01399nas 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-using01953nas a2200241 4500008004100000022001400041245011200055210006900167260000800236300001400244490000700258520110100265653003301366653003001399653002601429653001401455653002301469653001701492100002401509700002601533700002301559856012901582 2020 eng d a1083-616000aEfficient processing of reactions involving diazonium salts: meerwein arylation in an impinging-jet reactor0 aEfficient processing of reactions involving diazonium salts meer cSEP a1658-16640 v243 a

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.

10acomputational fluid dynamics10ahigh throughput synthesis10aimpinging-jet reactor10aIR camera10aMeerwein arylation10aNumbering-up1 aShukla, Chinmay, A.1 aAtapalkar, Ranjit, S.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/efficient-processing-reactions-involving-diazonium-salts-meerwein-arylation-impinging-jet01832nas a2200265 4500008004100000022001400041245013700055210006900192260000800261300001400269490000600283520090800289653001901197653001701216653002001233653002601253100002301279700002301302700002401325700002601349700002301375700002101398700002301419856012401442 2020 eng d a2193-580700aNew TBAF complex, highly stable, facile and selective source for nucleophilic fluorination: applications in batch and flow chemistry0 aNew TBAF complex highly stable facile and selective source for n cJUL a1022-10260 v93 a

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.

10aFlow synthesis10afluorination10agreen chemistry10aSustainable Chemistry1 aSaid, Madhukar, S.1 aKhonde, Nilesh, S.1 aThorat, Meghana, N.1 aAtapalkar, Ranjit, S.1 aKulkarni, Amol, A.1 aGajbhiye, Jayant1 aDastager, Syed, G. uhttps://library.ncl.res.in/content/new-tbaf-complex-highly-stable-facile-and-selective-source-nucleophilic-fluorination01454nas a2200169 4500008004100000022001400041245010100055210006900156260000900225300001200234490000600246520083400252100002401086700002601110700002301136856012501159 2020 eng d a2058-988300aSelectivity engineering of Meerwein arylation in a continuous flow reactor: a modelling approach0 aSelectivity engineering of Meerwein arylation in a continuous fl cAPR  a736-7460 v53 a

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.

1 aShukla, Chinmay, A.1 aAtapalkar, Ranjit, S.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/selectivity-engineering-meerwein-arylation-continuous-flow-reactor-modelling-approach01605nas a2200241 4500008004100000022001400041245010400055210006900159260000900228300001600237490000700253520076200260653002001022653003201042653001601074653002401090653002701114100002201141700002601163700002401189700002301213856012701236 2021 eng d a0947-653900aMulti-step synthesis of miltefosine: integration of flow chemistry with continuous mechanochemistry0 aMultistep synthesis of miltefosine integration of flow chemistry cDEC  a17695-176990 v273 aHerein 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.10acontinuous flow10acontinuous mechanochemistry10amiltefosine10amultistep synthesis10areactive intermediates1 aPatil, Niteen, B.1 aAtapalkar, Ranjit, S.1 aChavan, Subhash, P.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/multi-step-synthesis-miltefosine-integration-flow-chemistry-continuous-mechanochemistry01355nas a2200181 4500008004100000022001400041245008600055210006900141260000800210300001400218490000700232520072200239100002600961700002500987700002101012700002301033856011701056 2021 eng d a1463-926200aScalable, sustainable and catalyst-free continuous flow ozonolysis of fatty acids0 aScalable sustainable and catalystfree continuous flow ozonolysis cMAR a2391-23960 v233 a

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.

1 aAtapalkar, Ranjit, S.1 aAthawale, Paresh, R.1 aReddy, Srinivasa1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/scalable-sustainable-and-catalyst-free-continuous-flow-ozonolysis-fatty-acids01705nas a2200205 4500008004100000022001400041245009200055210006900147260000900216300001000225490000600235520104200241653001001283653001101293653001001304653001201314100002601326700002301352856012401375 2023 eng d a2058-988300aBatch and continuous flow mechanochemical synthesis of organic compounds including APIs0 aBatch and continuous flow mechanochemical synthesis of organic c cDEC  a10-250 v93 a

Mechanochemistry is becoming an enabling technology for the synthesis of organic and inorganic compounds as well as for the synthesis of polymers as it underlines sustainability in a significant manner. Continuous mechanochemical synthesis further adds value to the approach through consistency, smaller footprint, and better energy efficiency. This review gives an indepth view of the present status of this subject along with critical engineering aspects that one needs to measure and monitor as eventually synthesis needs to be transformed into a process. The examples covered herein include the synthesis of organic compounds, viz., APIs, agrochemical intermediates, catalysts, and polymers. In the end, we also discuss the safety aspects of mechanochemical synthesis and recommendations for exploring this field further. Mechanochemistry is becoming an enabling technology for the synthesis of organic and inorganic compounds as well as for the synthesis of polymers as it underlines sustainability in a significant manner.

10aacids10aAmides10aForce10asolvent1 aAtapalkar, Ranjit, S.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/batch-and-continuous-flow-mechanochemical-synthesis-organic-compounds-including-apis01362nas a2200157 4500008004100000022001400041245009300055210006900148260000900217300001400226490000700240520079900247100002601046700002301072856010901095 2023 eng d a1359-734500aDirect amidation of acids in a screw reactor for the continuous flow synthesis of amides0 aDirect amidation of acids in a screw reactor for the continuous  cJUL  a9231-92340 v593 a

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.

1 aAtapalkar, Ranjit, S.1 aKulkarni, Amol, A. uhttps://library.ncl.res.in/content/direct-amidation-acids-screw-reactor-continuous-flow-synthesis-amides