Reactions of methyl 1-acetylenyl-9,10-anthraquinone-2-carboxylates with hydrazine

Methyl 1-acetylenyl-9,10-anthraquinone-2-carboxylates react with NH₂NH₂ in ethanol at 80°C to give commensurable amounts of substituted 7H-dibenzo[de,h]quinolin-7-ones and 3,4-dihydro-3-aminonaphtho[2,3-f]isoquinoline-4,7,12-triones. The main, route of the reaction apparently includes nucleophilic addition of the reagent to the triple bond of the ester followed by intramolecular cyclization of the adduct with either the carbonyl or the methoxycarbonyl groups involved. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10 pp. 2031–2035, October, 1998.     

A novel heterocyclization of 1-acetylenyl-9,10-anthraquinones

I-Acetylenyl-9,10-anthraquinones react with an excess of NH₂NH₂ at 80–115°C to give a mixture of substituted 7H-dibenzo[de,h]quinolin-7-ones and anthra[9,1-cd]-1,2-diazepin-8-ones. The latter compounds undergo reductive contraction of the sevenmembered ring to give the corresponding 7H-dibenzo[de,h]quinolin-7-ones. Bulky substituents in position 2 of the initial acetylenylanthraquinones prevent the formation of the sevenmembered heterocycle. A scheme of the cyclocondensation was proposed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2027–2030, October, 1998.     

Cascade Transformations of 1-R-Ethynyl-9,10-anthraquinones with Amidines: Expanding Access to Isoaporphinoid Alkaloids

The interaction of acetamidine and phenylamidine with peri-R-ethynyl-9,10-anthraquinones in refluxing n-butanol leads to the formation of cascade transformations products: addition/elimination/cyclization―2-R-7H-dibenzo[de,h]quinolin-7-ones and(or) 2-R-3-aroyl-7H-dibenzo[de,h]quinolin-7-ones. The anti-inflammatory and antitumor properties of the new 2-R-7H-dibenzo[de,h]quinolin-7-ones were investigated in vivo, in vitro, and in silico. The synthesized compounds exhibit high anti-inflammatory activity at dose 20 mg/kg (intraperitoneal injection) in the models of exudative (histamine-induced) and immunogenic (concanavalin A-induced) inflammation. Molecular docking data demonstrate that quinolinones can potentially intercalate into DNA similarly to the antitumor drug doxorubicin.     

Reaction of guanidine with peri-substituted (R-ethynyl)-9,10-anthraquinones bearing electron-donating substituents

2-Amino-3-aroyl-7H-dibenzo[de,h]quinolin-7-ones were synthesized by the reaction of guanidine with peri-(R-ethynyl)-9,10-anthraquinones in boiling n-butanol.     

Synthesis and total assignment of 1H and 13C NMR spectra of new oxoisoaporphines by long-range heteronuclear correlations

The new oxoisoaporphines 7H-dibenzo[de,h]quinolin-7-one, 5-methoxy-7H-dibenzo[de,h]quinolin-7-one, 5-methoxy-6-hydroxy-7H-dibenzo[de,h]quinolin-7-one, 5-hydroxy-7H-dibenzo[de,h]quinolin-7-one and 5-methoxy-6H-dibenzo[de,h]quinolin-6-one were prepared either by oxidation of their 2,3-dihydro derivatives or by heating (2'-(3,4-dihydro-6,7-dimethoxyisoquinolin-1'-yl)phenyl)methylbenzoate with an acetic acid/sulfuric acid mixture at 100 degrees C. The structures were confirmed and 1H and 13C NMR spectra were completely assigned using two-dimensional NMR techniques.     

A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

Complete structural and spectral assignment of oxoisoaporphines by HMQC and HMBC experiments

The oxoisoaporphines 2,3‐dihydro‐7H‐dibenzo[de,h]quinolin‐7‐one, 2,3‐dihydro‐5‐methoxy‐7H‐dibenzo [de,h] quinolin‐7‐one, 5‐methoxy‐6‐hydroxy‐2,3‐dihydro‐7H‐dibenzo[de,h]quinolin‐7‐one, 5,6‐dimethoxy‐2,3‐dihydro‐7H‐dibenzo[de,h]quinolin‐7‐one and 5,6‐methylenedi‐oxy‐2,3‐dihydro‐7H‐dibenzo[de,h]quinolin‐7‐one were prepared by cyclization of phenylethylaminophthalides with polyphosphoric acid or by treating 1‐(2‐carboxyphenyl)‐3,4‐dihydroisoquinoline hydrochloride with sulfuric acid at 0 °C. The structures were confirmed and ¹H and ¹³C NMR spectra were completely assigned using a combination of one‐ and two‐dimensional NMR techniques. Copyright © 2003 John Wiley & Sons, Ltd.     

Unambiguously confirmed structure of 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one

To determine the structures of two isomeric products, 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (2) and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (3) obtained by condensation of 2,3-diaminopyridine (1) with ethyl benzoylpyruvate [1–3], these compounds were hydrolyzed to give 2-methyl-4H-pyrido[2,3-b]pyrazin-3-one (4) and 3-methyl-1H-pyrido[2,3-b]pyrazin-2-one (5) , respectively [4,5]. Both hydrolysates 4 and 5 were hydrogenated to afford 2-methyl-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (6) and 3-methyl-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (7) . The latter compound was identical with an unequivocally synthesized compound providing proof for the structures of all these compounds.     

4-Hydroxy-2-quinolones 147. Synthesis and tautomerism of 2-methyl-9H-furo-[2,3-<Emphasis Type="Italic">b</Emphasis>]quinolin-4-one

In the presence of aqueous solutions of alkali, 2-bromomethyl-3,9-dihydro-2H-furo[2,3-b]quinolin-4-one is subjected to dehydrobromination and converted to 2-methyl-9H-furo[2,3-b]quinolin-4-one which exists in acid solution in the 4-oxo-and in base in the 4-hydroxy tautomeric forms. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1039–1043, July, 2008.     

Application of N,3-diaryl-3-oxo-propanethioamide in synthesis: an efficient and mild domino approach to highly substituted fused chromenones

A convenient and rapid synthesis of hitherto unknown 3-aroyl-4-aryl-2-phenylamino-4H-benzo[g]chromene-5,10-diones in high yield from β-aroyl-thioacetanilide, aromatic aldehyde, and 2-hydroxy-1,4-naphthoquinone via InCl₃ catalyzed one-pot three-component tandem Knoevenagel condensation–Michael addition–intramolecular cyclization–elimination reaction sequence is disclosed for the first time. This domino protocol has been used to obtain highly substituted pyrano[3,2-c]chromen-5(4H)-ones and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-ones from N,3-diaryl-3-oxo-propanethioamide, aromatic aldehyde, and 4-hydroxycoumarine or dimedone under mild reaction conditions. A plausible reaction mechanism is proposed. The 4H-pyrano[3,2-c]chromen-5-one and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one derivatives possessing 3-(2-chlorobenzoyl)-2-phenylamino-substituents further cyclized under basic conditions to yield penta-cyclic 7,13-diaryl-5,14-dioxa-13-aza-benzo[a]naphthacen-6,8(7H,13H)-dione and tetra-cyclic 6,12-diaryl-3,3-dimethyl-3,4-dihydro-2H-chromeno[2,3-b]quinolin-1,11(6H,12H)-dione, respectively.     

The synthesis of benzofuroquinolines. III. Two dihydroxybenzofuroquinolinones

Two dihydroxybenzofuroquinolinones, 3,9-dihydroxy-5H-benzofuro[3,2-c]quinolin-6-one (V) and 3,8-dihydroxy-6H-benzofuro[2,3-b]quinolin-11-one (VI), were obtained by the demethyl-cyclization of 3-(2,4-dimethoxyphenyl)-4-hydroxy-7-methoxy-1H-quinolin-2-one (IV). By the methylation with diazomethane, V gave a dimethylated compound (VII), while VI gave a trimethylated compound (VIII).     

A clean synthesis of oxazino[5,6-<Emphasis Type="Italic">f</Emphasis>]quinolinone and naphtho[1,2-<Emphasis Type="Italic">e</Emphasis>]oxazinone derivatives

A clean, simple, one-pot, and efficient synthesis of 1,2-dihydro-1-aryl[1,3]oxazino[5,6-f]quinolin-3-one and 1,2-dihydro-1-arylnaphtho[1,2-e]-[1,3]oxazine-3-one derivatives was accomplished in good yields via reaction between 6-quinolinol or 2-naphthol, aromatic aldehydes, and methyl carbamate in aqueous medium catalyzed by TEBA (triethylbenzylammonium chloride). Correspondence: Mohammad Hossein Mosslemin, Department of Chemistry, Islamic Azad University, Yazd 8916871967, Iran.     

Heterocycles structurally influenced by a side chain. X. Effect of temperature and side chain on the imine-enamine tautomerism in the quinoxalinone and pyridopyrazinone systems

3-(1-Benzoyl)ethyl-1H-pyrido[2,3-b]pyrazin-2-one ( 7 ), 3-(1-ethoxycarbonyl)ethyl-1H-pyrido[2,3-b]-pyrazin-2-one ( 8 ), and 3-(1-benzoyl)ethyl-1H-quinoxalin-2-one ( 9 ) exist only in the imine form due to the steric effect of the methyl substituent. As regards the imine-enamine tautomerism, 3-(β-carbonylmethylene) derivatives of 1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one such as 12 and 15–18 gradually change from the enamine form to the imine form with elevated temperatures; however, 3-(carbonylmethylene) derivatives of 3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one such as 10, 19 and 20 show little temperature effect. 2-Phenacylidene-1,2-dihydro-4H-pyrido[3,4-b]pyrazin-3-one ( 21 ) and 3-phenacylidene-3,4-dihydro-1H-pyrido[3,4-b]pyrazin-2-one ( 22 ), which exist in the enamine form, show no temperature effect.     

Studies on quinazolinones. 2. Synthesis of 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-oxazolo[2,3–6]quinazolin-5-one and -2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one

To search for novel antihypertensive heterocycles in the condensed quinazoline series, two representative compounds were synthesized via a suitable reaction sequences. Treating anthranilonitrile with allyl isocyanate gave 2-(allylureido)benzonitrile ( 10 ) in a quantitative yield. Compound 10 was cyclized to 3-allylquinazoline-2(1H, 4(3H)-dione ( 11 ). Bromination of 11 in carbon tetrachloride converted it into the corresponding 3-(2,3-dibromopropyl) derivative ( 12 ) in 92% yield. Ring closure of 12 was effected by the action of alkali to afford 2-bromomethyl-2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-one ( 13 ). The title compound, 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-one ( 7 ) could be obtained by a reaction of either 12 or 13 with 1-benzylpiperazine respectively. Starting from the readily available 3-allyl-2H-thioxoquinazolin-4(3H)-one ( 16 ) via the analogous reactions gave the 2-bromomethyl-2,3-dihydro-5H-thiazolo[2,3-b]-quinazolin-5-one ( 19 ) in good yield. However, the reaction of 19 with 1-benzylpiperazine provided another target compound, 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one ( 8 ) only in poor yield (8%). As major product, the dehydrobrominated compound, 2-methylene-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one ( 22 ) was isolated. A preliminary pharmacological evaluation revealed that both compounds 7 and 8 are devoid of the antihypertensive activity.     

3-Arylazo-2-thioxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-quinazolin-4-ones as Azodisperse Dyes for Dyeing Polyester Fabrics

Summary. Diazotized 3-amino-2-thioxo-2,3-dihydro-1H-quinazolin-4-one was coupled with various hydroxy aromatics to give the corresponding 3-arylazo-2-thioxo-2,3-dihydro-1H-quinazolin-4-ones in reasonable yields. The dyes produced were applied to polyesters as disperse dyes and their fastness properties were elevated.     

Complete 1H and 13C NMR spectral assignment of hydrogenated oxoisoaporphine derivatives

2,3,8,9,10,11‐Hexahydro‐7H‐dibenzo[de,h]quinolin‐7‐one, 5‐methoxy‐2,3,8,9,10,11‐hexahydro‐7H‐dibenzo[de,h]quinolin‐7‐one, 5‐methoxy‐6‐hydroxy‐1,2,3,7a,8,9,10,11,11a,11b‐decahydro‐7H‐dibenzo[de,h]quinolin‐7‐one, 5‐methoxy‐5,6,8,9,10,11‐hexahydro‐4H‐dibenzo[de,h]quinolin‐7‐ol, 5,6,8,9,10,11‐hexahydro‐4H‐dibenzo[de,h]quinolin‐7‐ol and 5,6‐dihydro‐4H‐dibenzo[de,h]quinolin‐7‐ol were prepared by catalytic hydrogenation of oxoisoaporphines or their 2,3‐dihydro derivatives over PtO₂ in acetic acid under mild conditions. Their structures were confirmed and ¹H and ¹³C NMR spectra were completely assigned using a combination of one‐ and two‐dimensional NMR techniques. Copyright © 2003 John Wiley & Sons, Ltd.     

A facile synthesis of isoindolo[2,1-a]quinolin-11-one via [4+2] reactions of N-acyliminium intermediates with olefines

A facile synthesis of isoindolo[2,1-a]quinolin-11-one has been developed to attain new molecules of this family via [4+2] reactions of N-acyliminium cation, produced from 2,3-dihydro-3-hydroxy-2-arylisoindol-1-one, in the presence of BF₃·OEt₂ with olefins in moderate to good yields at ambient temperature.     

New heterocyclic structures. [1,2,5]Thiadiazolo[3′,4′:4,5]pyrimido-[2,1-b][1,3]thiazine and thiazolo[3,2a][1,2,5]thiadiazolo[3,4-d]pyrimidine

Derivatives of two new molecular structures, namely, 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one and 6,7-dihydro-9H-thiazolo[3,2-a][1,2,5]thiadiazolo[3,4-d][pyrimidin-9-one, and derivatives of N-substituted sulfamic acid, namely, (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-on-7-yl)sulfamic acid and (7-amino-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin-5-on-6-yl)sulfamic acid, were separated out as by-products in the reduction reaction of 8-amino-3,4-dihydro-7-nitroso-2H,6H-pyrimido[2,1- b][1,3]thiazin-6-one and 7-amino-2,3-dihydro-6-nitroso-5H-thiazolo[3,2-a]pyrimidin-5-one derivatives, respectively, with sodium hydrosulfite. A mechanism of reaction, which hypothesizes the action of sodium hydrosulfite in an asymmetic form, is proposed. The results of single-crystal X-ray investigation on 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one (R = 0.032 for 863 reflections) and (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b]- [1,3]thiazin-6-on-7-yl)sulfamic acid, sodium salt (R = 0.028 for 3507 reflections) are reported.     

Chemistry of 2-methylene-2,3-dihydro-3-furanones

2-p-Chlorobenzoylmethylene-5-phenyl-2,3-dihydro-3-furanone reacts with arylamines orN-arylideneamines to form the products of ring opening, 1,6-diaryl-1-arylamino-4-hydroxy-1,4-hexadiene-3,6-diones. The reaction of 5-aryl-2-p-chlorobenzoylmethylene-2,3-dihydro-3-furanones witho-aminophenol afforded 3-p-chlorobenzoylmethylene-3,4-dihydro-2H-benzo[b]-1,4-oxazin-2-one. Nucleophilic attack of amines is directed either to electrophilic centers at the C(5) and C(2) atoms or to the carbonyl group of the 2-phenacylidene substituent of the 3-oxofuran ring. For communication 15, see Ref. 1. Translated fromIzestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1340–1345, July, 1997.     

Synthesis of some benzo[h]quinoline derivatives

Reaction between 6-methoxy-1-tetralone, methyl propiolate and an ammonia-saturated methanolic solution led to 5,6-dihydro-8-methoxybenzo[h]quinolin-2(1H)-one in good yields. Subsequent aromatization, chlorination, substitution and demethylation enabled us to prepare 2-amino-substituted benzo[h]quinoline derivatives. These compounds, which are structurally related to the antitumor benzo[c]phenanthridine alkaloids by deletion of a ring, were tested on cultured murine lymphoblastic leukaemia cells (L1210). Results showed that they are devoid of cytotoxicity.