Intramolecular Electrophilic Cyclization Research Articles

Synthesis of Selenocyanated Indoles via PhICl2‐Induced Electrophilic Intramolecular Cyclization of 2‐Alkynylanilines or 2‐Alkenylanilines

AbstractThe 3‐selenocyanato‐substituted indoles were readily synthesized via (dichloroiodo)benzene (PhICl2)‐induced reaction of 2‐alkynylanilines or 2‐alkenylanilines with KSeCN in MeCN under metal‐free conditions. The reaction sequence was postulated to encompass the formation of a reactive selenocyanogen chloride species, generated in situ from the reaction of PhICl2 and KseCN, followed by electrophilic addition and intramolecular cyclization steps.

Synthesis of Trifluoromethylthiolated Quinolinones via Trifluoromethanesulfanamide‐Induced Electrophilic Intramolecular Cyclization of N‐Arylpropynamides

AbstractThe reaction of N‐arylpropynamides with the commercially available trifluoromethanesulfanamide in the presence of BiCl3 was found to afford quinolin‐2‐ones in a selective manner via electrophilic trifluoromethylthiolation enabled by the in‐situ generated CF3S−Cl and the followed intramolecular cyclization. Differing from the existing analogous cyclization route that solely produces spiro[4,5]trienones, this alternative approach exclusively affords the biologically interesting quinolin‐2‐ones as the major products.

Synthesis of raloxifene-like quinoxaline derivatives by intramolecular electrophilic cyclization with disulfides

The intramolecular electrophilic cyclization of alkynes with disulfides to form thieno[2,3–b]quinoxaline structures and to introduce thioether substituents afforded quinoxaline derivatives (7a-7d, 8a-8d). Among obtained eight derivatives, the raloxifene analogues (7c, 8b) showed specifically high cytotoxicity against breast cancer cells (SK-BR-3), and raloxifene analogues (8a) showed the highest cytotoxicity against human leukemia cells (HL-60). None of the raloxifene analogues (7a-7d, 8a-8d) showed cytotoxicity against human lung fibroblasts (WI-38), which are normal cells.

REGIOSELECTIVITY OF THE TELLURIUM-INDUCED CYCLISATION OF TERMINALLY SUBSTITUTED ALLYL, BUTENYL AND PROPARGYL THIOETHERS OF THIENOPYRIMIDINE

The method of electrophilic intramolecular cyclization is widely used for the synthesis of condensed thienopyrimidine derivatives. In this work, the regioselectivity of the process of electrophilic intramolecular cyclization of terminally substituted allylic derivatives, but-1-enyl and propargyl thioethers of thienopyrimidine with p-methoxyphenyltellurttrichloride was investigated.
 It was established that as a result of the tellurium-induced cyclization of butenyl thioethers of 5,6-dimethyl-3-phenylthieno[2,3-d]pyrimidin-4(3H)-one with p-methoxyphenyltellurium trichloride, angular tricyclic chlorides ― 8-(dichloro(4-methoxyphenyl)-tellanyl)-2,3,9-trimethyl-4-oxo-5-phenyl-5,7,8,9-tetrahydro-4H-thieno[3',2':5,6]pyrimido[2,1-b][1,3]thiazine-10-ium and 9-((dichloro(4-methoxyphenyl)-tellanyl)methyl)-2,3-dimethyl-4-oxo-5-phenyl-5,7,8,9-tetrahydro-4H-thieno­[3',2':5,6]pyrimido[2,1-b][1,3]thiazine-10-ium with an annealed six-membered ring in the form of complexes with p-methoxyphenyltellurium trichloride. It was proved that the electrophilic intramolecular cyclization of 5,6-dimethyl-2-(prop-2-yn-1-ylthio)-3-phenylthieno[2,3-d]pyrimidin-4(3H)-one with aryltellurium trichloride occurs with the formation of an aryltellurium trichloride complex with angular chloride 8-((dichloro(4-methoxyphenyl)-tallanyl)methylidene)-2,3-dimethyl-4-oxo-5-phenyl-4,5,7,8-tetrahydrothiazolo[3,2-a]thieno [3,2-e]pyrimidin-9-ium in the form of one geometric isomer.
 Keywords: electrophilic heterocyclization; p-methoxyphenyltellurium trichloride; organotellurium compounds; chloride 4H-thieno[3',2':5,6]pyrimido[2,1-b][1,3]thiazine-10-ium; chloride 4H-thieno[3',2':5,6]pyrimido[2,1-b][1,3]thiazine-10-ium; chloride thiazolo[3,2-a]thieno[3,2-e]pyrimidin-9-ium.

TELLURO-INDUCED CYCLISATION 2-(BUT-2-ENYLTHIO)QUINOLINECARBALDEHYDE AND QUINOLINE-4-ONE

Aryltellurium trichlorides have proven themselves as good cyclizing reagents in electrophilic intramolecular cyclization reactions, mainly of propenyl derivatives of heterocycles. On the other hand, information on the use of butenyl derivatives in reactions with p-alkoxyphenyltellurtrichlorides is limited. In this work, the regioselectivity of the process of electrophilic intramolecular cyclization of but-2-enyl thioethers of quinoline-3carbaldehyde and quinazolin-4-one with p-methoxyphenyltellurium trichloride was investigated.
 It was established that, as a result of the tellurium-induced cyclization with p-methoxyphenyltellurium trichloride of but-2-enyl thioethers of quinoline and quinazoline, angular tricyclic chlorides – 2-(dichloro(4-methoxyphenyl)-tellanyl)-1-methyl-5-formyl-2,3- dihydro-1H-[1,3]thiazino[3,2-a]quinolin-11-ium and 2-(dichloro(4-methoxyphenyl)-tellanyl)-1-methyl-6-oxo-5-phenyl-2, 3,5,6-tetrahydro-1H-[1,3]thiazino[3,2-a]quinazolin-11-ium, respectively, with an annealed six-membered ring in the form of complexes with p-methoxyphenyltellurium trichloride. Optimal conditions for the electrophilic intramolecular cyclization reaction were selected.
 Keywords: electrophilic heterocyclization; p-methoxyphenyltellurium trichloride; organotellurium compounds; chloride 2-(dichloro(4-methoxyphenyl)-tellanyl)-1-methyl-5-formyl-2,3-dihydro-1H-[1,3]thiazino[3,2 -a]quinolin-11-ium, chloride 2-(dichloro(4-methoxyphenyl)-tellanyl)-1-methyl-6-oxo-5-phenyl-2,3,5,6-tetrahydro-1H-[1,3]thiazino[3,2-a]quinazolin-11-ium

Synthesis and conversion of thiazinobenzothiazolium salts

This paper presents the results of research into the process of electrophilic intramolecular cyclization of 2-cinnamylthiobenzothiazole with halogens and tellurium halides. 2-Cinnamylthiobenzothiazole was prepared by alkylation of mercaptobenzothiazole with cinnamyl chloride in the presence of sodium alcoholate in an alcoholic medium. It was established that as a result of halocyclization of the model 2-cinnamylthiobenzothiazole with an excess of halogen, the thiazine ring is annealed with the formation of 3-halogeno-4-phenyl-3,4-dihydro-2H-[1,3]thiazino[2,3-b][1,3 ]benzothiazolium tribromide trihalides, which are effectively dehalogenated with acetone or sodium sulfite to form monohalides. Halocyclization of cinnamyl thioether of benzothiazole with iodine bromide in chloroform isolated 3-iodo-4-phenyl-3,4-dihydro-2H-[1,3]thiazino[2,3-b][1,3]benzothiazolium bromide, which was converted into 3-iodo-4-phenyl-3,4-dihydro-2H-[1,3]thiazino[2,3-b][1,3]benzothiazolium iodide by ion exchange reaction under the action of potassium iodide in acetone. The corresponding perchlorate was synthesized by the action of sodium perchlorate in methanol on 3-bromo-4-phenyl-3,4-dihydro-2H-[1,3]thiazino[2,3-b][1,3]benzothiazolium bromide. Spectral characteristics (1H NMR) of trihalides, monohalides and perchlorate indicate the preservation of the structure of the thiazinobenzothiazolium cation during ion exchange reactions. Tellurium-induced cyclization of cinnamyl thioether of benzothiazole does not occur. When 2-cinnamylthiobenzothiazole is treated with tellurium dioxide in an excess of halide acid, the nitrogen of the benzothiazole cycle is protonated and aquacomplexes of benzothiazolinium hexahalogenotellurates are formed. Instead, the action of p-alkoxyphenyltellurttrichloride on cinnamyl thioether benzothiazole leads to the formation of molecular complexes in the ratio of thioether:electrophile of 2:1. As a result of the conducted research, potentially biologically active thiazinobenzothiazolium halides were synthesized.

ARYLTELLUROCHLORINATION OF 4,5-DIARYL-SUBSTITUTED 3-ALLYLTHIO-1,2,4-TRIAZOLES

Thiazolotriazole derivatives have a number of biological activities. Electrophilic intramolecular cyclization of unsaturated alkyl derivatives of 1,2,4-triazole under the action of various electrophilic reagents (halogens, tetrahalides of chalcogenides) is the most effective and simple method of synthesis of thiazolotriazoles.
 It was previously reported that 3-metalylthio-4,5-diphenyl-1,2,4-triazole reacts with aryltellur-trichloride to form an adduct of the substrate-electrophile composition 1: 1. Therefore, the aim of this research is to study the regioselectivity of aryltelluriumchlorination of allyl thioethers 1,2,4-triazole. It was found that in different solvents 3-allylthio-4-phenyl-5- (3-chlorophenyl) -4H-1,2,4-triazole with p-methoxyphenyltellurium trichloride forms a molecular adduct of similar composition. Instead, the addition of sodium perchlorate as doping additive to the reaction medium changes the direction of the reaction and leads to the formation of 6-(dichloro-(4-methoxyphenyl)-4-tellanyl) methyl)-5,6-dihydro-3H-thiazolo perchlorate [3,2- b][1,2,4]triazolium-7.
 Thus, thiazolo[3,2-b][1,2,4]triazolium salts were obtained as a result of aryl telluriumchlorination of 4,5-diaryl-substituted 3-allylthio-1,2,4-triazoles. Optimal conditions for proceeding of tellurium-induced cyclization have been found.

COMPARISON OF FUNGICIDAL ACTIVITY OF FLUCONAZOLE AND FLUORINE-CONTAINING 1,2,4-TRIAZOLES VIA IN VITRO AND IN SILICO METHODS

Diseases caused by fungal infections affect millions of people and plants every year. Candida albicans is one of the most common fungi, causing a variety of fungal diseases that are life-threatening, especially for cancer patients and HIV-positive people. At the same time, drug therapy aimed at treating these diseases is limited by the small number of drugs used. Among them, one of the most commonly used both in human treatment and as part of the active components of agricultural fungicides is fluconazole - a drug that combines the nucleus of 1,2,4-triazole and fluorine atoms.
 Previously, we have investigated the antifungal activity of condensed salts of thiazolo[3,2-b][1,2,4]triazole obtained by electrophilic intramolecular cyclization, bis-triazoles and their alkylated derivatives, and proved the feasibility of their use as bactericides and fungicides.
 The aim of this work is to investigate the interaction of fluconazole and synthesized fluorine-containing compounds of class 1,2,4-triazole with the enzyme "EC 2.2.1.6 Acetolactate synthase" in the crystal structure of Candida albicans and to evaluate the possible use of the obtained substances as fungicides.
 In the current study, we investigated the antifungal action of fluorine-containing derivatives of 1,2,4-triazole-3-thione. Molecular docking was performed for the compounds with the highest fungicidal activity and the preparation of fluconazole for the enzyme "EC 2.2.1.6 Acetolactate synthase" Candida albicans. The results showed that one of the tested substances showed a higher affinity for binding in the active site of the enzyme than fluconazole. Therefore, the test substances are promising antifungal agents.
 Keywords: 1,2,4-triazole-3-thione; fungicidal activity; molecular docking; Candida albicans.

Synthesis of 3,6,8,11-tetramethyl-5H,9H-quino[3,2,1-de]acridine-5,9-dione

The latest progress in the construction of organic light-emitting diodes (OLEDs) has created a demand for the development of new, convenient and efficient methods of synthesis of completely organic phosphors with an elongated π-system and a set of electrochemical and photophysical properties. Nowadays, the last generation of organic emitters for high-performance OLEDs is materials that demonstrate thermally activated delayed fluorescence (TADF) phenomenon. Such materials can convert into light energy, both emitting singlet and dark triplet excitons and, thus, the internal efficiency of OLEDs, based on such compounds, reaches 100 %. Two main approaches have been developed for a targeted synthesis of organic TADF materials. The first and most studied of these is the synthesis of donor-acceptor conjugates, in which the donor and acceptor units are placed relative to each other at a significant angle, close to 90°. The second approach to the molecular design of TADF materials is to construct polynuclear heterocyclic compounds with a rigid framework, in which HOMO and LUMO are localized on the atoms of the cycles through one. The first example of a successful implementation of such strategy was the boro-azo-heterocyclic compound DABNA-1, the synthesis and characterization of which was first published in 2016. It was later discovered that boron acceptor atoms in the design of such compounds can be successfully replaced by carbonyl moieties, and, thus, it can simplify the synthesis and design of such compounds. Therefore, the attention of researchers was attracted by 5 H ,9 H -quino[3,2,1-de]acridine-5,9-dione heterocyclic system. The Ullmann reaction between 3,5-dimethyl-2,6-dicyanoaniline and 4-iodotoluene gave 2- (bis(4-methylphenyl)amino)-4,6-dimethylisophthalonitrile, which was heated in polyphosphoric acid for 4 hours. As a result intramolecular electrophilic cyclization involving both nitrile groups with the formation of 3,6,8,11-tetramethyl-5 H ,9 H -quino[3,2,1-de]acridine-5,9-dione take place. Keywords: 3,5-dimethyl-2,6-dicyanoaniline, 5H,9H-quino[3,2,1-de]acridine-5,9-dione, Ullmann reaction, cyclization, polyphosphoric acid.

Electrophilic cyclization of propargyl thioethers of 3-methyl(phenyl)-2-(prop-2-yn-1-ylthio)-7-(trifluoromethyl)quinazolin-4(3H)-ones by tellurium tetrahalides

The paper presents the results of the study of the process of electrophilic intramolecular cyclization of 3-methyl(phenyl)-2-(prop-2-yn-1-ylthio)-7-(trifluoromethyl)quinazolin-4(3H)-ones by tellurium tetrahalides. 3-Methyl(phenyl)-2-(prop-2-yn-1-ylthio)-7-(trifluoromethyl)quinazolin-4(3H)-ones were prepared by the alkylation of the corresponding thions with propargyl bromide in an alkaline alcohol medium. It is found that the interaction of propargyl thioethers of 3-substituted 2-thioxo-7-(trifluoromethyl)-2,3-dihydroquinazolin-4(1H)-ones with tellurium tetrahalides, which were obtained in situ from tellurium dioxide and six equivalents of corresponding concentrated hydrohalic acid, leads to the formation of halides of angular 4-methyl(phenyl)-5-oxo-1-((trihalotellanyl)methylidene)-8-(trifluoromethyl)-1,2,4,5-tetrahydrothiazolo[3,2-a]quinazolin-10-iums. The most optimal conditions for the tellurium-induced electrophilic heterocyclization of propargyl thioethers with tellurium terahalides are the use of glacial acetic acid as a solvent and stirring of the reaction mixture at room temperature for 24 hours. It is found that the electrophilic cyclization of 3-methyl(phenyl)-2-(prop-2-yn-1-ylthio)-7-(trifluoromethyl)quinazolin-4(3H)-ones by tellurium tetrahalides occurs stereoselectively with the formation of one configurational isomer. The influence of the nature of halogen in the electrophilic reagent and the substituent in position 3 of quinazoline is examined and it is found that these factors do not affect the regioselectivity of the electrophilic intramolecular cyclization process. As a result of the conducted study, potentially biologically active salts of tellurofunctionalized thiazolinoquinazolines of angular structure were received.

Divergent Synthesis of Chalcogenylated Quinolin-2-ones and Spiro[4,5]trienones via Intramolecular Cyclization of N-Aryl­propynamides Mediated by Diselenides/Disulfides and PhICl2

AbstractThe reaction of N-arylpropynamides with (dichloroiodo)benzene (PhICl2) and diselenides/disulfides resulted in a divergent synthesis of chalcogenylated quinolinones and spiro[4.5]trienes through intramolecular electrophilic cyclization and chalcogenylation. The chalcogenyl functional group was introduced by an electrophilic reactive organosulfenyl chloride or selenenyl chloride species, generated in situ from the reaction of disulfides/diselenides and PhICl2. Notably, the divergent cyclization pathways were determined by the substituent type on the aniline ring in N-arylpropynamide substrates. Substrates bearing a fluoro, methoxy or trifluoromethoxy group at the para-position of the aniline underwent an alternative spiralization pathway to give the 3-chalcogenylated spiro[4,5]trienones.

An Interrupted Pummerer Reaction Mediated by a Hypervalent Iodine(III) Reagent: In Situ Formation of RSCl and Its Application for the Synthesis of 3-Sulfenylated Indoles.

An interrupted Pummerer reaction of PhICl2 and sulfoxides was found to in situ generate reactive organosulfenyl chloride, which enabled the intramolecular electrophilic cyclization of 2-alkynylanilines, generating 3-sulfenylated indole with a good to excellent yield under metal-free conditions. One striking feature of the approach is that sulfoxide regeneration can be realized via the oxidation of the formed sulfides by the generated hypervalent iodine species.

CHALCOGENATION OF N-ALKENYL DERIVATIVES OF 2-THIOXO-2,3-DIHYDRO QUINAZOLINE-4(1H)-ONE

Oxo- and thio-substituted quinazolines are promising biologically active objects. A special place in a number of quinazolines is occupied by its condensed analogues, namely thiazoloquinazolines, which exhibit antioxidant, antimicrobial and antitumor activity. An effective method for the synthesis of condensed quinazoline derivatives is electrophilic intramolecular cyclization of its unsaturated derivatives. The usage of pharmacoformic chalcogen-containing electrophiles in these reactions has been insufficiently studied. Organochalcogen-containing heterocyclic compounds are the promising biologically active substances with different pharmacological action. Therefore, the study of reactions of electrophilic intramolecular cyclization of N(3)-alkenyl derivatives of 2-thioxo-2,3-dihydroquinazolin-4(1H)-one under the action of chalcogen tetrahalides is an urgent task.
 N (3)-alkenyl derivatives of 2,3-dihydroquinazolin-4(1H)-one were used as the object of study. It was found that the interaction of tellurium tetrabromide with N(3)-alkenyl-2-thioxoquinazolin-4-ones in glacial acetic acid leads to linear hydrobromides of 2-[(tribromotelluro) methyl]-2,3-dihydro-5H-[1,3]thiazolo[2,3-b]quinazolin-5-one.
 In the reaction with N(3)-methallyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one, individual tellurium tetrachloride was used, which was obtained by passing chlorine over the tellurium. It is proved that halotellurium-induced cyclization of N-methallyl quinazolone with tellurium tetrachloride occurs regioselectively with the formation of 2-methyl-2-[(trichlorotelluro)methyl]-2,3-dihydro-5H- [1,3]thiazolo[2,3-b]quinazoline-5-one hydrochloride of linear structure.
 In order to study the influence of the nature of chalcogen in the electrophilic reagent on the regiochemistry of cyclization in the reaction with N(3)-methallyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one, obtained in situ selenium tetrachloride was used. The selenochlorination reaction of N(3)-methallyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one in chloroform gave a linear hydrochloride of 2-methyl-2-[(trichloroseleno)methyl]-2,3-dihydro-5H-[1,3]thiazolo[2,3-b]quinazolin-5-one.
 Thus, the regiochemistry of electrophilic intramolecular cyclization of N(3)-alkenyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones by chalcogentetrahalides was investigated and it was proved that the annulationof the thiazoline cycle occurs with the formation of bioperspective bundles of tricyclic heterocycles of linear constitution independently from nature and origin of electrophilic reagent.

SYNTHESIS AND BROMINATION OF 2-METALLYLTHIO-3-HYDROXYIMINOMETHYLQUINOLINE

Quinoline and its condensed analogues are an important class of heterocycles with a wide range of biological activity. Many quinoline derivatives are used as substrates in organic synthesis and molecular design of pharmacologically active substances with different effects. Its reported a number of natural compounds containing a quinoline fragment are used as drugs. The annulation of azole and azine heterocycles to the quinoline backbone expands the search for biologically active compounds in this series. The most convenient and most effective method of annulation of additional cycles to quinoline is the reaction of electrophilic intramolecular cyclization of its unsaturated derivatives with various electrophilic reagents. Therefore, the synthesis of previously unknown polycyclic quinoline derivatives is an urgent problem.
 The purpose of this work is to study of the regio-selectivity of the process of electrophilic intramolecular cyclization of 2-methallylthio-3-(hydroxyiminomethyl)quinoline.
 The model oxime was obtained by the condensation reaction of 3-formyl-2-methalylthioquinoline with hydroxylamine hydrochloride in an alcohol-alkaline medium. 2-Methallylthio-3-(hydroxyiminomethyl)quinoline has several nucleophilic centers for studying of the regioselectivity of electrophilic heterocyclization - a multiple bond of a methallyl fragment, an endocyclic nitrogen atom of quinolone cycle, an exocyclic nitrogen atom of an imino group and an exocyclic atom oxygen of ОН- group. During the bromination of such an oxime, the formations of both a linear and angular tricyclic system are possible. It was found that when brominated with a double excess of bromine in chloroform medium, the thiazole cycle is annealed to the quinoline backbone to form 1-bromomethyl-4-((hydroxyimino)methyl)-1-methyl-1,2-dihydrothiazolo[3,2-a]-quinolin-10-ium tribromide.
 Thus, as a result of the performed research, the 2-methallylthio-3-(hydroxyiminomethyl) quinoline was obtained and its bromination was carried out. It is proved that the bromocyclization of the model oxime occurs regio-selectively with the formation of angular tribromide of 1-bromomethyl-4 -((hydroxyimino)methyl) -1-methyl-1,2-dihydrothiazolo [3,2-a] quinolin-10-ium. This tricyclic salt has the potential to have high biological activity.

Unexpected Substituent Effects in Spiro-Compound Formation: Steering N-Aryl Propynamides and DMSO toward Site-Specific Sulfination in Quinolin-2-ones or Spiro[4,5]trienones.

A highly substituent-dependent rearrangement allows for the novel and SOCl2-induced divergent synthesis of 3-methylthioquinolin-2-ones and 3-methylthiospiro[4.5]trienones through intramolecular electrophilic cyclization of N-aryl propyamides. DMSO acts as both solvent and sulfur source, and use of DMSO-h6/d6 enables the incorporation of SCH3 or SCD3 moieties to the 3-position of the heterocyclic framework. Different para-substituents trigger divergent reaction pathways leading to the formation of quinolin-2-ones for mild substituents and spiro[4,5]trienones for both electron-withdrawing and -donating substituents, respectively. On the basis of both computational and experimental results, a new mechanism has been put forward that accounts for the exclusive spirolization/defluorination process and the surprising substituent effects.

N-(4-Methoxyphenyl)-substituted bicyclic isothioureas: effect on morphology of cancer cells

Bicyclic isothioureas of N -(4-methoxyphenyl)-2-aminocycloalkane[ d ]thiazole type were obtained using intramolecular electrophilic cyclization of N -(cycloalk-2-enyl)- N ′-(4-methoxyphenyl)thioureas. Isothiourea fused with sevenmembered ring caused noticeable changes of the morphology of human lung carcinoma cells A549, but without affecting their microtubule net.

N-(4-Methoxyphenyl)-substituted bicyclic isothioureas: effect on morphology of cancer cells

Bicyclic isothioureas of N-(4-methoxyphenyl)-2-aminocycloalkane[d]thiazole type were obtained using intramolecular electrophilic cyclization of N-(cycloalk-2-enyl)-N′-(4-methoxyphenyl)thioureas. Isothiourea fused with sevenmembered ring caused noticeable changes of the morphology of human lung carcinoma cells A549, but without affecting their microtubule net.

Silver/Rhodium Relay Catalysis Enables C−H Functionalization of In Situ Generated Isoquinolines with Sulfoxonium Ylides: Construction of Hexahydrodibenzo[a,g]quinolizine Scaffolds

AbstractEmploying silver/rhodium relay catalysis strategy, an intramolecular electrophilic cyclization and C−H activation followed by cascade hydrogenation and reductive amination has been developed. The acylmethylated isoquinoline derivatives could be afforded with broad substrate scope in 23–88% yields, which could be further transformed to the core skeleton of hexahydrodibenzo[a,g]quinolizine as drug‐candidates. Moreover, this reaction was achieved in a gram‐scale. A reasonable reaction mechanism has been proposed based on a series of control and KIE experiments.magnified image

Access to a Phthalazine Derivative Through an Angular cis-Quinacridone.

Intramolecular electrophilic cyclization of a bisanthranilate afforded an angular cis-quinacridone compound, which condensed with hydrazine to give a phthalazine derivative. A [2+2+2] cyclization reaction occurred at the C-N double bond position of phthalazine when reacted with dimethyl acetylenedicarboxylate. The structures of these novel compounds were confirmed by crystallographic analysis. The phthalazine derivative decomposes back to quinacridone at ambient condition in the dark and as a solid with a half lifetime of about 22 months.

Regioselectivity of Intramolecular Electrophilic Cyclization of 2-(Alkenylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-ones with p-Methoxyphenyltellurium Trichloride

3-Phenyl-2-(prop-2-en-1-ylsulfanyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one reacted with 4-methoxyphenyltellurium trichloride in a regioselective manner to give angularly fused 1-{[dichloro(4-methoxyphenyl)-λ4-tellanyl]methyl}-4-oxo-5-phenyl-1,2,4,5,6,7,8,9-octahydrobenzo[4,5]thieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidinium chloride. Electrophilic cyclization of 2-(prop-2-en-1-ylsulfanyl)- and 2-(2-methylprop-2-en-1-ylsulfanyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-ones with 4-methoxyphenyltellurium trichloride afforded linearly fused 3-{[dichloro(4-methoxyphenyl)-λ4-tellanyl]methyl}-2,3,6,7,8,9-hexahydro-5H-benzo[4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidin-5-one hydrochlorides. Regardless of the reactant ratio, the products were isolated as 1:1 complexes with 4-methoxyphenyltellurium trichloride.