5-Benzyl-1H-tetrazols from the reaction of 1-aryl-5-methyl-1H-tetrazoles with 1,2-dehydrobenzene

A series of 1-aryl-5-benzyl-1H-tetrazoles has been obtained during the reaction of 1-aryl-5-methyl-1H-tetrazoles with 1,2-dehydrobenzene. The mechanism of product formation was investigated.     

Synthesis of substituted 4-(1H-indol-6-yl)-1H-indazoles as potential PDK1 inhibitors

The development of a preparative route to a series of novel 4-(1H-indol-6-yl)-1H-indazole compounds as potential PDK1 inhibitors is described. The synthetic strategy centres on the late-stage Suzuki cross-coupling of N-unprotected indazole and indole fragments. The use of a monoligated palladium catalyst system was found to be highly beneficial in the cross-coupling reaction. The indazole and indole fragments were constructed by diazotisation/cyclisation and S_NAr/reductive cyclisation sequences, respectively.     

A novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles and its application in the synthesis of Rizatriptan

In this study, a novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles (8) is presented starting from (1H-1,2,4-triazol-1-yl)methanol (5) and indolines (6) under 98% H₂SO₄ at room temperature for 4–24 h, followed by deacetylation and dehydrogenation. Based on this finding, a novel route to synthesize Rizatriptan starting from tryptamine was designed and accomplished with 48.5% overall yield in 6 steps. Compared with operational art, the new route afforded higher yield and more pure products requiring no chromatographic purification, which may further be applied in industrialization.     

On the explosive properties of 1H-benzotriazole and 1H-1,2,3-triazole

For 1H-benzotriazole, no explosive properties are observable, but the relative high exothermic decomposition energy of 1590 J/g should be kept in mind. Nevertheless, an endothermic melting barrier at 100 °C ensures safe handling at lower temperatures. For 1H-1,2,3-triazole, the exothermic decomposition energy is as high as 2600 J/g, but explosive properties are also not detectable. Therefore, both reagents are hazardous with regard to the exothermic decomposition potential and can be handled safely with precautions.     

Synthesis and reactions of 5-tributylstannyl-4-fluoro-1H-pyrazole

The palladium-catalyzed cross-coupling reactions of 5-tributylstannyl-4-fluoro-1H-pyrazole with aryl iodides provided high yields of the corresponding 5-aryl-4-fluoro-1H-pyrazoles. Furthermore, these cross-coupling reactions proceeded smoothly under an atmosphere of carbon monoxide (CO) to afford the corresponding 5-acyl-4-fluoro-1H-pyrazoles as CO-insertion products.     

Facile hydroboration of (Z)-1-trimethylsilyl-1-alkenes with dichloroborane-dioxane complex: An easy access to gem-dimetalloalkanes containing boron and silicon

(Z)-1-trimethylsilyl-1-alkenes easily prepared by the hydroboration of the corresponding 1-trimethylsilyl-1-alkynes followed by protonolysis with acetic acid, readily react with dichloroborane-dioxane complex in dichloromethane for 6 h. The resulting solution is then treated with 1,3-propane diol in dichloromethane at 0 °C for half an hour to provide the corresponding gem-dimetalloalkanes containing boron and silicon. These α-trimethylsilylalkylboronate esters are purified by vacuum distillation in high yields (72-84%) and the structures of these novel intermediates are further confirmed by selective oxidation with alkaline hydrogen peroxide to provide the corresponding alcohols containing α-trimethylsilyl group in 78-88% isolated yields.     

Efficient synthesis of new 3-heteroaryl-1-functionalized 1H-indazoles

The efficient synthesis of novel 3-heteroaryl N-1-functionalized indazoles, via palladium cross-coupling reactions of ethyl (3-iodo-1H-indazol-1-yl)acetate with 2- and 3-pyrrolylboronic acids, 2-, 4- and 5-thiazolylstannanes, and other heteroarylmetallated derivatives are reported.     

Efficient and rapid synthesis of 1-substituted-1H-1,2,3,4-tetrazoles in the acidic ionic liquid 1-n-butylimidazolium tetrafluoroborate

An efficient synthesis leading directly to 1-substituted-1H-1,2,3,4-tetrazoles from easily available amines and sodium azide in stoichiometric proportions using a room-temperature ionic liquid, namely, 1-n-butylimidazolium tetrafluoroborate in excellent yields is described. The inherent Brønsted acidity and high polarity of the IL results in a significant enhancement in the reaction rate.     

Novel rearrangement of 1H-2,3-benzoxazines to cyclic N-acyl hemiaminals: application to the synthesis of 1-arylnaphthalene skeletal congeners

The rearrangement of 1H-2,3-benzoxazine derivatives has been investigated. The reaction affords cyclic hemiaminal derivatives for their conversion to the corresponding 1-arylisobenzofurans, which can be trapped by various dienophiles to afford skeletal congeners of 1-arylnaphthalene lignans.     

Synthesis of 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-ones via Pd-catalyzed regioselective cross-coupling reaction and cyclization

An efficient and novel route for the synthesis of 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-one 1 via palladium-catalyzed site-selective cross-coupling reaction and cyclization process was described. Reaction of 3-bromo-4-trifloxy-quinolin-2(1H)-one 3 with arylboronic acid catalyzed by PdCl₂(PPh₃)₂ afforded 3-bromo-4-aryl-quinolin-2(1H)-one 4, which then reacted with 2-ethynylaniline 5 via Pd-catalyzed Sonogashira coupling and CuI-mediated cyclization leading to the desired 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-one 1 in good yields.     

A hetero-Diels-Alder approach to functionalized 1H-tetrazoles: synthesis of tetrazolyl-1,2-oxazines, -oximes and 5-(1-aminoalkyl)-1H-tetrazoles

This work describes the first and unprecedented examples of inverse electron demand Diels-Alder reactions of 5-(1-nitrosovinyl)-1-phenyl-1H-tetrazole, generated in situ from the corresponding bromooxime, with electron rich alkenes and heterocycles, providing in good overall yields tetrazolyl-1,2-oxazines and -oximes. Upon subsequent reduction these allowed the access to 5-(1-aminoalkyl)-1H-tetrazoles, paving the way for a new entry into this important class of compounds, bioisosteres of α-amino acids.     

Alternatives to 1-H-tetrazole in the preparation of phosphonate diesters and phosphonamidates from phosphonyl dichlorides

5-Ethylthio-1-H-tetrazole (SET) and 4,5-dicyanoimidazole (DCI) were examined as alternatives to 1-H-tetrazole to mediate the synthesis of phosphonate diesters and phosphonamidates from phosphonyl dichlorides through a two-step one-pot reaction in various organic solvents. SET and DCI were comparable to 1-H-tetrazole for catalyzing these reactions. SET afforded slightly greater yields than DCI while benzene was universally the best solvent for this reaction.     

Flash vacuum pyrolysis of 2,2-dioxo-1H,3H-pyrrolo[1,2-c]thiazoles and 2-vinyl-1H-pyrroles

The flash vacuum pyrolysis of new 1,1-dimethyl- and 1-methyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides gave penta-substituted 2-vinyl-1H-pyrroles via sigmatropic [1,8]-H shift of the corresponding azafulvenium methide intermediates. In some cases these 1H-pyrroles underwent rearrangement to 2-allyl-1H-pyrroles. Di-substituted 2-vinylpyrroles have also been prepared and their reactivity studied. Under FVP N-benzyl-pyrrol-2-ylpropenoates were converted into 3H-pyrrolizin-3-ones. On the other hand, microwave-assisted reaction of 1-benzyl-2-vinyl-1H-pyrrole gave a 4,5,6,7-tetrahydro-1H-indole derivative.     

Library construction of 1-(1H-imidazol-1-yl)-1,2-dihydroisoquinolines via three-component reaction of 2-alkynylbenzaldehyde, amine, and imidazole

Parallel diversity-oriented synthesis of diverse 1-(1H-imidazol-1-yl)-1,2-dihydroisoquinolines via AgOTf-catalyzed three-component reaction of 2-alkynylbenzaldehyde, amine, and imidazole is described. This reaction works efficiently under mild conditions to generate a small library of imidazole-incorporated 1,2-dihydroisoquinolines.     

Morita-Baylis-Hillman route to 4H-pyrrolo[1,2-a][1]benzazepine derivatives

A simple method for synthesizing substituted 4H-pyrrolo[1,2-a][1]benzazepines using acid-assisted cyclization of the Morita-Baylis-Hillman adducts of 2-(1H-pyrrol-1-yl)benzaldehydes with methyl acrylate or methyl vinyl ketone as a key step has been developed.     

Synthesis of (Z)-1-bromo-1-alkenes and terminal alkynes from anti-2,3-dibromoalkanoic acids by microwave-induced reaction

(Z)-1-Bromo-1-alkenes were stereoselectively prepared in high yields in a short reaction time by microwave irradiation of the corresponding anti-2,3-dibromoalkanoic acids in a Et₃N/DMF system. A one-pot synthesis of terminal alkynes and enynes from 2,3-dibromoalkanoic acids were also developed by microwave-induced reaction.     

Preparation of telechelic oligomers by controlled thermal degradation of isotactic poly(1-butene) and poly(propylene-ran-1-butene)

It was found that telechelic isotactic oligo(1-butene) and telechelic oligo(propylene-ran-1-butene) could be isolated as nonvolatile oligomers from polymer residues resulting from the thermal degradation of isotactic poly(1-butene) and poly(propylene-ran-1-butene), respectively. Their structures were determined by ¹H and ¹³C NMR with attention being paid to their reactive end groups. The maximum average number of terminal vinylidene groups per molecule (f_TVD) was 1.8, indicating that about 80 mol% were α,ω-diene oligomers having two terminal vinylidene groups. This useful new telechelic oligomer had a lower polydispersity than the original polymer, in spite of its lower molecular weight and T_m. The composition of end groups of nonvolatile oligomers obtained by thermal degradation of poly(propylene-ran-1-butene) could be explained by the differences in bond dissociation energy and activation energy of elementary reactions during thermal degradation, based on the monomer composition of the original polymer.     

Reductive allylation of 1H-pyridine-2-(thio)ones by means of the novel lithium allyldibutylmagnesate reagent

A new, highly efficient allylation reagent—lithium allyldibutylmagnesate (allylBu₂MgLi)—was obtained by mixing allyl-magnesium chloride (1 equiv) and n-BuLi (2 equiv). N-Lithiated and N-methyl substituted 1H-pyridine-2-thiones and -ones were successfully and regioselectively allylated by treatment with allylBu₂MgLi yielding 6-allyl-3,6-dihydro-1H-pyridine-2-(thio)ones and 4-allyl-3,4-di-hydro-1H-pyridine-2-(thio)ones. The latter were formed by a 3,3-sigmatropic Cope rearrangement of the former.     

Synthesis of zwitterionic 4-hydroxy-2(1H)-quinolinone derivatives

Zwitterionic 4-hydroxy-2(1H)-quinolinone derivatives were synthesized through a unique reaction of 4-hydroxy-2(1H)-quinolinone with p-benzoquinone and N-heterocyclic aromatics. The zwitterions possessed astropisomeric nature. A possible mechanism of the reaction was presented.     

[2+2] Cycloaddition of electron-poor acetylenes to (E)-3-dimethylamino-1-heteroaryl-prop-2-en-1-ones: synthesis of highly functionalized 1-heteroaroyl-1,3-butadienes

Microwave-assisted [2+2] cycloaddition of (E)-3-dimethylamino-1-heteroaryl-prop-2-en-1-ones to dimethyl acetylenedicarboxylates gives (2E,3E)-dimethyl-2-[(dimethylamino)methylene]-3-(substituted)succinates in 8-91% yield. In the case of a 4,5-dihydrothiazoline derivative, cycloaddition also took place at the endocyclic CN double bond.