Vilsmeier-Haak formylation of 3,5-dimethylpyrazoles

Formylation of N-alkyl-3,5-dimethyl-1H-pyrazoles according to Vilsmeier-Haak led to the formation of the corresponding 4-formyl derivatives. 3,5-Dimethyl-1H-pyrazole having no substituent on the nitrogen atom failed to undergo formylation at the 4 position under analogous conditions. 3,5-Dimethyl-1H-pyrazole-4-carbaldehyde was synthesized by alkaline hydrolysis of methyl β-(4-formyl-3,5-dimethyl-1H-pyrazol-1-yl)propionate and subsequent heating of the acid thus formed.     

Reactions of fluorine-containing 3-oxo esters with aldehydes

Fluoroalkylcontaining 3-oxo esters react with aldehydes to form 2-benzylidene-3-fluoroacyl-esters or 4-aryl(alkyl)-3,5-dialkoxycarbonyl-2,6-dihydroxy-2,6-di(fluoroalkyl)tetrahydropyranes depending on the conditions. Ethyl pentafluorobenzoylacetoacetate with benzaldehyde affords 3,5-diethoxy-carbonyl-4-phenyl-2-pentafluorophenyl-7,8,9,10-tetrafluoro-4,5-dihydrobenzo[b]oxacin-6-one.     

Regioselective bromination and iodination of aromatic substrates promoted by trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane

Selective and efficient bromination and iodination of aromatic compounds by ammonium bromide and ammonium iodide, respectively, under promotion of trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane have been explored. Mild reaction conditions, high selectivity and yield, and high reaction rate are some of the major advantages of this synthetic method.     

Photolysis of the Insensitive Explosive 1,3,5-Triamino-2,4,6-trinitrobenzene (TATB)

The explosive 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) is of particular interest due to its extreme insensitivity to impact, shock and heat, while providing a good detonation velocity. To determine its fate under environmental conditions, TATB powder was irradiated with simulated sunlight and, in water, under UV light at 254 nm. The hydrolysis of particles submerged in neutral and alkaline solutions was also examined. We found that, by changing experimental conditions (e.g., light source, and mass and physical state of TATB), the intermediates and final products were slightly different. Mono-benzofurazan was the major transformation product in both irradiation systems. Two minor transformation products, the aci-nitro form of TATB and 3,5-diamino-2,4,6-trinitrophenol, were detected under solar light, while 1,3,5-triamino-2-nitroso-4,6-dinitrobenzene, 1,3,5-triamino-2,4-dinitrobenzene and mono-benzofuroxan were produced under UV light. The product identified as 3,5-diamino-2,4,6-trinitrophenol was identical to the one formed in the dark under alkaline conditions (pH 13) and in water incubated at either 50 °C or aged at ambient conditions. Interestingly, when only a few milligrams of TATB were irradiated with simulated sunlight, the aci-isomer and mono-benzofurazan derivative were detected; however, the hydrolysis product 3,5-diamino-2,4,6-trinitrophenol formed only much later in the absence of light. This suggests that the water released from TATB to form mono-benzofurazan was trapped in the interstitial space between the TATB layers and slowly hydrolyzed the relatively stable aci-nitro intermediate to 3,5-diamino-2,4,6-trinitrophenol. This environmentally relevant discovery provides data on the fate of TATB in surface environments exposed to sunlight, which can transform the insoluble substrate into more soluble and corrosive derivatives, such as 3,5-diamino-2,4,6-trinitrophenol, and that some hydrolytic transformation can continue even without light.     

Remarkable Chichibabin-type cyclotrimerisation of 3-nitrotyrosine, tyrosine and phenylalanine to 3,5-diphenylpyridine derivatives induced by hypochlorous acid

Reaction of 3-nitrotyrosine with HOCl in aqueous phosphate buffer (pH 7.4) leads to a mixture of extractable products, including 3,5-di(4-hydroxy-3-nitrophenyl)pyridine (15% isolated yield) and 3,5-di(4-hydroxy-3-nitrophenyl)-2-(4-hydroxy-3-nitrophenylmethyl)pyridine (3%) arising by a Chichibabin-like pyridine synthesis via N-chloroimine intermediates. Under the same conditions, phenylalanine gives 3,5-diphenylpyridine in 9% isolated yield, while tyrosine leads to 3,5-di(4-hydroxyphenyl)pyridine (3%) and 3-(3-chloro-4-hydroxyphenyl)-5-(4-hydroxyphenyl)pyridine (3%).     

A mild and efficient method for halogenation of 3,5-dimethyl pyrazoles by ultrasound irradiation using N-halosuccinimides

The 4-halo-3,5-dimethyl pyrazoles have been synthetisized in good yields in short reaction times in the absence of a catalyst by reaction of 3,5-dimethyl pyrazoles with N-halosuccinimides (NBS, NCS and NIS) under ultrasound irradiation. Finally, the halogenation of pyrazoles with Br₂, ICl and I₂ was showed in similar conditions.     

Reactions of benzazole-2-thiones with 3,5-di-<Emphasis Type="Italic">tert</Emphasis>-butyl-4-hydroxybenzyl acetate

The benzylation of benzothiazole(oxazole, imidazole)-2-thiones with 3,5-di-tert-butyl-4-hydroxybenzyl acetate involves either the sulfur or nitrogen atom depending on the reaction conditions. The S- and N-benzylation products of benzazole-2-thiones are kinetically and thermodynamically controlled products, respectively. The use of 3,5-di-tert-butyl-4-hydroxy-benzyl acetate allows sterically hindered hydroxybenzyl derivatives of benzаzole-2-thiones to be generally synthesized under milder conditions than in known methods of their synthesis.     

Biomimetic oxidation of metribuzin with hydrogen peroxide catalyzed by 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides

The biomimetic oxidation of metribuzin, a pre- and post-emergence herbicide with hydrogen peroxide catalyzed by 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides [TAPFe(III)Cl], has been studied yielding 6-t-butyl-3-methylthio-1,2,4-triazine-5(4H)-one, 4-amino-6-t-butyl-3,5(2H,4H)-dione and 6-t-butyl-1,2,4-triazin-3,5(2H,4H)-dione under various reaction conditions.     

Polyhalogenoheterocyclic compounds: Part 54: [1] Suzuki reactions of 2,4,6-tribromo-3,5-difluoropyridine

Palladium catalysed Suzuki cross-coupling reactions between 2,4,6-tribromo-3,5-difluoropyridine and a short series of aromatic boronic acid derivatives gave 4-bromo-3,5-difluoro-2,6-diphenylpyridine derivatives arising from displacement of bromine atoms attached to positions ortho to ring nitrogen or the corresponding triaryl systems depending on the reaction conditions. Consequently, the use of polybromofluoropyridine scaffolds for the synthesis of polyfunctional heteroaromatic derivatives is expanded further.     

An alternative model for the asymmetric addition of cyanide to aldehydes catalysed by titanium–salen complexes based on a structurally related iron–salen complex

X-ray crystallographic analysis of [(Fe(3,5-Bu^t-salen))₂O] 4 allied with comparison of structurally related analogues is used to support an alternative transition state in the titanium–salen catalysed addition of cyanide to aldehydes. Experimental conditions for the preparation and isolation of [(Fe(3,5Bu^t-salen))₂O] are also reported.     

Chiral 1,2,4-triazoles: stereoselective acylation and chlorination

Acyl groups are transferred from diverse N- and O-acyl derivatives of chiral 3,5-bis-(1-hydroxyethyl)-[1,2,4]-triazole to amino acid esters enantioselectively, with 7% to 68% ee, depending on the temperature conditions and nature of the reagents. Thionyl chloride replaced the hydroxyl groups of (S)-1-[4-amino-5-((S)-1-hydroxy-ethyl)-[1,2,4]-triazol-3-yl]-ethanol 3 stereospecifically with inversion, as confirmed by X-ray analysis, which also revealed unusual crystal structures with asymmetric units comprising three molecules of 4-amino-3,5-bis(R-1-chloroethyl)-1,2,4-triazole 5 and four of 3,5-bis((R)-1-chloroethyl)-1H-1,2,4-triazole 6.     

Effects of solvation on charge distribution of 1,2-semiquinonato/catecholatocobalt complexes containing bis(3-pyridyl) phenylvinylsilane

Recrystallization of [Co(3,5-dbbq)₂(L)₂] (3,5-dbbq?=?3,5-di-tert-butyl-1,2-benzoquinone; L?=?bis(3-pyridyl)phenylvinylsilane) from diethyl ether at ?20?°C produces trans-[Co(3,5-dbbq)₂(L)₂] while the recrystallization from toluene at ?20?°C gives trans-[Co(3,5-dbbq)₂(L)₂]·2PhMe. The complex exists as trans-[Co^III(3,5-dbsq)(3,5-dbcat)(L)₂] (3,5-dbsq?=?3,5-di-tert-butyl-1,2-semiquinonato; 3,5-dbcat?=?3,5-di-tert-butylcatecholato) in the solid state at 173?K. Differences in charge distribution between trans-[Co(3,5-dbbq)₂(L)₂] and trans-[Co(3,5-dbbq)₂(L)₂]·2PhMe have been observed based on the effective magnetic moments and IR spectra of the complexes along with their X-ray crystal structures.     

A new method for enol lactone synthesis by a Michael addition/cyclization sequence

Reactions of cyclic 1,3-dicarbonyl compounds with 1-(2-alkenoyl)-4-bromo-3,5-dimethylpyrazoles under the double catalytic activation conditions using both catalytic amounts of Lewis acid and amine catalysts provide a new direct synthetic route to enol lactones. Thus, 1,3-cyclohexanedione is allowed to react with 4-bromo-1-crotonoyl-3,5-dimethylpyrazole, in tetrahydrofuran at room temperature in the presence of both catalytic amounts (10 mol% each) of nickel(II) perchlorate hexahydrate and 2,2,6,6-tetramethylpiperidine, to give 4,7,7-trimethyl-3,4,5,6,7,8-hexahydrobenzopyran-2(H),5-dione in a good yield. This reaction does not proceed or is too slow under the reaction conditions other than the double catalytic activation conditions.     

Solvent-free combinatorial synthesis of tetrazolo[1,5-a]thiopyrano[3,4-d]pyrimidine derivatives

A series of novel tetrazolo[1,5-a]thiopyrano[3,4-d]pyrimidine derivatives were synthesized by reaction of aryl aldehyde, 2H-thiopyran-3,5(4H,6H)-dione, and 5-aminotetrazole under solvent-free conditions. The features of this procedure are mild reaction conditions, high yields, and operational simplicity.     

Synthesis of methylated resveratrol and analogues by Heck reactions in organic and aqueous solvents

The Heck reaction under phosphane free conditions using oxime-derived palladacycles or Pd(OAc)₂ as catalysts is a general methodology for the synthesis of methoxylated (E)-stilbene derivatives. Couplings can be performed either with (dicyclohexyl)methylamine as base and TBAB in aqueous DMA or in neat water and with Et₃N as base in DMA in air and under thermal and microwave conditions. The arylation of different styrenes are performed with 3,5-dimethoxyiodobenzene to afford a series of important biologically active (E)-stilbene derivatives containing the 3,5-dimethoxyphenyl moiety, including resveratrol, piceatannol and pinosilvine, which are efficiently prepared with high regioselectivity and total stereoselectivity (TON up to 10⁴).     

Synthesis of 2-diphenylphosphinoyl-3,5-diaryl-3,4-dihydro-2H-telluropyrans by reaction of chalcones with bis[(diphenylphosphinoyl)methyl]telluride

The NaH-promoted tandem Michael addition/intramolecular Wittig-Horner reaction of bis[(diphenylphosphinoyl) methyl]telluride with chalcones stereoselectively afforded trans-2-diphenylphosphinoyl-3,5-diaryl-3,4-dihydro-2H-telluropyran derivatives in 51-72% yield, under mild conditions.     

Benzochromenopyrimidines: Synthesis,Antiproliferative Activity against Colorectal Cancer and Physicochemical Properties

Ten new differently substituted 3-benzyl-5-aryl-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidin-4,6,11-triones 3 were synthesized by a simple and cost-efficient procedure in a one-pot, three-component reaction from readily available ethyl 2-amino-4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene-3-carboxylates, benzylamine and triethyl orthoformate under solvent- and catalyst-free conditions. All the new compounds were screened for their antiproliferative activity against two colorectal-cancer-cell lines. The results showed that the compounds 3-benzyl-5-phenyl-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidine-4,6,11-trione (3a) and 3-benzyl-5-(3-hydroxyphenyl)-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidine-4,6,11-trione (3g) exhibited the most potent balanced inhibitory activity against human LoVo and HCT-116 cancer cells.     

Substitution at C-4 in 3,5-disubstituted 4H-1,2,6-thiadiazin-4-ones

3,5-Diaryl-4H-1,2,6-thiadiazin-4-ones react with NaBH₄ to give the 3,5-diaryl-4H-1,2,6-thiadiazin-4-ols and with MeLi to give 4-methyl-3,5-diaryl-4H-1,2,6-thiadiazin-4-ols. The latter dehydrate with p-toluenesulfonic acid to give (3,5-diarylthiadiazin-4-ylidene)methanes. (3,5-Diphenyl-4H-1,2,6-thiadiazin-4-ylidene)methane 15 suffers mono bromination with NBS to give bromo(3,5-diphenyl-4H-1,2,6-thiadiazin-4-ylidene)methane 17. Dichloro- and dibromo(3,5-diphenyl-4H-1,2,6-thiadiazin-4-ylidene)methanes 18 and 19 are formed directly from the 3,5-diphenylthiadiazin-4-one 9 via the Appel reaction using Ph₃P and CCl₄ or CBr₄, respectively. 3,5-Diarylthiadiazin-4-ones treated with P₂S₅ give 3,5-diarylthiadiazine-4-thiones that react with tetracyanoethylene oxide to give the (thiadiazin-4-ylidene)malononitriles. Finally, the 3,5-diphenylthiadiazine-4-thione 20 reacts with ethyl diazoacetate to give ethyl 2-(3,5-diphenyl-4H-1,2,6-thiadiazin-4-ylidene)acetate 26. The above reactions show that a variety of substitutions at C-4 of 3,5-diaryl substituted 1,2,6-thiadiazin-4-ones can be achieved, which extends the potential applications of this heterocycle. All compounds are fully characterized and a brief comparison of their spectroscopic properties is given.     

Total synthesis of verbalactone: an efficient, carbohydrate-based approach

A carbohydrate-based strategy for the total synthesis of verbalactone has been described. (3R,5R)-3,5-dihydroxydecanoic acid was dimerised under Yamaguchi conditions to provide verbalactone in an overall yield of 17% starting from 3-deoxy-1,2:5,6-di-O-isopropylidine-α-d-glucofuranose.     

Reaction of 3,4-diiodo-2,5-dimethyl-1H-pyrrole with thioamides

3,4-Diiodo-2,5-dimethyl-1H-pyrrole reacted with thioacetamide in polar solvents or under solvent-free conditions to give 2,4,6-trimethyl-5H-pyrrolo[3,4-d][1,3]thiazole. The major product in the reaction of the title compound with thiobenzamide was 3,5-diphenyl-1,2,4-thiadiazole.