Tandem transformations and multicomponent reactions utilizing alcohols following dehydrogenation strategy.

The construction of new C-C, C-N and C-O bonds by replacing hazardous and waste generating chemicals with alcohols as the greener and sustainable reagents is one of the emerging areas of research. In consequence, the borrowing hydrogen and acceptorless dehydrogenative coupling principles have received significant momentum to synthesize various alkylated molecules and N-heterocycles. In the tandem transformations and multi-component reactions, simple substrates are directly converted to new functionalities or complex molecular systems using a single reaction set-up. In this review, the progress of tandem transformation of nitro, nitrile and azide functionalities as well as multi-component reactions utilizing alcohols is summarised. These transformations lead to the atom-economical synthesis of a wide range of alkylated imines, amines, amides and N-heterocycles such as pyrrole, pyridine, pyrimidine, quinoxaline, etc.

Bifunctional Ru(ii) complex catalysed carbon-carbon bond formation: an eco-friendly hydrogen borrowing strategy.

The atom economical borrowing hydrogen methodology enables the use of alcohols as alkylating agents for selective C-C bond formation. A bifunctional 2-(2-pyridyl-2-ol)-1,10-phenanthroline (phenpy-OH) based Ru(ii) complex (2) was found to be a highly efficient catalyst for the one-pot ß-alkylation of secondary alcohols with primary alcohols and double alkylation of cyclopentanol with different primary alcohols. Exploiting the metal-ligand cooperativity in complex 2, several aromatic, aliphatic and heteroatom substituted alcohols were selectively cross-coupled in high yields using significantly low catalyst loading (0.1 mol%). An outer-sphere mechanism is proposed for this system as exogenous PPh3 has no significant effect on the rate of the reaction. Notably, this is a rare one-pot strategy for ß-alkylation of secondary alcohols using a bifunctional Ru(ii)-complex. Moreover, this atom-economical methodology displayed the highest cumulative turn over frequency (TOF) among all the reported transition metal complexes in cross coupling of alcohols.

The use of methanol as a C1 building block.

Methanol is a key building block in the chemical industry. In recent years, it has been used as a C1 source in various organic transformations in the presence of a transition-metal catalyst. This protocol describes the ruthenium- and cobalt-catalyzed utilization of methanol in different types of methylation reactions and heterocycle synthesis. Initially, we describe the synthesis of tridentate ligands (L1-L3) and their corresponding Ru(II) complexes (Ru-1, -2 and -3) and then detail how to apply these Ru(II) complexes and Co/PP3 (PP3 = P(CH2CH2PPh2)3) in various methanol dehydrogenative coupling reactions. We discuss six types of transformations by using methanol or a methanol/water mixture. The experimental setup for all the catalytic reactions is similar and involves adding all the respective reagents and solvents to an argon-filled pressure tube, which is sealed (by screw cap) and refluxed at the indicated temperature before the desired products are isolated and characterized. The catalytic systems described in this protocol work well for both small-scale and preparative-scale synthesis of various N-methylated amines/amides, C-methylated products and quinazolinones. These catalytic reactions are greener and more sustainable than conventional synthesis methods, with only H2 and/or H2O as by-products, and we evaluate the 'green chemistry metrics' for a typical substrate. The total time required for the catalytic experiments described in this protocol is 16-28 h, and the operation time is 4 h. An average level of expertise in organic synthesis is required to carry out these protocols.

Synthesis of N-heterocycles through alcohol dehydrogenative coupling.

Nitrogen heterocycles are found in the structures of many biologically important compounds, as well as materials used in the synthesis of fine chemicals. Notably, ~59% of US Food and Drug Administration-approved small-molecule drugs contain nitrogen heterocycles. It is therefore meaningful to explore greener or more sustainable methods for their synthesis. The use of alcohols as reagents is attractive as they can be readily obtained from biomass derived natural resources. In the last two decades, alcohol dehydrogenative coupling reaction to synthesize various heterocycles were extensively explored which furnished hydrogen (H2) and water (H2O) as the two greener byproducts. In this protocol, we describe several efficient catalytic transformations to synthesize quinolines, 1,8-naphthyridines, quinoxalines, quinazolines, pyrimidines, benzimidazoles, pyrroles and pyridines, using alcohol as starting materials. We also describe the synthesis of several homogeneous iridium/ruthenium catalysts and heterogeneous cobalt/copper catalysts that can be used in these transformations. The reaction setup is simple; in a Schlenk/reaction tube with magnetic stir-bar, alcohol, corresponding coupling reagents (nucleophiles), catalyst, base and solvent (water or organic solvent such as toluene, dioxane or p-xylene) are added. The reaction mixture is refluxed at the specified temperature (110-150 °C)-either in air or under argon-to furnish these heterocycles. Synthesis of the catalysts takes 3-5 h and the coupling reactions take 4-5 h depending on the target product. The cobalt- and copper-based heterogeneous catalytic systems displayed an good catalyst recyclability.

Synthesis of Heterocycle-Substituted Bicyclo[3.1.1]heptanes and Aza-bicyclo[3.1.1]heptanes via Photocatalytic Minisci Reaction.

A route toward heterocycle-functionalized bicyclo[3.1.1]heptanes (BCHeps) and aza-bicyclo[3.1.1]heptanes (aza-BCHeps) has been developed, using mild, photocatalytic Minisci-like conditions to introduce various heterocycles at the bridgehead position from readily available N-hydroxyphthalimide esters of the corresponding carboxylic acids. This chemistry enables access to heterocycle-functionalized BCHep-containing structures that are highly relevant in medicinal chemistry research as potential bioisosteres of meta-substituted arenes and pyridines.

Room-temperature deformation of single crystals of ZrB2 and TiB2 with the hexagonal AlB2 structure investigated by micropillar compression.

The plastic deformation behavior of single crystals of two transition-metal diborides, ZrB2 and TiB2 with the AlB2 structure has been investigated at room temperature as a function of crystal orientation and specimen size by micropillar compression tests. Although plastic flow is not observed at all for their bulk single crystals at room temperature, plastic flow is successfully observed at room temperature by the operation of slip on {1[Formula: see text]00}<11[Formula: see text]3> in ZrB2 and by the operation of slip on {1[Formula: see text]00}<0001> and {1[Formula: see text]00}<11[Formula: see text]0> in TiB2. Critical resolve shear stress values at room temperature are very high, exceeding 1 GPa for all observed slip systems; 3.01 GPa for {1[Formula: see text]00}<11[Formula: see text]3> slip in ZrB2 and 1.72 GPa and 5.17 GPa, respectively for {1[Formula: see text]00}<0001> and {1[Formula: see text]00}<11[Formula: see text]0> slip in TiB2. The identified operative slip systems and their CRSS values are discussed in comparison with those identified in the corresponding bulk single crystals at high temperatures and those inferred from micro-hardness anisotropy in the early studies.

Hospital-based perinatal outcomes and complications in teenage pregnancy in India.

Teenage pregnancy is a worldwide problem bearing serious social and medical implications relating to maternal and child health. A cross-sectional observational study was undertaken to compare the different sociodemographic characteristics and perinatal outcomes of teenage primigravida mothers with those of adult primigravida mothers in a tertiary-care hospital in eastern India. A sample of 350 each in cases and comparison group comprised the study subjects. Data were collected through interviews and by observations using a pretested and predesigned schedule. Results revealed that the teenage mothers had a higher proportion (27.7%) of preterm deliveries compared to 13.1% in the adult mothers and had low-birthweight babies (38.9% vs 30.4% respectively). Stillbirth rate was also significantly higher in teenage deliveries (5.1% vs 0.9% respectively). The teenage mothers developed more adverse perinatal complications, such as preterm births, stillbirths, neonatal deaths, and delivered low-birthweight babies, when compared with those of the adult primigravida mothers. Teenage pregnancy is still a rampant and important public-health problem in India with unfavourable perinatal outcomes and needs to be tackled on a priority basis.

Ruthenium-Catalyzed Synthesis of N-Methylated Amides using Methanol.

An efficient synthesis of N-methylated amides using methanol in the presence of a ruthenium(II) catalyst is realized. Notably, applying this process, tandem C-methylation and N-methylation were achieved to synthesize α-methyl N-methylated amides. In addition, several kinetic studies and control experiments with the plausible intermediates were performed to understand this novel protocol. Furthermore, detailed computational studies were carried out to understand the mechanism of this transformation.

Tandem Transformation of Nitro Compounds into N-Methylated Amines: Greener Strategy for the Utilization of Methanol as a Methylating Agent.

A simple air- and moisture-stable, highly efficient ruthenium NNN pincer complex is reported for the first time to catalyze the tandem transformation of various aromatic and aliphatic nitro compounds into the corresponding N-methylated amines in up to 98 % yield by using methanol as a green methylating agent. Gram-scale reactions of challenging nitro substrates demonstrated the practical application aspects of this catalytic system. Importantly, the N-methylamine moiety could be smoothly introduced to various complex molecular structures without using any expensive palladium/phosphine/amine-based cross-coupling reactions.

Utilization of MeOH as a C1 Building Block in Tandem Three-Component Coupling Reaction.

Ru(II) catalyzed tandem synthesis of α-branched methylated ketones via multicomponent reactions following the hydrogen borrowing process is described. This nonphosphine-based air and moisture stable catalyst efficiently produced various methylated ketones using methanol as a methylating agent. This system was found to be highly effective in three-component coupling between methanol, primary alcohols, and methyl ketones. A proposed catalytic cycle for the α-methylation is supported by DFT calculations as well as kinetic experiments.

Optimum bifunctionality in a 2-(2-pyridyl-2-ol)-1,10-phenanthroline based ruthenium complex for transfer hydrogenation of ketones and nitriles: impact of the number of 2-hydroxypyridine fragments.

Considerable differences in reactivity and selectivity for 2-hydroxypyridine (2-HP) derived ruthenium complexes in transfer hydrogenation are described. Bifunctional Ru(ii)-(phenpy-OH) [phenpy-OH: 2-(2-pyridyl-2-ol)-1,10-phenanthroline] complex () exhibited excellent catalytic activity in transfer hydrogenation (TH) of ketones and nitriles. Notably, in comparison with all the reported 2-hydroxypyridine (2-HP) derived ruthenium complexes in transfer hydrogenation, complex displayed significantly higher activity. Additionally, exploiting the metal-ligand cooperativity in complex , chemoselective TH of ketones was achieved and sterically demanding ketones were readily reduced. An outer-sphere mechanism is proposed for this system as exogenous PPh3 has no significant effect on the rate of this reaction. This is a rare example of a highly active bifunctional Ru(ii) catalyst bearing only one 2-HP unit.

Unusual presentation of metastasis in adenocarcinoma cervix.

Metastatic carcinoma in an abdominal wall incision from carcinoma cervix is an uncommon and often a preterminal event. It has been reported mostly in advanced cases, often previously treated with radiotherapy. Here a case of cervical cancer with subcutaneous and rectus sheath recurrence 4 months after abdominal hysterectomy in a previously unsuspected case of adenocarcinoma cervix is reported. The patient was treated with excision of the metastatic masses followed by chemoradiation and is doing well at 5 months since presentation.

Evaporation-induced self assembly of nanoparticles in non-buckling regime: volume fraction dependent packing.

Hierarchically structured micrometric spheres are synthesized by evaporation-induced self assembly of silica colloids using spray drying technique. Packing of nanoparticles during drying of droplets is an important issue. The motivation of the present work is to investigate the effects of concentration of initial colloidal dispersion on the packing of the nanoparticles in assembled grains in non-buckling regime of drying. It has been observed that the packing of nanoparticles inside the dried grains, even in the non-buckling regime, varies significantly with concentration. Although, the packing of nanoparticles remains uniform in an assembled grain at smaller concentration, the same becomes non-uniform at higher concentration. Further, the average packing fraction of the nanoparticles within the assembled grains, decreases with increasing colloidal concentration. These observations have been attributed to the modification in viscosity of the initial dispersion. Electron microscopy, light scattering measurements have been performed to probe overall morphology of the dried grains, while inter-particle correlation inside the grains has been investigated by small angle neutron scattering.