Benzacridines VI.. Functional derivatives of 5,6-dimethylbenz[c]acridine

5,5-Dimethyl-5,6-dihydrobenz[c]acridone has been synthesized by three different routes: a, from a condensation of anthranilic acid with 4,4-dimethyl-1-tetraIone; b, by a catalytic hydrogenation of 2-(o-nitrobenzal)-4,4-dimethyl-1-tetralone oxide followed by an acid catalyzed cleavage of the oxide ring and closure of the nitrogen heterocyclic ring; c, a multi-step process starting with 7-carboxy-5,5-dimethyl-5,6-dihydrobenz[c]acridine. Several new functional derivatives of both 5,5-dimethyl-5,6-dihydrobenz[c]acridine and of 5,6-dimethylbenz[c]acridine were also produced for biological study by others.     

Synthesis of 5,6,7-trimethylbenz[c]acridine

A new potential carcinogenic aromatic heterocyclic compound, 5,6,7-trimethylbenz[c]acridine ( 1 ), has been synthesized from the known 5,5-dimethyl-6-keto-5,6-dihydrobenz[c]acridine ( 4 ) using a series of reactions which includes an interesting new type of 1,4-conjugate addition cmploying lithium dimethylcopper.     

Synthesis of 2-(3-coumarinyl)pyrrolo[2,1-<Emphasis Type="Italic">a</Emphasis>]isoquinoline derivatives by the chichibabin reaction

2-(3-Coumarinyl)-5,5-dimethyl-5,6-dihydropyrrolo[2,1-a]isoquinolines were synthesized by the Chichibabin reaction of 3,3-dimethyl-1,2,3,4-tetrahydroisoquinoline with 3-bromoacetylcoumarin. Derivatives of benzo[f]isoquinoline and benzo[f]coumarin were obtained similarly.     

5,6-Dimethylbenz[c]acridine functionalized in the 7-position

5,6-Dimethylbenz[c]acridines, functionalized in the 7-position by the carboxy, carbomethoxy, carboxamido, N-ethylcarboxamido, acetyl, cyano, chloro, methoxy or amino group are reported for the first time. Also various related 5,5-dimethyl-5,6-dihydrobenz[c]acridines including the 7-carbomethoxy, 6-hydroxy-7-carboxy, 6-bromo-7-carbomethoxy, 6-methoxy-7-carboxy, 6-methoxy-7-carbomethoxy, and 6-hydroxy-7-N-ethylcarboxamido derivatives which serve as precursors to the completely aromatized 5,6-dimethylbenz[c]acridines are also reported for the first time.     

The Use of 4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one as “Masked” α-Bromo-α'-Hydroxy Ketone in the Synthesis of Heterocyclic Systems

4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one was obtained on the basis of the readily obtainable 4-methylene-5,5-dimethyl-1,3-dioxolan-2-one. It forms 2-imidazo[1,2-a]pyridin-2-yl-2-propanol with 2-aminopyridine, 11a-hydroxy-1,1-dimethyl-3-oxo-1,5,11,11a-tetrahydro[1,3]oxazolo[3,4-a]pyrido[1,2-d]-10-pyrazinium bromide with 2-(aminomethyl)pyridine, and the corresponding derivative of 4-hydroxyoxazolidin-2-one with 2-(3,4-dimethoxyphenyl)ethylamine. The last product was converted by intramolecular amidoalkylation without isolation into 10b-(bromomethyl)-8,9-dimethoxy-1,1-dimethyl-1,5,6,10b-tetrahydro[1,3]oxazolo[3,4-a]isoquinolin-3-one.     

Some Transformations of 2-(Chloromethyl)-5,5-dimethyl-5,6-dihydrobenzo[<Emphasis Type="Italic">h</Emphasis>]quinazolin-4(3<Emphasis Type="Italic">H</Emphasis>)-one

The condensation of 1-amino-3,3-dimethyl-3,4-dihydronaphthalene-2-carbonitrile with chloroacetyl chloride afforded chloro-N-(2-cyano-3,3-dimethyl-3,4-dihydronaphthalen-1-yl)acetamide which underwent cyclization to 2-(chloromethyl)-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin-4(3H)-one. The latter reacted with various nucleophiles (alkali metal alkoxides, piperazine, 2-sulfanylethanol) to give 2-(alkoxymethyl)-, 2-(piperazin-1-ylmethyl)-, and 2-{[(2-hydroxyethyl)sulfanyl]methyl}-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin- 4(3H)-ones. The condensation of 2-(chloromethyl)benzo[h]quinazoline with 2-thioxo derivatives of quinazoline and benzo[h]quinazolines led to the formation of bis-quinazolines in which 5,5-dimethyl-5,6- dihydrobenzo[h]quinazolin-4(3H)-one fragment is linked to quinazoline or benzo[h]quinazoline system through a CH₂S bridge.     

Synthetic experiments related to the indole alkaloids V. mercuric acetate oxidation of 2-[2-(3-indolyl)ethyl]-1,2,3,4-tetrahydroisoquinolines and the formation of benz[a]indolo[3,2-h]quinolizine derivatives

Oxidation of 2-[2-(3-indolyl)ethyl]-1,2,3,4-tetrahydroisoquinoline (I) with mercuric acetate gave 5,6,8,9,14,14b-hexahydrobenz[a]indolo[3,2-h]quinolizine (IV) and 8,9-dihydro-14H-benz[a]indolo[3,2-h]quinolizin-7-ium iodide (VI), as well as starting material. The base (IV) was oxidized with iodine and potassium acetate to VI and on Palladium carbon - maleic acid dehydrogenation yielded 5,6-dihydro-14H-benz[a]indolo[3,2-h]-quinolizin-7-ium iodide (IX), and 14H-benz[a]indolo[3,2-h]quinolizin-7-ium iodide (X). Heating the iodide (VI) with Palladium-carbon brought about an irreversible rearrangement to VII and both these salts with base yielded the red anhydro base 8, 9-dihydrobenz[a]indolo[3,2-h]quinolizine (VIII). This base was also obtained from IV by oxidation in air. The corresponding 8, 9-dehydroanhydro base (XI), benz[a]indolo[3,2-h]quinolizine, was readily obtained from X and alkali. The quinolizinium salts (VI), (VII), and (IX), on catalytic, zinc dust and acetic acid, or sodium borohydride reduction, regenerated the base (IV). Selenium degradation of IV gave, among other products, 1-(2-ethylphenyl)-β-carboline. An analogous series of products was obtained with the 6, 7-dimethoxy derivative of I. Various other aspects of these and related transformations are described.     

Synthesis and Transformations of 2-Hydroxy-2-(benzotriazol-1-yl)-1,4-naphthoquinone

2-Hydroxy-3-(benzotriazol-1-yl)-1,4-naphthoquinone reacts with o-phenylenediamine and 4-chloro-2-aminophenol to give cyclization products: 5-oxo-6-(benzotriazol-1-yl)-5,6H-benzo[a]phenazine and 5-oxo-6-(benzotriazol-1-yl)-10-chlorobenzo[a]phenoxazine; the reaction with aniline yields the quaternary anilinium salt, and benzoyl chloride and benzenesulfonyl chloride acylate the nitrogen atom of the benzotriazolyl moiety.     

The syntheses of 4b,5a-dihydro-5H-benzo[3,4]-phenanthro[1,2-b]azirine and 1a,11b-dihydro-6,11-dimethyl-1H-benz[3,4]anthra[1,2-b]azirine

The syntheses of the K-imine derivatives of carcinogenic benzo[c]phenanthrene and 7,12-dimethylbenz-[a]anthracene are described. Treatment of trans-5-azido-5,6-dihydrobenzo[c]phenanthren-6-ol ( 3 ) and trans-6-azido-5,6-dihydrobenzo[c]phenanthren-5-ol ( 5 ) with thionyl chloride yielded the corresponding β-chloro azides, which in turn, were reacted with lithium aluminium hydride to give 4b,5a-dihydro-5H-benzo[3,4]-phenanthro[1,2-b]azirine ( 2 ). In a similar manner trans-5-azido-5,6-dihydro-7,12-dimethylbenz[a]anthracen-6-ol ( 11 ) and trans-6-azido-5,6-dihydro-7,12-dimethylbenz[a]anthracen-5-ol ( 13 ) were transformed to the respective chloro azides and, converted into 1a,11b-dihydro-6,11-dimethyl-1H-benz[3,4]anthra[1,2-b]azirine ( 10 ).     

Fluorénacènes et fluorénaphènes Synthèses dans la série des indéno-fluorènes,XVI. Méthyl-5-, diméthyl-5, 6- et diphényl-5, 6-dihydro-11, 12-indéno [2.1-a] fluorène

Starting from 2-methyl- and from 2,3-dimethyl-1,4-diphenyl-butadiene-1, 3 respectively, the 5-methyl- and the 5,6-dimethyl-11, 12-dihydro-indeno[2.1-a]fluorene are synthesized in 4 steps. The 5, 6-diphenyl-11, 12-dihydro-indeno[2.1-a]fluorene is obtained by reduction of the already known 11, 12-dioxoderivative. Accesorily a new preparation of the unsubstituted hydrocarbon is described.     

Synthesis and reactions of ethyl 3-acetyl-8-cyano-6,7-dimethylpyrrolo[1,2-a]pyrimidine-4-carboxylate and related compounds

The reactions of 3-acetyl-4-ethoxycarbonyl- or 3,4-diethoxycarbonylpyrrolo[1,2-a]pyrimidine derivatives 7a,b , which were prepared by condensation of the 2-aminopyrrole ( 4 ) with ethyl 3-ethoxymethylene-2,4-dioxovalerate ( 5a ) or ethyl ethoxymethyleneoxaloacetate ( 5b ), with diazomethane are described. Thus, reaction of 7a , with diazomethane gave ethyl 2a-acetyl-7-cyano-2a,3a-dihydro-5,6-dimethyl-3H -cyclopropa[e]pyrrolo[1,2-a]pyrimidine-3a-carboxylate ( 11 ) in 74% yield, which was readily transformed into the 1-pyrrol-2-yl-pyrrole ( 18 ) by treatment with potassium hydroxide. On the other hand, reaction of 7b with diazomethane afforded three products whose structures were assigned as diethyl 7-cyano-2a,3a-dihydro-5,6-dimethyl-3H-cyclopropa[e]pyrrolo[1,2-a]pyrimidine-2a,3a-carboxylate ( 20 ), 6-cyano-7,8-dimethyl-3a,3b,5,9a-tetrahydro-4H -aziridino[c]-1H or 3H-pyrazolo[3,4-e]pyrrolo[1,2-a]pyrimidine-3a,9a-dicarboxylates ( 21,22 ). Ring Transformation of 20 to 25 was not observed.     

Thiophene systems. 13. The synthesis of novel thienopyranones

The syntheses and spectral properties of novel dimethyl-substituted thieno[3,2-b]-, [3,4-b]- and [2,3-b]pyran-ones are described. The uv spectra of the three systems are distinctly different as supported by HOMO/LUMO calculations. 5,6-Dihydro-5,5-dimethyl-7H-thieno[3,4-b]pyran-7-one ( 10 ) and 5,6-dihydro-6,6-dimethyl-4H-thieno[2,3-b]pyran-4-one ( 20 ) represent the first members of these thienopyranone ring systems.     

A facile synthesis of pyrrolo[1,2-a]pyrimidines and pyrrolo[1,2-a]imidazoles

The one-step synthesis of 8-t-butoxycarbonyl-6,7-dimethyl-2-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidine from acetyl methyl carbinol, 3-aminopropionic acid, and t-butyl cyanoacetate is reported. Utilizing a similar technology under basic conditions, 7-substituted 5,6-dimethyl-2-oxo-2,3-dihydro-(1H)-pyrrolo[1,2-a]imidazole is synthesized from acetyl methyl carbinol, ethyl glycinate, and the appropriate acetonitrile.     

Potential metabolites of carcinogenic aza aromatic hydrocarbons synthesis of K-region oxide,phenol and dihydrodiols of 7-methylbenz[c]acridine

The potential K-region metabolites, $\text{trans}$- and $\text{cis}$-5,6-dihydroxy-7-methyl-5,6-dihydrobenz[c]acridine, 5,6-epoxy-7-methyl-5,6-dihydrobenz[c]acridine and 5-hydroxy-7-methylbenz[c]acridine, of 7-methylbenz[c]acridine have been synthesised.     

Cyclocondensation reaction of a 1,5-diketone with 1,2-diamines

Reaction of 2-acetonyl-4,5-dimethoxy-3′-chlorobenzophenone (1) with ethylenediamine afforded the imidazo[2,1-a]isoquinoline 2, whereas 6-(3-chlorophenyl)-8,9-dimethoxybenzo[b]phenazine (3) and naphthol 4 were obtained with ortho-phenylenediamine.     

Synthesis and Spectroscopic Study of Iron(III) and Copper(II) Chloride Complexes with 2-(3,3-Dimethyl-1,2,3,4-tetrahydroisoquinolylidene-1)-5,5-dimethyl-2,3,5,6-tetrahydroimidazo[2,1-a]isoquinoline-3-one (L). The Crystal Structure of L

Complexes of Fe(III) and Cu(II) chlorides with 2-(3,3,-dimethyl-1,2,3,4-tetrahydroisoquinolylidene-1)-5,5-dimethyl-2,3,5,6-tetrahydroimidazo[2,1-a]isoquinoline-3-one (L) were synthesized and studied by IR and electronic absorption spectroscopy. X-ray diffraction analysis of compound L was carried out. The molecule of L was found to crystallize in the form of cis-isomer with the proton localized on the nitrogen atom of the dihydroisoquinoline fragment.     

Synthesis and reactions of 1-(4-bromo-, 4-fluoro-, and 4-trifluoromethylphenyl)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles

From 2-formyldimedone and 4-bromo-, 4-fluoro-, and 4-trifluoromethylphenylhydrazines we have obtained the corresponding 2-arylhydrazinomethylenedimedones, which in acid medium undergo ring closure to form 1-substituted 6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles. Oxidation of the latter by selenous acid leads to the corresponding 4,5-dioxo-4,5,6,7-tetrahydroindazoles, which then were converted to derivatives of 4,5-dihydro-3H-pyrazolo[4,3-a]phenazine and 4,5-dihydro-1H(3H)-indazolo[4,5-d]imidazole.Riga Technical University, Riga LV-1658. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1669–1675, December, 1997.     

Reaction of pyrrolo[2,1-a]isoquinoline-2,3-diones with carbon-centered nucleophiles

Knoevenagel condensations of 5,5-dimethyl-2,3,5,6-tetrahydropyrrolo[2,1-a]isoquinoline-2,3-diones with malononitrile, ethyl cyanoacetate, indan-1,3-dione, and Drotaverine base involved the ketone carbonyl group in the former with formation of deeply colored dark blue substances. The lactam ring in the products can be opened by the action of nitrogen-centered nucleophiles, e.g., p-toluidine. The reaction of 5,5-dimethyl-2,3,5,6-tetrahydropyrrolo[2,1-a]isoquinoline-2,3-dione with methyl magnesium iodide gave 2-hydroxy-2,5,5-trimethyl-2,3,5,6-tetrahydropyrrolo[2,1-a]isoquinolin-3-one.     

Fused polycyclic nitrogen-containing heterocycles 20. Thiazolo[3,4-<Emphasis Type="Italic">a</Emphasis>]quinoxalines from 4-hydroxy-2-phenyliminothiazolidines and C-substituted 1,2-phenylenediamines

The condensation of 4-hydroxy-3,5-diphenyl-2-phenyliminothiazolidine with 4,5-dimethyl-1,2-phenylenediamine affords 7,8-dimethyl-3-phenyl-1-phenyliminothiazolo[3,4-a]quinox-alin-4(5 H)- one; the condensation with 1,2-phenylenediamines containing different substituents at positions 4 and 5 gives both theoretically possible isomeric thiazolo[3,4-a]quinoxalines, which differ in the distribution of these substituents between positions 7 and 8 in the benzene ring of the quinoxaline system. 3a-Hydroxy-7,8-dimethyl-3-phenyl-l-phenylimino-3,3a-di-hydrothiazolo[3,4-a]quinoxalin4(5 H)- one was isolated and characterized as the intermediate of the reaction giving rise to thiazolo[3,4-a]quinoxaline from 4,5-dimethyl-1,2-phenylene-diamine. This intermediate is a covalent hydrate of the final product.     

Studies on quinones. Part 25. Synthetic approaches to 6,9-dioxygenated-benzazepinones

The Schmidt and Beckmann rearrangement of 3,4-dihydro-4,4-dimethyl-1(2H)-naphthalenones bearing oxygenated groups at the 5,8-positions, and some of their oximes are reported. Depending upon the structure of the substrates and the reaction conditions 4,5-dihydro-3H-naphth[1,8-cd]isoxazol, benzazepin-2-one and 5,6-dihydro-7H-tetrazolo[1,5-a][2]benzazepine derivatives were generated.