. uhttps://library.ncl.res.in/content/chapter-9-continuous-flow-synthesis-nanomaterials00441nas a2200133 4500008004100000245004700041210004700088260003100135300001200166490000700178100002300185700002000208856007900228 2020 eng d00aContinuous Flow Synthesis of Nanomaterials0 aContinuous Flow Synthesis of Nanomaterials bRoyal Society of Chemistry a316-3390 v621 aKulkarni, Amol, A.1 aJundale, R., B. uhttps://library.ncl.res.in/content/continuous-flow-synthesis-nanomaterials01650nas a2200241 4500008004100000022001400041245008700055210006900142260000800211300001200219490000700231520080900238653003401047653002701081653003101108653002801139653002501167100002701192700002401219700002301243700002301266856011901289 2020 eng d a0930-751600aContinuous interfacial centrifugal separation and recovery of silver nanoparticles0 aContinuous interfacial centrifugal separation and recovery of si cMAR a582-5920 v433 a

Continuous-flow separation and recovery of silver nanoparticles (AgNPs) using an annular centrifugal extractor (ACE) is demonstrated. Separation was achieved at the liquid-liquid interface based on the balance between centrifugal force and the solubility of the capping agent. A mathematical model is presented to understand the mechanism in greater detail. The separation of poly(vinylpyrrolidone) (PVP)-coated AgNPs in an ACE using a strong immiscible solvent was performed. The material accumulated at the interface was separated periodically without discontinuing the operation. The method is also suitable for separation of large particles or 1D/2D nanostructures even employing a single annular centrifugal extractor. Stable AgNPs were selected for a detailed antimicrobial activity study.

10aAnnular centrifugal extractor10aAntimicrobial activity10aContinuous-flow separation10aLiquid-liquid interface10asilver nanoparticles1 aDeshpande, Jaydeep, B.1 aNavale, Govinda, R.1 aDharne, Mahesh, S.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-interfacial-centrifugal-separation-and-recovery-silver-nanoparticles02366nas a2200313 4500008004100000022001400041245008600055210006900141260000800210300001200218490000700230520135200237653002901589653001801618653002001636653002101656653001901677100002201696700002701718700002101745700003201766700001601798700001501814700003001829700002301859700002801882700002601910856011601936 2021 eng d a2062-249X00aContinuous citrate-capped gold nanoparticle synthesis in a two-phase flow reactor0 aContinuous citratecapped gold nanoparticle synthesis in a twopha cSEP a553-5670 v113 aA continuous manufacturing platform was developed for the synthesis of aqueous colloidal 10-20 nm gold nanoparticles (Au NPs) in a flow reactor using chloroauric acid, sodium citrate and citric acid at 95 degrees C and 2.3 bar(a) pressure. The use of a twophase flow system - using heptane as the continuous phase - prevented fouling on the reactor walls, while improving the residence time distribution. Continuous syntheses for up to 2 h demonstrated its potential application for continuous manufacturing, while live quality control was established using online UV-Vis photospectrometry that monitored the particle size and process yield. The synthesis was stable and reproducible over time for gold precursor concentration above 0.23 mM (after mixing), resulting in average particle size between 12 and 15 nm. A hydrophobic membrane separator provided successful separation of the aqueous and organic phases and collection of colloidal Au NPs in flow. Process yield increased at higher inlet flow rates (from 70% to almost 100 %), due to lower residence time of the colloidal solution in the separator resulting in less fouling in the PTFE membrane. This study addresses the challenges for the translation of the synthesis from batch to flow and provides tools for the development of a continuous manufacturing platform for gold nanoparticles.10aContinuous manufacturing10aNanomaterials10aOnline analysis10aphase separation10asegmented flow1 aDamilos, Spyridon1 aAlissandratos, Ioannis1 aPanariello, Luca1 aRadhakrishnan, Anand, N. P.1 aCao, Enhong1 aWu, Gaowei1 aBesenhard, Maximilian, O.1 aKulkarni, Amol, A.1 aMakatsoris, Charalampos1 aGavriilidis, Asterios uhttps://library.ncl.res.in/content/continuous-citrate-capped-gold-nanoparticle-synthesis-two-phase-flow-reactor02050nas a2200217 4500008004100000022001400041245008700055210006900142260000800211300001200219490000700231520134100238653002701579653001301606653002001619653001701639653001501656100002601671700002301697856011201720 2024 eng d a2062-249X00aContinuous flow ozonolysis of cardanol for greener synthesis of bio-based monomers0 aContinuous flow ozonolysis of cardanol for greener synthesis of  cJUN a417-4260 v143 a

Synthesis of bio-based monomers via continuous flow ozonolysis of cardanol using a simple tubular reactor is demonstrated. The direct ozonolysis of cardanol produces unique monomer 8-(3-hydroxyphenyl) octanal (HPOA) and heptanal along with several other oxidation products. Maximum 47% yield of HPOA with 54.3% conversion of cardanol was obtained at 0 degrees C in 9 s. The complete conversion of cardanol was obtained at the ozone to cardanol molar flow ratios greater than 2 at all temperatures varied in the range of -10 degrees C to 20 degrees C. Owing to large gas-liquid ratios, the mass transfer limitation for transfer of ozone from gas to liquid was negligible; however, the extent of axial dispersion in the liquid phase was significant at lower liquid flow rates. The non-ideal behavior was incorporated in the axial dispersion model to predict the conversion of cardanol. Examination of kinetic rates by both ideal plug-flow model and plug-flow with axial dispersion model revealed that the reaction is fast and is least influenced by the axial-dispersion in the reactor at prevailing operating conditions. The findings of the current study show that continuous flow technique enables a simple and safer synthesis of high-value bio-based monomers via ozonolysis of cardanol compared to traditional batch methods.

10aAxial-dispersion model10aCardanol10acontinuous flow10aHelical coil10aOzonolysis1 aKulkarni, Sphurti, P.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-flow-ozonolysis-cardanol-greener-synthesis-bio-based-monomers01794nas a2200181 4500008004100000022001400041245009300055210006900148260000800217300001400225490000700239520114800246100002601394700003101420700001801451700002301469856012001492 2024 eng d a0888-588500aContinuous flow synthesis of mesoporous silica particles with tunable size and structure0 aContinuous flow synthesis of mesoporous silica particles with tu cJAN a1843-18520 v633 a

We have developed a continuous process to prepare mesoporous silica particles of different sizes and narrow size distribution in a tubular reactor. The method is based on the use of well-known Stober synthesis in the presence of cationic surfactant in methanol-water solvent system and trimethylbenzene as pore swelling agent to form porous silica particles. We observed that reaction parameters had enormous effects on particle size, distribution, and numerous morphological aspects. We demonstrated that these properties may be modified by adjusting the reaction temperature, base concentration, and surfactant concentration. MSPs of spherical morphology with variable size from 400 to 1000 nm produced with the surface area >600 m(2)/g and pore diameter of 2-4 nm. Large scale production is demonstrated by increasing reactor volume using 1/4 in. PTFE tubing from 20 to 163 mL, with this production of MSPs increased from 0.35 to 3 g/h. The method has been extended for high yield production at the kilogram scale using this approach, which will pave the way toward the industrialization of mesoporous silica based materials.

1 aJundale, Rajashri, B.1 aPrasad, Bhagavatula, L. V.1 aDevi, Nandini1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-flow-synthesis-mesoporous-silica-particles-tunable-size-and-structure02143nas a2200241 4500008004100000022001400041245010300055210006900158260000800227300001200235490000700247520126500254653003301519653003501552653003001587653002901617100002801646700002301674700002601697700002401723700002301747856013101770 2025 eng d a1083-616000aConfined impinging jet reactor for high-throughput continuous flow mononitration of salicylic acid0 aConfined impinging jet reactor for highthroughput continuous flo cJAN a479-4890 v293 a

Novel approach is reported for highly efficient continuous mononitration of salicylic acid using confined impinging jet reactor (CIJR) with a vent. Initially, controlled semibatch reactions are optimized to achieve complete conversion and formation of mononitro products with very high selectivity for 5-nitrosalicylic acid (5-NSA). Further, the combination of computational fluid dynamics simulations and experiments is employed to optimize CIJR design and operating flow conditions, suitable to yield only mononitro products with excellent control over mixing, heat transfer, and liberation of fumes during continuous flow reaction. Detailed analysis of internal flow patterns, rate of heat generation, and concentration distribution inside the CIJR facilitated the optimization of present exothermic reaction in a safe manner. In less than a minute, complete salicylic acid (SA) conversion with good yield and better selectivity for 5-NSA is achieved using the CIJR. Safety and clogging issues are addressed effectively, even at a relatively lower mole ratio (1:5) of SA:acetic acid (AcOH). The present approach is quite scalable using the numbering-up strategy, with advantages viz. nonfouling, high throughput, and the small footprint of CIJR.

10acomputational fluid dynamics10aconfined impinging jet reactor10ahigh-throughput synthesis10asalicylic acid nitration1 aKhan, Muzammilanwar, S.1 aShaikh, Tabrez, R.1 aKulkarni, Sphurti, P.1 aPatil, Abhishek, A.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/confined-impinging-jet-reactor-high-throughput-continuous-flow-mononitration-salicylic-acid01146nas a2200169 4500008004100000022001400041245012000055210006900175260000900244300001400253490000700267520050100274100002000775700002800795700002300823856013000846 2025 eng d a1359-734500aContinuous flow solvent-free and catalyst-free mechanochemical production of rhodamine B dyes and their derivatives0 aContinuous flow solventfree and catalystfree mechanochemical pro cJAN  a2131-21340 v613 a

In this communication, we have described a simple and efficient, catalyst free and solvent-free protocol for the continuous flow synthesis of rhodamine B dyes developed from 3-diethyl amino phenol and phthalic anhydride. Nearly 95% conversion was achieved within 12 min using a jacketed single screw reactor. This method is further used for the synthesis of six derivatives with 70-84% yield, which can be compared to 85% yield from a 1-hour long batch synthesis involving a catalyst.

1 aPurohit, Mukesh1 aShaikh, Tabrez, Rafique1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-flow-solvent-free-and-catalyst-free-mechanochemical-production-rhodamine-b-dyes02599nas a2200169 4500008004100000022001400041245011000055210006900165260000800234300001200242490000700254520197700261100002502238700002202263700002302285856012102308 2025 eng d a2051-634700aContinuous flow synthesis of metal nanowires: protocols, engineering aspects of scale-up and applications0 aContinuous flow synthesis of metal nanowires protocols engineeri cJAN a364-4000 v123 a

This review comprehensively covers the translation from batch to continuous flow synthesis of metal nanowires (i.e., silver, copper, gold, and platinum nanowires) and their diverse applications across various sectors. Metal nanowires have attracted significant attention owing to their versatility and feasibility for large-scale synthesis. The efficacy of flow chemistry in nanomaterial synthesis has been extensively demonstrated over the past few decades. Continuous flow synthesis offers scalability, high throughput screening, and robust and reproducible synthesis procedures, making it a promising technology. Silver nanowires, widely used in flexible electronics, transparent conductive films, and sensors, have benefited from advancements in continuous flow synthesis aimed at achieving high aspect ratios and uniform diameters, though challenges in preventing agglomeration during large-scale production remain. Copper nanowires, considered as a cost-effective alternative to silver nanowires for conductive materials, have benefited from continuous flow synthesis methods that minimize oxidation and enhance stability, yet scaling up these processes requires precise control of reducing environments and copper ion concentration. A critical evaluation of various metal nanowire ink formulations is conducted, aiming to identify formulations that exhibit superior properties with lower metal solid content. This study delves into the intricacies of continuous flow synthesis methods for metal nanowires, emphasizing the exploration of engineering considerations essential for the design of continuous flow reactors. Furthermore, challenges associated with large-scale synthesis are addressed, highlighting the process-related issues. This review comprehensively covers the translation from batch to continuous flow synthesis of metal nanowires (i.e., silver, copper, gold, and platinum nanowires) and their diverse applications across various sectors.

1 aSonawane, Jayesh, R.1 aJundale, Rajashri1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-flow-synthesis-metal-nanowires-protocols-engineering-aspects-scale-and01755nas a2200205 4500008004100000022001400041245009300055210006900148260000800217300001200225490000700237520104000244653003401284653001901318653002201337653002701359100002201386700002301408856011801431 2025 eng d a1083-616000aContinuous flow telescopic synthesis of 3-methoxy propiophenone by the grignard reaction0 aContinuous flow telescopic synthesis of 3methoxy propiophenone b cJAN a450-4590 v293 a

The synthesis of 3-methoxypropiophenone 1, a crucial intermediate in the production of the analgesic tapentadol hydrochloride, was investigated using a multistep continuous flow process. The approach is based on the Grignard reaction. A series of continuously stirred tank reactors (CSTRs) were employed: the first reactors facilitated the continuous generation of Grignard reagents 3, which then reacted with propionitrile in the next CSTR to yield 1. This was followed by quenching, neutralization, and phase separation, conducted under varying temperatures and residence times. When compared to a 50% yield from an optimized batch synthesis protocol, a continuous flow synthesis helped achieve an 84% yield of the desired product in a much shorter reaction time. A kinetic model was developed to predict the Grignard reagent formation and product yield, revealing that the mass transfer effect is insignificant at a higher stirring rate. The approach is highly scalable for the synthesis of pharmaceutical intermediates.

10abatch and continuous reaction10aflow chemistry10aGrignard reaction10aheterogeneous kinetics1 aWankhede, Pranali1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/continuous-flow-telescopic-synthesis-3-methoxy-propiophenone-grignard-reaction