Synthesis and Antibacterial Activity of Some New S-Triazole Derivatives

Abstract

Alkylation of 4-anilino-5-phenyl-4H-1,2,4-triazole-3-thiol (1) with some halo compounds yielded the corresponding sulfides 2a–f. Some sulfides 2e,f were cyclized to give triazolothiadiazines 3 and 4. Triazolothiadiazoles 5 and 6 were prepared through the reaction of compound 1 with carbon disulfide or ethyl orthoformate, respectively. Treatment of compound 1 with ethyl chloroformate or phenyl isothiocyanate yielded triazolo-thiadiazole and triazole 9 and 10, respectively. Reaction of compound 1 with Lawesson's reagent gave triazolothiadiazaphosphole derivative 11. Also, compound 1 underwent cyclocondensation reactions with some bidentate reagents to give triazolothiazines 4, 12, and 13. Triazolo-thiazepines and triaziepine 14–16 were synthesized via the reaction of compound 1 with β-ketoesters or ethyl cyanoacetate. Tricyclic systems 19 and 20 were prepared through the reaction of compound 4 with the appropriate reagent. Some synthesized compounds were tested for antibacterial activity.

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NEW PRODUCTS OF REACTION OF LAWESSON'S REAGENT WITH DIOLS

Reaction of the Lawesson's reagent (LR) with aliphatic 1,2- and 1,3-diols as well as with aromatic 2,2′-dihydroxybiphenyl led to new products. Stable di-tert-butylammonium salts of bis-anisyldithiophosphonic acids 6 were isolated and were then converted into unique 9-, 9-, and 10-membered cyclic disulfides 7 and into S,S-dimethyl esters 8. The salts of bis-anisyldithiophosphonic acids 6 were shown to be capable of splitting the disulfide bond of Ellman's reagent.     

One-pot synthesis of 1,3,4-thiadiazoles using Vilsmeier reagent as a versatile cyclodehydration agent

A simple and efficient synthetic method for the one-pot synthesis of 1,3,4-thiadiazoles utilizing Vilsmeier reagent was developed. In this method carboxylic acids and hydrazine were converted to 1,3,4-thiadiazoles in the presence of Vilsmeier reagent and Lawesson's reagent. The influence of the thionation reagent, solvent, temperature and time, in this reaction was discussed. The developed methodology for 1,3,4-thiadiazole synthesis has the advantage of simplicity, ambient reaction conditions, easy purification and good to excellent yield of products.     

Studies on Organophosphorus Compounds VII1,2: Transformation of Steroidal Ketones with Lawesson's Reagent into Thioxo and Heterofused Steroids. Results of Antimicrobial and Antifungal Activity

The reactivity of Lawesson's reagent (LR) toward some steroidal hormones was studied, 4-androsten-3,17-dione 2 reacted with LR to produce the corresponding thioxosteroids 3 and 4. Epi-androsterone 5 showed a great activity to LR and produced 3β-mercaptospiro-(androstan-17,4′dithiaphosphetan)thione 8 and the sulfide derivative 9. Also progesterone 10 reacted with LR to yield the thiaphospholo[3′, 4′:16,17]androsten-3-one 13 and the sulfide product 16. The new modified steroidal derivatives thieno[2′,3′:2,3]cholestan 18 and thieno[2′,3′:2,3]-androstan 20 were synthesized and examined against LR, the corresponding thiazaphosphorinothieno steroidal derivatives 23 and 24 were isolated respectively. The in vitro biological activity of some newly synthesized compounds against bacteria, yeast, and fungi was studied.     

Synthesis of Phosphonodithioate,Oxathiaphosphinin, Oxathiaphosphole,and Dithiaphosphole Derivatives from the Reaction of Lawesson's Reagent with Phenolic Mannich Bases and Oxime Derivatives

The reaction of Lawesson's reagent 1a, with niclosamide 2 proceeded by thionation and formation of carbothioamide 3 and the zwitterionic oxathiaphosphinin 4a. LR reacted with 8-hydroxyquinoline (5), 2-methylquinoline-4-ol (7), and β-naphthol (9) to give the phosphonodithioates 6, 8, or 10. The reaction of LR with the Mannich bases 11 and 14 afforded the oxathiaphosphinins 13 and 15, whereas the phosphonodithioates 17 and 19 were isolated in the case of Mannich bases 16 and 18. LR reacted with phthalimide Mannich base 20 to give the dithione 21 and N-methylphthalimide (22). Reaction of ketone monoxime 23 with LR resulted in the formation of the oxathiaphosphole 24 and the dithiaphosphole 25, whereas the monoxime 26 afforded the thioxoethanone thioxime 27. Ketone dioximes 28 and 34 afforded the phosphonodithioates 29 and 36, respectively, when they were allowed to react with LR, whereas the dioxime 30 gave compounds 32 and 33. Moreover, the molluscicidal potency of the newly synthesized compounds against Biomphalaria glabrata snails was studied, too.     

A NOVEL ROUTE TO SPIRO PHOSPHORUS-HETEROCYCLE VIA LAWESSON'S REAGENT

ABSTRACT

2-Aryl-spiro-[5,5]-1,3,2-dioxaphosphorinane-2-sufides were prepared by the cyclization reaction of Lawesson's reagent with pentaerythritol and monobenzalpentaerythritol, respectively.     

REACTIONS OF TETRAPHOSPHORUS DECASULFIDE AND LAWESSON'S REAGENT WITH SILANES CONTAINING A FEW Si-O BONDS

Abstract

The reactions of tetraphosphorus decasulfide and Lawesson's reagent with tetra-, tri- and dialkoxysilanes were studied. On the basis of these reactions, new S-silyl esters of phosphorus(V) thioacids have been prepared. The prepared compounds were identified by IR, ¹H, and ³¹P NMR and mass spectra as well as elemental analyses.     

Facile Synthesis of α-Polythienyls via 1,4-Diketones

Unsubstituted and substituted linear polythienyls including thiophenes in both even and odd numbers are conveniently prepared from the Michael addition of thiophenecarboxaldehydes to Mannich bases and the vinyl sulfone. Cyclization of the resulting 1,4-diones with Lawesson's reagent gives α-polythienyls.     

Synthesis of New Benzoxazaphosphinine/Benzoxazaphosphole/Diazaphosphaphenalene‐2‐sulfides using Lawesson's Reagent

Synthesis of new benzoxazaphosphinine/benzoxazaphosphole/diazaphosphaphenalene 2‐sulfides were accomplished by the reaction of Lawesson's reagent (LR) with 4‐bromo‐2‐[(phenylamino) methyl]phenol (1a), 4‐bromo‐2‐[(4‐chloro/bromo/methoxy/methylphenyl‐amino)methyl]phenol (1b–e), 4‐bromo‐2‐[(benzylamino)methyl]phenol (1f), 2‐amino‐4‐chlorophenol (2a)/2‐amino‐4‐methylphenol (2b), 1,8‐diaminonaphthalene (3) respectively in anhydrous toluene. Products 4a–f, 5a–b and 6 were characterized by IR, ¹H, ¹³C, ³¹P NMR and Mass spectra.     

One‐Pot Approach to Organo‐Phosphorus–Chalcogen Macrocycles Incorporating Double OP(S)SCn or OP(Se)SeCn Scaffolds: A Synthetic and Structural Study

The development of new methodology for the preparation of functional macrocycles with practical applications is an important research area in macromolecular science. In this study, we report a new one‐pot route for the synthesis of a series of macro‐heterocycles by incorporating two phosphorus atoms and two chalcogen atoms and two oxygen atoms (double OP(S)SC_n or OP(Se)SeC_n scaffolds). The three‐component condensation reactions of 2,4‐diferrocenyl‐1,3,2,4‐diathiadiphosphetane 2,4‐disulfide ( FcLR , a ferrocene analogue of Lawesson's reagent) or 2,4‐bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane 2,4‐disulfide ( LR , Lawesson's reagent), or 2,4‐diphenyl‐1,3,2,4‐diselenadiphosphetane 2,4‐diselenide ( WR , Woollins’ reagent), disodium alkenyl‐diols, and dihalogenated alkanes are performed, giving rise to soluble and air or moisture‐stable macrocycles in good‐to‐excellent yields (up to 92 %). This is the first systemically preparative and readily scalable example of one‐pot ring opening/ring extending reaction of three‐components to prepare phosphorus–chalcogen containing macrocycles. We also provide a systematic crystallographic study.     

The role of Lawesson's reagent in the total synthesis of macrocyclic natural products

This review, including 111 references, describes the applications of Lawesson's reagent (LR) [2,4-bis(p-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-dithione] for the total synthesis of macrocyclic natural products. LR is a versatile reagent and shows excellent regioselectivity, chemoselectivity, and offers the products in high yield. The thionation of carbonyl moieties present in macrocyclic natural products, and cyclization to construct key heterocyclic fragments is described. Moreover, this review highlights the medicinal significance of the natural products.     

Synthesis and Properties of Thiophene and Dithiin Functionalized Tetrathiafulvalenes

Abstract

Syntheses of two analogues of tetrathiafulvalene (TTF), fused to 1,4-dithiin and thiophene rings, substituted with thiophene moieties, have been illustrated. The syntheses were accomplished through the reaction of a 1,8-diketone with phosphorus pentasulfide or Lawesson's reagent in boiling dry toluene. Conversion of the thioketones to their the oxo forms with mercury (II) acetate, was followed by self-coupling in freshly distilled boiling triethyl phosphite. Attempts for their electro-polymerizations through the thiophene groups at the peripherals were unsuccessful. Computational chemistry studies revealed that the thiophene groups did not exhibit enough spin densities to perform polymerization.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Nucleosides: Synthesis of Some New Naphthimidazole Ribonucleosides as Potential Antibacterial Agents

Reaction of 2-trifluoromethyl- or 2-cyanonaphth[2,3-d] imidazole (1 or 2) with 1-O-acetyl-2,3,5-tri-O- benzoyl-β-D-ribofuranose (3), using the triflate or fusion method afforded 2-trifluoromethyl-1-(2,3,5-tri- O-benzoyl-α-D- or -β-D-ribofuranosyl)naphth[2,3-d]imidazole (4 or 6) and 2-cyano-1-(2,3,5-tri-O-benzoyl-α-D- or β-D-ribofuranosyl)naphth[2,3,-d] imidazole (5 or 7), respectively. The products 4 and 5 or 6 and 7 were separated by chromatography on silica gel. Treatment of the blocked nucleosides 4-7 with methanolic NH₃ at 0 °C furnished the deblocked nucleosides 8-11 respectively. Treatment of 10 with 5% NH₃ (aq) at 60 °C gave 11. Structural elucidation is based on elemental analysis, UV, FAB-MS and ¹H NMR spectra. Compounds 4-11 were subjected to antibacteial testing. Compounds 5, 7 and 10 have significant activity against Staphylococous aureus (gram positive) and Esherichia coli (gram negative) bacteria, whereas the other tested compounds showed no significant activity.     

Efficient Synthesis of N-[(2-Hydroxyethoxy)methyl]-2-alkyl-3-hydroxy-4-pyridinone by a Modified Hilbert-Johnson Reaction

Ethyleneglycol derivatives of 2-methyl (and ethyl)-3-hydroxy-4-pyridinone were synthesized by a modified Hilbert-Johnson reaction. The synthesis proceedes by reaction of O-protected 2-alkyl-3-hydroxy-4-pyridinone with hexamethyldisilazane in the presence of chlorotrimethylsilane followed by trimethylsilyl trifluoromethanesulfonate catalized alkylation with benzyloxy-ethoxymethylchloride in dichloroethane and deprotection by hydrogenation. The overall yield was 87%. This method provides a useful way to produce oligo- or polyethyleneglycol substituted hydroxypyridinones.     

Synthesis of Some New Fluorine Containing Thiadiazolotriazinones as Potential Antibacterial Agents

2,4-dichloro-5-fluorophenyl, 4-fluoro-3-(Phenoxy)phenyl, 4-fluorophen-yl groups are known pharmacophores and can be used in the synthesis of new biologically active molecules. Therefore, 4-amino-6-arylmethyl-3-mercapto-1,2,4-triazin5(4H)-ones 1 are condensed with 3-phenoxy-4-fluoro-benzoic acid, 2,4-dichloro-5-fluorobenzoic acid, and 4-fluorobenzoic acid 2 to give 7-substituted-3-arylmethyl-4H-1,3,4-thiadiazolo[2,3-c]-1,2,4-triazin-4-ones 3 . Phosphorous oxychloride was used as cyclizing agent. All the newly synthesized compounds 3a-l was screened for their antibacterial activities. Most of them showed promising activity in the range of 10 w g/mL concentrations.     

New Supramolecular Triorganotin(IV) Dithiocarboxylates as Potential Antibacterial Agents

Four triorganotin derivatives of general formula C₁₀H₁₀NS₂SnR₃,_, where R = CH₃ ( 1 ), C₄H₉ ( 2 ), C₆H₁₁ ( 3 ), and C₆H₅ ( 4 ), have been synthesized by the metathesis reaction of 1,2,3,4‐tetrahydroisoquinolnium salt of ligand with triorganotin(IV) chloride in the 1:1 ratio. These complexes were characterized by elemental analysis, Raman, IR, multinuclear NMR (¹H, ¹³C, and ¹¹⁹Sn), and mass spectrometry. The crystal structure confirmed a supramolecular zig‐zag chain structure mediated by S–H (2.968 Å) for complex 4 with the central Sn atom exists in a distorted trigonal bipyramidal geometry. A subsequent antibacterial study indicates that the compounds are biologically active.     

Synthesis and Spectroscopic Characterization of Novel Aryl-Dithiofluorophosphonate Derivatives and X-Ray Studies of [(4-CH3OC6H4)(F)P(S)S−][PH4P+]

Abstract

Potassium and tetraphenylphosphonium salts of novel aryldithiofluorophosphonic acids were synthesized. Lawesson's Reagent was allowed to react with KF in acetonitrile to yield the potassium salt of p-methoxyphenyldithiofluorophosphonic acid. Treatment of the latter with tetraphenylphosphonium chloride resulted in the formation of the tetraphenylphosphonium salt. The structures of the compounds were elucidated by FTIR, ¹H, ¹³C, ¹⁹F, and ³¹P NMR spectroscopy as well as by ESI-mass spectrometry. The molecular and crystal structure of the tetraphenylphosphonium salt, determined by single crystal X-ray diffraction, is also presented.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis and Antimicrobial Evaluation of 1,4-Naphthoquinone Derivatives as Potential Antibacterial Agents

1,4-Naphthoquinones are an important class of compounds present in a number of natural products. In this study, a new series of 1,4-naphthoquinone derivatives were synthesized. All the synthesized compounds were tested for in vitro antimicrobial activity. In this present investigation, two Gram-positive and five Gram-negative bacterial strains and one pathogenic yeast strain were used to determine the antibacterial activity. Naphthoquinones tested for its antibacterial potencies, among seven of them displayed better antimicrobial activity against Staphylococcus aureus (S. aureus; 30–70 μg/mL). Some of the tested compounds showed moderate to low antimicrobial activity against Pseudomonas aeruginosa (P. aeruginosa) and Salmonella bongori (S. bongori; 70–150 μg/mL). In addition, most active compounds against S. aureus were evaluated for toxicity to human blood cells using a hemolysis assay. For better understanding, reactive oxygen species (ROS) generation, time-kill kinetic study, and apoptosis, necrosis responses were investigated for three representative compounds.