@article { ISI:000259450800027, title = {Continuous flow nitration of salicylic acid}, journal = {Organic Process Research \& Development}, volume = {12}, number = {5}, year = {2008}, month = {SEP}, pages = {995-1000}, publisher = {AMER CHEMICAL SOC}, type = {Article}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

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.

}, issn = {1083-6160}, doi = {10.1021/op800112u}, author = {Kulkarni, Amol A. and Nivangune, Nayana T. and Kalyani, Vishwanath S. and Joshi, Ramesh A. and Joshi, Rohini R.} } @article { ISI:000269892100029, title = {Continuous flow nitration of benzaldehyde}, journal = {Organic Process Research \& Development}, volume = {13}, number = {5}, year = {2009}, note = {235th American-Chemical-Society National Meeting, New Orleans, LA, APR 06-10, 2008}, month = {OCT}, pages = {999-1002}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

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.

}, issn = {1083-6160}, doi = {10.1021/op000129vv}, author = {Kulkarni, Amol A. and Kalyani, Vishwanath S. and Joshi, Ramesh A. and Joshi, Rohini R.} } @article { ISI:000332784900001, title = {Continuous flow nitration in miniaturized devices}, journal = {Beilstein Journal of Organic Chemistry}, volume = {10}, year = {2014}, month = {FEB}, pages = {405-424}, publisher = {BEILSTEIN-INSTITUT}, type = {Review}, address = {TRAKEHNER STRASSE 7-9, FRANKFURT AM MAIN, 60487, GERMANY}, abstract = {

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.

}, keywords = {continuous flow, flow chemistry, microreactors, nitration, nitric acid, Tubular reactor}, issn = {1860-5397}, doi = {10.3762/bjoc.10.38}, author = {Kulkarni, Amol A.} } @article { ISI:000346134300012, title = {Continuous-flow meerwein arylation}, journal = {Journal of Flow Chemistry}, volume = {4}, number = {4}, year = {2014}, month = {DEC}, pages = {211-216}, publisher = {AKADEMIAI KIADO RT}, type = {Article}, address = {PRIELLE K U 19, PO BOX 245,, H-1117 BUDAPEST, HUNGARY}, abstract = {

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.

}, keywords = {diazonium salt, flow chemistry, homogeneous catalyst, Meerwein arylation, micromixer, multistep synthesis}, issn = {2062-249X}, doi = {10.1556/JFC-D-14-00023}, author = {Bhaya, Vinay G. and Joshi, Ramesh A. and Kulkarni, Amol A.} } @article { ISI:000357907800052, title = {CRE for magic(modular, agile, intensified \& continuous) processes}, journal = {Chemical Engineering Journal}, volume = {278}, number = {SI}, year = {2015}, note = {23rd International Symposium on Chemical Reaction Engineering (ISCRE), Bangkok, THAILAND, SEP 07-10, 2014}, month = {OCT}, pages = {454-468}, publisher = {ELSEVIER SCIENCE SA}, address = {PO BOX 564, 1001 LAUSANNE, SWITZERLAND}, abstract = {

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.

}, keywords = {Agile, Continuous, CRE, Intensified, Modular}, issn = {1385-8947}, doi = {10.1016/j.cej.2014.12.050}, author = {Ranade, Vivek V. and Sharma, Mrityunjay K. and Kulkarni, Amol A.} } @article {42544, title = {Continuous flow doebner{\textendash}miller reaction and isolation using continuous stirred tank reactors}, journal = {Organic Process Research \& Development}, volume = {20}, year = {2016}, month = {AUG}, pages = {1621{\textendash}1625}, abstract = {

Continuous flow Doebner{\textendash}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.

}, doi = {10.1021/acs.oprd.6b00179}, author = {Yadav, Maruti B. and Kulkarni, Sourabh and Joshi, Ramesh A. and Kulkarni, Amol A.} } @article {43566, title = {Continuous flow telescopic oxidation of alcohols via generation of chlorine and hypochlorite}, journal = {Reaction Chemistry \& Engineering}, year = {2017}, month = {MAR}, abstract = {A 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 {\textquotedblleft}TEMPO{\textquotedblright}, 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.}, doi = {10.1039/C6RE00225K}, author = {Sharma, Y. and Moolya, S. and Joshi, Ramesh A. and Kulkarni, Amol A.} } @article {46321, title = {Continuous flow solvent free organic synthesis involving solids (reactants/products) using a screw reactor}, journal = {Green Chemistry}, volume = {21}, year = {2019}, month = {OCT }, pages = {5639-5646}, type = {Article}, abstract = {

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.

}, issn = {1463-9262}, doi = {10.1039/c9gc02447f}, author = {Sharma, Brijesh M. and Atapalkar, Ranjit S. and Kulkarni, Amol A.} } @inbook {47326, title = {Chapter 9. continuous flow synthesis of nanomaterials}, booktitle = {Flow Chemistry }, year = {2020}, pages = {316-339}, publisher = {RSC}, organization = {RSC}, abstract = {

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.

}, doi = {10.1039/9781788016094-00316}, author = {Kulkarni, Amol A. and Jundale, Rajashri B.} } @inbook {47145, title = {Continuous Flow Synthesis of Nanomaterials}, booktitle = {Continuous Flow Synthesis of Nanomaterials}, volume = {62}, number = {RSC Green Chemistry Series}, year = {2020}, pages = {316-339}, publisher = {Royal Society of Chemistry}, organization = {Royal Society of Chemistry}, author = {Kulkarni, Amol A. and Jundale, R. B.} } @article {46963, title = {Continuous interfacial centrifugal separation and recovery of silver nanoparticles}, journal = {Chemical Engineering \& Technology}, volume = {43}, year = {2020}, month = {MAR}, pages = {582-592}, type = {Article}, abstract = {

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.

}, keywords = {Annular centrifugal extractor, Antimicrobial activity, Continuous-flow separation, Liquid-liquid interface, silver nanoparticles}, issn = {0930-7516}, doi = {10.1002/ceat.201800722, Early Access Date = FEB 2020}, author = {Deshpande, Jaydeep B. and Navale, Govinda R. and Dharne, Mahesh S. and Kulkarni, Amol A.} } @article {47739, title = {Continuous citrate-capped gold nanoparticle synthesis in a two-phase flow reactor}, journal = {Journal of Flow Chemistry}, volume = {11}, year = {2021}, month = {SEP}, pages = {553-567}, type = {Article}, abstract = {A 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.}, keywords = {Continuous manufacturing, Nanomaterials, Online analysis, phase separation, segmented flow}, issn = {2062-249X}, doi = {10.1007/s41981-021-00172-3}, author = {Damilos, Spyridon and Alissandratos, Ioannis and Panariello, Luca and Radhakrishnan, Anand N. P. and Cao, Enhong and Wu, Gaowei and Besenhard, Maximilian O. and Kulkarni, Amol A. and Makatsoris, Charalampos and Gavriilidis, Asterios} } @article {49187, title = {Continuous flow ozonolysis of cardanol for greener synthesis of bio-based monomers}, journal = {Journal of Flow Chemistry}, volume = {14}, year = {2024}, month = {JUN}, pages = {417-426}, type = {Article}, abstract = {

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.

}, keywords = {Axial-dispersion model, Cardanol, continuous flow, Helical coil, Ozonolysis}, issn = {2062-249X}, doi = {10.1007/s41981-024-00308-1}, author = {Kulkarni, Sphurti P. and Kulkarni, Amol A.} } @article {49061, title = {Continuous flow synthesis of mesoporous silica particles with tunable size and structure}, journal = {Industrial and Engineering Chemistry Research}, volume = {63}, year = {2024}, month = {JAN}, pages = {1843-1852}, type = {Article}, abstract = {

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.

}, issn = {0888-5885}, doi = {10.1021/acs.iecr.3c03304}, author = {Jundale, Rajashri B. and Prasad, Bhagavatula L. V. and Devi, R. Nandini and Kulkarni, Amol A.} } @article {49501, title = {Confined impinging jet reactor for high-throughput continuous flow mononitration of salicylic acid}, journal = {Organic Process Research \& Development}, volume = {29}, year = {2025}, month = {JAN}, pages = {479-489}, type = {Article}, abstract = {

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.

}, keywords = {computational fluid dynamics, confined impinging jet reactor, high-throughput synthesis, salicylic acid nitration}, issn = {1083-6160}, doi = {10.1021/acs.oprd.4c00467}, author = {Khan, Muzammilanwar S. and Shaikh, Tabrez R. and Kulkarni, Sphurti P. and Patil, Abhishek A. and Kulkarni, Amol A.} } @article {49608, title = {Continuous flow solvent-free and catalyst-free mechanochemical production of rhodamine B dyes and their derivatives}, journal = {Chemical Communications}, volume = {61}, year = {2025}, month = {JAN }, pages = {2131-2134}, type = {Article}, abstract = {

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.

}, issn = {1359-7345}, doi = {10.1039/d4cc04197f}, author = {Purohit, Mukesh and Shaikh, Tabrez Rafique and Kulkarni, Amol A.} } @article {49609, title = {Continuous flow synthesis of metal nanowires: protocols, engineering aspects of scale-up and applications}, journal = {Materials Horizons}, volume = {12}, year = {2025}, month = {JAN}, pages = {364-400}, type = {Review}, abstract = {

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.

}, issn = {2051-6347}, doi = {10.1039/d4mh00781f}, author = {Sonawane, Jayesh R. and Jundale, Rajashri and Kulkarni, Amol A.} } @article {49512, title = {Continuous flow telescopic synthesis of 3-methoxy propiophenone by the grignard reaction}, journal = {Organic Process Research \& Development}, volume = {29}, year = {2025}, month = {JAN}, pages = {450-459}, type = {Article}, abstract = {

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.

}, keywords = {batch and continuous reaction, flow chemistry, Grignard reaction, heterogeneous kinetics}, issn = {1083-6160}, doi = {10.1021/acs.oprd.4c00447}, author = {Wankhede, Pranali and Kulkarni, Amol A.} }