- Methylthiolation for Electron-Rich Heteroarenes with DMSO-TsCl
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DMSO-TsCl has been developed for direct methylthiolation of various electron-rich heteroarenes (more than 40 examples) with high regioselectivity in moderate to excellent yields (up to 96 %). Especially, pyrroles, furans, and thiophenes can be efficiently mono-methylthiolated. This practical method features scalable, metal-free, mild conditions and is compatible with air and moisture. Several applications of methylthiolated products were demonstrated for the first time. Based on controlled experimental results, a plausible mechanism was proposed with two key intermediates involved in the mechanism being detected by HRMS.
- Zhang, Lei-Yang,Wu, Yue-Hua,Wang, Nai-Xing,Gao, Xue-Wang,Yan, Zhan,Xu, Bao-Cai,Liu, Ning,Wang, Bo-Zhou,Xing, Yalan
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supporting information
p. 1446 - 1451
(2021/02/26)
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- Structural reorganization of allyl isothiocyanate into pyrrole ring under superbase: A straightforward access to NH-2-(Alkylsulfanyl)-1H-pyrroles and N-Alkyl-2-(alkylsulfanyl)-1H-pyrroles
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A novel and facile synthetic route to NH-2-(alkylsulfanyl)-1H-pyrroles and N-alkyl-2-(alkylsulfanyl)-1H-pyrroles is reported. This was achieved by deprotonation of allyl isothiocyanate with the superbasic pair lithium diisopropylamide and potassium tert-butoxide (1:1 molar mixture), followed by intramolecular ring closure, deprotonation of cyclic anion with a second equivalent of the superbase, and final sequential N-protolysis/S-alkylation or N,S-dialkylation of the formed N,S-centered pyrrol-2-ylsulfide dianion. Georg Thieme Verlag Stuttgart · New York.
- Nedolya, Nina A.,Brandsma, Lambert,Trofimov, Boris A.
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- Access to indoles via Diels-Alder reactions of 5-methylthio-2-vinylpyrroles with maleimides
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Diels-Alder reactions of 5-methylthio-2-vinyl-1H-pyrroles with maleimides followed by isomerization gave tetrahydroindoles in moderate to good yield. Aromatization using activated MnO2 in refluxing toluene gave the corresponding 2-methylthioindoles in good yields, and demethylthioation using Raney nickel gave the 2-H indoles in excellent yields. The protection of the adducts produced aromatization in improved yield, demonstrating the effectiveness of the methylthio group as a protecting group for pyrroles; however, 5-methylthio-2-vinylpyrrole was shown to perform with slightly less efficiency than 2-vinylpyrrole in Diels-Alder reactions, indicating the protective group was more deactivating than desired. This route toward indoles offers high convergency and conveniently available starting materials that are easily purified. Bis-methylthioated vinylpyrroles were shown to have potential as highly activated Diels-Alder dienes.
- Noland, Wayland E.,Lanzatella, Nicholas P.,Dickson, Rozalin R.,Messner, Mary E.,Nguyen, Huy H.
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p. 795 - 808
(2013/08/23)
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- Geometric synthesis of porphyrin rods
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A method of making a compound of Formula I′ comprises reacting a compound of the formula DLCHO, with a compound of the formula to produce the compound of Formula I′. Methods of using the compounds are also described, particularly as intermediates for the synthesis of porphyrin rods, which porphyrin rods are in turn useful for (among other things) the production of molecular memory devices.
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Page/Page column 17-18
(2010/11/27)
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- MODULATORS OF CELLULAR ADHESION
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The present invention provides compounds having formula (I): and pharmaceutically acceptable derivatives thereof, wherein R1-R4, n, p, A, B, D, E, L and AR1 are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of disorders mediated by the CD11/CD18 family of cellular adhesion molecules (e.g., LFA-1).
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Page/Page column 107-108
(2010/02/11)
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- Accelerated arene ligand exchange in the (arene)Cr(CO)2L series
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Arene ligand exchange in the (η6-arene)Cr(CO)2L series can be accelerated if the ligand L is an electronically unsymmetrical bidentate ligand. The system evaluated here employs derivatives of tris(pyrrolyl)-phosphine as L. A series of 2-L′-substituted pyrroles was prepared, where the substituents include: L′= -SMe, -CH2SMe, -SPh, -CH2SPh, -SCF3, -S-tBu, -CO2Me, -CONMe2, -2-pyridinyl, and -PPh2. Reaction with CIP(pyrrolyl)2 gave a new series of phosphines, (2-L′-pyrrolyl) (pyrrolyl)2P. Each of these phosphines was converted to (arene)Cr(CO)2[P(2-L′-pyrrolyl)(pyrrolyl)2P) complexes. The substituents L′ are proposed to provide temporary coordination to the Cr and to lower the barrier to arene exchange. The series was evaluated where the arene in the complex (departing) is benzene, fluorobenzene, toluene, o-oxylene, m-xylene, or p-xylene and the incoming arene is C6D6, chlorobenzene-d5, anisole-d 8, fluorobenzene-d5, toluene-d8, o-oxylene-d10, m-xylene-d10, p-xylene-d10, or mesitylene-d12. Most of the new complexes showed a significant increase in the rate of arene exchange due to the side chain unit L′. The strongest effects were seen with the examples where X = -CO2Me, -CONMe2, and -(2-pyridinyl), allowing exchange with a half lifetime as low as 8 h/22 °C.
- Semmelhack,Chlenov, Anatoly,Ho, Douglas M.
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p. 7759 - 7773
(2007/10/03)
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- A simple preparative method for 2-alkylthiopyrroles
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A number of 2-alkylthiopyrroles have been obtained in fair yields by metallation of allyl isothiocyanate with a mixture of lithium diisopropylamide and potassium tert-butoxide, followed by successive addition of water and alkyl halide.
- Nedolya, Nina A.,Brandsma, Lambert,Verkruijsse, Hermann D.,Trofimov, Boris A.
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p. 7247 - 7248
(2007/10/03)
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- N-(Triisopropylsilyl)pyrrole. A Progenitor "Par Excellence" of 3-Substituted Pyrroles
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A very effective strategy has been devised for the synthesis of 3-substituted pyrroles based on the use of the triisopropylsilyl (TIPS) moiety as a sterically demanding nitrogen substituent to obstruct the attack of electrophilic reagents at the α positions. 1-(Triisopropylsilyl)pyrrole (1) undergoes highly preferential kinetic electrophilic substitution at the β position with a variety of electrophiles (Br+, I+, NO2+, RCO+, etc.) and fluoride ion induced desilylation of the products provides the corresponding 3-substituted pyrroles in good overall yields.Competitive trifluoroacetylation experiments demonstrate that substitution of TIPS-pyrrole at the α positions is decelerated by a factor of >104, vs pyrrole at the same sites, without affecting reactivity at the β positions. 1-(Triisopropylsilyl)-3-bromopyrrole (2) is readily converted into the 3-lithio compound 44 by bromine-lithium interchange with alkyllithium reagents.This previously unavailable, formal equivalent of 3-lithiopyrrole is itself an excellent source of a wide range of β-substituted pyrroles, many of which would not be directly preparable from 1.TIPS-pyrrole can be 3,4-dihalogenated and these compounds undergo sequential halogen-metal interchange trapping reactions.This process is exemplified by an efficient, three-step synthesis of the antibiotic verrucarin E (63) from the dibromo compound (5).
- Bray, Brian L.,Mathies, Peter H.,Naef, Reto,Solas, Dennis R.,Tidwell, Thomas T.,et al.
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p. 6317 - 6328
(2007/10/02)
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- NOVEL AND EFFECTIVE METHODS FOR α-THIOALKYLATION OF AROMATIC COMPOUNDS
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Convenient and effective methods for the introduction of a methylthiomethyl group and other α-thioalkyl group into aromatic compounds are described.
- Torisawa, Yasuhiro,Satoh, Atsushi,Ikegami, Shiro
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p. 1729 - 1732
(2007/10/02)
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- THE SYNTHESIS OF 1-ALKYLTHIOPYRROLES
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Reaction of various S-substituted thiophthalimides or thiosuccinimides and pyrrole, under phase transfer conditions, provides an efficient way to prepare 1-alkylthiopyrroles in high yield.
- Gilow, Helmuth M.
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p. 4689 - 4692
(2007/10/02)
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- Protecting groups for the pyrrole nitrogen atom. The 2-chloroethyl, 2-phenylsulfonylethyl, and related moieties
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The 2-chloroethyl and 2-phenylsulfonylethyl moieties are versatile protecting groups for the pyrrole nitrogen atom.The 2-chloroethyl group is easily attached under phase transfer conditions using 1,2-dichloroethane.The 2-phenylsulfonylethyl moiety is read
- Gonzalez, Carlos,Greenhouse, Robert,Tallabs, Ramon,Muchowski, Joseph M.
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p. 1697 - 1702
(2007/10/02)
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- Process for preparing 5-aroyl 1,2-dihydro-3-H pyrrolo[1,2-a]pyrrole-1-carboxylic acids and novel intermediates therein
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5-Substituted-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids of the formula STR1 wherein: X is hydrogen or lower alkyl; Ar is a moiety selected from the group consisting of STR2 in which: Y is oxygen or sulfur; R is hydrogen, methyl, chloro, or bromo, the R substitution being at the 3, 4 or 5 position of the ring; R1 is hydrogen, lower alkyl, lower alkoxyl, lower alkoxycarbonyl, lower alkylcarbonyl, fluoro, chloro or bromo, the R1 substitution being at any available position in the ring; R2 is hydrogen or lower alkyl; are prepared by β-decarboxylation of the corresponding dialkyl-1,1-dicarboxylates. Certain substituted pyrroles are useful as intermediates for preparing the compounds of formula I.
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- Process for preparing 5-aroyl 1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and novel intermediates therein
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5-Substituted-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids of the formula STR1 wherein: X is hydrogen, lower alkyl, chloro or bromo; Ar is a moiety selected from the group consisting of STR2 in which: Y is oxygen or sulfur; R is hydrogen, methyl, chloro, or bromo, the R substitution being at the 3, 4 or 5 position of the ring; R1 is hydrogen, lower alkyl, lower alkoxyl, lower alkoxycarbonyl, lower alkylcarbonyl, fluoro, chloro or bromo, the R1 substitution being at any available position in the ring; R2 is hydrogen or lower alkyl; are prepared by β-decarboxylation of the corresponding dialkyl-1,1-dicarboxylates. Certain substituted pyrroles are useful as intermediates for preparing the compounds of formula I.
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- Novel Syntheses of 5-Aroyl-1,2-dihydro-3H-pyrrolopyrrole-1-carboxylic Acids
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A fundamentally new approach to the synthesis of the title compounds was devised in which the crucial step was the intramolecular displacement of methanesulfinate ion or bromide ion by the sodium enolates of properly disposed substituted malonate esters such as 13a-13c and 20.As integral parts of the above process, a new four-carbon alkylation of the pyrrole nitrogen atom, a novel synthesis of 2-(methylthio)pyrroles, and the use of the dimethylsulfonium moiety as meta directing group in the pyrrole system were developed.
- Franco, Fidencio,Greenhouse, Robert,Muchowski, Joseph M.
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p. 1682 - 1688
(2007/10/02)
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- Synthesis and Rearrangement of 2-(Arylsulfinyl)- and 2-(Alkylsulfinyl)pyrroles
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Pyrrole and N-methylpyrrole reacted with aryl- and alkylsulfinyl chlorides, at 0 deg C, to give the corresponding 2-sulfinylpyrroles as the major products only when contact of the products with the liberated hydrogen chloride was minimized or eliminated.If this precaution was not taken, the 3-sulfinylpyrroles were the principle products.In contrast, N-(phenylsulfinyl)succinimide (2a) reacted, at room temperature, with a variety of pyrroles to produce the 2-phenylsulfinyl compounds in good yields.The 2-(arylsulfinyl)- and 2-(alkylsulfinyl)pyrroles undergo a remarkably facile acid-promoted rearrangement to the isomeric 3-sulfinylpyrroles.This transposition is, at least in part, an intermolecular process as demonstrated by crossover experiments.
- Carmona, Olga,Greenhouse, Robert,Landeros, Rosita,Muchowski, Joseph M.
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p. 5336 - 5339
(2007/10/02)
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