Regioselective Synthesis ofPyrano[3,2-f]quinolin-2(7H)-onesand Furo[3,2-f]quinolin-2-ones

Summary.  A simple and efficient synthesis of the hitherto unreported ring systems pyrano[3,2-f]quinolin-2(7H)-one and furo[3,2-f]quinolin-2-one was accomplished via a thermal [3,3]-sigmatropic rearrangement. Received March 7, 2000. Accepted May 4, 2000     

Syntheses of 5H-benzoxazolo[3,2-a] quinolin-5-ones

Treatment of N-(2-hydroxyphenyl)anthranilic acid with acetic anhydride, under refluxing conditions provided a simple method for the synthesis of 5H-henzoxazolo[3,2-a] quinolin-5-one (IVa), a heretofore unreported ring system. When propionic anhydride was used in the above reaction, 6-methyl-5H-benzoxazolo[3,2-a]quinolin-5-one (Va) was obtained. Other examples prepared in this fashion were IVb, IVc and Vb. Treatment of IVa with methoxyethylamine afforded 1,2-dihydro-1-(2-hydroxyphenyl)-2-(methoxyethylimino)-4-quinolinol (VII). A possible mechanism for the cyclization reaction is discussed.     

Synthesis of tricyclic and tetracyclic thieno[3,2-f]-1,4-thiazepines

Treatment of 5-methylthio-2,3-dihydrothieno[3,2-f]-1,4-thiazepine ( 9 ) with acylhydrazines gave 5,6-dihydrothieno[3,2-f]-1,2,4-triazolo[4,3-d][1,4]thiazepines 10, 11 , and that of 9 with ethyl anthranilate gave 5,6-dihydrothieno[3′,2′:6,7][1,4]thiazepino[5,4-b]quinazolin-8-one ( 14 ). Reaction of 9 with hydrazine hydrate or 4-chlorophenylhydrazine afforded 5-hydrazino compounds 12, 15 , which were subsequently cyclized to ethyl 5,6-dihydrothieno[3,2-f]-1,2,4-triazolo[4,3-d][1,4]thiazepine-3-carboxylate ( 13 ), 2-(4-chlorophenyl)-5,6-dihydrothieno[3,2-f]-1,2,4-triazolo[4,3-d][1,4]thiazepin-3(2H)-one ( 16 ) and 2-(4-chlorophenyl)-6,7-dihydro-2H-thieno[3,2-f][1,2,4]triazino[4,3-d][1,4]thiazepine-3,4-dione ( 17 ). New thieno-anellated heterocycles were prepared with the aim of studying their affinity for the benzodiazepine receptors.     

Synthesis of 1-benzyl-8,9-dihydroimidazo[4,5-c]pyrrolo[3,2-g]quinolin-4(5H)-one via palladium-catalyzed intramolecular arylation

The synthesis of a novel tetracyclic structure, 8,9-dihydroimidazo[4,5-c]pyrrolo[3,2-g]quinolin-4(5H)-one, has been achieved by a convergent pathway. Coupling of the weakly nucleophilic hindered aromatic amine with 1-benzylimidazole-4-carboxylic acid, 7, afforded the corresponding amide 9 using a DCP/DMF complex; subsequent Heck-type arylation leading to desired tetracyclic molecule imidazo[4,5-c]-pyrrolo[3,2-g]quinolin-4(5H)-one.     

Synthesis of 4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine

4-Methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine ( 3 ) was synthetized from 2-acetylfuro[3,2-f]benzo[b]furan ( 4 ) or from 2-acetyl-5,6-dihydrofuro[3,2-f]benzo[b]furan ( 10 ). The key step involves a rearrangement-cyclization of azides 6 and 12 to form 4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridin-1(2H) one ( 7 ) and 8,9-dihydro-4-methylfuro[3′,2′:5,6]benzofuro[3,2c]pyridin-1(2H)-one ( 13 ). Introduction of an aminoalkyl chain on carbon 1 was effected by substitution of 1-chloro-4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine ( 8 ).     

An anomalous reaction of 10-chloro-5H-benzoxazolo[3,2-a]quinolin-5-one with sodium diethyl malonate to form 9-chloro-8-ethoxy-12-hydroxy-5H-dibenz[c,f]quinolizin-5-one

Treatment of 10-chloro-5H-benzoxazole[3,2-a]quinolin-5-one (I) with an excess of sodium diethyl malonate at 190° for 3 hours in hexamethylphosphoramide gave, in 38% yield, 9-chloro-8-ethoxy-12-hydroxy-5H-dibenz[c,f]quinolizin-5-one (IV) which, on heating with acetic anhydride, afforded monoacetylated product, V. A possible reaction mechanism for the novel ring expansion reaction is suggested.     

Synthesis of 5-methylfuro[3,2-c]quinolin-4(5H)-one via palladium-catalysed cyclisation of N-(2-iodophenyl)-N-methyl-3-furamide

A new synthesis of the furo[3,2-c]quinolin-4(5H)-one heterocycle has been developed using a palladium-catalysed cyclisation of N-(2-iodophenyl)-N-methyl-3-furamide. By varying the catalyst, base and solvent, the yield of the cyclisation was optimised. It was found that the use of palladium oxide with potassium acetate in N,N-dimethylacetamide (DMA) with a small amount of tetrabutylammonium chloride gave the highest yield of 5-methylfuro[3,2-c]quinolin-4(5H)-one (9).     

1,4-Cyeloaddition reactions. IV. preparation of Cyclopenta[g]furo[3,2-c]quinolines,Cyclopenta- [f]furo[3,2-c]quinolines,Benzo[H]furo[3,2-c]quinolines,and Furo- [3,2-c]indeno[1,7-gh] quinolines from 2,3-Dihydro-5-methylfuran and schiff bases

The boron trifluoride catalyzed 1,4-addition of 2,3-dihydro-5-methylfuran to N-(p-methoxybenzylidene)-5-indanamine (VI) gave 2 pairs of epimers, dl-3,3a,4,5,7,8,9,10b-octahydro-4-(p-methoxyphenyl)-10b-methyl-2H-cyclopenta[g]furo[3,2-c]quinoline (VIIa and b) and dl-3,3a, 4,-5,8,9,10,10c-octahydro-4-(p-methoxyphenyl)-10c-methyl-2H-cyclopenta[f]furo[3,2-c]quinoline (VIIIa and b). When 4-(benzylideneamino)-1-naphthol (IXa) was condensed with 2,3-dihydro-5-methylfuran in an analogous manner, a mixture of two isomers of dl-1,2,2a,3,4,5a-hexahydro-5a-methyl-2-phenylbenzo[h]furo[3,2-c]quinolin-7-ol [Xa and b (R ? H)] was obtained. Likewise, 4-[(p-hydroxybenzylidene)amino]-1-naphthol (IXb) and 4-(p-methoxybenzylidene)amino]-1-naphthol (IXc) gave a mixture of two isomers of dl-1,2,2a,3,4,5a-hexahydro-2-(p-hydroxyphenyl)-5a-methylbenzo[h]furo[3,2-c]quinolin-7-ol [Xa and b (R ? OH)] and dl-1,2,2a,3,4,5a-hexahydro-2-(p-methoxyphenyl)-5a-methylbenzo [h]furo[3,2-c]quinolin-7-ol [Xa and b (R ? OCH₃)], respectively. The condensation of N-(p-methoxybenzylidene)-5-acenaphthenamine (XI) with 2,3-dihydro-5-methylfuran afforded a mixture of two isomers of dl-2,3,3a,4,5,9,10,-11b-octahydro-4-(p-methoxyphenyl)-11b-methylfuro[3,2-c]indeno[1,7-gh]quinoline (XIIa and b). Structural assignments for all of the products were made from NMR spectra. None of these compounds possessed appreciable biological activity.     

A clean synthesis of oxazino[5,6-f]quinolinone and naphtho[1,2-e]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).     

Convenient synthesis of linear pyrano[3,2-g]-, [2,3-g]- and angular pyrano[3,2-f]coumarins from 4[(1,1-dimethyl-2-propynyl)oxy]phenol

An easy preparation of new 4-alkoxycarbonyl angular and linear pyranocoumarins starting from 4-[(1,1-dimethyl-2-propynyl)oxy]phenol and their transformation to the known coumarins xanthyletin, 8,8-dimethylpyrano[3,2-f]chromen-3(8H)-one and 7,7-dimethylpyrano[2,3-g]chromen-2(7H)-one is described.     

Synthesis of methyl derivatives of new polycyclic systems of 4H-furo[3,2-g]pyrrolo[3,2,1-ij]quinolin-4-one,of 1H,5H- and 3H,5H-benzofuro[5,6,7-ij]quinolizin-5-one

The synthesis of new tetracyclic 4H-furo[3,2-g]pyrrolo[3,2,1-ij]quinolin-4-ones, 15–17 , 1H,5H-benzofuro[5,6, 7-ij]quinolizin-5-ones, 18–20 , and 3H,5H-benzofuro[5,6,7-ij]quinolizin-5-ones, 21–23 is described. The planarity of the structure of benzofuroquinolizin-5-one 18 was determined by X-ray single-crystal analysis.     

Synthesis of novel fluorinated 4H-benzo[h]chromen-4-one and 4H-pyrano[3,2-h]quinolin-4-one derivatives

New fluorinated 4H-benzo[h]chromen-4-one and 4H-pyrano[3,2-h]quinolin-4-one derivatives are obtained in moderate to good yields, through a one-pot aldolization-intramolecular S_NAr process, from the tetrakis(dimethylamino)ethylene (TDAE) mediated reductive cleavage of two N,N-dimethylamino-bis-chlorodifluoroacetyl substrates in the presence of heteroaryl aldehydes.     

水相中2-氨基-4-芳基-5,6-二氢化-4H-吡喃并[3,2-c]喹啉-5-酮衍生物的合成

以芳亚甲基丙二腈或2-氰基-3-芳基丙烯酸酯和4-羟基喹啉-2-酮为原料, 水为溶剂, 在TEBA(三乙基苄基氯化铵)催化下90 ℃, 合成了2-氨基-4-芳基-5,6-二氢化-4H-吡喃[3,2-c]喹啉-5-酮衍生物. 和其它方法相比, 该反应具有反应条件温和, 产率高(87%～96%)和环境友好等优点. 产物的结构通过熔点, IR, ¹H NMR和元素分析表征. 化合物3m的结构通过X单晶衍射分析确证.     

Synthesis of Some 1,3-Thiazole, 1,3,4-Thiadiazole, Pyrazolo[5,1-c]-1,2,4-triazine, and 1,2,4-Triazolo[5,1-c]-1,2,4-triazine Derivatives Based on the Thiazolo[3,2-a]benzimidazole Moiety

3-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile was synthesized by refluxing ethyl 3-methylthiazolo[3,2-a]benzimidazole-2-carboxylate, acetonitrile, and sodium hydride. Treatment of 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile with phenyl isothiocyanate, in the presence of KOH, furnished the corresponding potassium salt which was converted into thioacetanilide derivative upon neutralization. The thioacetanilide derivative reacts with α-chloroacetylacetone and ethyl α-chloroacetoacetate to give the 1,3-thiazole derivatives, while the reaction of the'thioacetanilide derivative with hydrazonyl chlorides gave 1,3,4-thiadiazole derivatives. On the other hand, 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile reacted with the diazonium salt of both 3-phenyl-5-amino-(1H)-pyrazole and 5-amino-l,2,4-(1H)-triazole to afford the corresponding hydrazones. The latter hydrazones underwent an intramolecular cyclization upon boiling in pyridine to give pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives. Moreover, the behavior of thiazolo[3,2-a]benzimidazol-3(2H)-one towards phenyl isothiocyanate followed by the reaction with α-chloroketones or hydrazonyl chlorides was investigated. Some of the latter compounds exhibited moderate effects against some bacterial and fungal species.     

Synthesis of 2,3-Dihydrothiazolo[3,2-a]pyrimidin-5-ones by a Michael-type Tandem Reaction

Although various thiazoles are known in literature for their biological and pharmacological properties only a few multi-step synthesis pathways for the preparation of thiazolo[3,2-a]pyrimidinones have been reported, which are tedious and time-consuming. An alternative synthesis pathway is described, which allows the preparation of 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-ones in a one-step process based on a Michael-type tandem reaction. By heating of 2-thiobarbituric acid with ethyl 4-bromocrotonate in ethanol at 60°C for 2 h, a 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-one was obtained in 73% yield, whereas carrying out the reaction at room temperature results in the formation of an unstable unsaturated ester. The structures of both, the α,β-unsaturated ester as well as the 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-one were confirmed by NMR spectroscopy. Additionally, the structure of the 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-one was investigated by single-crystal X-ray analysis. The described approach offers a significant improvement over previously reported synthesis pathways because it allows the simple preparation of 2,3-dihydrothiazolo[3,2-a]pyrimidin-5-ones with good yields in a one-step reaction.     

Synthesis of Some 1,3-Thiazole, 1,3,4-Thiadiazole, Pyrazolo[5,1-c]-1,2,4-triazine, and 1,2,4-Triazolo[5,1-c]-1,2,4-triazine Derivatives Based on the Thiazolo[3,2-a]benzimidazole Moiety

Summary. 3-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile was synthesized by refluxing ethyl 3-methylthiazolo[3,2-a]benzimidazole-2-carboxylate, acetonitrile, and sodium hydride. Treatment of 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile with phenyl isothiocyanate, in the presence of KOH, furnished the corresponding potassium salt which was converted into thioacetanilide derivative upon neutralization. The thioacetanilide derivative reacts with α-chloroacetylacetone and ethyl α-chloroacetoacetate to give the 1,3-thiazole derivatives, while the reaction of the'thioacetanilide derivative with hydrazonyl chlorides gave 1,3,4-thiadiazole derivatives. On the other hand, 3-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-3-oxopropionitrile reacted with the diazonium salt of both 3-phenyl-5-amino-(1H)-pyrazole and 5-amino-l,2,4-(1H)-triazole to afford the corresponding hydrazones. The latter hydrazones underwent an intramolecular cyclization upon boiling in pyridine to give pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives. Moreover, the behavior of thiazolo[3,2-a]benzimidazol-3(2H)-one towards phenyl isothiocyanate followed by the reaction with α-chloroketones or hydrazonyl chlorides was investigated. Some of the latter compounds exhibited moderate effects against some bacterial and fungal species.     

Convenient synthesis of fused pyrano[3,2-h]- and furo[3,2-h]benzo[f]coumarins from naphthalene-2,3-diol

The treatment of 8-propargyloxy-benzo[f]coumarin with boron trifluoride diethyl etherate in N,N-dimethylformamide under reflux or MW irradiation resulted in pyrano[3,2-h]benzo[f]coumarin, while the furo[3,2-h]benzo[f]coumarin is received from the treatment with N-methylformamide under MW irradiation.     

A green, efficient, and rapid procedure for the synthesis of 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one derivatives catalyzed by ammonium acetate

A green, efficient, and rapid procedure for the synthesis of 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one derivatives has been developed by one-pot condensation of 4-hydroxyquinolin-2(1H)-one, aldehyde, and malononitrile in the presence of ammonium acetate in EtOH. This method has the advantages of operational simplicity, mild reaction conditions, short reaction time, and little environmental impact.     

2-Benzyliden-2H-thieto[3,2-b]quinoline: a new heterocycle and its rearrangement to 2-phenylthieno[3,2-b]quinoline

Synthesis of the strained 2H-thieto[3,2-b]quinoline ring system is reported for the first time. Treatment of (Z)-2-benzyliden-2H-thieto[3,2-b]quinoline derivatives of this heterocycle with base, at reflux in ethanol, causes a novel rearrangement to 2-phenylthieno[3,2-b]quinolines. Indeed, the one-pot reaction of 2-aminobenzaldehydes and (Z)-2-benzylidenethietan-3-one in refluxing basic ethanol leads directly to 2-phenylthieno[3,2-b]quinolines in good yields.     

Quinolizines and indolizines. Part 16 . Synthesis of pyrrolo[3,2,1-ij]quinolin-4-ones with potential fungicidal activity

The synthesis of some derivatives of 1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (pyroquilon) having potential fungicidal activity has been accomplished starting with readily available 6-hydroxy-1,2-dihydro-4-pyrrolo[3,2,1-ij]quinolin-4-ones 3, 7. Functionalization in 6- or 5-position gave rise to the corresponding 6-and 5-substituted derivatives 8-12, 17 and 13-16, 20, 21 respectively. The formation of pyrrolo[3,2,1-ij]-pyrano[3,2-c]quinolines ( 5, 22, 23 ) and their degradation to acyl-substituted derivatives of 7 was studied.