2-Substituted imidazoles. 1. Reactions of 1-methyl-2-(2-furyl)imidazole with electrophiles

1-Methyl-2-(2-furyl)imidazole has been synthesized. Electrophilic attack (bromination, nitration, formylation, acylation, and hydroxymethylation) occurs in most cases at the free -position of the furan ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1396–1400, October, 1989.     

A facile ring opening reaction of furfuryl selenides. Highly efficient method for dienones

Treatment of furfuryl phenyl selenides with butyllithium or metallic lithium induces the facile ring opening reaction of their furan ring and the corresponding dienones are obtained in high yields.     

1-Bromo-2-trifluoroacetylcyclobutenes as novel building blocks for the construction of trifluoromethyl substituted heterocycles. Part 1: Synthesis of 5-(trifluoromethyl)-2(5H)-furanones condensed with substituted cyclobutenes

The regioselective reduction of substituted 1-bromo-2-trifluoroacetylcyclobutenes by lithium aluminium hydride affords corresponding brominated alcohols, which, under the treatment of two equivalents of butyllithium, give new lithiated cyclobutenes. Their carboxylation followed by lactonization induced by trifluoroacetic anhydride appeared to be an effective approach towards 5-trifluoromethylated furanones condensed with substituted cyclobutene rings.     

Synthesis and deprotonation of 2-(halophenyl)pyridines and 1-(halophenyl)isoquinolines

The ability of the 2-pyridyl and 1-isoquinolyl groups to direct metalation was studied in the benzene series. For this purpose, 2-(halophenyl)pyridines and 1-(halophenyl)isoquinolines were prepared. Interestingly, nucleophilic addition reactions on the azine ring were not observed under kinetic control using butyllithium, and the substrates were cleanly deprotonated on the benzene ring: the azine ring acidifies the adjacent hydrogen H2' (N-H2' interaction through space and/or inductive electron-withdrawing effect) and probably favors the approach of butyllithium (chelation). Under thermodynamic conditions using lithium dialkylamides, the presence of the azine group makes the lithio derivative at C2' more stable (chelation and/or inductive electron-withdrawing effect). This was evidenced in two ways: (1) syntheses of 2-halophenyllithiums (F, Cl, Br) substituted at C6 by a 2-pyridyl or 1-isoquinolyl group without elimination of lithium halide and (2) iodine migration from C2' to C4' when treating 2-(3-halo-2-iodophenyl)pyridines or 1-(3-fluoro-2-iodophenyl)isoquinoline with LTMP. Comparisons between the 2-pyridyl and fluoro units showed the latter was the stronger directing group for deprotonation.     

Research on the chemistry of 2-hetarylbenzimidazole. 3. Reaction of 1-methyl-2-(5′-methyl-2′-hetaryl) benzimidazoles with electrophilic reagents

A number of new derivatives of 1-methyl-2-(5-methyl-2-hetaryl)benzimidazole were synthesized by electrophilic substitution. The substituent enters the position of the 4-hetaryl ring. A furan ring that contains a methyl group in the 5 position undergoes profound destructive oxidation under the influence of acetyl nitrate. Depending on the conditions, bromination leads to the formation of bromo derivatives that are substituted in the benzene or hetaryl ring.See [7] for Communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 520–523, April, 1981.     

Reaction of 5-(2-furyl)-1-methyl-1<Emphasis Type="Italic">H-</Emphasis> and 1-methyl-5-(2-thienyl)-1<Emphasis Type="Italic">H</Emphasis>-imidazoles with electrophilic reagents

5-(2-Furyl)-1-methyl-1H- and 1-methyl-5-(2-thienyl)-1H-imidazoles were synthesized. The electronwithdrawing effect of the 5- and 2-imidazole substituents on the furan ring was studied by ¹H NMR spectroscopy and quantum-chemical calculations. Some electrophilic substitution reactions were investigated (nitration, bromination, sulfonation, hydroxymethylation, formylation, and acylation). In some cases, depending on the reaction conditions, both the furan and thiophene ring and the imidazole fragment undergo electrophilic attack.     

Steric interactions in 2-substituted imidazoles. The molecular structure of 1-methyl-2-phenylimidazole and 1-methyl-4-phenylimidazole

The crystal and molecular structures are reported for two isomeric imidazoles: 1-methyl-2-phenylimida-zole ( 1 ) and 1-methyl-4-phenylimidazole ( 2 ). In molecule 2 the phenyl ring is rotated by 7.3° from the het-erocyclic plane due to steric interactions. The steric congestion is much more severe in 1 , with the adjacent methyl and phenyl substituents mininizing nonbonded interactions via a 32.3° rotation of the phenyl ring and a 0.159 Å displacement of the methyl carbon from the heterocyclic plane.     

Chemistry of 2-hetarylbenzimidazoles. 10. Synthesis and properties of 2-(3′-furyl)-1-methyl-1H-benzimidazole

A study was carried out on the electrophilic substitution reactions such as chloromethylation, bromination, sulfonation, nitration, and acylation of 2-(3′-furyl)-1-methyl-1H-benzimidazole in acid media. All these reactions proceed at C₍₂₎ and C₍₅₎ of the furan ring. Quantum-chemical calculations of the three-dimensional structure of such heterocyclic systems are given. Communication 9, see ref. [1]. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1815–1820, December, 2005.     

Reaktionen und Verknüpfungen von 1,2-Diaza-3-sila-5-cyclopentenen

Reactions and Bridging of 1,2-Diaza-3-sila-5-cyclopentenes 1,2-Diaza-3-sila-5-cyclopentenes react with butyllithium to give lithium salts. In reactions of the lithium salts with halosilanes ( 1–7 ), trimethyltinchloride (8) or methyliodide ( 9 ) substituted compounds are obtained by LiHal elimination. Bromosuccinimide brominates the methylene group of the ring system ( 10 ). Bridging of 1,2-diaza-3-sila-5-cyclopentenes by boryl and silyl groups are described ( 11–13 ). In the reaction of trifluorophenylsilane with lithiated 1 , 2-tert.-butyl-4-lithio-3,3,5-trimethyl-4-fluorodimethylsilyl-1,2-diaza-3-sila-5-cyclopentene, which is stable in solution, a second substitution takes place ( 14 ). The thermal elimination of LiF from lithiated 1 leads to the formation of the spirocyclic compound 15 . The n.m.r. and mass spectra of the compounds are reported.     

Studies in ring-opening polymerization. III. 5-methyl-5-propyl and 5-methyl-5-isopropyl-1,3,2-dioxathiolan-4-one 2-oxide

5-Methyl-5-propyl-1,3,2-dioxathiolan-4-one 2-oxide (MPAS) and 5-methyl-5-isopropyl-1,3,2-dioxathiolan-4-one 2-oxide (MiPAS), which are isomers of the previously studied 5,5-diethyl-1,3,2-dioxathiolan-4-one 2-oxide (DEAS), have been synthesized and their polymerizability compared with that of the last compound. The two unsymmetrically substituted monomers polymerize by a mechanism which is substantially identical to that of their symmetrically substituted counterpart. In dry nonhydroxylic solvents the rate-determining process is the primary scission of the ring, which takes place with elimination of sulfur dioxide and concurrent ring contraction to form an α-lactone intermediate. In this reaction, the parent acid, produced by reaction of the monomer with adventitious traces of moisture, acts as the initiating species. The resultant polymers are all hydroxyl/carboxyl-terminated, but, whereas those derived from the two unsymmetrically substituted monomers are amorphous and readily soluble in a variety of organic solvents, those derived from the diethyl-substituted ring have been shown to be highly crystalline materials which dissolve in very few solvents. The relative polymerization rates are illustrated by the first-order rate constants for decomposition in nitrobenzene at 90°C: DEAS, 20.1 × 10^?5 sec^?1; MiPAS, 11.0 × 10^?5 sec^?1; MPAS, 9.7 × 10^?5 sec^?1. The role of the substituents in determining the magnitude of these constants is discussed in terms of both the Thorpe-Ingold effect and electron donation at C-5.     

Substituted 2-methyl- and 2-methyleneindolines. 6. Adducts of dialkylphosphites with 1,3,3-trimethyl-2-methyleneindoline. Reagents for synthesizing 5-substituted 2-methyl- and 2-methyleneindolines

The readily formed addition products of dialkylphosphites and 1,3,3-trimethyl-2-methyleneindoline have been used to synthesize 1,2,3,3-tetramethyl-3H-indolium salts and their derivatives substituted in the benzene ring. In most cases the protecting phosphorus group can be readily removed by adding mineral acids.For Communication 5, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1049–1054, August, 1993.     

2-Bis (dimethylamino)phosphinoyl-1-lithio-1, 2, 3, 4-tetrahydroisoquinoline. A highly nucleophilic d1-reagent for the preparation of 1-substituted tetrahydroisoquinolines

The title compound 4 is generated from the phosphoric amide 5 in tetrahydrofuran with butyllithium. The lithium reagent 4 is stable at room temperature; its reactions with electrophiles furnish the products 6–22 , 26 , 27 , see Table 1 and the Scheme. A second alkylation is also possible, see 23–25 . The cleavage to tetrahydroisoquinolines is accomplished in refluxing aqueous-methanolic hydrochloric acid, see Table 2. Phosphinoylation, lithiation, reaction with electrophiles and cleavage constitute an efficient sequence for 1-alkylation of the isoquinoline nucleus.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 10. Reactions with ester enolates. Synthesis of 4-hydroxy-1-methyl-3-prenyl-2(1H)-quinolinones,Crucial intermediates in the synthesis of quinoline alkaloids

N-Methylisatoic anhydride reacts with the lithium enolates of esters to produce β-ketoesters 4 in nearly quantitative yield. Thermal cyclization of these relatively unstable intermediates afford the corresponding 3-substituted-4-hydroxy-1-methyl-2(1H)-quinolinones (5) in good yields. The reaction of the lithium enolate of 5-methyl-4-hexenoic acid ethyl ester ( 14 ) with various nuclear substituted isatoic anhydrides gives 4-hydroxyl-methyl-3-prenyl-2(1H)-quinolinones 8, 9 , and 18 which are highly desirable intermediates in the synthesis of a variety of quinoline alkaloids. Treatment of 18 with DDQ furnishes oricine in 73% yield.     

3-Chloroalkylfurans in the reaction with sodium diethyl phosphite

Reduction of 3-acylfurans with lithium alumohydride in ether yields stable secondary alcohols. By treatment with thionyl chloride in the presence of pyridine, they are converted to the corresponding chlorides. 3-(1-Chloroethyl)furan and 5-methyl-3-(1-chloroethyl)furan react with sodium diethyl phosphite to give two products: 3-(1-diethoxyphosphorylethyl)furans and 3-ethyl-2-(diethoxyphosphoryloxy)furans. The methyl group in position 5 of the furan ring increases the relative phosphate content of the mixture by a factor of approximately 2.5. Blocking of position 2 or both positions 2 and 5 of the ring with methyl groups leads to phosphoate formation only. The reaction of 2,5-dimethyl-3-(1-chloro-2-methylpropyl)furan also occurs according to the Michaelis-Becker scheme. The products of the side chain dehydrohalogenation with sodium diethyl phosphite were not found.     

New Gilman-type lithium cuprate from a copper(II) salt: synthesis and deprotonative cupration of aromatics

Deprotonative cupration of aromatics including heterocycles (anisole, 1,4-dimethoxybenzene, thiophene, furan, 2-fluoropyridine, 2-chloropyridine, 2-bromopyridine, and 2,4-dimethoxypyrimidine) was realized in tetrahydrofuran at room temperature using the Gilman-type amido-cuprate (TMP)₂CuLi in situ prepared from CuCl₂·TMEDA through successive addition of 1 equiv of butyllithium and 2 equiv of LiTMP. The intermediate lithium (hetero)arylcuprates were evidenced by trapping with iodine, allyl bromide, methyl iodide, and benzoyl chlorides, the latter giving the best results. Symmetrical dimers were also prepared from lithium azine and diazine cuprates using nitrobenzene as an oxidative agent.     

4′-Bromo(and azido)-10,10-dimethylspiro[9,10-dihydro-10-sila-2-azaanthracene-9,2′-tetrahydrofuran]

Dehydrobromination of 10,10-dimethyl-9-(2,3-dibromoprop-1-y1)-9,10-dihydro-10-sila-2-aza-9-anthrol with butyllithium follows two routes to give the Z- and E-isomers of furan ring-brominated spiro(dihydrosilaazaanthracene-9,2-tetrahydrofuran), and the cis- and trans-isomers of 10,10-dimethyl-9-(3-bromoallyl)-9,10-dihydro-10-sila-2-aza-9-anthrol. Analogous compounds have been obtained bearing an azidogroup in the tetrahydrofuran ring, and a spiran with a dihydrofuran fragment. The pure isomers have been isolated, and their structures established.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 696–700, May, 1989.     

Chemistry of 2-hetarylbenimidazoles. 7. Transformations of trans-1-methyl-2-[Β-(2′-furyl)vinyl] benzimidazole

Electrophilic substitution reactions in the furylvinylbenzimidazole series were studied. In nitration, sulfonation, bromination, acylation, formylation, and hydroxymethylation reactions, the substituent enters at the -position of the furan ring. The presence of a vinylene group reduces the influence of the benzimidazole fragment on the furan ring, and therefore the reactions in the latter proceed considerably more rapidly and under milder conditions than in the case of furylbenzimidazole. Calculated data are given for the -electronic density on the carbon atoms of furyl-vinylbenzimidazole, obtained by the CNDO method.For Communication 6, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1078–1081, August, 1986.The authors wish to express their gratitude to Yu. N. Sheinker for help in the interpretation of the PMR spectra.     

Synthesis,structure and cytotoxic activity of 2‐acetyl‐5‐trimethylsilylthiophene(furan) and their oximes

5‐Trimethylsilylderivatives of 2‐acetylthiophene and ‐furan have been regioselectively prepared by a one‐pot procedure from the corresponding 2‐acetylfuran or 2‐acetylthiophene using lithium N‐methylpiperazide (LNMP)–butyllithium–trimethylchlorosilane–water as the sequence of reagents. The ketones obtained were converted to the corresponding oximes. The structure of 2‐acetyl‐5‐trimethylsilylthiophene oxime (E‐isomer) has been studied by X‐ray diffraction. Formation of centrosymmetric dimers by means of H‐bonds has been observed. The intermolecular hydrogen bond O9? H…N8 length is 2.842(5) Å [H…N8 = 1.87 (6) Å, O9? H…N8 = 157(4)°]. Copyright © 2006 John Wiley & Sons, Ltd.     

An efficient synthesis of 4,5-dihydronaphtho[2,1-b]furan through a novel ring transformation of 2H-pyran-2-one

An innovative route for the synthesis of substituted naphtho[2,1-b]furan has been delineated through a ring transformation reaction of suitably functionalized 2H-pyran-2-ones by reaction with 6,7-dihydro-5H-benzofuran-4-one, in good yield.     

Furopyridines. XXIII. Synthesis and reactions of chloropyridine derivatives of furo[2,3-b]-, -[2,3-c]- and -[3,2-c]pyridine

Chlorination of the N-oxides of furo[2,3-b]- 1a , -[2,3-c]- 1b and -[3,2-c]pyridine 1c with phosphorus oxychloride afforded compounds substituted normally at the α- or λ-position to the ring nitrogen, 2a, 2′a, 2b, 2c, 2′c and 2′c , and in addition, in the case of 1b , compounds substituted on the furan ring, 2′b and 2″b . The structures of these compounds were confirmed from their ir, nmr and mass spectra. The major chlorinated products 2a, 2b and 2c were converted to methoxy- 5a, 5b and 5c , N-pyrrolidyl- 7a, 7b and 7c , and phenylthiofuropyridines 8a, 8b , and 8c .