Synthesis and structure of some azo coupled cyclic beta-enaminones

The reaction of 3-phenylaminocyclopent-2-en-1-one with 4-methyl, 4-methoxy and 4-chlorobenzenediazonium tetrafluoroborates was used to prepare the azo coupling products 3a-c. It was found that these compounds are present in both CDCl(3) solution and solid phase practically exclusively as (E)-3-phenylamino-2-(4-subst.phenyldiazenyl)cyclopent-2-en-1-ones with N--H...N intramolecular hydrogen bond. The substitution of the phenyl residue of the diazonium salt has no effect on the position of the tautomeric equilibrium. On the other hand, the compounds 4a, b formed by the reaction of 3-phenylamino-1H-inden-1-one with 4-methylbenzene- or benzenediazonium tetrafluoroborates exist in CDCl(3) solution and in solid phase as hydrazone compounds. In the solution they occur as a mixture of three forms, out of which two were identified as E/Z isomers with different types of hydrogen bonds. Compound 5 formed by the reaction of 3-amino-5,5-dimethylcyclohex-2-en-1-one with 4-methoxybenzenediazonium tetrafluoroborate is converted into a stable hydrochloride 5.HCl on standing in CHCl(3) solution; this product exhibits a high degree of delocalization of the positive charge. Its structure was studied by means of X-ray.     

Synthesis, NMR and X-ray characterisation of 6-substituted 4-amino-5-aryldiazenyl-1-arylpyridazinium salts

A new simple method has been used to prepare 6-substituted 4-(subst. amino)-5-aryldiazenyl-1-arylpyridazinium salts from N-methyl- or N-aryl-3-amino-1-phenylbut-2-en-1-ones and 4-aminopent-3-en-2-ones and substituted benzenediazonium tetrafluoroborates or hexafluorophosphates. The structure of selected derivatives was studied by means of ¹⁵N NMR spectra and X-ray.     

An NMR and X-ray study of the structure of the azo coupling product of 4-dimethylaminopent-3-en-2-one and benzenediazonium-tetrafluoroborate

4-Dimethylaminopent-3-en-2-one reacts with two molecules of benzenediazonium-tetrafluoroborate to give compound 1. The structure of this compound was determined by means of X-ray analysis of its crystal and 1H, 13C and 15N NMR spectra of its solution in CDCl3. The molecule of this compound contains one azo group and one hydrazone group. The substance exists, both in crystal form and in solutions of concentrations above 0.1 mol l(-1), in the form of a dimer, in which the pair of molecules are bound by two hydrogen bonds N-H...N. On diluting the solution, the dimers decompose, the two forms being in an equilibrium that is rapid on the NMR time scale.     

Dibenzodiazepines in reactions of 2-acetyl-dimedone with 3,4-diaminobenzophenone

The reactions of 2-acetyldimedone and 2-acetyl-3-methoxy-5,5-dimethylcyclohex-2-en-1-one with 3,4-diaminobenzophenoneproduce2-[1-(2-amino-5-benzoylphenyl)amino]ethylidene-5,5-dimethyl-1,3-cyclohexanedioneand 2-acetyl-3-(2-amino-5-benzoylphenyl)amino-5,5-dimethylcyclohex-2-en-1-one, which are cyclized by the action of hydrochloric acid, yielding the respective hydrochlorides of 8-benzoyl- and 7-benzoyl-3,3,11-trimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepin-2-ones. Hydrolytic cleavage of the 8-benzoyl derivative leads to 2-acetyl-3-(2-amino-4-benzoylphenyl)amino-5,5-dimethylcyclohex-2-en-1-one. A similar cleavage to form 2-acetyl-3-(2-aminophenyl)amino-5,5-dimethylcyclohex-2-en-1-one is observed for the known hydrochloride of 3,3,11-trimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepin-2-one. The structures of the products were confirmed by PMR spectra and x-ray diffraction data.Riga Technical University, Riga LV-1658. Latvian Institute of Organic Chemistry, Riga LV-1006. University of Cincinnati, Ohio, USA. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 379–391, March, 1997.     

Cytotoxic diterpenoids from Vietnamese medicinal plant Croton tonkinensis GAGNEP

Six new ent-kaurane-type diterpenoids were isolated from the leaves of the endemic Vietnamese medicinal plant Croton tonkinensis GAGNEP. (Euphorbiaceae) together with three known ent-11alpha-acetoxy-7beta,14alpha-dihydroxykaur-16-en-15-one (1), ent-kaur-16-en-15-one 18-oic acid (5) and ent-18-hydroxykaur-16-ene (7). Their structures were determined by spectroscopic analyses to be ent-7beta-acetoxy-11alpha-hydroxykaur-16-en-15-one (2), ent-18-acetoxy-11alpha-hydroxykaur-16-en-15-one (3), ent-11alpha-acetoxykaur-16-en-18-oic acid (4), ent-15alpha,18-dihydroxykaur-16-ene (6), ent-11alpha,18-diacetoxy-7beta-hydroxykaur-16-en-15-one (8), and ent-(16S)-1alpha,14alpha-diacetoxy-7beta-hydroxy-17-methoxykauran-15-one (14). ent-Kaurane-type diterpenoids from Croton tonkinensis 2-4, 6, and 9-13, were tested for toxicity in the brine shrimp lethality assay. Compounds 9, 10, and 12 demonstrated significant activity, compounds 2, 3, 6, and 11 showed weak activity, and compounds 4 and 13 were inactive.     

13C NMR spectra of non-labelled and 15N-mono-labelled azo dyes

¹³C NMR spectra of four types of azo coupling products from benzenediazonium chloride have been measured and interpreted, viz. hydrazo compounds with an intramolecular hydrogen bond (3-methyl-1-phenylpyrazole-4,5-dione 4-phenylhydrazone), azo compounds without an intramolecular hydrogen bond (4-hydroxyazobenzene), azo compounds with an intramolecular hydrogen bond (2-hydroxy-5-tert-butylazobenzene) and an equilibrium mixture of both the tautomers of 1-phenylazo-2-naphthol. The absolute values of the J(¹⁵N¹³C) coupling constants have been determined by recording the spectra of the ¹⁵N isotopomers, and have been used, in some cases, for ¹³C signal assignment. A relationship has been found between the chemical shifts of the C-1′ to C-4′ carbons of the phenyl group (from the benzenediazonium ion) or the ¹J(¹⁵N¹³C) coupling constant, and the composition of the tautomeric mixture.     

Brominations of steroidal hormone having alpha,beta-unsaturated ketone, 17-O-acetyltestosterone, in the presence of silver triflate

Bromination of 17-O-acetyltestosterone (17beta-acetoxyandrost-4-en-3-one) (1) was performed with 1, 5, and 10 eq of Br2 in AcOH-Et2O at room temperature. In all cases 2alpha,6beta- (2) and 2alpha,6beta-dibromo-17beta-acetoxyandrost-4-en-3-one (3) were obtained, although the yields were dependent upon the conditions used. Bromination of compound 1 with 10 eq of Br2 in the presence of silver trifluoromethanesulfonate (silver triflate, AgOTf) at room temperature for 12 h gave 2,7alpha-dibromo- (4) and 2,4,7alpha-tribromo-17beta-acetoxy-3-hydroxy-1-methylestra-1,3,5(10)-triene-6-one (5). The formations of the products were inferred on the basis of products obtained under controlled brominations of 1 in the presence of AgOTf, and of those obtained by the brominations of compounds 9-13 also in the presence of AgOTf.     

2,3-Diferrocenylcyclopropenone in the reaction with organomagnesium compounds

The reactions of 2,3-diferrocenylcyclopropenone with ethyl- and benzylmagnesium chlorides afford 3,3-diethyl- and 3,3-dibenzyl-1,2-diferrocenylcyclopropenes along with products of nucleophilic opening of the three-membered ring: ,-unsaturated and saturated ketones (cis-1,2-diferrocenylpent-1-en-3-one and cis-1,2-diferrocenyl-4-phenylbut-1-en-3-one, 4,5-diferrocenylheptan-3-one, and 3,4-diferrocenyl-1,5-diphenylpentan-2-one). The products of insertion of intermediate diferrocenyl(vinyl)carbene at one of the -bonds of the starting 2,3-diferrocenylcyclopropenone were also isolated: 4-(2-oxo-1-ferrocenylbutyl)- and 4-(2-oxo-3-phenyl-1-ferrocenylpropyl)-2,3,4-triferrocenylcyclobutenones. 3,3-Dibenzyl-1,2-diferrocenylcyclopropene and one of the diastereomers of 4,5-diferrocenylheptan-3-one were studied by X-ray diffraction analysis.     

Trifluoromethyl-substituted Di- and Tetrahydroazolopyrimidines

The condensation of 4,4,4-trifluoro-1-phenylbut-1-en-3-one with 2-aminobenzimidazole, 3-amino-1,2,4-triazole, and 5-aminotetrazole gives hydroxy-substituted tetrahydro derivatives of pyrimido[1,2-a]benzimidazole, and of 1,2,4-triazolo-, and tetrazolo[1,5-a]pyrimidine. Dehydration of them to the corresponding dihydroazolopyrimidines has been carried out. An X-ray structural investigation was carried out and the molecular structure of 5-hydroxy-7-phenyl-5-trifluoromethyl-4,5,5,7-tetrahydrotetrazolo[1,5-a]pyrimidine is discussed.     

Two New Diterpenoids from Isodon rubescens

In order to further study on minor diterpenoid constituents of lsodon rubescens, wereinvestigated this species, which was collected in Taibai mountain, Shaanxi Province.TWo new diterpenoids, taibairubescensins A (l) and B (2), were isolated. In this paper,we present the structure elucidation of these two new diterpenoids.Taibairubescensin A (l ), C,.H,#O, (FABMS m/z 435[M 11 ), an amorphous powder,showed UV and iR absorption bands for the existence of hydroxyl, acetoxyl and a fivemembe…     

Ring-expansion of thioacetal ring via bicyclosulfonium ylide. Effect Of protic nucleophile on ylide intermediate

The reaction of 2-(3-diazo-2-oxopropane-1-yl)-2-methyldithiolane 9a, 2-(4-diazo-3-oxobutane-2-yl)-2-methyldithiolane 9c, and 2-(3-diazo-2-oxopropane-1-yl)-2-methyl-1,3-dithiane 9b with Rh(2)(OAc)(4) gave three-carbon ring-expansion products dithiocan-2-en-1-ones 13a, 13c and dithionan-2-en-1-one 13b, respectively. 2-(5-Diazo-4-oxopentyl)-2-methyldithiolane 9e also gave the five-carbon ring-expansion products dithionan-3-en-1-one 13e and 5-methylenedithionane-1-one 13'e. On the other hand, reaction of 2-(4-diazo-3-oxobutyl)-2-methyldithiolane 9d in the presence of AcOH gave the four-carbon ring-expansion product 16d substituted by an acetoxyl group. In addition, the reaction of 2-(3-diazo-2-oxopropyl)-2-methyl-3-oxathiolane 9f in the absence of AcOH gave 4-oxa-7-thiocan-2-en-1-one 19 via a sulfonium ylide intermediate, whereas, in the presence of AcOH, an alternative regioisomer 20 was also formed competitively with 19 via an oxonium ylide intermediate.     

Synthesis of 5-(trifluoromethyl)cyclohexane-1,3-dione and 3-amino-5-(trifluoromethyl)cyclohex-2-en-1-one: new trifluoromethyl building block

A simple synthesis of 5-(trifluoromethyl)cyclohexane-1,3-dione and 3-amino-5-(trifluoromethyl)cyclohex-2-en-1-one from the sodium salt of methyl or ethyl-4-hydroxy-2-oxo-6-(trifluoromethyl)cyclohex-3-en-1-oate is demonstrated. The compounds represent highly functionalized reactive intermediates for the synthesis of organic and heterocyclic compounds containing a trifluoromethyl group.     

The microbial hydroxylation of levonorgestrel

The microbial transformation of levonorgestrel (1) by Cunningham elegans resulted in the formation of five hydroxylated metabolites, 13-ethyl-10beta, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one(2), 13-ethyl-6beta,17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (3) 13-ethyl 6beta, 10beta, 17beta-trihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (4) 13-ethyl-15alpha-17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (5) and 13-ethyl-11alpha, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4en-20-yn-3-one. The fermentation of one with Rhizopus stolonifer, Fusarium lini and Curvularia lunata afforded compound 2 as a major metabolise. These metabolites were structurally characterized on the basis of spectroScopic techniques. Metabolite 6 was identified as a new compound. Compounds 2 2 ad 5 displayed inhibitory activity against the acetylcholinesterase ( AChE, EC. 3.1.1.7) with IC50 values of 79.2 and 24.5 microM, respectively. The metabolites 2 and 5 also showed inhibitory activity against the butyryLcholinesterase ( BChE, E.C 3.1.1.8) with IC50 values ranging between 9.4 and 309.8 microM.     

MMT/FeCl_3催化的α-羰基二硫缩烯酮与二苯甲醇的Friedel-Crafts烷基化反应

研究了MMT/FeCl_3催化α-羰基二硫缩烯酮与二苯甲醇的Friedel-Crafts烷基化反应,合成了22个二硫缩烯酮类化合物(3a~3v),其中3b,3d~3f,3h~3r和3t为新化合物,其结构经1H NMR和13C NMR表征。以3a的合成为例,对反应条件进行优化。结果表明:在最优反应条件[1-(1,3-二噻烷-2-亚甲基)-4-苯基-3-丁烯-2-酮(1a)0.25 mmol,二苯甲醇0.3 mmol,MMT/FeCl_315 mmol%,CH_2Cl_22 m L,回流反应2 h]下,3a产率93%;MMT/FeCl_3循环使用3次,收率基本维持不变。     

Novel cyclohexene and benzamide derivatives from marine-associated Streptomyces sp. ZZ502

Three new compounds and the known benzamides of 2-acetamido-3-hydroxybenzamide, 2-amino-3-hydroxybenzamide, and 2-aminobenzamide were isolated from the culture of a marine actinomycete Streptomyces sp. ZZ502. Structures of the new compounds were determined as 3-amino-2-carboxamine-6(R)-chloro-4(R),5(S)-dihydroxy-cyclohex-2-en-1-one, 3-amino-2-carboxamine-4(S),6(S)-dihydroxy-cyclohex-2-en-1-one, and 3-hydroxy-2-propionamidobenzamide based on extensive NMR spectroscopical analysis, HRESIMS data, ECD calculation, and X-ray diffraction analysis. None of these isolated compounds showed activity in inhibiting the proliferation of glioma cells nor the growth of methicillin-resistant Staphylococcus aureus, Escherichia coli, and Candida albicans.     

Three-Component Spiro Heterocyclization of Pyrrolediones with Indan-1,3-dione and Acyclic Enamines

Ethyl 4,5-dioxo-2-phenyl-4,5-dihydro-1H-pynole-3-carboxylates reacted with indan-1,3-dione and 3-amino-1-phenylbut-2-en-1-one or 3-aminobut-2-enenitrile to give 3-benzoyl-2-methyl-2′,5-dioxo-5′-prienyl-1,1′,2′,5-tetrahydrospiro[indeno[1,2-b]pyridine-4,3′-pyrroles] and 2-methyl-2′,5-dioxo-5′-phenyl-1,1′,2′,5-tetrahydrospiro[indeno[1,2-b]pyridine-4,3′-pyrrole]-3-carbonitriles, respectively.

     

Piperidine-mediated synthesis of thiazolyl chalcones and their derivatives as potent antimicrobial agents

A series of new thiazolyl chalcones, 1-[2-amino-4-methyl-1,3-thiazol-5-yl]-3-aryl-prop-2-en-1-one were prepared by piperidine mediated Claisen-Schmidt condensation of thiazolyl ketone with aromatic aldehyde. These chalcones on cyclisation gave 2-amino-6-(2-amino-4-methyl-1,3-thiazol-5-yl)-4-aryl-4H-pyridine-3-carbonitrile and 2-amino-6-(2-amino-4-methyl-1,3-thiazol-5-yl)-4-aryl-4H-pyran-3-carbonitrile. The result showed that the compounds exhibited marked potency as antimicrobial agents.     

Transformations of stereoisomeric 2-chloro-3-R-pentane-1,5-diones in reaction with phenylhydrazine

Monophenylhydrazones were prepared from three monochloro derivatives of arylaliphatic 1,5-diketones, and some their transformations were investigated. The monophenylhydrazones formed regiospecifically, and the direction of the reaction was governed by the substituent attached to C³ atom in the initial chlorodiketones. Formerly unknown products of transformations suffered by monophenylhydrazones obtained were described: 2-amino-1,3-diphenyl-3-(2-phenylindolyl-3)-propan-1-one, 3-benzoyl-2,4,6-triphenyl-2,3,4,5-tetrahydropyridazine, and 3-methyl-1,5-diphenyl-5-phenylazopent-4-en-1-one.     

Synthesis of novel acyclonucleosides. Reactions of 1-(1-bromo or 3-bromo-2-oxopropyl)pyridazin-6-ones

Reaction of 1-(3-bromo-2-oxopropyl)pyridazin-6-ones 1 and 2 with sodium azide at room temperature gave the corresponding 1-(3-azido-2-oxopropyl)pyridazin-6-ones 3 and 4 , whereas reaction of 1-(1-bromo-2-oxo-propyl)pyridazin-6-ones 5 and 6 with excess sodium azide afforded 4-azido-5-chloropyridazin-6-one 7 and 4,5-diazido-3-nitropyridazin-6-one 8 by dealkylation. Some 1-(2-hydroxypropyl)pyridazin-6-ones 9, 10, 11 were synthesized from the corresponding 1-(2-oxopropyl) derivatives 1, 2, 3 . 4,5-Dichloro-1-(2,3-dihydroxypropyl)-pyridazin-6-one 13 was also prepared from compound 9 via the corresponding 2,3-epoxypropyl derivative 12 . Treatment of compound 5 with thiourea gave 4,5-dichloro-1-(2-amino-4-methylthiazol-5-yl)pyridazin-6-one 14 . Reaction of compounds 1 and 2 with thiourea at 20° afforded the corresponding 3-formamidinylthio-2-oxo-propyl derivatives 15 and 16 , whereas treatment of compound 1 with thiourea at 45° gave 4,5-dichloro-1-[(2-aminothiazol-5-yl)methyl]pyridazin-6-one 17 . Compound 17 was also prepared from compound 15 by refluxing in ethanol.     

Different supramolecular hydrogen bond structures and significant changes in magnetic properties in dinuclear mu 2-1,1-N3 copper(II) complexes with very similar tridentate Schiff base blocking ligands

Three new basal-apical, mu(2)-1,1-azide bridged complexes, [CuL(1)(N(3))](2) (1), [CuL(2)(N(3))](2) (2) and [CuL(3)(N(3))](2) (3) with very similar tridentate Schiff base blocking ligands [L(1) = N-(3-aminopropyl)salicylaldimine, L(2) = 7-amino-4-methyl-5-azahept-3-en-2-one and L(3) = 8-amino-4-methyl-5-azaoct-3-en-2-one) have been synthesised and their molecular structures determined by X-ray crystallography. In complex 1, there is no inter-dimer H-bonding. However, complexes 2 and 3 form two different supramolecular structures in which the dinuclear entities are linked by strong H-bonds giving one-dimensional systems. Variable-temperature (300-2 K) magnetic susceptibility measurements and magnetization measurements at 2 K reveal that complexes and have antiferromagnetic coupling while has ferromagnetic coupling which is also confirmed by EPR spectra at 4-300 K. Magnetostructural correlations have been made taking into consideration both the azido bridging ligands and the existence of intermolecular hydrogen bonds in complexes 2 and 3.