Synthesis and photochemical properties of trans‐2‐(2‐aryl‐ or heteroarylvinyl)‐4,5‐dichloropyridazin‐3(2H)‐ones

trans‐2‐(2‐Aryl‐ or heteroarylvinyl)‐4,5‐dichloropyridazin‐3(2H)‐ones 3 were synthesized from 4,5‐dichloropyridazin‐3(2H)‐one via 2 step. The photochemical behavior of 3 in THF, methylene chloride, acetonitrile and methanol is dependent on the kind of aryl or heterocyclic ring and the solvent polarity     

Stereoselective Synthesis of (Z)‐4‐(2‐Bromovinyl)benzene‐sulfonyl Azide and Its Synthetic Utility for the Transformation to (Z)‐N‐[4‐(2‐Bromovinyl)benzenesulfonyl]imidates

A novel method for the stereoselective synthesis of (Z)‐4‐(2‐bromovinyl)benzenesulfonyl azide by simultaneous azidation and debrominative decarboxylation of anti‐2,3‐dibromo‐3‐(4‐chlorosulfonylphenyl)propanoic acid using NaN₃ only was developed. Facile transformation of (Z)‐4‐(2‐bromovinyl)benzenesulfonyl azide to (Z)‐N‐[4‐ (2‐bromovinyl)benzenesulfonyl]imidates was also achieved by Cu‐catalyzed three‐component coulping of (Z)‐4‐(2‐bromovinyl)benzenesulfonyl azide, terminal alkynes and alcohols/phenols.     

Synthesis of 1‐acyl‐2‐oxo‐3‐pyrrolidinecarbonitriles by the reaction of 2‐acylamino‐4,5‐dihydro‐3‐furancarbonitriles with sodium iodide

The reaction of 2‐acylamino‐4,5‐dihydro‐3‐furancarbonitriles 1 with sodium iodide in N,N‐dimethyl‐formamide gave the corresponding 1‐acyl‐2‐oxo‐3‐pyrrolidinecarbonitriles 2 in good yields. Successive treatment of 1 with titanium(IV) chloride and potassium carbonate resulted in the formation of N‐acyl‐1‐cyanocyclopropanecarboxamides 4 . The same compounds 2 were also obtained by treatment of 4 with sodium iodide. The starting compounds 1 were synthesized by the reaction of 2‐amino‐4,5‐dihydro‐3‐furan‐carbonitrile with acyl chlorides in pyridine.     

One‐Pot Synthesis of 2‐Substituted 4‐Aryl‐4,5‐dihydro‐3,1‐benzoxazepines from 2‐(2‐Aminophenyl)‐1‐arylethanols via Dehydration of the Corresponding Amides

An efficient method for the preparation of 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepine derivatives under mild conditions has been developed. The reaction of 2‐(2‐aminophenyl)ethanols 1 with acid chlorides in the presence of excess Et₃N in THF at room temperature gave the corresponding N‐acylated intermediates 2 , which were dehydrated by treatment with POCl₃ to give 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepines 3 in a one‐pot reaction.     

Synthesis,Structure of Zwitterionic 2‐Amino‐N′‐(imidazolidin‐2‐ylidene)benzohydrazides,and Their Transformation into 3‐(Imidazolidin‐2‐ylideneamino)quinazolin‐4(1H)‐one Derivatives

The reaction of 2‐chloro‐4,5‐dihydroimidazole ( 5 ) with 2‐aminobenzohydrazides 6a–e led to the formation of 2‐amino‐N′‐(imidazolidin‐2‐ylidene)benzohydrazides as zwitterions 7a–e , which on treatment with carbon disulfide in the presence of triethylamine afforded 3‐(imidazolidin‐2‐ylideneamino)‐2‐thioxo‐2,3‐dihydroquinazolin‐4(1H)‐ones 8a–e . Compounds 8a–d were further converted into the corresponding 3‐(imidazolidin‐2‐ylideneamino)quinazoline‐2,4(1H,3H)‐diones 9a–d using hydrogen peroxide–sodium hydroxide solution. The structures of the compounds prepared were established by elemental analyses, IR and NMR spectra as well as X‐ray crystallographic analyses of 7e and 9a .     

Reactions of a,ß‐unsaturated N‐benzenesulfonyl Imine – N‐[(2E)‐3‐phenyl‐2‐propen‐1‐ylidene]benzenesulfonamide with Methyllithium

α,β‐Unsaturated N‐benzenesulfonyl imine 1 was treated with 1.1 eq methyllithium to afford 1,2‐addition adduct as a sole product. However, when compound 1 was treated with 2 eq MeLi, 1,2‐addition product, benzenesulfonamide derivative 3 and 2H‐1,2‐benzothiazine 1,1‐dioxide derivatives 4 and 5 were isolated.     

Synthesis and Anticancer and Antiviral Activities of New 2‐Pyrazoline‐Substituted 4‐Thiazolidinones

2‐(4,5‐Dihydropyrazol‐1‐yl)‐thiazol‐4‐ones ( 2–5 ) have been synthesized starting from 3‐phenyl‐5‐aryl‐1‐thiocarbamoyl‐2‐pyrazolines via [2+3]‐cyclization with 2‐bromopropionic acid, maleic anhydride, N‐arylmaleimides, and aroylacrylic acids. The in vitro anticancer activity of 2a , 3a , 4a , 5b , and 5c were tested by the National Cancer Institute. Compounds 4a , 5b , and 5c demonstrated selective inhibition of leukemia cell lines growth at a single concentration (10^?5 M). The screening of antiviral activity for a broad panel of viruses revealed that N‐(4‐methoxyphenyl)‐2‐{2‐[5‐(4‐methoxyphenyl)‐3‐phenyl‐4,5‐dihydropyrazol‐1‐yl]‐4‐oxo‐4,5‐dihydrothiazol‐5‐yl}‐acetamide 4a was highly active against Tacaribe TRVL 11 573 virus strain (EC₅₀ = 0.71 μg/mL, selectivity index = 130).     

The synthesis of n‐substituted isothiazol‐3(2h)‐ones from nsubstituted 3‐benzoylpropionamides

N‐Substituted isothiazol‐3(2H)‐ones can be easily prepared from N‐substituted 3‐benzoylpropi‐onamides in two experimentally simple steps, in satisfactory overall yields. Reaction of the amides with excess thionyl chloride results in the formation of N‐substituted 5‐benzoylisothiazol‐3(2H)‐ones, which are readily debenzoylated with alkali to the corresponding N‐substituted isothiazol‐3(2H)‐ones. This method has now been successfully applied to the synthesis of isothiazolones N‐substituted with a bulky alkyl group, such as the tert‐butyl group, and with a phenyl group bearing either a strong electron‐withdrawing substituent, such as the 3‐nitrophenyl and 4‐nitrophenyl group, or an electron‐releasing substituent, such as the 4‐methylphenyl and 4‐methoxyphenyl group.     

Thionation of N‐(ω‐Halogenoalkyl)‐Substituted Amides with Lawesson's Reagent: Facile Synthesis of 4,5‐Dihydro‐1,3‐thiazoles and 5,6‐Dihydro‐4H‐1,3‐thiazines

The thionation and cyclization of N‐(ω‐halogenoalkyl)‐substituted amides (and related compounds) with Lawesson's reagent (LR=2,4‐bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane 2,4‐disulfide) has been investigated. Treatment of the amides 1 with LR gave the corresponding thioamides 2 in moderate to good yields (Table). The latter, upon treatment with base, afforded, either in a separate step or in a one‐pot procedure, the cyclized title compounds, i.e., the 4,5‐dihydro‐1,3‐thiazoles 3 or the corresponding 5‐6‐dihydro‐4H‐thiazines 4 via dehydrohalogenation.     

Synthesis of alkyl or aryl pyridazinyl ethers

This paper presents the synthesis of some alkyl or aryl pyridazinyl ethers from 2‐alkyl‐4‐halo‐5‐hydroxy‐and 2‐alkyl‐4,5‐dichloropyridazin‐3(2H)‐ones or 3,6‐dichloropyridazine. Reaction of 2‐alkyl‐4‐halo‐5‐hydroxypyridazin‐3(2H)‐ones 1 with 1,2‐dibromoethane or 1,3‐dibromopropane gave the corresponding monopyridazin‐5‐yl ethers 2 and α,ω‐[di(pyridazin‐5‐oxy)]alkanes 3 . Treatment of 4 with 4‐substituted‐phenol afforded 5‐(4‐substituted‐phenoxy)‐2‐(4‐substituted‐phenoxymethyl) derivatives 5 . Reaction of 2‐alkyl‐4,5‐dichloro derivatives 7 with 1 gave the corresponding di(pyridazin‐5‐yl) ethers 8 in good yields. Compound 10 was reacted with catechol to give monopyridazin‐3‐yl ether 11 and/or di(pyridazin‐3‐yl) ether 12 . Also we described the results for the reaction of 2‐alkyl‐4‐chloro‐5‐(4‐substituted‐phenoxy)pyridazin‐3(2H)‐ones with nucleophiles.     

Synthesis of benzo[c][1,8]phenanthrolin‐6‐one through cyclization of N‐(isoquinol‐5‐yl)‐2‐bromo‐benzamide derivatives

In the course of our search for compounds with potential antitumor properties we have undertaken the synthesis of benzo[c][1,8]phenanthroline derivatives. Our project required the preparation of 8,9‐dimethoxy benzo[c][1,8]phenanthrolin‐6‐ones. This was first attempted by the lithiumdiisopropylamide cyclization of N‐(isoquinol‐5‐yl)‐2‐bromo‐4,5‐dimethoxybenzamide. The reaction led to 40% of the unexpected internal Diels‐Alder adduct 3,4‐dimethoxy‐6H‐pyrido[2,3‐i]6,8a‐ethenoindolo[cd]isoquinoline‐2(1H)‐one, which arose from a benzyne intermediate. In a second and more successful approach, the internal biaryl palladium diacetate‐assisted coupling reaction of properly N‐protected N‐(isoquinol‐5‐yl)‐2‐bromo‐4,5‐dimethoxybenzamide was studied. The optimisation of the protecting group necessary for this procedure led to a 64% yield of the target compound starting from N,N‐(isoquinol‐5‐yl)‐bis‐(2‐bromo‐4,5‐dimethoxybenzamide).     

2‐Chloro‐4,5‐dihydroimidazole,Part X. Revisiting route to N‐heteroarylimidazolidin‐2‐ones

The ureidation reactions of 2‐ and 4‐picoline N‐oxides with 2‐chloro‐4,5‐dihydroimidazole are described. A mechanism of novel thioureidation reaction of 4‐picoline N‐oxide with 2‐(4,5‐dihydro‐1H‐imidazol‐2‐ylthioxy)‐4,5‐dihydro‐1H‐imidazole is proposed. Structural assignment is confirmed by ¹H and ¹³C nmr as well as by X‐ray crystallography.     

Preparation of substituted 1,3‐dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐ones

A new synthetic route to 6‐substituted‐imidazo[4,5‐c]pyridin‐2‐ons from 4‐aminopyridine has been investigated. 4‐Aminopyridine protected as alkyl carbamates were nitrated with dinitrogen pentoxide to the corresponding methyl, i‐propyl and t‐butyl 3‐nitropyridin‐4‐yl carbamates ( 5a‐c ) in 51‐63 % yields. Attempts to substitute these in the 6‐position by the ONSH and the VNS techniques succeeded with butyl‐amine and the t‐butyl carbamate 9 . From the methyl or t‐butyl 3‐nitropyridin‐4‐yl carbamates 5a, 5c 1,3‐dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐one ( 1 ) was formed in 73 and 39 % yields, respectively. t‐Butyl 6‐N‐butylamin‐3‐aminopyridin‐4‐yl carbamate ( 6 ) gave 6‐butylamino‐1,3‐dihydro‐2H‐imidazo[4,5‐c]‐pyridin‐2‐one (7) in 53 % yield.     

Synthesis of Imidazole Derivatives Using 2‐Unsubstituted 1H‐Imidazole 3‐Oxides

The reaction of 1,4,5‐trisubstituted 1H‐imidazole 3‐oxides 1 with Ac₂O in CH₂Cl₂ at 0 – 5° leads to the corresponding 1,3‐dihydro‐2H‐imidazol‐2‐ones 4 in good yields. In refluxing Ac₂O, the N‐oxides 1 are transformed to N‐acetylated 1,3‐dihydro‐2H‐imidazol‐2‐ones 5 . The proposed mechanisms for these reactions are analogous to those for N‐oxides of 6‐membered heterocycles (Scheme 2). A smooth synthesis of 1H‐imidazole‐2‐carbonitriles 2 starting with 1 is achieved by treatment with trimethylsilanecarbonitrile (Me₃SiCN) in CH₂Cl₂ at 0 – 5° (Scheme 3).     

Utility of Pyridine‐2(1H)‐thiones in the Synthesis of Novel Bis‐Thieno[2,3‐b]pyridines and Their Fused Azines

The starting materials pyridine‐2(1H)‐thiones are prepared and reacted with halogen‐containing reagents in ethanolic sodium acetate solution to give the corresponding 2‐S‐alkylpyridines, which cyclized upon their boiling in methanolic sodium methoxide solution at reflux to give the corresponding thieno[2,3‐b]pyridines in excellent yields. Bis (thieno[2,3‐b]pyridine‐2‐carboxamides), incorporating 2,6‐dibromophenoxy moiety, are prepared by the bis‐O‐alkylation of thieno[2,3‐b]pyridine‐2‐carboxamide derivatives. Two synthetic routes are designed to prepare the target molecules pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4(3H)‐ones, pyrido[3′,2′:4,5]thieno[3,2‐d][1,2,3]triazin‐4(3H)‐ones, and their bis‐analogues using thieno[2,3‐b]pyridine‐2‐carboxamides and their bis‐analogues. The structure of the target molecules is elucidated using elemental analyses as well as spectral data.     

New 1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidine derivatives II

The 7‐chloro‐3‐(2‐chlorobenzyl)‐ and 7‐chloro‐3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐d]pyrimidines ( 1 and 4 ), by nucleophilic replacement with some hydrazides, gave the corresponding 7‐hydrazidoderivatives ( 2a‐e and 5a‐e ). These, by heating in Dowtherm, underwent an intramolecular cyclization to form the new tricyclic 7‐substituted‐3‐(2‐chlorobenzyl)‐ and 3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidines ( 3a‐d and 6a‐d ). The 7‐hydrazino‐3‐(2‐chlorobenzyl)‐ and 7‐hydrazino‐3‐(2‐fluorobenzyl)‐triazolo‐pyrimidines ( 9a and 9b ) were also prepared via the corresponding mercapto ( 7a and 7b ) and thiomethyl ( 8a and 8b ) derivatives.     

The diastereoisomers methyl 5‐(S)‐[2‐(R)/(S)‐methoxycarbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methylphenyl)‐4,5‐dihydropyrazole‐3‐carboxylate

The title diastereoisomers, methyl 5‐(S)‐[2‐(S)‐methoxy­carbonyl)‐2,3,4,5‐tetra­hydro­pyrrol‐1‐yl­carbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate and methyl 5‐(S)‐[2‐(R)‐methoxycarbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxylate, both C₁₉H₂₃N₃O₅, have been studied in two crystalline forms. The first form, methyl 5‐(S)‐[2‐(S)‐methoxy­carbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methylphenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate–methyl 5‐(S)‐[2‐(R)‐methoxy­carbonyl)‐2,3,4,5‐tetra­hydro­pyrrol‐1‐yl­carbonyl]‐1‐(4‐methylphenyl)‐4,5‐dihydropyrazole‐3‐carboxylate (1/1), 2(S),5(S)‐C₁₉H₂₃N₃O₅·2(R),5(S)‐C₁₉H₂₃N₃O₅, contains both S,S and S,R isomers, while the second, methyl 5‐(S)‐[2‐(S)‐methoxycarbonyl)‐2,3,4,5‐tetrahydro­pyrrol‐1‐ylcarbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate, 2(S),5(S)‐C₁₉H₂₃N₃O₅, is the pure S,S isomer. The S,S isomers in the two structures show very similar geometries, the maximum difference being about 15° on one torsion angle. The differences between the S,S and S,R isomers, apart from those due to the inversion of one chiral centre, are more remarkable, and are partially due to a possible rotational disorder of the 2‐­(methoxycarbonyl)tetrahydropyrrole group.     

Luminescent properties of three structures built from 3‐cyano‐4‐dicyanomethylene‐5‐oxo‐4,5‐dihydro‐1H‐pyrrol‐2‐olate and cadmium

Yellow–orange tetraaquabis(3‐cyano‐4‐dicyanomethylene‐5‐oxo‐4,5‐dihydro‐1H‐pyrrol‐2‐olato‐κN³)cadmium(II) dihydrate, [Cd(C₈HN₄O₂)₂(H₂O)₄]·2H₂O, (I), and yellow tetraaquabis(3‐cyano‐4‐dicyanomethylene‐5‐oxo‐4,5‐dihydro‐1H‐pyrrol‐2‐olato‐κN³)cadmium(II) 1,4‐dioxane solvate, [Cd(C₈HN₄O₂)₂(H₂O)₄]·C₄H₈O₂, (II), contain centrosymmetric mononuclear Cd²⁺ coordination complex molecules in different conformations. Dark‐red poly[[decaaquabis(μ₂‐3‐cyano‐4‐dicyanomethylene‐5‐oxo‐4,5‐dihydro‐1H‐pyrrol‐2‐olato‐κ²N:N′)bis(μ₂‐3‐cyano‐4‐dicyanomethylene‐1H‐pyrrole‐2,5‐diolato‐κ²N:N′)tricadmium] hemihydrate], [Cd₃(C₈HN₄O₂)₂(C₈N₄O₂)₂(H₂O)₁₀]·0.5H₂O, (III), has a polymeric two‐dimensional structure, the building block of which includes two cadmium cations (one of them located on an inversion centre), and both singly and doubly charged anions. The cathodoluminescence spectra of the crystals are different and cover the wavelength range from UV to red, with emission peaks at 377 and 620 nm for (III), and at 583 and 580 nm for (I) and (II), respectively.     

Microwave‐assisted synthesis of some 1,2,4‐triazol‐5‐one derivatives

A series of 3‐alkyl(aryl)‐4‐(p‐hydroxy‐phenyl)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 2 were obtained from the reaction of alkyl (aryl) ester ethoxycarbonyl hydrazones 1 with p‐hydroxy aniline. The reaction of 1 with 1,4‐diamino benzene (1:1) to afford 3‐alkyl(aryl)‐4‐(p‐aminophenyl)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 3 . The reaction of 3 with benzaldehyde gave 3‐alkyl(aryl)‐4‐(4′‐benzilidenamino)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 4 . All of the above reactions occurred under microwave heating and conventional methods. Their structures were confirmed by ¹H NMR, ¹³C NMR, IR, and elemental analyses. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:38–42, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20381     

Report on an Unusual Cascade Reaction between Azulenes and 2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (=4,5‐Dichloro‐3,6‐dioxocyclohexa‐1,4‐diene‐1,2‐dicarbonitrile; DDQ)

The oxidation of 1‐(3,8‐dimethylazulen‐1‐yl)alkan‐1‐ones 1 with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (=4,5‐dichloro‐3,6‐dioxocyclohexa‐1,4‐diene‐1,2‐dicarbonitrile; DDQ) in acetone/H₂O mixtures at room temperature does not only lead to the corresponding azulene‐1‐carboxaldehydes 2 but also, in small amounts, to three further products (Tables 1 and 2). The structures of the additional products 3 – 5 were solved spectroscopically, and that of 3a also by an X‐ray crystal‐structure analysis (Fig. 1). It is demonstrated that the bis(azulenylmethyl)‐substituted DDQ derivatives 5 yield on methanolysis or hydrolysis precursors, which in a cascade of reactions rearrange under loss of HCl into the pentacyclic compounds 3 (Schemes 4 and 7). The found 1,1′‐[carbonylbis(8‐methylazulene‐3,1‐diyl)]bis[ethanones] 4 are the result of further oxidation of the azulene‐1‐carboxaldehydes 2 to the corresponding azulene‐1‐carboxylic acids (Schemes 9 and 10).