Efficient Synthesis of N‐Oxide Derivatives: Substituted 2‐(2‐(Pyridyl‐N‐oxide)methylsulphinyl)benzimidazoles

Different substituted 2‐chloromethylpyridyl derivatives (6a–d) were oxidized with mCPBA to give the respective 2‐chloromethylpyridine‐N‐oxide derivatives (7a–d) at low temperature, which on condensation with 2‐mercapto‐1H‐benzimidazole (8a–c) in the presence of aprotic solvents give the 2‐[[(pyridin‐2‐yl‐1‐oxide)methyl]sulfanyl]‐1H‐benzimidazole (9a–d) in good yield. Finally, 9a–d oxidized with mCPBA in chlorinated solvent gives a mixture of 2‐[[(pyridin‐2‐yl‐1‐oxide)methyl]sulfonyl]‐1H‐benzimidazole (3a–d, 10%) and 2‐[[(pyridin‐2‐yl‐1‐oxide) methyl]sulfinyl]‐1H‐benzimidazole (4a–d, 90%) derivatives.     

Efficient Method for the Synthesis of Benzimidazoquinazoline Derivatives with Three‐Point Diversity

An efficient strategy for the preparation of a novel heterocyclic ring system of benzimidazoquinazolines with three‐point diversity has been described. The compounds were obtained by treating o‐phenylene diamines with o‐nitrobenzaldehyde to give benzimidazoles, followed by reduction of the nitro group to give an amine. Derivatization of the resulting amine with isothiocyanates followed by in situ cyclodesulfurization at rt furnished the title compounds in high yields and purities.     

Practical Synthesis of N‐Alkyl‐N‐alkyloxycarbonylaminomethyl Prodrug Derivatives of Acetaminophen,Theophylline, and 6‐Mercaptopurine

We report a novel synthesis of N‐alkyl‐N‐alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of acetaminophen, theophylline, and 6‐mercaptopurine by alkylation of the corresponding drug molecule with N‐alkyl‐N‐alkyloxycarbonylaminomethyl chlorides in good yield. Most of the alkylating agents were efficiently synthesized by chloromethylation of N‐alkyl carbamic acid alkyl esters, which in turn were made from alkyl amines and alkyl chloroformates. In cases where the alkyl chloroformates were not available, synthesis of N‐alkyl carbamic acid alkyl esters was accomplished by converting an alcohol to a chloroformate or to an activated acylating agent such as acyl imidazoles or p‐nitrophenylcarbonate esters, followed by their reaction with alkyl amines.     

New Method for the Synthesis of 5‐Hydroxycamptothecin Derivatives

Abstract

An efficient hydroxylation at the 5‐position of the C ring of camptothecins was accomplished with the complex of CuI and organic amines as catalyst in the presence of oxygen at room temperature in dimethyl formate (DMF). To be successfully hydroxylated, the insoluble camptothecin analogue was transformed to the corresponding 20 carbonates.     

Synthesis of 1,1‐Dimethyl‐4‐indanol Derivatives

The synthesis of 1,1‐dimethyl‐4‐indanols (3a,b) has been achieved by intramolecular Friedel–Crafts cyclization of 2‐(3‐methyl‐2‐butenyl)phenols (5a,b) or 1‐methoxy‐2‐(3‐methyl‐2‐butenyl)benzenes (6a,b) followed by demethylation, respectively.It was found that the solvent was critical for the formation of different products in the intramolecular Friedel–Crafts reactions of 6. The unexpected product 4‐methoxy‐1,1,6,6‐tetramethyl‐as‐hydrindacene (11) was obtained from the Friedel–Crafts reactions of 6a, and its structure was confirmed by X‐ray diffraction analysis. The key intermediates 5a,b were prepared by ortho‐alkenylation of phenols with 1‐bromo‐3‐methyl‐2‐butene, and the reaction temperature exerted an obvious impact on the yield of 2‐(3‐methyl‐2‐butenyl)phenol (5a).     

Interaction between Anionic and Zwitterionic Surfactants: Sodium Dodecyl Sulfate and N‐alkyl‐N,N‐dimethylsulfobetain,N‐lauroylsarcosine

The interaction between anionic and zwitterionic surfactant has been investigated through the measurements of surface tension and pH. These systems are sodium dodecyl sulfate (SDS) and N‐alkyl‐N,N‐dimethylsulfobetain(SB) N‐lauroylsarcosine(NL). As the molar ratio of SDS to SB is 7:3, the cmc of these systems exhibits minimum and the surface activity is in‐depend on pH. As the molar ratio of NL to SDS is from 3:7 to 7:3, the synergistic effect of the systems exhibits significantly, the surface tension increases with decreasing of pH and deposits has formed.     

Novel Synthesis of 5‐Substituted‐3‐phenylindole‐2‐(1,2,4‐triazole) Derivatives

Various substituted 3‐phenylindole 2‐carboxylates (1a–c) were prepared according to the literature methods. These carboxylates (1a–c) on reaction with thiosemicarbazide yielded 5‐substituted‐3‐phenylindol‐2‐(1,2,4‐triazole‐3‐thione) (2a–c) on refluxing in pyridine for 8 h. The 5‐substituted‐3‐phenylindole‐2‐[1,2,4‐triazolo‐3‐thioacetic acid] (3a–c) were prepared from 5‐substituted‐3‐phenyl indole‐2‐[1,2,4‐triazole‐3‐thione] (2a–c) on reaction with an appropriate alkylating agent and sodium acetate in acetic acid. Further, (3a–c) were reacted with acetic anhydride to bring about a cyclocondensation reaction to yield 5‐substituted‐3‐phenylindol‐2‐thiazolo(2,3‐b)‐triazole (4a–c). The 5‐substituted‐3‐phenylindole‐2‐[1,2,4‐triazolo‐3‐acetic acid] (3a–c) were reacted with o‐phenylenediamino dihydrochloride in ethylene glycol to yield 5‐substituted‐3‐phenylindole‐1,2,4‐triazolo‐3′‐yl‐thiomethyl)benzimidazoles (5a–c).     

Efficient One‐Step Synthesis of a Key Intermediate for the Synthesis of Azole Antifungals Using the Mitsunobu Protocol

A simple and single‐step process for coupling (2R,1S)‐1‐[2‐(2,4‐difluorophenyl)‐2‐oxiranyl]ethanol and various 1,2,4‐triazolones utilizing the Mitsunobu protocol is described. The product so formed is a key intermediate in the synthesis of azole antifungals with potent and broad‐spectrum activity against yeast and filamentous fungi.     

Synthesis of azoles based on N,N′-bis(hydrazinocarbonyl-ethyl)-1,4-phenylenediamine

N,N′-Bis[(1-methyl-3-oxobutylidene)hydrazinocarbonylethyl]-, N,N′-bis[(2,5-dimethylpyrrol-1-yl)carbamoylethyl]-, N,N′-bis(phenylureidocarbamoylethyl)-, N,N′-bis(phenylcarbamoyl)-, N,N′-bis(phenylureidocarbamoylethyl)-, and N,N′-bis[(4,5-dihydro-5-oxo-4-phenyl-1,2,4-triazol-3-yl)ethyl]-1,4-phenylene-diamines, and their thio analogs were obtained by the condensation of N,N′-bis-(hydrazinocarbonylethyl)-1,4-phenylenediamine with 2,4-pentanedione, 2,5-hexanedione, phenyl isocyanates, or phenyl isothiocyanates (with subsequent treatment of the obtained semicarbazides with alkali), and carbon disulfide respectively.     

Convenient Synthesis of N,N′‐bis‐protected‐3,3′‐diiodo‐2,2′‐biindoles

A convenient synthesis of N,N′‐bis‐protected 3,3′‐diiodo‐2,2′‐biindoles 4–7 from 2,2′‐biindole (1) is described.     

Synthesis of New 1,3‐bis(Heteroaryl)‐4,5‐imidazolidinediones Through Reaction of N,N′‐bis(Heteroaryl)methanediamines with Oxalyl Chloride

Reaction of N,N′‐bis(2‐pyridinyl, 3‐pyridinyl, 4‐pyridinyl, 2‐thiazolyl, 4‐nitrophenyl, and 2‐benzothiazolyl)methanediamines 1a–f with oxalyl chloride in dry dichloroethane in the presence of pyridine affords the corresponding 1,3‐bis (heteroaryl)‐4,5‐imidazolidinediones 3a–f in good to excellent yields. The essential role of pyridine in the reaction mixture is described, and reaction details as well as product characterization is discussed.     

Y(OTf)3‐Catalyzed,One‐Pot Synthesis of 1,2,4‐Oxadiazole Derivatives

Direct one‐step synthesis of 1,2,4‐oxadiazole from ketones, nitriles, and nitric acid is described using yttrium triflate [Y(OTf)₃] as the catalyst. The salient features of this method include a simple procedure, mild condition, easy purification, and good yields.     

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.     

A New Route of Synthesis of 5‐(N‐Phenethylamino)salicylic Acid Derivatives by Rapid and Selective Reduction of the Amide Group with NaBH4/Acetic Acid

A good yield of 5‐(N‐phenethylamino)salicylic acid derivatives was successfully obtained from the corresponding methyl 2‐acetoxy‐5‐(N‐phenethylamino)benzoate esters by rapid and selective reduction of the amide group in the acyl protected salicylic acid with NaBH₄/acetic acid in dioxane followed by hydrolysis of the ester group.     

Synthesis of 1,4‐Diaryl‐piperazine‐2,5‐diones: New Behavior of N,N‐Dimethylformamide Dimethyl Acetal (DMFDMA)

Reactions of chloroacetamides (5) with N,N‐dimethylformamide dimethyl acetal gave 1,4‐diaryl‐piperazine‐2,5‐diones 11a–e in good yield, rather than 1,5‐diaryl‐3,7‐dimethoxy‐1H,5H‐[1,5]diazocine‐2,6‐diones (9a–e).     

Synthesis of 3‐Aryl‐2‐benzoylbenzofuran Derivatives using Manganese(III) Acetate–Mediated Addition of Dimedon to Chalcone Derivatives

3‐Aryl‐2‐benzoylbenzofurans were synthesized by the reaction of α‐carboradical produced from dimedon by oxidizing with manganese(III) acetate in acetic acid and the chalcone derivatives.     

Novel Synthesis and Characterization of N‐Substituted‐calix[4]azacrown Derivatives

Novel calix[4]azacrown derivatives from the reaction between calix[4]amidocrown and the different N‐(4‐bromoacetamidephthalimido)alkanes derivatives, which may be useful intemediate compounds of pseudorotaxane, have been synthesized and structurally characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analyses. From their analysis data, it was found that compounds 6a–d adopted a cone conformation.     

Microwave‐Assisted One‐Pot Synthesis of 2‐(Substituted phenyl)‐1H‐benzimidazole Derivatives

A series of 2‐(substituted phenyl)‐1H‐benzimidazole derivatives with various 5‐and 6‐position substituents (‐H, ‐CH₃, ‐CF₃) were synthesized via microwave irradiation using a short synthetic route and Na₂S₂O₅ as oxidant. This simple, fast, and efficient preparation of benzimidazole derivatives has been developed using readily available and inexpensive reagents (aldehydes and 1,2‐phenylenediamines) under solvent‐free conditions.     

Synthesis of 3,3′‐Di(2‐Pyridyl)‐1,1′‐Bi‐2‐Naphthol Derivatives

Abstract

A new kind of (S)‐3,3′‐dipyridyl BINOLs (3a–d) with C ₂‐symmetry were synthesized in 79–84% yields by Suzuki coupling of the diboronic acid dipinacol ester (S)‐1 containing a (S)‐binaphthyl group with bromopyridine derivatives (2a–d) followed by hydrolysis.     

Synthesis of 4‐Arylpiperazine Derivatives of Moclobemide: Potential Antidepressants with a Dual Mode of Action

Abstract

We report here the synthesis of substituted 4‐chloro‐N‐[3‐oxo‐3‐(4‐aryl‐1‐piperazinyl)‐propyl] benzamides (5–9), as potential new antidepressants, incorporating in a single molecule structural moieties related to a dual pharmacological profile: MAO‐A inhibitor and 5‐HT_1A receptor affinity.