Previously unknown spiroderivatives of 3,1-benzoxazines were synthesized by the reaction of anthranilic acid with cyclic ketones. The interaction of 3,1-spirobenzoxazines with Vilsmeier-Haack reagent (POCl3 (PBr3)/DMF), depending on the amount of formulation agent, leads to the formation of hydroacridones or hydroacridines. Under catalyst- and additive-free conditions, N-arylmaleimides, like Michael's acceptors, are added to the hydroacridines in DMSO to form the corresponding adducts. The reaction proceeds stereoselectively with the formation of a mirror pair of diastereomers, if the products have only two chiral centers. In the presence of three chiral centers in the structure of Michael's adducts, the reaction is not stereoselective. The reaction proceeds by the sp3 hybrid carbon atom under non-catalytic conditions due to the imin-enamine tautomerism of chloro(bromo)hydroacridines. The presented reaction can also be considered as an effective atom-economical aza-ene reaction, which fully meets today's requirements for eco-friendly reaction. The synthesized compounds are potential biologically active substances and can also be used as "building-blocks" for organic synthesis.

We have proposed a method for the synthesis of previously unknown bromo xanthenes using the reagent PBr3/DMF as a rearrangement initiator. Bromo derivatives of xanthenes in the form of organic perchlorates were prepared by reacting the corresponding benzo(naphtho)dioxin-4(1)-ones with a three-fold excess of Vilsmeier-Haack PBr3/DMF reagent at 1100C for 2 hours, followed by the addition of sodium perchlorate. The conditions for the synthesis of formyl derivatives of xanthenes under conditions of acid hydrolysis were selected. The structure of the compounds was confirmed by 1H and 13C NMR spectral data and mass spectrometry. Preliminary studies showed that it is possible to selectively replace the dimethylamino group and the bromine atom with various nucleophiles in bromo derivatives of xanthenes, which opens up wide possibilities for the synthesis of low-molecular building blocks and dyes.

The catalyst-free sp3 C–H functionalization of tetrahydroacridine(quinolines) derivatives has been achieved using a Michael-type reaction with N-arylmaleimides. This method enables the facile synthesis of biologically important N-aryl bearing tetrahydroacridine(quinolines) moieties in a single step with high yields. The reaction occurs under non-catalytic conditions by heating of hydroacridines(quinolines) in DMSO within 4 h at 100–1200C. The reaction between starting compounds allows synthesizing (3S/4R)-3-[(3R/4S)-9-chloroacridine(quinoline)-4-yl]-1(-N-aryl)pyrrolidine-2,5-diones with a good yield. The structure of compounds was proved by spectral methods of analysis. The 1H NMR spectrum shows characteristic signals of protons of the CH-groups in acridine(quinoline) (3.4–3.5 ppm) and pyrrolidine (3.8–3.9 ppm) cycles. It is interesting to note that the main direction of the fragmentation is the Michael retro-reaction, which is accompanied by the elimination of 1-(2-nitrophenyl)-1H-pyrrole-2,5-dione and leads to the formation of m/z ions of starting chloroacridines(quinolines).

Keywords: thieno[2,3-d]pyrimidines, thieno[2,3-b]pyridines, spiroheterocycles, Vilsmeier-Haack reaction, docking studies, anticancer activity, kinase inhibitors

Arylhydrazones of 2,3,5,6,7,8-hexahydroacridin-4(1H)-ones and 7-amino-6-(arylhydrazono)-7-oxoheptanoic acids were cyclized by Fischer reaction, providing previously unknown polysubstituted indole derivatives. The starting hydrazones were synthesized under Japp–Klingemann reaction conditions by using 1,2,3,4,5,6,7,8-octahydroacridine-4-carboxamide and 2-oxocyclohexanecarboxamide as starting materials. It was established from the spectral data that the obtained 7-amino-6-(arylhydrazono)-7-oxoheptanoic acids existed as mixtures of (Z)- and (E)-isomers, but were converted to an individual (Z)- or (E)-isomer in DMSO solution.

The improved syntheses of 5-(indol-3-yl)-5-hydroxypyrimidine-2,4,6(1H,3H,5H)-trione ( 1) , 5-(5-methylfuran-2-yl)-5-hydroxypyrimidine-2,4,6(1H,3H,5H)-trione ( 2) , 5-(5-N,N-dimethylhydrazonylfuran-2-yl)-5-hydroxypyrimidine-2,4,6(1H,3H,5H)-trione ( 3) , 5-(4-N,N-di-methyl-aminophenyl)-5-hydroxypyrimidine-2,4,6(1H,3H,5H)-trione ( 4a) , and 5-(4-N,N-diethylaminophenyl)-5-hydroxypyrimidine-2,4,6 (1H,3H,5H)-trione ( 4b) from alloxane in mild conditions were reported. The structure of 5-(indol-3-yl)-5-hydroxypyrimidine-2,4,6(1H,3H,5H)-trione ( 1) has been determined by XRD study.

Reaction products have been isolated from SO 2 –L–H 2 O–О2 systems (L = ethylenediamine, N , N , N ′, N ′-tetramethylethylenediamine, piperazine, and morpholine) as onium salts [H 3 NCH 2 CH 2 NH 3 ]SO 4 , [(CH 3 ) 2 NHCH 2 CH 2 NH(CH 3 ) 2 ]SO 4 , [(CH 3 ) 2 NHCH 2 CH 2 NH(CH 3 ) 2 ]S 2 O 6 ⋅ H 2 O, [C 4 H 8 N 2 H 4 ]SO 3 ⋅ H 2 O, [C 4 H 8 N 2 H 4 ]S 2 O 6 , [C 4 H 8 N 2 H 4 ]SO 4 ⋅ H 2 O, [O(C 2 H 4 ) 2 NH 2 ] 2 SO 4 ⋅ H 2 O. The prepared compounds have been characterized by X-ray diffraction analysis, X-ray powder diffraction, IR and mass spectroscopy.

Взаємодією похідних лезо-заміщених порфіринів з гідразидом 7-бром-2-оксо-5-феніл- 2,3-дигідробензо[e][1,4]діазепін-1-іл)-оцтової кислоти отримана низка нових сполук - потенційних протипухлинних агентів.

A simple and effective method has been developed for the synthesis of previously unknown cyclopenta- and cyclohexa[4',5']thieno-[2',3':4,5]pyrimido[1,6-b][1,2,4]triazines in a single step by reaction of 4-hydrazinocyclopenta- and 4-hydrazinocyclohexa[4,5]thieno-[2,3-d]pyrimidines with sodium salts of methyl 4-aryl(heteryl)-2,4-dioxobutanoates. It was shown that the determining factor in the formation of tetracyclic products was isomerization by intramolecular recyclization with mechanism analogous to the Dimroth rearrangement.

Fragmentation of series RGD-peptidomimetics containing piperazine fragment was studied by positive and negative mode of fast atom bombardment mass spectrometry. Main decay pathways and analytical characters of analyzed compounds were determined.

3-Acyloxy-7-bromo-5-(2’-chloro)phenyl-1,2-dihydro-3.H-1,4-benzodiazepin-2-ones (2-8) were synthesized by the interaction of the 7-bromo-3-hydroxy-5-(2’-chloro)phenyl-1,2-dihydro-3.H-1,4-benzodiazepin-2-one (1) with chloroanhy-drides of corresponding carboxylic acids. The formation of hydrogen bonds in solutions of the obtained esters was studied by the method of IR spectroscopy. The molecular and crystalline structure of lauroiloxyderivative 5 was determined by the method of X-ray diffraction analysis. It was noted, that enantic ester of 7-bromo-3-hydroxy-5-(2’-chloro)phenyl-1,2-dihydro-3.H-1,4-benzodiazepin-2-one (3) has showed the highest anticonvulsant activity. This activity is observed in half an hour after injection and remain on the level 200% of control values over 24 hours.

Molecular and crystal structures of N -alkoxy- N -chloroureas and N , N -dialkoxyureas were studied together with those of N -alkoxyureas as reference compounds. N -Alkoxy- N -chloroureas were found to have an elongated N—Cl bond and a shortened N–O(Alk) bond due to the n O(Alk) →σ* N–Cl anomeric effect. Alcoholysis of N -alkoxy- N -chloro derivatives of urea, N ′-arylureas, and carbamates in the presence of silver trifluoroacetate leads to sterically hindered N , N -dialkoxyureas, N , N -dialkoxy- N ′-arylureas, and N , N -dialkoxycarbamates, respectively.

Ethyl ethers of N-[4-(isoindoline-5-yl)amino-4-oxobutyryl]-D,L-β-substituted-β-alanines were synthesized. Estimation of antiaggregatory activity of the compounds obtained has showed that the compounds possess an oral activity ex vivoin mice with the use of human rich platelet plasma.

The complexes of composition [SnL2] have been obtained by SnCl4 interaction with 2-hydroxybenz-(-1-naphth)aldehydes benzoyl-(2-hydroxybenzoyl)hydrazones (2-naphthoyl-(3-hydroxy-2-naphthoyl)hydrazones) (Н2L) in aqua-organic and low alkali media (ethanol in the presence of sodium ethylate and methanol with the addition of ammonia solution). It was proved by methods of mass, electronic and IR spectroscopy ligands molecules to be coordinated by tin atom as tridentate ones via azomethine group nitrogen atom and enol and oxy-groups oxygen atoms. The thermal stability of obtained compounds has been studied. The structure schemes are offered.

New method of preparation of multisubstituted benzylammonium cations via interaction in the SO 2 -L-H 2 O systems (L is benzylamine, α-phenylethylamine, N,N -dimethylbenzylamine, or dibenzylamine) has been developed. The products have been studied by X-ray diffraction, IR, Raman spectroscopy, and mass spectrometry.

The products of interaction in the systems «hydrazides of 2-R-benzoic, 3-R-2-naphthoic acids (R = H, OH) – SnCl4 – R’- benzoic aldehydes (R’ = H, 4-N(CH3)2) – CH3CN» were studied and was found, that in the case of (R, R’ = H) were isolated hydrazones (HL), while all the others – complexes, non-electrolytes with them [SnCl4(HL)]·n CH3CN (n= 1 (I), 2 (II); R = ОН, R’= H) and [SnCl4(L∙H)]·n CH3CN (n = 0, 1; R = H, ОН, R’= 4-N(CH3)2 (III-VI). In the complexes is realized bidentate O(C=O/C-O), N(CH=N) – coordination of ketone (R’ = H) or the enol, the protonated tertiary nitrogen atom of the aldehyde fragment (R’ = 4-N(CH3)2) form of the ligand. Degradation of I-VI begins dehydrochlorination, but in case I, II removal of chlorine proceeds in one stage in the range of 230-310 °С and in the case of III-VI – in two stages at higher temperatures (280-310 and 320-405 °С). The behavior of I - VI under electron impact was investigated.

Literature data about the reaction of arylglyoxals with thiourea has been discussed. It has been shown that no systematic studies in this issue had ever been carried out, furthermore some data is contradictory. The reaction of arylglyoxals with thiourea is reported to be a stepwise process that depends on at least two factors: temperature and solvent. Also the nature of glyoxal may have crucial influence on the structure of products. The convincing evidence of formation three different kinds of heterocyclic systems upon reaction of psubstituted phenylglyoxals with N-methyl-and N-phenylthiourea have been shown.

Literature data about the reaction of arylglyoxals with thiourea has been discussed. It has been shown that no systematic studies in this issue had ever been carried out, furthermore some data is contradictory. The reaction of arylglyoxals with thiourea is reported to be a stepwise process that depends on at least two factors. It is reaction conditions such as temperature and solvent. Also the nature of glyoxal may have crucial influence on the structure of products. In this article has been provided the convincing evidence of formation three different kinds of heterocyclic systems upon reaction of p-substituted phenylglyoxals with N-methyl and N-phenylthiourea.