Studies in the chemistry of benzobicyclo systems

Reactions of tetrahalogenobenzynes with certain tertiary arylamines afford products which are derived by both 1,2- and 1,4-cyclo-addition as well as from a betaine. The tetrahalogenobenzynes and benzyne react with eneamines to give benzocyclobutene-derivatives via betaines; the tetrahalogenobenzyne derivatives are readily hydrolysed to 2-tetrahalogenophenyl cycloalkanones. 1-N-alkylamino derivatives of 5,6,7,8-tetrahalogeno-1,4-dihydronaphthalene also undergo cleavage reactions in protic media. Thus, for example, 1-N, N-dimethylamino-tetrafluorobenzobarrelene gives 2,3,4,5- tetrafluoro-k'-N, N-dimethylaminobiphenyl in high yield and 1,2,3,1- tetrafluoro-5,8-dihydro-5,8-N-(-methyl)-iminonaphthalene affords 2'- (2,3,4,5-tetrafluorophenyl)-N-methyl. pyrrole. Apparent similarities between mass spectral and thermal processes have been investigated in connection with retro-Diels-Alder reactions leading to k, 5,6,7-tetrahalogeno-isobenzofurans and 1,5,6,7-tetrafluoro- 2-methylisoindole. These derivatives are more stable than the nonhalogenated compounds. The rearrangement reactions of 1-methoxybenzobarrelene derivatives in strong acids have been studied. Various possible mechanistic pathways have been investigated by deuterium labelling methods. Benzobicyclo[3.2.1] derivatives arise via a 2-carbonium ion while a 3-carbonium ion leads to benzobicyclo[2.2.2)dien-2-one derivatives. The solvolyses of certain toluene-p-sulphonates have been used to check mechanistic predictions. The position of protonation and the extent of the rearrangement can be controlled by the use of alkyl substituents. Thus 2,6-dimethyl-l-methoxytetrafluorobenzobarrelene affords only derivatives of benzobicyclo[3.2.1]- octadiene while 3,5-dimethyl-l-methoxy-tetrafluorobenzobarrelene gives products derived by rearrangement to the benzobicyclo[2.2.2] system

A Mild and Efficient Flow Procedure for the Transfer Hydrogenation of Ketones and Aldehydes using Hydrous Zirconia

A flow chemistry Meerwein–Ponndorf–Verley (MPV) reduction procedure using partially hydrated zirconium oxide <i>via</i> a machine-assisted approach is reported. The heterogeneous reductive system could be applied to a wide range of functionalized substrates, allowing clean and fast delivery of the alcohol products within a few minutes (6–75 min). In three examples the system was scaled to deliver 50 mmol of product

A Novel Internet-Based Reaction Monitoring, Control and Autonomous Self-Optimization Platform for Chemical Synthesis

We have developed a modular software system that enables researchers to monitor and control chemical reactions via the Internet, using any device from any location in the world. It facilitates the automation of synthetic procedures and is able to autonomously self-optimize reaction parameters to find the best conditions meeting customizable, multicomponent optimization functions. In this report, we demonstrate its utility as applied to reaction automation to maximize the output from a fixed volume of catalyst. We also showcase its ability to optimize a three-dimensional heterogeneous catalytic reaction and a five-dimensional Appel reaction against various target functions

Continuous Multiple Liquid–Liquid Separation: Diazotization of Amino Acids in Flow

A second-generation laboratory-scale, modular liquid–liquid separation device based on computer-controlled high-pressure pumps and a high-resolution digital camera has been invented. The diazotization of amino acids to produce valuable chiral hydroxyacids is demonstrated in flow for the first time. The use of a triple-separator system in conjuction with the developed diazotization process allows the safe and efficient production and automated isolation of multigram quantities of valuable chiral hydroxyacids

Real-Time Spectroscopic Analysis Enabling Quantitative and Safe Consumption of Fluoroform during Nucleophilic Trifluoromethylation in Flow

The productive use of toxic waste materials derived from industrial processes is one of the main goals of modern chemical research to increase sustainability of the large-scale production. Here we devise a simple and robust strategy for the utilization of trifluoromethane, obtained in large quantities from polytetrafluoroethylene manufacture, and the conversion of this greenhouse gas into valuable fluorinated compounds. The generation of the trifluoromethyl carbanion and its direct and complete consumption through trapping with a number of electrophiles were achieved by a fully contained flow reactor setup. The adoption of modern in-line analytical tools, such as portable Fourier transform infrared and nuclear magnetic resonance devices, allowed the accurate reagent dosing with considerable benefits in terms of controlling the environmental impact during this continuous process. The advantages of the method, with respect to the batch procedure, will be discussed and demonstrated experimentally

Rotamers or Diastereomers? An Overlooked NMR Solution

The existence of rotamers in a solution of analyte complicates ¹H NMR analysis, especially when the presence of diastereomers is also possible. Organic chemists have often responded to this problem by conducting variable-temperature (VT) NMR experiments, changing NMR solvents, or adding complexing agents. Here, with specific examples, we illustrate the use of simple yet widely overlooked chemical-exchange NMR experiments which allow the nonintrusive rapid distinguishment of rapidly equilibrating small molecules such as rotamers from nonequilibrating diastereomers

Continuous Multiple Liquid–Liquid Separation: Diazotization of Amino Acids in Flow

A second-generation laboratory-scale, modular liquid–liquid separation device based on computer-controlled high-pressure pumps and a high-resolution digital camera has been invented. The diazotization of amino acids to produce valuable chiral hydroxyacids is demonstrated in flow for the first time. The use of a triple-separator system in conjuction with the developed diazotization process allows the safe and efficient production and automated isolation of multigram quantities of valuable chiral hydroxyacids

Mild and Selective Heterogeneous Catalytic Hydration of Nitriles to Amides by Flowing through Manganese Dioxide

A sustainable flow chemistry process for the hydration of nitriles, whereby an aqueous solution of the nitrile is passed through a column containing commercially available amorphous manganese dioxide, has been developed. The product is obtained simply by concentration of the output stream without any other workup steps. The protocol described is rapid, robust, reliable, and scalable, and it has been applied to a broad range of substrates, showing a high level of chemical tolerance

Rapid development of bromodomain probes using flow synthesis methods and frontal affinity chromatography

<p>This poster illustrates aspects of a project involving the development of new probes for bromodomain 9 protein.</p> <p>Flow chemistry technologies and remote monitoring techniques were used for the synthesis, and Frontal Affinity Chromatography assays were used for analysis of the products.</p

Sustainable Flow Oppenauer Oxidation of Secondary Benzylic Alcohols with a Heterogeneous Zirconia Catalyst

A flow chemistry process for the Oppenauer oxidation of benzylic secondary alcohols using partially hydrated zirconium oxide and a simple carbonyl containing oxidant such as acetone, cyclohexanone, and neopentanal is reported. The heterogeneous oxidative system could be applied to a wide range of functionalized alcohol substrates, allowing clean and fast delivery of ketone products within a few minutes between 40 and 100 °C