Condensed isoquinolines. 9. Alkylation of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones

The alkylation of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one proceeds at N₍₆₎ or C_(–) depending on the type of alkylating agent and reaction conditions. C_(–)-Alkylation occurs in the presence of base. The secondary alkylation of the 7-alkyl derivatives occurs at the same position under these conditions. Depending on the conditions, the reaction with o-xylylene dibromide leads to spiro[5H-isoquino[2,3-a]quinazolin-7(12H).2-indane]-5-one or 11-oxo-4b,5,10,16-tetrahydro-11H-10a-azonia-15b-azadibenz[a,e]pleiadene bromide, which are derivatives of new heterocyclic systems.Communication 8, see ref. [1].See also Letter to Editor [2].Taras Shevchenko Kiev University, 252017 Kiev, Ukraine. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 643–652, May, 2000.     

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 Imidazo-1,2,4-azines. 31. Synthesis and Chemical Transformations of Substituted 1,2,4-Triazepino[2,3-a]benzimidazoles

By reaction of 1,2-diaminobenzimidazole with 1,3-diketones, acetoacetic ester and its derivatives, we have synthesized substituted 1,2,4-triazepino[2,3-a]benzimidazole and 5H-1,2,4-triazepino[2,3-a]benzimidazol-4-one. By reaction of 5H-2-methyl-1,2,4-triazepino[2,3-a]benzimidazol-4-one with aromatic aldehydes or phenyldiazonium chloride, we have obtained 3-arylidene(phenylazo) derivatives of this compound, and by reaction with P₂S₅ we have obtained 5H-2-methyl-1,2,4-triazepino[2,3-a]benzimidazole-4-thione. We have shown that when reacted with ammonia, primary or secondary amines, the latter forms 4-amino-substituted 2-methyl-1,2,4-triazepino[2,3-a]benzimidazole.     

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.     

Reactions of isomeric 6-methyl-2-methylthio-4cyanomethoxypyrimidine and 6-methyl-2methylthio-3-cyanomethylpyrimidinone-4 with n-nucleophiles

It was found that 6-methyl-2-methylthio-4-cyanomethoxypyrimidine (O-isomer) reacted via the cyano group with ammonia and hydroxylamine to give an amldine and an amidoxime respectively. The O-isomer did not react with either primary or secondary amines under similar conditions, but nucleophilic substitution at position 2 of the O-isomer was effected by converting the 2-methylthio group into a 2-methylsu fonyl. 6-Methyl-2methylthio-3-cyanomethylpyrimidinone-4 (N₃-isomer) formed imidazo[1, 2-a]pyrirnidinones-5 with ammonia and primary amines, 2-amino-6-methyl-3-cyanomethylpyrirrtidinones-4 with secondary amines and either an amidoxime or an imidazo[1, 2-a]pyrimidinone-5 with hydroxylamine, depending on the reaction temperature.Vilnius University. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 703-707, May, 1996. Original article submitted November 3, 1995.     

Condensed isoquinolines. Part 6. Synthesis of 5-aryl-7,12-dihydroisoquino[2,3-a]quinazolinium salts

2-(o-Aroyl)phenyl-1, 4-dihydroisoquinolin-3(2H)-imine hydrobromides have been synthesized by the reaction of o-bromomethylphenylacetonitrile with o-aminobenzophenones. The products were cyclized into 5-aryl-7,12-dihydroisoquino[2,3-a]quinazolinium perhclorates.T. G. Shevchenko University, Kiev 252017. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 664–666, May, 1995. Original article submitted April 15, 1995.     

Hydroxy- and aminomethylation of 1-methyl-2-amino-4-imidazolinone

The corresponding imidazolo[3,2-a]-1,3,5-triazines are formed as a result of the aminomethylation of 1-methyl-2-amino-4-imidazolinone (creatinine) and its 5-benzylidene derivative with paraformaldehyde and primary aliphatic amines. Hydroxymethylation is directed to the C₍₅₎, position of the creatinine heteroring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 767–770, June, 1991.The authors thank A. V. Dogadin for recording and discussing the PMR spectra.     

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.     

Nitrogen and sulfur heterocycles. 45. Dual reactivity of 1,2-dioxo-3a-alkyl-7-chloroimidazolidino[3,2-f]-pyrido[2,3-b]-1,4-thiazines

1,2-Dioxo-3a-alkyl-7-chloroimidazolidino[3,2-f]pyrido[2,3-b]-1,4-thiazines react with o- and p-nitroanilines, alkyl and acyl halides, and heterocyclic amines to give C₍₂₎- and N₍₃₎-substituted 3a-alkyl-7-chloroimidazolidino[3,2-f]pyridol[2,3-b]-1,4-thiazines.For Communication 44, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1688–1693, December, 1987.     

Reactions of 6-Amino-5-Cyano-3-Methyl-1,4-Diphenyl-1H 4H-Pyrano[2,3-C]Pyrazole and its Methanimidate

Reaction of 6-amino-5-cyano-3-methyl-1,4-diphenyl- 1H,4H-pyrano[2,3-c]pyrazole 1 with triethyl orthoformate in acetic anhydride gave its methanimidate 2, which reacts with primary aliphatic and aromatic amines to give 4,6-dihydro-3-methyl-1,4-diphenyl-6- (alkyl)pyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5(lH)- imine 3 and the starting compound 1 , respectively. Treatment of 1 with o-aminophenol gave 5-(2-benzoxalyl)- 1,4-dihydro-3-methyl-1,4-diphenylpyrano[2,3-c]pyrazol- 6-amine 9.     

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.     

Some chemical properties of 2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-one and 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones

We have studied the reaction of 2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-one and 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones with amines, alkylating reagents, and hydrogen peroxide. We have shown that the presence of an aryl substituent at the 2 position of [1,3-thiazino[3,2-a]benzimidazol-4-ones has a substantial effect on the direction of the reactions. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 445–452, March, 2006.     

1,2,4-triazines. 7. Regioselective n2-amination of 3-methylthio-1,2,4-triazin-5(2H)-ones.A novel synthesis of [1,2,4]triazolo[2,3-b][1,2,4]triazinones and -triazine

A regioselective synthesis of 2-aminotriazinones 6a-d is reported, by reaction of 3-methylthio-1,2,4-triazinones 5a-d with O-(2,4-dinitrophenyl)hydroxylamine (2) as an amino-transfer agent. A spectroscopic study and an unequivocal synthesis of 2-amino-4-methyl-6-phenyl-1,2,4-triazinedione ( 11a ) has shown the site of amination to be N2 of the 1,2,4-triazinone ring. Subsequent reaction of 2-amino-1,2,4-triazinones 6a-b with amines, followed by ring closure with aliphatic acids provided [1,2,4]triazolo[2,3-b][1,2,4]triazine-7(1H)ones 13a-e. Conversion of [1,2,4]triazolo[2,3-b][1,2,4]triazinone 13c to unsubstituted [1,2,4]triazolo[2,3-6][1,2,4]triazine (15) was attained.     

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.     

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.     

Synthesis of 7-iodo(arylsulfanyl)methyl-7,8-dihydro-[1,3]thiazolo[2,3-i]purinium pentaiodide (perchlorates) and their transformation into 4-amino-5-(1,3-thiazol-2-yl)imidazole derivatives

Intramolecular electrophilic cyclization of 6-allylsulfanylpurine by the action of iodine and arenesulfenyl chlorides gave 7-iodomethyl-7,8-dihydro[1,3]thiazolo[2,3-i]purin-6-ium pentaiodide and 7-arylsulfanylmethyl-7,8-dihydro[1,3]thiazolo[2,3-i]purin-6-ium perchlorates, respectively. 7-Iodomethyl-7,8-dihydro-[1,3]thiazolo[2,3-i]purin-6-ium iodide reacted with sodium and potassium alkoxides to produce alkyl N-[5-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-4-yl]formimidates, and its reaction with secondary cyclic amines afforded 5-(4-methyl-1,3-thiazol-2-yl)-N-[morpholin-4-yl(or piperidin-1-yl)methylidene]-1H-imidazol-4-amines. Successive treatment of 7-arylsulfanylmethyl-7,8-dihydro[1,3]thiazolo[2,3-i]purin-6-ium perchlorates with sodium acetate and morpholine led to the formation of 5-(4-arylsulfanylmethyl-4,5-dihydro-1,3-thiazol-2-yl)-N-(morpholin-4-ylmethylidene)-1H-imidazol-4-amines.     

Synthesis and some heterocyclization reactions of new diethyl (1,1-difluoro-3,3-dicyano-2-trifluoromethylallyl)phosphonate and ethyl 3,3-dicyano-2-[(diethoxyphosphoryl)difluoromethyl]acrylate

A new CF₂X-analogue of 1,1-bis(trifluoromethyl)-2,2-dicyanoethylene (X = P(O)(OEt)₂), diethyl (1,1-difluoro-3,3-dicyano-2-trifluoromethylallyl)phosphonate, has been synthesized from diethoxyphosphoryl pentafluoroacetone 1. A similar phosphoryl analogue of ethyl 3,3-dicyano-2-trifluoromethylacrylate, ethyl 3,3-dicyano-2-[(diethoxyphosphoryl)difluoromethyl]acrylate, has been obtained from ethyl 3-(diethoxyphosphoryl)-3,3-difluoro-2-oxopropionate 2. By heterocyclization of these new ethylenes with 3-methyl-2-pyrazoline-5-ones, 3(5)-aminopyrazoles, dimedone, 2-aminopyridines, 1-aryl-3-methyl-5-aminopyrazoles, 1,3,3-trimethylisoquinolines, as well as by condensation with anilines and ketones, the difluoromethylphosphonate-substituted derivatives of 1,4-dihydropyrano[2,3-c]pyrazole, 4,5-dihydropyrazolo[1,5-a]pyrimidine, 5,6,7,8-tetrahydro-4H-chromene, 2H-pyrido[1,2-a]pyrimidine, 4,7-dihydro-1H-pyrazolo[3,4-b]pyridine, 1,4-dihydropyridine, 4,5,6,7-tetrahydro-1H-[1]pyrindine, 1,4,5,6,7,8-hexahydroquinoline, and 6,7-dihydro-2H-pyrido[2,1-a]isoquinoline have been obtained in one stage.     

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.     

[3+2] Cycloaddition of Dimethyl Acetylenedicarboxylate, Methyl Acrylate, and Ethyl Acrylate to 4,5-Dihydro-5-methyl-3H-spiro[benz-2-azepine-3,1'-cyclohexane] N-Oxide

The cycloaddition of methyl acrylate and ethyl acrylate to 4,5-dihydro-5-methyl-3H-spiro[benz-2-azepine-3,1'-cyclohexane] N-oxide proceeds without either regiospecificity or stereospecificity. Eight geometrical isomers of spiro[isoxazolidino[3,2-a]benz-2-azepine-5,1'-cyclohexane] were formed, of which several were isolated as pure samples. The cycloaddition of dimethyl acetylenedicarboxylate proceeds stereoselectively, leading to spiro[isoxazolino[3,2-a]benz-2-azepine-5,1'-cyclohexane] with cis arrangement of the protons at C₍₇₎ and C_(11b).     

Condensed isoquinolines 28*. Synthesis and properties of 10a,15b-diazadibenzo[a,e]-pleiaden-11-ones

The reaction of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones with o-xylidene dibromide leads to 11-oxo-4bH,5H,10H,11H,16H-10a-aza-15b-azoniadibenzo[a,e]pleiadene bromides, which are converted to 11-oxo-10H,11H,16H-10a-aza-15b-azoniadibenzo[a,e]pleiadene salts upon oxidation using nitrobenzene. The reaction of these salts with benzylamine leads to 6-{2-[(benzylimino)methyl]phenyl}-7,12-dihydroisoquino[3,2-b][2]benzazepin-14(6H)-ones, which recyclize to 11-oxo-5H,10H,11H-10a-aza-15b-azoniadibenzo[a,e]pleiadene perchlorates upon the action of perchloric acid. The reactions of the 10a,15b-diazadibenzo[a,e]pleiadene salts obtained with NaBH₄ were studied and the structures of the reduction products were determined by spectral methods. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 280–292, February, 2008.