A Convenient Regiospecific Synthesis of New Conjugated Tetrazole Derivatives via the Reaction of Dienones with the Tetrachlorosilane-Sodium Azide Reagent and their NMR Structural Assignment

Summary. Several new 1-aryl-, aralkyl-, and heteroaryl-5-(4-phenylbuta-1,3-dienyl)tetrazole derivatives and annulated tetrazole derivatives were efficiently and regiospecifically prepared in nearly quantitative yield via a facile one step reaction of dienones with a combination of tetrachlorosilane and sodium azide in acetonitrile under mild conditions. A complete structure assignment of three representative examples of the tetrazoles was achieved by advanced 2D NMR measurements including COSY, TOCSY, HSQC, HMBC, NOESY, and ROESY experiments.Received March 17, 2003; accepted March 18, 2003 Published online July 28, 2003     

Novel High Energy Intermediate Analogues with Triazasterol-related Structures as Inhibitors of the Ergosterol Biosynthesis V [1]. Synthesis of Hexahydro-5H-imidazo[1'', 2'': 1,2]pyrimido-[4,3-a]isoquinolines and 1-Alkyl Analogues Representing New 8,13,15-Triazasteroids

Summary. The synthesis of 1,2,6,10b,11,12-hexahydro-5H-imidazo[1,2:1,2]pyrimido[4,3-a]isoquinolines representing new types of 8,13,15-triazasteroids is described. The tetracyclic title compounds were prepared from 4-(2-hydroxyalkylamino)tetrahydro-2H-pyrimidoisoquinolines, which furnish after conversion to the corresponding bromoalkylamino compounds and base-catalyzed intramolecular nucleophilic displacement cyclization of the latter the desired 1-substituted 8,13,15-triazasteroids with aromatic ring A. The structures of the compounds were proved and assigned on the basis of homo- and heteronuclear correlated 1D and 2D NMR experiments. The title compounds represent triaza-analogues of selected high energy intermediates (HEI) of steroidal substrates formed during the enzymatic transformation of squalene into ergosterol and are designed to act as inhibitory mimicries of HEIs and potential antimycotics.Received March 4, 2003; accepted March 7, 2003 Published online June 23, 2003     

Synthesis of Pyrimidine Annelated Heterocycles [1]. Regioselective Heterocyclization of 6-Cyclopent-2-enyl-5-hydroxy-1,3-dimethyl-pyrimidine-2,4( 1H, 3H)-dione and 5-Cyclopent-2-enyl-6-hydroxy-1,3-dimethylpyrimidine-2,4( 1H, 3H)-dione

Summary. Two hitherto unreported pyrimidine annelated heterocycles were synthesized from 6-cyclopent-2-enyl-5-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione and 5-cyclopent-2-enyl-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione by reaction with pyridine hydrotribromide or hexamethylenetetramine hydrotribromide. The first one was also obtained by reaction with concentrated sulfuric acid.Received October 28, 2002; accepted October 30, 2002 Published online June 2, 2003     

Synthesis and Reactions of Some Fused Oxazinone,Pyrimidinone, Thiopyrimidinone,and Triazinone Derivatives with a Thiophene Ring as Analgesic,Anticonvulsant, and Antiparkinsonian Agents

Summary. A series of 2,6-disubstituted pyridine ester derivatives and the corresponding amides were prepared. The esters were hydrolysed to the sodium salts, which were treated with acetic anhydride to afford oxazinone derivatives. These were treated with ammonium acetate to afford 2-methylpyrimidinone derivatives, which were methylated to yield 2,3-dimethylpyrimidinone derivatives. In addition, they were reacted with aniline or hydrazine hydrate to give 3-phenyl- or 3-aminopyrimidinone derivatives. The latter reacted with 2-thiophenecarbaldehyde or phthalic anhydride to afford the corresponding Schiffs base and imide derivatives. Diazotization of amides gave thienotriazinone derivatives, which were treated with ethyl iodide to afford the corresponding 3-ethyltriazinone derivatives. Also, they were reacted with phenyl isothiocyanate to give the corresponding thiopyrimidinone derivatives, which were alkylated with ethyl iodide or chloroacetic acid to afford the corresponding thioethyl- or thioglycolic acid pyrimidinone derivatives.The pharmacological screening showed that many of these obtained compounds have good analgesic, anticonvulsant, and antiparkinsonian activities comparable to Voltarene®, Carbamazepine®, and Benzotropene® as reference drugs.Received January 23, 2003; accepted (revised) March 17, 2003 Published online September 15, 2003     

An Efficient Synthesis of <Emphasis Type="Italic">O</Emphasis>-Methyl Protected Emodin Aldehyde and Emodin Nitrile

Summary. An efficient synthesis of tri-O-methylemodin aldehyde was achieved via bromination of tri-O-methylemodin utilizing N-bromosuccinimide yielding the monobromo and dibromo derivatives. Sommelet reaction of the monobromomethyl derivative as well as hydrolysis of the dibromomethyl analog with aqueous silver nitrate afforded the protected aldehyde in good yield. Accordingly, both bromo derivatives can be used even when they are obtained as a mixture of the bromination reaction, which could not be controlled easily to yield the bromo products selectively. From the aldehyde the tri-O-methylemodin nitrile was prepared in a one-pot reaction using hydroxylamine-O-sulfonic acid.Received February 18, 2003; accepted March 3, 2003 Published online June 2, 2003     

Synthesis and Structural Features of 1-Acyl-1-nitro-2-furyl(thienyl)ethenes

A one-stage synthesis of 1-acyl-1-nitro-2-furyl(thienyl)ethenes was developed and structural assessment of the products was performed by means of ¹H, IR, and UV spectroscopy and dipole moment measurements. The acetyl derivatives have Z configuration, and the benzoyl derivatives, E configuration. The UV and IR spectra, as well as the rather high dipole moments ( 5-6 D) point to an essential contribution in the structures of dipolar forms.     

Synthesis and Dynamic NMR Spectroscopic Study of Dialkyl 4-Ethoxy-1-(1-naphthyl)-5-oxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2,3-dicarboxylates

Summary. Protonation of the reactive 1:1 intermediate produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates with ethyl 2-(1-naphthylamino)-2-oxoacetate, leads to a vinylphosphonium salt, which undergoes intramolecular Wittig reaction to produce dialkyl 4-ethoxy-1-(1-naphthyl)-5-oxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates in excellent yields. A dynamic NMR effect is observed in the ¹H NMR spectra of the title compounds as a result of restricted rotation around the single bond linking the naphthalene moiety and the heterocyclic system, which is attributed to the peri interaction between the pyrrole residue and the peri CH group. The free energy of activation (G ) for this process is 58±2kJmol^–1.Received December 6, 2002; accepted December 11, 2002 Published online June 12, 2003     

Synthesis of Highly Functionalized Cyclobutene Derivatives

Summary. Protonation of the reactive 1:1 intermediates produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates with CH-acids, such as ethyl 2,4-dioxo-hexanoate and ethyl 2,4-dioxo-5-methylhexanoate, lead to vinyltriphenylphosphonium salts, which undergo an intramolecular Wittig reaction to produce cyclobutene derivatives in fairly high yields.Received November 8, 2002; accepted November 29, 2002 Published online July 3, 2003     

Study of the Microtexture of Recrystallized Aluminium

The nucleation of recrystallized grains in deformed, high-purity aluminium were examined in relation to the microstructural heterogeneities in the form of shear bands (SBs) and transition bands (TBs). The experiments were carried out on single crystals deformed in channel-die compression at 77 K to true strains within the range of 1–1.5. The substructures were identified by means of a combination of transmission (TEM) and scanning (SEM) electron microscopes. Local texture measurements in particular places of samples were mostly investigated by means of TEM and convergent beam electron diffraction (CBED), with on-line diffraction pattern analysis. The coarser analyses were performed by SEM and electron back scattered diffraction (EBSD). The and the oriented single crystals are stable in the global sense and form clearly defined SBs. The , and the shear orientations are very unstable and tend to form TBs. The nuclei of new grains formed along the band are misoriented by ( ) with respect to the orientations identified within the neighbouring banded material. The author attempts to explain, from the crystallographic point of view, the processes operating within high stacking fault energy metals at the very early stages of recrystallization.     

Derivatives of 1-aryl-5-methoxyindoles

By fusion with potassium hydroxide, derivatives of 1-aryl-3-ethoxycarbonyl-5-methoxy-2-methylindole are converted into the corresponding indole-3-carboxylic acids. When the indole-3-carboxylic acids are heated to their melting points, they are readily converted into derivatives of 1-arylindoles with unsubstituted -positions. A similar cycle of conversions has been carried out for 3-ethoxycarbonyl-5-methoxy-2-methyl-1-phenylbenzoindole. The reactions of derivatives of 1-aryl-5-methoxy-2-methylindoles with formaldehyde and dimethylamine hydrochloride gives Mannich bases.     

Conversion of N-(1-oximino-1-phenylpropyl-2)-α-phenylnitrone into imidazole N-oxide derivatives

Treatment of N-(1-anti-oximino-1-phenylpropyl-2)--phenylnitrone with benzoic anhydride in benzene leads to simultaneous formation of benzoyl derivatives both of the corresponding nitrone and of 1-hydroxymethyl-2, 4-diphenyl-3-imidazoline-3-oxide. Treatment of the latter with hydrogen chloride led to the isolation of 5-methyl-2, 4-diphenylimidazol-3-oxide. Its isomer 4-methyl-2, 5-diphenylimidazol-3-oxide is formed by the action of HCl on syn and anti isomers of N-(1-oximino-1-phenylpropyl-2)--phenylnitrone. IR and UV spectra are used to determine the structures of the compounds, which are confirmed by synthesis.     

N-nitration of 1(2)-substituted 5-aminotetrazoles with tetranitromethane

1(2)-Methyl-5-aminotetrazoles and 2-(-cyanoethyl)-5-aminotetrazole are nitrated by tetranitromethane in the presence of bases with the formation of salts of the corresponding 5-nitroaminotetrazole derivatives. In contrast to this, decyanoethylation takes place in nitration of 1-(-cyanoethyl)-5-aminotetrazole by tetranitromethane with the formation of 5-nitroaminotetrazole salt. The structure of the 2-methyl-5-nitroaminotetrazole salts (using the 2-methyl-5-nitroaminotetrazole potassium salt) was confirmed by x-ray structural analysis.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1067–1071, August, 1991.     

Synthesis of substituted derivatives of imidazo [5, 1-b] benzimidazole

Heating, either molten or in high-boiling solvents, 1-methyl-2-[(N-phenylthiocarbamoyl)amino] (pyrid-4-yl)-methylbenzimidazole, or refluxing with phosphorus oxychloride in benzene acyl derivatives of 1-methyl-2-[(pyrid-4-yl)(amino)]- and 1-methyl-2 [(phenyl)(amino)]-methylbenzimidazoles, gives the corresponding derivatives of the imidazo [5, 1-b] benzimidazole system, hitherto undescribed in the literature.     

Synthesis of 1-(3-halotetrahydro-2-furyl) derivatives of uracil, 5-substituted uracils,and cytosine

The cis and trans isomers of 1-(3-halotetrahydro-2-furyl) derivatives of uracil, 5-substituted uracils, and cytosine were obtained by alkylation of 2,4-bis(trimethylsilyl) derivatives of uracil, 5-substituted uracils, and cytosine with 2,3-dihalotetrahydrofurans. 2,3-Anhydro compounds are also formed in the alkylation of 5-halouracil derivatives. The physicochemical properties of the compounds obtained and the antineoplastic activities of the 5-fluorouracil derivatives were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 94–99, January, 1987.     

Metal Sorption,Solid Phase Extraction and Preconcentration Properties of Two Silica Gel Phases Chemically Modified with 2-Hydroxy-1-Naphthaldehyde

Active silica gel phase (I) was chemically modified to the corresponding amino- (SiNH₂) and chloro- (SiCl) derivatives via silylation reactions. These were used to synthesize two newly modified silica gel phases (II, III) by direct chemical reaction with 2-hydroxynaphthaldehyde (2-HNA). The surface coverage values are 370, 432µmolg^–1 and 320, 355µmolg^–1 for (II) and (III), on the basis of thermal desorption and metal probe testing method, respectively. The metal sorption properties of silica gel phases (II, III) were studied and compared with active silica gel phase (I). The maximum determined metal capacity values were found to be 10–110, 20–290 and 20–370µmolg^–1 for phases I, II and III, respectively. The distribution coefficient values (K_d) were also determined for a series of metal ions, and the results showed that the two new chemically modified phases (II and III) were highly selective for Cu²⁺, Zn²⁺, Cd²⁺, Hg²⁺ and Pb²⁺. The potential applications of silica gel phases (II, III) as solid phase extractors for the same five metal ions spiked in drinking tap water (1.000µgmL^–1) were found to give percentage recovery values in the range of 90.2–96.3±4.1–6.3%, while pre-concentration of the same five metal ions spiked in drinking tap water (50.0ngmL^–1) was successfully accomplished with a percentage recovery range of 92.6–95.8±4.8–5.7%.Received December 16, 2002; accepted May 14, 2003 published online September 1, 2003     

Synthesis of Side Chain Substituted 3-Butylisocoumarins and Absolute Configurations of Natural Isocoumarins from <Emphasis Type="Italic">Artemisia dracunculus</Emphasis>

Summary. A series of 3-hydroxy- and 3-bromobutyl-substituted isocoumarins was synthesized. The absolute configurations of three isocoumarin derivatives from Artemisia dracunculus, namely (–)-epoxyartemidin, (–)-2-methoxydihydroartemidin, and (+)-3-hydroxyartemidin were determined by chemical means via derivatization, kinetic racemate resolution (Horeau method), and comparison of the circular dichroism (CD) spectra.DeceasedReceived March 17, 2003; accepted March 19, 2003 Published online August 18, 2003     

Enantio-, Regio-, and Chemoselective Reduction of Aromatic α-Diketones by Baker’s Yeast

Summary. The enantio- and regioselective reduction of several symmetric and nonsymmetrically para-substituted benzil derivatives (21–92%) was achieved by means of Saccharomyces cerevisiae (bakers yeast). After modification of the reaction conditions reduction of nonsymmetric -diketones led chemoselectively to chiral -hydroxy ketones with up to 82% ee.Received December 16, 2002; accepted (revised) January 9, 2003 Published online July 28, 2003     

Synthesen von Derivaten des 1-Phenyl-1,2,3,4-tetrahydrochinolins

Zusammenfassung 1-Phenyl-1,2,3,4-tetrahydrochinolinderivate mit Substituenten (Methyl, Äthyl, Chlor, Methoxyl) in Stellung 6 und/oder 4 wurden dargestellt: Cyclisierung der entsprechenden -(Diphenylamin-N)-propionsäuren lieferte die 4-Oxoverbindungen. Die 4-Aminoderivate wurden durch Reduktion der 4-Hydroximinoverbindungen hergestellt.

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1-Phenyl-1,2,3,4-tetrahydroquinoline derivatives with substituents (methyl, ethyl, chloro, methoxyl) in position 6 and/or 4 were synthesized: cyclization of the corresponding diphenylaminopropionic acids yielded the 4-oxo compounds. The 4-amino derivatives were prepared by reduction of the 4-hydroximino compounds.

     

Regioselective Synthesis of Substituted Triazolium Salts <Emphasis Type="Italic">via</Emphasis> 1,3-Dipolar Cycloaddition Reactions

Summary. The regioselectivity of 1,3-dipolar cycloaddition reactions of 1-aza-2-azoniaallene salts with ,-unsaturated nitriles such as acrylonitrile or cyclohexylidene acetonitrile afforded only 1,2,4-triazolium salts via addition to the nitrile group, while the other expected pyrazolium salts were not observed. Moreover, 1-aza-2-azonia-allene salts reacted with other competitive systems such as -iminonitrile derivatives yielding only triazolium salts via addition to the nitrile and not to the imino group. Treatment of cumulene with 3-pyridylnitrile afforded the pyridinium salt. However, 2,3-dimethyl-5-(2,6-dimethoxyphenyl)-[1,2,4]triazole could be prepared from cumulene and 2,6-dimethoxybenzonitrile. Some reactions of nitriles with 1-aza-2-azonia-allene salts prepared from 1,2,3-indantrione and 9-acetylphenanthrene are discussed.     

Flow-Through Bulk Optode for the Spectrophotometric Determination of Perchlorate

A flow-through spectrophotometric bulk optode for the flow-injection determination of perchlorate is described. As active constituents, the optode incorporates the lipophilic pH indicator 5-octadecanoyloxy-2-(4-nitrophenylazo) phenol and methyltridodecyl ammonium chloride, dissolved in a plasticized poly(vinyl chloride) membrane which is entrapped in a cellulose support. The optode is applied in conjunction with the flow injection technique at pH 8.2 (TRIS buffer). The sensor is readily regenerated with a 10^–2M NaOH carrier solution. The analytical characteristics of this optode with respect to response time, dynamic measurement range, reproducibility and selectivity are discussed. The proposed FI method is applied to the determination of perchlorate in waters from different sources.Received December 16, 2002; accepted May 16, 2003 Published online August 8, 2003