Link to the SI via primary direct methods

The possible approaches to realising a link to the SI system and the status of primary direct methods in the traceability chain of chemical measurements are discussed. Some results obtained with the new coulometric standard system are presented.     

Component reconstruction in the primary space of spectra and concentrations. Alternating regression and related direct methods

A set of methods that extract the spectral components in a chromatographic run is considered. The methods do not need libraries of previously known spectra or retention times. The methods have been developed for two-dimensional spectra but they can also be used for chromatographic analyses with a single-channel detector. The methods are direct; they do not use principal components as the starting point. Alternating regression (AR) remains in the primary space of spectra and concentrations during the calculations. Random numbers are used as the starting spectra. Regression is used to solve first for the concentrations, then for the spectra. The method uses two kinds of constraints: all spectra and concentrations are forced to be positive; and all concentration profiles are forced to a unimodal shape with a single local maximum. It is assumed that all observations are a linear sum of components. Compact alternating regression (CAR) is a new variant of the basic AR. The idea is to replace multiplication of a large matrix by two multiplications of smaller matrices. This typically speeds up the iterations by a factor of ten. AR and CAR have been successfully used with combined techniques such as gas chromatography—mass spectrometry and liquid chromatography with UV—visible detection. The reliability of the solution is checked by repeatedly injecting noise and performing the analysis several times. This produces estimates of confidence intervals. AR and CAR have recently been extended to handle single-dimensional signals. Examples are single-channel detectors such as the flame ionization detector in gas or liquid chromatography with a fixed-wavelength UV detector. A batch of samples is used as the observation matrix. As a result, one obtains both the concentrations and the elution shapes of individual chromatographic peaks.     

Allocolchicinoid synthesis via direct arylation

[reaction: see text] A formal enantioselective synthesis of allocolchicine and a synthesis of a C-ring analogue have been achieved by employing an intramolecular direct arylation of an aryl chloride to form the biaryl carbon-carbon bond and the seven-membered ring.     

A traceability protocol to the SI by gravimetric analysis

 An example is presented of a traceability protocol for the measurement of a single-element strontium reference material solution, executed by a "primary" method of measurement for certification. The method of measurement is briefly described together with the measurement equation and the associated calculations for the estimation of uncertainties. This is followed by a discussion and estimate of each component of uncertainty associated with the measurement, together with a final estimate of uncertainty. The final estimate of uncertainty compares well with observed uncertainties for two previous laboratory measurements of the reference material. Received: 21 February 1998 · Accepted: 17 August 1998     

A facile route to isoflavone quinones via the direct cross-coupling of chromones and quinones

A straightforward and efficient method for the palladium-catalyzed direct cross-coupling of chromones with various quinones has been developed to rapidly construct isoflavone quinone structural motifs.     

Efficient route to 2-deoxy beta-O-aryl-d-glycosides via direct displacement of glycosyl iodides

[reaction: see text]. The conversion of glycals to 2-deoxy glycosyl acetates followed by reaction with trimethylsilyl iodide affords the corresponding glycosyl iodides, which readily undergo substitution with aryl alkoxy anions to provide 2-deoxy-beta-O-aryl glycosides. Direct displacement of the anomeric iodide alleviates the need to introduce temporary C-2 stereodirecting groups that require subsequent removal. The only observable byproducts from the glycosylations result from elimination of HI giving the starting glycals, which can be recycled through the reaction sequence.     

Glycopeptide ligation via direct aminolysis of selenoester

In this work, the selenoester of unprotected glycopeptide was readily prepared, and the direct aminolysis of glycopeptide selenoester was successfully applied to synthesize MUC1 mucin sequence.     

Thiophenoanthracene-based conjugated polymers via direct arylation polycondensation

3,4-Appended thiophene monomers furnish unique optoelectronic properties due to electronic and steric effects on the donor unit. Here, we have demonstrated a new polymer synthesis by direct arylation polycondensation of 9,10-dihydro-9,10-[3,4]thiophenoanthracene, a thiophene-based monomer. Chloride-promoted direct arylation polycondensation of 9,10-dihydro-9,10-[3,4]thiophenoanthracene with dibromo monomers with acetate in N,N-dimethylacetamide gave conjugated alternating copolymers. The obtained polymer had a molecular weight of 38,000 and exhibited high film-forming ability. The optical and electrochemical properties of the polymers were also discussed.     

Tin-free intermolecular addition of primary alkyls to imines via the dimethylzinc-air radical process

[reaction: see text] A dimethylzinc-air initiator was applied to the generation of primary alkyl radicals from alkyl iodides. The addition of the generated primary alkyl radicals to N-tosylimines was accelerated by the action of boron trifluoride-diethyl etherate and copper(II) triflate to give the corresponding adducts in good yields after 2-3 h. Air oxygen was essential for the reaction to proceed, showing involvement of a radical process in the reaction.     

Basic equations and uncertainties in isotope-dilution mass spectrometry for traceability to SI of values obtained by this primary method

A current interest in chemistry concerns traceability of analytical measurements to the International System of Units (SI) and the estimation of their uncertainties in accordance with principles of metrology, that is, measurement science. “Primary methods of measurement” achieve traceability to SI directly without intermediate reference standards or materials and without significant empirical correction factors. Isotope-dilution mass spectrometry should be regarded as such a method. It has the potential of smallest presently achievable uncertainties for analytical measurements directly or for the certification of reference materials including those with abnormal isotopic composition. A simple explanation of the method including its basic equations is given. Full uncertainty estimation is emphasized in terms of these equations. The wider use of concepts of metrology in chemistry is discussed.     

On the existence of primary methods of measurement

 There is much discussion in chemical metrology about the definition of primary methods of measurement, just as a couple of years ago there was debate about its predecessors, absolute methods and definitive methods. It is argued in this paper that the designation of certain methods as being primary only makes sense if there is an outstanding property identified that is common to all primary methods, and not present for all non-primary methods. The aim to identify primary methods should not blur our notion that it is the good practice of analytical chemistry that produces good results, not a particular method of analysis.     

TPAP-catalyzed direct oxidation of primary alcohols to carboxylic acids through stabilized aldehyde hydrates

We present a simple, mild, and highly effective method for the direct conversion of primary alcohols to carboxylic acids. TPAP serves as the catalyst, and NMO·H(2)O plays a dual role, acting as the co-oxidant and as a reagent for aldehyde hydrate stabilization. This previously unknown stabilizing effect of geminal diols by N-oxides is the key for the efficiency of the overall transformation.     

Combining fixed- and moving-grid methods to study direct dissociation processes involving nonadiabatic transitions

We present a novel quantum-dynamics approach suitable for computing direct dissociation processes, including electronic transitions. This approach combines quantum trajectories in the Lagrangian reference frame with standard fixed-grid wave packets in order to overcome the limitations and difficulties of both techniques. As a model application, we consider the ultrafast photodissociation of H2 excited by a femtosecond extreme UV laser pulse.     

Mild and direct conversion of quinoline N-oxides to 2-amidoquinolines with primary amides

[reaction: see text] A simple, one-pot procedure is described for the direct conversion of quinoline N-oxides to alpha-amidoquinolines with primary amides. This methodology is complimentary to the Abramovich reaction, which is limited to the introduction of secondary amides via imidoyl chlorides. Although reaction conditions are quite similar, omission of the base is key for successful reaction with primary amides, which were found not to proceed through the intermediacy of an imidoyl chloride but rather through an acyl isocyanate.     

Heterocycle synthesis via direct C-H/N-H coupling

A method for five- and six-membered heterocycle formation by palladium-catalyzed C-H/N-H coupling is presented. The method employs a picolinamide directing group, PhI(OAc)(2) oxidant, and toluene solvent at 80-120 °C. Cyclization is effective for sp(2) as well as aliphatic and benzylic sp(3) C-H bonds.     

Synthesis of new eburnamine-type alkaloid via direct hydroalkoxylation

This study concerns the preparation of a new eburnamine-type alkaloid, methyl (3α,14β,15β,16α)-17,18-didehydro-14,15-dihydroeburnamine-15-methoxy-14-carboxylate (VIII). This alkaloid was prepared from (+)-17,18-dehydroapovincamine (V) using Lewis acid and/or ion exchange resin as catalyst. The hydroalkoxylation reaction of V with methanol was investigated in terms of catalyst, solvent, temperature, and time of reaction. A one-pot method for synthetising this alkaloid was established. The optimal conditions for the reaction are discussed.     

Nucleic acid X-ray crystallography via direct selenium derivatization

X-ray crystallography has proven to be an essential tool for structural studies of bio-macromolecules at the atomic level. There are two major bottle-neck problems in the macromolecular crystal structure determination: phasing and crystallization. Although the selenium derivatization is routinely used for solving novel protein structures through the MAD phasing technique, the phase problem is still a critical issue in nucleic acid crystallography. The background and current progress of using direct selenium-derivatization of nucleic acids (SeNA) to solve the phase problem and to facilitate nucleic acid crystallization for X-ray crystallography are summarized in this tutorial review.     

Synthesis of dragmacidin D via direct C-H couplings

Dragmacidin D, an emerging biologically active marine natural product, has attracted attention as a lead compound for treating Parkinson's and Alzheimer's diseases. Prominent structural features of this compound are the two indole-pyrazinone bonds and the presence of a polar aminoimidazole unit. We have established a concise total synthesis of dragmacidin D using direct C-H coupling reactions. Methodological developments include (i) Pd-catalyzed thiophene-indole C-H/C-I coupling, (ii) Pd-catalyzed indole-pyrazine N-oxide C-H/C-H coupling, and (iii) acid-catalyzed indole-pyrazinone C-H/C-H coupling. These regioselective catalytic C-H couplings enabled us to rapidly assemble simple building blocks to construct the core structure of dragmacidin D in a step-economical fashion.