Saturated heterocycles. Part 209. Synthesis of 1-cyclohexyl-substituted isoquinoline derivatives

In contrast with earlier literature data [7], both acrylic esters and acrylonitrile underwent Michael addition to l-methyl-3,4-dihydroisoquinolines 1-4 to yield the diesters 5-9 or the dinitrile 10 , respectively. Compounds 5-10 were converted by Claisen condensation to 1-[(3′-methoxycarbonyl- or 1-[(3′-ethoxycarbonyl-4′-oxo)-l'-cyclohexyl]-3,4-dihydroisoquinoline derivatives 11-16 . Several derivatives of 12 were prepared. The new compounds possess various pharmacological actions.     

Application of an androgen receptor assay for the characterisation of the androgenic or antiandrogenic activity of various phenylurea herbicides and their derivatives.

The potency of different substances for [3H]dihydrotestosterone ([3H]DHT) displacement from the bovine androgen receptor was tested. The phenylurea herbicide linuron and its derivative 3,4-dichloroaniline (3,4-DCA), which are found in sediments and surface waters, are known to displace bound testosterone from the rat androgen receptor. Because 3,4-DCA is rapidly taken up by fish and metabolised into 3,4-dichloroacetanilide (3,4-DCAc), it was investigated whether the displacement effects are attributable to 3,4-DCA or to 3,4-DCAc. The potency of 3,4-DCAc androgen receptor binding was compared with that of several phenylurea compounds. In a radioreceptor assay with calf uterus cytosol as androgen receptor preparation, the specific binding of [3H]DHT, the endogenous ligand, was completely displaceable by increasing concentrations of 3,4-DCAc. The relative binding affinities (RBA) of the various compounds were about 1/10(4) to 1/10(5) of that of DHT. 3,4-DCAc had the relative highest affinity (1.31 x 10(-4)), followed by linuron, 3,4-dichlorophenylurea, flutamide, 3,4-DCA and diuron with the lowest RBA (2.4 x 10(-5)). Hence the metabolism of xenobiotic compounds has to be considered to estimate potential ecotoxiocological effects. This test not only can be used to screen for androgen- and antiandrogen-like substances in environmentally relevant samples such as surface waters, but might also be applied for drug testing and for residue monitoring.     

Vanadium reactions with 3,4–dihydroxyphenylethanoic acid in alcohol solutions. Aromatic ring degradation

The reaction of Vv with 3,4–dihydroxyphenylethanoic acid (3,4–DHPE) was studied by various spectroscopic techniques. Vanadium-catechol complexation is the first step, and is followed by stepwise ligand degradation, leading to several products, including AcOH. The mechanism of this degradation is investigated.     

Chemistry of Azobenzazole Systems. 3. Reactions of 2-Hydrazinobenzoxazole with Carbonyl Compounds

The reaction of 2-hydrazinobenzoxazole with various carbonyl compounds was studied. Only the corresponding azides were obtained with acylating agents such as acid anhydrides and acid chlorides and products with a fused triazole ring were not obtained. Only the corresponding hydrazones were obtained from furfural and 2-carboxy-3,4-dimethoxybenzaldehyde.     

An efficient approach to 3,4-disubstituted pyridin-2-ones. Formal synthesis of mappicine ketone

Treatment of 3,4-dihydro-3-tosylpyridin-2-one 5 with sodium hydride and then alkyl halides gave various 3,4-disubstituted pyridin-2-ones 6. Formal synthesis of mappicine ketone (1) was also reported.     

Directed lithiation of 4-halopyridines: Chemoselectivity,regioselectivity and application to synthesis

4-Chloro and 4-fluoropyridines were ortho-lithiated by n-butyllithium-TMEDA chelate or lithium diiso-propylamide at low temperature. The resulting 3-lithio 4-halopyridines were reacted with electrophiles which led to various 3,4-disubstituted pyridines. The versatility of this functionalization is enhanced by the 4-halogen reactivity towards nucleophiles such as water, methylate and amines. Some of the 3,4-disubstituted synthons were annelated to naphthyridine, xanthone and coumarin or condensed to Hantsch-ester or to “chlotrimazol” analogues. Lithiation of 4-fluoropyridine led in one step to 3,4-pyridyne, which was trapped by cycloaddition with furans.     

Constituents of Psiadia terebinthina A.J. Scott, an endemic Asteraceae from Mauritius

Kaemferol-3-methyl ether (1), quercetin-3-methyl ether (2), kaemferol-3,7-dimethyl ether (3), 3-caffeoyl quinic acid (4) and 3,4-O-dicaffeoyl quinic acid (5) have been isolated for the first time from the leaves of Psiadia terebinthina A.J. Scott (Asteraceae). The identity of the compounds 1-5 were confirmed by various spectroscopic methods.     

Pyridazines. XXXVII. Novel triazanaphthalene derivatives via intramolecular cyclization reactions of vic-disubstituted pyridazines

8-Phenylpyrido[3,4-d]pyridazines bearing various amino substituents at C-5 ( 7a-d, 8 ) were prepared from ethyl 5-benzyl-4-pyridazinecarboxylate 1 via the fused pyridone 5 . The isomeric 4-phenylpyrido[2,3-d]pyridazines having the amino functions attached to C-2 ( 10a-f ) were obtained by a one-pot cyclization of the amino ketone 1 with appropriate acetamide acetals. These novel triazanaphthalene derivatives are of interest as analogues of diuretic and antithrombotic agents.     

Growing graphene sheets from reactions with methyl radicals: a quantum chemical study.

Hydrogen abstraction reactions by methyl radicals on the zigzag and armchair edges of perylene are studied by density functional theory (DFT) to explore various growth pathways that seem to be in line with experimental observations. The DFT approach is validated by comparing the results obtained from calculations with six different functionals with those obtained from correlated ab initio methods, thereby emphasizing the calculation of reaction barriers. A useful compromise between accuracy and computational cost is provided by DFT, and possible pathways are studied in detail at this level of calculation. Our computational study is carried out by ordering, as a first step, all of the isomers that arise from the abstraction of one or two H atoms from 1,12-dimethyl-1,12-dihydroperylene and 3,4-dimethyl-3,4-dihydroperylene with respect to their energies. Subsequently, only those pathways that connect low-energy isomers are investigated. The calculations reveal that the selected pathways are favored thermodynamically, and also that the reaction barriers are somewhat higher than the energy locally available for the respective reaction. Notably, in the case of 3,4-dimethyl-3,4-dihydroperylene, the first two reaction steps have no or only a very low reaction barrier. The final conclusion of our study is that a cascade of reactions is possible that leads to the growth of a graphene sheet on a graphite surface.     

Studies on the syntheses of heterocyclic compounds. CLXXIV. An approach to the synthesis of oxyacanthine and berbamine

Schotten-Baumann reaction of the amine (X) with 4-benzyloxy-3,4′-oxydiphenylacetyl chloride (XI) gave two amides, (XIIa) and (XIIb), which were cyclized to give the corresponding 3,4-dihydroisoquinolines, respectively. Methylation of the above 3,4-dihydro-isoquinolines, followed by hydrolysis, afforded the compounds having the same composition as berbamine (Ia) and oxyacanthine (Ib), whose structures are under examination.     

First nucleophilic aromatic substitution of annelated pyrazole.

3-Chloropyrazolo[3,4-c]quinoline 5, 3-chloropyrazolo[3,4-c]isoquinoline 6, 1,2-dihydro-1,2-dimethylpyrazolo[3,4-c]quinolin-3-one 8, and 1,2-dihydro-1,2-dimethylpyrazolo[3,4-c]isoquinolin-3-one 10 were obtained by acid-induced nucleophilic aromatic substitution (S(N)H) of H-3 in N-hydroxypyrazolo[3,4-c]quinoline 1b and in N-hydroxy pyrazolo[3,4-c]isoquinoline 3b. In the acid-induced chlorination, 3b was far more reactive than 1b, whereas the related N-hydroxypyrazolo[4,3-c]quinoline 2b and N-hydroxypyrazolo[4,3-c]isoquinoline 4b were completely unreactive toward S(N)H under identical conditions.     

Ionic liquid phase organic synthesis (IoLiPOS) methodology applied to the preparation of new 3,4-dihydropyrimidine-2(1H)-ones bearing bioisostere group in N-3 position

The ionic liquid phase organic synthesis (IoLiPOS) methodology has been used for the preparation of new 3,4-dihydropyrimidine-2(1H)-ones (DHPMs) bearing bioisostere group in N-3 position. For the 3,4-DHPMs substituted with various thiazole rings, the strategy involved a three-component Biginelli condensation in the second step with good yields (93-96%) from ILP bound acetoacetate, aromatic aldehyde (93-97% yield), and N-methyl urea followed by N-3 alkylation with chloroacetonitrile on the ILP bound 3,4-DHPM. Quantitative thionation of the nitrile group grafted on the ILP bound 3,4-DHPM was realized in MeOH with a 40-48% solution of ammonium sulfide and subsequent addition of α-bromoketone produced the thiazole ring appended on the 3,4-DHPM core. After cleavage by transesterification, the target compounds were obtained in good overall yields (47-50%). The efficiency of the IoLiPOS methodology was also demonstrated by the preparation of new 3,4-DHPMs with a tetrazole ring in N-3 position in 5 steps (53-61% overall yield) via the ILP bound 3-cyanomethyl 3,4-DHPM as key intermediate.     

The Synthesis and Reactions of Dialkyl 1-Vinylvinyl-Phosphates

3,4-Dichlorobutanone reacts with trialkyl phosphites to give dialkyl 1,3-butadien-2-yl phosphates. Their structures were determined by spectroscopic methods and various chemical reactions.     

An enantioselective approach toward 3,4-dihydroisocoumarin through the bromocyclization of styrene-type carboxylic acids

A facile and enantioselective approach toward 3,4-dihydroisocoumarin was developed. The method involved an amino-thiocarbamate catalyzed enantioselective bromocyclization of styrene-type carboxylic acids, yielding 3-bromo-3,4-dihydroisocoumarins with good yields and ee's. 3-Bromo-3,4-dihydroisocoumarins are versatile building blocks for various dihydroisocoumarin derivatives in which the Br group can readily be modified to achieve biologically important 4-O-type and 4-N-type 3,4-dihydroisocoumarin systems. In addition, studies indicated that, by refining some parameters, the synthetically useful 5-exo phthalide products could be achieved with good yields and ee's.     

Novel heteropentalenes. Synthesis of heteropentalenes from tetrahydroimidazo [1.2-d]-(1,2,4)-thiadiazoles and conversion of certain heteropentalenes to benzothiazole derivatives

Oxidation of 1 - phenylcarbamoylidazolidine - 2 - thione gives 2,3,5,6 - tetrahydro - 2 - phenylimidazo [1,2-d]- (1,2,4) - thiadiazole - 3 - one which undergoes addition reactions with heterocumulenes leading to various heteropentalenes. Oxidation of 1 - phenylthiocarbamoylimidazlidine- 2 - thione yields 1- (benzothiazol - 2- yl) - imidazolidine - 2 - thione, also obtained by acid catalysed decomposition of 3,4 - ethano - 2,3,4,5 - tetrahydro - 2, 5 - bisphenylimino - 1,6,6aS^IV - trithia - 3,4 - diazapentalene. A similar acid catalysed decomposition to a benzothiazole occurs with 2,3,4,5 - tetrahydro - 1,6 - diphenyl - 3,4 - propano - 6aS^IV - thia - 1,3,4,6 - tetraazapentalene -2, 5- dithione.     

Synthesis and antioxidative properties of some 3,4-dihydropyrimidin-2(1H)ones (-thiones)

3,4-Dihydropyrimidinones (-thiones) were prepared by ternary condensation of various aromatic aldehydes with ethyl acetoacetate and urea (thiourea) in the presence of trichloroacetic acid in ethanol.     

Studies on phenothiazines. Part 16 . Synthesis and spectral studies of substituted 1,2-dichlorophenothiazines

Synthesis of the title compounds by the Smiles rearrangement has been reported. 1,2-Dichloro-7-substituted phenothiazines have been prepared by the Smiles rearrangement of 3,4-dichloro-2-formamido-2′-nitro-4′-substituted-diphenyl sulphides. The latter were obtained by the formylation of the diphenyl sulphides obtained by the condensation of 2-amino-3,4-dichlorobenzenethiol with o-halogenonitrobenzenes. 9-Nitrophenothiazines have been prepared by the reaction of 2-amino-3,4-dichlorobenzenethiol with substituted o-halonitrobenzenes containing a nitro group at both ortho positions to the halo atom in which Smiles rearrangement occurs in situ. The ir, nmr and mass spectral studies are also included.     

Oxidation of Polyisoprene Popcorn Polymer. V. Raman Spectra of Polyisoprene Popcorn Polymer Following Oxidation

From Raman spectral data, no decrease in the double-bond content of polyisoprene popcorn polymer was detected following various periods of oxidation. No conclusion could be made concerning the fate of the 1,2 or 3,4 vinyl-group attachments.     

Measurement uncertainty arising from trueness of the analysis of two endocrine disruptors and their metabolites in environmental samples. Part I: ultrasonic extraction from diverse sediment matrices

The validation of preconcentration strategies for the simultaneous determination of two endocrine disrupting compounds (EDCs) and their metabolites present in the aquatic environment including natural waters and freshwater sediments as well as the estimation of uncertainty arising from trueness using fully nested experimental designs are presented in a series of two papers. In this work, we present Part I of our ongoing study, the validation of an analytical method based on ultrasonic extraction of the target analytes from various freshwater sediments and the estimation of the method measurement uncertainty. The selected endocrine disruptors included two widely used herbicides, diuron (1-(3,4-dichlorophenyl)-3,3-dimethylurea) and linuron (3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea) and their common degradation products namely, 3,4-dichloroaniline (3,4-DCA), 1-(3,4-dichlorophenyl) urea (DCPU) and 1-(3,4-dichlorophenyl)-3-methylurea (DCPMU). A high-performance liquid chromatography system coupled to UV-diode array detector (HPLC/UV-DAD) was used for the target analytes quantification. A fully nested experimental design was applied to study the measurement uncertainty arising from trueness by estimating proportional bias (in terms of recovery). The overall recoveries, that is, those determined by the nested experiments were in the range of 59.5-85.1%, except 3,4-DCA for which a low overall recovery of 29.0% was observed. The analytical method was shown to be linear over the studied range of concentrations (5-100 microg/kg), exhibiting satisfactory repeatability and reaching limits of detection usually in the 0.6-4.6 microg/kg range on dry sediment basis. The method used permitted the determination of the target EDCs and their metabolites in sediment samples collected from selected study stations in the region of Epirus (N.W. Greece) at the concentration levels demanded by current legislation.     

3, 6-二芳基-5, 6-二氢均三唑[3, 4-b][1, 3, 4]噻二唑的合成 及生物活性

研究了在L-(+)-酒石酸存在下3-芳基-4-氨基-5-巯基-1,2,4-均三唑与醛的Mannich反应及分子内的加成反应,合成了15个新的手性稠杂环化合物3,6-二芳基-5,6-二氢均三唑[3,4-b][1,3,4]噻二唑,利用IR、^1HNMR和MS确证了其结构,并测试了部分化合物的生物活性。