Synthesis of 1,2,3,4-tetrachlorohexafluorobutane

The condensation of 1-iodo-1,2,2-trifluoro-1,2-dichloroethane induced by granulated Zn in the presence of catalytic amounts of AcOEt without a solvent results in 1,2,3,4-tetrachlorohexafluorobutane in high yield.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2236–2238, October, 2004.     

Synthesis of first nonannulated 1,2,3,4-tetrazine 1,3-dioxides

Thermolysis of o-diazidobenzotetrazine 1,3-dioxides was accompanied by cleavage of the C-C bond of the benzene ring to give nonannulated 1,2,3,4-tetrazine 1,3-dioxides. The structures of these first representatives of nonfused 1,2,3,4-tetrazines were confirmed by ¹³C and ¹⁴N NMR spectroscopy. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1589–1594, September, 2006.     

Synthesis of 1-iodo-1,2,3,4,4a,9a-hexahydrocarbazoles and their isomerization into 3-iodo-2,4-propano-1,2,3,4-tetrahydroquinolines

The reactions of 2-(cyclohex-2-enyl)-4,5-difluoroaniline or N-methyl-2-(cyclohex-2-enyl)aniline with I₂ in CCl₄ in the presence of NaHCO₃ give 1-iodo-1,2,3,4,4a,9a-hexahydrocarbazoles, which isomerize in MeCN into the corresponding 3-iodo-2,4-propano-1,2,3,4-tetrahydroquinolines in quantitative yields.     

Borane-Catalyzed Tandem Cyclization/Hydrosilylation Towards Enantio- and Diastereoselective Construction of trans-2,3-Disubstituted-1,2,3,4-Tetrahydroquinoxalines

Recent years have witnessed marked progress in the efficient synthesis of various enantioenriched 1,2,3,4-tetrahydroquinoxalines. However, enantio- and diastereoselective access to trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines remains much less explored. Herein we report that a frustrated Lewis pair-based catalyst generated via in situ hydroboration of 2-vinylnaphthalene with HB(C₆F₅)₂ allows for the one-pot tandem cyclization/hydrosilylation of 1,2-diaminobenzenes and 1,2-diketones with commercially available PhSiH₃ to exclusively afford trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with excellent diastereoselectivities (>20 : 1 dr). Furthermore, this reaction can be rendered asymmetric by using an enantioenriched borane-based catalyst derived from HB(C₆F₅)₂ and a binaphthyl-based chiral diene to give rise to enantioenriched trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with almost complete diastereo- and enantiocontrol (>20 : 1 dr, up to >99 % ee). A wide substrate scope, good tolerance of diverse functionality and up to 20-gram scale production are demonstrated. The enantio- and diastereocontrol are achieved by the judicious choice of borane catalyst and hydrosilane. The catalytic pathway and the origin of the excellent stereoselectivity are elucidated by mechanistic experiments and DFT calculations.     

Über die Oxo‐cyclotetraphosphane (PBut)4O1–4

Contributions to the Chemistry of Phosphorus. 243 On the Oxocyclotetraphosphanes (PBu^t)₄O_1–4 Under suitable conditions, the reaction of tetra‐tert‐butylcyclotetraphosphane, (PBu^t)₄, with dry atmospheric oxygen gives rise to the corresponding monoxide (PBu^t)₄O ( 1 ) which has been isolated by column chromatography. The reaction with hydrogen peroxide furnishes a mixture of oxocyclotetraphosphanes (PBu^t)₄O_1–4 consisting of two constitutionally isomeric dioxides (PBu^t)₄O₂ ( 2 a , 2 b ), the trioxide (PBu^t)₄O₃ ( 3 ), and the tetraoxide (PBu^t)₄O₄ ( 4 ), in addition to 1 . According to the ³¹P NMR parameters the oxygen atoms are exclusively exocyclically bonded to the phosphorus four‐membered ring. Which of the P atoms are present as λ⁵‐phosphorus follows from the different low‐field shifts of the individual P nuclei compared with the starting compound. Accordingly, 1 is 1,2,3,4‐Tetra‐tert‐butyl‐1‐oxocyclotetraphosphane, 2 a and 2 b are 1,2,3,4‐Tetra‐tert‐butyl‐1,2‐dioxo‐ and ‐1,3‐dioxocyclotetraphosphane, respectively, 3 is 1,2,3,4‐Tetra‐tert‐butyl‐1,2,3‐trioxocyclotetraphosphane, and 4 is 1,2,3,4‐Tetra‐tert‐butyl‐1,2,3,4‐tetraoxocyclotetraphosphane. When the oxidation reaction proceeds a fission of the P₄ ring takes place.     

Synthesis and structures of pyridoannelated 1,2,3,4-tetrazine 1,3-dioxides

Treatment of 2- and 4-amino-3-(tert-butyl-NNO-azoxy)pyridines with nitrating agents (N₂O₅or NO₂BF₄) afforded the first representatives of pyridoannelated 1,2,3,4-tetrazine di-N-oxides, viz., pyrido[2,3-e][1,2,3,4]tetrazine 1,3-dioxide (9), 7-nitropyrido[2,3-e][1,2,3,4]tetrazine 1,3-dioxide (10), and pyrido[3,4-e][1,2,3,4]tetrazine 2,4-dioxide (11). These compounds were studied by ¹H, ¹³C, and ¹⁴N NMR spectroscopy. The 1:1 complex of compound 10 with benzene was studied by X-ray diffraction analysis.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2471–2477, November, 2004.     

Three-component condensation of diethyl isophthaloyldiacetate, aromatic aldehyde, and urea as a new method for the synthesis of 1,3-bis(2-oxo-1,2,3,4-tetrahydropyrimidin-6-yl)benzenes

Condensation of diethyl isophthaloyldiacetate, aromatic aldehyde, and urea in the presence of Me₃SiCl proceeds efficiently and faster than in the absence of the latter to form 1,3-bis(2-oxo-1,2,3,4-tetrahydropyrimidin-6-yl)benzene derivatives capable to give inclusion complexes with DMF. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1233–1239, June, 2008.     

3-芳基-1,2,3,4-噁三唑-5-亚胺与阿司匹林偶联物的合成和抗血栓活性研究

取代苯胺经重氮化、还原得苯肼盐酸盐, 与硫氰酸钾作用得苯基取代的氨基硫脲, 再在亚硝酸异戊酯、盐酸的作用下环合、成盐, 加碱中和后生成3-芳基-1,2,3,4-噁三唑-5-亚胺, 最后与乙酰水杨酰氯反应得目标物6a～6l, 其结构经MS, IR, ¹H NMR和元素分析确证. 体外血小板聚集试验和小鼠肺血栓生成试验结果表明, 部分目标物在体内、外均显示出较好的抗血栓活性, 值得深入进行研究.     

N-Methylmorpholinium 4-aryl-5-cyano-3-methoxycarbonyl-2-oxo-1,2,3,4-tetrahydropyridine-6-thiolates: synthesis and properties

Reactions of aromatic aldehydes with cyanothioacetamide and dimethyl malonate in the presence ofN-methylmorpholine affordedN-methylmorpholinium 4-aryl-5-cyano-3-methoxycarbonyl-2-oxo-1,2,3,4-tetrahydropyridine-6-thiolates. The latter were used to synthesize substituted 6-(alkylthio)-2-oxo-1,2,3,4-tetrahydropyridines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 485–487, March, 2000.     

Synthesis of 1,2,3,4-tetrazino[5,6-g]benzo-1,2,3,4-tetrazine 1,3,7,9-tetraoxides

1,2,3,4-Tetrazino[5,6-g]benzo-1,2,3,4-tetrazine 1,3,7,9-tetraoxides, which possess an-thracene-type annulation of the benzene ring with two 1,2,3,4-tetrazine 1,3-dioxide fragments, were obtained for the first time from aminobenzenes containing tert-butyl-NNO-azoxy groups in appropriate positions. Complete assignments of the signals in the ¹H, ¹³C, and ¹⁴N NMR spectra of the compounds obtained were carried out. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1595–1599, September, 2006.     

Synthesis and X-ray structural investigation of 6-chloro-10-phenyl-1,2,3,4-tetrahydroacridine

An X-ray structural study of 6-chloro-10-phenyl-1,2,3,4-tetrahydroacridine prepared by the reaction of cyclohexanone with 2-amino-5-chlorobenzofenone was carried out. At 20°Ca=24.215(6),b=8.967(2),c=15.006(3) Å, =115.57(2)°,V= 2939(1) ų,d _calc=1.310 g cm^–3,Z=4, space groupC2/c, 1324 reflections, MoK,R=0.038. The cyclohexene ring has a half-chair conformation. The phenyl substituent is rotated 71.2° with respect to the plane of the quinoline fragment.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1467–1468, August, 1994.     

Syntheses,separation of enantiomers and barriers to racemization of some sterically hindered N-aryl-1,2,3,4-tetrahydro-3,3-dimethyl-2,4-quinolinediones and their thio analogues

Summary The novel N-aryl-1,2,3,4-tetrahydro-3,3-dimethyl-2,4-quinolinediones1,4 and8 were thiated with Lawesson reagent and P₄S₁₀ to yield the monothio derivatives2 and5 and the dithio compounds3, 6 and9. Their enantiomers were separated by liquid chromatography on triacetyl- or tribenzoylcellulose. Rotation barriers for1–4 and8 were determined by thermal racemization and discussed in terms of steric effects.

---

Synthese, Enantiomerentrennung und Barrieren zur Racemisierung einiger sterisch gehinderter N-Aryl-1,2,3,4-tetrahydro-3,3-dimethyl-2,4-chinolindione und ihrer Thio-Analogen

Zusammenfassung Die neuen N-Aryl-1,2,3,4-tetrahydro-3,3-dimethyl-2,4-chinolindione1, 4 und8 wurden mit Lawesson-Reagens und P₄S₁₀ zu den Monothioderivate2 und5 und den Dithioverbindungen3, 6 und9 thioniert. Ihre Enantiomeren wurden mittels Flüssigchromatographie an Triacetyloder Tribenzoylcellulose getrennt. Die Rotationsbarrieren für1–4 und8 wurden mittels thermischer Racemisierung bestimmt und aufgrund der sterischen Gegebenheiten diskutiert.

     

5‐Morpholino‐1,2,3,4‐thiatriazole as a Sulfur‐Transfer Reagent in the Reactions with Thioketones

The thermal decomposition of 5‐morpholino‐1,2,3,4‐thiatriazole ( 7 ), which leads to the extrusion of an active form of sulfur, in the presence of different thioketones is described. The interception of the S‐atom by the C?S bond leads to in situ formation of an elusive thiocarbonyl S‐sulfide of type 5 . This intermediate is a prone 1,3‐dipole, which undergoes effectively [2+3] cycloadditions with thioketones to yield 1,2,4‐trithiolane derivatives in a regioselective manner. Unexpectedly, 3,3‐dichloro‐2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone ( 1c ) does not lead to the expected symmetrical 1,2,4‐trithiolane. This result can be explained by the reduced stability of the corresponding thiosulfine 5c . Three‐component reactions, which were carried out in the presence of equimolar amounts of two different thioketones, result in the formation of ‘mixed’ 1,2,4‐trithiolanes of type 8 .     

Reaction of N-nitroaryl-1,2,3,4-tetrahydroisoquinoline derivatives with oxygen

Heating N-4′-methyl-2′-nitrophenyl-1,2,3,4-tetrahydroisoquinoline ( 1 ) in the presence of oxygen gave both products derived from cleavage of the C8a? Cl bond and oxidation at the 1-position. Under similar conditions N-4′-nitrophenyl-1,2,3,4-tetrahydroisoquinoline ( 4 ) gave only the oxidation product.     

DEB-FAPy-dG Adducts of 1,3-Butadiene: Synthesis,Structural Characterization,and Formation in 1,2,3,4-Diepoxybutane Treated DNA**

Metabolic activation of the human carcinogen 1,3-butadiene (BD) by cytochrome 450 monooxygenases gives rise to a genotoxic diepoxide, 1,2,3,4-diepoxybutane (DEB). This reactive electrophile alkylates guanine bases in DNA to produce N7-(2-hydroxy-3,4-epoxy-1-yl)-dG (N7-DE-dG) adducts. Because of the positive charge at the N7 position of the purine heterocycle, N7-DEB-dG adducts are inherently unstable and can undergo spontaneous depurination or base-catalyzed imidazole ring opening to give N⁶-[2-deoxy-D-erythro-pentofuranosyl]-2,6-diamino-3,4-dihydro-4-oxo-5-N-1-(oxiran-2-yl)propan-1-ol-formamidopyrimidine (DEB-FAPy-dG) adducts. Here we report the first synthesis and structural characterization of DEB-FAPy-dG adducts. Authentic standards of DEB-FAPy-dG and its ¹⁵N₃-labeled analogue were used for the development of a quantitative nanoLC-ESI⁺-HRMS/MS method, allowing for adduct detection in DEB-treated calf thymus DNA. DEB-FAPy-dG formation in DNA was dependent on DEB concentration and pH, with higher numbers observed under alkaline conditions.     

Synthesis and characterization of some metal(II) and sodium ions with cyclopentane-1,2,3,4-tetracarboxylate anion

New divalent metal cyclopentane-1,2,3,4-tetracarboxylate (CPTC) hydrates of empirical formula M₂C₅H₆(COO)₄ · nH₂O, where M = Ni, Co, Cu, or Zn and n = 3?6, and sodium CPTC Na₃C₅H₆COOH(COO)₃ · 7H₂O have been prepared and characterized by elemental analysis, magnetic measurements, thermal, and infrared spectral studies. For the sodium salt, a single crystal (Na₃C₅H₆COOH(COO)₃ · 8H₂O) was also obtained. IR spectra of the metal(II) complexes indicate the coordination of metal ions through all carboxylates. For the sodium compound, a band at 1681 cm^?1 indicates that some carboxylic groups have not been deprotonated. The presence of protonated carboxylic group was also confirmed by an X-ray single crystal analysis. On heating in air atmosphere, all complexes lose water molecules and next anhydrous compounds decompose to corresponding metal oxides and sodium carbonate.     

Synthese einiger 8-substituierter 2-Methyl-1,2,3,4-tetrahydroisochinoline

Synthesis of Some 8-Substituted 2-Methyl-1,2,3,4-tetrahydroisoquinolines A general route to 8-substituted tetrahydroisoquinolines is exemplified by the preparation of the 2-methyl-1,2,3,4-tetrahydroisoquinolin-8-ol ( 11 ), the -8-carbaldehyde oxime ( 12 ) and the -8-carbonitrile ( 13 ). It involves the conversion of isoquinoline ( 1 ) by partially modified Steps 1, 2, 3, and 5 (see the Scheme) into the 5-bromo-8-nitro derivative 5 , reduction of the latter to the 8-amino derivative 8 and replacement of the NH₂-group with an appropriate substituent by a Sandmeyer-like reaction. The selective reductions of the N-containing ring in 6 (Steps 5, 6, and 8) and of the NO₂-group in 5 (Steps 4 and 7) were also studied.     

Synthesis and stereochemistry of 1-acyl-2-alkyl-1,2,3,4-tetrahydroquinoline-3,4-epoxides

Summary Analogous to the recently described synthesis of Reissert epoxides the treatment of 1-acyl-2-alkyl-1,2-dihydroquinolines withm-chloroperoxybenzoic acid gave diasteromeric pure epoxides which are stable in crystalline state, but reactive in solution versus nucleophiles. Acting as useful intermediates to stereocontrolled functionalized 1,2,3,4-tetrahydroquinolines an X-ray analysis was performed to confirm the relative stereochemistry of the epoxides.

---

Synthese und Stereochemie von 1-Acyl-2-alkyl-1,2,3,4-tetrahydrochinolin-3,4-epoxiden

Zusammenfassung Analog zu der kürzlich beschriebenen Synthese von Reissert-Epoxiden liefern 1-Acyl-2-alkyl-1,2-dihydrochinoline bei Behandlung mitm-Chlorperbenzoesäure diastereomerenreine Epoxide, die sich als Festsubstanzen außerordentlich stabil, in Lösung aber reaktiv gegenüber Nucleophilen erweisen. Da sie wertvolle Ausgangsverbindungen zu 1,2,3,4-substituierten Tetrahydrochinolinen mit definierter relativer Konfiguration darstellen, wurde die Stereochemie der Epoxide mittels Röntgenstrukturanalyse abgesichert.

     

A novel convenient synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones via 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones

A novel four-step methodology for the synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with Na-enolates of 1,3-diketones or β-oxoesters followed by heterocyclization-dehydration of the oxoalkylureas formed gave 5-acyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of NaH, eliminate CHCl₃ to give the target compounds.     

Synthesis and structures of 3-hydroxy-6-(R-phenylazo)-7,8-benzo-1,2,3,4-tetrahydroquinolines as products of analytical test reactions for nitrite and nitrate anions

An improved procedure was proposed for the synthesis of 3-hydroxy-7,8-benzo-1,2,3,4-tetrahydroquinoline, which is used as a reagent for the analytical test reaction for nitrate and nitrite anions based on azo coupling with diazo compounds. 3-Hydroxy-6-(R-phenylazo)-7,8-benzo-1,2,3,4-tetrahydroquinolines (R = 2-COOH, 4-COOH, or 4-SO₃H) were synthesized by azo coupling reactions in 65–70% yields. The structures of these compounds were confirmed by elemental analysis, ¹H NMR and IR spectroscopy, and X-ray diffraction. Based on the X-ray data, the bathochromic shift in the UV spectrum of the o-carboxy isomer compared to the p-carboxy isomer (Δλ_max = 50 nm) is attributed to a strong intramolecular hydrogen bond. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1027–1031, June, 2006