Table of Contents

Synthesize esters and amides from 2,2,2-trihalo ethyl esters in one pot. Normally, amidation of carboxylic acids requires some sort of activation. Phosphines will reduce trihaloethylesters and activate carboxylic acids to promote condensations with amines or alcohols—combining deprotection and activation in one step. J. J. Hans, R. W. Driver, and S. D. Burke* report that when tribromoethyl esters, amine hydro chloride, and an equivalent amount of triethylamine are reacted at –55 °C with 1.2 equiv of (Me₂N)₃P, the corresponding secondary or tertiary amides are formed in good yields. Similarly, esters of primary and secondary alcohols have been prepared.

The authors found that tribromoethyl esters are better than trichloroethyl esters for this reaction. The method conveniently bypasses the carboxylic acid form of the substrate and provides a one-step conversion to product. (J. Org. Chem. 2000, 65, 2114–2121; RM)

Silica gel can now be easily functionalized with surface carboxyl groups via silane coupling agents. K. Yamaguchi and co-workers describe a novel approach based on a series of alkene-modified nitrobenzyl esters of carboxylic acids, which they reacted with trimethoxysilane to form the coupling agents. The silica gel surface was treated with this agent, followed by photo-irradiation to cleave the benzyl groups and generate the free carboxyls.

The authors found that in several cases, the carboxyl groups could be generated almost quantitatively after irradiation for 3 h. They suggest using this technique to form patterned functionalized monolayers. (Chem. Lett. 2000, 3, 228–229; WJP)

A new family of solid oxides exhibits fast oxide–ion conductivity. Main oxide–ion conductors typically belong to four distinct structural groups including the fluorite type (shown).

However, the new family reported by P. Lacorre and co- workers doesn’t adopt any of these traditional types. Its parent compound, La₂Mo₂O₉ (1), is a good ionic conductor above 400 °C. The authors found that when 1 is heated, it experiences a phase transition at 580 °C accompanied by an abrupt increase in conductivity of ~2 orders of magnitude. Partial substitutions on the cationic lattice do not significantly alter the conductivity despite changes in cell parameter. The high-temperature structure of 1 is similar to that of β-SnWO₄, so that 1 can be viewed as β-SnWO₄, where tin is replaced by lanthanum (with identical size but without a lone pair) and tungsten by its iso-element molybdenum. Stereochemical considerations suggest a way to design new oxide–ion conductors starting from a mixed oxide of a lone-pair element, then substituting the lone-pair element with oxidation state n⁺ by a non-lone-pair element of the same size and oxidation state (n+1)⁺ (Nature 2000, 404, 856–858).

In an accompanying article, J. B. Goodenough summarizes the design of oxide–ion conductors and stresses the need for oxide ceramics with higher conductivity at lower temperatures. Meeting these goals would lower the cost of fabrication and operation, as well as extend the life of devices. (Nature 2000, 404, 821–823; DLN)

Polyaniline-sheathed emitters replace gold for nanoelectrospray ionization mass spectrometry. By manually applying a polyaniline (PANI) overcoat to tapered borosilicate capillaries, T. D. Wood and co-workers fashioned simple, reusable, robust, and less costly alternatives to gold-coated nanospray emitters—the gold standard for nanoelectrospray ionization (nano-ESI). They used the synthetic metal PANI for establishing electrical contact within the ESI source, realizing several advantages over gold-coated emitters, including lower incidence of electrical arcing, greater tip longevity, and optical transparency. During analysis of commercial (ternary polymer mixtures) and biological (equine cytochrome c) samples, PANI-coated emitters performed as well or better than their metallized counterparts with reduced labor, cost, and time. The authors point out that the protracted lifetimes of their emitters and their stability to electrical discharge make them useful for applications in capillary electrophoresis technologies. (J. Am. Soc. Mass Spectrom. 2000, 11, 659–663; GAB)

Design of biologically active polypeptides requires careful control of macromolecular architecture. Synthesis of such molecules with b-hairpin turns can be accomplished by using organic templates that direct the synthesis in the desired direction. J. A. Robinson discusses a range of such templates that stabilize specific geometries during the synthesis of molecules for drug discovery and other protein applications. The figure illustrates some aromatic templates used in peptidomimetic design.

These templates are alternatives to generating combinatorial libraries based on disulfide-bridged peptides, which are relatively flexible and sometimes fail to restrict the syntheses to the desired geometries. Combining such specific geometries with the rapidly maturing methods in solid-phase and parallel synthesis gives the potential for even more efficient “combinatorial biomimetic chemistry”. (Synlett 2000, 429–441; DAS)

Confocal microscopy can be used to examine the interior structure of materials, much as a CT scan is used to image living tissues. M. Srinivasarao and co-authors used this nondestructive technique to study the diffusion and absorption of a fluorescent dye into a trilobal fiber extruded from nylon-66. The confocal microscope, using laser light to produce images, was operated in a time-dependent mode and in a planar-section mode. The planar-section mode produced a 3-D reconstruction of the individual fibers with ~200-nm resolution. In time-dependent mode, the rate of dye absorption with time was determined. The authors observed that spatial distribution of dye molecules in a fiber can cause differences in the perceived color, even at the same dye concentrations. (Macromolecules 2000, 33, 4478–4485; DAS)

Raman spectroscopy enjoys a resurgence. J. B. Miller offers a refreshing perspective on the use of Raman spectro scopy as a high-throughput tool in fields such as the material sciences and biomedical analysis. An old standby in the spectroscopist’s laboratory, Raman spectroscopy is experiencing a renaissance that extends its use to monitor on-line polymerization and curing reactions, as well as being useful in forensics, pharmaceuticals, and the microelectronics and textile industries. Recently, Raman spectroscopy was used to analyze res veratrol in red wine and grape juice (in the study of the cor- relation between red wine consumption and low incidence of heart disease), and to detect domoic acid (a neurotoxic amino acid implicated in outbreaks of amnesic shellfish poisoning). (Today’s Chemist at Work 2000, 9 [6], 19–20; GAB)

A family of taste receptor proteins is specifically expressed in human taste receptor cells. Unlike taste receptors for salt that detect Na⁺ and receptors for acid that detect H⁺, the receptors that identify sweet (sugar), bitter (6-n-propyl-2-thiouracil), and umami (glutamate) tastes are sensitive to many other substances. Taste receptor cells in our taste buds contain proteins that are linked to guanine nucleotide binding (G-proteins). Shown are examples of extremely bitter substances with widely divergent chemical structures, which lead one to suspect the presence of a family of bitter-taste receptors in the mouth.

In this same issue, S. Firestein discusses why it has taken so long to discover the new family of G-proteins and points out that the taste buds take up only a small area of the tongue. The taste buds are difficult to isolate and don’t provide much material with which to work. (Nature 2000, 404, 552–553; DLN)

Benzoic acid derivatives can be para-alkylated using electrophiles. The selective ortho- or para-alkylation of unsubstituted benzoic acids generally is not a common event. However, S. Sinha, B. Mandal, and S. Chandrasekavan have found that direct para-alkylation of 3-methoxy- and 3,5-dimethoxybenzoic acids occurs using n-BuLi–KO-t-Bu without ortho-alkylation.

This unexpected observation led to the synthetic procedure for alkylation of 3,5-dimethoxybenzoic acid with a variety of electrophiles (alkyl halides, benzophenone, activated aldehydes, chloroethyl formate) in moderate-to-good yields. The trick is to prepare the potassium salt of the acid with 4 equiv of KO-t-Bu in THF at –78 °C, and then add 4 equiv of n-BuLi, followed by an electrophile. They expect that direct para-alkylation of unprotected 3-methoxybenzoic acids should be useful in natural product synthesis. (Tetrahedron Lett. 2000, 41, 3157–3160; RM)

Organotin monomers build antibacterial properties into polymers. S. S. Al-Diab and co-workers have produced two different tin monomers, each bearing C=C bonds. These were copolymerized with styrene under normal reaction conditions to form copolymers 1 and 2 that exhibited antibacterial properties, especially against Gram-positive organisms such as Staphylococcus aureus.

The copolymers were less effective against Gram-negative organisms. The authors did not comment on the persistence of this antibacterial property, but because the antimicrobial tin is an integral part of the polymer matrix (in contrast to a surface treatment), one could expect this effect to be permanent. (J. Appl. Polym. Sci. 2000, 77, 740–745; DAS)

Friedel–Crafts acylations are promoted by ytterbium catalysts in a fluorous biphase reaction. A.G.M. Barrett and co-workers found that Yb(III) tris(perfluoroalkanesulfonyl)-methides were effective catalysts for the acylation of aromatics with acid anhydrides. A typical ytterbium methide salt is shown.

They carried out the acylation reactions in benzotrifluoride, which is described as a hybrid between classical organic solvents and perfluorinated (fluorous) solvents. Extraction of the reaction products with perfluoromethyldecalin removed the catalyst, allowing recycling for additional use. A range of isomers should be obtainable from acylation of substrates such as toluene and anisole, although these were not discussed. One might expect the major products to come from 1,4-substitution, with byproducts from 1,2-substitution, based on similar chemistry (patented by Celanese in the 1980s as part of its commercial acetaminophen process) for the acylation of phenol in HF solvent. (Synlett 2000, 847–849; DAS)