Chloride 1a Research Articles

Synthesis of Some Prospective Bioactive Azeto[2,1-d][1,5]benzothiazepinones

Ten azeto[2,1-d][1,5]benzothiazepinone derivatives 6a–j were synthesized starting from 4-acetyl-2-phenyl-1,2,3-triazole 1. First, condensation of 1 with various aldehydes 2a–e afforded α,β-unsaturated carbonyl compounds 3a–e, which subsequently underwent cyclization with o-aminothiophenol to yield the corresponding 2,4-disubstituted-1,5-benzothiazepines 4a–e. Treatment of 4a–e with chloroacetyl chloride 5a or phenoxyacetyl chloride 5b by [2+2] cycloaddition reaction gave the title compounds 6a–j. The assignment of the structures of 6a–j was made by 1H NMR, MS, and elemental analyses.

ChemInform Abstract: Some Properties of Cyclopropenone Oximes Under Beckmann Reaction Conditions.

The reaction of diphenylcyclopropenone oxime (1a) with acetyl or tosyl isocyanate, carboxylic anhydrides, or nitrohalobenzenes yielded the cyclopropenone O-substituted oxime derivatives. Treating with thionyl bromide and chloride 1a gave 3-haloacrylonitriles. Whereas 1a as well as other cyclopropenone oximes, were stable under acidic conditions, heating in methanolic sodium hydroxide gave the ring-opened α,α-dimethoxyketones oximes.

ChemInform Abstract: Unexpected Reactions of 2-Nitro-fluorene-9-carboxylic Acid.

Reaction of 2-nitro-fluorene-9-carboxylic acid with SOCl2 unexpectedly gave 2 dimeric carbonyl chlorides (2a and 2b) whose structure was determined on the basis of NMR and mass spectroscopy and X-ray crystallography. The same methods also allowed to establish the stereochemistry of the compounds obtained.

Synthesis of bioactive polyheterocyclic ring systems as 5α-reductase inhibitors

Simple synthetic strategies for the hitherto unreported [1,2,4]triazolo[4,3- a]pyrido[4,3- d]pyrimidines 8 and [1,2,4]triazolo[4′,3′:1,2]pyrimido[4,5- b][1,6]naphthyridine-5-one 15 are described based on reaction of thione 3 and 12 with hydrazonoyl chloride 1a– h, respectively. The structures of products 8 and 15 were confirmed by spectroscopic and X-ray crystallographic analyses. Also, the mechanism of such reactions was discussed. In addition, reaction of compound 12 with bromoacetic acid and hydrazine hydrate was investigated. Compounds were screened against 5α-reductase and showed activities with good LD 50 and LD 90 for all compounds.

A Rapid, Solvent‐Free Phase‐Transfer Catalysis Procedure for N‐Alkylation of Dihydropyridones and Construction of the Indolizidine, Quinolizidine and Pyridoazepine Structures

AbstractWe have developed a solvent‐free phase‐transfer catalysis (PTC) method for the N‐alkylation of sulfur‐substituted dihydropyridone 4a to give products 5 with varying side‐chains and functional groups. Treatment of the chlorides 5a and 5c with NaI in acetone at reflux gave high yields of the iodides 6a and 6b. The reaction of iodides 7a and 7b with t‐BuLi at low temperature, followed by sequential treatment with HOAc and NaBH4, resulted in the formation of quinolizidine 8a and pyridoazepine 8b, respectively. Similar reaction of bromide 5j with t‐BuLi gave indolizidine 11.

Regioselective synthesis and molecular modeling study of vasorelaxant active 7,9-dioxa-1,2-diaza-spiro[4.5]dec-2-ene-6,10-diones

Nitrilimines (PhC −:N +:NR′) generated in situ from hydrazonoyl chlorides 2a,b reacted regioselectively with 5-arylidene-2,2-dimethyl[1,3]dioxane-4,6-diones 1a-f to afford 1,3,4-triaryl-8,8-dimethyl-7,9-dioxa-1,2-diaza-spiro[4.5]dec-2-ene-6,10-diones 3a-l. In vitro vasodilation activity screening of the synthesized compounds using isolated thoracic aortic rings of male Wister rats pre-contracted with norepinephrine hydrochloride revealed considerable vasodilation activity; compounds 3f and 3j had IC 50 (concentration necessary for 50% reduction of maximal norepinephrine hydrochloride induced contracture) of 0.325, 0.321 mM, respectively. Molecular modeling, including fitting to a 3D-pharmacophore model using Discovery studio 2.1 programs and their docking into optimized α 1-AR homology models as α 1-AR antagonist showed high-docking score and fit values. The experimental in vitro vasodilation activity of compounds 3a-l was consistent with the molecular modeling.

Regioselective control using a catalyst switch in the reaction of diarylmethyl chlorides with allyltributylstannane

Regioselective control in the reaction of diarylmethyl chlorides 5a with allyltributyltin is described. The reaction pathway (allylative dearomatization vs cross-coupling) can be easily controlled using different catalysts. When reactions are performed in the presence of Pd 2(dba) 3 and PPh 3, allylative dearomatization proceeds to provide satisfactory yield of the desired products. However, when Cy 3P·HBF 4 is employed as a catalyst instead of palladium, a Stille-type cross-coupling reaction takes place exclusively to give excellent yields of the corresponding products.

Propargylic and Allenic Carbocycle Synthesis through Palladium-Catalyzed Dearomatization Reaction

The dearomatization reaction of benzylic chlorides (1a-k), chloromethylnaphthalenes (1l-r), and naphthalene allyl chlorides (3a-d) with allenyltributyltin proceeded smoothly in the presence of Pd(PPh(3))(4) catalyst at room temperature to give the corresponding propargylated and/or allenylated dearomatization products (5, 5'; 6, 6'; and 7, respectively) in high to fair yields. The reaction of 1a-k proceeded smoothly in the presence of TBAF, whereas it was not necessary to use TBAF as an additive in the reactions of 1l-k and 3a-d. These reactions provided a new and efficient method for the synthesis of propargylic and allenic carbocycles.

Identification of the [1,3]dithiolo[4,5- d]dithiazolyl radical

The synthesis of 5-oxo[1,3]dithiolo[4,5-d][1,3,2]dithiazol-1-ium chloride 1a from easily available zink chelate, TEA[Zn(DMIT)2], has been developed; salt 1a has been converted to the first representative of [1,3]dithiolo[4,5-d]dithiazolyl radical, which was identified by EPR and CV data.

A Facile Access to Some New Pyrazole, 1,3,4-Thiadiazole, and Thiophene Derivatives via β-Ketosulfones

3-Bromoacetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1) reacts with sodium benzenesulfinate to give the corresponding ketosulfone 2. Treatment of 2 with hydrazonoyl chlorides 3a,b gives the 3,3′-bipyrazoles 5a,b. Ketosulfone 2 reacts also with arylidenemalononitriles to give the pyrazolylpyridones 10a,b. The reaction of compound 2 with phenylisothiocyanate and potassium hydroxide and treating intermediate with hydrazonoyl halides and with α-haloketones gives the 1,3,4-thiadiazoles 18a–c and thiophenes 21a–f, respectively.

New pyrazoles incorporating pyrazolylpyrazole moiety: Synthesis, anti-HCV and antitumor activity

Three series of novel pyrazole derivatives 2b– d, 4a– d and 6a– d were synthesized via two step procedure that utilizes hydrazonoyl chlorides 1a– d and enaminones 3a– d and 5a– d, respectively as starting materials. The structures of all the newly synthesized products have been established on the basis of analytical and spectral data. Moreover, some of the products 2– 6 were tested against HCV and Subacute Sclerosing Panencephalitis (SSPE). In addition, compounds 2– 6 were also tested for the inhibition of peroxynitrite-induced tyrosine nitration and antioxidant activity. The tested compounds are highly effective at very low concentration as anti-HCV, SSPE antioxidant and anticancer in the following ascending order 2d, 4c, 6b, 3b, 6c, 4d, 2b, 2c, 2a, 6a, 5b, 5a, 3a, 4b and 5c. It is worth to mention that all tested compounds are more potent than the reference standards used for comparing activity. All the measurements revealed that the mechanism of action of the anti cancer activities of all the tested compounds is topoisomerase I inhibitor.

Stereoselective synthesis and antimicrobial activity of benzofuran-based (1 E)-1-(piperidin-1-yl)- N2-arylamidrazones

The reaction of 2-oxo- N-arylpropanehydrazonoyl chlorides 3a– e with 3-methyl-2-benzofurancarboxylic acid hydrazide ( 7) furnished N-(aryl)propanehydrazonoyl chlorides 8a– e. X-Ray of 8c revealed the (1 Z,2 E) configuration of structure 8. Nucleophilic substitution reaction of 8a or 8d with piperidine resulted in the formation of 1-(piperidin-1-yl)- N 2-arylamidrazones 9a, b. The X-ray diffraction of 9b showed its (1 E,2 E) configuration and it confirmed the stereoselectivity of the latter reaction. (1 E,2 Z,3 E)-1-(Piperidin-1-yl)-1-(arylhydrazono)-2-[(3-methylbenzofuran-2-oyl)hydrazono]-4-arylbut-3-enes 11 were synthesized in stereoselective reaction from 8 or alternatively from 9. X-ray analysis of 11b showed a conversion of configuration respect to 8d or 9b. X-Ray analysis of 9b and 11b revealed the role of hydrogen interactions in the stereochemistry of their solid state structure. The in vitro antimicrobial activity of the newly synthesized compounds demonstrated an excellent growth inhibition of compounds 9 and 11 against clinically isolated strains of human fungal pathogens and exhibited a significant potency against Gram-positive bacteria. Griseofulvin and Amoxicilline were used as references for antifungal and antibacterial screening. The effect of most potent antifungal compound 9b on morphological features of Aspergillus fumigatus and Candida albicans using image analyzer was studied. Furthermore, the effect of 9b on the ultra-structures of the latter fungi was occurred by transmission electron microscope.

Synthesis and characterization of soluble aromatic azopolyamides containing sulfone and ether units

A series of new polyamides 3a–d containing aryl-azo, ether and sulfone groups in the main chain were synthesized from bis[4-(4-aminophenoxy)phenyl sulfone] 1 and several azo aromatic diacyl chlorides 2a–d by the low temperature solution polycondensation technique. FTIR spectroscopy, nuclear magnetic resonance (NMR) and elemental analyses confirmed the structure of these polymers. Owing to the aryl and amide groups in the main chain, these polymers exhibit photochromic properties as well as excellent thermal stabilities. The transition temperatures (Tg) are between 242 and 265 °C, and the char yields at 800 °C in nitrogen atmosphere were above 39%. Based on incorporation of flexible ether linkages and polar sulfone groups, the polyamides show desirable solubility in organic solvents such as DMAc, N,N-dimethylformamide (DMF), N-methyl-2-pyrroidinone (NMP) and dimethylsulfoxide (DMSO). And it is exemplified that polyamide containing 2 and 2′ substitutes performed better solubility.

Synthesis of N-perfluoroalkenyl(chlorosulfanyl)formimidoyl chlorides

(40 mmol) cooled in a glass ampule (50 mL) to –78 °С. The sealed ampule was heated for 4 h at 70 °С. Unreacted chlorine was removed on a rotary evaporator, and the residue was distilled in vacuo. N (Perfluoro 2 methylpent 2 en 3 yl)chlorosulfanyl formimidoyl chloride (2a). The yield was 72%, b.p. 90—91 °С (60 Torr). Found (%): С, 19.88; F, 49.95; N, 3.25; S, 7.61. C7Cl2F11NS. Calculated (%): C, 20.50; F, 50.97; N, 3.42; S, 7.82. IR, ν/cm–1: 1660 (С=С, N=C). 19F NMR, δ: –111.8 (m, CF2); –80.9 (m, C(3)F3); –59.0 (m, C(2)F3); –55.4 (m, C(1)F3). MS, m/z (Irel (%)): 374 [M – Cl] + (3); 304 (24); 119 [C2F5] + (45); 69 [CF3] + (100). N (Perfluoro 2 methylcyclopentenyl)chlorosulfanyl formimidoyl chloride (2b). The yield was 69%, b.p. 108—109 °С (60 Torr). Found (%): С, 22.07; F, 45.02; N, 3.51; S, 8.44. C7Cl2F9NS. Calculated (%): C, 22.60; F, 45.96; N, 3.76; S, 8.62. IR, ν/cm–1: 1670 (С=С); 1710 (N=C). 19F NMR, δ: –131.2 (m, C(3)F2); –115.4 (m, C(2)F2); –109.0 (m, C(1)F2); –61.0 (m, CF3). MS, m/z (Irel (%)): 336 [М – Cl] + (13); 304 [M – SCl]+ (24); 301 [М – 2 Cl]+ (63); 251 [М – 2 Cl—F]+ (32); 243 [C6F9] + (18); 84 (100); 69 [CF3] + (68).

Regioselective synthetic approaches towards 1,2,8,9-tetraazadispiro[4.1.4.2]trideca-2,9-dien-6-ones of potential antimicrobial properties

Reaction of 2,5-bis(arylmethylidene)cyclopentanones 1a– d with nitrilimines (generated in situ via triethylamine dehydrohalogenation of the corresponding hydrazonoyl chlorides 2a, b) in 1:2 molar ratio proceeds in a high regioselective manner affording monocycloadducts 3 and dicycloadducts in the form of two isomers 4, 5. Single crystal X-ray diffraction studies of the isolated crystalline form of 3c support the established structure and indicate that the formed product is 7 E, 4 S, 5 R. Antimicrobial activity screening of the synthesized compounds 3– 5, utilizing a variety of Gram-positive ( Staphylococcus aureus, Enterococcus fecalis and Streptococcus agalactiae), Gram-negative bacteria ( Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris) and yeast ( Candida albicans), exhibited that all the prepared analogues acquire promising activities against both Gram-positive and Gram-negative bacteria especially compounds 3b, 4a (antimicrobial active agents against Gram-positive bacteria) and 3c (antimicrobial active agent against Gram-negative bacteria).

5,6-Membered palladium pincer complexes of 1-thiophosphoryloxy-3-thiophosphorylbenzenes. Synthesis, X-ray structure, and catalytic activity

Novel unsymmetrical ligands, 1-thiophosphoryloxy-3-thiophosphorylbenzenes 3a-d, bearing phosphine sulfide and thiophosphoryloxy moieties as coordinating sites, were found to undergo cyclometalation at the C-2 position of the central benzene ring in a reaction with bis(benzonitrile)palladium dichloride affording rare examples of nonsymmetrical pincer complexes, namely [2-{(thiophosphoryl)oxy}-6-(diphenylthiophosphoryl)phenyl]palladium chlorides 4a-d, containing 5- and 6-membered fused metallacycles with kappa3-SCS'-coordination. Molecular structures of the complexes were characterized by X-ray diffraction. These complexes demonstrated high catalytic activity for the Suzuki cross-coupling reactions of aryl bromides with phenylboronic acid.

Synthesis of Some Novel Bis(pyrazole), Bis(pyridine) and Bis(pyrazolo[5,1-c]-1,2,4-triazine Derivatives

Treatment of N,N'-(ethane-1,2-diyl)bis(cyanoacetamide) (1) with hydrazonoyl chlorides 2a,b afforded bis(aminopyrazoles) 5a,b. Heating of compound 1 with arylmethylenepropanedinitrile 9a-c afforded bis(pyridine) derivatives 13a-c. Also, compound 1 coupled smoothly with the arenediazonium salt generated from 3-chloroaniline or 5-amino-4-methyl-3-phenylpyrazole (16) to afford the corresponding hydrazones 15 or bis(pyrazolo[5,1-c]-1,2,4-triazine-3- carboxamide) 19. Refluxing of compound 1 with N,N-dimethylformamide dimethyl acetal (DMF-DMA) in xylene afforded bis(2-cyano-3-(dimethylamino)-acrylamide) (20) which reacted with hydrazine hydrate to afford the novel bis(cyanoopyrazole) 23.

Conversion of novel palladacycles into oxopyrrolo[3,4-b]quinolines

The quinolinylcyclopalladated complexes 3a– b were synthesised in good yields (81% and 77%) by the insertion reaction of the prepared dinuclear palladium complexes [Pd( C,N-2-C 9H 4N-CHO-3-R-6)Cl(PPh 3)] 2 [(R = H ( 2a), R = OMe ( 2b)] with isonitrile XyNC (Xy = 2,6-Me 2C 6H 3). The cyclopalladated complexes 3a– b were also obtained in low yields (39% and 33.5%) via a one pot oxidative addition reaction of quinoline chloride 1a– b with isonitrile XyNC:Pd(dba) 2 (4:1). The reactions of 3a– b with Tl(TfO) (TfO = triflate, CF 3SO 3) in the presence of H 2O or EtOH causes depalladation reactions of the complexes to provide the corresponding organic compounds 4a– b, 5a– b and 6a– b in yields (41%, 27% and 18–19%). The products were characterized by satisfactory elemental analyses and spectral studies (IR, 1H, 13C and 31P NMR). The crystal structures of 2a, 3a and 3b were determined by X-ray diffraction studies.

Palladium N‐heterocyclic‐carbene‐catalyzed ortho‐arylation of benzaldehyde derivatives

AbstractNew, sterically demanding 1,3‐dialkylbenzimidazolium salts (2a–c) as N‐heterocyclic‐carbene precursors have been synthesized and characterized. The ortho position of aromatic aldehydes was directly and selectively arylated with aryl chlorides in the presence of a catalytic system prepared in situ from Pd(OAc)2, 1,3‐dialkylbenzimidazolium chlorides (2a–c), and Cs2CO3. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:569–574, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20479

Ruthenium(II) and iron(II) complexes of N-pyridyl substituted imidazolin-2-ylidenes

N-mesityl- N′-pyridyl-imidazolium chloride 1a and the corresponding bromide salt 1b have been deprotonated with NaH in THF giving the free N-heterocyclic carbene N-mesityl- N′-pyridyl-imidazolin-2-ylidene 2 in 80% yield (starting from 1a). Imidazolium salt 1a reacts with RuCl 3 · xH 2O to give a racemic mixture of dinuclear di-μ-chloro bridged ruthenium complexes [(κ 2- 2) 2Ru(μ-Cl) 2Ru(κ 2- 2) 2] 2+ [ 3a] 2+. The carbene carbon atoms as well as the halides are arranged in cis-positions to each other whereas the nitrogen atoms adopt a trans-configuration. The di-μ-bromo bridged derivative [(κ 2- 2) 2Ru(μ-Br) 2Ru(κ 2- 2) 2] 2+ [ 3b] 2+ was obtained from RuCl 3 · xH 2O and 1b. The bridging halide ligands can be removed by the reaction with silver or sodium salts of bidentate Lewis acids. Complex [ 3a] 2+ reacts with silver pyridylcarboxylate to give a racemic mixture of the mononuclear complex [ 4] +. Reaction of [ 3a] 2+ with the sodium salt of l-proline resulted in a diastereomeric mixture of complexes [ 5] +. The free N-heterocyclic carbene 2 reacts with [FeCl 2(PPh 3) 2] to give after anion exchange with NaBPh 4 cis/ cis/ trans coordinated [Fe(κ 2- 2) 2(MeCN) 2](BPh 4) 2 [ 6](BPh 4) 2. The molecular structures of [ 3b](PF 6) 2, [ 4]PF 6 and [ 6](BPh 4) 2 · H 2O are reported.