4-alkyl(aryl)-1-germacyclohexa-2,5-diene

enThe 1(Z),4(Z)-1,5-dilithium-3R-3-methoxypenta-1,4-dienes react with diaryldichlorogermanes and dialkyldichlorogermanes to give the 1,1-diaryl- and 1,1-dialkyl-4R-4-methoxy-1-germacyclohexa-2,5-dienes, respectively.With phenyltrichlorogermane, methyl- and ethyl-trichlorogermanes the E/Z-isomeric 1-phenyl(methyl,ethyl)-1-chloro-4R-4-methoxy-1-germacyclohexa-1,3-dienes are obtained, reduction of these with LiAlH₄ makes the corresponding 1-aryl-(alkyl)-1H-4R-4-methoxy-1-germacyclohexa-2,5-dienes available.Reduction of 1-ethyl-1-chloro-4-phenyl-4-methoxy-1-germacyclohexa-2,5-diene with LiAlH₄ yields by additional ether cleavage 1-ethyl-1H-4-phenyl-1-germacyclohexa-2,4-diene.The ¹H NMR (60 MHz, 90 MHz), ¹³C NMR, IR and mass spectra are discussed, several ¹H NMR spectra are calculated according to the LAOCOONLAME program.     

A facile synthesis of (E)-3-styryl-1-phenyl cyclohepta[c]pyrazol-8(1H)-ones

A facile synthesis of some novel (E)-3-styryl-1-phenylcyclohepta[c]pyrazol-8(1H)-ones via the condensation reaction of 3-cinnamoyltropolones with phenylhydrazine is described. All the synthesized compounds were obtained in good yields of 62–69 % and their structures were characterized by IR, ¹H NMR, MS, and elemental analysis. This procedure offers easy access to tropone-fused pyrazole derivatives in short reaction times, and the products are achieved in good yields.     

Ultrasound- and microwave-assisted synthesis of (E)-1-aryl-3-[2-(piperidin-1-yl)quinolin-3-yl]prop-2-en-1-ones and (E)-1-aryl-3-[2-(pyrrolidin-1-yl)quinolin-3-yl]prop-2-en-1-ones,and their antimicrobial activity

Series of new (E)-1-aryl-3-[2-(piperidin-1-yl)quinolin-3-yl]prop-2-en-1-ones and (E)-1-aryl-3-[2-(pyrrolidin-1-yl)quinolin-3-yl]prop-2-en-1-ones have been efficiently prepared via the Claisen-Schmidt condensation of 2-(piperidin-1-yl)quinoline-3-carbaldehyde and 2-(pyrrolidin-1-yl)quinoline-3-carbaldehyde, respectively, with aryl methyl ketones under conditions of ultrasound and microwave irradiation. Structures of the products have been confirmed by IR, ¹H NMR, ¹³C NMR, and mass spectroscopy, as well as by elemental analysis. Evaluation of the in vitro antibacterial activity against bacterial (Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli) and fungal (Aspergillus niger and Candida metapsilosis) strains has revealed good antimicrobial activity of some of the tested compounds.     

Synthesis,spectral characterization and biological evaluation of novel 1-(2-(4,5-dimethyl-2-phenyl-1H-imidazol-1-yl)ethyl)piperazine derivatives

A simple, highly useful synthesis of 1-(2-(4,5-dimethyl-2-phenyl-1H-imidazol-1-yl)ethyl)piperazine derivatives is achieved by a four component cyclo condensation of diacetyl, aromatic aldehyde, 2-(piperazin-1-yl)ethanamine and ammonium acetate using SO₄²⁻/Y₂O₃ as a catalyst in ethanol. The synthesized compounds were characterized by IR, ¹H and ¹³C NMR and mass spectral studies. All the synthesized compounds were screened for their in vitro antimicrobial studies. Among the newly synthesized compounds 5d, 5e, 5h and 5m showed excellent antibacterial and antifungal activities when compared to the standard drugs.     

Synthesis and structure of bis[1-(1-adamantyl)-4,4,4-trifluorobutane-2,4-dionato]copper

Previously unknown 1-(1-adamantyl)-4,4,4-trifluorobutane-2,4-dione and its copper complex, bis [1-(1-adamantyl)-4,4,4-trifluorobutane-2,4-dionato]copper, were synthesized. The ¹H NMR, IR, and ESR spectra and X-ray diffraction patterns of the synthesized compounds were obtained. Volatilily and thermal stability of the copper complex were studied by thermogravimetric analysis and differential scanning calorimetry.     

Synthesis of newN-acylantipyrylureas and the crystal structure ofN-benzoyl-N′-[4-(2,3-dimethyl-1-phenylpyrazol-5-one)]urea

New derivatives of acylheterylureas were synthesized by reactions of acylisocyanates with 4-amino-2,3-dimethyl-l-phenylpyrazol-5-one. The structures of the compounds obtained have been established by IR and¹H NMR spectroscopy.N-Benzoyl-N′-[4-(1-phenyl-2,3-dimethylpyrazol-5-one)]urea has been studied by X-ray structural analysis. It was found that the molecule adopts ananti-syn conformation stabilized by an intermolecular hydrogen bond. In the crystal, molecules are linked in centrosymmetric dimers via intermolecular hydrogen bonds.     

Synthesis and Structure of Metal Complexes of 1-(1-R-3-Methylpyrazole-5-onilidene-4)-1,2,3,4-tetrahydroisoquinoline Derivatives

Twenty new complexes were synthesized by reacting Co(II), Cu(II), Zn, Cr(III), Fe(III), Cd and Ag salts with 3,3-dimethyl-1-(3-methylpyrazole-5-onilidene-4)-1,2,3,4-tetrahydroisoquinoline (L¹), spiro{cyclohexane-1,3"-[1-(1-phenyl-3-methylpyrazole-5-onilidene-4)-1,2,3,4-tetrahydroisoquinoline]} (L²), and 3,3-dimethyl-1-(1-phenyl-3-methylpyrazole-5-onilidene-4)-1,2,3,4-tetrahydroisoquinoline (L³). These compounds were studied by IR and electronic absorption spectroscopy. The type of coordination of their ligands was discussed on the basis of the results obtained and X-ray diffraction data for L³ and [CuL₂ ² Cl₂] · 2L² obtained previously.     

Steric mode of enzymic hydroxylation at primary carbon atoms: Hydroxylation of (1R)- and (1S)-[1-3H, 2H, 1H][1-14C]-octanes by Pseudomonas Oleovorans

(1R)- and (1S) [1-³H, ²H, ¹H]-octanes and mixed with [1-¹⁴C]-octane, were synthesized. The mixed samples were incubated with homogenats of P. oleovorans strain TF4-1L and the biosynthesized mixtures of octanols isolated. It was shown that mainly the achiral termini [-C¹H₃] were hydroxylated and that chiral methyls were oxygenated to the extent of 20–30%. In all instances the products derived from hydroxylation at the chiral methyls [-C-³H, ²H, ¹H] were mixtures of (1R)- and (1S)-octanols, the major component of which was the alcohol obtained by displacement of ¹H. The results indicate that hydroxylation proceeded with a normal isotope effect k_h>k_d>k_t. The amount of (1R)-octanol in the mixtures of octanols derived from (1R)- and (1S)-octane was determined. It was found that the C-1 hydroxylation of octane proceeded with retention, i.e. the incoming hydroxyl assumed the orientation of the displaced hydrogen (or isotopic hydrogen) atom.     

1-( p -Fluorophenyl)-2-(2′-pyridyl)ethanol and 1-( p -fluorophenyl)-2-(2′-pyridyl)ethene obtained from the condensation reaction of 2-picoline and p -fluorophenylaldehyde under catalyst-and solvent-free conditions

The novel intermediate 1-(p-fluorophenyl)-2-(2′-pyridyl)ethanol or 2-[2′-(1-hydroxy-1-(p-fluorophenyl)ethyl]pyridine and the corresponding novel dehydration compound 1-(p-fluorophenyl)-2-(2′-pyridyl)ethene or 2-[p-fluorophenylvinyl]pyridine were obtained from the condensation reaction of p-fluorophenylaldehyde and 2-picoline under catalyst-and solvent-free conditions. The intermediate 1-(p-fluorophenyl)-2-(2′-pyridyl)ethanol was obtained at 42 h reaction time and temperature of 120°C, respectively. ¹H-NMR, IR spectroscopic data of the 1-(p-fluorophenyl)-2-(2-pyridyl)ethanol clearly showed the presence of the-CH₂-CHOH-group. The compound was obtained as a white powder with m.p. 121–122°C and a yield of 8%. For 1-(p-fluorophenyl)-2-(2-pyridyl)ethene, the reaction conditions were similar, but the reaction temperature was increased to yield the double bond in the 1-(p-fluorophenyl)-2-(2′-pyridyl)ethene. At the reaction temperature of 140°C, the compound was a slightly brown powder with a m.p. of 78°C and yield of 18%. ¹H-NMR, IR spectroscopic data for the 1-(p-fluorophenyl)-2-(2′-pyridyl)ethene showed the presence of a double bond in trans configuration (-CH=CH-), characteristic of a styrylpyridine.     

Synthesis and antifungal activity of novel 1-(1H-benzoimidazol-1-yl)propan-2-one oxime-ethers containing the morpholine moiety

A series of 1-(2-(4-morpholinomethyl)-1H-benzoimidazol-1-yl)propan-2-one oxime-ethers have been synthesized from 2-chloromethyl-1H-benzoimidazole, morpholine, bromoacetone, hydroxylamine, and a haloalkane (or benzyl halide). Their structures were elucidated by IR, ¹H NMR, elemental analysis, and MS. Antifungal activity against Botrytis cinerea, Sclerotinia sclerotiorum, and Beans sclerotia was evaluated by the mycelium growth-rate method; the results indicated that many of the target compounds have excellent antifungal activity, even higher than that of the control fungicide (carbendazim).     

Extraction of Iridium(IV) by 1-(2-(2,4-Dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl-methyl)-1H-1,2,4-triazole from Hydrochloric Solutions

Extraction of iridium(IV) by 1-(2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl-methyl)-¹H-1,2,4-triazole from hydrochloric solutions was studied. Optimal extraction parameters were determined. The mechanism of iridium(IV) extraction in this system is ion exchange (3.0 mol/L HCl and τ_cont = 5 min). Electronic, ¹H NMR, ¹³C NMR, and IR spectroscopy and elemental analysis were used to determine the composition of the extracted compound.     

Gold(III) and palladium(II) extraction from hydrochloric acid solutions with (RS)-1-[2-(2,4-dichlorophenyl)pentyl]-1H-1,2,4-triazole

Gold(III) and palladium(II) extraction from 3 mol/L hydrochloric acid solutions with (RS)-1-[2-(2,4-dichlorophenyl)pentyl]-1H-1,2,4-triazole (chloroform diluent) was studied. Optimal extraction conditions were found. Coordination mechanism of extraction was established on the basis of IR and NMR spectra of extracted compounds. Concentrational extraction constants were calculated and thermodynamic parameters of the process were assessed.     

Hydrogen Bonds in 2-(Diorganylphosphorylhydroxymethyl)-1-organylimidazoles

Structures of 2-(diorganylphosphorylhydroxymethyl)-1-organylimidazoles were studied by IR and ¹H and ^{3 1}P NMR spectroscopy, and also by ab initio calculations (HF/6-31G*). Formation of intramolecular O-H+++O = P hydrogen bonds in solutions of these compounds in CCl₄ and CHCl₃ was established.     

Solution properties of poly[1-(9-carbazyl)-2,3-(diethoxycarbonyl)-butane-1,4-diyl]

Poly[1-(9-carbazyl)-2,3-(diethoxycarbonyl)-butane-1,4-diyl] (I), obtained by radical copolymerization of 9-vinylcarbazole with diethylfumarate, has been characterized by viscometry and light scattering. The Huggins constant in benzene at 25 is k_H = 0.33. The Mark-Houwink relationship suggests that benzene is a good solvent for the alternating copolymer I (a = 0.67; K = 1.46·10^?2 ml/g). The unperturbed dimension of the chain is given by value (R₀²/M)^0.5 = 5.73·10^?9 cm·mol^0.5 g^?0.5. The steric factor σ = 2.51 indicates a higher flexibility for this polymer than for poly[1-(9-carbazyl)ethylene].     

Radioiodination of 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine, 4-(3-iodobenzyl)-1-(benzylsulfonyl)piperazine and their derivatives via isotopic and non-isotopic exchange reactions

A mild and simple technique for preparing of 4-benzyl-1-(3-[¹²⁵I]iodobenzylsulfonyl)piperidine, 4-(3-[¹²⁵I]iodobenzyl)-1-(benzylsulfonyl)piperazine and their derivatives, as sigma-1 receptor ligands, with relatively high radiochemical yields via nucleophilic substitution reaction by means of isotopic and non-isotopic exchange reactions is described. Some factors affecting the radiochemical yield were commonly studied in presence of acidic medium at elevated temperature. Unfortunately, the radiochemical yields were weak. Some attempts were carried out in presence of polar aprotic solvents to enhance the radiochemical yield. N,N-Dimethylformamide was proved highly efficient for preparing of radioiodinated 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine (4-B-[¹²⁵I]-IBSP, 70 ± 5.7 %) and 4-(3-iodobenzyl)-1-(benzylsulfonyl)piperazine (4-[¹²⁵I]-IBBSPz, 72 ± 6.0 %) at moderate temperature (100–105 °C) within 8 h. The specific activities of 4-B-[¹²⁵I]-IBSP and 4-[¹²⁵I]-IBBSPz (6,534.2 and 5,927.4 MBq/mmol) were obtained respectively.     

Synthesis and characterization of the two enantiomers of a chiral sigma-1 receptor radioligand: (S)-(+)- and (R)-(-)-[18F]FBFP

Racemic [¹⁸F]FBFP ([¹⁸F]1) proved to be a potent σ₁ receptor radiotracer with superior imaging properties. The pure enantiomers of unlabeled compounds (S)- and (R)-1 and the corresponding iodonium ylide precursors were synthesized and characterized. The two enantiomers (S)-1 and (R)-1 exhibited comparable high affinity for σ₁ receptors and selectivity over σ₂ receptors. The Ca²⁺ fluorescence assay indicated that (R)-1 behaved as an antagonist and (S)-1 as an agonist for σ₁ receptors. The ¹⁸F-labeled enantiomers (S)- and (R)-[¹⁸F]1 were obtained in >99% enantiomeric purity from the corresponding enantiopure iodonium ylide precursors with radiochemical yield of 24.4% ± 2.6% and molar activity of 86–214 GBq/µmol. In ICR mice both (S)- and (R)-[¹⁸F]1 displayed comparable high brain uptake, brain-to-blood ratio, in vivo stability and binding specificity in the brain and peripheral organs. In micro-positron emission tomography (PET) imaging studies in rats, (S)-[¹⁸F]1 exhibited faster clearance from the brain than (R)-[¹⁸F]1, indicating different brain kinetics of the two enantiomers. Both (S)- and (R)-[¹⁸F]1 warrant further evaluation in primates to translate a single enantiomer with more suitable kinetics for imaging the σ₁ receptors in humans.     

An efficient synthesis of dialkyl 2-(diphenoxyphosphoryl)-3-(alkylthio)succinates from alkylthiols, triphenyl phosphite and dialkyl acetylenedicarboxylates

An efficient synthesis of dialkyl 2-(diphenoxyphosphoryl)-3-(alkylthio)succinates, as a mixture of two diastereomers, in 78–90% yields, is described via reaction between alkylthiols, dialkyl acetylenedicarboxylates, and triphenyl phosphite. The structures of products were deduced from their high-field ¹H, ¹³C, and ³¹P NMR spectra, and IR spectral data. Since these hosphonate esters possess two stereogenic centers, two diastereomers with gauche HCCH arrangements are possible. Observation of ³ J _HH = 3.5-4.6 Hz for the vicinal methine protons confirmed the dominance of the gauche arrangement. A mechanism is proposed for the formation of products.     

Homochiral (R)- and (S)-1-heteroaryl- and 1-aryl-2-propanols via microbial redox

Preparation of various heteroaryl propanols 2a–g and of the corresponding propanones 3a–g as starting materials for microbial redox is described. The kinetic resolution of the racemic propanols 2a–g is obtained via oxidation with Pseudomonas paucimobilis and Bacillus stearothermophilus [(R)-alcohols, ee 74–100%]. Similar results are achieved with 3-(2-hydroxypropyl)trifluoromethylbenzene 7 (44%, ee 100% of the (R)-alcohol 6). The reduction of the propanones 3a–d and 3g with baker's yeast and other fungi gives the (S)-alcohols (ee 100%). The pure (S)-alcohols are also obtained by reduction of 1-[3-(trifluoromethyl)phenyl]-2-propanone 7. 1-[(4,4-Dimethyl)-2-(Δ²)oxazolinyl]-2-propanone 3e and 1[2-(Δ²)-thiazolinyl)-2-propanone 3f are not reduced. The heterocyclic rings of (S)-5-(2-hydroxypropyl)-3-methylisoxazole 2d and of (S)-2-(2-hydroxypropyl)-4-methylthiazole 2g are deblocked to the homochiral enamino ketone 8 (78%) and to the protected β-hydroxy aldehyde 9 (73%), respectively. The (R)-3-(2-hydroxypropyl)trifluoromethylbenzene 6 is transfomed into the homochiral precursor of (S)-fenfluramine 10 (overall yield 65%).     

Preparation of highly enantiopure stereoisomers of 1-(2,6-dimethylphenoxy)-2-aminopropane (mexiletine)

Mexiletine [1-(2,6-dimethylphenoxy)-2-aminopropane], an orally effective antiarrhythmic agent, exhibits enantioselective pharmacokinetics and pharmacodynamics during mexiletine therapy. The purpose of this paper is to emphasize the advantage of tetrahydropyranyl-protected mandelic acid (THPMA) in the resolution of mexiletine enantiomers. Both enantiomers of mexiletine were obtained in 99% enantiomeric excess. Judging by the differential shielding effects in the ¹H and ¹³C NMR analyses, we have observed the opposite predominant conformation for the mexiletine mandelates in comparison with the O-methylmandelates.     

2-Alkyl-4-amino-5-(tert-butyl-NNO-azoxy)-2H-1,2,3-triazole 1-oxides: synthesis and reduction

A new approach to the synthesis of 4-amino-5-(tert-butyl-NNO-azoxy)-2-R-2H-1,2,3-triazole 1-oxides 1 was developed. Compounds 1 were obtained by reactions of 3-amino-4-(tert-butyl-NNO-azoxy)furoxan with aliphatic amines RNH₂ (R = Me, Et, Prⁱ, Bu, and Bu^t). 4-Amino-5-(tert-butyl-NNO-azoxy)-2-tert-butyl-2H-1,2,3-triazole 1-oxide was transformed under the action of acids into 4-amino-5-(tert-butyl-NNO-azoxy)-1-hydroxy-1H-1,2,3-triazole. Methylation of the latter with diazomethane mainly involves the O atom of the triazole oxide ring. Reduction of compounds 1 gave 4-amino-5-(tert-butyl-NNO-azoxy)-2-R-2H-1,2,3-triazoles and 4-amino-5-(tert-butyldiazenyl)-2-R-2H-1,2,3-triazoles (R = Me, Prⁱ, and Bu^t). The structures of the compounds obtained were confirmed by ¹H, ¹³C, and ¹⁴N NMR spectroscopy.