Heterocyclic nitro compounds

Reaction of 1-methyl-3,5-dinitro-1,2,4-triazole with alcohols or phenols in the presence of bases (tertiary amines) leads to replacement of the nitro group in the 5-position by an alkoxy or phenoxy group.For part IV, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 5, pp. 702–704, May, 1970.     

Perturbating Intramolecular Hydrogen Bonds through Substituent Effects or Non-Covalent Interactions

An analysis of the effects induced by F, Cl, and Br-substituents at the α-position of both, the hydroxyl or the amino group for a series of amino-alcohols, HOCH₂(CH₂)_nCH₂NH₂ (n = 0–5) on the strength and characteristics of their OH···N or NH···O intramolecular hydrogen bonds (IMHBs) was carried out through the use of high-level G4 ab initio calculations. For the parent unsubstituted amino-alcohols, it is found that the strength of the OH···N IMHB goes through a maximum for n = 2, as revealed by the use of appropriate isodesmic reactions, natural bond orbital (NBO) analysis and atoms in molecules (AIM), and non-covalent interaction (NCI) procedures. The corresponding infrared (IR) spectra also reflect the same trends. When the α-position to the hydroxyl group is substituted by halogen atoms, the OH···N IMHB significantly reinforces following the trend H < F < Cl < Br. Conversely, when the substitution takes place at the α-position with respect to the amino group, the result is a weakening of the OH···N IMHB. A totally different scenario is found when the amino-alcohols HOCH₂(CH₂)_nCH₂NH₂ (n = 0–3) interact with BeF₂. Although the presence of the beryllium derivative dramatically increases the strength of the IMHBs, the possibility for the beryllium atom to interact simultaneously with the O and the N atoms of the amino-alcohol leads to the global minimum of the potential energy surface, with the result that the IMHBs are replaced by two beryllium bonds.     

New trifluoromethyl triazolopyrimidines as anti-Plasmodium falciparum agents

According to the World Health Organization, half of the World's population, approximately 3.3 billion people, is at risk for developing malaria. Nearly 700,000 deaths each year are associated with the disease. Control of the disease in humans still relies on chemotherapy. Drug resistance is a limiting factor, and the search for new drugs is important. We have designed and synthesized new 2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine derivatives based on bioisosteric replacement of functional groups on the anti-malarial compounds mefloquine and amodiaquine. This approach enabled us to investigate the impact of: (i) ring bioisosteric replacement; (ii) a CF? group substituted at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine scaffold and (iii) a range of amines as substituents at the 7-position of the of heterocyclic ring; on in vitro activity against Plasmodium falciparum. P. falciparum dihydroorotate dehydrogenase (PfDHODH) through strong hydrogen bonds. The presence of a trifluoromethyl group at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine ring led to increased drug activity. Thirteen compounds were found to be active, with IC?? values ranging from 0.023 to 20 μM in the anti-HRP2 and hypoxanthine assays. The selectivity index (SI) of the most active derivatives 5, 8, 11 and 16 was found to vary from 1,003 to 18,478.     

1,2,4-triazines in organic synthesis. 8. Intramolecular diels-alder reaction of 5-acyl-1,2,4-triazineoxime ethers. New route of synthesis of alkylhetarylketones

Intramolecular diene cycloaddition of 5-acyl-1,2,4-triazineoxime ethers involving a dienophile substituent in the 3-position of the triazine ring is studied. New alkylhetarylketones are synthesized by hydrolysis of the condensed N- and O-containing heterocyclic products. The starting materials are prepared by oxidation of 5-acetyl- and 5-butyryl-3-methylthio-1,2,4-triazineoxime ethers with KMnO₄ to the sulfonyl derviatives with subsequent replacement of the CH₃SO₂ group by sodium 3-butyn-1-oxide, 4-pentyn-1-oxide and o-cyanophenoxide.For Communication 7, see [1].Institute of Chemistry, Agricultural and Teachers University, Siedlce, 08–110, Poland.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 381–389, March, 1999.     

Cyclic unsaturated compounds

Conclusions Reversible structural isomerization of 1,3- and 1,2-dimethylsubstituted cyclopentadienes, proceeding according to a mechanism of 1,2-shift of the methyl group from the 5-position of the cyclopentadiene ring, accompanied by the migration of the system of intracyclic double bonds, is carried out at the temperatures 400–500°. In conjunction with the 1,2-shift of hydrogen, the indicated conversion leads to the formation of an equilibrium mixture of structural isomers, containing 38% 1,3-dimethylcyclopentadienes and 62% 1,2-and 2,3-dimethylcyclopentadienes (total).For communication 36 of this series, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 1978–1983, September, 1971.     

Synthesis and structure of bromonitro-6(5H)-phenanthridinones

Treatment of 2-bromo-6(5H)-phenanthridone with nitrating mixture or fuming nitric acid results in nitration, debromination, and bromination in the 10-position. The brominating agent is apparently Br⁺, formed in the reaction mixture following replacement of the bromine in the 2-position by a nitro-group. Monocrystals of 2-bromo-1,4,8-trinitro-6(5H)-phenanthridinone and 10-bromo-2,4,8-trinitro-6(5H)-phenanthridinone have been subjected to x-ray diffraction examination. PMR has been used for structural identification.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 789–795, June, 1990.We thank A. N. Sobolev for assistance in calculating the structure of (III).     

2-Substituted imidazoles. 3. Metallation of 1-methyl-2-phenyl- and 1-methyl-2-(furyl-2)imidazoles

1-Methyl-2-phenylimidazole reacts with butyllithium to give 5-lithium substituted products. On the other hand, 1-methyl-2-(furyl-2)imidazole is metallated under the same conditions exclusively on the furan ring and primarily in the 3 position. The introduction of triethylamine into the reaction mixture, or replacement of butyllithium by lithium 2,2,6,6-tetramethylpiperidide leads to the formation of a lithium derivative substituted at the 5-position of the furan ring exclusively.For Communication 2, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 61–66, January, 1992.     

Hydroacridines and related compounds

One hydrogen atom is replaced by lithium in the reaction of 1,2,3,4-tetrahydroacridine and sym-octahydroacridine with phenyllithium; effective replacement of a second hydrogen atom by lithium becomes possible after replacement of the first lithium by an alkyl group. This makes it possible to achieve step-wise alkylation.See [1] for communication VIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 673–675, May, 1972.     

Reaction of 5-alkylidenerhodanines with diazonium salts

In the action of diazonium salts on 5-alkylidenerhodanines, azo compounds are formed by the replacement of one or two hydrogen atoms in the methyl group. In the case of 5-ethylidenerhodanines, the formation of an azorhodanine through the replacement of the alkylidene residue by an arylazo group takes place simultaneously. In the formazyl derivatives the long-wave absorption maximum is displaced hypsochromically by 15–20 nm as compared with the dyes having a single azo group.     

Imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]benzimidazole derivatives: XXIX. 1-allyl-2-amino-3-acylmethylbenzimidazolium halides and syntheses on their base

Cyclization of 1-allyl-2-amino-3-acylmethylbenzimidazolium halides under alkaline conditions gave 9-allyl-substituted imidazo[1,2-a]benzimidazoles. Cyclization of the same compounds on heating in concentrated hydrobromic acid was accompanied by addition of hydrogen bromide at the exocyclic double bond. Competing cyclizations with participation of the 1-(2-bromopropyl) and 3-acylmethyl substituents in 2-imino-2,3-dihydro-1H-benzimidazole were studied. Functionalization of the imidazo[1,2-a]benzimidazole system was performed via introduction of substituents into the 3-position and replacement of bromine in the 2-bromopropyl group in the 9-position.     

Specific intramolecular C-H...O interactions in 1-vinyl-2-formylimidazole and 1-vinyl-2-formylbenzimidazole studied by1H and13C NMR spectral data

According to the¹H and¹³C NMR spectral data, the vinyl group in 1-vinyl-2-formylimidazole and 1-vinyl-2-formylbenzimidazole istrans-oriented with respect to the formyl fragment, while the carbonyl group occupies theanti-position with respect to the N atom of pyridine cycle. A specific intramolecular C—H...O interaction of a weak hydrogen bond type is realized between the -H atom of the vinyl group and O atom of the carbonyl group.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1197–1201, May, 1996.     

The nitration of iodoimidazoles

Treatment of iodoimidazoles with nitric acid of various concentrations results in replacement of the iodine atoms by nitro groups, including those in the 2-position, which is not activated towards electrophilic substitution in acid media. The use of a nitric acid- sulfuric acid nitrating mixture also results in the replacements of the iodine atom in the 4(5)position.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 5, pp. 664–668, May, 1970.     

苯并呋喃酮衍生物结构对其DPPH捕获能力的影响

采用自由基比色法考察苯并呋喃酮衍生物结构对其DPPH捕获能力的影响。结果发现,母体苯环5,7位上甲基和叔丁基的改变以及取代苯环上强供电子取代基的存在对苯并呋喃酮衍生物的DPPH捕获能力没有明显影响。取代苯环2’位存在明显的位阻作用,对苯并呋喃酮衍生物的DPPH捕获能力具有明显的抑制作用：并且当此位为不含活泼氢的氢键受体取代基时,苯并呋喃酮衍生物的DPPH捕获能力会由于取代基与3位活泼氢的氢键作用而被进一步削弱;但此位为含有活泼氢的氢键受体取代基时,此取代基的氢将会由于3位活泼氢与取代基的氢键作用而活化,从而使其位阻作用得到一定程度的抑制。     

Probing the Binding Requirements of Modified Nucleosides with the DNA Nuclease SNM1A

SNM1A is a nuclease that is implicated in DNA interstrand crosslink repair and, as such, its inhibition is of interest for overcoming resistance to chemotherapeutic crosslinking agents. However, the number and identity of the metal ion(s) in the active site of SNM1A are still unconfirmed, and only a limited number of inhibitors have been reported to date. Herein, we report the synthesis and evaluation of a family of malonate-based modified nucleosides to investigate the optimal positioning of metal-binding groups in nucleoside-derived inhibitors for SNM1A. These compounds include ester, carboxylate and hydroxamic acid malonate derivatives which were installed in the 5′-position or 3′-position of thymidine or as a linkage between two nucleosides. Evaluation as inhibitors of recombinant SNM1A showed that nine of the twelve compounds tested had an inhibitory effect at 1 mM concentration. The most potent compound contains a hydroxamic acid malonate group at the 5′-position. Overall, our studies advance the understanding of requirements for nucleoside-derived inhibitors for SNM1A and indicate that groups containing a negatively charged group in close proximity to a metal chelator, such as hydroxamic acid malonates, are promising structures in the design of inhibitors.     

Structure effect of benzofuranone on the antioxidant activity in polypropylene

This work deals with the antioxidant activity of benzofuranone compounds in polypropylene (PP). The antioxidant activities of ten benzofuranone compounds in PP were compared using melt flow index (MFI) values of PP stabilized by benzofuranone compounds primarily. The results show: firstly, that the increase of electron donating ability of substituent in 3-substituted benzene ring is beneficial to the improvement of antioxidant activity. Secondly, it has been verified that the steric hindrance of 2′-position substituent can weaken the antioxidant activity of benzofuranone. But when 2′-position substituent forms a hydrogen bond with 3-position reactive hydrogen, the steric hindrance is offset efficiently. Finally, the methyl and tert-butyl groups in the 5 and 7-position of parent benzene ring do not affect the antioxidant activity of benzofuranone compounds in PP obviously.     

Reaction of 2-arylazobenzimidazolium quaternary salts with amines

Different behaviors of aromatic and nonaromatic amines with respect to a change in the structure of the salt and variations in the reaction conditions were revealed in a study of the reaction of 2-arylazobenzimidazolium quaternary salts with amines. Aliphatic and secondary cyclic amines react at comparable rates via pathways involving cleavage of the azo group and replacement of the hydrogen in the para position relative to the azo group. The reaction with aromatic amines proceeds primarily via the amination pathway, and a methyl group in the meta position relative to the azo group facilitates replacement of the hydrogen atom significantly.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 817–824, June, 1982.     

3-Aryl-4,5-dichloro-1,2,3-thiadiazolium salts — Synthons for the preparation of mesoionic compounds of the 1,2,3-thiadiazole series

The high mobility of the chlorine atom at the 5-position of 3-aryl-4,5-dichloro-1,2,3-thiadiazolium salts facilitates a ready preparation of mesoionic 3-aryl-1,2,3-thiadiazoles with an exocyclic oxygen, sulfur or arylimino group at the 5-position. In an aqueous alcoholic solution of sodium nitrite, the halogens in the 4- and 5-positions are substituted with the formation of 3-aryl-5-nitro-1,2,3-thiadiazolium-4-olates.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1552–1554, November, 1989.     

Synthesis of carbon-bridged 8,5'-cyclopurine nucleosides: Nucleosides and nucleotides—XXIV1

Treatment of 2',3'-O-isopropylidene-5'-deoxy-8,5'-cycloadenosine with selenium oxide afforded the 5'-oxo-compound. Reduction of the product with sodium borohydride proceeded stereoselectively to give the 8,5'(S)-cycloadenosine. The 5'-R-isomer was obtained by the inversion of the 5'-OH group of the S-epimer via the mesyloxy derivative. Hydrolytic deamination of 8,5'-cycloadenosines gave the inosine counterparts. Photo-irradiation of 2',3'-O-isopropylidene-5'-deoxy-5'-phenylthio-N²-benzoylguanosine afforded the 8,5'-cyclo-5'-deoxyguanosine, which was also converted to the 5'-oxo-derivative. Reduction of the product also afforded to give the 8,5'-(S)-cycloguanosine. The CD spectra of these cyclonucleosides reflect the chiralities at the 5'-position.     

Reaction of benzimidazoles with chlorosulfonic acid

The reaction of benzimidazole and its 2-substituted derivatives with chlorosulfonic acid is examined. It is shown that only compounds containing electrophilic substituents in the 2-position yield sulfonic chlorides. Benzimidazole and its 2-methyl derivative give the sulfonic acids. Substitution occurs at the 5-position of the benzimidazole nucleus.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 5, pp. 681–683, May, 1970.     

Syntheses based on furancarboxylic acid amides. 1. Synthesis and structure of 2-(5-R-2-furyl)-4-oxoquinazolines

2-(5-R-2-Furyl)-4-oxoquinazolines are formed in the condensation of furancarboxylic acid primary amides with anthranilic acid in the presence of phosphorus oxychloride. It was determined by x-ray diffraction analysis, IR and PMR spectroscopy, and mass spectrometry that a labile hydrogen atom is bonded to the nitrogen atom in the 3-position and that the molecule has an s-NH,0-trans conformation.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1463–1466, November, 1989.