A new procedure for the cyclization of 2-indole- and 3-indolecarbohydrazones to 5H-pyridazino[4,5-b]indole derivatives

A new procedure for the cyclization of 2-indolecarbohydrazones (5) to 1,2,3,4-tetrahydro-4-oxo-5H-pyridazino[4,5-b]indoles (6) and for the cyclization of 3-indolecarbohydrazones (7) to 1-oxo-1,2,3,4-tetrahydro-5H-pyridazino[4,5-b]indoles (8 and 9) is described. The hydrazones (5 or 7) were treated with an acyl halide (acetyl or benzoyl chlorides) and triethylamine in ethyl acetate of chloroform as solvents to give the compounds 6 (20–70%) from the compounds 5 , and the compounds 8 (20–60%) from the compounds 7 . Through refluxing with ethanol-hydrochloric acid the compounds 8a-8f selectively separate the acetyl group on N⁵ to give the respective compounds, 9a-9f. The ir and ¹H-nmr spectra of all the compounds 5, 6, 7, 8 and 9 and the uv, mass and ¹³C-nmr spectra of the compounds 7h, 7i, 8h and 8i are discussed.     

Synthesis and alkylation ofN-methylmorpholinium 5-cyano-4-(3- and 4-hydroxyphenyl)-2-oxo-1,2,3,4-tetrahydropyridine-6-thiolates

The reactions of 3- or 4-hydroxybenzaldehydes with cyanothioacetamide and Meldrum's acid in the presence ofN-methylmorpholine affordedN-methylmorpholinium 5-cyano-4-(3-or 4-hydroxyphenyl)-2-oxo-1,2,3,4-tetrahydropyridine-6-thiolates, respectively. The resulting compounds were used in the synthesis of substituted 6-alkylthio-1,2,3,4-tetrahydropyridin-2-ones. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2333–2336. December, 1999.     

Synthesis of Some New 1,2,3,4‐Tetrahydropyrimidine‐2‐thione and Their Thiazolo[3,2‐a]pyrimidine,Thiazino and Benzothiazepine Derivatives

The starting N‐(2‐pyridyl)‐6‐methyl‐4‐phenyl‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxamide ( 4 ) was used as a key intermediate for the synthesis of new 1,2,3,4‐tetrahydropyrimidine‐2‐thione and their thiazolo[3,2‐a]pyrimidine, thiazino and benzothiazipen derivatives. The reaction of 4 with haloketones in ethanol catalyzed by base afforded the corresponding thiophenopyrimidine and pyrimidothiazipine derivatives 5 , 6 , 7 , 8 , 9 , 10 . Methylation and formylation of 4 led to the pyrimidine derivatives 15 and 16 , respectively. The preventative compounds were established on the basis of elemental and spectral data.     

Synthesis of 5-amino-1,2,3,4-tetrahydrobenzo[b][1,7]naphthyridines and 2,3,4,4a,5,6-hexahydrobenzo[c][2,6]naphthyridines

This paper describes the synthesis of some 5-amino-1,2,3,4-tetrahydrobenzo[b][1,7]naphthyridines and 2,3,4,4a,5,6-hexahydrobenzo[c][2,6] naphthyridines starting from anilines and 1-benzyl-4-ethoxycarbonylpiperidin-3-one. The compounds were prepared in order to study their potential acetylcholinesterase inhibitory activity.     

Synthesis of hexa-, tetra-, and dihydroxanthene derivatives from salicylaldehyde aminals

Salicylaldehyde aminals react with cyclohexanone upon heating to form tetrahydroxanthene derivatives. The structure of one of these derivatives,viz., 5,7-dichloro-4a-morpholino-1,2,3,4-tetrahydro-4aH-xanthene, was established by X-ray diffraction analysis. The scheme of the reaction was suggested, which involves cycloaddition of intermediateo-methylenequinone (from aminal) and enamine (from cyclohexanone). The reactions of salicylaldehyde aminals with enamines that formed from cyclohexanone can successively afford derivatives of hexahydroxanthene, tetrahydroxanthene, and dihydroxanthene. Procedures were developed for the synthesis of these compounds.N-Substituted 4a-amino-7-nitro-1,2,3,4-tetrahydro-4aH-xanthenes were also prepared by the reactions of dialkylammonium 2-formyl-4-nitrophenoxides with the above-mentioned enamines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 959–965, May, 1999.     

New α‐Tetralone Galloylglucosides from the Fresh Pericarps of Juglans sigillata

Three new α‐tetralone galloylglucosides, 1 – 3 , were isolated from the fresh pericarps of Juglans sigillata (Juglandaceae), together with six known compounds. The structures of the new compounds were determined as 1,2,3,4‐tetrahydro‐7‐hydroxy‐4‐oxonaphthalen‐1‐yl 6‐O‐[(3,4,5‐trihydroxyphenyl)carbonyl]‐β‐D ‐glucopyranoside ( 1 ), (1S)‐1,2,3,4‐tetrahydro‐8‐hydroxy‐4‐oxonaphthalen‐1‐yl 6‐O‐[(3,4,5‐trihydroxyphenyl)carbonyl]‐β‐D ‐glucopyranoside ( 2 ), and 1,2,3,4‐tetrahydro‐7,8‐dihydroxy‐4‐oxonaphthalen‐1‐yl 6‐O‐[(3,4,5‐trihydroxyphenyl)carbonyl]‐β‐D ‐glucopyranoside ( 3 ), respectively, on the basis of detailed spectroscopic analyses, and acidic and enzymatic hydrolysis. The antimicrobial activities of the isolated compounds 2, 4 , and 7 – 9 were evaluated.     

Synthesis and Antitumor Activity of Heterocycles Related to Carbendazim

Three types of compounds were synthesized from carbendazim ( 1 ), a benzimidazole derivative (Scheme 1 ). They included a group of esters at N1 prepared by treating carbendazim with isocyanates bearing ester groups ( 2a , 2b , 2c ), carboxyalkyl‐1,2,3,4‐tetrahydro‐s‐triazino[1,2‐a]benzimidazole‐2,4‐dione esters ( 3a and 3b , 3d and 3c derived from 3a . The antitumor potencies of the N1 esters were in the range of 7 to 40 μM, which compares favorably with carbendazim, but their water solubilities were low. The s‐triazine derivatives showed activity against pancreatic tumor cells, and one of them ( 3b ) was active in mice, but they were not effective against other tumor types. Treatment of carbendazim with 3‐bromopropionyl chloride produced 1‐methoxycarbonyl‐4‐oxo‐1,2,3,4‐tetrahydropyrimido[1,2‐a]benzimidazole ( 4 ), which gave 1‐(3‐aminopropionyl)benzimidazole 2‐methylcarbamates, substituted on the amino nitrogen ( 5a , 5b , and 5d ), when treated with amines. These products showed some antitumor activity in cell cultures, and an ethoxy derivative ( 5c ), obtained by treating 1‐methoxycarbonyl‐4‐oxo‐1,2,3,4‐tetrahydropyrimido[1,2‐a]benzimidazole with sodium ethoxide, was active in the 67–150 μM range. Some of the new compounds had good water solubility. Carbendazim kills tumor cells by inhibiting tubulin; however, s‐triazine 3b , which differs from it in size and functional groups, does not act by this mechanism.     

Synthesis of the 1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridine ring system

As part of an on-going research project, we required an efficient method for the preparation of compounds containing the 1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridine ring nucleus. The parent compound 1 has not been described in the literature, and there is only one reference to the N-methyl analog 2 [1]. A series of structurally related compounds, the 2-substituted-4-hydroxy-1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridines, has been described [2].     

Selenium heterocycles XXIII. Synthesis of 4,5-dihydrophenanthro[1,3-d]-1,2,3-selenadiazoles and 10,11 -dihydrophenanthro[1,2-d]-1,2,3-selenadiazoles

The selenium dioxide oxidation of a series of 1,2,3,4-tetrahydrophenanthrone and 1,2,3,4-tetrahydrophenanthren-4-one semicarbazones afforded 4,5-dihydrophenanthro[4,3-d]-1,2,3-selenadiazoles and 10,11-dihydrophenanthro[1,2-d]-1,2,3-selenadiazoles. The latter series which represent a new type of selenaazasteroidal compounds were pyrolyzed and gave the corresponding 1,4-deselenine derivatives.     

Trapping of thiaziridinimines with thiocarbonyl compounds

Thermolysis of 4-benzyl-5-tosylimino-1,2,3,4-thiatriazoline at 60–70° in the presence of representative C = S unsaturated compounds furnished 1,2,4-dithiazolidin-5-imines in moderate yields. The reaction is assumed to proceed via the inlermediacy of an unstable thiaziridinimine which is trapped by the C=S compound in a regiospecific manner. Among the thiocarbonyl compounds used are p,p′-dimethoxythiobenzophenone, xanthates and 3-benzylrhodanine, the latter giving rise to a spiro adduct.     

Synthesis of 2-[mercapto(cyano)methylene]-1,2,3,4-tetrahydro-quinazolin-4-ones and 2-amino-4-methylpyrazolo-[1,5-a]quinazolin-5(4H)-one

A series of 2-[mercapto(cyano)methylene]-1,2,3,4-tetrahydroquinazolin-4-ones and 2-amino-4-methylpyrazolo[1,5-a]quinazolin-5(4H)-one were prepared from 2-cyanomethylquinazolin-4(3H)-ones via α-bromo derivatives 4 and amide oxime 8, respectively. The new compounds have been characterized by elemental analyses and ¹H-nmr, in some cases by ir and ¹³C-nmr investigations.     

Preparation and thermal degradation of α,ω-alkylene bis[5-(1,2,3,4-thiatriazolyl)] sulfides

Syntheses of some extremely shock sensitive α,ω-alkylene bis[ 5-(1,2,3,4-thiatriazolyl)] sulfides via reaction of sodium 1,2,3,4-thiatriazoline thionate (1) and α,ω-dihaloalkanes are described. Dichloromaleic imide reacted analogously with 1 to give 3,4-bis(5-(1,2,3,4-thiatriazolyl)thio)maleic imide. The compounds decompose thermally in solution with formation of α,ω-alkylene bis(thio-cyanates), nitrogen and sulfur. The infrared spectra are discussed.     

The synthesis of propellance compounds from 2,3-disubsituted indoles and o-benzoquinones

The reaction of 2,3-dihydro-1H-cyclopent[b]indole 3 and 1,2,3,4-tetrahydrocarbazole 4 with substituted o-benzoquinones yielded [4.3.3]- and [4.4.3]propellanes, respectively. The physical and chemical properties of the propellane compounds were investigated and a mechanism for the formation of the propellane compounds was discussed.     

Synthesis of Triazoles,Oxadiazoles and Condensed Heterocyclic Compounds Containing Cinchopheny and Studies on Biological Activity of Representative Compounds

Compounds 2‐arylamino‐5‐cinchophenyl‐1,3,4‐oxadiazoline ( 7 ) and 3‐thio‐4‐amino‐5‐cinchophenyl‐1,2,4‐triazole ( 3 ) have been synthesized utilizing cinchophen as the starting material. The compound 3‐cinchopheny‐s‐triazolo[3,4‐b]‐1,2,3,4‐thiatriazole ( 4 ) was prepared from compound 3 . Condensation of 3 with aromatic acid in the presence of POCl₃ gave 10 new 6‐aryl‐3‐cinchopheny‐1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazoles ( 5 ). Some of the representative compounds were screened for antibacterial activity. The structures of these new compounds have been confirmed by means of elemental analysis, IR, ¹H NMR and MS.     

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.     

微波辐射下合成3-芳基-9-氨基-1,2,3,4-四氢吖啶-1-酮衍生物

在微波辐射和对甲基苯磺酸的催化作用下, 5-芳基-1,3-环己二酮与邻氨基苯甲腈进行缩合反应, 得到了N-取代的2-氨基苯甲腈衍生物, 在K₂CO₃和Cu₂Cl₂的催化作用下进一步合环, 得到3-芳基-9-氨基-1,2,3,4-四氢吖啶-1-酮衍生物, 用LiAlH₄还原羰基得到3-芳基-9-氨基-1,2,3,4-四氢吖啶-1-醇衍生物. 新合成化合物的结构均经元素分析、红外光谱和核磁共振光谱予以确认.     

Synthesis,characterization, and investigations of antimicrobial activity of 6,6-dimethyl-3-aryl-3′,4′,6,7-tetrahydro-1′H,3H-spiro[benzofuran-2,2′-naphthalene]-1′,4(5H)-dione

Chalcone-like compounds 3a–l, 2-(benzylidene)-3,4-dihydronaphthalen-1(2H)-one, were synthesized from the addition of different benzaldehyde derivatives (2a–l) to 1,2,3,4-tetrahydro-1-napthalone (1) in basic medium. Mn(OAc)₃-mediated addition of dimedone (4) to chalcone-like compounds gave the spirobenzofuran derivatives (5a-l), 6,6-dimethyl-3-aryl-3′,4′,6,7-tetrahydro-1′H,3H-spiro[benzofuran-2,2′-naphthalene]-1′,4 (5H)-dione, in good yields. The structures of synthesized compounds 5a–l were elucidated on basis of spectral data (NMR, IR) and elemental analysis. In addition, their antibacterial activities were screened against some human pathogenic microorganisms.     

Reaction of 3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-diones with ethyl(triphenylphosphoranylidene)acetate

The Wittig reaction of 3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-diones 2 with ethyl (triphenyl-phosphoranylidene)acetate 3 proceeds stereoselectively to give E-4-carbethoxymethylene-1,2,3,4-tetra-hydro-2-quinolones 4 , which were hydrolyzed to corresponding acids 6 Butenolides 5 were detected and, in some cases, isolated as a minor product of the Wittig reaction.     

Efficient access to some new pyrimidine derivatives and their antimicrobial evaluation

1-[4-(3-Hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl]ethanone ( 1 ) was used as a precursor for heterocyclic synthesis. Condensation of compound 1 with monochloroacetic acid and benzaldehyde gave thiazolopyrimidine 2 which in turn underwent cyclization with malononitrile dimmer to afford malononitrile derivative 3 . Also, the reaction of compound 1 with benzaldehyde under a basic condition produced chalcone 4 . Chalcone 4 can be used as a key intermediate for further preparation of heterocyclic compounds. In addition, compound 1 was allowed to react with malononitrile dimmer and/or ethyl chloroacetate to give pyrimidines 8 and 9 , respectively. Alkylation of compound 8 with ethyl chloroacetate afforded S-alkylated product 10 which was treated with hydrazine hydrate to yield the hydrazino derivative 11 . Alternative synthesis of compound 10 was taken place through reaction of compound 9 with malononitrile dimmer. The biological activity of the synthesized compounds was investigated. Compounds 1 , 4 , 5 , and 8 recorded high activities against Gram positive bacteria (S. aureus). Structures of the new synthesized compounds were elucidated by elemental analysis and spectral data.     

Silyl modification of biologically active compounds. 11. Synthesis,physico‐chemical and biological evaluation of N‐(trialkoxysilylalkyl)tetrahydro(iso,silaiso) quinoline derivatives

N‐(trialkoxysilylalkyl) derivatives of 1,2,3,4‐tetrahydroquinoline, 1,2,3,4‐tetrahydroisoquinoline and 4,4‐dimethyl‐4‐sila‐1,2,3,4‐tetrahydroisoquinoline were prepared and characterized by elemental analysis, ¹H, ¹³C and ²⁹Si NMR spectroscopy. In vivo psychotropic properties and in vitro cytotoxic effects of 3‐[N‐(1,2,3,4‐tetrahydroisoquinolyl)]propyltriethoxysilane methiodide and 3‐[N‐(1,2,3,4‐tetrahydroisoquinolyl)]propylsilatrane are reported. Comparative study of ²⁹Si shifts in newly synthesized compounds suggested donor–acceptor interaction between nitrogen and silicon atom, which increased electron density at Si nuclei, revealing a stronger increment of N → Si transannular bond in comparison with N → Si α‐effect. The molecular structure of 3‐[N‐(1,2,3,4‐tetrahydroisoquinolyl)]propylsilatrane features a penta‐coordinate silicon atom having CSiO₃ pattern and Si…N intramolecular interaction. Copyright © 2005 John Wiley & Sons, Ltd.