Synthesis of 6-imino-5-tetrahydro-1H-2-pyrrolylidenhexahydro-2,4-pyrimidinediones as intermediates for the synthesis of C-azanucleosides

The method for the synthesis of 6-imino-5-tetrahydro-1H-2-pyrrolylidenhexahydro-2,4-pyrimidinediones is described. It is shown that the reaction of phosphorus trichloride, 2-pyrrolidones and 6-aminopyrimidines brings to condensation producing 6-imino-5-tetrahydro-1H-2-pyrrolylidenhexahydro-2,4-pyrimidinediones as intermediates for the synthesis of C-azanucleosides. The reaction of 6-imino-1,3-dimethyl-5-tetrahydro-2-pyrrolylidenhexahydro-2,4-pyrimidinedione with benzoyl chloride produces 10-benzoyl-2,4-dimethyl-6-phenyl-1,2,3,4,8,9-hexahydropyrimido[5,4-e]pyrrolo[1,2-c]pyrimidine-1,3-dione. A method for the selective reduction of the carbomethoxy group of methyl 5-(4-imino-1,3-dimethyl-2,6-dioxohexahydro-5-pyrimidinyliden)-2-pyrrolidine carboxylate by system NaBH₄/1,4dioxane/CoCl₂/PEG-400 is described.     

Theoretical Study of Tautomerization in 1,5-Dimethyl-6-Thioxo-1,3,5-Triazinane-2,4-Dione

In this work, the tautomeric transformations of a 1,5-dimethyl-6-thioxo-1,3,5-triazinane-2,4-dione molecule are explored at the M062X/6-311G(d,p) level of theory in gas and solution phases. These calculations show that the 1,5-dimethyl-6-thioxo-1,3,5-triazinane-2,4-dione isomer is more stable than its tautomer (4-hydroxy-1,5-dimethyl-6-thioxo-5,6-dihydro-1,3,5-triazin-2(1H)-one) in gas and solution phases. The frontier molecular orbitals and band gap energy calculations are performed at the M062X/6-311G(d,p) level in gas and various solvents. Solvent effects are analyzed using the self-consistent reaction field method based on the polarizable continuum model in chloroform, chlorobenzene, tetrahydrofurane, dichloromethane, and quinoline. The solvent effect on the N–H and C=O vibrations is explored. Also, natural bond orbital (NBO) analysis was used to understand the structure and bonding of the molecule.     

Three-component synthesis of 5:6 and 6:6 fused pyrimidines using KF-alumina as a catalyst

A series of fused pyrimidine derivatives were synthesized by the three-component reaction of an aryl aldehyde, urea, or guanidine in ethyl alcohol/dioxane in presence of 1-methyl-1H-pyrrol-2(3H)-one 1, 1-methylpiperidin-2-one 2, 1-methylindolin-2-one 3, or 1,3-dimethyl-dihydropyrimidine-2,4-dione 9 at 80 °C catalyzed by KF-Al₂O₃. For example, when 1-methyl-1H-pyrrol-2(3H)-one 1, arylaldehyde 4, and urea 5 were treated with KF-Al₂O₃ in ethyl alcohol at 80 °C for 3-5 h, we obtained pyrrolo[2,3-d]pyrimidine derivatives in good yield.     

Oxygen replacement by fluorine in carbonyl derivatives of perfluoroaromatic compounds and isomerization of perfluoroindan-1,3-dione to perfluoro-3-methylenephthalide under the action of HF/SbF5

When acted upon by HF/SbF₅ at 95 °C, carbonyl groups of perfluorinated acetophenone (10), 3,4-dihydronaphthalen-1(2H)-one (8), 2,3-dihydronaphthalene-1,4-dione (9), benzocyclobutenone (6), benzocyclobutenedione (7) and indan-1-one (1) are converted into difluoromethylene groups to give the corresponding perfluoroaromatic products. Perfluoroindan-2-one (5), under the same conditions, is transformed to bis(perfluoroindan-2-yl) ether (21). On heating with HF/SbF₅, perfluoroindan-1,3-dione (2) isomerizes into perfluoro-3-methylenephthalide (4) at 95 °C, and gives 4,5,6,7-tetrafluoro-3-trifluoromethyl-phthalide (14) at 130 °C. Compound 4 in the absence of a solvent dimerizes giving perfluorodispiro[phthalide-3,1′-cyclobutane-2′,3″-phthalide] (18), and when heated with SbF₅ at 130 °C, it is converted into perfluoro-3-methylphthalide (3). When acted upon by HF/SbF₅ at 95 °C, perfluorinated benzoic acid (12) and phthalic anhydride (13) give the corresponding products with trifluoromethyl groups.     

Reaction of 2-imino-3-aryl-4-oxothiazolidines with phenyl isothiocyanate

2-Phenylthiocarbamoylimino-3-aryl-4-oxothiazolidines, which are hydrolyzed at the C=N and N₃=C₄ bonds of the thiazolidine ring to give 3-arylthiazolidine-2,4-diones, N-phenylthiocarbamoylarylpseudothiohydantoic acids, and 3-phenylthiocarbamoylthiazolidine-2,4-dione, were synthesized by reaction of 2-imino-3-aryl-4-oxothiazolidines with phenyl isothiocyanate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 903–905, July. 1976.     

Synthesis of 5-[2-(Phenoxy)ethyl] Derivatives of 6-Methyluracil, 6-Methyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one,and 2-Imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one

A synthesis of novel derivatives of 6-methyluracil, 6-methyl-2-thioxo-, and 2-imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one containing a 2-(phenoxy)ethyl substituent at position 5 of the pyrimidine ring has been carried out. It was found that 5-[2-(phenoxy)ethyl] derivatives of 6-methyl-2-thioxo- and 2-imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one are obtained by the condensation of the corresponding ethyl 3-oxo-2-(2-phenoxyethyl)butanoates with thiourea or guanidine. 6-Methyl-5-[2-(phenoxy)ethyl]uracils can be prepared by treating 6-methyl-5-[2-(phenoxy)ethyl]-2-thioxo-2,3-dihydro-1H-pyrimidin-4-ones with an excess of aqueous monochloroacetic acid solution. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1213–1217, August, 2005.     

Investigation of the reactivities and tautomerism of azolidines. 53. Synthesis of 5-arylidene-2-allylamino-δ2-thiazolin-4-ones and 5-arylidene-2-imino-3-allylthiazolidin-4-ones

Depending on the reaction conditions, 2-allylamino-5-arylidene-²-thiazolin-4-ones, 2-imino-3-allyl-5-arylidenethiazolin-4-ones, and 3-allyl-5-arylidene-thiazolidine-2,4-diones are obtained by condensation of 2-allylamino-²-thiazolin-4-one and 2-imino-3-allylthiazolidin-4-one with aromatic aldehydes.See [1] for communication 52.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 494–497, April, 1985.     

4-Thiazolidines,derivatives and analogs

Heating thiazan-2, 4-dione (I) with P₂S₅ in xylene or toluene gives a hitherto unknown isomer of propiorhodanine (II), 4-thione-1, 3-thiazan-2-one (III), with an active thione group and more acidic properties than II. Reaction of I with P₂S₅ in dioxane gave 2, 4-dithionethiazane, (IV) in high yield, this being the most convenient method of preparing IV.     

Allylsilane and diallylsilane reactions with functionalized ethylene ketals or benzodioxoles

The bis-allylation of ethylene ketal and catechol ketal derivatives of 2,5-hexanedione occurred with a great stereoselectivity. The tetraallylation of bis-catechol ketal derivatives of 2,5-hexanedione and 2-methyl-1,3-cyclohexanedione or the diallylation of 4-phenylbutan-2-one derivatives arise in good yields and these compounds were suitable substrates for ring-closing metathesis leading to 4,4-dialkylcyclopentenes. Condensation of 1,8-bistrimethylsilyl-2,6-octadiene (Bistro) with 4-phenylbutan-2-one catechol ketal derivatives or 2-methylcyclohexan-1,3-dione mono catechol ketal afforded in good yields cyclic and tricyclic products 12 or 23, respectively.     

Synthesis and cytotoxic activity against human tumor cells of heterocyclic systems derived from 2-thioxo-1,2-dihydro-4H-3,1-benzothazin-4-one

The title compound was prepared and converted to 2-hydrazinyl-1,2-dihydro-4H-benzo[d][1,3]thiazin-4-one which was utilized to synthesize fused heterocyclic systems, namely benzotriazolothiazinone derivatives, as well as, nonfused heterocyclic systems such as pyrazolyl-benzothiazinones, benzothiazinylpyridazine and imidazolylbenzothiazinone derivatives via reaction with formamide, acetic acid, ethyl cyanoacetate, maleic anhydride and benzaldehyde followed by treatment with glycine, respectively. All compounds have been structurally characterized by means of IR, MS, and ¹H-NMR spectra. The synthesized compounds were evaluated in vitro for their antiproliferative activity against HePG-2 and MCF-7 cell lines. 2H-Benzo[d][1,3]thiazine-2,4(1H)-dithione and 2-thioxo-1,2-dihydro-4H-benzo[d][1,3]thiazin-4-one were the most potent against the two cancer cells compared to that of the reference compound doxorubicin. Most of the synthesized compounds also exhibited good cytotoxic activity.     

Reactions of N , N -Disubstituted 5-Arylmethylidene-2-amino-thiazol-4(5 H )-ones with CH Acids

 N,N-Disubstituted 5-arylmethylidene-2-aminothiazol-4(5H)-ones reacted with diethyl malonate, ethyl benzoylacetate, acetylacetone, or cyclopentadiene in refluxing toluene and in presence of powdered sodium to give the respective 5-arylmethylidene-2′-amino-2,5′-bithiazolylidene-4,4′-dione derivatives in moderate yields. 5-Benzylidene-2-morpholin-4-yl-2-thiazol-4(5H)-one reacted with malononitrile in toluene and in presence of powdered sodium under mild conditions to afford the 1:1 adduct, benzylmalononitrile, and 2-morpholin-4-yl-2-thiazol-4(5H)-one. However, similar treatment of 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-one with malononitrile yielded the 2,5′-bithiazolylidene-4,4′-dione derivative together with 4-methoxyphenylmethylidene malononitrile. Treatment of 5-benzylidene- and 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-ones with 3-phenyl-4-oxo-2-thioxo-1,3-thiazolidine in refluxing toluene and in presence of powdered sodium produced 5-arylmethylidene-3-phenyl-4-oxo-2-thioxo-1,3-thiazolidines in good yields. The structures of all products were deduced from microanalytical and spectroscopic data, mechanistic details are discussed.     

Über die Reaktionen von Guanidin bzw. Harnstoff mit Cyanhydrinen

Action of guanidine or urea on cyclohexanone-, cyclopentanone-, cycloheptanone-and acetonecyanohydrine3 a?3 d generates very different products: 3 a reacts with guanidine inDMF to yield 1,3-diazaspiro[4.5]decane-2,4-diimine (5 a). Heating the components without solvent affords 7,14-diazadispiro[5.1.5.2]pentadecan-15-one(7)^15–17, the guanidine not participating in the reaction; similarly3 b is transformed by guanidine to a pentacyclic dispirocompound (possible formulae19 and20), whereas3 d reacts to give 3,3,5,5-tetramethylpiperazine-2,6-dione(21)¹⁹. In 3-pentanone guanidine-cyanide condensates itself to give 2,4-diamino-triazine (22)^{21, 22}. Action of urea on3 a?3 d yields the 4-imino-1,3-diazaspiroalkan-2-ones6 a?6 c and the 4-imino-5,5-dimethylimidazolidin-2-one6 d ^6–8 resp. If the reaction of urea and3 d is carried out inDMF, however, 5,5-dimethyl-4-ureido-3-imidazolin-2-one (28) (or the tautomeric carbamoyliminoimidazolidinone27) is produced. The structures of the compounds prepared are proved by NMR-, IR- and mass spectra.     

Multiple pathways in the synthesis of new annelated analogues of 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (emivirine)

Condensation of 3-(3,5-dimethylphenyl)-2-oxocyclopentanecarboxamide (11) with oxalyl chloride and condensation of ethyl 2-benzylamino-5-methyl-3-phenylcyclopent-1-enecarboxylate (17a) with trimethylsilyl isothiocyanate gave 7-(3,5-dimethylphenyl)-6,7-dihydro-5H-cyclopenta[e][1,3]oxazine-2,4-dione (12) and 1-benzyl-5-methyl-7-phenyl-2-thioxo-1,2,3,5,6,7- hexahydrocyclopentapyrimidin-4-one (18a), respectively. Acid catalyzed ring-closure of 6-(4-methyl-1-phenylpent-3-enyl)-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (26) and radical mediated ring-closure of 1,3-bis(benzyloxymethyl)-5-bromo-6-(1-phenylbut-3-enyl)-1H-pyrimidine-2,4- dione (32a) gave 5,5-dimethyl-8-phenyl-5,6,7,8-tetrahydro-1H-quinazoline-2,4- dione (28) and 1,3-bis(benzyloxymethyl)-5-methyl-7-phenyl-1,5,6,7- tetrahydrocyclopentapyrimidine-2,4-dione (33), respectively. Annelated emivirine analogues 7-(3,5-dimethylphenyl)-1- ethoxymethyl-1,5,6,7-tetrahydrocyclopentapyrimidine-2,4-dione (4), 1-ethoxymethyl-5,5-dimethyl-8-phenyl-5,6,7,8-tetrahydro-1H-quinazoline- 2,4-dione (5) and 1-ethoxymethyl-5-methyl-7-phenyl-1,5,6,7- tetrahydrocyclopentapyrimidine-2,4-dione (6) were obtained in few steps from 12, 28 and 18a/33, respectively. These new analogues can be considered as conformationally locaTed analogues of emivirine. However, the compounds 4 6 showed lower activities against HIV-1 than emivirine and it is concluded that the locked conformation disfavours activity against HIV-1.     

A convenient one-pot synthesis of 2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one derivatives and their further transformations

The trifluoromethyl containing heterocycles, 2-hydroxy-4-aryl-3-(thien-2-oyl)-2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one derivatives 4, were synthesized via a one-pot three-component reaction of aldehyde 1 with 1,3-cyclohexanedione 2 and 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-dione 3 in the presence of a catalytic amount of Et₃N. The effect of bases and solvents on the reaction efficiency and yield was briefly investigated. Treatment of 4 with an excess amount of NH₄OAc in ethanol afforded 2-trifluoromethyl-1H-quinolin-5-one derivatives 5. Refluxing of 4 with TsOH in CHCl₃ gave the corresponding dehydrated products 8.     

Fluorinated 1,3-diketones, 2-trifluoroacetyl phenols and their derivatives: versatile reactants in phosphorus chemistry

The role of fluorinated β-diketones, their tautomers (keto–enols) and their derivatives as reagents towards λ³P compounds is reviewed, including 2-trifluoroacetyl phenols, possessing formally a keto–enol system, and their derivatives. In an ‘insertion’ reaction phosphine and the keto–enol tautomers of 1,1,1,5,5,5-hexafluoro- and 1,1,1-trifluoropentan-2,4-dione furnished primary (S) or (R) α-hydroxy phosphines, whose enol functions probably isomerized the corresponding keto compounds. Further addition and isomerisation furnished 1,3α,5,7β-tetrakis(trifluoromethyl)-2-phospha-6-oxa-9-oxabicyclo[3.3.1]-nonan-3β,7α-diol and 1,7-trifluoromethyl-3,5-methyl-2,4,8-trioxa-6-phophaadamantane, exclusively one diastereomer in each case. The main mechanistic feature of these reactions is a consecutive diastereoselective hemiketal cyclization. 1,1,1,5,5,5-Hexafluoro- and 1,1,1-trifluoropentan-2,4-dione, as well as 2-trifluoroacetyl phenol and its imino derivatives reacted diastereospecifically with phosphonous acid dichlorides, RPCl₂ to give in a concerted mechanism thermally stable tricyclic λ⁵σ⁵P phosphoranes containing two five-membered rings and one six-membered ring. Surprisingly, the two CF₃ groups bonded to an sp³-hybridized carbon were in a cisoid arrangement having closest non-bonding FF distances of 301.4 or 273.5 pm. These findings reflect the ‘through space’ F---F coupling constants of the tricyclic phosphoranes (J_FF=4.0–7.0 Hz), in solution. 4,4,4-Trifluoro-3-hydroxy-1-phenyl-butan-1-one and methyl or phenyl phosphonous acid dichlorides gave similar tricyclic phosphoranes decomposing at ambient temperature to furnish 1,2λ⁵σ⁴-oxaphospholanes and (E)-1,1,1-trifluoro-4-phenyl-but-2-en-4-one. Dialkylphosphites and 1,1,1,5,5,5-hexafluoropentan-2,4-dione reacted to give either the (Z)-enol phosphonates or the respective γ-ketophosphonates from which in two cases four diastereomeric 2-oxo-2,5-dialkoxy-3,5-bis(trifluoromethyl)-3-hydroxy-1,2λ⁵σ⁴-oxa-phospholanes were obtained. 2-Trifluoroacetyl cyclohexanone, 4,4,4-trifluoro-3-trimethylsiloxy-1-phenylbutan-1-one, 1-benzoyl-2-trifluormethyloxirane, 1-benzoyl-2-trifluoro-methylaziridine, 2-trifluoroacetyl-1-trimethylsiloxybenzene and (trifluoroacetyl-1-phenyl) diethyl phosphate reacted with tris(trimethylsilyl) phosphite to give functionalized α-trimethylsiloxy phosphonates, which could easily be transferred into the respective phosphonic acids. In the case of an oxirane and an aziridine ketone no ring cleavage was observed. For 1,1′-(2-hydroxy-5-methyl-m-phenylene)-bis-ethanone and 1,1′-(2-trimethylsiloxy-5-methyl-m-phenylene)-bis-ethanone benzoxaphospholanes were obtained. Trialkyl phosphites and 1,1,1,5,5,5-hexafluoropentan-2,4-dione furnished cyclic phosphoranes containing the 3-hydroxy-3,5-bis(trifluoromethyl)-1,2λ⁵σ⁵-oxaphospholene structural element, stable at ambient temperature only in the case of one cyclic phosphite precursor. (E)-1,1,1-Trifluoro-4-phenyl-but-2-en-4-one and trimethylphosphite reacted to form 1,2λ⁵σ⁵-oxaphosphol-4-ene as the sole product. Results similar to the reaction of 1,1′-(2-hydroxy-5-methyl-m-phenylene)-bis-ethanone with diethyltrimethylsilylphosphite were obtained for trimethylphosphite and 2-trifluoroacetyl phenol where a deoxygenated phosphorane was found, easily hydrolyzed to give the respective phosphonic acid. With dialkylisocyanato phosphites and the keto components, 1,1,1,5,5,5-hexafluoro- and 1,1,1-trifluoropentan-2,4-dione, 4,4,4-trifluoro-1-phenyl-1,3-butandione, 2-trifluoroacetyl cyclohexanone, 2-trifluoroacetyl phenol and 1,1′-(2-hydroxy-5-methyl-m-phenylene)-bis-ethanone reacted in a ‘double’ cycloaddition to form bicyclic phosphoranes containing the 4,8-dioxa-2-aza-1λ⁵σ⁵-phosphabicyclo[3.3.0]-oct-6-en-3-one ring system; for the imino derivatives of 2-trifluoroacetyl phenol a corresponding 8-oxa-2,4-diaza- system was generated. For (E)-1,1,1,5,5,5-hexafluoro-4-trimethylsiloxy-3-penten-2-one however, a cyclic spiroimino phosphorane was obtained which underwent a [2+2] cyclodimerization to form a diazadiphosphetidine. Dimethylpropynyl phosphonite and 1,1,1,5,5,5-hexafluoropentan-2,4-dione yielded diastereoselectively a bisphosphorane, namely 1,4-bis(trifluoromethyl)-3,6-dioxa-2,2,7,7-tetramethoxy-2,7-di(1-propynyl)-2,7-diphosphabicyclo[2.2.1] heptane. When trimethylsilanyl–phosphenimidous acid bis-trimethylsilanyl–amide, Me₃SiN=PN(SiMe₃)₂, was allowed to react with 1,1,1,5,5,5-hexafluoro- and 1,1,1-trifluoropentan-2,4-dione, (E)-1,1,1,5,5,5-hexafluoro-4-trimethylsiloxy-3-penten-2-one, 2-trifluoroacetyl cyclopentanone, 2-trifluoroacetyl phenol and its imino derivatives, 2-imino-1,2λ⁵σ⁴-oxaphospholenes were found containing two diastereomers in each case, which added hexafluoroacetone across the P=N bond to give 1,3,2λ⁵σ⁵-oxazaphosphetanes.     

Reactions of N,N-Disubstituted 5-Arylmethylidene-2-amino-thiazol-4(5H)-ones with CH Acids

Summary.  N,N-Disubstituted 5-arylmethylidene-2-aminothiazol-4(5H)-ones reacted with diethyl malonate, ethyl benzoylacetate, acetylacetone, or cyclopentadiene in refluxing toluene and in presence of powdered sodium to give the respective 5-arylmethylidene-2′-amino-2,5′-bithiazolylidene-4,4′-dione derivatives in moderate yields. 5-Benzylidene-2-morpholin-4-yl-2-thiazol-4(5H)-one reacted with malononitrile in toluene and in presence of powdered sodium under mild conditions to afford the 1:1 adduct, benzylmalononitrile, and 2-morpholin-4-yl-2-thiazol-4(5H)-one. However, similar treatment of 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-one with malononitrile yielded the 2,5′-bithiazolylidene-4,4′-dione derivative together with 4-methoxyphenylmethylidene malononitrile. Treatment of 5-benzylidene- and 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-ones with 3-phenyl-4-oxo-2-thioxo-1,3-thiazolidine in refluxing toluene and in presence of powdered sodium produced 5-arylmethylidene-3-phenyl-4-oxo-2-thioxo-1,3-thiazolidines in good yields. The structures of all products were deduced from microanalytical and spectroscopic data, mechanistic details are discussed. Corresponding author. E-mail: kamalkandeel@hotmail.com Received November 5, 2001. Accepted (revised) December 17, 2001     

New organic nitrates. I. Synthesis of 1,3-benzoxazine-2,4-dione, 1,3-benzoxazine-2-thion-4-one, 1,3-benzothiazine-2,4-dione and quinazoline-2,4-dione derivatives

The preparation and the physico-chemical characterization of new heterocyclic organic nitrates containing 1,3-benzoxazine-2,4-dione, 1,3-benzoxazine-2-thion-4-one, 1,3-benzothiazine-2,4-dione and quinazo-line-2,4-dione moieties, are reported.     

The syntheses of pteridin-2-one derivatives from diaminomaleonitrile (DAMN)

1,3-Dimethyl-4-iminopteridin-2-one, 1,3-dimethylpteridine-2,4-dione, 1-methylpteridine-2,4-dione, 4-alkoxy-1-methylpteridin-2-one, and 4-alkylamino-1-methylpteridin-2-one were synthesized from diaminomaleonitrile (DAMN) through pyrazine-2,3-dicarbonitrile. The synthetic procedures consist of the condensation of DAMN with glyoxal, the nucleophilic substitution of pyrazine-2,3-dicarbonitrile with methylamine, the reaction of 3-methylaminopyrazine-2-carbonitrile with electrophiles such as methyl isocyanate and methyl chloroformate in the presence of sodium hydride, and the transformation of 3-(methoxycarbonylmethyl)aminopyrazine-2-carbonitrile into the pteridine derivatives.     

Synthesis and Antimicrobial Activities of Some 6-Methyl-3-Thioxo-2,3-Dihydro-1,2,4-Triazine Derivatives

Abstract

4-Arylidene-imidazole derivatives (4a,b) were readily prepared by reacting 4-am- ino-6-methyl-3–thioxo-2,3–dihydro[1,2,4]triazin-5(4H)-one (1) with 4-arylidene-2-phenyl- 4H-oxazol-5-one (2). Reaction of 1 with some aromatic aldehydes in presence of triethylphosphite exclusively afforded the corresponding aminophosphonates 5a-c. Reaction of 1 with 3-phenyl-1H-quinazoline-2,4-dione (6a) and/or 3-phenyl-2-thioxo-2,3-dihydro- 1H-quinazolin-4-one (6b) gave 2-(6-methyl-5-oxo-3-thioxo-2,5-dihydro-3H-[1,2,4]triazin-4-ylimino)-3-phenyl-2,3-dihydro-1H-quinazolin-4-one (7). Moreover, on treating 1 with 2-phenylbenzo[d][1,3]thiazine-4-thione (8), 6-methyl-4-(2-phenyl-4-thioxo-4H-quinazolin-3-yl)-3-thioxo-3,4-dihydro-2H-[1,2,4]triazine-5-one (9) was obtained in 65% yield. Reaction of 1 with 4-sulfonylaminoacetic acid derivatives (10a,b) afforded the corresponding sulfonamides (11a,b), respectively. Acid hydrolysis of 11a afforded 7-aminomethyl-3-methyl[1,3,4]thiadiazole[2,3-c][1,2,4]triazin-4-one (12). 4-Amino-6-methyl-3-(morpholine-4-ylsulfanyl)-4H-[1,2,4]triazin-5-one (14) was prepared by reacting compound 1 with morpholine in presence of KI/I₂, while 3,3′-bis(4-amino-6-methyl-5-oxo-triazinyl)disulfide (16) was obtained by oxidation of 1 with lead tetraacetate. The antimicrobial activity of the products was evaluated against Gram-positive and Gram-negative bacteria as well as the fungus Candida albicans.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]     

The synthesis and properties of some derivatives of 2-oxo-4-thioxo- and 2, 4-dithioxo-1h, 3h-pteridines

Some new derivatives of 2-oxo-4-thioxo- (I) and 2,4-dithioxo-1H, 3H-pteridine (II) have been prepared by treatment of 2,4-dioxo- (III) and 2-thioxo-4-oxo-1H,3H-pteridines (IV) with P₂S₅ in dioxane solution. The corresponding 4-phenylhydrazones, and the products of reaction of the pteridinethiones with aliphatic and aromatic amines and amino acids, have been obtained.