Condensed isoquinolines. 19. Synthesis of 1′-R-spiro[6a,11b-diazabenz[e]aceanthrylene-6(7H),4′ (1′H)-pyridine]-5,7(12H)-diones

During acylation of 7-isonicotinoyl-6,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one or its alkylation followed by treatment with organic bases, spirocyclization occurs with formation of derivatives of a novel heterocyclic system: 1′-acyl-and 1′-alkylspiro[7H,12H-6a,11b-diazabenz[e]aceanthrylene-6(5H),4′(1′ H)-pyridine]-5,7-diones. We have studied the spectral properties of the synthesized spirans. We have shown that 7-nicotinoyl-6,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one does not undergo an analogous reaction of repeated acylation, while treatment of its quaternary salt with bases leads to a complex mixture of unidentified products. For Communication 18, see [1]. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 113–122, January, 2006.     

Condensed Isoquinolines. 10. Borohydride Reduction in the 5H-Isoquino[2,3-a]quinazolin-5-one Series

Borohydride reduction in a series of 7-benzyl- and newly synthesized 7-arylmethylene-7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones leads stereoselectively to erythro-7-benzyl-6,6a,7,12-tetrahydro-5H-isoquino[2,3-a]quinazolin-5-ones. 7,7-Disubstituted 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones are inert to the action of sodium borohydride, but spiro[5H-isoquino[2,3-a]quinazolin-7(12H),2'-indane]-5-one is reduced under rigid conditions to 6,6a-dihydrospiro[5H-isoquino[2,3-a]quinazolin-7(12H),2'-indan]-5-one. 7-Acetyl- and 7-benzoyl-6,11-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones are converted in an aqueous alcoholic solution of sodium borohydride to the previously described 6,6a,7,12-tetrahydro-5H-isoquino[2,3-a]quinazolin-5-one. The structure and special features of the conformational behavior of the reduction products obtained were demonstrated by ¹H NMR spectroscopy.!     

Condensed isoquinolines 24. Reaction of 6,11-dihydro-13H-isoquino[3,2-<Emphasis Type="Italic">b</Emphasis>]quinazolin-13-one with carbonyl compounds

The reaction of 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one with carbonyl compounds occurs at the C₍₆₎ and/or N₍₅₎ atoms depending on the nature of the reagent and the conditions. Condensation with aldehydes gives 6-arylidene-6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-ones. Acylation using acid anhydrides or acid chlorides gave 5-acyl-, 6-acyl-, and 5,6-diacyl-5,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-ones depending again on the reaction conditions. Acylation using chloroacetyl chloride is accompanied by an intramolecular alkylation to give 7H,8H-2a, 7a-diaza-cyclopenta[f,g]naphthacene-1,7(2H)-dione. Phenyl isocyanate gave the derivative containing a CONHPh group at position 6. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1509–1520, October, 2007.     

Condensed isoquinolines. 21. Condensation of <Emphasis Type="Italic">o</Emphasis>-bromomethylphenylacetonitrile with substituted anthranilic acids

The reaction of substituted anthranilic acids and esters with o-bromomethylphenylacetonitrile give 2,3-R,R¹-7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one hydrobromides. It was found that 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones can exist in the two tautomeric imine and enamine forms. The tautomeric equilibrium position depends on the nature and position of the substituent in the quinazoline fragment. The borohydride reduction, oxidation, and reaction of 2,3-R,R¹-7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones with electrophilic reagents has been studied. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 562–573, April, 2007.     

Condensed isoquinolines 25. Alkylation of 6,11-dihydro-13H-isoquino[3,2-<Emphasis Type="Italic">b</Emphasis>]quinazolin-13-one

Interaction of 6,11-dihydro-13H-isoquino[2,3-b]quinazolin-13-one with alkylating agents occurs at two positions depending on their nature and the reaction conditions-at C₍₆₎ or N₍₅₎. Fusion with methyl tosylate leads to 5-methyl-13-oxo-6,13-dihydro-11H-isoquino[3,2-b]quinazolin-5-ium salts, while interaction with benzyl halides in the presence of i-PrONa gave 6-benzyl-and 6,6-dibenzyl-6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-ones. Alkylation with olefins led to two types of products. In the case of maleinimides and maleic acid anhydride Michael adducts at C₍₆₎ were formed and in the case of cyanocinnamic acid esters the reaction was accompanied by intramolecular acylation at N₍₅₎ to give 1-aryl-3,9-dioxo-3H,9H,11H-benzo[5,6][1,8]naphthyridino[1,8-ab]quinazoline-2-carbonitrile. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.11, 1698–1708, November 2007.     

Condensed isoquinolines 23. Reaction of <Emphasis Type="Italic">o</Emphasis>-bromomethylphenyl-acetonitrile with anthranilic acids: Synthesis of 6H, 12H,17H-dibenzo[3,4:6,7][1,8]-naphthyridino[1,8-<Emphasis Type="Italic">ab</Emphasis>]quinazoline-6,17-diones

The direction of the reaction of anthranilic acids with o-bromomethylphenylacetonitrile upon fusion depends on the temperature and nature of the substituent in the anthranilic acid. The reaction may lead to three types of products: Derivatives of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones below 150°C and to 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one or derivatives of 6H,12H,17H-dibenzo[3,4:6,7][1,8]naphthyridino[1,8-ab]quinazoline-6,17-diones above 150°C depending on the nature of the substituent in the anthranilic acid. A study was carried out on the mechanism for the formation of 6H,12H,17H-dibenzo[3,4:6,7][1,8]naphthyridino[1,8-ab]quinazoline-6,17-diones, which permitted the preparation of 6-(4-methylphenyl)-6,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1059–1067, July, 2007.     

Alkylation and reduction reactions in the isoquino[2,3-a]quinazoline series

Protonation and methylation of 5-oxo-7,12-dihydro-5H-isoquino[2,3-a]quinazoline occur at the N₍₆₎ atom, while methylation of 5-oxo- and 6-methyl-5-oxo-6,6a,7,12-tetrahydro-5H-isoquino[2,3-a]quinazolines takes place at the N₍₁₃₎ atom; the degree of stereoselectivity varies depending on the presence of a substituent attached to N₍₁₃₎. Based on PMR spectral analysis utilizing the nuclear Overhauser effect, we have established the structure and studied the conformational behavior of the tosylate derivatives of cis-13-methyl-, trans-13-methyl-, and cis-6,13-dimethyl-5-oxo-6,6a,7-12-tetrahydro-5H-isoquino[2,3-a]quinazolinium ions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 389–394, March 1991,     

Condensed isoquinolines 31. Reaction of 5-aryl-3-halo-12H-isoquino[2,3-a]quinazolines with electrophilic reagents

Treatment of 5-aryl-3-halo-12H-isoquino[2,3-a]quinazolines with electrophilic reagents readily forms their oxidation products. Acylation of the 3-chloro-5-phenyl-7,12-dihydroisoquino[2,3-a]quinazolinium perchlorate with Ac₂O in the presence of pyridine gave the product of electrophilic substitution at the C-7 atom 1-(3-chloro-5-phenyl-12H-isoquino[2,3-a]quinazolin-7-yl)-1-ethanone. By the same route phenacyl bromides react with the anhydro base 1 to give 5-aryl-7-(2-aryl-2-oxoethyl)-3-halo-isoquino[2,3-a]quinazolin-13-ium bromides. These salts readily react with nucleophilic reagents to form the products of addition at the C-12 atom. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1044–1052, July, 2008.     

Condensed isoquinoline. 5. Reaction of the 6-methyl-5-oxoisoquino[2,3-a] Quinazolinium cation with certain nucleophiles

It has been shown that nucleophilic reagents react with the 6-methyl-5-oxoisoquino[2,3-a]quinazolinium cation at the C₍₂₎ atom. The structure of the reaction product is determined by the type of reagent. On reaction with sodium borohydride and secondary amines, 12H- and 12-dialkylamino-12H-6-methyl-5-oxo-5, 6-dihydroisoquino[2,3-a]quinazolines are formed. In the case of primary amines the reaction is accompanied by fission of the C₍₁₂₎-N_(t3) bond with the formation of 2-[o-(N-alkylformimidoyl)-benzyl]-3-methyl-4-oxoquinazolines.See [1) for the preceding communication.T. G. Shevchenko Kiev University, Kiev 252017. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 522–526, April, 1995. Original article submitted March 24, 1995.     

Condensed isoquinolines. 20. Characteristic features of thermal rearrangement of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one to form 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one

We studied the dependence of the direction of conversions for salts of angular 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one on temperature and the nature of the anion: heating in high-boiling solvents leads either to aromatization of the heterosystem or to the rearrangement product, the linear 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one. When its hydrobromide is heated in high-boiling solvents, along with dimerization of the linear isomers, processes of oxidation at the positions 6 and 11 of the heterosystem occur. The dimer obtained in the reaction with morpholine is readily cleaved, with formation of a 6-(4-morpholyl)-substituted linear compound. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 430–439, March, 2007.     

Condensed isoquinolines 30. Acylation and alkylation of 5,13-dihydro-11H-isoquino-[3,2-<Emphasis Type="Italic">b</Emphasis>]quinazolin-11-one

It was shown that 6-acyl-5,13-dihydro-11H-isoquino[3,2-b]quinazolin-11-ones are formed when 5,13-dihydro-11H-isoquino[3,2-b]quinazolin-11-one is heated with the chlorides and anhydrides of carboxylic acids in the presence of bases (pyridine, NaOAc) while 5-acyl-5,13-dihydro-11H-isoquino[3,2-b]quinazolin-11-ones are formed in the presence of NaH. In the presence of NaH 6-acyl-5,13-dihydro-11H-isoquino[3,2-b]quinazolin-11-ones form the products from acylation and alkylation at position 5. The action of heat on 5,13-dihydro-11H-isoquino[3,2-b]quinazolin-11-one in oxalyl chloride leads to 7H,8H-2a,7a-diazacyclopenta[fg]naphthacene-1,2,8-trione. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 741–750, May, 2008.     

Condensed isoquinolines 33*. Synthesis of 1′-R-spiro-[7H,8H-2a,7a-diazacyclopenta-[fg]naphthacene-2,4′-(1′H)-pyridine]-1,8(2H)-diones

Heating 5,13-dihydro-11H-isoquino[3,2-b]quinazolin-11-one with isonicotinoyl chloride in pyridine gives 6-isonicotinoyl-5,13-dihydro-11H-isoquino[3,2-b]quinazolin-11-one. The 1-alkyl-4[(11-oxo-5,13-dihydro-11H-isoquino[3,2-b]quinazolin-6-yl)carbonyl]pyridinium iodides obtained by alkylation of 6-isonicotinoyl-5,13-dihydro-11H-isoquino[3,2-b]quinazolin-11-one using alkyl iodides in the presence of NaH are converted to 1′-R-spiro[7H,8H-2a,7a-diazacyclopenta[fg]naphthacene-2,4′(1′H)-pyridine]-1,8(2H)-diones. The chemical and spectroscopic properties of the spiro compounds obtained were studied. For Communication 32 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 52–58, January, 2009.     

Condensed isoquinolines 29. Oxidation reactions of 5-aryl-7,12-dihydroisoquino[2,3-a]quinazolinium salts

5-Aryl-7,12-dihydroisoquino[2,3-a]quinazolinium perchlorates are readily oxidized by atmospheric oxygen to form the products of oxidative coupling 5,5′-bis(aryl)-3,3′-dihalo[7,7′]bi[isoquino-[2,3-a]quinazoline-13,13′-diylium perchlorates. Heating 3-chloro-5-phenyl-7,12-dihydroisoquino-[2,3-a]quinazolinium perchlorate in nitrobenzene gives the 3-chloro-5-phenylisoquino[2,3-a]quinazolin-13-ium perchlorate. The aromatic 5-arylisoquino[2,3-a]quinazoline derivatives obtained react with nucleophilic reagents to form addition products at the C-12 atom. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 428–439, March, 2008.     

Condensed Isoquinolines. 17. Enamine Properties of Benzimidazo[1,2-b]isoquinolin-11(5H)-one in Alkylation Reactions

The alkylation of benzimidazo[1,2-b]isoquinolin-11(5H)-one has been studied. This occurs at N₍₅₎ or C₍₆₎ depending on the type of alkylating agent and the reaction conditions. It was shown that C₍₆₎ alkylation is effected in reactions with reactive alkyl halides. A repeat alkylation occurs preferentially at the same position. Interaction with o-xylylidene dibromide leads to spiro[benzimidazo[1,2-b]-isoquinolin-6,2'-indan]-11-one and 1,6-dihydro-11H-6a,11b-diazobenzo[b]benzo[5,6]cyclohepta[1,2,3-l,m]fluoren-11-one, which are derivatives of new heterocyclic systems.     

Synthesis of Novel 2-Methylsulfanyl-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one and Derivatives

A novel 2-methylsulfanyl-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one was synthesized using dimethyl-n-cyanoimidodithiocarbonate and 2-hydrazinobenzoic acid as building blocks. Chemical transformation of the inherent lactam moiety in the targeted 2-methylsulfanyl-[1,2,4]triazolo[1,5-a]quinazolin-5-one offered access to a variety of derivatives.     

Condensed isoquinolines 26. Oxidation reactions of 6,11-dihydro-13H-isoquino-[3,2-<Emphasis Type="Italic">b</Emphasis>]quinazolin-13-one derivatives

Oxidation of the hydrobromide of 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one with dimethyl sulfoxide leads to 11-hydroxy-11H-isoquino[3,2-b]quinazoline-6,13-dione, and with hydrogen peroxide to the hydrobromide of 2-[(4-oxo-3,4-dihydro-2-quinazolinyl)carbonyl]benzoic acid. Salts of 5-and 6-alkyl-substituted isoquino[3,2-b]quinazolines are readily oxidized on boiling in nitrobenzene, which leads to aromatization of the isoquino[3,2-b]quinazoline system to 5-methyl-13-oxo-5H,13H-isoquino[ 3,2-b]quinazolinium perchlorate and 6-benzyl-13H-isoquino[3,2-b]quinazolin-13-one. The structures of the dehydrogenation products were established from ¹H NMR and UV spectra. The interaction of the obtained compounds with NaBH₄ has been studied. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1833–1840, December, 2007.     

Condensed isoquinolines 22. Synthesis and properties of 6,11-dihydro-13H-isoquino-[3,2-<Emphasis Type="Italic">b</Emphasis>]quinazolin-13-ones

The reaction of 3-haloanthranilic acids with o-bromomethylphenylacetonitrile gave 2-(2-carboxy-6-halophenyl)-1,4-dihydro-3(2H)-isoquinolinium bromides. 2-Chlorophenylisoquinolinium bromides are readily converted into 4-R-6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-ones by heating >145°C, but 2,4-dibromophenylisoquinolinium bromide only on fusing with anthranilic acid. The effect of the nature and position of substituents in the quinazoline fragment of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones on the rate of the rearrangement into 6,11-dihydro-13H-isoquino[3,2-b]quinazol-13-ones has been studied. The oxidation and borohydride reduction of 6,11-dihydro-13H-isoquino[3,2-b]quinazol-13-ones has been studied. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, 899–909, June, 2007.     

Studies of imidazo[1,2-a]benzimidazole derivatives. 21. Synthesis of haloketones in the imidazo[1,2-a] benzimidazole series

Methods for the synthesis of imidazo[1,2-a]benzimidazole haloketone derivatives have been investigated. It has been found that -bromoketone derivatives of this heterocycle can be prepared either by bromination of 3-acylimidazo[1,2-a]benz-imidazoles with bromine in glacial acetic acid or by acylation of 3-unsubstituted imidazo[1,2-a]benzimidazoles with haloanhydride derivatives of -bromoalkanoic acids. Treatment of imidazo[1,2-a]benzimidazoles with 3-chloropropionyl chloride results in the formation of imidazo[1,2-a]benzimidazolyl-3-propionyl chloride and bis(imidazo[1,2-a]benzimidazolyl)propan-3-one derivatives as side products. Reaction of 2-phenylimidazo[1,2-a]benzimidazoles with 3-bromopropionic acid in polyphosphoric acid gives benzocyclohepten[5,6:4,5]imidazo[1,2-a]benzimidazole derivatives.For Communication 20, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 339–345, March, 1986.     

Condensed imidazo-1,2,4-azines. 21. Synthesis of 2-arylfuro(pyrrolo-, thieno-)[2,3-e]-1,2,4-triazino[2,3-a]benzimidazoles by cyclization of 2-aroyl-1,2,4-triazino[2,3-a]benzimidazol-4H-3-ones

2-[(-Ethyl-, arylimino)phenethyl]-1,2,4-triazino[2,3-a]benzimidazoles were obtained by reaction of 2-aroylmethyl-1,2,4-triazino[2,3-a]benzimidazol-4H-3-ones with ethyl(aryl)amines or urea. By the action of phosphorus oxychloride, these benzimidazoles cyclize into substituted pyrrolo[2,3-e]-1,2,4-triazino[2,3-a]benzimidazoles, heating of which in polyphosphoric acid leads to the formation of furo[2,3-e]-1,2,4-triazino[2,3-a]benzimidazoles, while by the action of P₄S₁₀, they are transformed into thieno[2,3-e]-1,2,4-triazino[2,3-a]benzimidazoles.For Communication 20, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1109–1113, August, 1989.     

Cycloaddition in condensed isoindoles 1. Preparation of 2-aryl-3-methyl-4-oxo-3,4-dihydroquinazoline

Reaction of 6-methyl-5,6-dihydroisoindolo[2,1-a]quinazolin-5-one with maleimide derivatives has been studied under conditions of thermodynamic control. X-ray diffraction structural analysis showed that the reaction products are 2{2-[(E)-1-R-2,5-dioxopyrrolidinidenemethyl]phenyl}-3-methyl-4-oxo-3,4-dihydroquinazolines. These products are supposed to be formed by rearrangement of the corresponding Diels-Alder adducts formed involving the isoindole part of the molecule. Taras Shevchenko Kiev University, 252033 Kiev, Ukraine; Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 669–677, May, 1999.