@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.} } @article {46707, title = {Efficient processing of reactions involving diazonium salts: meerwein arylation in an impinging-jet reactor}, journal = {Organic Process Research \& Development}, volume = {24}, year = {2020}, month = {SEP}, pages = {1658-1664}, type = {Article}, abstract = {

This work reports a novel approach for performing high-throughput synthesis of Meerwein arylation in an impingingjet reactor. The multistep reaction was performed in a single reactor via in situ diazonium salt generation followed by Meerwein arylation. The work involves many iterations between experiments and simulations (where we integrate simulating the flow, heat transfer, and reaction simultaneously) for optimization of conditions in an inverted impinging-jet reactor. The effect of design variables viz. catalyst concentration, inlet temperature, and monomer mole ratio on the yield of the desired product was studied in detail, and the simulation results were used to plan the continuous experiments. An infrared camera was used to monitor the transient reactor temperature for steady-state analysis. The lab-scale inverted impinging-jet reactor with over 93\% isolated yield can offer a space-time yield of 277.78 tons/m(3)/day. The numbering-up of an inverted impinging-jet reactor can be an effective way for cleaner production of products through typical Meerwein arylation.

}, keywords = {computational fluid dynamics, high throughput synthesis, impinging-jet reactor, IR camera, Meerwein arylation, Numbering-up}, issn = {1083-6160}, doi = {10.1021/acs.oprd.0c00271}, author = {Shukla, Chinmay A. and Atapalkar, Ranjit S. and Kulkarni, Amol A.} } @article {46803, title = {New TBAF complex, highly stable, facile and selective source for nucleophilic fluorination: applications in batch and flow chemistry}, journal = {Asian Journal of Organic Chemistry}, volume = {9}, year = {2020}, month = {JUL}, pages = {1022-1026}, type = {Article}, abstract = {

Natural polysaccharides supported tetrabutylammonium fluoride (TBAF) complexes are prepared and found to be highly stable and selective fluoride source for well-renowned nucleophilic (SN2 type) fluorination reactions for the first time. Bacterial cellulose, plant cellulose, pectin, and starch derived TBAF complexes are synthesized, characterized (using SEM, TEM, and NMR techniques) and studied for their stability and reactivity. Heterogeneous bacterial cellulose-TBAF complex (NBu4(Bac-cell-OH)F) 1 was found to be highly stable and non-hygroscopic among all complexes, which gave high yields of fluorinated products in multi-gram scale in shorter reaction time. The primarily developed batch protocol was extended to solid-solid continuous flow reaction using an in-house built screw reactor, which furnished products in a few seconds of residence time (tR=20-25 sec) and excellent yields.

}, keywords = {Flow synthesis, fluorination, green chemistry, Sustainable Chemistry}, issn = {2193-5807}, doi = {10.1002/ajoc.202000235}, author = {Said, Madhukar S. and Khonde, Nilesh S. and Thorat, Meghana N. and Atapalkar, Ranjit S. and Kulkarni, Amol A. and Gajbhiye, Jayant and Dastager, Syed G.} } @article {46906, title = {Selectivity engineering of Meerwein arylation in a continuous flow reactor: a modelling approach}, journal = {Reaction Chemistry \& Engineering}, volume = {5}, year = {2020}, month = {APR }, pages = {736-746}, type = {Article}, abstract = {

This paper presents a methodology for selectivity engineering of Meerwein arylation in a flow reactor. The reaction was optimized in batch mode and reaction kinetics were obtained over a range of temperatures and catalyst concentrations. A lumped kinetic model was formulated and the parameters were estimated using nonlinear regression. Furthermore, telescopic flow synthesis for Meerwein arylation via in situ diazonium salt generation and coupling was demonstrated. A non-isothermal model was developed and experimentally validated. The effect of initial concentration and inlet temperature on the yield of the desired product was estimated for various catalyst concentrations. The results from the simulations in terms of nondimensional numbers were used to find suitable operating conditions for Meerwein arylation.

}, issn = {2058-9883}, doi = {10.1039/c9re00477g}, author = {Shukla, Chinmay A. and Atapalkar, Ranjit S. and Kulkarni, Amol A.} } @article {47615, title = {Multi-step synthesis of miltefosine: integration of flow chemistry with continuous mechanochemistry}, journal = {Chemistry-A European Journal}, volume = {27}, year = {2021}, month = {DEC }, pages = {17695-17699}, type = {Article}, abstract = {Herein we report for the first time, an advanced continuous flow synthesis of the blockbuster Leishmaniasis drug miltefosine from simple starting materials by a sequence involving four steps of chemical transformation including a continuous mechanochemical step. First three reaction steps were performed in simple tubular reactors in a telescopic mode, while in the last step the product precipitated from the 3(rd) step was used for a continuous mechanochemical synthesis of miltefosine. When compared to a typical batch protocol that takes 15 h, miltefosine was obtained in 58 \% overall yield in flow synthesis mode at the laboratory scale in a total residence time 34 min at synthesis rate of 10 g/hr, which is sufficient to treat 4800 patients per day.}, keywords = {continuous flow, continuous mechanochemistry, miltefosine, multistep synthesis, reactive intermediates}, issn = {0947-6539}, doi = {10.1002/chem.202103499}, author = {Patil, Niteen B. and Atapalkar, Ranjit S. and Chavan, Subhash P. and Kulkarni, Amol A.} } @article {47423, title = {Scalable, sustainable and catalyst-free continuous flow ozonolysis of fatty acids}, journal = {Green Chemistry}, volume = {23}, year = {2021}, month = {MAR}, pages = {2391-2396}, type = {Article}, abstract = {

A simple and efficient catalyst-free protocol for continuous flow synthesis of azelaic acid is developed from the renewable feedstock oleic acid. An ozone and oxygen mixture was used as the reagent for oxidative cleavage of double bond without using any metal catalyst or terminal oxidant. The target product was scaled up to more than 100 g with 86\% yield in a white powder form. Complete recycling and reuse of the solvent were established making it a green method. The approach is significantly energy efficient and also has a very small chemical footprint. The methodology has been successfully tested with four fatty acids making it a versatile platform that gives value addition from renewable resources.

}, issn = {1463-9262}, doi = {10.1039/d0gc04021e}, author = {Atapalkar, Ranjit S. and Athawale, Paresh R. and Reddy, D. Srinivasa and Kulkarni, Amol A.} } @article {48679, title = {Direct amidation of acids in a screw reactor for the continuous flow synthesis of amides}, journal = {Chemical Communications}, volume = {59}, year = {2023}, month = {JUL }, pages = {9231-9234}, type = {Article}, abstract = {

A simple and efficient solvent-free protocol for continuous flow synthesis of amides at room temperature is developed using easily available starting materials. N-(3-Dimethylaminopropyl)-N \& PRIME;-ethylcarbodiimide hydrochloride (EDC.HCl) was used as the reagent for the formation of an amide bond without using any metal catalyst or additives. A jacketed screw reactor when operated over a residence time of 30 300 s helped achieve almost complete conversion. This approach is extended for the synthesis of 36 derivatives and 2 bioactive molecules using different substrates having different aliphatic mono and di-acids as well as aromatic acids, including aromatic hetero-acid compounds and phenyl hydrazine. The target amide was scaled up to 100 g with an average 90\% yield.

}, issn = {1359-7345}, doi = {10.1039/d3cc02402d}, author = {Atapalkar, Ranjit S. and Kulkarni, Amol A.} }