A facile synthesis of 3-alkylchromanones and chromones

A simple and high yielding route to 3-alkylchromanones and 3-alkylchromones has been achieved from 3-alkyl-3-phenyl-sulphonyl-4-chromanones.

A simple and high yielding route to 3-alkylchromanones and 3-alkylchromones has been achieved from 3-alkyl, 3-phenylsulphonyl-4-chromanones.     

Investigation of 2,3'-Biquinolyl. 11. Regioselectivity in the Hydroxylation of 1-Alkyl-3-(2-quinolyl)quinolinium Halides

The hydroxylation of 1-alkyl-3-(2-quinolyl)quinolinium halides by an alkaline solution of K₃[Fe(CN)₆] in aqueous 1,4-dioxane leads to a mixture of 1-alkyl-3-(2-quinolyl)-1,2-dihydro-2-quinolones and 1-alkyl-3-(2-quinolyl)-1,4-dihydro-4-quinolones with predominance of the former. The use of the system of K₃[Fe(CN)₆]/Mg(OH)₂ in aqueous 1,4-dioxane leads to the regiospecific formation of 1-alkyl-3-(2-quinolyl)-1,4-dihydro-4-quinolones.     

Nucleophilic substitution in 1-alkyl-4,5-dichloro-3-nitropyridazin-6-ones

Treatment of 1-alkyl-4,5-dichloro-3-nitropyridazin-6-one with C-nucleophiles and with ambident nucleophiles (2-azahetarylacetonitriles) leads to a selective substitution of a chorine atom by the quaternary carbon atom of the carbanion formed from a substituted acetonitrile. The pK_a of the CH-acid 2-(1-alkyl-5-chloro-3-nitro-6-oxo-1,6-dihydro-4-pyridazinyl)malononitrile was determined by potentiometric titration. Reaction of 2-(1-alkyl-5-chloro-3-nitro-6-oxo-1,6-dihydro-4-pyridazinyl)-2-hetarylacetonitriles with primary amines gives 6,7-dihydro-1H-pyrrolo[2,3-d]pyridazin-7-ones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 556–564, April, 2006.     

Synthesis of 4-alkyl-3-pyridinols from 3-benzyloxypyridine

The addition of Grignard reagents to the 1-phenoxycarbonyl salt of 3-benzyloxypyridine and a catalytic amount of cuprous iodide afforded 4-alkyl-3-benzyloxy-1-phenoxycarbonyl-1,4-dihydropyridines in good yield. The crude dihydropyridines were aromatized with o-chloranil to give 4-alkyl-3-benzyloxypyridines, which were debenzylated with hydrogen and 10% palladium on carbon to provide 4-alkyl-3-pyridinols.     

3-Phenyl-4-aminopiperidin und am Ring-N alkylierte Abkömmlinge

Zusammenfassung Die Oxime (II) von 1-Alkyl-3-phenylpiperidindionen-(2,4) (I)⁴ gaben bei der LiAlH₄-Reduktion ein Stereomerengemisch an 1-Alkyl-3-phenyl-4-aminopiperidinen (III). Die 1-Benzylverbindung III b wurde durch katalyt. Hydrogenolyse in das 3-Phenyl-4-aminopiperidin (IV) übergeführt.

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The oximes (II) of 1-alkyl-3-phenyl-2,4-dioxopiperidines (I)⁴ on LialH₄ reduction yielded a mixture of steroisomeric 1-alkyl-3-phenyl-4-aminopiperidines (III). The 1-benzyl derivative III b was converted into 3-phenyl-4-aminopiperidine (IV) by catalytic hydrogenolysis.

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Meinem verehrten Lehrer Herrn Professor Dr.H. Bretschneider zum 60. Geburtstag.     

The Synthesis of 2-Alkylthio-3-alkyl-5-arylmethylidene4H-imidazol-4-ones

2-alkylthio-3-alkyl-5-arylmethylidene-4H-imidazol-4-ones were synthesized by the S-alkylation and N-alkylation of 2-thioxo-5-arylmethylidene-4-imidazolidinones, which were obtained via a tandem aza-Wittig reaction of vinyliminophosphoranes, carbon disulfide, and excess ammonium hydroxide (28% NH₃ in water).     

Highly anti-diastereoselective reduction of 2-alkyl-3-oxo amides by potassium triethylborohydride

Potassium triethylborohydride was found to reduce 2-alkyl-3-oxo amides to the corresponding 3-hydroxy amides with excellent $\text{anti}$-diastereoselectivity (>99:1), and in combination with asymmetric acylation, a useful route to optically active $\text{anti}$-2-alkyl-3-hydroxy acids was developed.     

2-Aminopyrrole-2,5-diones 2. Vinyl nucleophilic substitution of the alkylamino group in 1-alkyl-3-alkylaminopyrrole-2,5-diones by arylamines

In vinyl nucleophilic substitution (S_N vin) with the hydrochlorides or 4-toluenesulfonates of primary arylamines 1-alkyl-3-alkylaminopyrrole-2,5-diones form the corresponding 1-alkyl-3-arylaminopyrrole-2,5-diones, which are also produced in situ from the corresponding arylaminofumarates and primary alkylamines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 668–675, May, 2008.     

Synthesis of 3-alkenyl-2-arylchromones and 2,3-dialkenylchromones via acid-catalysed retro-Michael ring opening of 3-acylchroman-4-ones

3-Acylchromones and 3-acylflavones, readily available by acylation of 2′-hydroxydibenzoylmethane with acid anhydrides in the presence of base, undergo efficient conjugate reduction with NaBH₄ in pyridine to give the corresponding chroman-4-ones/flavanones in high yields. The reduction is both regio- and chemoselective. Treatment of the chroman-4-ones with MeSO₃H generates the 3-alkenyl-2-arylchromones by a dehydrative rearrangement initiated by retro-Michael cleavage of the pyranone ring. This reduction-rearrangement sequence can be extended to 2-alkyl-3-alkenoylchromones to generate 3-alkenyl-2-styrylchromones, the first examples of 2,3-dialkenylchromones.     

Study of the electrophilic substitution of alkyl-, aryl-, and aralkyl-5(6)-hydroxybenzimidazoles

A series of new 4-sulfo-5(6)-hydroxybenzimidazoles was obtained including mono-, di-, and trinitro derivatives of 2-phenyl- and 2-benzyl-5-hydroxybenzimidazoles. Aromatic groups at C², in contrast to alkyl groups, enhance the reactivity of the benzimidazole system in electrophilic substitution.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1888–1892, August, 1990.     

A palladium-promoted route to 3-alkyl-4-(1-alkynyl)-hexa-1,5-dyn-3-enes and/or 1,3-diynes

Reaction of benzene solutions of arylacetylenes with 1 equiv. of chloroacetone and 2 equiv. of Et₃N, using a mixture of (PPh₃)₄ Pd and CuJ as catalyst, affords 1,4-diaryl-butadiynes in very good yields. Under similar reaction conditions aliphatic 1-alkynes yield mixtures of simmetrically disubstituted 1,4-dialkyl-1,3-butadiynes and of 3-alkyl-4-(1-alkynyl)-hexa-1,5-diyn-3-enes.     

4-取代-3-烷基-4,5-二氢-1-(3-氯-4-氟苯基)-1,2,4-三唑-5-酮的合成及生物活性

为寻找活性强、作用时间长的新型非肽类血管紧张素II AT₁受体拮抗剂, 从易得原料3-烷基-4,5-二氢-1-(3-氯-4-氟苯基)-1,2,4-三唑-5-酮出发, 经过N-烃化反应、1,3-偶极反应、氢解、水解和酰化等反应, 合成得到一系列4-取代-3-烷基-4,5-二氢-1-(3-氯-4-氟苯基)-1,2,4-三唑-5-酮类衍生物, 总收率为58%～87%, 其结构经IR, ¹H NMR, MS和元素分析确证. 初步药理试验结果表明: 所有目标化合物均有一定的AT₁受体拮抗活性, 其中化合物12d抑制AII诱导的兔主动脉环收缩的IC₅₀值为4.0×10^－9 mol/L, 与阳性药坎地沙坦(candesartan)相当, 具有进一步的研究意义.     

Theoretical study of the mechanism of the formation of 3-unsubstituted 4,4-disubstituted beta-lactams by silver-induced ring expansion of alkoxycyclopropylamines: a new synthetic route to 4-alkoxycarbonyl-4-alkyl-2-azetidinones

The mechanisms of formation of 4,4-dialkyl- and 4-alkoxycarbonyl-4-alkyl-2-azetidinones by silver-induced ring expansion of the corresponding 2,2-disubstituted N-chloro-1-hydroxycyclopropylamines were theoretically investigated by means of the B3LYP method and the PCM solvation model. The obtained results indicate that these reactions are facile two-step regioselective processes proceeding through a short-life nitrenium intermediate. The theoretical results thus predict that this synthetic strategy, which has already been used to obtain 4,4-dialkyl-2-azetidinones, could also be a new route to efficiently obtain in a regio- and stereoselective way 4-alkoxycarbonyl-4-alkyl-2-azetidinones, which are precursors of conformationally constrained amino acids.     

Simple and Efficient Synthesis of 5-Substituted-3-phenyl-2-thioxoimidazolidin-4-one Derivatives from S-Amino Acids and Phenylisothiocyanate in Et3N/DMF-H2O

A concise approach for the transformation of various S-amino acids into the 5-alkyl-3-phenyl-2-thioxoimidazolidin-4-one heterocycles using phenylisothiocyanate is described. Phenylthiohydantoins of amino acid were synthesized at room temperature in Et₃N/DMF-H₂O with easy workup and excellent yields.     

Formylation of 5-alkyl-3H-furan-2-ones

3-Formyl derivatives of 3H-furanones and 2-chlorofurans are formed in the reaction of 5-alkyl-3H-furan-2-ones with POCl₃ and DMF. The conditions for the purposeful synthesis of these compounds were found. The transformations of the formyl group in reactions with dinitrophenylhydrazine and aniline were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 456–458, April, 1993.     

The chemistry of coumarin derivatives. Part 3. Synthesis of 3-alkyl-4-hydroxycoumarins by reductive fragmentation of 3,3′-alkyiidene-4,4′-dihydroxybis[coumarins]

Treatment of 3,3′-alkylidene-4,4′-dihydroxybis[coumarins] 1 with NaBH₃CN in refluxing MeOH affords 3-alkyl-4-hydroxycoumarins 2 and 4-hydroxycoumarin ( 3 ; Scheme 1). The reaction might take place via hydride trapping of alkylidenechromandiones C formed from 1 in a retro-Michael reaction. Such a retro-Michael reaction of 1 might be biologically relevant. The presence of C during the reductive fragmentation 1 → 2 is suggested by Diels-Alder and nucleophilic trapping of the alkylidenechromandiones C as well as from cross-over experiments with coumarins other than 3 (see Scheme 2). The reductive fragmentation of 1 allows the chemo- and regioselective synthesis of a variety of 3-alkyl-4-hydroxycoumarins 2 (see Table).     

Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-one reexamined: formation of isomeric angular fused quinazolinoquinazolinones and their spectroscopic identification

Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-ones on to N₃ and on to N₁ leading to 6-alkyl-(8H)-quinazolino[4,3-b]quinazolin-8-one and 6-alkyl-(13H)-quinazolino[3,4-a]quinazolin-13-one, respectively was described for the first time. The differences in the IR and carbon NMR data of these isomeric fused quinazolinoquinazolinones afford a useful method for distinguishing between the two series.     

Synthesis of highly substituted quinolines via heterocyclization of fluorinated acetylenephosphonates with ortho-aminoaryl ketones

A synthetic route to a series of 4-alkyl- or arylquinolines, bearing in 2- and 3-position fluorinated and phosphonate functions at the same time, is reported for the first time. These compounds are synthesized via regioselective heterocyclization of XCF₂-alkynylphosphonates (X=F, Cl, Br, H, CF₃) with ortho-aminoaryl ketones (R=CH₃, CF₃, Ph) in the presence of K₂CO₃ or Li₂CO₃/TMEDA as mediators. 2-Fluoro- and 3-phosphorus-containing 4-Me, 4-CF₃ or 4-Ph quinolines are obtained in good to excellent yields. The influence of substituents in the aromatic ketone, the XCF₂-group in the alkyne as well as mediators and the reaction medium on the reactivity and specificity of the reaction is also investigated.     

FeCl3·6H2O-promoted skeleton-rearrangement of 1-substituted-3-benzazepines: substrate extension and product utilization

FeCl₃·6H₂O-promoted skeleton-rearrangement of 1-substituted-3-benzazepines was further exploited. Both 1-aryl- and 1-alkyl- or 1-alkenyl-benzazepines underwent this reaction smoothly. The rearrangement products were used to prepare a series of novel derivatives containing both tetrahydroisoquinoline (THIQ) and tetrahydropyrimidin-4(1H)-one scaffolds through a Mannich-type process.     

Azacarbazoles

Alkylation of 5H-pyridazino [4, 5-b] indole with halogen compounds or dimethyl sulfate in the presence of alkaline reagents gives 2-alkyl-2H-pyridazino [4, 5-b] indoles. Reduction of the methiodide or chlorobenzylate of 5H-pyridazino [4, 5-b] indole also gives 2-alkyl derivatives. LiAlH₄ reduction of 3-alkyl-3H-pyridazino [4, 5-b] indolones-4 gives 3-alkyl-3H-pyridazino [4, 5-b] indoles.For Part I see [1]. The main results of the research were reported at the Conference on Heterocyclic Rings in Organic Synthesis, Kiev, June 1964.