Substrate and Positional Selectivity in Electrophilic Substitution Reactions of Pyrrole, Furan, Thiophene, and Selenophene Derivatives

The relative reactivity (substrate selectivity) of five-membered heterocycles on electrophilic substitution (pyrrole >> furan > selenophene > thiophene) and their positional selectivity (furan > selenophene thiophene > pyrrole) are not consistent. The indicated differences in positional selectivity ( : ratios) of the parent heterocycles show up essentially in orientation on electrophilic substitution reactions of their derivatives and the corresponding benzannelated systems. It was shown that the positional selectivity was reduced in a sequence corresponding to the change in relative stability of the onium states of the elements (O⁺ < Se⁺ S⁺ < N⁺) and reflects the predominant role of the heteroatoms in stabilizing the -complexes formed on -substitution, in which the positive charge is distributed between the heteroatom and one -carbon atom (in -isom ers four atoms of the ring participate in delocalization of the charge). This interpretation was confirmed by quantum-chemical calculations carried out by the RHF/6-31G(d), MP2/6-31G(d)//RHF(6)-31G(d), and B3LYP/6-31G(d) ab initio methods.     

Synthesis and characterization of 9,9-dialkylfluorene capped benzo[c]thiophene/benzo[c]selenophene analogs as potential OLEDs

The synthesis of soluble benzo[c]thiophene analogs capped with 9,9-dialkylfluorene at one end is described.     

Condensed Pyridine Bases. Synthesis and Reactions of Benzofuro[2,3-c]indeno[2,1-e]-, Benzothieno[2,3-c]Indeno[2,1-e]-, Benzofuro-[3,2-c]Indeno[2,1-e]- and Thieno[2,3:4′,5′]-thieno[3,2-c]indeno[2,1-e]pyridines

Condensation of hetarene carboxaldehydes with phthalide gave 2-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 2-(3-hydroxy-1-oxoinden-2-yl)-5-ethylthieno[2,3-b]thiophene. Starting from hetaryl acetic acids gave 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]thiophene. Acylation of 3-hydroxy-1-oxoinden-2-yl-substituted heterocycles using acetic anhydride in the presence of 70% HClO₄ leads to the formation of pentacyclic pyrilium salts. Pentacyclic indenopyridines are prepared by treating the pyrilium salts with ammonia. The reaction of the carbonyl group in the indenopyridines with hydroxylamine, hydrazine hydrate, and in reduction using NaBH₄ has been studied.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 435–443, March, 2005.     

Kinetics and mechanisms of homogeneous catalytic reactions. Part 8. Regioselective reduction of benzo[ b ]thiophene catalyzed by OsH(CO)(κ3-OCOCH3)(PPh3)2

The complex OsH(CO)(κ³-OCOCH₃)(PPh₃)₂ (1) catalyzes the reduction of benzo[b]thiophene (BT) to 2,3-dihydrobenzo[b]thiophene (DHBT), under mild reaction conditions. A kinetic study lead to the rate law: r = K ₁ K ₂ k ₃ /{1 + K ₁ (1+K ₂ )[BT]}[Os][BT][H₂]. A catalytic cycle was proposed, which involves the oxidative addition of hydrogen as rate-determining step.     

Ab initio study of atropisomers of derivatives of 1,8-di-pyridine 9H-fluorene, dibenzo[b,d]furan, 9H-carbazole and dibenzo[b,d]thiophene

Ab initio calculation at HF/6-31G^* and MP2/6-31G^* levels of theory for geometry optimization of some syn- and anti-1,8-di-pyridine 9H-fluorene, dibenzo[b,d]furan, 9H-carbazole and Dibenzo[b,d]thiophene are reported. The rotational barrier energy, heat of formation and Gibbs energy are determined for the conversion of the anti-(syn) to the syn (anti)-isomers at 25 °C in the gas phase. The models are chosen as isomers of 9H-fluorene, dibenzo[b,d]furan, 9H-carbazole and dibenzo[b,d]thiophene as scaffold with pyridine as module. Results obtained show that (at equilibrium) for most of atropisomers the syn- is favored over the anti-isomer. Moreover, the ground state structures show that the modules are not parallel to each other but are tilted away in order to increase separation and there by minimize electrostatic repulsion. In atropisomers of 9H-carbazole the isomers are showing an attraction due to the presence of nitrogen atom. Influence of the position of nitrogen atom on the magnitude of the rotational barriers in these atropisomers is also studied.     

Purines, pyrimidines, and related fused systems. 20. Heterocyclizations of 6-alkynyl-1,3-dimethyllumazines. Synthesis of pyrrole and thiophene analogs of some natural pteridines

Sonogashira cross-coupling of 6-chloro-1,3-dimethyllumazine with terminal alkynes gave 6-alkynyl derivatives in good yields. Oxidative amination of the latter with primary alkylamines was accompanied by the pyrrole-ring closure to form 1-R"-2-R-6,8-dimethylpyrrolo[3,2-g]pteridine-5,7(6H,8H)-diones. The addition of bromine to 6-alkynyllumazines afforded the corresponding dibromoalkenes whose treatment with sodium trithiocarbonate gave rise to 2-R-6,8-dimethylthieno[3,2-g]pteridine-5,7(6H,8H)-diones. The latter compounds are close analogs of the metabolite of molybdenum cofactor (molybdopterine).     

Synthesis of Heterocycles from the Products of Anionic Arylation of Unsaturated Compounds. 7. Products of Haloarylation of Acrylic Acid and Its Esters in the Synthesis of Benzo[b]thiophene Derivatives

3-Chloro-2-chlorocarbonylbenzo[b]thiophenes were obtained on oxidation of Meerwein reaction products, viz. 3-aryl-2-halopropionic acids and their esters, with thionyl chloride in the presence of N-benzyl-N-methylmorpholinium chloride. Disubstituted thioureas were synthesized by the reaction of these compounds with ammonium thiocyanate and aromatic amines, and were cyclized by interaction with iodoacetic acid with the formation of 4-thiazolidinone derivatives. The same cyclization in the presence of aromatic aldehydes leads to the formation of the corresponding 5-arylidene-substituted 4-thiazolidinones.     

Synthesis of 2,3-disubstituted derivatives of pyrano-, thiopyrano-, and benzoannelated pyrido[2,3-<Emphasis Type="Italic">b</Emphasis>]thieno[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

A new methods have been developed for the synthesis of condensed pyrido[2,3-b]thieno[3,2-d]pyrimidines based on cyclic derivatives of 4-cyanopyridine-3-thiones. The presence of two different reactive functional groups NH₂ and CONH gives the possibility of carrying out different conversions of thieno[2,3-b]pyridines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1245–1252, August, 2008.     

Halogenation reactions in position 3 of quinoline-2,4-dione systems by electrophilic substitution and halogen exchange

Summary 3-Substituted 4-hydroxy-2(1H)-quinolones3,5,7 are halogenated with bromine or sulfuryl chloride to yield the quinolinediones9 or10. Reaction of3,5,7 with chloroform gives the dichloromethyl quinolinediones11. Halogen exchange leads from the chloro quinolinediones10 to fluoro quinolinedones12 and to azido quinolinediones13. Similarly the dichloro quinolinedione10 an reacts to the difluoro quinolinedione14, which is reduced to the 3-fluoro-4-hydroxyquinolone16 and reacts again with sulfuryl chloride to give the mixed 3-chloro-3-fluoroquinolinedione15.Herrn Prof. Dr. Erich Ziegler in freundschaftlicher Verbundenheit zum 80. Geburtstag gewidmet.     

Cross reactions of cyanoacetic acid derivatives with carbonyl compounds 3. One-step synthesis of substituted 2-amino-5-oxo-4,5-dihydropyrano[3,2-c]chromenes

Three-component reactions of 4-hydroxycoumarin, carbonyl compounds, and malono-nitrile or alkyl cyanoacetates in ethanol in the presence of Et₃N as a catalyst give substituted 2-amino-5-oxo-4,5-dihydropyrano[3,2-c]chromenes. Dedicated to Academician V. I. Minkin on the occasion of his 70th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 968–972, April, 2005.     

A novel three-component reaction of a secondary amine and a 2-hydroxybenzaldehyde derivative with an isocyanide in the presence of silica gel: an efficient one-pot synthesis of benzo[b]furan derivatives

Reaction of an isocyanide with an iminium ion intermediate, formed by reaction between an electron-poor 2-hydroxybenzaldehyde derivative and a secondary amine in the presence of silica gel proceeds smoothly at room temperature to afford benzo[b]furan derivatives in high yields.     

Condensed isoquinolines 27*. Synthesis and oxidation reactions of 5,13-dihydro-11H-isoquino[3,2-<Emphasis Type="Italic">b</Emphasis>]quinazolin-11-one

Condensation of 2-(cyanomethyl)benzoic acid with 2-aminobenzylamine gave 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-11-one. Its oxidation in nitrobenzene led to the formation of 5,13,5′,13′-hexahydro[6,6′]bi[isoquino[3,2-b]quinazoline]-11,11′-dione, but in dichlorobenzene in the presence of elemental sulfur and iodine it gave the rearrangement product 6H-dibenzo[b,f][1,8]naphthyridin-5-one. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.2, 273–279, February, 2008.     

Purines, pyrimidines, and related fused systems. 21. Oxidative amination of 3-chloro-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione

Oxidative amination of 3-chloro-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione with primary alkylamines and potassium amide in liquid ammonia gives rise to the corresponding 4-amino derivatives as the major products. The reactions with acyclic secondary amines are accompanied by annelation of the pyrrole moiety to the starting heterosystem to form 1-R-3-R"-6,8-dimethylpyrrolo[2",3";3,4]pyrimido[4,5-c]pyridazine-7,9(6H,8H)-diones. The reaction with piperidine as the aminating agent occurs exclusively as aminodehalogenation. The Sonogashira cross-coupling of 4-amino-3-chloro-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones with terminal alkynes affords 1-R-2-R"-6,8-dimethylpyrrolo[3",2";3,4]pyrimido[4,5-c]pyridazine-7,9(6H,8H)-diones.     

Investigations on 2,3′-biquinolines 22. Novel and convenient method for the synthesis of benzo[5,6]indolizino-[2,1-<Emphasis Type="Italic">b</Emphasis>]quinolinium-13-thiolates and benzo-[5,6]indolizino[1,2-<Emphasis Type="Italic">c</Emphasis>]quinoline-6(5H)-thiones

We have developed a method of synthesis of benzo[5,6]indolizino[2,1-b]quinolinium-13-thiolates and 5,6-dihydrobenzo[5,6]indolizino[1,2-c]quinoline-6-thiones based on the reaction of the corresponding 1′, 2′-dialkyl-1′,2′-dihydro-2,3′-biquinolines and 1′,4′-dialkyl-1′,4′-dihydro-2,3′-biquinolines with sulfur in DMF. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 849–851, June, 2007.     

Reaction of 6-methoxybenzo[b]furan-3(2H)-one and benzo[b]thiophen-3(2H)-one with 2-aryl-1,1-dicyanoethylenes as a convenient synthetic route to substituted 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]furans and 2-amino-4-aryl-3-cyano-4H-benzothieno[3,2-b]pyrans

The reactions of 6-methoxybenzo[b]furan-3(2H)-one with 2-aryl-1,1-dicyanoethylenes and malononitrile or with aromatic aldehyde and two moles of malononitrile afford 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]furans. The reactions of benzo[b]thiophen-3(2H)-one with 2-aryl-1,1-dicyanoethylenes or with aromatic aldehyde and one mole of malononitrile produce 2-amino-4-aryl-3-cyano-4H-benzothieno[3,2-b]pyrans.     

Purines,pyrimidines, and related fused systems. 19. Use of S N H methodology for the synthesis of a new heterocyclic system,pyrrolo[3",2":3,4]pyrimido[4,5-c]pyridazine

Sonogashira cross-coupling of 3-chloro-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione with terminal alkynes afforded the corresponding 3-(alkyn-1-yl) derivatives. Oxidative amination of the latter compounds with primary alkylamines was accompanied by heterocyclization to give 6,8-dimethylpyrrolo[3",2":3,4]pyrimido[4,5-c]pyridazine-7,9(6H,8H)-diones.     

Quantum chemical analysis of possible fragmentation of [M + H]<Superscript>+</Superscript> and [M + Na]<Superscript>+</Superscript> complexes of monosubstituted methane,cyclohexane, and benzene derivatives in mass spectrometric studies

The formation and fragmentation energies of the proton and sodium cation complexes with monosubstituted methane, cyclohexane, and benzene derivatives in which carbon atoms are bonded to substituents (NH₂, OH, F, Cl, Br, ONO₂, NO₂, COOH, CN, and Ph) were calculated by the B3LYP/6-31G(d) method. For [M + Na]⁺ complexes, the formation energies are much lower (and differ from one another to a much lesser extent), while the dissociation energies are much higher, than the corresponding energies of the [M + H]⁺ complexes. Na⁺ cation shows a lower selectivity toward localization at functional groups in molecules compared to H⁺. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 246–249, February, 2008.     

The behavior of <Emphasis Type="Italic">p</Emphasis>-bis{3-[N-(3-chloro-buten-2-yl)pyrrolidinio(piperidinio or morpholinio)]propyn-1-yl}benzene dichlorides in an aqueous base medium

In aqueous base medium p-bis{3-[N-(3-chlorobuten-2-yl)pyrrolidinio (piperidinio or morpholinio)]-propyn-1-yl}benzene dichlorides undergo a two-way dehydrochlorination-cyclization reaction to form benzo[5,6-a:5′,6′-c]bis(2,2-tetramethylene- or -2,2-pentamethylene-4-methylisoindolinium) and benzo-[5,6-a:5′,6′-c]bisspiro(4-methylisoindoline-2,4′-morpholinium) dichlorides. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 546–549, April, 2009.     

Synthesis,Structure, and Biological Activity of [2.2]Paracyclophane Derivatives. 8. α-Pyridyl([2.2]paracyclophan-4-yl)-phenylmethanol: Structure of the Complex with Cu(II) Chloride and Intramolecular Cyclization

The reaction of 2-benzoylpyridine with 4-([2.2]paracyclophanyl)lithium or of 4-benzoyl[2.2]paracyclophane with 2-pyridyllithium gave α-pyridyl([2.2]paracyclophan-4- yl)phenylmethanol. X-ray analysis has been used to study the molecular and crystalline structure of its complex with Cu(II) chloride. It was found that this triaryl-substituted methanol undergoes an intramolecular cyclocondensation in refluxing formic acid and involves the pyridine ring and the cyclophane substituent. Heterocyclization at the ortho-position of the latter gives 10-phenyl[2.2]paracyclophano[4,5-b]indolizine and cyclization at the pseudo-gem-position the 1-phenyl-1,1a-dehydro-6-aza[3.2.2](1,2,5)-6H-cyclophano[1,2-a]pyridine. The compounds prepared have luminescent properties. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 864–873, June 2005.     

Study of the behavior of p-bis{3-[N,N-dialkyl-N-(4-hydroxybut-2-ynyl)ammonio]prop-2-ynyl}-benzene dichlorides in relation to aqueous alkali. Double intramolecular recyclization of benzo[5,6;5′,6′-a,c]di(2,2-dialkyl-4-hydroxymethyl)isoindolinium dichlorides

p-Bis{3-[N,N-dialkyl-N-(4-hydroxybut-2-ynyl)ammonio]prop-2-ynyl}benzene dichloride in the presence of catalytic amounts of aqueous alkali is subject to a double intramolecular cyclization forming benzo[5,6;5′,6′-a,c]di(2,2-dialkyl-4-hydroxymethyl)isoindolinium dichloride in 40–42% yield. Simultaneously an intramolecular recyclization takes place with the formation of dialkyl(6-dialkylaminomethyl-7,9,10,12-tetrahydro-8,11-dioxadicyclopenta[c,g]phenanthren-1-ylmethyl)amines in 7–9% yield. The same compounds are obtained in 70–72% yield by the recyclization of benzo[5,6;5′,6′-a,c]di(2,2-dialkyl-4-hydroxymethyl)isoindolinium dichlorides under conditions of aqueous alkaline degradation. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1329–1335, September, 2006.