Cyclic thioureas as cumene oxidation inhibitors

Hexahydro-1,3,5-triazine-4-thiones were synthesized by ternary condensation of thiourea with various aldehydes and amines. The products were characterized by IR and NMR spectroscopy, and their inhibiting effect on cumene oxidation was examined.     

Cycloadditionen von Heterocumulenen an CN-Bindungssysteme. 3. Mitteilung. Bildung von Dihydro-1,3,5-oxadiazin- und Perhydro-s-triazinthionen bei der Reaktion von Iminodithiocarbonaten und Azomethinen mit Aroylisothiocyanaten

The iminodithiocarbonates 5a–5g and the N-(p-methoxybenzylidene)amines 6a–61 undergo 4 + 2-cycloaddition with the aroyl isothiocyanates 4a–4f to yield the expected dihydro-1,3,5-oxadiazine-4-thiones 7, 8 and 14 . The addition of the aroyl isothiocyanates 4a–4f to the azomethines 11a–11c and 15a–15f , however, furnishes both the 4 + 2-cycloaddition products 12 and 16 and the perhydro-s-triazine-2-thiones 13a–13j . The mechanism of formation is discussed.     

Condensed 1,3,5-triazines: 1,3,4-Thiadiazolo[3,2-a]-1,3,5-triazines and isoxazolo[2,3-a]-1,3,5-triazines

A convenient route is reported for the synthesis of substituted 1,3,4-thiadiazolo[3,2-a]-1,3,5-triazine-5,7-diones and isoxazolo[2,3-a]-1,3,5-triazines. Condensation of the appropriately substituted 2-amino-1,3,4-thiadiazole and 3-aminoisoxazole with phenoxycarbonyl isocyanate provides the desired target compounds in fair yield.     

Synthesis of tailor-made 1-aryl-2-arylamino-4-imino-1,4,5,6-tetrahydro-1,3,5-triazine-6-thiones

Reaction of 1-amidino-3-arylthioureas (1) with aryl isothiocyanates yielded 1-aryl-2-arylamino-4-imino-1,4,5,6-tetrahydro-1,3,5-triazine-6-thiones (3) which contained the more electron releasing aryl substituent at the ring nitrogen. The reaction of the S-benzyl derivatives of (1) with aryl isothiocyanates could be directed to give the same type of triazinethione derivatives but with the desired aryl substituent at the ring nitrogen.     

1,2,4-Triazine and triazole derivatives from α-keto acids and thiosemicarbazides

Thiosemicarbazides of 2-hydroxyphenylglyoxylic acid, which, depending on the conditions, undergo cyclization to interconvertible 5-(2-hydroxyphenyl)-6-oxo-1,2,4-triazine-3-thiones or (2-hydroxy-benzoyl)-²-1,2,4-triazoline-5-thiones, are formed by the action of thiosemicarbazide and its homologs on coumarindione. The thiosemicarbazones of 2-hydroxyphenylglyoxlyic and other 2-substituted phenylglyoxylic acids undergo cyclization to 6-(2-hydroxyphenyl)-5-oxo-1,2,4-triazine-3-thiones.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp, 116–121, January, 1977.     

ESCA-untersuchungen zur ladungsverteilung in alkylierten thioharnstoffderivaten und verwandten thiocarbonylverbindungen

The S 2p, N 1s and C 1s electron binding energies of some substituted thiourea derivatives, isothiouronium salts, thiazolthiones, 1,3,5-thiadiazin-2-thiones and 1,3,5-thiadiazinium salts have been measured using the X-ray photoelectron spectroscopy (ESCA). From binding energy shifts information concerning the charge distribution on the atoms in the molecules was obtained. The positive charge of the isothiouronium salts was found to concentrate on carbon and nitrogen atoms. The charge of the 1,3,5-thiadiazinium cations was found to be delocalized demonstrating the pseudoaromatic character of the electronic system.     

Synthesis of 3,5-disubstituted 1-amino-1,3,5-triazine-2,4,6-triones (or 1-aminocyanurates) by cyclic transformation of 1,3,4-oxadiazol-2(3H)-one derivatives

The 5-aryl(or methyl)-3-phenylcarbamoyl-1,3,4-oxadiazol-2(3H)-ones 2 , in the presence of sodium hydride in anhydrous dimethylformamide, were transformed into 1-benzamido(or acetamido)-3,5-diphenyl-1,3,5-triazine-2,4,6-trione derivatives 7 in poor yields. However, compounds 7 were obtained in better yields when the sodium salts of 5-aryl(or methyl)-1,3,4-oxadiazol-2(3H)-ones 1 were treated with two equivalents of aryl(or ethyl)isocyanates. Acidic hydrolysis of 1-acetamido-3,5-diphenyl-1,3,5-triazine-2,4,6-trione ( 7i ) provided the corresponding free N-amino derivative 9 . Nitrous deamination of 9 gave the known 3,5-diphenyl-1,3,5-triazine-2,4,6-trione ( 11 ). This cyclic transformation is the first one to be reported providing 1,3,5-triazine-2,4,6-trione derivatives.     

α-Thioureidoalkylation of 4-alkyl- and 4-phenylthiosemicarbazides

Previously unknown 1,3-dialkyl-4,5-bis[4-alkyl(phenyl)thiosemicarbazido]imidazolidine-2-thiones and 4,5,7-trialkylperhydroimidazo[4,5-e]-1,2,4-triazine-3,6-dithiones have been synthesized by the α-thio-ureidoalkylation of 4-alkyl(phenyl)thiosemicarbazides using 1,3-dialkyl-4,5-dihydroxyimidazolidine-2-thiones.     

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.     

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.     

Novel intramolecular diels-alder reactions with alkynylthio derivatives of 1,2,4-triazines. New routes to thieno[2,3-b]pyridines and thieno[2,3-c]pyridines.

S-Alkylation of 1,2,4-triazine-6-thiones with 4-iodobutyne, followed by oxidation to the sulfoxide and intramolecular cycloaddition (at room temperature),gives 2,3-dihydrothieno[2,3-$\text{c}$]pyridines, which are readily dehydrated with acetic anhydride to thieno[2,3-$\text{c}$]pyridines. The same series of reactions carried out on 1,2,4-triazine-3-thiones leads to thieno[2,3-$\text{b}$]pyridines.     

Solid phase synthesis of 3,4,7-trisubstituted 4,5,8,9-tetrahydro-3H-imidazo[1,2-a][1,3,5]triazepin-2(7H)-thiones and N-alkyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-a][1,3,5]triazepin-2-amines

The solid-phase parallel synthesis of 3,4,7-trisubstituted 4,5,8,9-tetrahydro-3H-imidazo[1,2-a][1,3,5]triazepin-2(7H)-thiones and N-alkyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-a][1,3,5]triazepin-2-amines starting from resin-bound dipeptides is described. The key synthetic steps involve the cylization of an amino and a guanidino functionality using thiocarbonyldiimidazole and the subsequent transformation of the resulting thiourea moiety to a substituted guanidine group using HgCl(2) and various amines. Following cleavage from the resin, the desired products were obtained in good yields and good to moderate purities, depending on the building blocks employed.     

Efficient solid-phase synthesis of 1,3,5-trisubstituted 1,3,5-triazine-2,4,6-triones

The solid-phase synthesis of 1,3-disubstituted and 1,3,5-trisubstituted 1,3,5-triazine-2,4,6-triones from MBHA and Wang resin is described. Reaction of resin-bound amino acids with isocyanates yield resin-bound ureas, which further react with chlorocarbonyl isocyanate in toluene at 65 degrees C to selectively afford the resin-bound 1,3-disubstituted 1,3,5-triazine-2,4,6-triones. Selective alkylation at the N-5 position of the resin-bound 1,3-disubstituted 1,3,5-triazine-2,4,6-triones was accomplished by treatment with alkyl halides in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The desired products were cleaved from their solid support and obtained in good yield and purity. The method can be employed in production of toltrazuril analogue libraries for identification of new anticoccidial agents.     

Formation of hexahydro-1,3,5-triazin-2-one and hexahydro-1,3,5-triazine2-thione derivatives in reactions of glycylglycine with paraformaldehyde andN,N′-disubstituted ureas and thioureas

Hexahydr-1,3,5-triazin-2-one and hexahydro-1,3,5-triazine-2-thione derivatives were shown to be formed selectively in reactions of glycylglycine with paraformaldehyde and N,N'-dialkylureas, NN'-diethylthiourea, and glycoluril.     

The design and synthesis of a herbicide targeted library of N-[1-(1,3-benzoxazol-2-yl)alkyl]-6-alkyl-1,3,5-triazine-2,4-diamines

Amino acids were immobilised by attaching them via a carbamate linker to Wang resin. These intermediates were converted to 1-(1,3-benzoxazol-2-yl)alkanamines over three steps, followed by coupling with 4-alkyl-6-chloro-1,3,5-triazine-2-amines to furnish the desired N-[1-(1,3-benzoxazol-2-yl)alkyl]-6-alkyl-1,3,5-triazine-2,4-diamines. Physico-chemical property profiles were used to support design and development of a combinatorial library. The synthetic methodology described herein was validated with the production of a herbicide targeted library of 300 members.     

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.     

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.     

The preparation of 3,5-disubstituted tetrahydro-4H-1,3,5-oxadiazine-4-thiones,tetrahydro-4H-1,3,5-thiadiazin-4-ones,and tetrahydro-4H-1,3,5-thiadiazine-4-thiones

The reaction of 1,3-disubstituted thioureas with formaldehyde under acidic conditions with removal of water yielded 3,5-disubstituted tetrahydro-4H-1,3,5-oxadiazine-4-thiones. When hydrogen sulfide was bubbled through the reaction mixture, the corresponding tetrahydro-4H-1,3,5-thiadiazine-4-thiones were formed. Similarly, starting from 1,3-disubstituted ureas, a number of tetrahydro-4H-1,3,5-thiadiazine-4-ones were prepared. The latter compounds were also oxidized to the corresponding sulfoxides and sulfones.     

Reactivity of the A-CH=N-NR-CX-B system. 4-R-5-hydroxy-5-phenyl-2,3,4,5-letrahydro-1,2,4-triazine-3-thiones

The behaviour of phenylglyoxal thiosemicarbazones towards aqueous sodium hydroxide have been studied. Examples of addition compounds, 5-hydroxy-5-phenyl-2,3,4,5-tetrahydro-1,2,4-triazine-3-thiones, are reported.     

2-nitroguanidine derivatives: X. Synthesis and nitration of 4-nitriminotetrahydro-1,3,5-oxadiazine and 2-nitriminohexahydro-1,3,5-triazine and their substituted derivatives

A new synthetic procedure was developed to obtain 1-hydroxymethyl-2-nitroguanidine from 2-nitroguanidine and formaldehyde without catalyst. Reactions of 2-nitroguanidine and its 1-methyl-and 1-phenylsubstituted derivatives with formaldehyde and urotropin under acid catalysis resulted in 4-nitriminotetrahydro-1,3,5-oxadiazine and 2-nitriminohexahydro-1,3,5-triazine and their methyl-and phenyl-substituted derivatives, whose nitration with concn. HNO₃ in the presence of acetic anhydride and concn. H₂SO₄ depending on the temperature conditions led to the formation of 4-nitrimino-3,5-dinitrotetrahydro-1,3,5-oxadiazine, 3-methyl-4-nitrimino-5-nitrotetrahydro-1,3,5-oxadiazine, 2-nitrimino-5-nitrohexahydro-1,3,5-triazine, and 1,3,5-trinitro-hexahydro-1,3,5-triazine-2-one.