4-Substituted-3-alkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones II (1,2). Solvolytic transformations of urea and thiourea derivatives into 1-alkyldihydro-6-(2-hydroxyaryl)-1,3,5-triazine-2,4-(1H,3H) diones

A series of 3,4-Dihydro-2-oxo-(3-substituted-2H-1,3-benzoxazin-4-yl)ureas (II, Table I) and 3,4-dihydro-2-oxo-(3-substituted-2H-1,3-benzoxazin-4-yl)thioureas (Table II) was prepared by treating 3,4-dihydro-4-hydroxy-3-substituted-2H-1,3-benzoxazin-2-ones with ureas and thioureas, respectively. In the presence of alcoholic alkali these compounds underwent transacylation to dihydro-6-(2-hydroxyaryl)-1,3,5-triazine-2,4-(1H,2H)diones (Table III) and their 4-thio analogues (Table IV).     

The Structure of New Host Molecules that form Channel Inclusion Compounds

1,3-Benzenediamine,N,N′-bis(4,6-dichloro-1,3,5-triazine-2-yl) and 1,3,5-Triazine,2,2′-[2-methyl-1,3-phenylenebis(oxy)] bis(4,6-dichloro) were synthesized as host molecules. The inclusion compound of 1,3-Benzenediamine,N,N′-bis(4,6-dichloro-1,3,5-triazine-2-yl) crystallizes in the monoclinic crystal system in space group C2/c. The host molecule occupies the space group 2-fold special position and packed in the crystal lattice in such a manner as to leave channels running along the c axis of a rectangular cross-section. It crystallizes with two molecules of acetone that are hydrogen bonded to the amino nitrogen atoms. Molecules of 1,3,5-Triazine,2,2′-[2-methyl-1,3-phenylene bis(oxy)]bis(4,6-dichloro) are packed in the crystal in such a manner as to leave channels of a trapezoid cross-section that are running along the a axis. Guest molecules such as metanol, ethanol, and ethyl acetate can be used to fill the channels. The crystal structures of two inclusion compounds are described.     

Synthesis of 1,3-dialkylpyrazolo [1,5-a]-1,3,5-triazine-2,4-diones isomers of 1,3-dialkylxanthines

The synthesis of a new series of alkylxanthine analogs containing a bridgehead nitrogen atom is reported. 1,3-Dialkylpyrazolo[1,5-a]-1,3,5-triazine-2,4-diones, were prepared by the treatment of 3-methylpyrazolo[1,5-a]-1,3,5-triazine-2,4-dione (3) with the corresponding alkyl iodide. Similarly, the reaction of 3-methyl-7-phenylpyrazolo[1,5-a]-1,3,5-dialkyl-7-phenylpyrazolo[1,5-a]-1,3,5-triazine-2,4-diones. The starting materials, 3 and 17 , were prepared via the reaction of an appropriate 3-aminopyrazole with ethoxycarbonyl isothiocyanate. Several 8-bromo derivatives were prepared by direct bromination of the 1,3-dialkylpyrazolo[1,5-a]-1,3,5-triazine-2,4-diones.     

New liquid crystal compounds ( )-4-[5-(2-Methylbutyl)-1,3-dioxan-2-yl]phenyl 4-alkoxybenzoate

New liquid crystal compounds, (+)-4-[5-(2-methylbutyl)-1,3-dioxan-2-yl] phenyl 4-alkoxybenzoates (5), were synthesized. The mesomorphic behaviour of these compounds is compared with that of (+)-4-(5-alkyl-1,3-dioxan-2-yl)-phenyl 4-(2-methylbutoxy)benzoates (6). While compounds 6 exhibited a chiral smectic C phase, the corresponding compounds 5 did not. This might mean that for the appearance of a chiral smectic C phase in these types of compounds, it is necessary that the carbonyl and the chiral groups exist at nearby positions. Transition temperatures to those isotropic state for compounds 5 were lower than those for compounds 6. This result is common in both cases of (+)-4-alkoxycarbonylphenyl-4-[5-(2-methylbutyl)-1,3-dioxan-2-yl]benzoates (7), and (+)-4-(2-methylbutoxy-carbonyl)phenyl 4-(5-alkyl-1,3-dioxan-2-yl)-benzoates (8).     

Synthesis, crystal structures, electrochemical and spectroscopic properties of ruthenium(II) complexes containing diamino-1,3,5-triazine derivatives

Three Ru(II) complexes [Ru(bpy)₂(1-IQTNH)](ClO₄)₂ (1), [Ru(bpy)₂(2-QTNH)](ClO₄)₂ (2) and [Ru(bpy)₂(3-IQTNH)](ClO₄)₂ (3) (bpy = 2,2′-bipyridine, 1-IQTNH = 6-(isoquinolin-1-yl)-1,3,5-triazine- 2,4-diamine, 2-QTNH = 6-(quinolin-2-yl)-1,3,5-triazine- 2,4-diamine, 3-IQTNH = 6-(isoquinolin-3-yl)-1,3,5-triazine-2,4-diamine) have been synthesized and characterized by elemental analysis, ¹H NMR spectroscopy, electrospray ionization mass spectrometry and X-ray crystallography. The electrochemical and spectroscopic properties of the complexes differ from those of [Ru(bpy)₃]²⁺ owing to the structural differences between the ligands and their complexes.     

In Vitro Anti-Candida Activity and Action Mode of Benzoxazole Derivatives

A newly synthetized series of N-phenacyl derivatives of 2-mercaptobenzoxazole, including analogues of 5-bromo- and 5,7-dibromobenzoxazole, were screened against Candida strains and the action mechanism was evaluated. 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-bromophenyl)ethanone (5d), 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,3,4-trichloro-phenyl)ethanone (5i), 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,4,6-trichlorophenyl)ethanone (5k) and 2-[(5-bromo-1,3-benzoxazol-2-yl)sulfanyl]-1-phenylethanone (6a) showed anti-C. albicans SC5314 activity, where 5d displayed MIC_T = 16 µg/mL (%R = 100) and a weak anti-proliferative activity against the clinical strains: C. albicans resistant to azoles (Itr and Flu) and C. glabrata. Derivatives 5k and 6a displayed MIC_P = 16 µg/mL and %R = 64.2 ± 10.6, %R = 88.0 ± 9.7, respectively, against the C. albicans isolate. Derivative 5i was the most active against C. glabrata (%R = 53.0 ± 3.5 at 16 µg/mL). Benzoxazoles displayed no MIC against C. glabrata. Benzoxazoles showed a pleiotropic action mode: (1) the total sterols content was perturbed; (2) 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(3,4-dichlorophenyl)ethanol and 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,3,4-trichlorophenyl)ethanol (8h–i) at the lowest fungistatic conc. inhibited the efflux of the Rho123 tracker during the membrane transport process; (3) mitochondrial respiration was affected/inhibited by the benzoxazoles: 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-chlorophenyl)ethanol and 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-bromophenyl)ethanol 8c–d and 8i. Benzoxazoles showed comparable activity to commercially available azoles due to (1) the interaction with exogenous ergosterol, (2) endogenous ergosterol synthesis blocking as well as (3) membrane permeabilizing properties typical of AmB. Benzoxazoles display a broad spectrum of anti-Candida activity and action mode towards the membrane without cross-resistance with AmB; furthermore, they are safe to mammals.     

Synthesis,DNA interaction and SOD-like activities of copper(II) complexes: investigation of their DNA-interaction mechanism

Transition Metal Chemistry - Two water-soluble 6-(pyrazin-2-yl)-1,3,5-triazine-2,4-diamine (pzta)-based Cu(II) complexes, [Cu(pzta)(l-LysH)(H2O)](ClO4)2·H2O (1) and...     

Synthesis of sterically-hindered peptidomimetics using 4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-methyl-morpholinium chloride

Our study demonstrated that 4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-methyl-morpholinium chloride (DMTMM) is a versatile coupling reagent for the synthesis of sterically-hindered peptidomimetics. It is superior to HBTU/HOBt and CDMT in controlling racemization and N-arylation, respectively.     

Solution-phase synthesis of a combinatorial library of 3-[4-(coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acid amides

The parallel solution-phase synthesis of a new combinatorial library of 3-[4-(R1-coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acid amides 9 has been developed. The synthesis involves two steps: 1) the synthesis of core building blocks - 3- [4-(coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acids, 6 - by the reaction of 3-(omega-bromacetyl)coumarins 1 with 3-amino(thioxo)methylcarbamoylpropanoic acid (5); 2) the synthesis of the corresponding 3-[4-(coumarin-3-yl)-1,3-thiazol-2-yl- carbamoyl]propanoic acids amides 9 using 1,1'-carbonyldimidazole as a coupling reagent. The advantages of the method compared to existing ones are discussed.     

4-Substituted-3-alkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones. IV (2-4). Keto-Enol tautomerism of β-keto ester derivatives. Reaction of β-dicarbonyl compounds with diamines

A series of α-[3-alkyl-3,4-dihydro-2-oxo-2H-1,3-benzoxazin-4-yl]-β-keto ester derivatives 1 (Table I) were synthesized by the condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazine-2-ones 3 (2) with β-keto esters 4 in the presence of traces of mineral acids under azeotropic conditions. Condensation of 1 with hydrazines 5 gave pyrazolone derivatives 2 (Table II). Condensation of β-diketone derivatives 6 with hydrazines 5 and with 1,2-benzenediamine ( 8 ) resulted in the formation of pyrazoles ( 7a-c ) and diazepine derivatives 12 (Table III) and 13 , respectively.     

Synthesis of 3-Acyl-1,2-benzisoxazoles

A convenient method for the synthesis of 3-acyl-1,2-benzisoxazoles, which are unstable toward bases, is described. Base-catalyzed cyclization of 2-alkyl- and aryl-1,3-dithian-2-yl o-chlorophenylketoximes 4a-1 gave 3-(2-alkyl- and aryl-1,3-dithian-2-yl)-1,2-benzisoxazoles 8a-1 , which were converted into the corresponding 3-acyl-1,2-benzisoxazoles 1a-1.     

Cyanoacetylene and Its Derivatives: XXVIII. Reactions of 2-Mercaptobenzothiazole with Nitriles of αα,ββ-Acetylene γγ-Hydroxyacids and with 3-Phenyl-2-propynonitrile

Nucleophilic addition of 2-mercaptobenzothiazole to 4-alkyl-4-hydroxy-2-alkynonitriles at 1:1 ratio in the presence of 4-6 wt% of Et₃N occurs regio- and stereospecifically to afford (Z)-4-alkyl-3-(benzothiazolyl-2-thio)-4-hydroxy-2-alkenonitriles (yield 40-51%). In the presence of 1.3 wt% of Dabco the thiazole and 4-hydroxy-4-methyl-2-pentynonitrile (1:1) give rise to a mixture of 2-alkenonitrile and 2-(3,3,6,6-tetramethyl-2-cyanomethyl-5-cyanomethylene-1,4-oxathian-2-yl)thiobenzothiazole. At the use of 4-6 wt% of LiOH arises an intractable mixture containing 1,4-oxathiane, benzothiazol-2-one, 2-[1-(5,5-dimethyl-2-cyanomethyl)-4-cyanomethylene-1,3-oxathiolan-2-yl)-1-methylethyl]thiobenzothiazole, bis(2,2,5,5-tetramethyl-6-cyanomethyl-3-cyanomethylene-1,4-oxathian-6-yl) disulfide, bis[1-(5,5-dimethyl-2-cyanomethyl-4-cyanomethylene-1,3-oxathiolan-2-yl)-1-methylethyl] disulfide, and 3-[1-(5,5-dimethyl-2-cyanomethyl-4-cyanomethylene-1,3-oxathiolan-2-yl)-1-methylethyl]benzothiazol-2-one (according to ¹H and ¹³C NMR data). 2-mercaptobenzothiazole adds to 3-phenyl-2-propynonitrile in the presence of 7 wt% of KOH with regio- and stereospecific formation of (Z)-3-(benzothiazolyl-2-thio)-3-phenyl-2-propenonitrile (88%).     

Polymorphism and spin crossover in mononuclear Fe(II) species containing new dipyridylamino-substituted s-triazine ligands

Four new dipyridylamino-substituted s-triazine ligands DBB (N(2),N(2),N(4),N(4)-tetrabenzyl-N(6),N(6)-di(pyridin-2-yl)-1,3,5-triazine-2,4,6-triamine), DDB (N(2),N(2),N(4),N(4)-tetrabutyl-N(6),N(6)-di(pyridin-2-yl)-1,3,5-triazine-2,4,6-triamine), DCCl (6-chloro-N(2),N(2)-dicyclohexyl-N(4),N(4)-di(pyridin-2-yl)-1,3,5-triazine-2,4-diamine) and DDT (N(2),N(2),N(4),N(4)-tetraphenyl-N(6),N(6)-di(pyridin-2-yl)-1,3,5-triazine-2,4,6-triamine), have been incorporated into eight new, 0D Fe(II) compounds of type [Fe(II)(NCX)(2)(L)(2)]·Solvent (where NCX = NCS(-), NCSe(-) or N(CN)(2)(-)). The polymorphic compounds α-trans-[Fe(II)(NCS)(2)(DBB)(2)] (1) and β-trans-[Fe(II)(NCS)(2)(DBB)(2)] (2) display, respectively, a relatively abrupt, complete, one-step spin transition with T(?) ~ 170 K, and a more gradual, complete, one-step spin transition with T(?) ~ 300 K. Gradual, one-step spin transitions are observed for trans-[Fe(II)(N(CN)(2))(2)(DBB)(2)]·2CH(3)CH(2)OH (3) and trans-[Fe(II)(NCSe)(2)(DCCl)(2)]·2CH(3)OH (6) with T(?) ~ 280 K for both, while the one-step spin transition observed for a desolvated sample of trans-[Fe(II)(NCSe)(2)(DDB)(2)]·2CH(3)OH (4) is relatively abrupt, showing hysteresis with T(?↑) = 285 K and T(?↓) = 275 K. The compounds cis-[Fe(II)(NCS)(2)(DDB)(2)] (5) and trans-[Fe(II)(NCS)(2)(DDT)(2)]·4CH(2)Cl(2) (7) remain high spin, while structural data on trans-[Fe(II)(NCSe)(2)(DDT)(2)]·4CH(2)Cl(2) (8) suggests a spin transition at low temperatures. It is likely that distortion of the Fe(II)N(6) octahedron, intermolecular interactions and molecular conformation are crucial in deciding both the T(?) and abruptness of the spin transition for these species, although the nature of their influence varies. Variable temperature powder X-ray diffraction measurements on the polymorphs 1 and 2 reveal anisotropy in the unit cell parameters as the spin transition occurs.     

Quantum-chemical study of mechanisms of reaction between 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde with 2-mercaptoethanol

By quantum-chemical method MP2/6-311+G**//B3LYP/6-31+G** competing reaction channels were studied of the formation of pyrazolyl-1,3-oxathiolane and/or bis(2-hydroxyethyl)dithioacetal from 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde and 2-mercaptoethanol. The kinetically controlled formation of bis(2-hydroxyethyl) dithioacetal is governed by the concentration in the reaction mixture of 2-mercaptoethanol dimers. The reaction by stages of 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde with the molecules of mercaptoethanol results in the prevailing formation of 2-(pyrazol-4-yl)-1,3-oxathiolane structures.     

Synthesis of 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones and their conversion into 2-aryl-1,2,4-triazine-3,5-(2H,4H)odiones. A new synthesis of 1-aryl-6-azauracils

Treatment of 6-amino-5-arylazo-1,3-dimethyluracils with urea or N,N′-carbonyldiimidazole gave the respective 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones, which were hydrolyzed with alkali to afford 2-aryl-2,3,4,5-tetrahydro-3,5-dioxo-1,2,4-triazine-6-carboxylic acids (1-aryl-6-azauracil-5-carboxylic acids). Thermal decomposition of these carboxylic acids gave the corresponding 2-aryl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-6-azauracils). Methylation of the latter with methyl iodide gave the corresponding 2-aryl-4-methyl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-3-methyl-6-azauracils).     

Proton-acceptor properties of azahomofullerene and fullerenoaziridine containing a cyanuric acid fragment

¹³C and ¹H NMR and UV spectral studies on 1,3-diallyl-5-[4-(azahomo[60]fullereno)butyl]hexahydro-1,3,5-triazine-2,4,6-trione ([5,6]-open isomer) and 1,3-diallyl-5-[4-(aziridino[60]fullereno)butyl]hexahydro-1,3,5-triazine-2,4,6-trione ([6,6]-closed isomer), as well as quantum-chemical calculations, showed that only the latter possesses weakly basic properties.     

Umsetzungen von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin mit Barbitursäure-Derivaten

Reactions of 3-(Dimethylamino)-2,2-dimethyl-2H-azirines with Barbituric-Acid Derivatives The reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and 5,5-disubstituted barbituric acids 5 in i-PrOH at ca. 70° gives 2-[5-(dimethylamino)-4,4-dimethyl-4H-imidazol-2-yl]alkanamides of type 6 in good yields (Scheme 1). The formation of 6 proceeds with loss of CO₂; various reaction mechanisms with a zwitterionic 1:1 adduct B as common intermediate are discussed (Schemes 2 and 5). Thermolysis of product 6 leads to 2-alkyl-5-(dimethylamino)-4,4-dimethyl-4H-imidazoles 8 or the tautomeric 2-alkylidene derivatives 8 ′ via elimination of HNCO (Scheme 3). The latter undergoes trimerization to give 1,3,5-triazine-2,4,6-trione. No reaction is observed with 1,5,5-trisubstituted barbiturates and 1 in refluxing i-PrOH, but an N-alkylation of the barbiturate occurs in the presence of morpholine (Scheme 4). This astonishing reaction is explained by a mechanism via formation of the 2-alkoxy-2-(dimethylamino )aziridinium ion H which undergoes ring opening to give the O-alkylated 2-amino-N¹,N¹-dimethylisobutyramide I as alkylating reagent (Scheme 4).     

A new tetrazole-containing 2-amino-4,6-di(aziridin-1-yl)-1,3,5-triazine derivative: synthesis,interaction with DNA,and antitumor activity

Russian Chemical Bulletin - ({5-[4,6-Di(aziridin-1-yl)-1,3,5-triazin-2-yl]amino}-2,2-dimethyl-1,3-dioxan-5-yl)-methyl 2-(5-phenyl-2H-tetrazol-2-yl)acetate was synthesized and characterized. The...     

Multicomponent Synthesis of 1,3-Bis[(alkylsulfanyl)methyl]-1,3,5-triazinan-2-ones

Russian Journal of Organic Chemistry - Previously unknown 5-alkyl-1,3-bis[(alkylsulfanyl)methyl]-1,3,5-triazinan-2-ones have been syn­thesized by three-component condensation of available...     

Reaction of 5-substituted-2-amino-2-oxazolines with ethoxycarbonyl isocyanate. A route to 2,3,6,7-tetrahydro-4H-oxazolo[3,2-a]-1,3,5-triazine-2,4-diones

The reaction of 2-amino-2-oxazolines with ethoxycarbonyl isocyanate was investigated in order to access to fused 1,3,5-triazine-2,4-diones with a potential 5-HT₂ antagonist activity. The reaction leads to 2,3,6,7-tetrahydro-4H-oxazolo[3,2-a]-1,3,5-triazine-2,4-diones and to 1-carbethoxy-3-(2-iminooxazolidine)ureas. During the carbamoylation the regioselectivity seems to be related to the strong nucleophilic character of the endo nitrogen atom of 2-amino-2-oxazolines. The structures of two compounds were studied by X-ray crystallography. N-Substituted compounds have been prepared by alkylation of the 2,3,6,7-tetrahydro-7-phenoxymethyl-4H-oxazolo[3,2-a]-1,3,5-triazine-2,4-dione.