Synthesis of Tetrahydro-1H,7H-benzo[ij]quinolizine-1,7-dione Derivatives

Tetrahydro-1H,7H-benzo[ij]quinolizine-1,7-diones have been obtained by the cyclization of N-alkoxyphenyl-N-(2-carboxyethyl)--alanines. Fission of the ester bond occurs on cyclization of N-(4-ethoxyphenyl)-N-(2-carboxyethyl)--alanine, but the cyclization of the 3,4-dialkoxyphenyl derivative leads to the formation of 9-alkoxy-8-hydroxy-2,3,5,7-tetrahydro-1H,7H-benzo[ij]quinolizine-1,7-diones. The corresponding dioximes and diphenylhydrazones were obtained.     

Phenanthrothiazoles

Phenanthro[3,4-d]thiazole and phenanthro[3,4-d]-2-methylthiazole were synthesized by the oxidative cyclization of 3-phenanthrylthiooxamic acid with subsequent decarboxylation and by the oxidative cyclization of 3-thioacetamidophenanthrene, respectively.See [1] for communication II.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1493–1497, November 1971     

Investigations in the Area of Amines and Ammonium Compounds. 237. Synthesis of 2,2-Dialkyl-4-Hydroxymethylbenzo[f]isoindolinium and 2,2-Dialkyl-4-hydroxymethylisoindolinium Salts

The ability of the 4-hydroxy-2-butynyl group to participate as ,-unsaturated fragment in base-catalyzed intramolecular cyclization was established. 2,2-Dialkyl-4-hydroxymethylbenzo[f]isoindolinium and 2,2-dialkyl-4-hydroxymethylisoindolinium salts were obtained by the cyclization of dialkyl(4-hydroxy-2-butynyl)(3-phenylpropargyl)- or dialkyl(4-hydroxy-2-butynyl)(3-alkenylpropargyl)ammonium salts.     

Research in the chemistry of heterocyclic quinone imines. 11. Effect of benzannelation on the oxidative cyclization of diarylamino-N-aryl-1,4-benzoquinone monoimines to phenazinone derivatives

2,5-Diarylamino-N-()-naphthyl-1,4-benzoquinone monoimines undergo oxidative cyclization to give benzannelated phenazinone derivatives. The effect of an N-aryl fragment on the ease of cyclization decreases in the order N--naphthyl>N--naphthyl>N-phenyl. 2-Arylamino-N-phenyl-1,4-naphthoquinone monoimines do not undergo oxidative cyclization to phenazinones.See [1] for Communication 10.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 786–790, June, 1991.     

Diazabicycloalkanes with nitrogen atoms in bridgehead positions.

1-Methyl-1-(-haloethyl)-1,2,3,4-tetrahydroquinoxalinium salts were synthesized and the dependence of the hydrolysis and cyclization rate constants on the acidity of the medium and presence of halide was found. It was determined that the monocations of tetrahydroquinoxalines participate in the formation of the benzo[b]-1,4-diazabicyclo[2.2.2]octene system, since blocking the free electron pair of the tertiary nitrogen atom with a methyl substituent significantly accelerates the cyclization and suppresses the hydrolytic side reaction.For Communication 17, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 372–378, March, 1989.     

Indole derivatives

It has been established that the cyclization of arylhydrazones of 3-(-ethoxycarbonylethyl)1-methylpiperidin-4-one is accompanied by a rearrangement and leads to a 1,2,3,4-tetrahydropyrimido[3,4-a]indole derivative [1], The cyclization of arylhydrazones of 2-(-methoxycarbonylethyl)cyclohexanone under the same conditions forms indole and 3H-indole derivatives.For Communication XXXI, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 7, pp. 927–930, July, 1970.     

Synthesis of phthalascidin analogs

We report a new approach to obtain phthalascidin analogs. 6-Phthalimidomethylpyrazino[1,2-b]isoquinoline-1,4-dione (5a) was obtained in a one-pot N-alkylation/cyclization of the corresponding 1-acetyl-3-arylmethyl-2,5-piperazinedione with N-phthalylacetaldehyde dimethyl acetal. Chemoselective reduction of the C(1)-carbonyl group in the 3-arylmethyl-11,11a-dehydroderivative 9a was followed by cyclization of an acyliminium intermediate, to give the 6,15-imino-7-oxo-14,14a-dehydroisoquino[3,2-b]3-benzazocin 11a. Alternatively, the octacyclic compound 13a was obtained through a novel double cyclization of a precursor in which the C(1)-carbonyl and one phthalimide carbonyl group were reduced.     

Transformation of octadehydrodibenzo[12]annulene to benzonaphthopentalene by successive nucleophilic and electrophilic transannular cyclizations

A nucleophile-induced cyclization of octadehydrodibenzo[12]annulene derivative 1b was investigated. Treatment of 1b with BuLi gave fused 5–9-membered ring products, dibenzobicyclo[7.3.0]tetraenediynes 2a and 2b, formed via a single transannular cyclization reaction. The reason why double cyclization did not occur is ascribed to the structure of a plausible anionic intermediate in which a negative charge locates apart from the remaining triple bond carbons. The second cyclization did not take place even when once-isolated product 2b was treated with BuLi because of the higher reactivity toward a nucleophile of the fulvene moiety compared to the triple bonds. On the other hand, heating a chlorobenzene solution of 2b containing cyclohexa-1,4-diene gave products 3a–c possessing a benzonaphthopentalene framework via a Bergman cyclization pathway albeit in low yields after inter- or intramolecular hydrogen abstraction. Moreover, iodine-induced transannular cyclization of 2b afforded the corresponding diiodide 3d.     

Reaction of aminoquinolines with unsaturated carboxylic acids. 2. Cyclization of N-quinolyl-β-alanines

The cyclization of N-(3-quinolyl)- and N-(6-quinolyl)--alanines was carried out to give uncondensed hexahydropyrimidine derivatives, while the cyclization of N-(5-quinolyl)- and N-(8-quinolyl)--alanines gave tetrahydrophenanthrolinone derivatives.Communication 1, see ref. [1].Kaunas Technological University, 3028 Kaunas, Lithuania, Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 653–657, May, 2000.     

Investigation of unsaturated lactones

Transesterification with subsequent cyclization to 4-carbethoxy-5,6,6-trialkyl-3-hydro-2-pyrones occurs during condensation of -keto alcohols with diethyl succinate. 4-Carbethoxy-5,6,6-trimethyl-3-hydro-2-pyrone was obtained by reaction of dimethylethynylcarbinol with the ethyl ester of succinic acid monochloride and subsequent hydration of the acetylenic ester and cyclization.See [1] for communication XXIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1604–1607, December, 1973.     

Heterocyclization of compounds containing diazo and cyano groups. 6. Theoretical and experimental investigations of cyclization of 2-cyano-2-diazoacetamides to 5-hydroxy-1,2,3-triazole-4-carbonitriles

A series of N-alkyl- and N-aryl-2-cyano-2-diazoacetamides was synthesized by the reaction of 2-amino-2-cyanoacetamides with sodium nitrite in hydrochloric acid. The mechanism of their heteroclectrocyclization to 5-hydroxy-1,2,3-triazoles was investigated kinetically and theoretically by the B3LYP/6-31+G^* method. The conclusion was made on the basis of the determined activation energy of the cyclization process. reaction parameters , and kinetic isotope effects, that there is a difference between the mechanisms of cyclization of the N-alkyl and N-aryl derivatives of 2-cyano-2-diazoacetamide; cyclization of the N-alkyl derivatives takes place by a monorotatory mechanism, while cyclization of the N-aryl derivatives takes place by a mechanism where one of the stages is heteroelectrocyclization of 2-diazoacetimidates.For Communication 5, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 26–41, January, 2000.     

Copper-catalyzed [3 + 1] cyclization of cyclopropenes/diazo compounds and bromodifluoroacetamides: facile synthesis of α,α-difluoro-β-lactam derivatives

We have developed a novel copper-catalyzed cyclization of cyclopropenes/diazo compounds and bromodifluoroacetamides, efficiently synthesizing a series of α,α-difluoro-β-lactams in moderate to excellent yields under mild reaction conditions. This reaction represents the first example of [3 + 1] cyclization for the synthesis of β-lactams utilizing a metal carbene intermediate as the C1 synthon.

A copper-catalyzed [3 + 1] cyclization of cyclopropenes and bromodifluoroacetamides/diazo compounds has been successfully developed, efficiently synthesizing a wide range of α,α-difluoro-β-lactams.     

Studies in the imidazole series

Methods were developed for the synthesis of dihydro and tetrahydro derivatives of imidazo-[1,2-a]- and imidazo[1,2-c]pyrimidine and imidazo[2,1-b]-5-quinazolone from 2-amino- and 4-aminopyrimidines, 2-amino-4-quinazolones, and -haloethanols or 1,2-dihaloethanes. Dihydroimidazo[1,2-c]quinazoline, which was also obtained by cyclization of 4-(-hydroxyethylamino)-quinazoline, was synthesized by reaction of 4-chloroquinazoline with -haloethylamines.See [1] for communication LXXXV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 834–836, June, 1976.     

Synthesis of spiro analogs of lilolidine alkaloids

The Friedel-Krafts intramolecular cyclization of N-chloroacetyl- and N--bromopropionyl-4-methylspiro[tetrahydroquinoline-2-cyclohexanes] was used to obtain 2-oxo-1,2,5,6-tetrahydro-4H-spiro[pyrrolo(3,2,1-i,j)quinoline-4,1-cyclohexanes]— spiro analogs of lilolidine alkaloids.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1504–1507, November, 1993.     

Synthesis of benzo[g]quinoline derivatives

It has been established that the cyclization of -(2-carboxy-3-naphthylamino)propionic acid into N-acetyl-4-oxo-1, 2, 3, 4-tetrahydrobenzo[g]quinoline takes place with the participation of acetic anhydride and an alkali metal acetate. In the absence of the alkali metal acetate cyclization takes place in a different direction. A mechanism for this reaction has been proposed as taking place through the formation of an internal mixed anhydride, which decomposes under the reaction conditions into N-acetyl-4-oxo-1, 2, 3, 4-tetrahydrobenzo[g]-quinoline and carbon dioxide.For part V, see [1].     

Transformed steroids. 104. The preparation of [16,17]oxazolidinones of 20-ketosteroids by intramolecular isomerization of 16,17α-N-carboethoxyepiminopregnenolone

Conclusions A new class of steroid compounds, namely, [16,17-d]oxazolidin-2-on-20-ketosteroids, was obtained by the intramolecular cyclization of the hydrazone of 16,17-N-carboethoxy-epiminopregnenolone which occurs by opening of the aziridine ring.Communication 103, see our earlier work [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2318–2322, October, 1979.     

6-Arylamino-3-methyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines: Novel N-Arylamidine Structures

We propose a method for obtaining derivatives of 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine by alkylation of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol by substituted -chloroacetanilides, followed by cyclization of the intermediate by phosphorus oxychloride.     

Investigations in the imidazole series

The reactions of 2-mercaptonaphth[1,2-d]imidazole with 1,2-dichloro- and 1,2-dibromoethanes and the cyclization of 3-(-hydroxyethyl)- and 2-(-hydroxyethyl)mercaptonaphth[1,2-d]imidazoles were studied. 2,3-Dihydro derivatives of naphth[1,2-d]imidazo[1,2-b]thiazole and naphth[1,2-d]imidazo[3,2-b]thiazole were obtained.See [1] for communication LXX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 257–259, February, 1972.     

An unexpected cyclization discovered during the synthesis of 8-substituted purines from a 4,5-diaminopyrimidine

Attempted conversion of 4-chloro-5-(N-4-bromobutanoyl)amino-6-phenethylaminopyrimidine (2) to 6-chloro-8-[1-(3-bromo)propyl]-9-phenethylpurine (1) under standard cyclization conditions did not give the targeted product. Instead, an unexpected cyclization occurred to give 6-chloro-5-[1-(3-hydroxy)propyl]-9-phenethylpurine (3), which can be viewed as a hydrolysis product of the resulting halide. The cyclization reaction was optimized and compound 3 was prepared in excellent yield. A mechanism involving transient generation of a spiro-tetrahydrofuran is also proposed.     

Facile ring-closure cyclization of arenes by nucleophilic C-alkylation reaction in ionic liquid

A novel synthetic method using an ionic liquid (IL) for a six-membered ring-closure cyclization is described. The ring-closure cyclization by nucleophilic C-alkylation was achieved with various halo- and alkanesulfonyloxyalkyl aromatic compounds in high yields with minimal byproducts using ILs as the reaction media in the absence of any catalyst. For example, the cyclization of 2-(3-methanesulfonyloxy-propoxy)naphthalene (1a) to 2,3-dihydro-1H-naphtho[2,1-b]pyran (2) in IL [bmim][PF₆] proceeded selectively at 150 °C for 24 h in 85% yield.