Effect of curing accelerators on thermal imidization of polyamic acids at low temperature

The effect of new additives on the thermal conversion of a range of polyamic acids to polyimides at temperatures lower than 100°C was investigated using infrared spectroscopy. Additives such as m-hydroxybenzoic acid, p-hydroxyphenylacetic acid, and p-hydroxybenzenesulfonic acid were found to be highly effective as curing catalysts or accelerators. The degree of imidization of polyamic acids in the presence of additives increased with an increase in the reaction temperature, and complete imidization was achieved at 140–200°C. The reaction was characterized by a rapid rate that slowed with time. © 1996 John Wiley & Sons, Inc.     

Non-protein amino acids in peptide design

An overview of the use of non-protein amino acids in the design of conformationally well-defined peptides, based on work from the author’s laboratory, is discussed. The crystal structures of several designed oligopeptides illustrate the useα-aminoisobutyric acid (Aib) in the construction of helices, D-amino acids in the design of helix termination segments and^DPro-Xxx segments for nucleating ofβ-hairpin structures.β- andγ-amino acid residues have been used to expand the range of designed polypeptide structures. Dedicated to Professor C N R Rao on his 70th birthday     

Synthesis and biological activity of alkylidene-substituted cephems and penams

The condensation of tert-butyl esters of 3-methyl-7-oxoceph-3-em-4-carboxylic and 6-oxopenicillanic acids with a series of 2-oxoalkylidene(triphenyl)phosphoranes gave tert-butyl esters of new cephalosporin and penicillin analogs with an alkylidene substituent in the β-lactam ring. Most of these products were oxidized by meta-chloroperbenzoic acid to the corresponding sulfones. The cephemes and penams synthesized including the oxidized products displayed high cytotoxicity relative to cancer cells in vitro. Some of the alkylidene-substituted cephems as the free acids, similar to Tazobactam, inhibit the catalytic activity of Enterobacter cloacae penicillinase.     

Technetium-99m labeling of hippuric and p-amino-hippuric acid in the presence of DTPA: Biological and pharmacokinetic evaluation and comparison with99mTc-DTPA

^99mTc-Hipp as a modified^99mTc-DTPA, and^99mTc-PAH as a new renal agent are developed. Each veal of lyophilised kit contain hippuric (Hipp) or p-aminohippuric acid (PAH), diethyltriaminepentaacetic acid as calciumtrisodium salt (CaNa₃DTPA) and stannouschloride (SnCl₂·xH₂O), in molar ratio Hipp/PAH:DTPA=4∶1. They are high radiochemical purity radiopharmaceuticals, with hydrophilic character and low percentage of protein binding. The ITL chromatography and HPLC analyses of these labeled compounds have shown almost identical results as^99mTc-DTPA, but their biological behavior in rats confirm certain differences.^99mTc-Hipp is a renal agent clearing by the glomerular system, with better pharmacokinetical parameters than^99mTc-DTPA:t _1/2(α)=4.1 min,t _1/2(β)=198.6 min,K _cl=1.2·10⁻²min⁻¹ and a twofold value for blood clearance (Cl=2.07 ml/min).^99mTc-PAH is a quite different renal agent, rapidly secreted by kidney as a tubular secretion agent. Its pharmacokinetical parameters:t _1/2(α)=2.5 min,t _1/2(β)=41.7 min andK _cl=5.1·10⁻⁴ min⁻¹ are almost equal to those of^99mTc-MAG₃, but the blood clearance of Cl=5.22 ml/min is even higher than that of IOH clearance.     

Ligand-Enabled Auxiliary-Free meta-C−H Arylation of Phenylacetic Acids

The meta-C−H arylation of free phenylacetic acid was realized using 2-carbomethoxynorbornene (NBE-CO₂Me) as a transient mediator. Both the modified norbornene and the mono-protected 3-amino-2-hydroxypyridine type ligand are crucial for this auxiliary-free meta-C−H arylation reaction. A series of phenylacetic acids, including mandelic acid and phenylglycine, react smoothly with various aryl iodides to provide the meta-arylated products in high yields.     

Umwandlung von 6-Methylen-tricyclo[3.2.1.02,7]oct-3-en-8-onen mit Ameisensäure in kernmethylierte Phenylessigsäuren

In a preceding communication [5] it was shown that 1, 5-dimethyl-6-methylene-tricyclo[3.2.1.0^2,7]oct-3-en-8-one ( 2 ) and related tricyclic ketones are converted by strong acids (CF₃COOH, FSO₃H) into polymethylated tropylium salts with loss of carbon monoxide, e.g. the 1, 2, 4-trimethyltropylium ion 4 from 2 (Scheme 1). Under the influence of neat formic acid at 20°, 2 gives rise to ring-methylated phenylacetic acids, i.e. 2, 4, 5-trimethylphenylacetic acid ( 5 , main product) as well as smaller amounts of 2, 4, 6-and 2, 3, 5-trimethylphenylacetic acids ( 6, 7 resp.; Scheme 2). –On rearrangement of 2 in HCOOD, ca. 2 D-atoms are incorporated (formula d₂-5) into the 2, 4, 5-trimethylphenylacetic acid. The tricyclic 15 , containing 3 methyl groups, gives 2, 3, 5, 6-tetramethylphenylacetic acid ( 11 ; Scheme 4) with formic acid; the isomeric tricyclic 16 , 2, 3, 4, 5-tetramethylphenylacetic acid ( 12 ; Scheme 5). From 1, 2, 4, 5-tetramethyl-6-methylene-tricyclo[3.2.1.0^2,7]oct-3-en-8-one ( 17 ) one obtains pentamethylphenylacetic acid ( 14 ; Scheme 6). Similarly from 18 , a phenylacetic acid derivative, most probably 4-ethyl-2, 5-dimethyl-phenylacetic acid ( 19 ; Scheme 17), has been obtained. –In no case was the formation of α-phenylpropionic acid derivatives observed, not even from the tricyclic 23 containing six methyl groups. From the tricyclic ketone 2 in 70% formic acid a trimethyl-cyclohepta-2, 4, 6-triene-1-carboxyclic acid with partial formula 24 , besides 2, 4, 5-trimethylphenylacetic acid ( 5 ), is formed. 24 remained practically unchanged on standing in neat formic acid and thus does not represent an intermediate product arising by the rearrangement of 2 in that solvent. On standing in methanolic sulfuric acid, tricyclic 2 furnishes the two stereioisomeric methanol-addition products Z- 26 and E- 26 (Scheme 10); these are converted into the phenylacetic acids 5 , 6 and 7 by neat formic acid. The conversion of 2 and related compounds into ring-polymethylated phenylacetic acids, represents a novel and rather complicated reaction. In our opinion the reaction paths represented in Schemes 12 and 18 are responsible for the conversion of 2 into the trimethylphenylacetic acids, compound 40 representing a key intermediate. Analogous reaction paths can be assumed for the other tricyclic ketone transformations. The use of shift reagents in the NMR. spectroscopy and the high-resolution gas-chromatography of the corresponding methyl esters proved particularly important for the analysis of the reaction mixtures. The majority of the polymethylated phenylacetic acids were independently synthesised by means of the Willgerodt-Kindler reaction (chap. 3.2.), whose course is strongly influenced by methyl groups in the ortho-positions of the acetophenone derivatives employed.     

Ligand‐Enabled Auxiliary‐Free meta‐C−H Arylation of Phenylacetic Acids

The meta ‐C−H arylation of free phenylacetic acid was realized using 2‐carbomethoxynorbornene (NBE‐CO₂Me) as a transient mediator. Both the modified norbornene and the mono‐protected 3‐amino‐2‐hydroxypyridine type ligand are crucial for this auxiliary‐free meta ‐C−H arylation reaction. A series of phenylacetic acids, including mandelic acid and phenylglycine, react smoothly with various aryl iodides to provide the meta ‐arylated products in high yields.     

A new spot test for aromatic hydrazides using 2,3,5-triphenyl tetrazolium chloride

Summary A spot test using 2,3,5-triphenyl tetrazolium chloride for the detection of benzoic acid hydrazide, and itsm- andp-nitro derivatives, isonicotinic acid hydrazide, salicylic acid hydrazide and phenylacetic acid hydrazide is described. The method consists of treating 0.1 to 0.2 ml of 0.001 % hydrazide (for benzoic acid hydrazide a 0.0001 %) solution with 0.2 to 0.4 ml of 0.02M sodium hydroxide, 0.2 ml of 1% 2,3,5-triphenyl tetrazolium chloride and 0.2 ml of nitrobenzene oriso-butyl methyl ketone in a micro test tube. A reddish-brown colour in the organic phase confirms the presence of an aromatic hydrazide. The identification limits for benzoic acid hydrazide, itsm- andp-nitro derivatives, isonicotinic acid hydrazide, salicylic acid hydrazide, phenylacetic acid hydrazide respectively are: 0.2, 1.0, 1.0, 3.5, 3.0, 2.0g in 1 ml in nitrobenzene and 0.2, 0.2, 0.1, 3.0, 0.2, 1.5g in 1 ml iniso- butyl methyl ketone. The interference of various substances and anions has been studied.

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Zusammenfassung Eine Tüpfelreaktion mit 2,3,5-Triphenyltetrazoliumchlorid zum Nachweis von Benzoesäurehydrazid und dessenm- undp-Nitroderivaten, von Isonikotinsäurehydrazid, Salicylsäurehydrazid und Phenylessigsäurehydrazid wurde angegeben. 0,1 bis 0,2 ml einer 0,001% igen (bei Benzoesäurehydrazid einer 0,0001% igen) Lösung werden mit 0,2 bis 0,4 ml 0,02-m Natronlauge, 0,2 ml 1%iger Triphenyltetrazoliumchloridlösung und 0,2 ml Nitrobenzol oderi-Butylmethylketon in einem Mikroreagensglas behandelt. Rotbraune Färbung der organischen Phase zeigt die Anwesenheit eines aromatischen Hydrazids an. Die Nachweisgrenzen der angeführten Säurehydrazide in 1 ml Nitrobenzol betragen 0,2, 1,0, 1,0, 3,5, 3,0 bzw 2,0g, in 1 mli-Butylmethylketon 0,2, 0,2, 0,1, 3,0, 0,2 bzw. 1,5g Die störende Wirkung verschiedener Substanzen und Anionen wurde geprüft.

     

Syntheses of (E)- and (Z)-3-styrylchromones

Several (E)- and (Z)-3-styrylchromones were prepared by two different methodologies, the Wittig reaction of chromone-3-carboxaldehyde with benzylic ylides and the Knoevenagel condensation of chromone-3-carboxaldehyde with phenylacetic acids in the presence of potassium tert-butoxide under microwave irradiation. The Knoevenagel reaction followed by a decarboxylation offered an efficient and diastereoselective method for preparing (E)-3-styrylchromones in a shorter reaction time. It was also demonstrated that phenylacetic acid can also be substituted with success by phenylmalonic acid. The stereochemistry of all products was assigned by NMR experiments.     

High-Performance liquid chromatographic separation of enantiomers of unusual amino acids possessing cycloalkane or cycloalkene skeletons on a chiral crown ether containing stationary phase

Summary Direct reversed-phase high-performance liquid chromatographic methods were developed for the separation and identification of the enantiomers of mono- and bicyclic racemic β-amino acids:cis- andtrans-2-aminocyclopentane-1-carboxylic acids,cis- andtrans-2-aminocyclohexane-1-carboxylic acids,cis- andtrans-2-amino-4-cyclohexene-1-carboxylic acids,diendo- anddiexo-3-aminobicyclo[2.2.1]heptane-2-carboxylic acids anddiendo- anddiexo-3-amino-5-bicyclo[2.2.1]heptene-2-carboxylic acids. Enantioseparation was carried out by the application of a chiral stationary phase, Crownpak CR(+). The conditions of separation were optimized by changing the temperature, the flow rate and the pH of the mobile phase. Presented at: Balaton Symposium on High-Performance Separation Methods, Siófok, Hungary, September 3–5, 1997.     

Estimation of hydrogen peroxide formed and residual ascorbate in the copper catalysed oxidation reaction of ascorbate at pH 7

A fluorescent method has been developed for determination of ascorbic acid concentrations. The method involves treatment of the ascorbic acid with Cu(II) and treating the hydrogen peroxide formed with horseradish peroxidase in the presence ofp-hydroxyphenylacetic acid, to form a fluorescentp-hydroxyphenylacetic acid dimer. The reaction is suitable for analysis of concentrations in the range from 50 M to 4 mM ascorbic acid solutions and can be used for analysis of pharmaceutical preparations but is unsuitable for analysis of ascorbate in preparations derived from natural sources. By using a slight modification of the analytical technique it is possible to measure the amount of hydrogen peroxide formed and the residual concentrations of ascorbic acid in solutions treated with varying amounts of copper ion.Abbreviations CySH cysteine - EDTA ethylenediamine tetraacetic acid - GSH reduce glutathione - HPAA hydroxyphenylacetic - HPLC high performance liquid chromatography - HRP horseradish peroxidase - TCA trichloracetic acid     

Syntheses of (<Emphasis Type="Italic">E</Emphasis>)- and (<Emphasis Type="Italic">Z</Emphasis>)-3-styrylchromones

Several (E)- and (Z)-3-styrylchromones were prepared by two different methodologies, the Wittig reaction of chromone-3-carboxaldehyde with benzylic ylides and the Knoevenagel condensation of chromone-3-carboxaldehyde with phenylacetic acids in the presence of potassium tert-butoxide under microwave irradiation. The Knoevenagel reaction followed by a decarboxylation offered an efficient and diastereoselective method for preparing (E)-3-styrylchromones in a shorter reaction time. It was also demonstrated that phenylacetic acid can also be substituted with success by phenylmalonic acid. The stereochemistry of all products was assigned by NMR experiments. Correspondence: Artur M. S. Silva, Chemistry Department, University of Aveiro, 3810-193 Aveiro, Portugal.     

Synthesis of 5,10,15,20-tetra[3-(o- andm-carboranyl)butyl]porphyrins containing the C−B σ-bond

5,10,15,20-Tetra[3-(o- andm-carboranyl)butyl]porphyrins containing carborane groups bonded to alkyl substituents of the porphyrin cycle by the C−B σ-bond were obtained by condensation of 4-(o- andm-carboran-9-yl)pentanals with pyrrole. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 347–349, February, 1998.     

Porous copolymer-based cation exchanger for the off-line preconcentration of aromatic amines from water

Summary A weakly polar porous copolymer and the sulfonic acid cation exchanger based on this copolymer were tested as sorbents for off-line preconcentration of aromatic amines from water. Minicolumns packed with the 1,4-di(methacryloyloxymethyl)naphthalene—divinylbenzene copolymer and the cation exchanger were used for the solid-phase extraction of polar amines. In order to study the sorption properties of these polymeric materials, the recoveries and breakthrough volumes ofp-aminophenol,o, m andp-phenylenediamine, aniline,o andp-anisidine,p-nitroaniline, ando-toluidine were determined.     

Determination of trace levels of pyrethroid metabolites in human urine by capillary gas chromatography-high resolution mass spectrometry with negative chemical ionization

Summary Applications of high-resolution gas chromatography and high-resolution mass spectrometry (GC-MS) for identification and quantitation of trace amounts of pyrethroid metabolites in human urine samples are demonstrated. The method covers the pyrethroid metabolitescis- andtrans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid (cis- andtrans-DCCA),cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DBCA), 4-fluoro-3-phenoxybenzoic acid (FPBA), and 3-phenoxybenzoic acid (3-PBA). After acid-induced hydrolysis of urine samples and exhaustive solvent extraction, a carbodiimide-coupled esterification of the free carboxylic acids with hexafluoroisopropanol (HFIP) is applied. Identification of the derivatives formed is achieved by low-resolution electron-impact mass spectrometry (EIMS) using an ion-trap detector. Quantitation was by capillary gas chromatography—high-resolution mass spectrometry using negative chemical ionization (GC-NCIMS). 2-Phenoxybenzoic acid (2-PBA) served as internal standard. The limits of detection forcis- andtrans-DCCA,cis-DBCA, FPBA and 3-PBA were 0.03 μg L⁻¹ or below. The applicability of the presented method was tested on urine samples of persons exposed to low levels of pyrethroids.     

Synthesis of polymers containing azo groups in the main chain from <Emphasis Type="Italic">m</Emphasis>-phenylenediamine: Study of doping

Synthesic approach to polymers containing azo groups was developed on the basis of diazotization and azo-coupling reaction of m-phenylenediamine (m-PDA) with various ratio m-phenylenediamine-sodium nitrite. Doping of poly(azoaminophenylenes) with iodine, perchloric and hydrochloric acids was examined. Electroconductivity increases in the case of iodine to 0.2 S mol⁻¹, of perchloric acid, to 7×10⁻³ S mol⁻¹, and at the action of hydrogen chloride it is virtually unaffected. According to the ESR spectra, at the doping with iodine and perchloric acid electroconductivity enhances generally due to the mobility increase of the charge carriers (polarons).     

Partial Molar Volumes of Some of α-Amino Acids in Binary Aqueous Solutions of MgSO4·7H2O at 298.15 K

The apparent molar volume, V ^o _{φ, 2}, of glycine, alanine, α-amino-n-butyric acid, valine and leucine have been determined in aqueous solutions of 0.25, 0.5 and 1.0 mol⋅dm⁻³ magnesium sulfate, and the partial specific volume from density measurements at 298.15 K. These data have been used to calculate the infinite dilution apparent molar volume, V ^o _2,m , group contribution of amino acids and partial molar volume of transfer, Δ_tr V _2,m ^o, from water to aqueous magnesium sulfate solutions. The linear correlation of V _2,m ^o for a homologous series of amino acids has been utilized to calculate the contributions of charged end groups (NH₃ ⁺, COO⁻), CH₂ - groups and other alkyl chains of amino acids to V _2,m ^o. The results for Δ_tr V _2,m ^o of amino acids from water to aqueous magnesium sulfate solutions have been interpreted in terms of ion-ion, ion-polar, hydrophilic-hydrophilic and hydrophobic-hydrophobic group interactions. The values of the standard partial molar volume of transfer for the amino acids with different hydrophobic contents, from water to aqueous MgSO₄ are in general positive, indicating the predominance of the interactions of zwitterionic/hydrophilic groups of amino acids with ions of the salt. The hydration number decreases with increasing concentration of salt. The number of water molecules hydrated to amino acids decreases, further strengthening the predominance of ionic/hydrophilic interactions in this system.     

Michael reaction. IV. NaNH2 catalyzed one stage reaction between phenylacetic acid dialkylamides and cinnamic acid methyl ester or dialkylamides. Influence of reaction conditions on the stereochemistry

The NaNH₂ catalyzed one stage reaction between phenylacetic acid dialkylamides and cinnamic acid methyl ester or dialkylamides was studied under various conditions. Conditions were found for easy preparation of each of the both possible diastereomeric derivatives of 2,3-diphenylglutaric acid. It was proved that catalytic amounts of NaNH₂ take part in the reaction. It is assumed that the observederythro/threo equilibrium ratios are determined by an isomerization via two different carbanions (at C₂ and C₄) of the reaction products.Part III:J. Stefanovsky andL. Viteva, Comun. Dept. Chem. Bulg. Acad. Sci.4, 159 (1971).     

Amino acid overproduction by analog resistant mutants of the nitrogen fixing cyanobacteriumAnabaena sp 287

Two amino acid analog resistant mutants of the cyanobacteriumAnabaena sp 287 were isolated after MNNG mutagenesis.Anabaena ST 16, a mutant resistant to the alanine analog D-α-aminobutyric acid andAnabaena ST 25, another mutant resistant to the histidine analog l,2,4-triazole-3-alanine, released alanine and histidine, respectively, into the medium upon immobilization in alginic acid during diazotrophic growth in fluidized bed reactors. The rates of amino acid production by the mutants were 4.3 μmol mg chl^-1 h^-1 of D-alanine byAnabaena ST 16 and 16.6 μnol mg chl^-1 h^-1 of L-histidine byAnabaena ST 25. Nitrogen fixation by the mutants was not affected by the extracellular amino acid concentration. While the radioactive carbon flow was followed, the parent strain retained 93% of fixed¹⁴C and released only 7% into the medium. On the other hand,Anabaena ST 16 released 13% andAnabaena ST 25 released 29% into the medium. These mutants are beneficial in the production of radioactive amino acids using diazotrophic photobiotechnology.     

Comparison of α- and β-trifluoromethylsubstituted acrylic acids in their reactions with thiols

α-(Trifluoromethyl)acrylic acid (1) and γ,γ,γ-trifluorocrotonic acid (2) add AcSH (exothermally and at 100 °C, respectively) in the absence of a catalyst to form products of β-thiolation, which can be easily hydrolyzed to the corresponding β-mercaptoalkanoic acids. Thiols also add regiospecifically to acids1 (in the absence of a catalyst) and2 only in the presence of trifluoromethanesulfonic acid as the catalyst) when heated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1230–1232, June, 1997.