New N-acyl, N-alkyl, and N-bridged derivatives of rac-6,6′,7,7′-tetramethoxy-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-bisisoquinoline

The preparation of potential new ligand systems based on the rac-1,1′,2,2′,3,3′,4,4′-octahydro-6,6′,7,7′-tetramethoxy-1,1′-bisisoquinoline skeleton has been investigated. Syntheses of N-(2-bromobenzyl), N-(3-acetoxybenzyl), N-acetyl, N-chloroacetyl, N-chlorocarbonyl, N-ethoxycarbonyl and N-tert-butyloxycarbonyl derivatives and five macrocyclic, polyether containing derivatives are described.     

Synthesis of triprenylated toluquinone and toluhydroquinone metabolites from a marine-derived Penicillium fungus

Two triprenylated toluquinone and toluhydroquinone marine fungal metabolites, 5-methyl-2-[(2′E,6′E)-3′,7′,11′-trimethyl-2′,6′,10′-dodecatrienyl]-2,5-cyclohexadiene-1,4-dione and 5-methyl-2-[(2′E,6′E)-3,7,11-trimethyl-2′,6′,10′-dodecatrienyl]-1,4-benzenediol, were synthesized in four and five steps, respectively, from 2-methyl-1,4-benzoquinone. The synthesis extends the applicability of the oxidative ether cleavage of hydroquinone dimethyl ethers with argentic oxide under acidic conditions to include the oxidative demethylation of polyprenylated-1,4-dimethoxy-toluhydroquinones with a quantitative survival of the oxidation- and acid-sensitive polyprenyl side chain.     

Reactions of 1,4-bis(tetrazole)benzenes: formation of long chain alkyl halides

The reactions of 1,4-bis[2-(tributylstannyl)tetrazol-5-yl]benzene with α,ω-dibromoalkanes were carried out in order to synthesise pendant alkyl halide derivatives of the parent bis-tetrazole. This led to the formation of several alkyl halide derivatives, substituted variously at N1 or N2 on the tetrazole ring. The crystal structures of 1,4-bis[(2-(4-bromobutyl)tetrazol-5-yl)]benzene (2-N,2-N′), 1,4-bis[(2-(4-bromobutyl)tetrazol-5-yl)]benzene (1-N,2-N′) and 1,4-bis[(2-(8-bromooctyl)tetrazol-5-yl)]benzene (2-N,2-N′) are reported. Further discussion involves the structure of 1,4-bis[2-(6-bromohexyl)-2H-tetrazol-5-yl]benzene (2-N,2-N′) previously reported.     

Domino reactions in water for the stereoselective synthesis of novel spiro dihydro-2′H-[indene-2,3′-thiophen]-1(3H)-ones with three contiguous stereocenters

The domino reactions of (E)-2-(aryl)-2,3-dihydro-1H-inden-1-ones and 1,4-dithiane-2,5-diol in the presence of triethylamine in water stereoselectively afforded a library of 2′-(aryl)-4′-hydroxy-4′,5′-dihydro-2′H-spiro[indene-2,3′-thiophen]-1(3H)-ones. This transformation presumably proceeds via the generation of 2-mercaptoacetaldehyde from 1,4-dithiane-2,5-diol followed by Michael addition–intramolecular aldol sequence with C–C and C–S bond formations and creation of three contiguous stereocenters in a one-pot operation.     

Regioselective synthesis of 1H,3H,6H[2]benzopyrano[4,3-d]pyrimidine-2,4-diones and 12H-benzopyrano[3,2-c][1]benzopyran-5-ones by radical cyclization

5-Hydroxy uracils or 4-hydroxy[1]benzopyran-2-ones were refluxed with 2-bromobenzyl bromides in acetone in the presence of anhydrous potassium carbonate to afford a number of 5-(2′-bromobenzyloxy) pyrimidine-2,4-dione (80-92%) or 4-(2′-bromobenzyloxy) benzopyran-7-ones (70-82%) respectively. These were then refluxed with tri-n-butyltin chloride and sodium cyanoborohydride in the presence of a catalytic amount of azobisisobutyronitrile (AIBN) for 3-4 h to give 1H,3H,6H [2]benzopyrano[4,3-d]pyrimidine-2,4-diones (75-85%) or 12H-benzopyrano[3,2-c][1]benzopyran-5-ones (70-85%) respectively.     

Synthesis of triaryls: hydroxy and amine dinaphthyl and diphenanthryl aryls by one-pot electron-transfer nucleophilic substitution reactions

A new one-pot synthetic route to achieve the preparation of hydroxy and amine binaphthyl and biphenanthryl aryls is here reported. This approach involves the reaction of 1,4-bromoiodobenzene, 4,4′-diiodobiphenyl, and 1,4- and 1,5-diiodonaphthalene with the anions of 2-naphthylamine, 2-naphthol, and 9-phenanthrylamine under irradiation in liquid ammonia. The reactions proceed to afford triaryl derivatives in moderate to good yields (∼45% of 1,4-phenylene- and 1,4-naphthylene-1,1′-dinaphthalen-2-ols as well as 1,4-phenylene-1,1′-dinaphthalen-2-amine and 10,10′-diphenanthren-9-amine). Lower yields (27%) of polyaryl derivatives are obtained by reaction of 4,4′-diiodobiphenyl with anions of 2-naphthol and 9-phenanthrylamine.     

Synthesis of conjugated (1E,3E)- and (1Z,3Z)-1,4-di(n-pyridyl) (or n-quinolyl)-1,3-butadienes from n-(2′-chloroethenyl)pyridine (or quinoline)

The homocoupling reaction between the conjugated n-(2-chloroethenyl)pyridine; n, 2-, 3- and 4- (or quinoline; n, 2- and 4-) mediated by zero-valent nickel complexes at room temperature affords to the corresponding 1,4-diaryl-1,3-butadiene, always as the 1E,3E stereoisomer. The yield in 1,4-diaryl-1,3-butadiene increases with the nickel catalyst and hence, the active zero-valent nickel catalyst is not regenerated during the homocoupling reaction.The stereospecific synthesis of (1Z,3Z)-1,4-di(4′-pyridyl)-1,3-butadiene stereoisomer was efficiently carried out by partial hydrogenation of the appropriate 1,4-di(4′-pyridyl)-1,3-butadiyne.     

Synthesis of n-chloroquinolines and n-ethynylquinolines (n=2, 4, 8): homo and heterocoupling reactions

The n-(ethynyl)quinolines were satisfactorily prepared by heterocoupling reaction between the appropriate n-chloroquinoline and 2-methyl-3-butyn-2-ol, catalyzed by palladium, followed by treatment with a catalytic amount of powdered sodium hydroxide in toluene. The n-(ethynyl)quinolines were transformed in the corresponding conjugate 1,4-bis[n′-(quinolyl)]buta-1,3-diynes by oxidative dimerization, catalyzed by cuprous chloride, with excellent yields. Moreover, the heterocoupling between n′-haloquinoline and n′-(ethynyl)quinoline (n′, 2′ or 3′), catalyzed by palladium, gives 2′,2′-bis(quinoline) or 1,2-di(3′-quinolyl)ethyne, respectively. The same coupling reaction with zerovalent nickel complexes, gives a mixture of 1,2,4- and 1,3,5-tri(n′-quinolyl)benzene.     

Synthesis of new bis(2-[1,8]naphthyridinyl) bridging ligands with multidentate binding sites

A series of new 2-[1,8]naphthyridinyl and bis(2-[1,8]naphthyridinyl) bridging ligands with multidentate binding sites were prepared using 2-amino-5-cyano-6-ethoxy-4-phenyl-3-carbaldehyde pyridine as excellent Friedländer synthon. Condensation with a series of acetyl(heteroaryl)aromatics provides the corresponding 2-aryl(heteroaryl)-1,8-naphthyridines. Reaction with 1,3-diacetylbenzene, 2,6-diacetylpyridine or 4-tert-butyl-2,6-diacetylpyridine provides the expected Friedländer product. Similar 2:1 condensation with 1,4-diacetylbenzene, 4,4′-diacetylbiphenyl, 1,4- and 1,6-diacetylpyrene, 2,6-diacetylpyrazine or 2,3-butanedione leads to a family of six new bis-1,8-nap ligands. The reaction with cyclic 1,2- or 1,3-diketones affords 3,3′-annelated derivatives of all-syn or all-trans planar 2,2′-nap, respectively. Examination of the electronic absorption and emission spectra of the bridging ligands was realized.     

A pentacyclic condensation product from 2,4-dimethyl-7-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid

2,4-Dimethyl-7-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid on preparation of a mixed anhydride, followed by reduction with sodium borohydride, affords 5,7a,13,13b-tetramethyl-2,10-dinitro-5a,7,7a,13,13a,13b-hexahydro-5H-[1,4]benzoxazino[3′,2′:4,5]pyrano[3,2-b][1,4]benzoxazine (3), the structure of which was established unambiguously by X-ray analysis.     

Naphthidine di(radical cation)s-stabilized palladium nanoparticles for efficient catalytic Suzuki-Miyaura cross-coupling reactions

Stable Pd(0) nanoparticles were prepared at room temperature in 1,4-dioxane from PdCl₂ using N,N′-bis(4-methoxyphenyl)-(1,1′-binaphthyl)-4,4′-diamine (naphthidine) as reducing and stabilizing agent. This procedure resulted in Pd(0) particles possessing an average diameter of ca. 25 nm stabilized against aggregation due to a barrier of the naphthidine di(radical cation) Napht^2.2+. These particles were evaluated for their capability to act as catalysts in Suzuki-Miyaura coupling reactions. The Pd(0)/Napht^2.2+ provides a general and convenient method to prepare biaryls from aryl bromides or iodides and boronic acids with a broad range of functional groups in 1,4-dioxane at 80 °C and under aerobic conditions.     

Synthesis and properties of 1,3,3-trimethylspiro[indoline-2,3′-naphtho[2,1-b][1,4]oxazin]-6′-amine, a novel, red colouring photochromic spirooxazine

The synthesis and photochromic properties of 1,3,3-trimethylspiro[indoline-2,3′-naphtho[2,1-b][1,4]oxazin]-6′-amine, a novel red-colouring photochromic spirooxazine and derivatives is reported. The synthesis proceeds via an unusual one-pot transamination, oxime formation, N-O bond cleavage, spirooxazine formation process.     

C-H activations on a 1H-1,4-benzodiazepin-2(3H)-one template

Air stable benzodiazepine containing palladacycles were synthesized by a C-H activation reaction and studied by mass spectrometry and X-ray crystallography. Catalytic C-H functionalizations of 1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one with diphenyliodonium hexafluorophosphate led to a mixture, which included the starting material and the expected product 1-methyl-5-(2′-biphenyl)-1H-1,4-benzodiazepin-2(3H)-one.     

Synthesis and anti-HIV activities of bis-(cycloSaligenyl) pronucleotides derivatives of 3′-fluoro-3′-deoxythymidine and 3′-azido-3′-deoxythymidine

Anti-HIV nucleoside monophosphates have limited cellular uptake due to the presence of negatively-charged phosphate group. Bis-(cycloSaligenyl) derivatives containing two anti-HIV nucleosides, 3′-fluoro-3′-deoxythymidine (FLT) and 3′-azido-3′-deoxythymidine (AZT) were synthesized to increase intracellular delivery of nucleoside monophosphates. 2,5-Bis(hydroxymethylene)benzene-1,4-diol was selected as a monocyclic bidentate scaffold and synthesized by three different methods from bis(hydroxymethylene)cyclohexan-1,4-diene-1,4-diol, or diethyl 2,5-dihydroxyterephthalate. The reaction of the tetraol with diisopropylphosphoramidous dichloride in the presence of 2,6-lutidine, followed by conjugation reactions with nucleosides (i.e., FLT and AZT) and oxidation afforded symmetrical and unsymmetrical bis-(cycloSaligenyl) diphosphate triester products, AZT-AZT, FLT-FLT, and FLT-AZT conjugates, in 63-74% overall yields and modest anti-HIV activities (IC₅₀ = 2.8-69.6 μM).     

Dimerization of a lattice-framework silanone into the corresponding 1,3-dioxa-2,4-disiletanes

A lattice-framework silanone, a racemate of (4R,6R)- and (4S,6S)-2,3,4,6,7,8-hexa-tert-butyl-1,5-disilatricyclo[4.2.0.0^1,4]octa-2,7-dien-5-one (4), was generated by the photoreaction of the corresponding lattice-framework disilene, a racemate of (4R,6R,4′R,6′R)- and (4S,6S,4′S,6′S)-2,3,4,6,7,8,2′,3′,4′,6′,7′,8′-dodeca-tert-butyl-[5,5′]bi{1,5-disilatricyclo[4.2.0.0^1,4]octylidene}-2,7,2′,7′-tetraene (dl-1), with mesitonitrile oxide. The silanone 4 was dimerized to produce a mixture of the corresponding dl- and meso-1,3-dioxa-2,4-disiletane derivatives 2. DFT calculations suggested that the non-selective dimerization of 4 to 2 is attributed to the irreversibility of the reaction.     

Cathodic reduction of hydroxycarbonyl compound trichloroacetyl esters

New coumarins and new 2-(2′,2′-dichlorovinyl) phenols have been prepared by cathodic reduction under potentiostatic conditions of trichloroacetyl esters of o-hydroxyketones and o-hydroxyaldehydes in aprotic media. Electroreductions of trichloroacetyl esters of α-hydroxy-1,4-naphthoquinone, 3-hydroxy-2-methyl-4-pyrone, methyl salicylate and benzoin have also been investigated.     

Access to thiomorpholin-3-one derivatives: [3 + 3]-cycloadditions of α-chlorohydroxamates and 1,4-dithiane-2,5-diol

A protocol of [3 + 3]-cycloaddition was proposed for the synthesis of 2H-1,4-thiazin-3(4H)-ones and thiomorpholine-3,5-diones from α-chlorohydroxamates and 1,4-dithiane-2,5-diol. This direct and practical method provides a novel and rapid approach for the synthesis of thiomorpholin-3-one derivatives under mild condition with moderate to good yield and wide functional group tolerance.     

DAB-Cy as an inexpensive and effective ligand for palladium-catalyzed homocoupling reaction of aryl halides

A novel catalytic system of PdCl₂(CH₃CN)₂ with N,N′-dicyclohexyl-1,4-diazabutadiene (DAB-Cy) ligand was successfully used in reductive coupling of aryl halides.     

Synthesis and optical properties of a poly(2′,5′-dioctyloxy-4,4′,4″- terphenylenevinylene) with high content of (Z) vinylene units

Poly(2′,5′-dioctyloxy-4,4′,4″-terphenylenevinylene) with (E) configuration of the vinylene double bonds was prepared by Suzuki-Miyaura polymerization of (E)-4,4′-dibromostilbene and 2,5-dioctyloxy-1,4-benzenediboronic acid. Attempts to extend this simple procedure to the synthesis of the polymer with (Z) configuration, starting from (Z)-4,4′-dibromostilbene, were unsuccessful. However, the use of (Z)-4,4′-diiodostilbene and a careful choice of Pd catalyst and experimental conditions, lead to a material with a >95/<5 (Z)/(E) ratio of vinylene units. The investigation of optical properties of both the (E) and (Z) polymers evidenced that (Z) linkages act as defects which reduce the effective conjugation length in the polymer backbone.