Furan derivatives. part 11 [1]. on substituent effects in the synthesis of 3,4,5,6-tetrahydrocyclohepta[cd]benzofurans

Tetrahydrocyclohepta[cd]benzofurans 7a-e were synthesized by the treatment of ( 5 -oxo-tetrahydro-5H-benzocyclohepten-4-yloxy)acetic acids 5a-e with sodium acetate in acetic anhydride or by heating of their esters 6a-e with sodium hydroxide or sodium hydride in dioxane. The yield of furans 7 decreased as a substituent R of acids 5 or esters 6 was changed from hydrogen to a methyl, ethyl, or isopropyl group. When R was a phenyl group furan 7e was always prepared in good yield. Sodium hydride was a useful base for synthesis of tetrahydrocyclohepta[cd]benzofurans.     

Synthesis,proton NMR stereochemical study and diels-alder reaction of (E)-7-arylidene-2H,6H-naphtho[1,8-bc]furan-2,6-diones

7-Arylidene-2H,6H-naphtho[1,8-bc]furan-2,6-diones 3 were prepared by a retro-Diels-Alder reaction of the corresponding dihydro 1,3-oxazines 2 or in a one pot synthesis from 6-hydroxy-2H-naphtho[1,8-bc]furan-2-one 1 . Their E configuration was established from the chemical shift's values of the vinylic proton and by ¹H nmr NOE difference spectroscopy. Cycloadditions of 3b upon styrene or stilbene were catalyzed by boron trifluoride etherate. The cycloadducts were obtained with the relative trans configuration.     

Photocyclization reactions. Part 4 . Synthesis of naphtho[1,8-bc]-furans and cyclohepta[cd]benzofurans using photocyclization of Ethyl 2-(8-Oxo-5,6,7,8-tetrahydro-1-naphthyloxy)acetates and ethyl 2-(5-Oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-4-yloxy)acetates

Photocyclization reactions were carried out on ethyl 2-(8-oxo-5,6,7,8-tetrahydro-1-naphthyloxy)acetates 1a-e and ethyl 2-(5-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-4-yloxy)acetates 2a-e in acetonitrile. Irradiation of 1a-e gave naphtho[1,8-bc]furanols 3a-e and naphtho[1,8-bc]furans 4a-e in 33–83% yields and ethyl acrylates 5b-d were produced in 3–25% yields during irradiation of 1b-d . On the other hand, 2a-e afforded cyclohepta[ad|benzofuranols 6a-e and cyclohepta[ad]benzofurans 7a-e in 44–87% yields. Ethyl acrylates 8b-d were also produced in 7–43% yields from irradiation of 2b-d . Substituent effects on photocyclization and reaction pathways are discussed.     

Pseudo-phenalenone und pseudophenaleniumsalze sowie ihre reaktionen

The reactivity of the thiapseudophenalenone ( 1, 2 -phenyl-5H-naphtho[1,8-bc]thiophen-5-one) and of the thiapseudophenalenium salt ( 2 , 2-phenyl-5-ethoxynaphtho[1,8-bc]thioliumtetra-fluoroborate) towards N-nucleophilic compounds R-NH₂ was of interest. We obtained the substituted iminothiapseudophenalenones ( 3a-3i, 4 ). With C-nucleophilic reactants we isolated 4a, 4b, 8-11 and with 2,3,4,5-tetrachlorocyclopentadiene we obtained thiapentapseudophena-fulvalene ( 7 ).     

Building up of a <Emphasis Type="Italic">peri</Emphasis>-Hydroxynaphthoyl Fragment on the Core of 2<Emphasis Type="Italic">H</Emphasis>-Naphtho[1,8<Emphasis Type="Italic">-bc</Emphasis>] furan

The reaction of 2-aryl-5-acetoxy-4,8-di-tert-butyl-2H-naphtho[1,8-bc]furan with dichloromethyl ethyl ether in the presence of aluminum chloride gave rise to 6-formyl derivatives of the title heterocyclic system, and at the use of aliphatic acids anhydrides in the presence of perchloric acid 6-acyl derivatives were obtained. The target products with a peri-hydroxycarbonyl group were obtained by the ester group elimination.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 2, 2005, pp. 237-242.Original Russian Text Copyright © 2005 by Tyurin, Antonov, Minyaeva, Mezheritskii.     

Ring closure reactions of cyclic 2-arylaminomethylene-1,3-diones

5-Arylaminomethylene compounds such as 5-arylaminomethylenepyrimidine-2,4,6-triones 2 or 2-phenylaminomethylenephenalene-1,3-dione 13 cyclize by thermolysis via migration of the arylamino group to pyrimido[4,5-b]quinoline-2,4-diones 6 or 7-oxo-7H-naphtho[1,8-bc]acridine 15 , respectively. 2-Phenylaminomethylenecyclohexane-1,3-dione 8 cyclizes to 9,9-dimethyl-9,10-dihydrophenanthridin-7(8H)-one 11 without rearrangement.     

Benzo[b] thiophene derivatives. XIV. Derivatives of naphtho[1,8-c] thiophene

In the course of our efforts to synthesize the sulfur isostere of lysergic acid, we have prepared a number of derivatives of the little known naphtho[1,8-bc]thiophene ring system. Two previously reported compounds, 2-bromo-3,4-dihydro-5-oxo-5H-naphtho[1,8-bc]thiophene and 2-bromo-5-hydroxy-3,4-dihydro-5H-naphtho[1,8-bc] thiophene have been obtained pure for the first time, and the syntheses and spectral data of eighteen new compounds are presented. The new compounds include alcohols, ketones, and halogen derivatives of partially reduced naphtho-[1,8-bc] thiophene, as well as the sulfones of several of these compounds.     

Reaktionsverhalten von 2-brom-thiapseudophenalenon und 2-brom-thia-pseudophenaleniumtetrafluoroborat

The reactivity of the 2-bromothiapseudophenalenone ( 1 ) 2-bromo-5H-naphtho[1,8-bc]-thiophen-5-one and of the 2-bromothiapseudophenalenium salt ( 2 ) 2-bromo-5-ethoxynaphtho-[1,8-bc]thiolium-tetrafluoroborate towards the N-nucleophilic compounds R-NH₂ ( 3 ) or R-NH-NH₂ and the C-nucleophilic molecules e.g., malonodinitrile, barbituric acid was of interest. We obtained the substituted hydroxyiminothiapseudophenalenone derivatives 4a-g, 6a-g, 7, 8, 9, 11a-o, 12 and 14 .     

Halogen effect on tandem [4+2] cycloaddition/aromatization sequence of allenyl 2-halo-3-vinylcyclohex-2-enyl ether

Steric and enthalpic effects of substituents on diene moieties play a crucial role in intramolecular cycloaddition reactions. Allenyl 2-halogenated-3-vinylcyclohex-2-enyl ethers underwent a tandem [4+2] cycloaddition/aromatization reaction to afford the corresponding tetrahydro-3H-naphtho[1,8-bc]furan compound in high yield.     

Gas-phase pyrolytic reactions. Part 6. [1] Behavior of ethyl (hetero)arylcarboxylate esters in thermal elimination reactions

Rates, Arrhenius parameters, and Hammett substituent constants are obtained for the gas-phase thermal elimination of ethyl benzoate (1) and ethyl 2—thienyl— (2), 3—thienyl— (3), 2—furyl— (4), 3—furyl— (5), 4—pyridyl— (6), 3—pyridyl— (7), and 2—pyridylcarboxylate (8) esters. The log A/s⁻¹ and the E_a/kJ mol⁻¹ values of these esters averaged 13.60 and 216.3, respectively. The present results are compared with data previously reported for the corresponding isopropyl and t-butyl analogues, and the findings are rationalized in terms of a plausible transition state for the elimination pathway. © 1997 John Wiley & Sons, Inc. Int J Chem Kinet 29: 289–293, 1997.     

Halide salts of antimigraine agents eletriptan and naratriptan

Molecules of eletriptan hydrobromide monohydrate (systematic name: (1S,2R)‐1‐methyl‐2‐{5‐[2‐(phenylsulfonyl)ethyl]‐1H‐indol‐3‐ylmethyl}pyrrolidinium bromide monohydrate), C₂₂H₂₇N₂O₂S⁺·Br⁻·H₂O, (I), and naratriptan hydrochloride (systematic name: 1‐methyl‐4‐{5‐[2‐(methylsulfamoyl)ethyl]‐1H‐indol‐3‐yl}piperidinium chloride), C₁₇H₂₆N₃O₂S⁺·Cl⁻, (II), adopt conformations similar to other triptans. The C‐2 and C‐5 substituents of the indole ring, both of which are in a region of conformational flexibility, are found to be oriented on either side of the indole ring plane in (I), whilst they are on the same side in (II). The N atom in the C‐2 side chain is protonated in both structures and is involved in the hydrogen‐bonding networks. In (I), the water molecules create helical hydrogen‐bonded chains along the c axis. In (II), the hydrogen bonding of the chloride ions results in macrocyclic R₄²(20) and R₄²(24) ring motifs that form sheets in the bc plane. This structural analysis provides an insight into the molecular structure–activity relationships within this class of compound, which is of use for drug development.     

Investigation of Steric Influences on Hydrogen‐Bonding Motifs in Cyclic Ureas by Using X‐Ray,Neutron, and Computational Methods

A series of urea‐derived heterocycles, 5N‐substituted hexahydro‐1,3,5‐triazin‐2‐ones, has been prepared and their structures have been determined for the first time. This family of compounds only differ in their substituent at the 5‐position (which is derived from the corresponding primary amine), that is, methyl ( 1 ), ethyl ( 2 ), isopropyl ( 3 ), tert‐butyl ( 4 ), benzyl ( 5 ), N,N‐(diethyl)ethylamine ( 6 ), and 2‐hydroxyethyl ( 7 ). The common heterocyclic core of these molecules is a cyclic urea, which has the potential to form a hydrogen‐bonding tape motif that consists of self‐associative (8) dimers. The results from X‐ray crystallography and, where possible, Laue neutron crystallography show that the hydrogen‐bonding motifs that are observed and the planarity of the hydrogen bonds appear to depend on the steric hindrance at the α‐carbon atom of the N substituent. With the less‐hindered substituents, methyl and ethyl, the anticipated tape motif is observed. When additional methyl groups are added onto the α‐carbon atom, as in the isopropyl and tert‐butyl derivatives, a different 2D hydrogen‐bonding motif is observed. Despite the bulkiness of the substituents, the benzyl and N,N‐(diethyl)ethylamine derivatives have methylene units at the α‐carbon atom and, therefore, display the tape motif. The introduction of a competing hydrogen‐bond donor/acceptor in the 2‐hydroxyethyl derivative disrupts the tape motif, with a hydroxy group interrupting the N? H???O?C interactions. The geometry around the hydrogen‐bearing nitrogen atoms, whether planar or non‐planar, has been confirmed for compounds 2 and 5 by using Laue neutron diffraction and rationalized by using computational methods, thus demonstrating that distortion of O‐C‐N‐H torsion angles occurs to maintain almost‐linear hydrogen‐bonding interactions.     

A new procedure for fusion of a five-membered ring. Building up of the naphtho[1,8-<Emphasis Type="Italic">bc</Emphasis>]furan system

Reactions of 2,6-di-tert-butylnaphthalene-1,5-diol with aminals derived from aromatic aldehydes afforded 2-aryl-4,8-di-tert-butyl-2H-naphtho[1,8-bc]furan-5-ols and 2-aryl-4,8-di-tert-butylnaphtho[1,8-bc]-furan-5-ones.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 9, 2004, pp. 1349–1351.Original Russian Text Copyright © 2004 by Tyurin, Minyaeva, Mezheritskii.     

取代基对有机钼化合物中α-氢转移反应势垒和产物稳定性的影响

使用B3LYP方法研究了发生在有机钼化合物R³R⁴Mo(≡CH)(CHR¹R²)和R³R⁴Mo(＝CH₂)(＝CR¹R²)之间的α-氢转移反应, 探讨了R¹, R², R³和R⁴位置上不同取代基对α-氢转移反应势垒和产物稳定性的影响. 研究发现, 金属钼有机化合物中, 发生α-氢转移的碳原子在过渡态中采用sp²杂化. R¹和R²位置上取代基对α-氢转移反应势垒的影响取决于取代基对过渡态中碳原子的未参与sp²杂化的p_z轨道上单电子的离域作用. 当R¹, R²位置是甲基时, 由于碳原子的p_z轨道与甲基的一个C—H键轨道间存在强的超共轭效应, 从而可以较大程度地降低α-氢转移反应的势垒. 研究结果还表明, 当R³, R⁴位置为SiH₃时的反应势垒较低. 所以当R¹和R² 位置为Me, R³和R⁴位置为SiH₃时, 反应势垒最低. 第一个甲基取代R¹或R²位置的H时, 反应势垒降低很大; 第二个甲基继续取代时, 反应势垒的降低约为第一个甲基的一半. 第一个SiH₃取代R³或R⁴位置的甲基时, 反应势垒降低较大; 第二个SiH₃继续取代时, 反应势垒的降低小于第一个SiH₃的一半. 对反应物和产物的相对稳定性的研究表明, 第一个甲基和第二个甲基对产物的相对能量的降低几乎相同; 第一个SiH₃降低产物的相对能量, 但是第二个SiH₃使产物的相对能量升高, 从而抵消了第一个SiH₃对产物的稳定作用.     

取代基对有机金属铼化合物中分子内α-氢转移反应势垒的影响

使用B3LYP方法研究了有机铼化合物R³R⁵(NHR⁴)Re(＝CHR¹)(＝NR²)中分子内α-氢转移反应, 探讨了不同取代基对α-氢转移反应势垒的影响. 研究发现, 可以通过改变取代基来影响过渡金属Re有机化合物中的α-氢转移反应. R¹位置的取代基为Me或CMe₃时, 可以较大程度降低α-氢转移反应的势垒. R²为H时, α-氢转移反应势垒最低. R³和R⁵位置为SiH₃时的反应势垒最低. R⁴为CMe₃时, α-氢转移反应势垒最低. 研究结果还表明, 取代基对于反应势垒的影响有加和性.     

Silylation of γ-nitro ketones as a convenient approach to the synthesis of 2-[N,N-bis(silyloxy)amino]-2,3-dihydrofurans and conjugated enoximes

Silylation of -nitro ketones of the general formula R¹COCH(R²)CH(R³)CH(R⁴)NO₂ proceeded stereoselectively to give 2-[N,N-bis(trimethylsilyloxy)amino]-2,3-dihydrofurans, conjugated enoximes, silylation products of the carbonyl group or both functional groups, or N,N-bis(trimethylsilyloxy)enamine depending on the nature and positions of the substituents in the carbon skeleton. Dihydrofuran derivatives are formed for R¹ = Ar or cyclo-C₃H₅. Enoximes are generated as the silylation products of the starting ketones with enhanced -proton mobility (R³ = CO₂Me or 4-NO₂C₆H₄). The presence of an alkyl group at the carbonyl function (R¹ = Alk) is favorable for the formation of enoximes. Finally, the introduction of a substituent at the position with respect to the nitro group (R⁴ = Me, CO₂Me, or Ph) leads to the formation of silyl enolates. Under the action of NH₄F in MeOH, dihydrofurans can be transformed into substituted furans in moderate yields.     

Substituent Effects on Oxidation‐Induced Formation of Quinone Methides from Arylboronic Ester Precursors

A series of arylboronic esters containing different aromatic substituents and various benzylic leaving groups (Br or N⁺Me₃Br^?) have been synthesized. The substituent effects on their reactivity with H₂O₂ and formation of quinone methide (QM) have been investigated. NMR spectroscopy and ethyl vinyl ether (EVE) trapping experiments were used to determine the reaction mechanism and QM formation, respectively. QMs were not generated during oxidative cleavage of the boronic esters but by subsequent transformation of the phenol products under physiological conditions. The oxidative deboronation is facilitated by electron‐withdrawing substituents, such as aromatic F, NO₂, or benzylic N⁺Me₃Br^?, whereas electron‐donating substituents or a better leaving group favor QM generation. Compounds containing an aromatic CH₃ or OMe group, or a good leaving group (Br), efficiently generate QMs under physiological conditions. Finally, a quantitative relationship between the structure and activity has been established for the arylboronic esters by using a Hammett plot. The reactivity of the arylboronic acids/esters and the inhibition or facilitation of QM formation can now be predictably adjusted. This adjustment is important as some applications may benefit and others may be limited by QM generation.     

α-Thioureidoalkylation of functionally substituted ureas: I. Tandem cyclization and esterification in reactions of <Emphasis Type="Italic">N</Emphasis>-(carboxyalkyl)ureas with 1,3-dialkyl-4,5-dihydroxy-4,5-diphenylimidazolidine-2-thiones in alcohols

Acid-catalyzed reactions of N-(carboxyalkyl)ureas with 1,3-dialkyl-4,5-dihydroxy-4,5-diphenylimidazolidine-2-thiones in methanol or propan-2-ol led to the formation of previously unknown ω-(4,6-dialkyl-2-oxo-3a,6a-diphenyl-5-thioxooctahydroimidazo[4,5-d]imidazol-1-yl)alkanoic acids and their methyl and isopropyl esters. The structure of some esters was proved by X-ray analysis. Methyl (4,6-diethyl-2-oxo-3a,6adiphenyl-5-thioxooctahydroimidazo[4,5-d]imidazol-1-yl)acetate showed anxiolytic effect.     

Ethyl 1,4-dihydropyridinecarbodithioates and the electronic effects of sulfur-containing ester substituents

Methods have been developed for the synthesis of the ethyl esters of 2,6-dimethyl-1,4-dihydropyridine-3,5-bis(carbodithioic) and 4-ary1-2-methyl-5-oxo-4,5-dihydro-1H-indeno[1,2-b]pyridine-3-carbodithioic acids. From the physicochemical properties (acid dissociation constants and electrochemical oxidation potentials of the 1,4-dihydropyridines with sulfur-containing substituents in the -positions, the electronic effects of these groups in the 1,4-dihydropyridine system have been determined. The inductive and resonance constants of these substituents in aromatic compounds have been found by ¹³C and ¹⁹F NMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 491–500, April, 1986.     

Two new conformationally restricted 4,5‐dihydroxynorvaline analogues with a norbornane skeleton

The structures of two conformationally restricted 4,5‐di­hydroxy­norvaline analogues with a norbornane skeleton, namely methyl (1S,2S,3R,4R)‐2‐benz­amido‐3‐(1,2‐di­hydroxy­ethyl)­bi­cyclo[2.2.1]­heptane‐2‐carboxyl­ate, C₁₈H₂₃NO₅, and methyl (1R,2S,3R,4S)‐2‐benz­amido‐3‐(1,2‐di­hydroxy­ethyl)­bi­cyclo[2.2.1]­heptane‐2‐carboxyl­ate, C₁₈H₂₃NO₅, exhibit a conformation in the helical region of the ?,ψ map but their handedness is opposite. In both cases, the torsion angles (χ^1,1) giving the relative orientation of the 1,2‐di­hydroxy­ethyl group of the amino acid side chain and the benz­amide group of the peptide chain indicate that these groups adopt a nearly eclipsed conformation. Both compounds show a complex hydrogen‐bonding pattern.