The Synthesis and Bioactivity of Dimethyl (2,3- Dihydrobenzo[b][1,4]Dioxin-6-Yl)(Aryl Amino)Methylphosphonates

Abstract

A new series of α-aminophosphonates have been synthesized by a one-pot three-component reaction of 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde, various amines, and dimethyl phosphite by using nano-TiO₂ as a catalyst under solvent-free conditions at 50°C. The major advantages of the present method are high yields, short reaction times, recyclable catalyst, and solvent-free reaction conditions. Among these new structurally diversified set of α-aminophosphonates, dimethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(3-nitrophenylamino) methylphosphonate and dimethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(4-fluoro-3-nitro-phenyl-amino) methylphosphonate have shown higher antioxidant activity in diphenyl picryl hydrazyl (DPPH) scavenging, reducing power assay, and lipid peroxidation methods.     

γ-Oxo Carboxylic Acids in Heterocyclic Synthesis IV. Synthesis of Some Pyridazines Containing Phthalyl and Tosyl Amino Acids Using Dcc as the Condensing Agent

The 3(2H)-oxo-, 3(2H)-thioxo- or 3-amino-pyridazine derivatives 4, 6 and 7 were coupled with N-phthalyl- or N-tosyl-amino acids in one-step using N,N′-dicyclohexyl-carbodiimide as the condensing agent to furnish the corresponding 3-(N-phthalyl- or N-tosyl-aminoacyl)pyridazine derivatives 8–10 respectively. Hydrazinolysis of the N-phthalyl derivatives in methanol yielded the corresponding unprotected derivatives 11–13. The antibacterial activities of the prepared compounds were tested.

     

Nucleophilic Displacements in Alkylphosphonates: P–O Versus P–C Bond Cleavage. A Combined DFT and Experimental Study

Abstract

Potential energy surfaces for the nucleophilic displacements at phosphorus in dimethyl methyl, chloromethyl, dichloromethyl, and trichloromethyl phosphonates have been computed by DFT methods. The results reveal that sequential introduction of chlorine substituents at the methyl group in methyl phosphonates increases the stability of transition states and intermediates, which facilitates P–C bond cleavage. While nonsubstituted dimethyl methylphosphonate may undergo exclusive P–O bond cleavage, the trichlorinated analogue reacts exclusively via P–C bond dissociation to form dichlorocarbene, which was trapped by various olefins to form the corresponding gem-dichlorocyclopropanes.     

SYNTHESIS OF THE BIOLOGICALLY ACTIVE 5-(INDOLYL-3-METHYLENE)THIAZOLIDINE-2,4-DIONE DERIVATIVES

Abstract

The cycloaddition reaction of the biologically active 5-(indolyl-3-methylene) derivatives of thiazolidi-none-4-thiones 2a-c to acrylonitrile, ethyl acrylate, N-phenylmaleimides and dimethyl fumarate has been evaluated.     

Preparation of Isoquinolin-(2(1H)-yl)but-2-enedioate Derivatives

One-pot, three-component reactions of isoquinoline, dimethyl/diethyl acetylenedicarboxylate, and indole, carbazole, pyrazole, or imidazole gave dimethyl/diethyl 2-(1-(1H-indol-1-yl)isoquinolin-2(1H)-yl)but-2-enedioate, dimethyl/diethyl 2-(1-(9H-carbazol-9-yl)isoquinolin-2(1H)-yl)but-2-enedioate, dimethyl 2-(1-(1H-pyrazol-1-yl)isoquinolin-2(1H)-yl)but-2-enedioate, or dimethyl 2-(1-(1H-imidazol-1-yl)isoquinolin-2(1H)-yl)but-2-enedioate respectively in good to excellent yields.     

Effective Synthesis of Polysubstituted Pyrroles from (E)-Dimethyl 2-(Bromomethyl)-3-(diethoxyphosphoryl) Fumarate

Methyl 1-alkyl-4-(diethoxyphosphoryl)-5-oxo-2,5-dihydro-1H-pyrroles-3-carboxylate 4 was synthesized from the reaction of dimethyl 2-(bromomethyl)-3-(diethoxyphosphoryl) fumarate 3- E and primary amines in good yields.     

One-Pot Synthesis and Methylation of 3-[2-(1H-Benzimidazol-2-yl-Sulfanyl)-Acetyl]-Chromen-2-Ones

Abstract

3-(2-Bromoacetyl)coumarins (I), when treated with 2-mercatobenzimidazole (II) in acetone containing K₂CO₃ (mild base) and tetrabutylammonium bromide (TBAB) as a phase transfer catalyst, at room temperature yielded the title compound 3-[2-(1H-benzimidazole-2-yl-sufanyl)-acetyl]-chromen-2-one (III) in a one-pot synthesis. Alternatively, III could also be prepared by treating dithiocarbonic acid O-ethyl ester, S-[2-oxo-2-(2-oxo-2H-chromen3-yl)-ethyl] ester (V), with o-phenylenediamine (VI). The methylation of the title compound III was performed with dimethyl sulfate (DMS), in acetonitrile containing TBAB and K₂CO₃ at room temperature, resulting in 3-[2-(N-methyl-benzimidazol-2-yl-sulfanyl)]-acetyl-chromen-2-ones (VII). Alternatively, methylation of III could also be performed with DMS in acetonitrile containing K₂CO₃ as base and clay as surface catalyst. All the compounds were synthesized in good yields and their structures were confirmed by spectral and analytical data.

[Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: ¹H NMR of IIIB, VB and VIIB]     

Efficient Synthesis of 2‐(N‐Substituted)‐2‐imidazolines and 2‐(N‐Substituted)‐1,4,5,6‐tetrahydropyrimidines

A general method for the preparation of 2‐(N‐Substituted)‐2‐imidazolines and 2‐(N‐Substituted)‐1,4,5,6‐tetrahydropyrimidines is described. These heterocycles can be synthesized from their respective anilines with 2‐chloro‐2‐imidazoline or 2‐chloro‐1,4,5,6‐tetrahydropyrimidine, generated in situ from imidazolidin‐2‐one and tetrahydropyrimidin‐2(1H)‐one activated by dimethyl chlorophosphate, in good to excellent yields.     

Synthesis and Properties of Polyamides and Polyimides Derived From Diamines Having 2-Phenyl-4,5-Oxazolediyl Units and Polyamide/Montmorillonite Composite

Aromatic polyamides were synthesized from 4,5-bis(4-aminophenyl)-2-phenyloxazole (APO) or 4,5-bis[4(4-aminophenoxy)phenyl]-2-phenyloxazole (APPO) containing 2-phenyl-4,5-oxazolediyl units with several aromatic carboxylic dichlorides by a low-temperature solution polycondensation method. The polyamides were obtained quantitatively, and their inherent viscosities ranged from 0.48 to 1.25 dL g^?1. The glass transition temperatures (T _gs) were displayed between 234 to 311°C, and the residual weight at 600°C (Res.wt₆₀₀) exceeded 52% in nitrogen atmosphere. The polyamides showed good solubility in several aprotic polar solvents, such as N,N-dimethylacetoamide (DMAc), N-methyl-2-pyrrolidone (NMP), and dimethyl sulfoxide (DMSO). Aromatic polyimides were derived from APO or APPO with aromatic carboxylic dianhydrides through polyamic acids. The inherent viscosities of the polyamic acids, which were 0.53 to 1.02 dL g^?1, T _gs of the polyimides were observed between 259 to 361°C and their Res.wts₆₀₀ were above 70%. The polyamides and polyimides were amorphous and afforded thin, flexible and tough films. We also prepared a nanocomposite of the polyamide derived from APPO with organophilic montmorillonite clay.     

Investigation of the Addition of Benzenethiol to p-Chlorophenylphenylacetylene

The addition of benzenethiol to p-chlorophenylphenylacetylene results in the formation of a mixture of two pairs of diastereomeric (E)- and (Z)-1-p-chlorophenyl-2-phenyl-1-phenylthioethylenes (1 and 2) and (E)- and (Z)-1-p-chlorophenyl-2-phenyl-2-phenylthioethylenes (3 and 4). The configurations of these compounds have been established by ¹ H NMR studies, by their preparation from benzyl p-chlorophenyl ketone and p-chloro-benzylphenyl ketone, and by the oxidation of the thioethylenes 1, 2, 3, and 4 to the corresponding sulphonylethylenes 5, 6, 7, and 8, respectively.     

Mixed Platinum(II) Halide Complexes with Sulfur Donors

Abstract

The reaction of platinum(II) halides with stoichiometric amounts of either dimethyl sulfoxide (DMSO) or thiocarbamic ester (L) in acetone yields the complexes cis-[Pt(L)(DMSO)X₂], where L α MTC (EtOSCNHMe), ETC (EtOSCNHEt) or TC (EtOSCNH₂) and X α Cl or Br. The compounds have been isolated and characterized by elemental analysis and by infrared and nmr (¹H and ¹³C) spectroscopy. Either dimethyl sulfoxide or thiocarbamic ester coordinate through the sulphur atom. In the MTC and ETC adducts the planar ligand molecule is present in the isomeric form bearing the N-alkyl group in an anti position with respect to the thiocarbonyl group.     

Synthesis,characterization, and antibacterial activities of two new copper(II) glycinate complexes incorporating 2-(4′-thiazolyl)benzimidazole/2-(2-pyridyl)benzimidazole

Two new complexes, [Cu(TBZ)(Gly)(H₂O)]Cl (1) and [Cu(HPB)(Gly)Cl]?·?2H₂O (2) (TBZ?=?2-(4′-thiazolyl)benzimidazole, HPB?=?2-(2-pyridyl)benzimidazole, and Gly?=?glycinate), have been synthesized and characterized by elemental analysis, molar conductivity, UV-Vis, and IR methods. The complexes, structurally characterized by single-crystal X-ray crystallography, show a slightly distorted square-pyramidal coordination geometry in which two nitrogen atoms of TBZ or HPB and the carboxylate oxygen and amino nitrogen of glycinate bind in the plane and a water or chloride coordinated at the axial site. The complexes, free ligands, and copper(II) chloride were tested for their ability to inhibit growth of Bacillus subtilis, Staphylococcus aureus, and Salmonella. The results show that the complexes have good antibacterial activities against the microorganisms compared with their ligands and copper(II) chloride.     

gem‐Dimethyl‐bearing C‐Glucosides as Sodium‐glucose Co‐transporter 2 (SGLT2) Inhibitors

Three novel gem‐dimethyl C‐glucosides were designed as sodium‐glucose co‐transporter 2 (SGLT2) inhibitors, and their syntheses started from D‐glucose and three 2‐substituted‐5‐bromobenzoic acids were achieved via a facile 8‐step protocol, with the key step being anhydrous aluminum chloride‐catalyzed Friedel‐Crafts alkylation of tertiary alcohols and phenetol. These three SGLT2 inhibitors were evaluated in vivo with a mice oral glucose tolerance test (OGTT), and the anti‐hyperglycemic activities of all these three compounds were comparable with that of the positive control Dapagliflozin.     

A new flavone from Malaysia Borneo Marsdenia tinctoria

Marsdenia tinctoria is an indigo producing plant commonly found in Borneo, Malaysia. In this present study, one new flavone kapitone (1) and three known compounds, that is 3,2’-dihydroxyflavone (2), 1-methylcyclobutene (3) and dimethyl isatoate (4) were isolated from the Malaysia Borneo M. tinctoria R. Br. (Apocynaceae). These compounds were isolated and characterised using extensive chromatographic and spectroscopic methods.     

Reaction of Dimethyl Acetylenedicarboxylate With 2-Mercaptoperimidine and 2-Mercaptobenzimidazole

A mixture of equimolar quantities of dimethyl acetylenedicarboxylate ( 2 ) with either 2-mercaptoperimidine ( 1 ) or 2-mercaptobenzimidazole ( 5 ) was heated in absolute benzene in the presence of triphenylphosphine as a catalyst under reflux conditions for 1 h (the reaction was monitored by TLC until the consumption of the starting materials). The solvent was concentrated under vacuum and the residue was subjected to chromatographic plates using toluene-ethylacetate (2:1) as an eluent. The products in each reaction were separated as two migrating zones. Each zone was removed from the plate and recrystallized from the appropriate solvent. The products of the first reaction are 10-methoxy-11-oxo-11H-8-thia-7,11a-diaza-benzo[de]anthracene-9-carboxylic acid methyl ester ( 3 ) and 8-thia-7,10a-diaza-cyclopenta[a]phenalene-9,10-dicarboxylic acid dimethyl ester ( 4 ), while the products of the second reaction are 3-methoxy-4-oxo-4H-1-thia-4a,9-diaza-fluorene-2-carboxylic acid methyl ester ( 10 ) and benzo[4, 5]imidazo[2,1-b]thiazole-2,3-dicarboxylic acid dimethyl ester ( 11 ). The mechanisms of the observed reactions are suggested.     

Über Reaktionen mit Betain, 24. Mitt.: Über Umsetzungen von Trimethylammoniumessigsäurebetain mit reaktiven Halogenverbindungen

Summary Diethyl bromomalonate and bromoacetonitrile, respectively, react with trimethylammonium acetic acid betaine in ethanol to give diethyl tartronate and glycolic acid nitrile, respectively. By analogy, ethyl -chloroacetonate and ethyl bromopyruvate yield the respective hydroxy derivatives which were identified by their osazones2 and3. Under the same experimental conditions, mesoxalic acid and its dimethyl ester, respectively, are formed from dibromo malonic acid and its dimethyl ester and were characterized by their known hydrazones8 and9.

Herrn o. Prof. Mag. pharm. Dr. H. Junek, Karl-Franzens-Universität Graz, zur Vollendung des 60. Lebensjahres mit besten Wünschen gewidmet     

Application of Organolithium and Related Reagents in Synthesis,Part 31: Effective Conversion of 3‐Arylphthalides into 2‐(1‐Aryl‐3‐oxo‐4‐alkoxycarbonyl‐butyl)benzoic Acids

A convenient three‐step protocol preparation of the ortho‐alkylated (long‐chain substituent with terminal methylcarbonyl or acetoacetate moiety) aromatic carboxylic acids 15 or 16 from benzoic acids anilides 10 was developed, which exploited the reductive alkylation of phthalides 13 with dimethyl‐6‐methylene‐4‐(trimethoxysiloxy)‐1,3‐diox‐4‐ene (9) as a key step.     

Synthesis of phosphorus‐containing dipeptide mimetics via the Kabachnik–Fields reaction

The synthesis of three novel dimethyl (2‐(4,4‐dimethyl‐2,5‐dioxoimidazolidin‐1‐ylamino)‐ 2‐oxoethylamino)methylphosphonate, dimethyl (1‐ (4,4‐dimethyl‐2,5‐dioxoimidazolidin‐1‐ylamino)‐4‐ methyl‐1‐oxopentan‐2‐ylamino)methylphosphonate, and dimethyl (1‐(4,4‐dimethyl‐2,5‐dioxoimidazolidin‐ 1‐ylamino)‐1‐oxo‐3‐phenylpropan‐2‐ylamino)methylphosphonate, respectively, is reported. The newly synthesized compounds were prepared via the Kabachnik–Fields reaction. Their structures have been characterized by elemental analysis, IR, and NMR (¹H, ¹³C, and ³¹P) spectra. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:669–672, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20731     

An Efficient Route to New 1,2,4,3-Triazaphosphole-3-Oxide Derivatives

The condensation of hexamethylphosphorotriamide and bis-(dimethylamino) methylphosphonate with amidrazones 1 constitutes a new route to the synthesis of 1,2,4,3-triazaphosphole-3-oxide derivatives 3. Structures of all the synthesized compounds have been established by NMR (¹H, ¹³C, ³¹P) and IR spectroscopy, as well as by elemental analysis and MS spectral data for some products.     

Methoden zur Darstellung von 4-Azido-2(1H)-chinolonen

4-Hydroxy-2-quinolones1 are generally found to be converted to the 4-azidocompounds3 via the 4-chloroquinolones2, the 4-tosyloxyquinolones6, or the 4-aminoquinolones4, respectively. Choice of the reaction conditions and yields depend on the substituent in position 3 of the quinoline nucleus. For comparison the O-analogous coumarin derivatives9 have been studied to give the 4-azidoderivatives11 via the 4-chlorocoumarins10.