Reaction of 3-Acetyl-4,6,6-trimethyl-5,6-dihydro-2-pyrone with Carboxylic Acid Hydrazides

The reaction of 3-acetyl-4,6,6-trimethyl-5,6-dihydro-2-pyrone with the hydrazides of a series of carboxylic acids led to the synthesis of 5-alkyl(cyanomethyl)carbonyl-3,5a,7,7-tetramethylpyrazolino-4,5-c]tetrahydro-2-pyrones, which are the products from cyclization of the intermediately formed alkyl(cyanomethyl)hydrazones of 3-acetyl-4,6,6-trimethyl-5,6-dihydro-2-pyran. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 998–1001, July, 2005.     

Synthesis and cytotoxicity of phenyl-vinyl derivatives of 4,6,6-trimethyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile

A series of phenylvinyl derivatives of 4,6,6-trimethyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitriles has been synthesized and their cytotoxic activity towards HT-1080 (human fibrosarcoma) and MG 22A (mouse hepatoma) tumor cells studied. It was found that the 2-nitro-, 2- and 3-chloro, 2-fluoro, and 2-bromophenyl derivatives showed high cytotoxic activity towards both cell lines. The toxicity towards NIH 3T3 normal mouse embryonic fibroblasts depends on the nature and position of the substituent in the phenyl ring. The greatest selectivity of cytotoxic effect was seen in the 2-bromophenyl derivative.     

N-3-Oxoalkylamides and -Thioamides in the Synthesis of Heterocyclic Compounds. 6. The Effect of Structural Factors on the Regiodirection of Cyclization of Pyridinium Derivatives of N-(3-Oxoalkyl)chloroacetamides. Structure of 1-(4-Hydroxy-4,6,6-trimethyl-2-oxo-3-piperidyl)pyridinium Chloride

The structure of 1-(4-hydroxy-4,6,6-trimethyl-2-oxo-3-piperidyl)pyridinium chloride has been established. Reasons have been found influencing the regiodirection of cyclization of pyridinium derivatives of N-(3-oxoalkyl)chloroacetamides.     

Unexpected formation of 4,4,6-trimethyl-2-oxo-1-phenyl-1,2,3,4-tetrahydropyridine-3-carbonitrile via Tandem Knoevenagel condensation-Michael addition-intramolecular cyclization

Knoevenagel condensation (Cope version) of acetone with cyanoacetanilide resulted in the formation of 4,4,6-trimethyl-2-oxo-1-phenyl-1,2,3,4-tetrahydropyridine-3-carbonitrile whose structure was determined by X-ray analysis.     

3,6,6-trimethyl-4-oxo-1-(2-pyridyl)-4,5,6,7-tetrahydroindazole in Schmidt reaction and Beckmann rearrangement conditions for the 4-hydroxyimino derivative

Treatment of 3,6,6-trimethyl-4-oxo-1-(2-pyridyl)-4,5,6,7-tetrahydroindazole with sodium azide in acids gives 3,7,7-trimethyl-5-oxo-1-(2-pyridyl)-5,6,7,8-tetrahydro(4H)pyrazolo[4,3-b]azepine. Heating 1-(2-pyridyl)-3,6,6-trimethyl- and 1-phenyl-6,6-dimethyl-4-hydroxyimino-4,5,6,7-tetrahydroindazoles in polyphosphoric acid gives 1-phenyl-5,6-dimethyl- and 1-(2-pyridyl)-3,5,6-trimethyl-4-aminoindazole respectively: The reactions of the latter with 4-dimethylaminobenzaldehyde gave the 4-(4-dimethylaminobenzalamino) derivative and with 2-formyldimedone the 4-(4,4-dimethyl-2,6-dioxocyclohexylidenemethylamino) derivative.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 830–834, June, 2000.     

Synthesis of unsymmetrical 4-oxo-2-vinyl-4H-chromene-3-carbonitrile dyes via Knoevenagel reaction

New 4-oxo-2-vinyl-4H-chromene-3-carbonitrile derivatives have been synthesized by the Knoevenagel reaction of 2-methyl-4-oxo-4H-chromene-3-carbonitrile with aromatic and heteroaromatic aldehydes. Spectral properties of the obtained compounds have been studied.     

Quantum-chemical investigation of the mechanism of cyclocondensation of 4-hydroxy-4-methylpentan-2-one with cyanoacetamide using the AM1 method

The mechanism of formation of 4,6,6-trimethyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile from 4-hydroxy-4-methylpentan-2-one and cyanoacetamide in the presence of ammonium acetate has been studied by the AM1 method. It was found that, under the reaction conditions, the amide is readily converted to an iminol tautomeric form which takes part in subsequent reaction. It was shown that the reaction is a cascade process forming two intermediates. The final product 4,6,6-trimethyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile is formed from the product of a Knoevenagel condensation via an intramolecular nucleophilic substitution mechanism. On the basis of the activation energies obtained it can be deduced that the limiting stage is the deprotonation process of the cyanoacetiminol. Dedicated to Professor L. I. Belen’kii with gratitude and deep respect. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 209–216, February, 2006.     

Cyanothioacetamide in Heterocyclic Chemistry: Synthesis of Piperidine-3-carbonitrile,Pyrazolopyridine, Thiinopyridine-3-carbonitrile Derivatives,and Their Theoretical Calculations

Cyanothioacetamide ( 1 ) reacted with acrylonitrile ( 2 ) to afford the corresponding 6-oxo-2-sulfanylpiperidine-3-carbonitrile ( 6 ), which oxidized to give compounds 7 and 8 under different conditions. Moreover, compound 6 was used as a starting material to synthesize 12a-c , 16a-d , 26a-c , 27a-c , and 30a-c via reactions with aromatic aldehydes 9a-c , diazonium chlorides 13a-d , and 3-arylpropennitrile derivatives 18a-i respectively. Considering the data of IR, 1 H NMR, mass spectra, elemental analyses, and theoretical calculations, all the structures of the newly synthesized heterocyclic compounds were elucidated.     

Plant Coumarins. 2. Beckmann Rearrangement of Oreoselone <Emphasis Type="Italic">E</Emphasis>- and <Emphasis Type="Italic">Z</Emphasis>-Oximes

Oximation of oreoselone to produce a mixture the E- and Z-oximes was investigated. The crystal and molecular structures of oreoselone Z-oxime and the Beckmann rearrangement product of oreoselone E- or Z-oximes and PCl₅, 7-(1-chloro-2-methylpropoxy)-2-oxo-2H-1-benzopyran-6-carbonitrile, were established by XSA. Hydrolysis of the latter produced 7-hydroxy-2-oxo-2H-1-benzopyran-6-carbonitrile. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 541–545, November–December, 2005.     

Synthesis and Photoisomerization of 3-Cyano-6,6-dimethyl-4-(4-nitrophenylvinyl)-5,6-dihydropyran-2-one

The condensation of 4-nitrobenzaldehyde with 3-cyano-4,6,6-trimethyl-5,6-dihydropyran-2-one leads to the formation of a crotonization product and a compound of the Michael adduct type. The main product of the photochemical conversion of (E)-3-cyano-6,6-dimethyl-4-(4-nitrophenylvinyl)-5,6-dihydropyran-2-one is the Z-isomer. Investigation of the photoisomerization of 3-cyano-6,6-dimethyl-4-(4-nitrophenylvinyl)-5,6-dihydropyran-2-one by the semiempirical AM1 method showed that in the ground state the E-isomer was thermodynamically more stable than the E-isomer. E-Z-photoisomerization is effected most probably through the lowest excited singlet state S₁.     

Quantum-chemical Modeling of the Reaction of 3-Pyridinecarbaldehyde with 3-Cyano-4,5,5-trimethyl-2(5H)-furanone

The condensation of pyridinecarbaldehydes with 3-cyano-4,5,5-trimethyl-2(5H)-furanone and 3-cyano-4,6,6-trimethyl-5,6-dihydro-2(2H)-pyranone leads to the formation of the products of crotonic condensation and compounds of the Michael adduct type. A model investigation of the mechanism by the semiempirical AM1 quantum-chemical method for the case of the reaction of 3-pyridinecarbaldehyde with 3-cyano-4,5,5-trimethyl-2(5H)-furanone showed that the products can be formed in parallel from one and the same intermediate compound.     

Anomalous Beckmann Reaction in a Series of Oximes of 4-Aryl-2,7,7-trimethyl-5-oxo-5,6,7,8-tetrahydroquinolines in Polyphosphoric Acid. 2. Unexpected Synthesis of 3'-Ethoxycarbonyl-4',7',7'-trimethyl-4-oxo-2',6',7',8'-tetrahydrospiro(cyclohexa-2,5-diene-1,2'-pyrrolo[4,3,2-d,e]quinolines)

Oximes of 3-ethoxycarbonyl-4-halo(methoxy)phenyl-2,7,7-trimethyl-5-oxo-5,6,7,8-tetrahydroquinolines are converted in polyphosphoric acid (PPA) into 3'-ethoxycarbonyl-4',7',7'-trimethyl-4-oxo-2',6',7',8'-tetrahydrospiro(cyclohexa-2,5-diene-1,2'-pyrrolo[4,3,2-d,e]quinoline). An X-ray structural analysis has been carried out on one of the synthesized compounds.     

2-氧代-3-芳基-丁二酸酯的合成与表征

在复杂的天然产物合成和生物合成中,醇醛缩合反应是一类重要的碳-碳键形成反应.不对称催化直接Aldol反应由于其原子经济性,操作简捷,符合绿色化学的要求等,成为近年来不对称合成研究的热点之一.     

Crystal structure of the 2-hydroxy-3,3,4-trimethyl-2-oxo-5-cyanimino-1, 4,2-diazaphospholidine diethylammonium salt

Crystal structure of the 2-hydroxy-3,3,4-trimethyl-2-oxo-5-cyanimino-1,4,2-diazaphospholidine diethylammonium salt (I) was studied by X-ray diffraction analysis: space group P2₁/c, a=9.773(1), b=12.7617(8), c=12.064(2) Å, β=95.02(1)°, Z=4; R=0.041 (CAD-4 automatic diffractometer, λCuK_α, 2518 independent reflections with I≥3δ). In anion I, the P atom (forming two Pō sesquibonds) has a considerably distorted tetrahedral coordination. In the extended flattened molecular fragment of anion I involving 7 atoms [P?N?C(?N)=N?C≡N], the π-electron densities of the atoms are conjugated. The five-membered heterocycle of anion I has a distorted P,C₃-half-chair conformation. The crystal structure of compound I has interionic hydrogen bonds linking anions I into centrosymmetric H-dimers and also linking anions I and Et₂NH ₂ ⁺ into centrosymmetric H-tetramers.     

Isopropylidenemalononitrile in the synthesis of 2-amino-4,6,6-trimethylcyclohexa-2,4-diene-1,1,3-tricarbonitrile, 6-amino-2-(4-methoxybenzoylmethylsulfanyl)-4,4-dimethyl-1,4-dihydropyridine-3,5-dicarbonitrile, and fused 2-aminopyrans according to Michael

Michael reactions of isopropylidenemalononitrile with cyanothioacetamide (in the presence of 4-methoxyphenacyl bromide), cyclohexane-1,3-dione, and 4-hydroxycoumarin, gave 6-amino-2-(4-methoxy-benzoylmethylsulfanyl)-4,4-dimethyl-1,4-dihydropyridine-3,5-dicarbonitrile, 2-amino-4,4-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile, and 2-amino-4,4-dimethyl-5-oxo-4H,5H-pyrano[3,2-c]-chromene-3-carbonitrile, respectively. In the reaction of isopropylidenemalononitrile with cyanoacetamide, only dimerization product of the former, 2-amino-4,6,6-trimethylcyclohexa-2,4-diene-1,1,3-tricarbonitrile, was isolated. Its structure was proved by X-ray analysis.     

4,5-Dialkyl-substituted 3-oxo-(2H)-isothiazole 1,1-dioxides in reactions with diazomethane

It has been established that the interaction of diazomethane with 4,5-dialkyl-substituted 3-oxo-(2H)-isothiazole 1,1-dioxides proceeds in two stages. Initially alkylation of the sulfonimide nitrogen atom and the carbonyl group oxygen atom occurs (in a ratio of ∼ 3:2), then there is a regioselective cycloaddition of diazomethane at the C=C double bond with the formation of the corresponding N-methyloxoisothiazolopyrazolines and 3-methoxyisothiazolopyrazolines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 595–604, April, 2008.     

Synthesis of 4,4, 6-trimethyl-2-arylamino-4h-1,3-thiazines

The reaction of 2-isothiocyano-2-methyl-4-pentanone with substituted anilines gave 4,6,6-trimethyl-3-aryl-1,2,3,6-tetrahydropyrimidine-2-thiones, which are converted to the isomeric 4,4,6-trimethyl-2-arylamino-4H-1,3-thiazines by intramolecular rearrangement by heating with hydrochloric acid. In order to study the structure and amino-imino tautomerism of the aminothiazines, their analogs with a fixed amine structure were obtained. The synthesis of model compounds was accomplished by reaction of 2-isothiocyano-2-methyl-4-pentanone with m- and p-substituted N-methylanilines and subsequent cyclization of the resulting N-methyl-N-aryl-N-(2-methyl-4-oxo-2-amyl)thioureas to 4,4,6-trimethyl-2-methylarylamino-4H-1,3-thiazines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 937–940, July, 197     

Synthesis of Heterocycles via 2-Thioxo-1,2-dihydropyridine-3-carbonitrile Derivative

The present study aimed to investigate the synthetic potentiality and chemical reactivity of 2-thioxo-1,2-dihydropyridine-3-carbonitrile derivative 1. This goal performed via its reaction with each of 1-chloroacetone and iodomethane to afford the corresponding 2-alkylthio derivatives 3 and 9, respectively. Compound 3 underwent intramolecular cyclization to afford the corresponding thieno[2,3-b]pyridine derivative 4 which in turn, reacted with dimethylformamide/dimethylacetal followed by hydrazine hydrate and nitrous acid to afford the corresponding pyridothienopyrimidine and pyridothienopyridazine derivatives 6 and 8, respectively. On the other hand, Compound 9 reacted with hydrazine hydrate to give 3-aminopyrazolo[3,4-b]pyridine derivative 10, which diazotized with nitrous acid to give the corresponding diazonium salt 11. Compound 11 coupled with several active –CH₂-containing reagents to synthesize the corresponding pyridopyrazolo-triazines 15, 24, 29, and 31. The formulas of all newly synthesized heterocyclic compounds were elucidated by considering the data of IR, ¹H NMR, Mass spectral data, as well as data from elemental analyses.     

Crystal structure of [CuL](NO<Subscript>3</Subscript>)(ReO<Subscript>4</Subscript>) and [CuL](ReO<Subscript>4</Subscript>)<Subscript>2</Subscript> (L = 4,6,6-trimethyl-1,9-diamino-3,7-diazanon-3-en)

The crystal structures of [CuL](NO₃)(ReO₄) and [CuL](ReO₄)₂ (L is 4,6,6-trimethyl-1,9-diamino-3,7-diazanon-3-en) are studied. The square coordination of the copper atom in [CuL](NO₃)(ReO₄) is completed to a distorted octahedron by two oxygen atoms: Cu…O (ReO ₄ ^? ) 2.393 Å and Cu…O (NO ₃ ^? ) 2.685 Å, and that in [CuL](ReO₄)₂, by Cu…O(ReO ₄ ^? ) 2.468 Å and 2.697 Å. The products of thermolysis of the salts in a hydrogen atmosphere at 800°C are mixtures of nanocrystalline metal powders with coherent scattering regions of ～45 nm.