Organic Reaction Mixtures Research Articles

Quantitative Determination of Water in Organic Liquids by Ambient Mass Spectrometry

AbstractThis study uses a rapid tandem mass‐spectrometry method to determine water content in complex organic solutions. Emphasis is placed on trace‐water analysis by a fast and accurate alternative to the Karl–Fischer method. In this new method, water is captured by a charge‐labeled molecular probe. Water binds strongly with high specificity to the strongly electrophilic aldehyde site in a charge‐labelled molecule (N‐methylpyridinium); competitive binding by other analytes is effectively discriminated against in the mass‐measurement step. Quantitative determinations are made over a wide concentration range, 0.001 % (10 ppm) to 99 %, with better than 10 % relative standard deviation, along with short (1 min) analysis times using small sample volumes (several μL). Applications include water measurement in simple organic solvents, for example, deuterated solvents, as well as in complex mixtures, for example, organic reaction mixtures. Additionally, this method allows for water monitoring in levitated droplets. Mechanistic investigations into the impact of water on important chemical processes in organic synthesis and environmental science are reported.

Quantitative Determination of Water in Organic Liquids by Ambient Mass Spectrometry.

This study uses a rapid tandem mass-spectrometry method to determine water content in complex organic solutions. Emphasis is placed on trace-water analysis by a fast and accurate alternative to the Karl-Fischer method. In this new method, water is captured by a charge-labeled molecular probe. Water binds strongly with high specificity to the strongly electrophilic aldehyde site in a charge-labelled molecule (N-methylpyridinium); competitive binding by other analytes is effectively discriminated against in the mass-measurement step. Quantitative determinations are made over a wide concentration range, 0.001 % (10 ppm) to 99 %, with better than 10 % relative standard deviation, along with short (1 min) analysis times using small sample volumes (several μL). Applications include water measurement in simple organic solvents, for example, deuterated solvents, as well as in complex mixtures, for example, organic reaction mixtures. Additionally, this method allows for water monitoring in levitated droplets. Mechanistic investigations into the impact of water on important chemical processes in organic synthesis and environmental science are reported.

Optimised Protocol for Drying Aqueous Enzyme Solutions in Organic Solvents – Comparison of Free and Immobilised Candida antarctica Lipase B

AbstractHere, we propose an optimised protocol for controlling the initial water activity (aw) in organic reaction mixtures with soluble lipase to ensure reproducible and consistent enzyme activity measurements. Pre‐equilibration above saturated salt solutions was used to set aw of the reaction media, where aw was tracked with a hygrometer. Consistent stirring of the suspension and volume correction to compensate for solvent evaporation were found to be critical. The protocol was tested on Candida antarctica lipase B (CALB) in soluble and immobilised forms in three organic solvents (acetonitrile, methyl tert‐butyl ether, and hexane) at four different water activities ranging from 0.12 to 0.97. Soluble and immobilised CALB had similar aw‐profiles and showed the highest enzyme activity in hexane. The optimised protocol expands the possibility to study enzyme kinetics from immobilised enzymes to soluble enzymes.

Electrospun Poly(Styrene-Co-Vinylbenzyl Chloride-Co-Acrylonitrile) Nanofiber Mat as an Anion Exchange Membrane for Fuel Cell Applications.

A nanofiber mat of styrene−co−vinylbenzyl chloride−co−acrylonitrile copolymer as an anion exchange membrane (AEM) was synthesized via the electrospinning of organic reaction mixtures. The synthesized membranes were characterized using FT-IR spectroscopy for structural analysis. The AEM demonstrated a high ionic conductivity mainly due to the phase segregation in the membrane structure, as analyzed by transmission electron microscopy (TEM). The membrane properties such as water uptake, swelling ratio, and ion exchange capacity, as well as ionic conductivity, varied with the chemical composition. With the molar ratio of styrene, vinylbenzyl chloride, and acrylonitrile at 3:5:2, the highest ionic conductivity of 0.214 S cm−1 at 80 °C was observed. Additionally, the AEM retained 94% of original conductivity after 72 h of soaking in 1 M KOH solution.

Microwave-Assisted Superheating and/or Microwave-Specific Superboiling (Nucleation-Limited Boiling) of Liquids Occurs under Certain Conditions but is Mitigated by Stirring.

Temporary superheating and sustained nucleation-limited “superboiling” of unstirred liquids above the normal atmospheric boiling point have been documented during microwave heating. These phenomena are reliably observed under prescribed conditions, although the duration (of superheating) and magnitude (of superheating and superboiling) vary according to system parameters such as volume of the liquid and the size and shape of the vessel. Both phenomena are mitigated by rapid stirring with an appropriate stir bar and/or with the addition of boiling chips, which provide nucleation sites to support the phase-change from liquid to gas. With proper experimental design and especially proper stirring, the measured temperature of typical organic reaction mixtures heated at reflux will be close to the normal boiling point temperature of the solvent, whether heated using microwave radiation or conventional convective heat transfer. These observations are important to take into consideration when comparing reaction rates under conventional and microwave heating.

Removal of Heavy Metals from Organic Reaction Mixtures: Preparation and Application of Functionalized Resins

Using a toolbox, sulfur and amine ligands are attached to a variety of hydrophobic and hydrophilic resins, and the combinations were tested for the removal of heavy metals from a number of products, prepared by metal-catalyzed reactions. As a result, cheap combinations of silica resins and simple polyamines proved to be among the most effective metal scavengers particularly in apolar solvents such as cyclohexane. Expensive cyclic polyamines are not suitable, owing to kinetic retardation of complexation. Functionalized PEG-based polymers, originally designed for solid phase synthesis, show promising performance as metal scavengers. The results are discussed and compared to alternative approaches for purification such as salt-formation and chemical downstream transformation.

“Soft” or “Hard” Ionisation? Investigation of Metastable Gas Temperature Effect on Direct Analysis in Real-Time Analysis of Voriconazole

The performance of the direct analysis in real-time (DART) technique was evaluated across a range of metastable gas temperatures for a pharmaceutical compound, Voriconazole, in order to investigate the effect of metastable gas temperature on molecular ion intensity and fragmentation. The DART source has been used to analyse a range of analytes and from a range of matrices including drugs in solid tablet form and preparations, active ingredients in ointment, naturally occurring plant alkaloids, flavours and fragrances, from thin layer chromatography (TLC) plates, melting point tubes and biological matrices including hair, urine and blood. The advantages of this technique include rapid analysis time (as little as 5 s), a reduction in sample preparation requirements, elimination of mobile phase requirement and analysis of samples not typically amenable to atmospheric pressure ionisation (API) techniques. This technology has therefore been proposed as an everyday tool for identification of components in crude organic reaction mixtures.

Atomic-absorption spectrometric determination of catalytic components (Pd, Ti, and Cu) in mixtures based on phenol

Procedures for the determination of palladium, titanium, and copper in organic reaction mixtures based on phenol were developed with the use of atomic absorption spectrometry and various sample preparation techniques: quantitative back extraction of the metals with a 2 M HCl solution; autoclave digestion in an acid mixture of HClO4, HF, and HNO3; and decomposition in a muffle furnace. The accuracy of analysis was demonstrated by a comparison between the results of the atomic-absorption spectrometric determination of the elements obtained with the use of all of the sample preparation techniques proposed and the standard addition method. The relative standard deviation in the determination of palladium, copper, and titanium was 7–10%.

Direct analysis of highly oxidised organic aerosol constituents by on-line ion trap mass spectrometry in the negative-ion mode.

On-line ion trap mass spectrometry (ITMS) enables the characterisation of constituents of biogenic secondary organic aerosols in complex organic reaction mixtures. This real-time analysis is achieved by directly introducing the airborne particles into the ion source of the mass spectrometer. Negative-ion chemical ionisation at atmospheric pressure (APCI(-)) was used as the ionisation method of choice. The aerosols were generated from the gas-phase ozonolysis of two C10H16-terpenes (alpha-pinene and limonene), and investigated by performing on-line APCI(-)-ITMS(n). Highly oxidised compounds were tentatively identified as important particle-phase products. Based on recent investigations of low-energy collision-induced dissociation pathways of a wide range of deprotonated multifunctional carboxylic acid species derived from monoterpene precursors (Warscheid B, Hoffmann T. Rapid Commun. Mass Spectrom. 2001; 15: 2259), the formation of structurally different C10H16O5 and C10H16O6 species, such as acidic esters from alpha-pinene and aldo-hydroxycarboxylic acids from limonene, is proposed.

Fluorous methods for synthesis and separation of organic molecules

Abstract Fluorous molecules partition out of an organic phase and into a fluorous (highly fluorinated) phase in a liquid-liquid extraction. New fluorous techniques allow simple yet substantive separations of organic reaction mixtures based on the presence or absence of a fluorous tag. Fluorous-tagged molecules can also be separated from nontagged molecules by solid phase extraction over fluorous reverse-phase silica gel. This technique is ideal for solution-phase parallel synthesis because it allows simple yet substantive separations of organic reaction mixtures.

Removal of Palladium from Organic Reaction Mixtures by Trimercaptotriazine

In an effort to remove residual palladium from a drug candidate prepared by palladium-catalyzed indolization, many treatments were examined. The most effective treatment was to precipitate palladium from solution using 2,4,6-trimercapto-s-triazine (TMT), which reduced palladium levels from 600−650 ppm to 20−60 ppm in an isolated indole intermediate. Subsequent crystallizations routinely afforded active pharmaceutical ingredient with <1 ppm of palladium. TMT treatment should prove useful to reduce the concentration of residual palladium in other reactions.

Fluorous synthesis: a fluorous-phase strategy for improving separation efficiency in organic synthesis.

Recovery and purification difficulties can limit the yield and utility of otherwise successful organic synthesis strategies. A "fluorous synthesis" approach is outlined in which organic molecules are rendered soluble in fluorocarbon solvents by attachment of a suitable fluorocarbon group. Fluorocarbon solvents are usually immiscible in organic solutions, and fluorous molecules partition out of an organic phase and into a fluorous phase in a standard liquid-liquid extraction. Simple yet substantive separations of organic reaction mixtures are achieved without resorting to chromatography. Because fluorous synthesis combines in many respects the favorable purification features of solid-phase synthesis with the favorable reaction, identification, and analysis features of traditional organic synthesis, it should prove valuable in the automated synthesis of libraries of individual pure organic compounds.

Application of Immobilized α-Chymotrypsin to Peptide Synthesis in Frozen Aqueous Systems

In order to combine the high potential of frozen state peptide synthesis and the advantages of the application of immobilized proteases, the capability of carrier-bound α-chymotrypsin (CT, EC 3.4.21.1) to form peptide bonds in frozen aqueous reaction mixtures was investigated. The properties of the support materials strongly influenced the peptide yields. CT bound to rather hydrophobic supports catalysed peptide synthesis as effectively as the soluble enzyme. The immobilized enzyme preparations could be successfully re-used at least 15 times. Peptide synthesis catalysed by immobilized chymotrypsin was also studied in low water organic reaction mixtures at sub-zero temperatures. The advantages and limitations of the different approaches are discussed.

Use of microwave heating to speed organic reactions continues to grow

Microwave heating of laboratoryscale organic reaction mixtures is moving into both the undergraduate laboratory and industrial production. In the chemistry lab, heating reaction mixtures for a few minutes in a conventional oven can sometimes replace long reflux times that take up so much laboratory time. And some chemical producers are developing processes that take advantage of the clean heating and the instant on-off features of ovens. Despite these promising applications, however, the question lingers whether microwaves excel in organic reactions simply by heating faster and hotter, or whether there is some unique microwave effect. Microwave radiation is the range of the electromagnetic spectrum between radiofrequency on the low end and infrared on the high-frequency end. The arbitrary cutoffs are 300 MHz to 30 gigahertz, or 1-meter to 1-cm wavelength. The world's telecommunications agencies have commandeered most of the spectrum for radar and telecommunications. Authori...

The recycling of organosilyl protecting species used in organic synthesis and the water binding ability of the silanol 1BuMe 2SiOH

The silanols formed on the cleavage of organosilyl protecting groups from organic compounds can be efficiently reconverted into the chlorosilanes used in the initial silylation reaction by treatment with SOCl 2. The silanol tBuMe 2SiOH is very readily removed from organic reaction mixtures as its remarkably volatile hemihydrate [ tBuMe 2SiOH] 2·H 2O.

Rates Of Enzymic Reactions In Predominantly Organic, Low Water Systems

This article makes a quantitative assessment of the activity of enzymes in predominantly organic reaction mixtures of very low water content (and thermodynamic water activity significantly less than 1). This is done by attempting to relate reaction rates to those in systems of higher water content, although several factors make fair comparison difficult. However, it seems that rates with lipases in low water systems can sometimes be at least as high as when the same amount of enzyme catalyses the same reaction in a more traditional system. Rates are usually higher when the catalyst is dispersed on a support, rather than with simple dried particles of enzymes. Rates per unit weight of catalyst are rather similar, even when the amount of active enzyme varies widely, suggesting that physical factors may be limiting. Little data is available for enzymes other than lipases.

Infrared identification of paper chromatographed compounds. II. Procedures for some acidic compounds

The isolation and identification of individual organic compounds, such as drugs and their metabolites, in biological systems is usually complicated by the presence of small quantities of the desired material and overwhelming amounts of many extraneous substances. Yermentation beers and complex organic reaction mixtures may present a similar problem. Paper chromatography has proved to be an excellent tool for the separation of minute amounts of material in crude mixtures,’ and techniques for the resolution of a wide variety of mixtures containing difficultly separable, similar compounds have been developed. Biological samples, in particular, have been very effectively handled by paper chromatographic methods. Unfortunately, the separatory powers of paper chromatography have not been matched by the ability to positively identify or characterize the compounds isolated. Infrared spectroscopy, however, affords the most generally useful and exact, identification that any single measurement can provide. Recently the separation of compounds by paper chromatography, followed by infrared characterization of the isolated material has been studied and found to be a useful procedure.2-4 To date, m&hods involving elution of a chromatographed spot and infrared examination of the eluate have been limited to situations where the compound was reasonably soluble in an acceptable solvent,. It has been found t]hat a great many types of compounds cannot bc