Compounds 3a-c Research Articles

Synthesis of various isoniazidothiazolidinones and their imidoxy derivatives of potential biological interest

A variety of phthalimido(2-aryl-3-(5'-(4''-pyridyl)-1',3',4'-thiadiazol-2'-yl)-4-oxothiazolidin-5- yl)ethanoates 7a-h and 3-N-alkoxyphthalimido-2-isonicotinoylhydrazido-1,3-thiazolidin-4-ones 9a-c were synthesized using thiosemicarbazide of isoniazid 2 by two alternative pathways. The structures of these compounds were confirmed by IR, NMR ( 1 H & 13 C) and Mass spectral studies. Synthesized compounds 7a-h and 9a-c were evaluated for their antimicrobial activity. Some of the compounds exhibited good antimicrobial activity compared to standard drugs. The structure activity relationships of synthesized compounds have also been studied in order to develop the most potential antimicrobial agent for preclinical evaluation.

Fluorine-Substituted Tetraphenylethene Systems

Synthesis of novel fluorinated tetraphenylethene systems 5a-c was carried out and resulting new materials were investigated for their mesomorphic properties. New materials (5a-c) were prepared by the esterification of 3 with either 4-trifluoromethoxybenzoic acid (5a), 3,4,5-trifluorobenzoic acid (5b), or 4- trifluoromethylbenzoic acid (5c). All compounds (5a-c) were fully characterized while stereochemical features of compound 5a were investigated by its single crystal X-ray analysis. Keywords: tetraphenylethene, mcmurry coupling, liquid crystals

Synthesis and Structure of Fused Nitrogen Heterocycles Obtained by the Reaction of o-Quinones with 2-Methylbenzimidazoles

-butyl groups at 1.00 and 1.38 ppm and the signalsof aromatic protons in the region 7.2–8.1 ppm. Thesignal of the proton in the 14-position of the polycy-cles is observed as a multiplet in the region 9.5–9.8 ppm. The splitting of the signal is caused by thestructural nonrigidity of this fragment of the mole-cule, which is due to the dynamic inversion of thepyramidal nitrogen atom of benzimidazole at theasymmetric carbon atom in the 13-position of polycy-clic compounds 3a–3c. The IR spectra of these com-pounds show the absorption band of the carbonylgroup at 1673 cm

Modification of the Gewald reaction for the synthesis of 3-amino-2-(1H-1,2,3-benzotriazol-1-yl) substituted benzofurans, benzothiophenes and 1H-indoles

Treatment of 1-chloromethylbenzotriazole (4) with salicylonitrile (5a), thiosalicylonitrile (5b), ethyl N-(2-cyanophenyl)carbamate (5c), and N-(2-cyanophenyl)methane-sulfonamide (5d) provided the corresponding intermediates 3. Cyclization of compounds 3a-3c with LDA gave 2- (1H-benzo(d)(1,2,3)triazol-1-yl)benzofuran-3-amine (2a), 2-(1H-benzo(d)(1,2,3)triazol-1- yl)benzo(b)thiophen-3-amine (2b), and ethyl 3-amino-2-(1H-benzo(d)(1,2,3)triazol-1-yl)-1H- indole-1-carboxylate (2c), respectively. Attempts to accomplish elimination of the benzotriazole nitrogen under both thermal and photolytic conditions failed.

Synthetic and Structural Studies of Cyclodistib(V)azanes

High-yielding syntheses of complexes based around the cyclodistibazane (Sb(2)N(2)) core are described from the reaction of organoantimony(V) chlorides with varying stoichiometric amounts of lithiated primary amines, LiN(H)R. Thus, mixing Ph(3)SbCl(2) with 2 equiv of LiN(H)R (R = CH(2)Ph) produces Ph(3)Sb(mu-NR)(2)SbPh(3) (1). Mixed amido/imido complexes of formula {R(H)N}Ph(2)Sb(mu-NR)(2)SbPh(2){N(H)R} (2) (R = CH(2)Ph, 2-OMe-5-(t)()Bu-C(6)H(3), and Cy) are made from the corresponding 3:1 molar ratio combination of LiN(H)R with Ph(2)SbCl(3). A similar reaction employing only 2 equiv of LiN(H)R (R = CH(2)Ph) with 1 equiv of Ph(2)SbCl(3) yields ClPh(2)Sb(mu-NR)(2)SbPh(2)Cl (3). Compounds 2a-c and 3 possess reactive functionality which may make them useful synthetic reagents in the preparation of more complex main group imido architectures. All of the complexes have been characterized by (1)H NMR spectroscopy, elemental analysis (CHN), and X-ray crystallography. An investigation of all known crystallographically characterized Sb-N fragments from the Cambridge Structural Database highlights a series of parameters that appear to influence the observed Sb-N bond lengths.

2-[3-(Trifluoromethyl)phenyl]furo[3,2-b]pyrroles: synthesis and reactions

AbstractThe synthesis and reactions of methyl 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole-5-carboxylate (1a) are described. Upon reaction with methyl iodide, benzyl chloride, or acetic anhydride, this compound gave N-substituted products 1b-d. By hydrolysis of compounds 1a-c, the corresponding acids 2a-c were formed, or by reaction with hydrazine-hydrate, the corresponding carbohydrazides 3a-c were formed. By heating 2-[3-(trifluoromethyl)phenly]-4H-furo[3,2-b]pyrrole-5-carboxylic acid (2a) in acetic anhydride, 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-b]pyrrole (4) was formed. By hydrolysis of 4, 2-[3-(trifluoromethyl)phenyl]-4H-furo[3,2-b]pyrrole (5a) was formed, and reactions with methyl iodide or benzyl chloride gave N-substituted products 5b-c. The reaction of 4 with dimethyl butynedioate gave substituted benzo[b]furan 6. Compound 3a reacted with triethyl orthoesters giving 7a-c, which afforded with phosphorus (V) sulphide the corresponding thiones 8a-c. The thiones 8a-c reacted with hydrazine hydrate to form hydrazine derivatives 9a-c. The reaction of triethyl orthoformiate with compounds 9a-c led to furo[2′,3′: 4,5]pyrrolo[1,2-d][1,2,4]triazolo[3,4-f][1,2,4]triazines 10a-c. Hydrazones 11a-c were formed from 3a-c and 5-[3-(trifluoromethyl)phenyl]furan-2-carboxaldehyde. The effect of microwave irradiation on some condensation reactions was compared with “classical” conditions. The results showed that microwave irradiation shortens the reaction time while affording comparable yields.

1,6- and 1,7-naphthyridines. IV. Synthesis of hydroxycarboxamide derivatives

A series of 8-hydroxy-1,6-naphthyridin-5(6H)-one-7-carboxamides 1 and the isomeric 5-hydroxy-1,7-naphthyridin-8(7H)-one-6-carboxamides 2 were synthesized. N-Lactam unsubstituted compounds 1a-c and 2a,b were obtained by alkoxide-induced rearrangement of the corresponding quinolinimidoacetamides 3. Compounds 1e,f and 2e,f were synthesized by heterocyclization of the corresponding quinolinamic esters 6 and 7. Spectroscopic properties (uv, ir, 1H and 13C nmr and ms) were analyzed and the proposed structures confirmed.

Synthesis of alkoxyphthalimide derivatives of p-bis-(2-hydroxy-4-aryl-6-iminothiazolidino[ 4,5-b ]pyrimidin-N6-yl)biphenyls

Biphenyl-yl-4,4'-bisthiourea 1 reacts with monochloroacetic acid in presence of anhydrous sodium acetate to furnish p-bis-(2-iminothiazolidin-4-one-N 2 -yl)biphenyl 2. Condensation of ω-bromoalkoxyphthalimides 3a-c with 2 gave corresponding alkoxyphthalimide derivatives 4a-c. In the compounds 4a-c, reactive methylene group of thiazolidinone ring at position-5 was condensed with araldehydes 5a-c to give p-bis-(3-n-alkoxyphthalimido-5-arylidene-2-iminothiazolidin-4-one-N 2 -y)biphenyls 6a-i. The titled compounds 7a-i were synthesized by cyclisation reaction of the compounds 6a-i with urea in the presence of anhydrous sodium acetate in acetic acid medium. In another reaction route, substituted benzaldehydes 5a-c were reacted first with 2 to give p-bis-(5-arylidene-2-iminothiazolidin-4-one-N - -yl)biphenyls 8a-c which could be cyclised with urea to furnish p-bis-(2-hydroxy-4-aryl-6-iminothiazolidino[4,5-b]pyrimidin-N 6 -yl)biphenyls 9a-c. The compounds 6a-i and 7a-i were also synthesized by condensation reactions of 8a-c and 9a-c with 3a-c respectively.

Novel carbamate derivatives of 4-β-amino-4′-O-demethyl-4-desoxypodophyllotoxin as inhibitors of topoisomerase II: synthesis and biological evaluation

A novel series of carbamate derivatives of 4-beta-amino-4'-O-demethyl-4-desoxypodophyllotoxin were synthesized. Their effect on human DNA topoisomerase II and antiproliferative activity was evaluated. Compounds 4a-c, 4g, 4j and 4k are topoisomerase II poisons that induce double-stranded breaks in DNA and exhibit increased cytotoxicity compared to etoposide.

Synthesis of Dihydrothieno[2,3‐b]pyridines Based on Titanium(IV) Chloride‐Mediated Michael Reactions of 2‐Amino‐4,5‐dihydro‐3‐thiophenecarbonitriles with α,β‐Unsaturated Ketones

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chiral Induction in Self-Assembled Helicates: CHIRAGEN Type Ligands with Ferrocene Bridging Units

The aim of this work was the preparation of enantiomerically pure bis(pinene-bipyridine) ligands containing the ferrocenyl moiety. Several such ligands (1-3) were synthesized and completely characterized. These molecules can be diastereoselectively deprotonated at the acidic methylene group of the pinene moiety using a strong and sterically hindered base such as LDA. Subsequent reaction of the formed anion with alkyl halides yield the family of C(2)-symmetric enantiopure compounds (1a-c). Copper(I), silver(I), or zinc(II) complexes with several ligands (C1-C8) were prepared and structurally characterized in the solid state and in solution. Self-assembled helical species are formed in several cases. It became evident that the chiral groups present in the ligand do not completely determined the helical configuration of the assemblages. Diastereoselectivity is thus not complete with this type of ligands, contrary to other, similar ligands studied before.

Synthesis of Naphtho[2,1‐b]furo[3,2‐e]‐1,4‐diazepin‐2‐ones and Naphtho[2,1‐b]furo[3,2‐e]‐1,3,4‐triazepin‐2‐ones of Pharmacological Interest.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and Characterization of Model Ultimate Carcinogens/Metabolites Derived from Lead Tetraacetate Oxidation of Arylnitrones: 2′-Deoxyguanosine Adducts

The synthesis of model reactive metabolites 4a-c by lead tetraacetate (LTA) oxidation of arylnitrones 3a-c is described. Compounds 4a-c react with deoxyguanosine (dG) to give N-benzoylated C8-adducts 5a-c. Following debenzoylation with the heterogeneous system (sodium carbonate/methanol) leads to the corresponding C8-adducts 6a-c.

Electronic and structural effects on the nonlinear optical behavior in push-pull TTF/tricarbonyl chromiun arene complexes.

A novel D-pi-A system in which tetrathiafulvalene (TTF) and pi-extended TTFs as strong electron donors are covalently connected to a tricarbonyl (eta(6)-arene)chromium complex as the acceptor moiety through a systematically increased conjugated bridge of vinylene units (12a-c, 16a-c) have been synthesized by Wittig-Horner olefination reaction. The electronic spectra as well as the electrochemical data reveal a different behavior of TTF derivatives (12a-c) and of exTTF derivatives (16a-c). Cyclic voltammetry shows the influence of the tricarbonylchromium arene on the oxidation potentials in compounds 12a-c, and no remarkable effect is observed for exTTFs (16a-c). The nonlinear optical properties of 12a-c and 16a-c have been calculated by using the ab initio CPHF/6-31G//B3P86/6-31G model, and the time-dependent density functional theory (TD-DFT) method has been used for the calculation of the electronic transitions. The calculations reveal that an intraligand charge-transfer transition (ILCT) and the metal to ligand charge-transfer transition (MLCT) are responsible for the nonlinear response. In addition, the large angles formed by the ground-state dipole moment and the vectorial hyperpolarizability are responsible for the mubeta values determined experimentally by the EFISH technique.

Unusual Ar-H/Rh-H J(HH) NMR coupling in complexes of rhodium(III): experimental evidence and theoretical support for an eta1-arene structure.

The synthesis and structural properties of three new hydridorhodium(III) complexes are reported. Hydrogenolysis of the cyclometalated rhodium dichloride complexes [RhCl(2)[(S,S)-benbox(Me(2))]] (2a-c) leads to formation of the new complexes [RhCl(2)(H)[(S,S)-ip-benbox(Me(2))H]] (3a-c) in 45% to 85% yield. Compounds 3a-c were found to have unusual features by NMR spectroscopy: in particular, downfield shifted aryl proton resonances (8.88-9.03 ppm) that were coupled to the rhodium hydride resonances. Using X-ray crystallographic studies, a variety of solid- and solution-state characterization techniques, and DFT calculations, these features were attributed to the presence of weak pi-type eta(1)-arene interactions in 3a-c.

Synthesis of simplified hybrid inhibitors of type 1 17beta-hydroxysteroid dehydrogenase via cross-metathesis and sonogashira coupling Reactions.

[structure: see text] The inhibitor of type 1 17beta-hydroxysteroid dehydrogenase EM-1745 (1) exhibits affinity for both the substrate (estrone or estradiol) and the cofactor (NAD(P)H) binding domains. However, to increase its bioavailability, this compound needs to be simplified. The efficient and convergent synthesis of simplified substrate/cofactor hybrid inhibitors (compounds 2) involving a cross-metathesis and a Sonogashira coupling reaction as key steps is described. Compounds 2a-c were also tested as enzyme inhibitors and compared to EM-1745.

Synthesis of 3‐Aryl(hetaryl)‐4‐ (2‐cyanophenyl)‐Δ2‐1,2,4‐triazolin‐5‐ones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Bis(iminophosphorano)methane Derivatives as Precursors of Unusual Ruthenium Carbene Complexes: A Synthetic and DFT Study

The symmetric bis(iminophosphorano)methanes CH 2 [P{=NP(=O)(OR) 2 }Ph 2 ] 2 (R = Ph (2a), Et (2b)) have been obtained by treatment of bis(diphenylphosphino)methane with a 2-fold excess of phosphorylated azides (RO) 2 P(=O)N 3 . The asymmetric ligand CH 2 [P{=NP(=O)-(OPh) 2 }Ph 2 ][P{=NP(=O)(OEt) 2 }Ph 2 ] (2c) has been prepared by oxidation of Ph 2 PCH 2 P{=NP-(=O)(OEt) 2 }Ph 2 (1b) with (PhD) 2 P(=O)N 3 . Compounds 2a-c can be deprotonated with sodium hydride, affording the corresponding methanide anions NaCH[P{=NP(=O)(OR) 2 }-Ph 2 ] 2 (R = Ph (3a), Et (3b)) and NaCH[P{=NP(=O(OPh) 2 }Ph 2 ] [P{=NP(=O)(OEt) 2 }Ph 2 ] (3c). Treatment of [{Ru(η 6 -p-cymene)(μ-Cl)Cl} 2 ] with 3a-c results in the formation of the neutral complexes [RuCl(η 6 -p-cymene)(κ 2 (C,N)-CH[P{=NP(=O)(OR) 2 }Ph 2 ] 2 )] (R = Ph (4a), Et (4b)) and [RuCl(η 6 -p-cymene)(κ 2 (C,N)-CH[P{=NP(=O)(OPh) 2 }Ph 2 ][P{=NP(=O)(OEt) 2 }Ph 2 ])] (4c), via selective κ 2 (C,N) coordination of the bis(iminophosphorano)methanide anions to ruthenium. The cationic species [Ru(η 6 -p-cymene)(κ 3 (C,N,O)-CH[P{=NP(-O)(OR) 2 }Ph 2 ] 2 )][SbF 6 ] (R = Ph (5a), Et (5b)) and [Ru(η 6 -p-cymene)(κ 3 (C,N,O)-CH[P{=NP(=O)(OPh) 2 }Ph 2 ][P{=NP-(=O)(OEt) 2 }Ph 2 ])] [SbF6] (5c/5c') have been also prepared by reaction of 4a-c with AgSbF 6 . Deprotonation of complexes 4a-c or 5a-c' with NaH generates the unprecedented ruthenium carbenes [Ru(η 6 -p-cymene)(κ 2 (C,N)- [P{=NP(=O)(OR) 2 }Ph 2 ] 2 )] (R = Ph (6a), Et (6b)) and [Ru(η 6 -p-cymene)(κ 2 (C,N)-C[P{=NP(=O)(OPh) 2 }Ph 2 ][P{=NP(=O)(OEt) 2 }Ph 2 ])] (6c). The structures of compounds 2a, 5a, and 6a have been confirmed by X-ray crystallography. DFT calculations on a model for complexes 6a-c, [Ru(η 6 -C 6 H 6 )(κ 2 (C,N)-C[P{=NP(=O)-(OMe) 2 )Me 2 ] 2 )], suggest a nucleophilic character for the carbon atom in Ru=C. In agreement with this theoretical prediction, protonation of complexes 6a-c with HCl or HBF 4 takes place selectively on the carbenic carbon, regenerating 4a-c or 5a-c', respectively.

Synthesis of Novel 2‐(5′‐Substituted‐2′‐phenylindole‐3′‐yl)‐5‐ (coumarin‐3′′‐yl)‐1,3,4‐oxadiazoles and 4‐(5′‐Substituted‐2′‐phenylindole‐3′‐yl)‐1‐ (coumarin‐3′′‐amido)azetidin‐2‐one and Their Antimicrobial Activity.

5-Substituted-2-phenylindol-3-carboxaldehydes 1a-c are reacted with coumarin-3-hydrazide 2 to get coumarin-(5'-substituted-2'-phenylindole-3'-carboxaldehyde)-3-carbonylhydrazone 3a-c. Compounds 3a-c on oxidation with FeCl 3 yield 2-(5'-substituted-2'-phenylindole-3'-yl)-5-(coumarin-3-yl)-1,3,4-oxadiazoles 4a-c and on reaction with acetylchloride produce 4-(5'-substituted-2'-phenylindole-3'-yl)-1-(coumarin-3-amido)azetidin-2-ones 5a-c. All the synthesized compounds have been screened for their antimicrobial activity.

Synthesis of 3-Aryl(hetaryl)-4-(2-cyanophenyl)-Δ2-1,2,4-triazolin-5-ones

1-Unsubstituted O-arylsulfonyl derivatives of isatin 3-oximes in the presence of aliphatic and aromatic amines readily rearrange with breaking of the intercarbonyl bond to form N-(2-cyanoaryl)-N'-R-carbamides [1]. Hypothesizing that the corresponding semicarbazides will be formed upon reaction with substituted hydrazines, we studied the reaction of arylsulfonates 1a-c with carboxylic acid hydrazides. In this case, we have established that even under relatively mild conditions (brief heating of the components in dioxane in the presence of triethylamine), compounds with molecular masses 18 units less than expected for the corresponding semicarbazides were formed in rather good yields. This indicated that under the reaction conditions, cyclodehydration of compounds 1a-c occurred to form 3-aryl(hetaryl)-5-oxo(4H-4-(2-cyanophenyl)-1,2,4triazolines 2a-c.