Nitrogen bridgehead compounds. Part 45 [1]. Synthesis of 6-arylhydrazono-6,7,8,9-tetrahydro-11H-pyrido-[2,1-b]quinazolin-11-ones

A series of 6-arylhydrazono-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-ones 3–37 , conveneint starting materials for indolopyridoquinazolines, were prepared by diazonium coupling between aryldiazonium chlorides and 6,7,8,9-tetrahydro- 2 , 6-formyl-5,7,8,9-tetrahydro- 39 , 6-(dimethylamino)methylene-6,7,8,9- 38 or 6-carboxyl-5,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-ones 43 . The arylhydrazono derivatives were also prepared from 6-bromo- 45 or 6,6-dibromo-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolines 46 with arylhydrazines. The structures of the 6-arylhydrazonopyridoquinazolines were characterized by uv and ¹H nmr spectroscopy. The 6-arylhydrazono derivatives show a solvent-dependent E-Z isomerism.     

Substituted 2,3,4,5-tetrahydro-1H-3-benzazepine and 2,3,4,5-tetrahydro-1H-naphth[1,2-d] azepine derivatives

The multi-step synthetic procedures to prepare a number of 2,3,4,5-tetrahydro-1H-benzazepine derivatives 1 through a series of intermediates are described. The condensation of arylaldehydes 2 with 2-nitropropanes 3 gave nitroalcohols 4 which were reduced to alcohol amines 5 . The condensation of 5 with arylacetaldehydes 6 gave imino derivatives 7 which on reduction with borohydride gave secondary amines 8 . By employing different methods, alcohol amines 5 were condensed with arylacetic acids 9 to give amides 10 which were then reduced to amines 8 . On treatment with mineral acids, amines 8 were cyclized to the target compounds 1 . Biological activities of 1 are also briefly discussed.     

The reaction between 3,3-bis(methoxyphenyl)-3H-naphtho[2,1-b]pyran and 1,3-bis(methoxyphenyl)-1H-naphtho[2,1-b]pyran, 2,2-diphenyl-2H-chromen and 2,4-diphenyl-4H-chromen,and related compounds

The reaction between 3,3-bis(methoxyphenyl)-3H-naphtho[2,1-b]pyran and 1,3-bis(methoxyphenyl)-1H-naphtho[2,1-b]pyran under acid conditions gives a 7a,15a-dihydro-7a,15-bis(methoxyphenyl)-16-[2,2-bis(methoxyphenyl)-l-vinyl]dinaphtho-[2,1-b:2,1-g]-4H,5H-pyrano[2,3-b]-pyran.     

Heterocycles [h]-fused onto 4-oxoquinoline-3-carboxylic acid, Part VI [1]. Synthesis and X-ray structure of model indolo[3,2-b]- and [2,3-b]pyrido[2,3-f]quinoxaline-3-carboxylic esters

Cyclocondensation reaction of ethyl 7,8-diamino-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate with 1-methylisatin produced a separable mixture of the corresponding indolo[3,2-b]- and [2,3-b]pyrido[2,3-f]quinoxaline-3-carboxylates, of which the latter isomer predominates. On the other hand, interaction with 1H-isatin or 5-chloroisatin gave the respective indolo[2,3-b]pyrido[2,3-f]quinoxaline-3-carboxylates as the sole regiospecific products. The structures of these new pentacyclic derivatives are based on microanalytical, spectral (IR, MS, and NMR) and X-ray crystal structure data.     

四氢咪啶[2,1-a]并-2,3-二苯基-1,4-二氮杂-3-环己烯的合成与结构

对由二乙烯三胺与联苯甲酰合成的标题化合物进行了MS、IR、UV、NMR谱的表征及X射线单晶衍射结构分析.该化合物M_r=277.39,晶体属P2_1/n空间群,晶胞参数a=0.9442(2)nm,b=1.4344(4)nm,c=1.1824(3)nm.β=112.92(2)°,Z=4,D_c=1.25g·cm~(-3).晶体结构由直接法解出,1827个可观察衍射参与最小二乘法修正,最终偏差因子R=0.050.结果表明标题化合物是一非平面型,具有部分不饱和键的氮杂稠二环化合物,其母体六元环为椅式构型、五元环为半椅式构型,2个取代苯基间的夹角为73.5°.     

Gas-phase kinetics of elimination reactions of pentane-2,4-dione derivatives. Part ii [1]. Thermolysis of derivatives and analogues of 3-phenylhydrazonopentane-2,4-dione

Six analogues and derivatives (1–6) of 3-phenylhydrazonopentane-2,4-dione (7) were subjected to gas-phase thermolysis. The Arrhenius log A (s⁻¹) and Ea (kJ mol⁻¹) of the analogues (1–5) are, respectively: 10.42 and 140.8 for 1-cyano-1-phenyl-hydrazonopropanone (1) , 11.19 and 135.4 for 1-cyano-1-( -nitrophenylhydrazono)-propanone (2) , 10.68 and 144.9 for 1-cyano-1-( -methoxyphenylhydrazono)propanone (3) , 11.76 and 137.8 for 1-cyano-3-phenyl-1-phenylhydrazonopropanone (4) , and 11.29 and 145.9 for 1-cyano-1-phenylhydrazonobutanone (5) . The corresponding values for ethyl 3-oxo-2-phenylhydrazonobutanoate (6) are 11.90 s⁻¹ and 143.3 kJ mol⁻¹. The rates of reaction at 600 K are compared with those of the title diketone (7) and of pentane-2,4-dione (8) and rationalized in terms of a plausible elimination pathway involving a semiconcerted six-membered transition state. © 1998 John Wiley & Sons, Inc. Int J Chem Kinet: 30: 457–462, 1998     

Photochromism of 1′,3′,3′-trimethyl-6-piperidinospiro [indoline-2′,3-3H-naphth [2,1-b][1,4]-oxazine]

The effect of the piperidine substituent on the spectral and photochromic properties of spiro(indoline-naphthoxazines) (SINO) in different solvents is studied. The introduction of this substituent into the naphthoxazine fragment of SINO results in the appearance of fluorescence of the initial formA of SINO at low temperatures. This fluorescence gradually disappears as the temperature increases. The temperature and concentration dependences of the spectral parameters of photoinduced formB of SINO make it possible to assume thatB molecules aggregate in non-polar solvents. In all solvents studied, form B, unlike the photoinduced form of the non-substituted spiro naphthoxazine, is stabilized as a bipolar ion with a positive charge on the nitrogen atom of the piperidine substituent. The increase in the rate of thermal decolorization as the medium polarity increases is explained.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 684–688, April, 1995.The authors are grateful to the Belarus' Foundation for Basic Research for financial support of this work.     

Acetylenic chemistry: Part 15 [1]. Reactions of 1,2,3,4-Tetrahydro-2,4-dioxopyrido[2,3-d]pyrimidine with 3-bromoprop-1-yne

Reaction of 1,2,3,4-tetrahydro-2,4-dioxopyrido[2,3-d]pyrimidine with 3-bromoprop-1-yne gave 1-prop-2′-ynylpyrido[2,3-d]pyrimidine-2,4-dione ( 4a ), 3-prop-2′-ynylpyrido[2,3-d]pyrimidine-2,4-dione ( 4b ), and 1,3-diprop-2′-ynylpyrido[2,3-d]pyrimidine-2,4-dione ( 4c ). Subsequent boiling of 1,3-diprop-2′-ynylpyrido-[2,3-d]pyrimidine-2,4-dione ( 4c ) in formic acid afforded 1-methylimidazo[1,2-a]pyridyl-N-prop-2′-ynylamide ( 5 ) and 1-acetonyl-3-prop-2′-ynylpyrido[2,3-d]pyrimidine-2,4-dione ( 6 ).     

Deoxypegan-1-one derivatives. synthesis and borohydride reduction of 3-[(E)-arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-ones

3-[(E)-Arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-ones were prepared by reaction of quinazolyl-2-propionic acid hydrochloride with aromatic aldehydes in acetic anhydride in the presence of Et₃N. 3-[(E)-Arylmethylidene]-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-1-ols were formed by reduction of the 3-arylidene derivatives with sodium borohydride in methanol, readily lost water when heated with acids, and were converted into 3-[(E)-arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolines. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 463–467, September–October, 2006.     

Cyclisation of (4S)-4-methyl-2-phenethyl-2,4-dihydro-(1H)-pyrazino[2,1-b]quinazoline-3,6-dione derivatives via N-acyliminium ions

Enantiomerically pure 1-methylene and 1-oxo derivatives (compounds 4 and 10, respectively) of compounds 1 were obtained and studied as precursors of N-acyliminium ions. 1-Substituted-1-hydroxyderivatives, obtained by regioselective syn-addition of organometallics to compounds 10 gave the desired species under acid treatment while compounds 4 did not. N-Phenethyl substituted N-acyliminium ions gave isoquino[1′,2′:3,4]pyrazino[2,1-b]quinazoline-8,11-diones through a Pictet–Spengler-type cyclisation.     

Synthesis,Structure and Antimicrobial Activity of 2'-Thioxo-2',3'-dihydro-1'H,2H-spiro[naphtho[2,1-b]furan-1,5'-pyrimido-[4,5-b]quinoline]-2,4'(10'H)-dione

A new 1,4-dihydroquinoline compound, 2'-thioxo-2',3'-dihydro-1'H,2H-spiro [naphtho[2,1-b]furan-1,5'-pyrimido[4,5-b]quinoline]-2,4'(10'H)-dione(C22H13N3O3S), has been synthesized by the condensation of isatin, 2-thiobarbituric acid and 2-naphthol in aqueous medium. The compound was characterized by IR, NMR, H RMS and single-crystal X-ray diffraction. The crystal belongs to the triclinic system, space group P21/c with a = 9.5187(18), b = 11.7706(19), c = 12.0450(19) ?, α = 89.201(5), β = 81.550(6), γ = 70.024(5)°, Mr = 399.41, V = 1253.6(4) ?3, Z = 2, Dc = 1.058 g/cm3, F(000) = 412, μ = 0.151 mm-1, R = 0.0636 and w R = 0.1648. The preliminary antibacterial activity results show that the title compound exhibits antibacterial activity against Micrococcus tetragenus, Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, S. albus and Escherichia coli.     

Condensed derivatives of benzazoles. 1. Synthesis of 6- and 5-substituted benzimidazo[2,1-b]quinazolin-12-ones

6(5)H-Benzimidazo[2,1-b]quinazolin-12-one was obtained in high yield by condensation of benzimidazole-2-sulfonic acid with anthranilic acid. Methods for the introduction of substituents selectively into the 5 and 6 positions of this heterocycle were developed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1673–1677, December, 1987.     

Synthesis of quaternary 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazolium salts

The reaction of dihydroimidazole-2-thiol with N-(3-chloro-2-oxopropyl)phthalimide gave 2-[3-(4,5-dihydroimidazol-2-ylsulfanyl)-2-oxopropyl]-1,3-dioxo-1H-isoindole which underwent intramolecular heterocyclization to dihydroimidazothiazole system by the action of a dehydrating agent. Treatment of 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazole with concentrated hydrochloric acid led to the formation of dihydroimidazo[2,1-b]thiazol-3-ylmethanamine. Water-soluble quaternary 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazolium salts were obtained by alkylation of 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazole with alkyl halides.     

Synthesis and cytotoxic activity of some novel N-pyridinyl-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide derivatives

A series of novel compounds bearing imidazo[2,1-b]thiazole scaffolds were designed and synthesized based on the optimization of the virtual screening hit compound N-(6-morpholinopyridin-3-yl)-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide (5a), and tested for their cytotoxicity against human cancer cell lines, including HepG2 and MDA-MB-231. The results indicated that the compound 2-(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl)-N-(6-(4-(4-methoxybenzyl)piperazin-1-yl)pyridin-3-yl)acetamide (5l), with slightly higher inhibition on VEGFR2 than 5a (5.72% and 3.76% inhibitory rate at 20 μM, respectively), was a potential inhibitor against MDA-MB-231 (IC(50) = 1.4 μM) compared with sorafenib (IC(50) = 5.2 μM), and showed more selectivity against MDA-MB-231 than HepG2 cell line (IC(50) = 22.6 μM).     

New synthesis of condensed heterocycles from isoxazole derivatives VI. 2,5-Dimethyl-3-aeetyl-7-amino-1H-pyrrolo[3,2-b] pyridine

A new synthesis of pyrrolo[3,2-b] pyridine starting with pyrrole ring is described. The procedure allows the synthesis of 4-azaindoles bearing a sensitive group at C-7. The nitration of 4b with nitric acid and acetic anhydride at ?15° gave 5 . The hydrogenation of 5 led to simultaneous reduction of N-hydroxy and nitro groups and to hydrogenolysis of the isoxazole nucleus, affording an appropriate chain of atoms to building up the pyrrolo[3,2-b] pyridine ring.     

Synthesis of benzo[g]indeno[2,1-b]quinoline derivatives via four-component and one-pot synthesis in presence of 3-methyl-1-sulfonic acid imidazolium hydrogen sulfate

A simple and facile synthesis of 12-arylbenzo[g]indeno[2,1-b]quinoline-6,11,13-trione deriv-atives was accomplished by the one-pot condensation of 2-hydroxynaphthalene-1,4-dione, aryl aldehydes, 2H-ind...     

Fluorocarbon derivatives of nitrogen. Part 16 [1]. Synthesis of some unsymmetrical aromatic azo-compounds via diazotisation of fluorinated aryl- and -heteroaryl-amines in hydrofluoric or sulphuric acid [2]

Coupling reactions of the type Ar_FN⁺₂ + ArH → Ar_FN=NAr + H⁺ have been accomplished between fluorinated arenediazonium ions selected from the benzenic, pyridinic and pyrimidinic classes [Ar_F = C₆F₅, 4---CF₃C₆F₄, 4---C₅F₄N, 4z.sbnd;C₅F₃N.Cl---3, 4---C₅F₂N.Cl₂---3,5, 2---C₅F₃N.CF(CF₃)2---4, 4---C₄F₃N₂] and one or more aromatic compounds activated towards electrophilic attack (ArH = 1,3,5,---ME₃C₆H₃, 1,3,5---Et₃C₆H₃, MeOC₆H₆, and napth-2-ol). The diazonium ions were generated by addition of solid sodium nitrite to solutions of the amines Ar_FNH₂ in anhydrous hydrogen fluoride, 80% hydrofluoric acid, or 98% sulphuric acid mixed with glacial acetic acid and propionic acid. This work has established that perfluorinated arenediazonium ions rank amongst the most electrophilic species of their general class.