A. S. Fisyuk

5,6-Dihydropyridin-2(1H)-ones and 5,6-dihydropyridine-2(1H)-thiones (review)

Data on methods for the production of 5,6-dihydropyridin-2(1H)-ones and 5,6-dihydropyridine-2(H)-thiones and their biological activity are reviewed.

Synthesis of 3-Aminopyridin-2(1H)-Ones and 1H-Pyrido[2,3-b][1,4]Oxazin-2(3H)-Ones

The interaction of 1,3-diketones with chloroacetamide produced N-(3-oxoalkenyl)chloroacetamides. Heating of N-(3-oxoalkenyl)chloroacetamides with an excess of pyridine in ethanol or butanol led to the formation of pyridin-2(1Н)-ones, substituted with a pyridine ring at position 3. The reactions of these compounds with hydrazine hydrate produced 3-aminopyridin-2(1Н)-ones. The synthesis of 1H-pyrido[2,3-b][1, 4]oxazin-2(3H)-ones was accomplished by a reaction of 3-aminopyridin-2(1Н)-ones with chloroacetyl chloride.

New Method for the Synthesis of 1,2,3,6,7,11b-Hexahydro-4H-pyrimido[6,1-a]isoquinoline-4-thiones and 2,3,6,7,12,12b-Hexahydropyrimido[6,1-a]-β-carboline-4(1H)-thiones

Pyrimido[6,1-a]isoquinolines hold interest as physiologically active compounds [1]. The structural fragment of pyrimido[6,1-a]-β-carbolines is found in several alkaloids such as elaeocapridine [2]. The methods reported for the preparation of such compounds involve multiple steps and have proved inefficient. As a rule, the synthesis of such compounds requires not readily available isoquinoline and β-carboline precursors. The pyrimidine ring is subsequently completed [3]. On the other hand, intramolecular amidoalkylation of heterocyclic acyliminium is often used for the preparation of isoquinolines and β-carbolines fused with other heterocycles [4]. Such an approach to the synthesis of pyrimido[6,1-a]isoquinolines and pyrimido[6,1-a]-βcarbolines has not yet been employed. We have shown that 6-hydroxytetrahydropyrimidine-2-thiones 5, obtained according to Unkovskii et al. [5] by the reaction of the corresponding isothiocyanatocarbonyl derivatives 1a and 1b [6] with homoveratrylamine 3 or tryptamine 4, are converted upon heating in acetic acid to 1,2,3,6,7,11b-hexahydro-4Hpyrimido[6,1-a]isoquinoline-4-thiones 8a and 8b and 2,3,6,7,12,12b-hexahydropyrimido[6,1-a]-β-carboline4(1H)-thiones 9a and 9b with satisfactory yields (method A). Thione 8b is formed as a 10:9 2,11b-cis/trans isomer mixture while thione 9b is formed as a 1:4 1,12b-cis/trans isomer mixture. Heterocyclic cation 6 may also be obtained from 3,4-dihydropyrimidine-2(1H)-thione 7 in acid medium. The use of amines 3 and 4 in reported methods for the synthesis of 7 based on the condensation of isothiocyanato ketones and amines [7] (method B) or of α,β-unsaturated ketones, thiocyanic acid, and amines [8] (method C) also leads to heterocyclic thiones 8 and 9 (Scheme 1). The yields of 8a relative to amine 3 obtained by methods A (overall yield in two steps), B, and C are 73, 65, and 64%, respectively. The reaction proceeds as an intramolecular amidoalkylation of the aryl or hetaryl fragment by heterocyclic cation 6 formed in acid medium from 5 or 7. General Method for the Synthesis of 8 and 9 (Method B). A mixture of isothiocyanatocarbonyl derivative (72.3 mmol) and 3,4-dimethoxyphenylethylamine (60.5 mmol) in glacial acetic acid (50 ml) was heated at reflux for 1.5 h. The reaction mixture was cooled to room temperature and poured onto ice. The crystals formed were filtered off, dried, and recrystallized from absolute ethanol.

Domino reactions in the synthesis of tetrahydropyrimidin-2(1H)-ones(thiones) annelated at the N(1)–C(6) bond (Review)

Information relating to the synthesis of tetrahydropyrimidin-2(1H)-ones(thiones), annelated at the N(1)–C(6) bond, by cascade cyclization of substituted N-(3-oxoalkyl)ureas and thioureas is classified. The general relationships of this process are presented.

SYNTHESIS AND BIOLOGICAL ACTIVITY OF 4H-THIENO(3,2-c)CHROMENE DERIVATIVES

The formyl group of 4H-thieno[3,2-c]chromene-2-carbaldehyde was transformed into the respective nitrile, amide, ester, carboxylic, hydroxamic, or hydroxy group. Electrophilic substitution in 4H-thieno[3,2-c]chromene-2-carbaldehyde was shown to occur at the С-8 atom, while oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in methanol led to 4-methoxy-4H-thieno[3,2-c]chromene-2-carbaldehyde. The latter compound was found to possess high antiulcer activity.

Synthesis of 4H-thieno[3,2-c]chromenes by intramolecular arylation of 4-aryloxy-methyl-5-iodothiophene-2-carbaldehydes

The iodination of 4-chloromethylthiophene-2-carbaldehyde by N-iodosuccinimide under solvent-free conditions gives 4-chloromethyl-5-iodothiophene-2-carbaldehyde, which is used to obtain 4-aryloxy-methyl-5-iodothiophene-2-carbaldehydes. The palladium-catalyzed intramolecular cyclization of 4-aryloxymethyl-5-iodothiophene-2-carbaldehydes yields 4H-thieno[3,2-c]chromene-2-carbaldehydes.

New approach to the synthesis of 1,3-chloroisothiocyanatoalkanes. Synthesis of tetrahydro-1,3-thiazine-2-thiones and 2-alkylamino-5,6-dihydro-1,3-thiazines

A method was developed to prepare 1,3-chloroisothiocyanatoalkanes by reducing 1,3-isothiocyanato ketones using sodium borohydride at pH ~7 and subsequent treatment of the resultant 1,3-isothiocyanato alcohols with thionyl chloride. The reaction of 1,3-chloroisothiocyanatoalkanes with sodium hydrosulfide or amines gives substituted tetrahydro-1,3-thiazine-2-thiones or 2-amino-5,6-dihydro-1,3-thiazines.

Synthesis of 3-isothiocyanatopropion-and -butyraldehyde diethyl acetals and their reactions with N-nucleophiles

A one-pot procedure was developed for the synthesis of 3-isothiocyanatopropionaldehyde and 3-isothiocyanatobutyraldehyde diethyl acetals from the corresponding α,β-unsaturated aldehydes. Reactions of 1,1-diethoxy-3-isothiocyanatobutane with aliphatic amines and hydrazines gave, respectively, substituted thioureas and thiosemicarbazides which underwent acid-catalyzed cyclization to form 6-ethoxytetrahydropyrimidine-2(1H)-thiones, 9,10-dimethoxy-2-methyl-1,2,3,6,7,11b-hexahydro-4H-pyrimido[6,1-a]isoquinoline-4-thiones, and 2-methyl-2,3,6,7,12,12b-hexahydropyrimido[1′,6′:1,2]pyrido[3,4-b]indole-4(1H)-thione.

Reactions of 1,3-isothiocyanato ketones with mineral acids. Synthesis of 3,4-dihydro-2H,1,3-thiazin-2-ones

Reactions of 1, 3-isothiocyanato ketones with mineral acids formed 3, 4-dihydro-2H, 1, 3-thiazin-2-ones or their mixtures with 6-alkylidenetetrahydro-1, 3-thiazin-2-ones. Subsequent acid hydrolysis of the thiazines obtained formed salts of 1,3-amino ketones. The direction and extent of the transformation depend on the nature of the acid, reaction temperature, and structure of the 1,3-isothiocyanato ketones.

Investigation of the ring-chain tautomerism of alkyl-substituted 6-hydroxytetrahydro-1,3-thiazine-2-thiones by IR spectroscopy and mass spectrometry

The ring-chain tautomerism of alkyl-substituted 6-hydroxytetrahydro-1,3-thiazine-2-thiones was studied by IR spectroscopy and mass spectrometry. The dependence of the tautomeric equilibrium on the number and location of the methyl groups in the molecule and the aggregate state of the substance was ascertained. Substituted 3,4-dihydro-2H-1,3-thiazine-2-thiones were obtained by the dehydration of the 6-hydroxytetrahydro-1,3-thiazine-2-thiones