Vinay Bhaya - Academia.edu (original) (raw)

Papers by Vinay Bhaya

Ibuprofen [2-(4-isobutyl-phenyl)-propionic acid] is a common analgesic pharmaceutical. It is subs... more Ibuprofen [2-(4-isobutyl-phenyl)-propionic acid] is a common analgesic pharmaceutical. It is substantially insoluble in water but quite soluble in organic solvents. Ibuprofen here has been crystallized from ethanol and aqueous ethanol. Batch experiments were undertaken from 10 to 40 o C to measure the solubility, the width of the metastable zone and the growth kinetics. The solubility in ethanol varies markedly with temperature. Generally solubilities fall as the water content increases for aqueous ethanol. At 40 o C, saturated solutions with solvent water contents from 35 to 65 % w/w show a phase separation into two liquid layers. The metastable zone width for primary nucleation is substantial, but is much narrower for secondary nucleation. None the less, growth rates in this narrow secondary metastable zone are still significant and this region, with care, can be used for non-nucleating seeded batch crystallizations. Crystal growth rates were found to be first order with supersaturation, with growth rate constants increasing with temperature [activation energy = 23.4 (±50%) kJ/mol] and within the accuracy of measurement not changing with the solvent water content.

Microreactors have brought significant improvements to chemical synthesis and production because ... more Microreactors have brought significant improvements to chemical synthesis and production because of their advantageous characteristics over batch reactors, which include highly efficient mixing, efficient heat and mass transfer ability, precise control of the residence time, large surface area-to-volume ratio and high operational safety. Microreactor technology has been found to be beneficial for gas-liquid biphasic reactions, for which the large interfacial area between the two phases is ensured. Carbonylation reactions with carbon monoxide, by which a wide range of carbonyl compounds can be prepared, deal with a variety of reactive species, such as organo transition metals, radicals, cations and anions. These reactions have long been carried out using a glass batch flask or a stainless-steel made autoclave, however, carbonylation reactions using a flow microreactor are now rapidly increasing in popularity. This review focuses on a new greener wave of carbonylation reactions using a flow microreactor.

Thus in the present research we were able to detect the presence of the corresponding aldehydes i... more Thus in the present research we were able to detect the presence of the corresponding aldehydes in the reaction mixtures from the chlorophenylation of 2-acetyl-and 2-propionylfuran.

The structure of the intermediate obtained in the c o m e of the nitration of 2-furancarboxaldehy... more The structure of the intermediate obtained in the c o m e of the nitration of 2-furancarboxaldehyde was investigated by means of 'H and "C NMR. It was shown unambiguously that this intermediate is 2-acetoxy-2-diacetogymethyl-5-nitro-2,5-dihydrofuran.

Nitrofurazone is one of the antibacterial nitrofuran agents used topically for skin infections. T... more Nitrofurazone is one of the antibacterial nitrofuran agents used topically for skin infections. The drug is effective on the majority of infectious microorganisms. Because of the importance of this drug in clinic, in this study various methods of synthesis of nitrofurazone were examined and the most appropriate method, applicable to pharmaceutical industry was chosen and optimized from the points of quality and yield.

Abstract Direct nitration of a variety of furans, pyrroles, thiophenes, pyrazoles, imidazoles, is... more Abstract Direct nitration of a variety of furans, pyrroles, thiophenes, pyrazoles, imidazoles, isoxazoles and thiazoles (17 compounds) with nitric acid/trifluoroacetic anhydride affords mononitro derivatives in average yield of 60 %.

In the transition-metal-catalyzed cross-coupling reactions, the use of the first row transition m... more In the transition-metal-catalyzed cross-coupling reactions, the use of the first row transition metals as catalysts is much more appealing than the precious metals owing to the apparent advantages such as cheapness and earth abundance. Within the last two decades, particularly the last five years, explosive interests have been focused on the nickel-catalyzed Suzuki-Miyaura reactions. This has greatly advanced the chemistry of transition-metal-catalyzed cross-coupling reactions. Most notably, a broad range of aryl electrophiles such as phenols, aryl ethers, esters, carbonates, carbamates, sulfamates, phosphates, phosphoramides, phosphonium salts, and fluorides, as well as various alkyl electrophiles, which are conventionally challenging, by applying palladium catalysts can now be coupled efficiently with boron reagents in the presence of nickel catalysts. In this review, we would like to summarize the progress in this reaction. even at room temperature 11 and in a short time, within only several minutes. 12 Moreover, the substrate scope for either coupling partner has been substantially expanded. Typically the electrophiles such as sterically very congested substrates, 11d,13 and the inert aryl and vinyl chlorides 11,14 and sulfonate derivatives, 15 as well as the nucleophiles such as thermally unstable polyfluorophenyl and 2-heteroaryl boron reagents, which are conventionally extremely challenging partners, can now be coupled readily. In addition, the palladium-catalyzed asymmetric Suzuki-Miyaura reaction has also been intensively developed. 17 Moreover, with the rapid development of nanotechnology, considerable progress has been achieved recently by carrying out the reaction in a heterogeneous system by means of anchoring the catalysts onto solid supports with nano size. 18 This development would make the reaction much more sustainable, 19 and, consequently, more practical for industrial applications in terms of the purification of products, as well as the separation, recovery, and reuse of the catalysts. Owing to these important advances, the palladium-catalyzed Suzuki-Miyaura cross-coupling has become the first choice for chemists in a wide range of communities if a C-C bond forming reaction is under consideration. By employing this reaction, almost all kinds of biaryl, aryl-vinyl, alkyl-aryl, and alkyl-alkyl compounds can be synthesized efficiently. Needless to elaborate any further, the importance of the palladiumcatalyzed Suzuki-Miyaura reaction has been well recognized with the 2010 Nobel Prize in chemistry together with Heck and Negishi couplings. Standing on the privileged and well-established platform, synthetic organic chemists have been devoted to the more challenging issues remaining both in industry and academia. To this end, much recent attention in Suzuki-Miyaura crosscoupling has been focused on the nickel catalysts because nickel is much cheaper and more earth abundant than the palladium metal. 22 Therefore, the use of nickel catalysts would be far more cost-effective, unless a coupling reaction is workable with a very low level of palladium loading, or only with a very high nickel catalyst loading. On the other hand, the redox state of palladium is typically Pd (0) /Pd (II) , albeit the catalysis chemistry of high valent palladium such as Pd (III) and Pd (IV) has been increasingly investigated in recent direct C-H functionalization. In contrast, the early transition metal nickel usually displays Ni (0) /Ni (II) as well as Ni (I) /Ni (III) oxidation states and is more nucleophilic due to its smaller size. 24b As such, nickel can not be simply considered to be a substitute for palladium, it possesses distinctive catalytic properties that palladium does not have. Indeed, extensive studies have clearly demonstrated that the nickel-based catalysts were more versatile and powerful catalysts for the C-C, 24 C-N, 24b,c and C-P 25 bond forming reactions of a diverse class of electrophiles, which are conventionally challenging in the presence of palladium catalysts .

Packed-bed microreactors are employed under flow conditions for studies of heterogeneous catalysi... more Packed-bed microreactors are employed under flow conditions for studies of heterogeneous catalysis: oxidation of 4-isopropylbenzaldehyde and hydrogenation of 2-methylfuran. They have been demonstrated to be a valuable platform for rapid screening of catalytic materials, efficient optimization of reaction conditions, inline monitoring of reaction progress, and extraction of kinetic parameters.

The application of heterogeneous catalysis in conjunction with microreactor technology can facili... more The application of heterogeneous catalysis in conjunction with microreactor technology can facilitate a cleaner and scalable flow methodology for organic synthesis. In this tutorial review we present recent advances in the design of supported catalysts for emerging synthetic applications within microreactor technology. Specifically, transition metal catalysts such as palladium, copper, ruthenium, and nickel are described on silica, monolithic, magnetic nanoparticles and polymer supports. These catalysts have been utilised to promote a range of reactions including Heck, Sonogashira, Suzuki, Kumada, olefin metathesis, hydrogenation and benzannulation reactions.

The microscale revolution in chemistry promises to transform classical batch wise laboratory proc... more The microscale revolution in chemistry promises to transform classical batch wise laboratory procedures into integrated systems capable of providing new understanding of fundamental chemical processes as well as rapid, continuous discovery and development of new products with less use of resources and waste generation. Applications of silicon based microreactors are illustrated with a broad range of cases studies, including high throughput experimentation in organic synthesis, integration of ultraviolet (UV), visible and infrared (IR) spectroscopy; investigations of high temperature heterogeneous catalytic reactions, obtaining high mass transfer rates in gas-liquid reactions over solid catalysts, enabling difficult to perform reactions, synthesis of solid nanoparticles, and high temperature conversion of hydrocarbons to hydrogen.

Ibuprofen [2-(4-isobutyl-phenyl)-propionic acid] is a common analgesic pharmaceutical. It is subs... more Ibuprofen [2-(4-isobutyl-phenyl)-propionic acid] is a common analgesic pharmaceutical. It is substantially insoluble in water but quite soluble in organic solvents. Ibuprofen here has been crystallized from ethanol and aqueous ethanol. Batch experiments were undertaken from 10 to 40 o C to measure the solubility, the width of the metastable zone and the growth kinetics. The solubility in ethanol varies markedly with temperature. Generally solubilities fall as the water content increases for aqueous ethanol. At 40 o C, saturated solutions with solvent water contents from 35 to 65 % w/w show a phase separation into two liquid layers. The metastable zone width for primary nucleation is substantial, but is much narrower for secondary nucleation. None the less, growth rates in this narrow secondary metastable zone are still significant and this region, with care, can be used for non-nucleating seeded batch crystallizations. Crystal growth rates were found to be first order with supersaturation, with growth rate constants increasing with temperature [activation energy = 23.4 (±50%) kJ/mol] and within the accuracy of measurement not changing with the solvent water content.

Microreactors have brought significant improvements to chemical synthesis and production because ... more Microreactors have brought significant improvements to chemical synthesis and production because of their advantageous characteristics over batch reactors, which include highly efficient mixing, efficient heat and mass transfer ability, precise control of the residence time, large surface area-to-volume ratio and high operational safety. Microreactor technology has been found to be beneficial for gas-liquid biphasic reactions, for which the large interfacial area between the two phases is ensured. Carbonylation reactions with carbon monoxide, by which a wide range of carbonyl compounds can be prepared, deal with a variety of reactive species, such as organo transition metals, radicals, cations and anions. These reactions have long been carried out using a glass batch flask or a stainless-steel made autoclave, however, carbonylation reactions using a flow microreactor are now rapidly increasing in popularity. This review focuses on a new greener wave of carbonylation reactions using a flow microreactor.

Thus in the present research we were able to detect the presence of the corresponding aldehydes i... more Thus in the present research we were able to detect the presence of the corresponding aldehydes in the reaction mixtures from the chlorophenylation of 2-acetyl-and 2-propionylfuran.

The structure of the intermediate obtained in the c o m e of the nitration of 2-furancarboxaldehy... more The structure of the intermediate obtained in the c o m e of the nitration of 2-furancarboxaldehyde was investigated by means of 'H and "C NMR. It was shown unambiguously that this intermediate is 2-acetoxy-2-diacetogymethyl-5-nitro-2,5-dihydrofuran.

Nitrofurazone is one of the antibacterial nitrofuran agents used topically for skin infections. T... more Nitrofurazone is one of the antibacterial nitrofuran agents used topically for skin infections. The drug is effective on the majority of infectious microorganisms. Because of the importance of this drug in clinic, in this study various methods of synthesis of nitrofurazone were examined and the most appropriate method, applicable to pharmaceutical industry was chosen and optimized from the points of quality and yield.

Abstract Direct nitration of a variety of furans, pyrroles, thiophenes, pyrazoles, imidazoles, is... more Abstract Direct nitration of a variety of furans, pyrroles, thiophenes, pyrazoles, imidazoles, isoxazoles and thiazoles (17 compounds) with nitric acid/trifluoroacetic anhydride affords mononitro derivatives in average yield of 60 %.

In the transition-metal-catalyzed cross-coupling reactions, the use of the first row transition m... more In the transition-metal-catalyzed cross-coupling reactions, the use of the first row transition metals as catalysts is much more appealing than the precious metals owing to the apparent advantages such as cheapness and earth abundance. Within the last two decades, particularly the last five years, explosive interests have been focused on the nickel-catalyzed Suzuki-Miyaura reactions. This has greatly advanced the chemistry of transition-metal-catalyzed cross-coupling reactions. Most notably, a broad range of aryl electrophiles such as phenols, aryl ethers, esters, carbonates, carbamates, sulfamates, phosphates, phosphoramides, phosphonium salts, and fluorides, as well as various alkyl electrophiles, which are conventionally challenging, by applying palladium catalysts can now be coupled efficiently with boron reagents in the presence of nickel catalysts. In this review, we would like to summarize the progress in this reaction. even at room temperature 11 and in a short time, within only several minutes. 12 Moreover, the substrate scope for either coupling partner has been substantially expanded. Typically the electrophiles such as sterically very congested substrates, 11d,13 and the inert aryl and vinyl chlorides 11,14 and sulfonate derivatives, 15 as well as the nucleophiles such as thermally unstable polyfluorophenyl and 2-heteroaryl boron reagents, which are conventionally extremely challenging partners, can now be coupled readily. In addition, the palladium-catalyzed asymmetric Suzuki-Miyaura reaction has also been intensively developed. 17 Moreover, with the rapid development of nanotechnology, considerable progress has been achieved recently by carrying out the reaction in a heterogeneous system by means of anchoring the catalysts onto solid supports with nano size. 18 This development would make the reaction much more sustainable, 19 and, consequently, more practical for industrial applications in terms of the purification of products, as well as the separation, recovery, and reuse of the catalysts. Owing to these important advances, the palladium-catalyzed Suzuki-Miyaura cross-coupling has become the first choice for chemists in a wide range of communities if a C-C bond forming reaction is under consideration. By employing this reaction, almost all kinds of biaryl, aryl-vinyl, alkyl-aryl, and alkyl-alkyl compounds can be synthesized efficiently. Needless to elaborate any further, the importance of the palladiumcatalyzed Suzuki-Miyaura reaction has been well recognized with the 2010 Nobel Prize in chemistry together with Heck and Negishi couplings. Standing on the privileged and well-established platform, synthetic organic chemists have been devoted to the more challenging issues remaining both in industry and academia. To this end, much recent attention in Suzuki-Miyaura crosscoupling has been focused on the nickel catalysts because nickel is much cheaper and more earth abundant than the palladium metal. 22 Therefore, the use of nickel catalysts would be far more cost-effective, unless a coupling reaction is workable with a very low level of palladium loading, or only with a very high nickel catalyst loading. On the other hand, the redox state of palladium is typically Pd (0) /Pd (II) , albeit the catalysis chemistry of high valent palladium such as Pd (III) and Pd (IV) has been increasingly investigated in recent direct C-H functionalization. In contrast, the early transition metal nickel usually displays Ni (0) /Ni (II) as well as Ni (I) /Ni (III) oxidation states and is more nucleophilic due to its smaller size. 24b As such, nickel can not be simply considered to be a substitute for palladium, it possesses distinctive catalytic properties that palladium does not have. Indeed, extensive studies have clearly demonstrated that the nickel-based catalysts were more versatile and powerful catalysts for the C-C, 24 C-N, 24b,c and C-P 25 bond forming reactions of a diverse class of electrophiles, which are conventionally challenging in the presence of palladium catalysts .

Packed-bed microreactors are employed under flow conditions for studies of heterogeneous catalysi... more Packed-bed microreactors are employed under flow conditions for studies of heterogeneous catalysis: oxidation of 4-isopropylbenzaldehyde and hydrogenation of 2-methylfuran. They have been demonstrated to be a valuable platform for rapid screening of catalytic materials, efficient optimization of reaction conditions, inline monitoring of reaction progress, and extraction of kinetic parameters.

The application of heterogeneous catalysis in conjunction with microreactor technology can facili... more The application of heterogeneous catalysis in conjunction with microreactor technology can facilitate a cleaner and scalable flow methodology for organic synthesis. In this tutorial review we present recent advances in the design of supported catalysts for emerging synthetic applications within microreactor technology. Specifically, transition metal catalysts such as palladium, copper, ruthenium, and nickel are described on silica, monolithic, magnetic nanoparticles and polymer supports. These catalysts have been utilised to promote a range of reactions including Heck, Sonogashira, Suzuki, Kumada, olefin metathesis, hydrogenation and benzannulation reactions.

The microscale revolution in chemistry promises to transform classical batch wise laboratory proc... more The microscale revolution in chemistry promises to transform classical batch wise laboratory procedures into integrated systems capable of providing new understanding of fundamental chemical processes as well as rapid, continuous discovery and development of new products with less use of resources and waste generation. Applications of silicon based microreactors are illustrated with a broad range of cases studies, including high throughput experimentation in organic synthesis, integration of ultraviolet (UV), visible and infrared (IR) spectroscopy; investigations of high temperature heterogeneous catalytic reactions, obtaining high mass transfer rates in gas-liquid reactions over solid catalysts, enabling difficult to perform reactions, synthesis of solid nanoparticles, and high temperature conversion of hydrocarbons to hydrogen.