Synthesis and properties of 1-methyl-2-phenyl-5-(2-furyl)- and 1-methyl-2-phenyl-5-(2-thienyl)imidazoles

2-Phenyl-5-(2-furyl)- and 2-phenyl-5-(2-thienyl)imidazoles were synthesized by condensation of 2-furoylmethyl and 2-thenoylmethyl acetates with benzaldehyde under the conditions of Weidenhagen reaction. The products were converted to N-methyl derivatives in the KOH-acetone system. The electrophilic substitution reactions of the products (acylation, bromination, nitration, sulfonation, hydroxymethylation) were studied.     

Synthesis of 1-(3-halotetrahydro-2-furyl) derivatives of uracil, 5-substituted uracils,and cytosine

The cis and trans isomers of 1-(3-halotetrahydro-2-furyl) derivatives of uracil, 5-substituted uracils, and cytosine were obtained by alkylation of 2,4-bis(trimethylsilyl) derivatives of uracil, 5-substituted uracils, and cytosine with 2,3-dihalotetrahydrofurans. 2,3-Anhydro compounds are also formed in the alkylation of 5-halouracil derivatives. The physicochemical properties of the compounds obtained and the antineoplastic activities of the 5-fluorouracil derivatives were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 94–99, January, 1987.     

The Silyl Method for the Synthesis of 1[-2(Phenoxy)ethyl]uracils

A modification of the method for the synthesis of N₍₁₎-substituted derivatives of uracil is proposed using the Gilbert-Johnson reaction, which consists of the alkylation of 5-substituted 2,4-bis(trimethylsiloxy)pyrimidines with 1-bromo-2-(phenoxy)ethanes of low reactivity at 180-185° without solvent. The corresponding 1-[2-(phenoxy)ethyl]uracils, which were obtained in 55-74% yield, contained no impurities of the N₍₁₎, N₍₃₎-disubstituted compounds. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, 1071–1075, July, 2005. cf E. Ya. Lukevics and A. E. Zablotskaya. The Silyl Method for the Synthesis of Nucleosides [in Russian], Zinatne, Riga, 1985, 440 p. (Editor's note).     

A Simple Route to New N(3)-Substituted 5-Aryl-2-(dialkylamino)-1,3-oxazolium Salts and N(1)-Substituted 4-Aryl-2-(dialkylamino)-1H-imidazoles

In the reaction of N,N-dialkyl-dichloromethaniminium chlorides 11 with 2-aminoacetophenones 12 , a general and simple route to heretofore unknown 5-aryl-substituted 2-(dialkylamino)-1,3-oxazolium salts 13 and 5-aryl-substituted 2-(dialkylamino)oxazoles 14 was found. From the 2-(dialkylamino)-1,3-oxazoles 14 , the corresponding oxazolium salts 13 were obtained after alkylation with (MeO)₂SO₂. The new oxazolium salts 13 were converted to 1-substituted 4-aryl-2-(dialkylamino)-1H-imidazoles 9 by treatment with NH₄OAc. The possible use of these 1H-imidazoles as dye educts was explored. Analytical data, as well as AM1 calculations, reveal some remarkable differences between the structures of the neutral imidazoles 9 and their positively charged oxazolium precursors 13 .     

2-Amino-4-[2-(5-nitro-furyl)vinyl]thiazole and its derivatives

The reactions of 4-bromo-1-(5-nitro-2-furyl)but-1-en-3-one and its 2-methyl and 2-chloro derivatives with thiourea and its N-allyl and N-phenyl derivatives have yielded 2-amino-4-[-5-nitro-2-furyl)-vinyl]thiazole and its - and N-substituted derivatives. 2-Amino-4-[-(5-nitro-2-furyl)vinyl]thiazole and its -methyl derivative have also been prepared by the direct reaction of the corresponding , -unsaturated ketones with bromine and an excess of thiourea in chloroform, as was shown by a comparison of UV spectra. A series of N-acyl derivatives of the aminothiazoles has been obtained. UV and IR spectra are given.     

Synthesis and Antiviral Activity of 1-{[2-(Phenoxy)ethoxy]methyl}uracil Derivatives

The synthesis of novel 1-{[2-(phenoxy)ethoxy]methyl}uracil derivatives with different substituents in positions and 6 of the pyrimidine ring has been carried out. It has been shown that the alkylation of trimethylsilyl derivatives of uracil with 2-(4-chlorophenoxy)- and 2-(4-methylphenoxy)ethoxymethyl chloride under Hilbert-Johnson reaction conditions gives N₍₁₎-substitution products. It was found that the 1-{ [2-(phenoxy)ethoxy]methyl}uracil derivatives show viral inhibition properties relative to human immunodeficiency type 1 virus in vitro. The most active compounds are 5-bromo-6-methyluracil derivatives which suppress viral reproduction by 50% at 7.2 and 7.8 micromolar concentrations.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 726–731, May, 2005.     

3-Nitro-1,2,4-triazol-5-one derivatives

3-Nitro-1,2,4-triazol-5-one and its monomethyl derivatives react with methyl vinyl ketone to give products of addition to the ring N₁ and N₄ atoms. The reaction with formaldehyde and N-methylolacetamide proceeds only at the N₁ atom. The keto derivatives of 3-nitro-1,2,4-triazol-5-one undergo the Schmidt reaction to give the corresponding acetamides. A number of compounds that include functional groups in the N₁-alkyl substituent of the 3-nitro ring were obtained by treatment of the bases of N₁-substituted 3,5-dinitro-1,2,4-triazoles in aprotic media.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 552–558, April, 1981.     

2-萘基-5-取代苯并噁唑的合成、紫外光谱和萤光光谱

在研究有机化合物的结构与光性能间关系的过程中,我们又通过4-取代-2-氨基酚或其盐酸盐分别与α-萘甲酸和β-萘甲酸缩合,制得了十种2-(α-萘基)-5-取代苯并噁唑(Ⅰ)和十种2-(β-萘基)-5-取代苯并噁唑(Ⅱ),测定了这些化合物的熔点,紫外吸收光谱和萤光发射光谱.     

Synthesis of [2-(vinyloxy)ethyl]uracil and [2-(allyloxy)ethyl]uracil

A synthesis is reported for N¹-mono- and N¹,N³-disubstituted uracil derivatives containing a terminal carbon-carbon double bond in the side-chain. Alkylation of vinyl 2-chloroethyl ether by uracil potassium salts leads to a mixture of 1-[2-(vinyloxy)ethyl] and 1,3-di[2-(vinyloxy)ethyl] derivatives while treatment of 2,4-bis(trimethylsilyloxy)pyrimidines by vinyl 2-chloroethyl ether leads exclusively to N¹-monosubstituted products. Alkylation of cytosine by this chloroether gave 1-[2-(vinyloxy)ethyl]cytosine. The synthesis of 1-[2-(allyloxy)ethyl]uracil derivatives was carried out by treatment of uracil potassium salts by 1-(allyloxy)-2-(p-toluenesulfonyloxy)ethane.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 393–397, March, 1993.     

A convenient synthesis of 5-(1,2,4-oxadiazol-5-yl)pyrimidine-2,4(1H,3H)-diones

The synthesis of 5-heteroaryl-substituted uracil derivatives is presented. The 1,3-dipolar cycloaddition reaction was applied for the construction of a heterocyclic ring. The nitrile oxides were obtained from the appropriate 4-substituted benzaldoximes using N-chlorosuccinimide (NCS) under basic conditions. [2+3] Cycloaddition of nitrile oxides with 5-cyanouracil as a dipolarophile gave the corresponding 5-(3-substituited-1,2,4-oxadiazol-5-yl)uracils in satisfactory yields under mild conditions. 5-Substituted uracils having an additional heterocyclic ring were obtained as a result of the [2+3] cycloaddition of 5-cyanouracil to nitrile oxides generated from thiophene-2-carbaldehyde and 5-formyluracil derivatives.     

Studies on furan derivatives. V. A novel ethoxycarbonylmethylation of the 5-nitro-2-furan ring in the reaction of α-(2-furyl)-β-(5-nitro-2-furyl)ethynyl with N-ethoxycarbonylmethylpyridinium ylide

An unexpected product, 1-(4-ethoxycarbonylmethyl-5-nitro-2-furyl)-2-(2-furyl)-3-ethoxycarbonyl-indolizine was obtained by the reaction of α-(2-furyl)-β-(5-nitro-2-furyl)ethynyl with N-ethoxy-carbonylmethylpyridinium ylide in N,N-dimethylformamide, together with 1-(5-nitro-2-furyl)-2-(2-furyl)-3-ethoxycarbonylindolizine.     

4-Substituted 5-nitroisoquinolin-1-ones from intramolecular Pd-catalysed reaction of N-(2-alkenyl)-2-halo-3-nitrobenzamides

4-Methyl- and 4-benzyl-5-aminoisoquinolin-1-ones are close analogues of the water-soluble PARP-1 inhibitor 5-AIQ. Their synthesis was approached through Pd-catalysed cyclisations of N-(2-alkenyl)-2-iodo-3-nitrobenzamides. Reaction of N,N-diallyl-2-iodo-3-nitrobenzamide with Pd(PPh₃)₄ gave a mixture of 2-allyl-4-methyl-5-nitroisoquinolin-1-one and 2-allyl-4-methylene-5-nitro-3,4-dihydroisoquinolin-1-one. N-Benzhydryl-N-cinnamyl-2-iodo-3-nitrobenzamide similarly gave 2-benzhydryl-4-benzyl-5-nitroisoquinolin-1-one and 2-benzhydryl-4-benzylidene-5-nitro-3,4-dihydroisoquinolin-1-one. The isomeric products are not interconvertible. A deuterium-labelling study indicated that the isomers were formed by different pathways: a π-allyl-Pd route and the classical Heck route. The corresponding secondary amides N-allyl-2-iodo-3-nitrobenzamide and N-((substituted)-cinnamyl)-2-iodo-3-nitrobenzamide gave good yields of the required 4-methyl- and 4-((substituted)-benzyl)-5-nitroisoquinolin-1-ones, respectively, under optimised conditions (Pd(PPh₃)₄, Et₃N, Bu₄NCl, 150 °C, rapid heating). Hydrogenation of the nitro groups gave 4-methyl- and 4-benzyl-5-aminoisoquinolin-1-ones, which were potent inhibitors of PARP-1 activity.     

超声法合成新型3-(5-氯/苯氧基-3-甲基-1-苯基-4-吡唑基)异噁唑N-取代苯基去甲去氢斑蝥酰亚胺衍生物

去甲去氢斑蝥素与取代芳胺反应得到了一系列N-取代苯基去甲去氢斑蝥酰亚胺, 再与5-氯/苯氧基-4-(α-氯-α-肟基甲基)-3-甲基-1-苯基吡唑甲酰基氯代肟发生1,3-偶极环加成反应生成一系列未见报道的3-(5-氯/苯氧基-3-甲基-1-苯基-4-吡唑基)异噁唑N-取代苯基去甲去氢斑蝥酰亚胺衍生物. 所合成化合物经元素分析, IR, ¹H NMR, ¹H-¹HCOSY, NOESY确证结构.     

Nitration of 2- and 4-[2-(2-furyl)vinyl]thiazole derivatives

Nitration of 4-methyl-2-[2-(nitro-2-furyl)vinyl]thiazole with a mixture of concentrated nitric and sulfuric acids leads to 4-methyl-5-nitro-2-[2-(3,5-dinitro-2-furyl)vinyl]thiazole. Under the same conditions 2-methyl- and 2-acetamido-4-[1-R-2-(5-nitro-2-furyl)vinyl]thiazoles (R=CH₃, Cl) are nitrated in the 3 position of the furan ring, 2-amino-4-[1-chloro-2-(5-nitro-2-furyl)vinyl]thiazole is nitrated in the 5 position of the thiazole ring and 2-acetamido-5-nitro-4-[2-(2-furyl)vinyl]thiazole undergoes profound changes. Under the influence of a mixture of of nitric acid and acetic anhydride the latter compound is converted quantitatively to the 5-nitro derivative (with respect to the furan ring), whereas 4-[2-(5-nitro-2-furyl)vinyl]thiazole derivatives do not undergo reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 314–317, March, 1977.     

Synthesis of 1-(dihydroxypropyl)-5-substituted uracils

Novel 1-(dihydroxypropyl)-5-substituted uracils were synthesized in the reaction of 1-(4-nitrophenyl)-5-substituted uracil derivatives with appropriate aminopropanediols under mild conditions. In the case of 3-amino-1,2-propanediol both racemic and enantiomerically enriched products were obtained. These compounds may be considered as new building blocks for oligonucleotide synthesis.     

Furan derivatives—III : Synthesis and properties of β-ketosulphides and sulphur derivatives of chalcones of 5-nitrofuran series

A series of 2-(5-nitro-2-furyl)-2-oxoethylarylsulphides 3a–3h has been prepared by the reaction of 5-nitro-2-furylbromomethylketone 1 with 4-substituted thiophenols 2a–2h. The determined rates of carbanion formation (log k'), pK values as well as ¹H NMR data show that in these compounds transmission of polar effects by the substituents through the -S- group occurs. Compounds 3a–3h react with aromatic aldehydes affording sulphur chalcone derivativěs of the 5-nitrofuran series 4a–4h. ¹H NMR, IR and UV spectra of prepared compounds are discussed.     

2-Polyfluoroalkylchromones. 14. Synthesis of 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles

3-Chloro-2-polyfluoroalkyl- and 3-chloro-6-nitro-2-polyfluoroalkylchromones were synthesized. These compounds react with N₂H₄·2HCl on boiling in ethanol to form 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles.     

Nitrofuranyl heterocycles. XIII N-methyl-3-methylthio-5-(5-nitro-2-furanyl)-1H-1,2,4-triazoles

A continuing search for new nitrofurans which might possess useful antimicrobial activity led to the synthesis of several 3-mercapto-5-(5-nitro-2-furanyl)-1H-1,2,4-triazoles and their methylated derivatives. This paper describes the preparation of these compounds together with proof of structure of the N-methylated products.     

Studies on furan derivatives IV. A simple preparation of α-substituted β-(5-nitro-2-furyl)ethynyls from α-substituted β-(5-nitro-2-furyl)vinylamines

α-Substituted β-(5-nitro-2-furyl)ethynyls were conveniently prepared by the deamination of α-substituted β-(5-nitro-2-furyl)vinylamines. Also the application of this reaction toward α,β-bis(p-nitrophenyl)vinylamine was examined and afforded α,β-bis(p-nitrophenyl)ethynyl as the main product.     

Mannich bases and methiodides of 6-(2-furyl)imidazo[2,1-b]thiazole and its substituted derivatives

The Mannich reaction in a number of 6-(2-furyl)-substituted imidazo[2,1-b]thiazoles is realized initially in the 5 position of the imidazothiazole system, whereas it is also realized in the 5 position of the furan ring in the presence of excess reagents if the latter position is not substituted. Iodomethylation occurs at the N₇ atom of imidazothiazole. The Mannich bases of 6-(5-nitro-2-furyl)imidazo[2,1-b]thiazole are iodomethylated only at the aminomethyl group. The pK_a values of the series of compounds were measured.