Dithiobiuretes in reactions with electrophilic acetylenes. New derivatives of 1,3,5-dithiazines,-thiadiazines and-triazines as the products of competing reactions of nucleophilic cycloaddition

The nucleophilic addition of 2,4-dithiobiurete, 1- and 1,4-substituted 2,4-dithiobiuretes (2 a-e) with benzoylacetylene (1) has been studied. 2-(Benzoylmethyl)-4-(R¹-imino)-6-(R²-imino)dihydro-4H-1,3,5-dithiazinium perchlorates (3 a-e) are obtained in glacial acetic acid (AcOH) in the presence of equimolar quantities of HClO₄. The reaction of benzoylacetylene with 1,5-diphenyl-2,4-dithiobiurete in either of MeOH, C₆H₆, or MeCN solvents proceeds non-selectively to give a mixture of products such as 2-(benzoylmethyl)-4,6-di(phenylimino)dihydro-4H-1,3,5-dithiazine (5), 2-(benzoylmethyl)-4-(β-benzoylvinyl)thio-3-phenyl-6-(phenylimino)-3,6-dihydro-2H-1,3,5-thiadiazine (8), 2-(benzoylmethyl)-1,3-diphenylhexahydro-1,3,5-triazine-4,6-dithione (7) and N-(β-benzoylvinyl)-N-phenylthioureas (6).     

The Use of Chiral Auxiliaries Prepared from (-)-β-Pinene in Stereoselective Reduction of β-Ketobutyrates

Chiral auxiliaries previously prepared from (-)-β---pinene (3), alcohols 5a-e and 6, were transformed into β---ketobutyrates 7a-e and 8 respectively. These compounds were stereoselectively reduced by NaBH₄ in the presence of additives (MnCl₂ or CaCl₂), leading to the corresponding β-hydroxy butyrates 10a-e and 11 in good chemical yield and poor to moderate stereoselectivities (de 0%-60%). The configuration at the newly generated stereogenic center in 10a was determined to be S through its transformation into S-(+)-butanediol.     

The effect of inversion of the ester group on the mesophase behaviour of some azo/ester compounds

Five homologous series of 4-substituted phenyl 4′-(4″-alkoxy phenylazo) benzoates (In_a–?e) were prepared in which, within each homologous series, the length of the terminal alkoxy group varies between 8, 10, 12, 14 and 16 carbons, while the other terminal substituent, X, is a polar group that alternatively changed from CH₃O, CH₃, H, Br, and CN groups. Compounds prepared were characterised by infrared, mass, and H¹-NMR spectroscopy and their mesophase behaviour investigated by differential scanning calorimetry (DSC) and polarised light microscopy (PLM). The results were discussed in terms of mesomeric and polarisability effects. Only for the lower group of compounds, I8_a-e, that showed a nematic phase, the nematic-to-isotropic transition temperatures (T_N–I) were successfully correlated to the polarisability anisotropy of bonds to the substituent X. A comparative study was made between the investigated compounds and two previously prepared isomeric groups. In the first group of isomers, 4-(4′alkoxy phenylazo) phenyl 4″-substituted benzoates (IIn_a–e), the ester groups are inverted. While in the second, 4-(4′-substituted phenylazo) phenyl 4″-alkoxy benzoates (IIIn_a–e), two modifications were made, inversion of the COO group, and exchange of the two wing substituents     

Hydrogen-bonded supramolecular complexes formed between isophthalic acid and pyridine-based derivatives

Two types of supramolecular liquid crystals were prepared through the formation of double hydrogen-bonded complexes between isophthalic acid (A) and two different groups of pyridine-based derivatives ( I n and I _a-e ). The first group of the base, I n (molecular formula 4-C_nH_2n+1OC₆H₄COOC₆H₄-N=N-C₅H₄N) homologues differ from each other by the number of carbon atoms (n) in the alkoxy chain, which varies between 8, 10, 12 and 14 carbons. The second group of the pyridine-based derivatives, I _a-e (molecular formula 4-X-C₆H₄COOC₆H₄-N=N-C₅H₄N) analogues differ from each other by the terminal polar substituent, X, that changes between OCH₃, CH₃, H, NO₂ and Br groups. In this manner two different groups of complexes are formed, one of them is A : 2I n, (Group A ), and the other is A : 2I _a-e , (Group B ). All complexes were investigated for their mesophase behaviour by differential scanning calorimetry and polarised light microscopy. The formation of 1:2 hydrogen-bonded complexes was confirmed by FTIR spectroscopy and binary phase diagrams. Most complexes A and B show nematic and/or SmA phases. X-ray diffraction of the SmA phase of a representative complex of type A indicates a layer distance corresponding to only half of the length of the H-bonded complexes which is interpreted by a phase structure where these complexes adopt a U-shape which intercalate and form non-polar SmA phases.     

New N-aryloxy-phthalimide derivatives. Synthesis,physico-chemical properties,and QSPR studies

Starting from N-hydroxyphthalimide 1 and the reactive fluoro- or chloro-nitroaryl derivatives 2, 3 and 4a-e (2-chloro-3,5-dinitropyridine; 3, NBD-chloride; 4a, 1-fluoro-2,4-dinitrobenzene; 4b, picryl chloride; 4c, 4-chloro-3,5-dinitrobenzotrifluoride; 4d, 2-chloro-3,5- dinitrobenzotrifluoride; 4e, 4-chloro-3,5-dinitrobenzoic acid) the corresponding N-(2-nitroaryloxy)-phthalimide derivatives 5a-e, or 6 and 7 were obtained and characterized by IR, UV-Vis ¹H-NMR and ¹³C-NMR spectroscopy. The TLC behavior and the hydrophobicity of these derivatives have been experimentally evaluated by R_M0 parameters (using RP-TLC). The experimental R_M0 parameters were compared with the calculated partition coefficient, log P. A QSPR study was also performed to establish possible correlations between the structure and physical properties (λ_max and R_M0) of compounds 5a-e, 6, and 7.      

Synthesis of 2, 5, 5-Trimethylhepta-2, 6-Dien-4-One (Artemisia Ketone): II. Using A Thioacetal Monoxide

The polymer-bound catalyst 3a-e inserted some spacer ([-NHCO(CH_{2 10- n}; n = 0,1,2,3,4) connecting the catalytic moiety [cyclo(-(S)-Phe-(S)-His)], [(S,S)-1] and 2% cross-linked Merrifield's polymer, have been prepared and their catalytic efficiency for the enantioselective hydrocyanation of 3-phenoxybenzaldehyde was studied.     

Angucycline antibiotics and its derivatives from marine-derived actinomycete Streptomyces sp. A6H

Vineomycin A₁ (1) and B₂ (2) were isolated from the culture broth of marine actinomycete Streptomyces sp. A6H. Five hydrolysis products were obtained by rational hydrolysis and methanolysis of the fermentation extract. Their structures were characterised as aquayamycin (3), vineomycinone B₂ (4), 9-C-_D-olivosyltetrangulol (5), 7-O-methylgaltamycinone (6) and vineomycinone B₂ methyl ester (7). In addition to these compounds, two ester derivatives, vineolactone A (8) and vineomycinone B₂ benzyl ester (9) of compound 4 were generated semisynthetically. Compound 6 is a new analogue of galtamycinone, while compounds 8 and 9 are new members of vineomycins. Cytotoxic activities and antimicrobial activities were determined for all compounds. The results indicate that only compound 1 showed significant activities with IC₅₀ value of 0.34 μM against H1975 and MIC value of 4 μg/mL against Staphylococcus aureus.     

Synthesis and Reactions of 4-Oxiranylmethylfuro[3,2-b]pyrroles and Their Benzo Derivatives

Methyl 4-oxiranylmethyl-4H-furo[3,2-b]pyrrole-5-carboxylates 2a-c and methyl 1-oxiranylmethyl-1H-benzo[4,5]furo[3,2-b]pyrrole-2-carboxylate (2d) were prepared by reaction of the appropriate starting compounds 1a-d with excess chloromethyloxirane. The compounds 2a-d undergo oxirane ring opening by heterocyclic amines (morpholine, pyrrolidine, piperidine or 4-methylpiperazine) giving N-2-hydroxy-3-heteroaminopropyl-substituted compounds 3a-f or substituted 4,5-dihydrofuro[2',3':4,5]pyrrolo[2,1-c][1,4]oxazin-8-ones 4a-e.     

Microwave-assisted Hantzsch thiazole synthesis of N-phenyl-4-(6-phenylimidazo[2,1-b]thiazol-5-yl)thiazol-2-amines from the reaction of 2-chloro-1-(6-phenylimidazo[2,1-b]thiazol-5-yl)ethanones and thioureas

N-Phenyl-4-(6-phenylimidazo[2,1-b]thiazol-5-yl)thiazol-2-amines (6a-q) have been synthesized by the Hantzsch thiazole reaction of 2-chloro-1-(6-phenylimidazo[2,1-b]thiazol-5-yl)ethanones (4a-e) with suitably substituted thioureas using microwave heating. The ethanones (4a-e) were prepared by the reaction of 6-phenylimidazo[2,1-b]thiazoles (3a-e) with chloroacetylchloride in refluxing 1,4-dioxane whereas the thiazoles (3a-e) were synthesized by the reaction of 2-bromo-1-phenylethanones (2a-e) with thiazol-2-amine in refluxing acetone.     

Liquid crystalline properties of dissymmetric molecules IV. The substituent effect on thermal properties of nematic and smectic A phases in three aromatic ring systems with ester linkages

This paper describes the effect of substituent and ester linkage on smectic properties for some derivatives of 4-R -phenyl 4-(4-octyloxybenzoyloxy)benzoates (1), 4-octyloxyphenyl 4-(4-R-benzyloxy)benzoates (2), 4-(4-octyloxybenzoyloxy)phenyl 4- R -benzoates (3), and 4-R-phenyl 4-octyloxyphenyl terephthalates (4) where R = OCH₃, CH₃, OC₈H₁₇, C8H17, halogens, CF₃, OCF₃, CN, NO2, etc. The thermal properties are discussed in terms of the electrostatic nature of the substituents and the relative orientation of the ester groups with respect to both terminal substituents. The substituent effect on the layer structure of the smectic A phase is also examined by means of a small angle X-ray analysis.     

One Pot Synthesis of 4-Arylbenzoxazolo[3,2-a]-s-triazine-2-thiones

The reaction of 2-aminobenzoxazoles (1a-b) with aroyl isothiocyanates in acetone gave 4-arylbenzoxazolo [3,2-a]-s-triazine-2-thiones (3a-g), aroylthioureas (5a-e) and 2-benzoxazolones (6a-b). A reasonable pathway for the formation of 3, 5 and 6 from 1 has been suggested.     

Syntheses and properties of fluorinated polyamides and poly(amide imide)s based on 9,9-bis[4-(4-amino-2-trifluromethylphenoxy)phenyl]fluroene, aromatic dicarboxylic acids, and various monotrimellitimides and bistrimellitimides

A diamine, 9,9-bis[4-(4-amino-2-trifluromethylphenoxy)phenyl]fluroene (I) containing the CF₃ group, was prepared from 9,9-bis(4-hydroxyphenyl)fluorene and 2-chloro-5-nitrobenzotrifluoride. The imide-containing diacids (V _a-j and VI _a,b) were prepared by condensation reaction of amino acids, aromatic diamines, and trimellitic anhydride. Then, a series of soluble fluorinated polyamides (VII _a-e) and poly(amide imide)s (VIII _a-j and X _a,b) were synthesized from diamine (I) with various aromatic diacids II _a-h and the imide-containing diacids (V _a-j and VI _a,b) via direct polycondensation with triphenyl phosphate and pyridine. All polymers showed excellent solubility in amide-type solvents such as N-dimethylforamide and can also be dissolved in pyridine, m-cresol, and tetrahydrofuran. Polymers afford transparent and tough films by solvent casting. The glass transition temperature of these polymers were in the range of 278–366°C, and the poly(amide imide)s had better thermal stability than polyamides. In comparison with the isomeric IX _a-d, VIII _a-d showed a lighter color with lower b* (yellowness index) values than the corresponding IX series.     

Zur Reaktion von Hydroxy- und Amino-pyridinen mit reaktiven Malonestern

Zusammenfassung Das Verhalten der Hydroxy- und Amino-pyridine gegenüber Malonsäure-bis-2,4,6-trichlorphenylestern (1) wird untersucht. Im besonderen werden die Reaktionen des 3-Hydroxy-pyridins (4) mit1 zu 4-Hydroxy-2H-pyrano[3,2-b]pyridin-2-onen (5 a-e) und die des 2-Amino-3-hydroxy-pyridins (15) zu 2,9-Dihydroxy-4H-pyrido[1,2-a]pyrimidin-4-onen (16 d-f) beschrieben.

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Syntheses of heterocycles, CLX: the reaction of hydroxy and amino pyridines with reactive malonic esters

The reaction of hydroxy and amino pyridines with 2.4.6-trichlorophenyl malonates (1) is discussed. Especially the reaction of 3-hydroxy-pyridine (4) with1 to 4-hydroxy-2H-pyrano[3.2-b]pyridine-2-ones (5 a-e), and the reaction of 2-amino-3-hydroxy-pyridine (15) to 2.9-dihydroxy-4H-pyrido-[1.2-a]pyrimidin-4-ones (16 d-f) is described.

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Herrn Prof. Dr. Dr. h. c.O. Kratky, Vorstand des Institutes für Physikal. Chemie der Universität Graz, zum 70. Geburtstag gewidmet.     

Zur Chemie des Maleinsäure-monoureides, 2. Mitt.: Reaktionen an der Doppelbindung der Maleinursäure

Electrolytic reduction of N-carbamoyl-maleamic acid and its N-alkyl derivatives (1 a-c) leads to mono-ureido-succinic acids in good yields, while alkylene-bis-N-carbamoyl-maleamic acids (3 a-e) are not attacked at the double bond under the same conditions. N-(Phenyl-carbamoyl)-maleamic acid (4) shows isomerisation to the fumaric acid derivative5 with pyridine, while NaOH causes cyclisation to an imidazolidine acetic acid6.Addition of formaldehyde to N-carbamoyl-maleamic alkyl esters9 yields 3-carbamoyl-4-oxo-5-oxazolidine acetic acids (10 a-c).     

Synthesis and thermal stability of silicon-containing esters of phosphorus acids

A number of trialkylsilylmethyl diphenyl phosphates MeRR′SiCH₂OP(O)(OPh)₂ (1a-e: R=Et (a), Pr (b), CF₃CH₂CH₂ (c, e), Me₃SiCH₂ (d); R′=Me (a-d), Et (e)) were synthesized and their thermal rearrangement, of the 1,2-shift type, was studied. The rearrangement consists of the migration of an alkyl group from Si atom to the methylene carbon atom and gives the corresponding silyl esters. The rate of the rearrangement was found to increase in the order1d<1b<1a<1 (R=R′=Me)<1c corresponding to the enhancement of the total inductive effect (−I) of the substituents at the Si atom. The relative migration ability of the substituents at the Si atom, determined by GC/MS analysis of the disiloxane fraction resulting from hydrolysis of pyrolyzed phosphates1a-e, increases in the order R=Pr<Et<CF₃CH₂CH₂<Me≪Me₃SiCH₂, which differs substantially from the order in which the rate of the rearrangement of phosphates1a-d changes. The electronegativity of the migrating group affects noticeably the relative ability to migrate. For Part 4, see Ref. 1. Deceased. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 9, pp. 1767–1772, September, 1998.     

Zur Chemie der vicinalen Triketone,XII Versuche zur Darstellung vonSchiffschen Basen aus cyclischen,vicinalen Triketonen

The quinolinetrionesTMCH, PCH, MCH and phenalene trione (PT) do not react with aryl isocyanates toSchiff bases^5a, but react by ring contraction to yield the spiro-imidazolidines2 a-d,3 a-e,4 a-b and5 a-cbd. However, reaction of ninhydrine with aryl isocyanates gives the 1:2 adductes1 a-e. Benzal aniline reacts withTMCH, PCH. andPT to yield known phenoxazine derivatives^2c,11. In contrast,PCH orMCH react with benzylidene benzalaniline to yield theSchiff bases7 a-b. which can be transformed into the bisamine8. comparable to the ninhydrine reaction.

Herrn emer. o. Univ. Prof. Dr.Erich Ziegler, Graz, mit besten Wünschen zur Vollendung des 70. Lebensjahres gewidmet.     

Syntheses of 2,6-Anhydro-3-Deoxy-D-Glycero-D-Galacto-Non-2-Enonic Acid (Kdn2En) and Its Hydrogenation Products 1

Abstract

Methyl 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-3-deoxy-D-glycero-D-galacto-enonate (5) was synthesized from KDN methyl ester 2 with a catalytic amount of concentrated sulfuric acid in acetic anhydride, or from 2-chloro-KDN methyl ester 4 with DBU in good yield. Hydrogenation of 4 and 5 with 10% Pd-C gave 2-deoxy-2-H_ax-KDN 8 and 2-deoxy-2-H_eq-KDN derivative 11 in high yield, respectively. The structures of these compounds were elucidated from the MS, elemental analysis, ¹H NMR and ¹³C NMR data.

     

Multistep synthesis and screening of heterocyclic tetrads containing furan,pyrazoline, thiazole and triazole (or oxadiazole) as antimicrobial and anticancer agents

In the present study novel heterocyclic tetrads containing furan, pyrazoline, thiazole and triazole (or oxadiazole) (1, 2, 3, 4a-e and 5a-e) were designed and synthesized and investigated for their antimicrobial (against selected bacteria and fungi) and anticancer potential. The molecules 4e and 5e containing 4-fluoro phenyl and 4-fluoro benzyl substituents showed promising antimicrobial (antibacterial and antifungal activities with MICs ranging between 0.5 and 8 µg/mL. Compounds 3 exhibited potent anticancer activity with an IC₅₀ value of 0.49 ± 1.45 µM against the human gastric cancer cell line (BGC-823) whereas compound 4e displayed an IC₅₀ value of 0.65 ± 0.53 µM against breast cancer (MCF-7) cell line respectively. All compounds showed selective toxicity against the cancer cell lines compared to human normal liver cell lines. Molecular docking studies of the most potent compounds (3 and 4e) against selected microbial and cancer proteins revealed the crucial binding interactions of the potent compounds with the target enzymes. Compounds 3 and 4e are promising lead molecules to be developed as potential drug candidates.     

Cyclization of 2′-Aminochalcones with Chlorosulfonyl Isocyanate

Cyclization of 2′-aminochalcones 1a-e with chlorosulfonyl isocyanate (CSI), at low temperature, afforded 2(1H)-quinazolinone 2a-e and 1H-2,1,3-benzothiadiazine 2,2-dioxide 3a-e derivatives.     

Electrospray Ionization Mass Spectrometry of Palladium(II) Quinolinylaminophosphonate Complexes

The mass spectrometric behavior of palladium(II) halide complexes of three types of quinolinylaminophosphonates, diethyl and dibutyl esters of [α-anilino-(quinolin-2-yl)methyl]phosphonic (L1, L2), [α-anilino-(quinolin-3-yl)methyl]phosphonic (L3, L4), and [α-(quinolin-3-ylamino)-N-benzyl]phosphonic acid (L5, L6), was investigated under positive ion electrospray ionization conditions. Each type of ligand forms complexes with different metal–ligand interactions. Mononuclear dihalide adducts cis-[Pd(L1/L2)X₂] (1–4) and trans-[Pd(L3/L4)₂X₂] (5–8) as well as dinuclear tetrahalide complexes [Pd₂(L5/L6)₃X₄] (9–12) (X = Cl, Br) are formed by metal bonding either through the quinoline or both the quinoline and amino nitrogen atoms. The sodiated molecule [M + Na]⁺ is observed in the mass spectra of all the complexes, and its abundance as well as the fragmentation pathway depend on the type of the complex. In the cis complexes (1–4) the initial decomposition goes under two fragmentation routes: those in which the sodium molecular adduct sequentially loses halides HX/NaX and those in which this loss is in the competition with the loss of dialkyl phosphite. The predominant pathways for decomposition of trans dihalide (5–8) and tetrahalide (9–12) complexes include three competitive reactions; the loss of halides, dialkyl phosphites and the intact phosphonate ligand molecule and its fragments formed by ester dissociation or complete loss of the phosphonate ester moiety. A series of acetonitrile adducts and cluster ions derived from dimolecular clusters [2M + Na]⁺ were also detected. The most important fragmentation patterns are rationalized and supported by the MS ⁿ studies.