Synthesis of N-arylcarbamates with tetrazole fragment and some their derivatives

Reactions of methyl(ethyl) N-(2-cyanophenyl)carbamates with sodium azide in dimethylformamide at 80–90°C in the presence of anhydrous CdCl₂ afforded the corresponding N-arylcarbamates with a 1,2,3,4-tetrazole fragment. The acylation of methyl N-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]carbamate with acetic anhydride followed by the condensation of the obtained N-acyl derivative with thiophene-2-carbaldehyde in the KOH methanol solution led to the formation of methyl N-(2-{1-[3-(2-thienyl)-2-propenoyl]-1H-1,2,3,4-tetrazol-5-yl}phenyl)carbamate. The reaction of cyclohexyl N-(4-aminophenyl)carbamate with a triethyl orthoformate and sodium azide in glacial AcOH yielded cyclohexyl N-[4-(1H-1,2,3,4-tetrazol-1-yl)phenyl]carbamate.     

[4+1] Cycloaddition of N-acylimine derivatives with isocyanides: efficient synthesis of 5-aminooxazoles and 5-aminothiazoles

[4+1] Cycloaddition reaction between isocyanides and N-acylimine derivatives generated from N-acyl N,O-acetals acting as isocyanophiles has been developed. These reactions proceeded smoothly and cleanly to afford the corresponding 5-aminooxazoles in high yields. This reaction was extended to the syntheses of 5-aminothiazoles by using N-thioacyl N,O-acetals. A wide range of N-acyl N,O-acetals, N-thioacyl N,O-acetals, and isocyanides were found to be applicable to this reaction.     

Reaction of methyl acrylate with N,N-dimethylethanolamine in the presence of a titanium alkoxide

The kinetic features were examined for transesterifi cation of methyl acrylate with N,N-dimethylethanolamine in the presence of tetra(N,N-dimethylaminoethyl) titanate at different molar ratios of the reactants and at temperatures within 50?C80°C, as well as for side reactions of Michael addition at 95?C125°C. The major parameters governing the selectivity of the synthesis of N,N-dimethylaminoethyl acrylate were determined.     

Synthesis of an O-acyl isopeptide by using native chemical ligation to efficiently construct a hydrophobic polypeptide

By using dimethylformamide to suppress the O-to-N acyl migration, we efficiently synthesized an O-acyl isopeptide by native chemical ligation of a peptide-thioester and a Cys-O-acyl isopeptide. The reaction mixture was then loaded onto an octadecylsilane reverse-phase HPLC column, and the isopeptide was purified by using a linear gradient of CH₃CN in 0.1% aqueous trifluoroacetic acid. The recovery rate of the O-acyl isopeptide was considerably higher than that of the corresponding native polypeptide. Synthesis of O-acyl isopeptides via native chemical ligation, with O-to-N acyl migration as the final step to give the native form, has potential as an efficient method of constructing hydrophobic polypeptides.     

Synthesis of the sphingolipid activator protein, saposin C, using an azido-protected O-acyl isopeptide as an aggregation-disrupting element

In order to achieve an efficient synthesis of highly hydrophobic proteins by the native chemical ligation (NCL) reaction, we examined to incorporate the O-acyl isopeptide method, which is known to improve the solubility of the segment, to the NCL reaction: a peptide thioester having O-acyl isopeptide structures is prepared by the Boc mode solid-phase method using an azido group as a protecting group for the isopeptide site, and then ligated with C-terminal segment with an in situ reduction of the azido group followed by an O- to N-acyl shift. This method was successfully applied to the synthesis of the sphingolipid activator protein, saposin C.     

Selective O-acylation of unprotected N-benzylserine methyl ester and O,N-acyl transfer in the formation of cyclo[Asp-Ser] diketopiperazines

The synthesis of two diastereomeric cyclo[Asp-N-Bn-Ser] diketopiperazines (2a and 2b) was investigated. Initial formation of the Boc-aspartyl-N-benzyl serine isopeptide methyl esters (4a and 4b) was observed, which derive from the selective O-acylation of unprotected (S)- or (R)-N-benzylserine. This unexpected O-acylation is preferred over the formation of the tertiary amide and the resulting ester bond is stable in solution to O,N-acyl transfer. The O,N-acyl migration is then triggered by cleavage of the Boc protecting group and treatment with base, which also promotes immediate cyclization to the diketopiperazines.     

Photo- and ionochromic properties of aza crown derivatives of enamino 1-benzothiophen-2-ones

2-(N-Acyl-N-arylaminomethylidene)-1-benzothiophen-3(2H)-ones exhibit photochromic properties due to photoinitiated Z/E isomerization with respect to the exocyclic C=C bond and subsequent fast thermal N→O migration of the acyl group and syn→anti isomerization of the N-acyl isomer. Introduction of a 15-azacrown-5 substituent into the para position of the aryl group reduces the quantum yield of the N→O rearrangement down to zero. By contrast, under irradiation with a mercury lamp, crown ether complexes with alkaline earth cations are converted almost completely into the O-acyl isomers which, unlike their N-acyl analogs, show no fluorescence. The highest quantum yields for the N→O acyl group migration are observed for the calcium complexes. The obtained compounds constitute a new class of acylotropic molecular switches operating under photoinitiation exclusively in the presence of alkaline earth cations.     

Contributionàl'étude du système formépar l'étain,le soufre et l'iode. Mise enévidence des deux variétés de l'iodosulfure stanneux Sn2SI2: Comportement thermique etétude structurale

We have found a new compound Mn₈O₁₀Cl₃. It is prepared by oxidation of anhydrous or hydrated MnCl₂ in streaming (N₂ + O₂) at temperatures less than 680°C. At room temperature the compound is tetragonal, a = b = 9.2898 Å, c = 13.0247 Å. The more symmetric space group is $\text{I4}\text{mmm}$. Mn₈O₁₀Cl₃ becomes cubic at 360°C with the c-axis as cubic parameter. In air, DTA and GTA have shown that Mn₈O₁₀Cl₃ is transformed at 580°C into Mn₂O₃ which gives Mn₃O₄ at 960°C. The exact formula has been determined only by crystal structure analysis.     

A novel solid-phase synthesis of di- and trisubstituted N-acyl ureas

A novel, mild method for the synthesis of di- and trisubstituted N-acyl ureas on solid support is described. Addition of carboxylic acids to a resin-bound carbimidoyl chloride gave, initially, an O-acyl isourea which subsequently rearranged to the corresponding N-acyl urea. Trisubstituted N-acyl ureas were assembled on a Wang resin from a wide range of Fmoc amino acids, secondary amines and carboxylic acids. Acid mediated cleavage yielded the products in good yields and excellent purities. In addition, the regioselective synthesis of disubstituted N-acyl ureas is demonstrated with four examples.     

Synthesis and crystal structure of a second polymorph of N,N′-bis(salicylidene)-3,5,3′,5′-tetramethyl-biphenyl-4,4′-diamine

The Schiff base compound N,N′-bis(salicylidene)-3,5,3′,5′-tetramethyl-biphenyl-4,4′-diamine was synthesized and crystal structure was determined by single-crystal X-ray diffractometry. The result shows that there is another polymorphic form (B) in structure besides published one (A) [1]. In structure B, there are four aromatic rings. The dihedral angles between the phenol rings and the adjacent dimethylbenzene rings are distinctly larger than that formed by the dimethylbenzene rings, possibly as a result of the steric hindrance of the methyl groups and the presence of intramolecular O-H…N hydrogen bonds. The remarkable defference between A and B lies in the angles of C1–C6 ring and C25–C30 ring, which are 51.64(13)° and 7.40(7)° in B and A, respectively. Crystal data for the title compolex C₃₀H₂₇N₂O₂: Monoclinic, P2(1)/c, a = 14.346(3) Å, b = 12.258(2) Å, c = 14.265(3) Å; β = 99.515(4)°, V = 2474.1(7) ų, Z = 4.     

Impedance-based total-NOx sensor using stabilized zirconia and ZnCr2O4 sensing electrode operating at high temperature

We report here a new-type zirconia-based sensor that can detect total NO_x content at high temperatures such as 700 °C. A closed-one-end yttria-stabilized zirconia (YSZ) tube was used as a base sensor material. An oxide sensing electrode (SE) and a Pt counter electrode (CE) were formed on the outer and inner surfaces of the YSZ tube, respectively. The complex impedance of the device using a ZnCr₂O₄-sensing electrode was measured with an impedance analyzer in the frequency and the temperature ranges 0.1 Hz–100 kHz and 600–700 °C, respectively. A large semicircular arc was observed in complex impedance plots (Cole–Cole plots) in the lower frequency range examined and it seemed to correspond to the electrolyte/electrode interface. The impedance value at 1 Hz of the present device was found to vary almost linearly with the concentration of NO (or NO₂) from 50 to 400 ppm in the sample gas at 600–700 °C. Furthermore, it is noted that the sensitivity of NO is almost equal to that of NO₂. This means that the present device can detect the total NO_x at higher temperatures.     

NMR studies in the heterocyclic series. XX—a carbon-13 NMR study of the structures of N-hydroxybenzotriazole and its acylated derivatives

Assignment of the carbon resonances in nine derivatives of N-hydroxybenzotriazole has been carried out. The ¹³C NMR method enables tautomeric N-hydroxy and N-oxide and isomeric O- and N-acyl structures to be identified. In DMSO, the predominant tautomer of N-hydroxybenzotriazole was found to be the N-hydroxy form. The structure of the benzoate and methyl and phenyl carbonate esters were likewise established, but for the two latter compounds, hydrolysis of the equilibrating O- and N-acyl isomers imposed some limitations on the usefulness of the technique.     

Synthesis and characterization of oligo-4-[(pyridin-3-ylimino)methyl]phenol

The oxidative polycondensation of 4-[(pyridin-3-ylimino)methyl]phenol (4-PIMP) with O₂, H₂O₂, and NaOCl was studied in an aqueous alkaline medium between 50°C and 90°C. Oligo-4-[(pyridin-3-ylimino)methyl]phenol (O-4-PIMP) prepared was characterized by ¹H-NMR, ¹³C-NMR, FT-IR, UV-VIS, size-exclusion chromatography, and elemental and thermal analyses techniques. At the optimum reaction conditions, the yield of O-4-PIMP was 18.9%, 39.4%, and 46.8% using H₂O₂, O₂, and NaOCl oxidant, respectively. According to the TG analysis, the initial degradation temperature of O-4-PIMP was 218°C, which was by 50°C higher than that of 4-PIMP. Thermal analyses of 4-PIMP and O-4-PIMP were carried out in N₂ atmosphere at 15–1000°C. The highest occupied molecular orbital, the lowest unoccupied molecular orbital, and electrochemical energy gaps of 4-PIMP and O-4-PIMP were determined from the onset potentials for n-doping and p-doping, respectively. Also, optical band gaps of 4-PIMP and O-4-PIMP were determined according to UV-VIS measurements.     

Conformational structure of N-ethylacetamide and N-isopropylacetamide. NMR shift reagent study

The structure of the stable conformers of N-ethylacetamide and N-isopropylacetamide was determined by NMR spectroscopy with lanthanide shift reagents. N-ethylacetamide was found to exist in the form of two mirror-image isomers, with the ethyl group twisted out of the plane of the amide bond by the angle ψ XXX ± 105°. Similarly N-isopropylacetamide exists in the form of two mirror-image isomers, with the isopropyl methyl groups in positions with ψ₁ XXX ± 90° and ψ₂ XXX ? 150°.     

Hindered rotation in N-acyloxy-4-methylthiazole-2(3H)-thiones

Experimentally determined barriers to O-acyl group topomerization in mixed anhydrides composed of β-disubstituted carboxylic acids and cyclic thiohydroxamic acid N-hydroxy-4-methylthiazole-2(3H)-thione were located in the range of ΔG^‡₃₂₀=68±8 kJ mol⁻¹ (DNMR). According to modeling studies, the underlying exchange process is proposed to occur via rotation about the N,O bond for torsional movement of the O-acyl group past the heterocyclic 4-methyl substituent. The energetically lowest pathway for passing the O-acyl entity by the thione sulfur, is predicted to occur via sequential rocking about the Csp²,O single bond in combination with an interlaced twist about the N,O axis.     

Gamma-radiolysis of hydrogen—Oxygen-mixtures— Part I. Influences of temperature,vessel wall,pressure and added gases (N2, Ar,H2) on the reactivity of H2/O2-mixtures

The influence of pressure, temperature, of “matrix gases” N₂, Ar, H₂ and of the pretreatment of the vessel wall on the rate of reaction from ⁶⁰Co γ-radiolysis of hydrogen—oxygen-mixtures, in the region of slow reaction, was investigated. The G(-H₂)-value2 of H₂/O₂-mixtures (H₂:O₂ = 1:9−2:1) ranges from 1 to 14 with only slight dependence on pressure, temperature, H₂/O₂-ratio, and surface/volume ratio (S/V). The temperature has little influence (35–210°C). Replacing most of the O₂ in the H₂:O₂ (1:9)-mixtures with N₂, Ar or excess H₂ at higher temperature, causes the G(-H₂)-values to increase. The influence of these matrix gases increases with increasing temperature (35–210°C) and decreasing S/V ratio (0.59 and 3.8 cm^-1) of the reaction vessel; it depends also on the pretreatment of the wall surface. Varying the total pressure, the G(-H₂)-values show a temperature and gas mixture dependent maximum between about 20 and 200 mb. At higher temperature (210°C) we observed an influence of dose for 50 mb H₂/air-mixtures, whereas at 1 b and 35–90°C no influence of the dose on the rate of reaction of such mixtures was found.The activation by N₂, Ar, H₂ is discussed on the base of the H₂/O₂-reaction being a radical-chain reaction, built up by at least 38 coupled elementary steps (Ref⁽¹⁾ or see part 2). O₂ reacts with H₂, at increased rates of conversions (> 25%), in the expected stoichiometric ratio of 2:1. Oxygen may however also be converted in non-stiochiometric amounts under certain conditions.     

The effect of ligand donor atoms on ternary complex stability

Formation constants of mixed ligand complexes of Cu²⁺, Zn²⁺, Ni²⁺, Co²⁺, and Mn²⁺,with cyadine-5′-monophosphoric acid (CMP) and various primary ligands such as 1,10-phenanthroline(phen), glycylglycine(glygly) and salicylic acid (sal) have been determined in aqueous solution at 35°C and 0.1 M (KNO₃) by potentiomeric measurements. The acid dissociation constants of all the above mentioned ligands together with their 1 : 1 binary metal complex formation constants were also measured at 35°C. In general all the 1 : 1 binary complexes follow the Irving-Williams order of stability. Further the binary metal complexes of primary ligands are more stable than their ternary complexes with CMP. For ternary complexes, Δ(log K) values seem to change from positive to highly negative as the coordinating atoms of the primary ligands were varied from N,N to N,O^? to O^?O^?. The higher stability of ternary complexes involving phen is due to its Π-bonding interaction with the above metal ions and the relative decrease in the stability of other ternary systems is due to the coulombic repulsion of donor oxygen atoms of primary and secondary ligands. Thus for ternary complexes the stabilities follow a decreasing order of M-phen-CMP > M-glygly-CMP > M-sal-CMP.     

The molecular structure of the N-chloroimine product of rearrangement of N,N-dichloroperfluoroaniline: A study by gas-phase electron diffraction

A gas-phase electron-diffraction study of the product of rearrangement of N,N-dichloro-perfluoroaniline has assisted in establishing it to be the N-chloroimine, I, rather than the azepine, II. The molecule is found to be planar apart from atoms Cl13 and F14. The detailed dimensions shown in Fig. 2 were obtained by least-squares refinements in which several structural constraints were applied to reduce the total number of independent parameters. Of particular interest is the evidence for overcrowding around the CN bond: ∠N7C1C2 = 128°, ∠C18N7C1 = 126°, ∠N7C1C6 = 118° ; the distance C18 β F9 is 2.73 Å.     

New Polymer Syntheses. 80. Linear,Star-Shaped,and Hyperbranched Poly(Ester-Amide)s from Silicon-Mediated One-Pot Condensations of 3-Acetoxy-, 3,5-Bisacetoxybenzoic Acid,and 3-Aminobenzoic Acid

Abstract

Acylation of N,O-bistrimethylsilyl-3-aminobenzoic acid with 3-acetoxybenzoylchloride yielded the trimethylsilylester of N-(3′-acetoxybenzoyl)-3-aminobenzoic acid, which was polycondensed in situ at 260 or 280°C. Cocondensation with acetylated tetraphenols yielded four-arm star copolymers with a random or preferentially alternating sequence of 3-hydroxy and 3-aminobenzoyl units. Due to ester-amide exchange detected by ¹H- and ¹³C-NMR spectroscopy, the sequences were never perfectly alternating. Methyl groups attached to the star centers allowed the determination of degrees of polymerization by ¹H-NMR spectroscopy. Acylation of N,O-bistrimethylsilyl-3-amino benzoic acid with 3,5-bisacetoxybenzoylchloride yielded a trifunctional monomer, the polycondensation of which yielded a hyperbranched poly(ester-amide). By cocondensation of the trifunctional monomer with acetylated tetraphenyl, star-shaped poly(ester-amide)s with four hyperbranched star arms were obtained. All these poly(ester-amide)s are amorphous materials with glass-transition temperatures in the 190–200°C range and good solubility in polar organic solvents.     

The double radio-isotope derivative technique for the assay of drugs in biological material: Part II. The simultaneous determination of opipramol and its deshydroxyethyl metabolite

The neuroleptic drug opipramol and its deshydroxyethyl metabolite can be determined simultaneously in the same biological sample. Known amounts of ¹⁴C-labelled opipramol and ¹⁴C-labelled metabolite are added to the sample to serve as internal standards. After suitable extraction, both compounds are acetylated by ³H-labelled acetic anhydride. Together with μg-amounts of carrier compounds, the O-acetyl derivative of opipramol and the N-acetyl derivative of the metabolite are purified and separated by two-dimensional thin-layer chromatography. Each of the derivatives is isolated and counted for ¹⁴C-and ³H-activity. The ¹⁴C-activities recovered serve to determine the overall yield of the opipramol and metabolite, and to convert the measured ³H-activity to 100 % theoretical yield. From analyses of standard samples, the specific ³H-activities of the acetyl derivatives were calculated, and these values were used to convert the measured ³H-activities from biological samples to concentrations of original opipramol and metabolite. For both compounds the standard deviations of blank samples were ±1 ng ml^?1. For concentrations up to 100 ng ml^?1 the standard deviation was ±3 ng ml^?1.