Vol 55, No 12 (2019)

New spiro heterocycles, spiro[benzo[h]chromene-4,3′-indoles] and spiro[benzo[f]chromene-1,3′-indoles], have been synthesized in 50–60% yield by three-component condensation of substituted isatins with malononitrile or ethyl cyanoacetate and naphthalen-1-ol or naphthalen-2-ol. The described reactions follow a cascade cyclization pathway and provide a regioselective method of synthesis of the title compounds.

With the goal of obtaining fused dilactones, the carbohydrate moiety of diastereoisomeric Michael adducts of levoglucosenone and cyclohexanone was converted to δ-lactone and its derivatives fused to an octahydrochromene fragment. The subsequent oxidative cleavage of the C-C bridge in the latter by the action of pyridiniun chlorochromate (PCC) afforded nonano-9-lactone fused at the C⁶-C⁷ bond to δ-lactone or methyl-δ-lactol. The presence of a carbonyl group in the carbohydrate moiety was found to prevent C-C bond cleavage.

Previously unknown 2-(arylsulfanyl)-3-hydroxymaleimide and 2-(arylsulfanyl)-3-chloromaleimide derivatives have been synthesized, and several synthetic approaches to 2-(arylamino)-3-(arylsulfanyl)-maleimides have been tested. The reactivities of 2-chloro-3-(4-methylphenylsulfanyl)maleimide and 2,3-bis(4-methylphenylsulfanyl)maleimide toward nitrogen and sulfur nucleophiles have been studied, and products of substitution of one or two arylsulfanyl groups have been obtained.

A new homogeneous reaction of dimethylformamide (DMF) with acrylic acid was studied. The reaction afforded previously unknown 3-[2-carboxyethyl(dimethyl)azaniumyl]propanoate and carbon monoxide. The product structure was determined by ¹H and ¹³C NMR spectroscopy, X-ray diffraction, and elemental analysis, and evolution of gaseous carbon monoxide was confirmed by GC/MS. The kinetic parameters of the described reaction and its overall order were determined.

Tetrabromo- and tetrachloroglycolurils have been shown to act as good oxidants capable of converting thioamides to the corresponding amides. This approach offers such advantages as good yields (81–99%), short reaction times (10–25 min), simple workup procedure, and environmental safety.

5-Acetyl-4-hydroxy-2H-1,3-thiazine-2,6(3H)-dione reacted with cyclohexyl and benzyl (4-aminophenyl)carbamates in boiling ethanol in the presence of a catalytic amount of glacial acetic acid to give the corresponding Schiff bases, cyclohexyl and benzyl (4-{[(E)-1-(4-hydroxy-2,6-dioxo-3,6-dihydro-2H-1,3-thiazin-5-yl)ethylidene]amino}phenyl)carbamates. Heating of the latter in dimethylformamide for 2 h was accompanied by evolution of COS with the formation of cyclohexyl and benzyl {4-[6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl]phenyl}carbamates. The condensation of the title compound with benzene-1,2-diamine in propan-2-ol, followed by addition of 5-arylfuran-2-carbaldehyde and trifluoroacetic acid afforded 5-(2-{5-[4-bromo(nitro)phenyl]furan-2-yl}-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-4-hydroxy-2H-1,3-thiazine-2,6(3H)-diones. 5-((E)-3-{5-[4-Bromo(nitro)phenyl]furan-2-yl}prop-2-enoyl)-4-hydroxy-2H-1,3-thiazine-2,6(3H)-diones were synthesized by condensation of 5-acetyl-4-hydroxy-2H-1,3-thiazine-2,6(3H)-dione with 5-[4-bromo(nitro)phenyl]furan-2-carbaldehydes in chloroform in the presence of catalytic amounts of pyridine and piperidine.

One-pot condensation of 2-substituted 6-aminopyrimidin-4(3H)-ones with aromatic aldehydes and 5,5-dimethylcyclohexane-1,3-dione (dimedone) in acetic acid without a catalyst afforded new substituted 5-aryl-5,8,9,10-tetrahydropyrimido[4,5-b]quinoline-4,6(3H,7H)-diones in good yields. The condensation of 2-memyl-6-aminopyrirnidin-4(3H)-one with aromatic aldehydes at a molar ratio of 2:1 under similar conditions led to the exclusive formation of uncyclized 5,5′-(arylmemylene)bis[6-amino-2-methylpyrimidin-4(3H)-ones].

5-(1H-Pyrrol-2-ylmethyl)-4H-thieno[3,2-b]pyrroles were synthesized by condensation of N-substituted (4H-thieno[3,2-b]pyrrol-5-yl)methanols with pyrrole in the presence of Amberlyst 15 as catalyst. Treatment of the products with N-bromosuccinimide led to the formation of dark blue polymers insoluble in organic solvents.

A number of new fused polyheterocyclic compounds were synthesized on the basis of 2-amino-6-sulfanylpyrirnidin-4(3H)-one. In particular, reactions of 2-amino-6-suffanylpyrirnidin-4(3H)-one with cinnamic acids, aroyl isothiocyanate, and acetic anhydride afforded imidazo[1,2-a]thieno[2,3-d]pyrimidine, [1,3]thiazino[6′,5′: 4,5]pyrimido[1,2-a][1,3,5]triazine, and imidazo[1,2-a]tWeno[2,3-d]pyrimidine derivatives, respectively. The alkylation of 2-amino-6-smfanylpyrirnidin-4(3H)-one with benzyl chloride gave 3-benzyl-6-(benzylsulfanyl)-2-imino-2,5-dihydropyrimidin-4(3H)-one which was converted to [1,3]thiazolo[5,4-d][1,2,4]triazolo-[4,3-a]pyrimidine, imidazo[1,2-a]pyrimidine, dihydropyrimido[4,5-b]quinoline, imidazo[1,2-a]pyrrolo[2,3-d]-pyrimidine, and benzo[g]imidazo[2,1-b]pteridine derivatives via reactions with nitrous acid, ethyl chloroacetate, and aniline (followed by treatment with carbon disulfide, cinnamic acid, or sodium nitrite in acetic acid). 2-Amino-3,4-dihydropyrimidin-6-sulfonic acid was obtained by oxidation of the same substrate with hydrogen peroxide in alkaline medium. Some of the synthesized compounds showed antimicrobial activity.

5-Methyl-4-(3-(2-oxopyrrolidin-1-yl)propyl)-2,4-dihydro-3H-1,2,4-triazol-3-one was synthesized and characterized by X-ray, FTIR and NMR spectroscopic techniques. The molecular geometry and spectral parameters of the title compound were also computed by the DFT/B3LYP76-311++G(d,p) method, and the theoretical data showed a good agreement with the experimental ones. The differences between the theoretical and experimental IR and NMR spectra supported the presence of inter- and intramolecular C-H⋯O and intermolecular N-H⋯O hydrogen bonds, which were revealed by X-ray analysis. Nonlinear optical (NLO) properties of the title compound were analyzed by the DFT/B3LYP/6-311++G(d,p) method by calculating the mean polarizability (α) and first-order hyperpolarizability values (β) (α = 22.0746454×10⁻²⁴, β = 10.1110649×10⁻³¹ esu). As compared with the corresponding data for urea (α = 4.9067×10⁻²⁴, β = 7.8782×10⁻³¹ esu), these values suggest promising NLO properties.

Some interesting nitrogen heterocycles, as well as other products, were synthesized by reactions of 2-cyano-N′-[(1,3-diphenyl-1H-pyrazol-4-yl)methylidene]acetohydrazide with phenyl isothiocyanate/elemental sulfur, 3,4,5-trimethoxybenzaldehyde, 4-hydroxy-1,1′-biphenyl-3-carbaldehyde, 2-oxoquinoline-3-caraldehyde, triethyl orthoformate, ethyl cyanoacetate, and thiosemicarbazide. The structures of all isolated compounds were established from their analytical and spectral data.

New pyridine-2,6-dicarboxamide derivatives containing sulfonamide groups were synthesized by the coupling of pyridine-2,6-dicarbonyl dichloride and various aminobenzenesulfonamides in a mixture of dichloromethane and acetone. The pyridinedicarboxamide-based sulfonamides were evaluated as carbonic anhydrase (CA) and cholinesterase (ChE) inhibitors, and they showed IC₅₀ values in the ranges 12.8–37.6 nM against human carbonic anhydrase I (hCA I), 17.8–46.7 nM against human carbonic anhydrase II (hCA II), 98.4–197.5 nM against acetylcholinesterase (AChE), and 82.2–172.7 nM against butyrylcholinesterase (BuChE). These results are comparable with those for known inhibitors such as acetazolamide (IC₅₀ = 32.1 nM for hCA I and IC₅₀ = 51.0 nM for hCA II) and rivastigmine (IC₅₀ = 60.2 nM for AChE and IC₅₀ = 14.0 nM for BuChE), which qualifies the synthesized compounds as candidates for a more in-depth study.

A series of novel 2-azetidinone derivatives have been obtained starting from pyromellitic dianhydride. Pyromellitic dianhydride was converted to pyromellitic diimide using sodium cyanate, and the diimide was alkylated with ethyl chloroacetate. The resulting diester was treated with hydrazine hydrate to obtain dihydrazide which reacted with substituted pyridine-2-carbaldehydes to give the corresponding Schiff bases, and [2+2]-cycloaddition of the latter with chloroacetyl chloride in the presence of triethylamine afforded the target azetidin-2-one derivatives. The newly synthesized compounds showed high antimicrobial activities against some bacterial and fungal strains.

Three-component S_N^HAr reaction of quinine, diphenylphosphine oxide, and furoylacetylene chemoselectively afforded the corresponding quinine vinyl ether and 2: 1 adduct of diphenylphosphine oxide to the triple bond of furoylacetylene instead of the expected cross-coupling product at the pyridine ring.

Previously unknown chloro-substituted 1,3-dithiolanes were synthesized by reaction of disodium 2-cyanoethene-1,1-bis(dithiolates) with 1,1,2-trichloroethane. The reaction of disodium 2-cyano-3-ethoxycarbonylprop-1-ene-1,1-bis(dithiolate) afforded ethyl 2-cyano-2-(2H-1,3-dithiol-2-ylidene)acetate.

Reactions of thioxanthylium tetrafluoroborate with pharmacophoric heterocyclic amines, pyrimidin-2-amine, 4,6-dimethylpyrimidin-2-amine, 2-aminopyrimidine-4,6-diol, and 1,3,4-thiadiazole-2,5-diamine, gave stable products of electrophilic substitution of one hydrogen atom per amino group. The product structure was confirmed by ¹H NMR and mass spectra and X-ray analysis of N-(9H-tmoxanthen-9-yl)pyrimidin-2-amine.