Rade Marković

A Base Promoted Cyclization of N-Propargylaminopyridines. Synthesis of Imidazo[1,2-a]pyridine Derivatives

A base promoted cyclization of the protected N-propargylaminopyridines was shown to be an efficient method for the preparation of imidazo[1,2-a]pyridine derivatives. The reactions were carried out with a small excess of base, at room temperature or slightly above producing the heterocyclic products in moderate to good yields. The stereoelectronic properties of substituents on the pyridine ring were shown to influence the cyclization process.

Stereo- and regiocontrol of electrophile-initiated rearrangement of push–pull 5-substituted 4-oxothiazolidine derivatives

Abstract Regioselective α-bromination of ( Z )-5-substituted-2-alkylidene-4-oxothiazolidine derivatives affords, under mild experimental conditions, vinyl bromides 3 in good yields. They undergo rearrangement providing a highly efficient route to the stereodefined 4-oxothiazolidine derivatives possessing two fully delocalized exocyclic double bonds at C(2) and C(5) positions. A mechanism of this novel rearrangement reaction via base-promoted proton transfer from one carbanionic site to another, followed by the bromination–dehydrobromination sequence, is proposed.

High regioselectivity in the heterocyclization of β-oxonitriles to 4-oxothiazolidines: X-ray structure proof

Base-catalyzed reactions of β-oxonitriles 1 with diethyl mercaptosuccinate favour heterocyclization to afford 2-alkylidene-4-oxothiazolidines 3, rather than 2-alkylidene-4-oxo-1,3-thiazinanes 4. The observed regioselectivity is based on spectroscopic and experimental evidence, including a single-crystal X-ray structure determination.

A novel and efficient 4-oxothiazolidine-1,2-dithiole rearrangement induced by Lawesson's reagent

Abstract Functionalized 1,2-dithioles have been synthesized by a ring opening–closing process of 5-substituted- and 5-unsubstituted-2-alkylidene-4-oxothiazolidines with Lawessons reagent. The 13 C NMR data confirmed the meso -ionic structure of these aromatic-type 1,2-dithioles.

Stereocontrolled synthesis of new tetrahydrofuro[2,3-d]thiazole derivatives via activated vinylogous iminium ions

Heterocyclization of (Z)-5-(2-hydroxyethyl)-3-methyl-4-oxothiazolidines, bearing electron-withdrawing groups conjugated to an exocyclic double bond at C(2)-position, afforded under reductive conditions, cis-tetrahydroftiro[2,3- d]thiazole derivatives. The reactions of these functionalized push-pull beta-enamines occur in a stereocontrolled fashion via activated vinylogous N-methyliminium ions, which are trapped by an internal hydroxyethyl group

Quantitative structure–retention relationship of new N‐substituted 2‐alkylidene‐4‐oxothiazolidines

A quantitative structure-retention relationship (QSRR) was built to investigate the relationship between the structural descriptors of 23 newly synthesized N-substituted 2-alkylidene-4-oxothiazolidines and their chromatographic retention. Retention was investigated by means of the reversed-phase thin-layer chromatography (RP-TLC) on the C(18) and CN stationary phases, using methanol, acetonitrile, and tetrahydrofuran as organic modifiers. Full geometry optimization based on the Austin Model 1 (AM1) semi-empirical molecular orbital method was carried out and a set of physicochemical molecular descriptors was calculated from the optimized structures. QSRR was built by means of multiple linear regression (MLR) and partial least squares regression (PLS). The best MLR and PLS models were chosen, on the basis of comparison of the statistical parameters (squared correlation coefficient (R(2)), cross-validated coefficient (R(cv)(2)), and Fischer significance value (F) were used for MLR and the square of the multiple correlation coefficients for the calibration objects (R(2)Y (cum)) and the square of the multiple correlation coefficients for the cross-validation segments (Q(2)Y (cum)) were used for PLS models). Statistically significant and physically meaningful QSRR provided better insight on understanding the retention behavior of the new series of compounds. Lipohilicity (expressed as log P) was included in all MLR and PLS models.

Sequential Bromination-Rearrangement of Push-Pull Thiazolidines Induced by Pyridinium Hydrobromide Perbromide under Homogenous Reaction Conditions

Regiospecific bromination-rearrangement of the 5-substituted 2-alkylidene-4-oxothiazolidine derivatives induced by pyridinium hydrobromide perbromide (PHBP) provides a new synthetic approach to the corresponding push-pullthiazolidines with two exocyclic double bonds. In comparison to a heterogenous alternative, this conversion, taking place in acetonitrile under homogenous reaction conditions, has the advantage of almost quantitative yields and a substantial rate enhancement.

SYNTHESIS AND X-RAY CRYSTAL ANALYSIS OF [Cu2(HCOO)tpmc]-[Cu2(CH3COO)tpmc](ClO4)6·6H2O(tpmc = N,N′,N″,N‴-TETRAKIS-(2-PYRIDYLMETHYL)-1,4,8,11-TETRAAZACYCLOTETRADECANE). PREPARATION AND CHARACTERIZATION OF [Cu2(HCOO)tpmc](ClO4)3·H2O

The new structure of [Cu2(HCOO)tpmc][Cu2(CH3COO)tpmc](ClO4)6·6H2O (tpmc = N,N′,N″,N‴-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetra-decane), consists of [Cu2(HCOO)tpmc]3+ and [Cu2(CH3COO)tpmc]3+ cations, perchlorate anions and water of crystallization. Two different binuclear transition metal complexes with the tpmc ligand form the same crystal lattice giving the monocrystals. The crystal structure of this compound has been solved by single crystal X-ray diffraction studies. It crystallizes in the triclinic system, space group with a = 14.176(3), Å, b = 16.864(4) Å, c = 20.681(3), Å, α = 100.68(3)○, β = 101.00(3)○, γ = 101.37(3)○, V = 4628.6(16), Å3, R = 0.0729. Each copper atom is penta-coordinated in a distorted square-pyramidal arrangement. In addition, [Cu2(HCOO)tpmc](ClO4)3·H2O was prepared and its properties were compared with the previously described μ-acetato analogue.

ESTIMATION OF LIPOPHILICITY OF N-SUBSTITUTED 2-ALKYLIDENE-4-OXOTHIAZOLIDINES BY MEANS OF REVERSED-PHASE THIN-LAYER CHROMATOGRAPHY

The chromatographic behavior of 23 new 2-alkylidene-4-oxothiazolidine derivatives was investigated by means of the reversed-phase thin-layer chromatography (RP TLC) on the C18 and CN stationary phases. Binary mixtures of methanol-water, acetonitrile-water, and tetrahydrofuran-water were used as mobile phases. Linear relationships between the volume fraction of the organic mobile phase modifier and the RM values were established for each solute with high correlation coefficient values (r > 0.99). The investigated 4-oxothiazolidines are a congeneric set of compounds, and significant correlations were obtained between the chromatographically determined and m values. The lipophilicity parameters obtained from the reversed-phase experiments were compared with the calculated log P values. Some of these correlations offer very good predicting models, which are important for a better understanding of the relationships between chemical structure and retention, and can prove helpful in the structure-activity studies as well. Finally, our investigation was focused on chemometric processing of the retention data in different chromatographic systems. To this effect, Principal Component Analysis (PCA) was performed, yielding the results helpful in interpretation of interactions among investigated substances, binary mobile phases, and the two different stationary phases.

Nucleophilic Functionalization of 2-Alkylidene-4-Oxothiazolidines at C(5)-Position Induced by Formation of Novel Pyridinium Salt

Abstract The synthesis of unsubstituted pyridinium salt containing the 4-oxothiazolidine moiety bondedviaC(5) to the N position of the pyridine nucleus is reported. The nucleophilic displacement of pyridine from pyridinium salt by the selected nucleophiles leads to the formation of new 5-substituted 4-oxothiazolidines in good yields.