01397nas a2200217 4500008004100000022001400041245005400055210005400109260008600163300001200249490000700261520069400268653002000962653001900982653001801001653001401019653001601033653002001049100002301069856008701092 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. uhttp://library.ncl.res.in/content/continuous-flow-nitration-miniaturized-devices-001698nas a2200241 4500008004100000022001400041245003900055210003800094260008300132300001200215490000600227520095700233653001901190653001901209653002501228653002301253653001501276653002401291100002101315700002201336700002301358856007501381 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. uhttp://library.ncl.res.in/content/continuous-flow-meerwein-arylation-002643nas a2200265 4500008004100000022001400041245013600055210006900191260000800260300001400268490000800282520168600290653002501976653004102001653002202042653003902064653001902103100002302122700002102145700002402166700001902190700002102209700002902230856011802259 2020 eng d a1011-372X00aOrganocatalytic cascade knoevenagel-michael addition reactions: direct synthesis of polysubstituted 2-amino-4H-chromene derivatives0 aOrganocatalytic cascade knoevenagelmichael addition reactions di cAUG a2331-23510 v1503 a

In this report, we documented novel strategy for the synthesis of bioactive polysubstituted 2-amino-4H-chromine derivatives under a heterogeneous Al-MCM-41-LDH@APTES (ALAM) catalysis. A synthetic procedure is developed to prepare Al-MCM-41-LDH@APTES (ALAM) heterogeneous basic catalysts. Mesoporous Al-MCM-41 is functionalized by known grafting chemistry via layered double hydroxide (LDH) nanosheets and (3-aminopropyl)triethoxysilane (APTES) moiety as a basic organocatalyst. The resulting catalysts contain amino group functionality on the external surface as well as inside the layers and the basicity can be tuned by the loading of APTES. The samples were fully characterized by Si-29 and C-13 CP/MAS NMR, infrared absorption spectroscopy, TEM, XPS, EDX, TGA, XRD, CO2-TPD, N-2 adsorption isotherms measurements, and they were successfully examined for the cascade type Knoevenagel-Michael addition reactions. The product yields associated with these substrates were optimized, and key reaction parameters affecting the yields were identified. The present catalytic method is simple and robust for diversity oriented synthesis which proceeds good to excellent yields without generating any hazards waste. The broad substrate scope, excellent functional group compatibility makes this protocol highly useful towards synthesis of polysubstituted alpha-cyanoacrylates, alpha-cyanoacrylonitriles and 2-amino-4H-chromenes with an electron-donating or electron-withdrawing group. We have also successfully established a flow reaction system, gram-scale synthesis as well as catalyst recyclability up to six catalytic cycles without appreciable loss of its activity. Graphic

10a2-Amino-4H-chromines10aAmine functionalized solid catalysts10acascade synthesis10aDiversity oriented syntheses (DOS)10aflow chemistry1 aJadhav, Sanjay, N.1 aPatil, Seema, P.1 aSahoo, Dipti, Prava1 aRath, Dharitri1 aParida, Kulamani1 aRode, Chandrashekhar, V. uhttp://library.ncl.res.in/content/organocatalytic-cascade-knoevenagel-michael-addition-reactions-direct-synthesis01754nas a2200205 4500008004100000022001400041245009300055210006900148260000800217300001200225490000700237520104000244653003401284653001901318653002201337653002701359100002201386700002301408856011701431 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. uhttp://library.ncl.res.in/content/continuous-flow-telescopic-synthesis-3-methoxy-propiophenone-grignard-reaction