Synthesis of N-substituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones

The synthesis of 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-dione hydrochlorides is reported starting from 1,4-dihydrobenz[g]isoquinoline-3(2H)-ones or ethyl (3-aminomethyl-1,4-dimethoxynaphth-2-yl)acetates. A third strategy relies on the synthesis of the title compounds via an N-protected 2-(3-bromomethyl-1,4-dimethoxynaphth-2-yl)ethylamine. The synthesized 1,2,3,4-tetrahydro-benz[g]isoquinoline-5,10-diones are a new class of quinones, which have not been reported yet.     

Straightforward palladium-mediated synthesis of N-substituted 1,2-dihydrobenz[g]isoquinoline-5,10-diones

Related to our research on structural modifications of pentalongin, the active principle of the medicinal plant Pentas longiflora Oliv., a new synthesis of N-protected 1,2-dihydrobenz[g]isoquinoline-5,10-diones and their 4-methyl derivatives, which represent a new class of compounds, is reported. In both cases, the benz[g]isoquinoline skeleton was constructed by an intramolecular Heck reaction of N-protected 2-((allylamino)methyl)-3-bromo-1,4-dimethoxynaphthalenes and N-protected 2-((allylamino)methyl)-3-bromo-1,4-naphthoquinones, respectively.     

First straightforward synthesis of 2,4-disubstituted benz[g]isoquinoline-3,5,10(2H)-triones, 1,2,3,5-substituted naphtho[3,2,1-de]isoquinoline-4,7-diones, and 6-substituted benzo[h]pyrido[3,4,5-kl]-1,2,3,4-tetrahydroacridine-5,8-diones

Structural modifications to the benz[g]isoquinoline skeleton of N-substituted benz[g]isoquinoline-3,5,10(2H)-triones were envisaged in order to make future SAR studies possible for this type of bioactive compounds. Several N-substituted benz[g]isoquinoline-3,5,10(2H)-triones were converted to novel 2,4-substituted benz[g]isoquinoline-3,5,10(2H)-triones, new tetracyclic 1,2,3,5-substituted naphtho[3,2,1-de]isoquinoline-4,7-diones, and 6-substituted benzo[h]pyrido[3,4,5-kl]-1,2,3,4-tetrahydroacridine-5,8-diones. All the synthesized target compounds represent new heterocyclic systems, which were previously undescribed in the literature.     

Investigation towards an efficient synthesis of benzo[g]isoquinoline-1,5,10(2H)-triones

As part of our research on 2-aza analogues of pentalongin, the active principle of Pentas longiflora Oliv., the first synthesis of 2,3-disubstituted benzo[g]isoquinoline-1,5,10(2H)-triones via 3,4-disubstituted 6-hydroxybenzo[g]furo[4,3,2-de]isoquinoline-2,5(4H)-diones as the key intermediates is reported. The latter compounds have been prepared by treating 2-methoxycarbonyl-1,4-naphthoquinone with N-substituted enaminoesters under acidic conditions. These reagents are easily accessible from readily available 1,4-dihydroxy-2-naphthoic acid, β-ketoesters and primary amines. Finally, a short synthesis of substituted benzo[g]isoquinoline-1,5,10(2H)-triones is achieved by an oxidative addition of N-substituted enaminoesters onto methyl 1,4-dihydroxynaphthalene-2-carboxylate.     

New and highly efficient synthesis of 3-substituted 1-hydroxybenz[g]isoquinoline-5,10-diones

A new and efficient strategy for the synthesis of 3-substituted 1-hydroxybenz[g]isoquinoline-5,10-diones by reaction of 2-methoxycarbonyl-1,4-naphthoquinone with different pyridinium salts under Kröhnke conditions is disclosed. This one-step reaction was found to be dependent on the substitution pattern of the aromatic nucleus in the pyridinium salts.     

Synthesis of a novel tetrahydroisoquinoline pentacyclic framework

N-Acyliminium cyclization of 6-substituted (3R^∗,6R^∗,11aS^∗)-3-arylmethyl-pyrazino[1,2-b]isoquinoline-1,4-diones gave with very good yields a novel tetrahydroisoquinoline pentacyclic core framework (29), while this reaction failed in all-cis-isomers to give instead conjugated enamines by deprotonation. Electronic and steric factors that govern the approach to both diastereomers from 6-substituted pyrazino[1,2-b]isoquinoline-1,4-diones have been studied.     

Short stereocontrolled synthesis of trans and cis-tetrahydro-pyrazinoisoquinolinediones

Addition of aldehyde dimethyl acetals (here acetaldehyde) to unisolated O-trimethylsilyl derivatives of 1-acetyl-3-arylmethylpiperazine-2,5-diones (here 2,5-dimethoxyphenyl), in the presence of TMSOTf as the catalyst, gave nearly quantitatively the corresponding N-methoxyalkyl derivatives which, under acidic treatment, gave in very good yield through a Pictet-Spengler-type reaction involving N-acyliminium cations (6S*,11aR*)-2-acetyl-6-alkyl-3,6,11,11a-tetrahydro-2H-pyrazino[1,2-b]isoquinoline-1,4-diones. Epimerization of the 11a-stereocentre was accomplished by radical bromination, spontaneous hydrobromide elimination and catalytic hydrogenation, to give the (6S*,11aS*)-isomers. We propose these compounds as precursors of tetrahydroisoquinoline antitumour antibiotics.     

Original synthesis of 2-substituted-4,11-dimethoxy-1-(phenylsulfonyl)-2,3-dihydro-1H-naphtho[2,3-f]indole-5,10-diones using TDAE and Cu-catalyzed reaction strategy

We report herein an original and rapid synthesis of 2-substituted-4,11-dimethoxy-1-(phenylsulfonyl)-2,3-dihydro-1H-naphtho[2,3-f]indole-5,10-diones by TDAE mediated synthesis of N-benzylsulfonamides followed by an intramolecular N-arylation using Cu-catalyzed system.     

Synthesis of 1-substituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones

1,2-Disubstituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones are prepared for the first time through an activated Pictet-Spengler reaction of the corresponding imines of 2-(1,4-dimethoxynaphth-2-yl)ethylamine in the presence of an acyl chloride and AlCl(3) followed by an oxidation with silver(II) oxide in nitric acid. Depending on the reaction conditions the N-trichloroacetyl protecting group could be cleaved off, converted to an N-methoxycarbonyl group or transformed to an N-(2-oxoacetamide) moiety. The synthesized 1,2-disubstituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones constitute a new class of quinones, which has not been reported yet.     

Pictet Spengler-type reactions in 3-arylmethylpiperazine-2,5-diones. Synthesis of pyrazinotetrahydroisoquinolines

The behavior of aldehydes and acetals as N-alkylating agents of 1-acetyl-3-arylmethylpiperazine-2,5-diones and the subsequent cyclization of the N-alkylated products was studied. Use of paraformaldehyde in different reaction conditions gave 6-unsubstituted 3,6,11,11a-tetrahydro-2H-pyrazino[1,2-b]isoquinoline-1,4-diones and, in some cases, benzo[f]pyrazino[1,2-c]1,3-oxazepine-1,4-diones. Succesful reactions with benzaldehyde required a first activation of the lactam function and a catalyzed N-alkylation with the aldehyde dimethyl acetal. The isolated O,N-amidoacetals thus obtained were submitted to a diastereoselective Pictet Spengler-type reaction that worked with arenes at several degrees of ring activation and with thiophene to give 6-phenylpyrazinoisoquinolinediones and the corresponding thieno analog.     

Solvent-free sonochemical one-pot three-component synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones

A rapid and efficient one-pot three-component protocol for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones 4 and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 6 has been developed by domino coupling of phthalhydrazide, 1,3-diketones, and aldehydes under solvent-free conditions at 80 °C as well as under solvent-free ultrasound irradiation at room temperature promoted by (S)-camphorsulfonic acid.     

Synthesis of regioisomeric difluoro- and 8-chloro-9- fluorobenz [g] isoquinoline-5,10-diones and SNAr displacements studies by diamines: bis(aminoalkyl)aminobenz[g] isoquinoline-5,10-diones

Convenient pathways have been developed for the synthesis of 6,7−, 6,8-, 7,9- and 8,9-difluorobenz[g] isoquinoline-5,10-diones and 8-chloro-9-fluorobenz [g] isoquinoline-5,10-dione. The crucial step in these synthesis involved the Ni-catalyzed coupling of the difluoro- or chlorofluorobenzylic zinc bromides with ethyl 3-chloroisonicotinate or ethyl 4-chloronicotinate. The reactions of the 6,7- or 8,9-difluoro regioisomers with N,N-dimethylethylenediamine led to quaternary salts which were formed by intramolecular displacements from the initial mono displacement products. These cyclizations could be obviated with the use of 3-dimethylaminopropylamine in the displacements which led to the desired bis (aminoalkyl) amino substitution products. Treatment of 8-chloro-9-fluorobenz [g] isoquinoline-5,10-dione with N,N-dimethylethylenediamine led to the regioselective displacement of fluoride. Treatment of this mono substitution product with excess N,N-dimethylethylenediamine led only to the intramolecular cyclization product which was also obtained by reaction of 8,9-difluorobenz[g] isoquinoline-9,10-dione with N,N-dimethylethylenediamine. The 6,8- and 7,9-difluoro analogues on treatment with N,N-dimethylethylenediamine or 3-dimethylaminopropylamine led to the expected bis substitution products.     

Thermal decomposition of 2-amino-3-aziridino-1,4-naphthoquinones

The course of the thermal decomposition of various 2-amino-3-substituted aziridino-1,4-naphthoquinones (Ia-g) was investigated. In all the cases, the thermal decomposition gave variable amounts of 2,3-diamino-1,4-naphthoquinone (II) and of substituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxaline-5,10-diones (IIIa-g) with complete stereospecificity. The decomposition of the aziridines Ib,f also gave significative amounts of 2-amino-3-allylamino-1,4-naphthoquinones (IVb,f). In the case of 2-amino-3-(2′-phenyl-3′-ethylaziridino)-1,4-naphthoquinone (Ig), the formation of trans-1-phenyl-1-butene (V), 2-(1-phenylpropyl)-1H-naphtho-imidazole-4,9-dione (VI), 2-phenyl-3-ethyl-3,4,5,10-tetrahydrobenzo[g]quinoxaline-5,10-dione (VII), 2-phenyl-3-ethyl-5,10-dihydrobenzo[g]quinoxaline-5,10-dione (VIII), and a mixture of cis- and trans-4H-2,3,5,6-tetra-hydro-2-phenyl-3-ethyl-5-iminonaphtho[1,2-b]oxazin-6-one (IX) also occurred. Hypotheses concerning the mechanism and the steric course of this reaction are given. The reaction is a general method for the stereospecific synthesis of 2,3-disubstituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxalines.     

A highly efficient green synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives and their photophysical studies

A task-specific ionic liquid, [Bmim]OH, has been used for an efficient synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones by one-pot cyclocondensation reaction of phthalhydrazide, aromatic aldehydes, and malononitrile or ethyl cyanoacetate under microwave irradiation. The advantages of this method include the use of green catalyst, no organic solvent, easy work-up and excellent yields. The photophysical properties for some 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives have been investigated for the first time.     

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.     

Acid-induced rearrangement of cycloadducts from N-aryl itaconimides and 1,3-diphenylisobenzofuran

Treatment of several Diels–Alder adducts of N-aryl itaconimides and 1,3-diphenylisobenzofuran with a strong acid triggers a skeletal rearrangement resulting in 2-aryl-6,10b-diphenylbenzo[h]isoquinoline-1,3(2H,10bH)-diones.     

Synthesis and antibacterial studies of azodispersed dyes derived from 2-(thiazol-2-yl)phthalazine-1,4-diones

Abstract  

A dibenzobarrelene derivative was used as key intermediate for the synthesis of 2-(4-(methyl/phenylthiaz-ol-2-yl)-2,3,4a,5,10,10a-hexahydro-5,10-benzenobenzo[g]phthalazine-1,4-diones. These compounds were coupled with the appropriate diazonium chlorides to give the corresponding 5-(arylazo)thiazole derivatives. The synthesized dyes were applied to polyester as disperse dyes, and their antibacterial, color measurement, and fastness properties were evaluated.     

Electrocatalytic multicomponent assembling of phthalhydrazide,aldehydes and malononitrile: An efficient approach to 1H-pyrazolo[1,2-b]phthalazine-5,10-diones

Electrocatalytic multicomponent transformation of phthalhydrazide, aromatic aldehydes and malononitrile in n-propanol in an undivided cell in the presence of sodium bromide as an electrolyte leads to 1H-pyrazolo[1,2-b]phthalazine-5,10-diones in short reaction times (4–8 min) and high yields (85–98%) at room temperature. The developed efficient electrocatalytic approach to the corresponding 1H-pyrazolo[1,2-b]phthalazine-5,10-diones is beneficial from the viewpoint of diversity-oriented large-scale processes and represents a new example of the ecologically pure synthetic concept for electrocatalytic multicomponent reactions strategy.     

Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-carbethoxy-6-(trifluoromethyl)-2-pyrones and their reaction with sodium azide leading to new carbostyril derivatives

Treatment of ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates, prepared from 4,4,4-trifluorobutane-1,3-diones, PCl₅ and sodium diethyl malonate, with sulfuric acid afforded the intramolecular Friedel–Crafts acylation products, 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones, from which 2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-diones were obtained via the Schmidt reaction in moderate yields. The latter reacted with sodium azide to give 2-oxo-4-(5-trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acids in good yields.     

One pot conversion of azido arenes to N-arylacetamides and N-arylformamides: synthesis of 1,4-benzodiazepine-2,5-diones and fused [2,1-b]quinazolinones

Sodium iodide in acidic media has been employed for the synthesis of N-arylformamides and N-arylacetamides. The NaI/acetic acid reagent system has also been extended for the synthesis of 1,4-benzodiazepine-2,5-diones, pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones, and fused [2,1-b]quinazolinones.