- Synthesis of 4-chalcogenyl pyrazoles via electrophilic chalcogenation/cyclization of α,β-alkynic hydrazones
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A facile method for the synthesis of 4-chalcogenylated pyrazoles has been developed via electrophilic chalcogenation/cyclization of α,β-alkynic hydrazones. The cyclization of α,β-alkynic aldehyde hydrazones could be induced by using either sulfenyl chloride or the S-electrophiles generated in situ from the reaction of NCS and arythiol. The developed method was successfully applied to the synthesis of the sulfenyl analogue of celecoxib.
- Cheng, Yu-Fei,Gao, Wen-Chao,Niu, Yulan,Shang, Yu-Zhu,Tian, Jun,Yu, Xinzhang
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p. 1806 - 1811
(2020/03/17)
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- Increasing Scope of Clickable Fluorophores: Electrophilic Substitution of Ylidenemalononitriles
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Recently, we demonstrated that ylidenemalononitriles (YMs) react with amines to form cyclic amidines and that the starting linear YMs are nonemissive in solution and the cyclic amidines are fluorescent. These turn-on systems were of interest to us because of their potential as biosensors and synthons for accessing functionalized pyridines. While our original method was promising, several limitations persisted, including access to more functionalized and polar-solvent-soluble structures as well as increased control over the rate of cyclization. Herein, we report a new approach that allows the electrophilic substitution of YMs. These substituted YMs exhibit faster turn-on rates, color tunability, access to polar-solvent-soluble species, and increased control over cyclization rate. This allowed us to significantly expand the fluorophore's chemical space.
- De Souza, Juliana M.,Abdiaj, Irini,Chen, Jiaqi,Hanson, Kenneth,De Oliveira, Kleber T.,McQuade, D. Tyler
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p. 11822 - 11834
(2020/10/23)
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- Tryptophan trimers and tetramers inhibit dengue and Zika virus replication by interfering with viral attachment processes
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Here, we report a class of tryptophan trimers and tetramers that inhibit (at low micromolar range) dengue and Zika virus infection in vitro. These compounds (AL family) have three or four peripheral tryptophan moieties directly linked to a central scaffold through their amino groups; thus, their carboxylic acid groups are free and exposed to the periphery. Structure-activity relationship (SAR) studies demonstrated that the presence of extra phenyl rings with substituents other than COOH at the N1 or C2 position of the indole side chain is a requisite for the antiviral activity against both viruses. The molecules showed potent antiviral activity, with low cytotoxicity, when evaluated on different cell lines. Moreover, they were active against laboratory and clinical strains of all four serotypes of dengue virus as well as a selected group of Zika virus strains. Additional mechanistic studies performed with the two most potent compounds (AL439 and AL440) demonstrated an interaction with the viral envelope glycoprotein (domain III) of dengue 2 virus, preventing virus attachment to the host cell membrane. Since no antiviral agent is approved at the moment against these two flaviviruses, further pharmacokinetic studies with these molecules are needed for their development as future therapeutic/prophylactic drugs.
- Fikatas, Antonios,Meyen, Eef,Noppen, Sam,Pannecouque, Christophe,Schols, Dominique,Vervaeke, Peter,Camarasa, María-José,Martí-Marí, Olaia,Martínez-Guald, Belén,San-Félix, Ana
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supporting information
(2020/02/29)
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- In Situ Activation of Disulfides for Multicomponent Reactions with Isocyanides and a Broad Range of Nucleophiles
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Activation of disulfides with N-halogen succinimide in the presence of TEMPO allows insertion reaction by an isocyanide, the product of which can further accept a wide range of nucleophiles for the generation of isothioureas and related molecular moieties. This new procedure overcomes previous methods that accept essentially only aryl amines as the third nucleophilic component. The diverse nucleophiles usable in our new protocol make this approach a general method for de novo synthesis of many S-containing heterocycles.
- Lei, Xiaofang,Wang, Yuanyuan,Fan, Erkang,Sun, Zhihua
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supporting information
p. 1484 - 1487
(2019/02/26)
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- Reactivity of the nitrogen-centered tryptophanyl radical in the catalysis by the radical SAM enzyme NosL
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The radical SAM tryptophan (Trp) lyase NosL involved in nosiheptide biosynthesis catalyzes two parallel reactions, converting l-Trp to 3-methyl-2-indolic acid (MIA) and to dehydroglycine and 3-methylindole, respectively. The two parallel reactions diverge from a nitrogen-centered tryptophanyl radical intermediate. Here we report an investigation on the intrinsic reactivity of the tryptophanyl radical using a chemical model study and DFT calculations. The kinetics of the formation and fragmentation of this nitrogen-centered radical in NosL catalysis were also studied in detail. Our analysis explains the intriguing catalytic promiscuity of NosL and highlights the remarkable role this enzyme plays in achieving an energetically highly unfavorable transformation.
- Qianzhu, Haocheng,Ji, Wenjuan,Ji, Xinjian,Chu, Leixia,Guo, Chuchu,Lu, Wei,Ding, Wei,Gao, Jiangtao,Zhang, Qi
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supporting information
p. 344 - 347
(2017/01/03)
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- Diaryl and heteroaryl sulfides: Synthesis via sulfenyl chlorides and evaluation as selective anti-breast-cancer agents
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A mild protocol for the synthesis of diaryl and heteroaryl sulfides is described. In a one-pot procedure, thiols are converted to sulfenyl chlorides and reacted with arylzinc reagents. This method tolerates functional groups including aryl fluorides and chlorides, ketones, as well as N-heterocycles including pyrimidines, imidazoles, tetrazoles, and oxadiazoles. Two compounds synthesized by this method exhibited selective activity against the MCF-7 breast cancer cell line in the micromolar range.
- Yonova, Ivelina M.,Osborne, Charlotte A.,Morrissette, Naomi S.,Jarvo, Elizabeth R.
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p. 1947 - 1953
(2014/04/03)
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- Synthesis and evaluation of novel sulfenamides as novel anti Methicillin-resistant Staphylococcus aureus agents
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A total of 29 novel sulfenamide compounds were synthesized, spectroscopically characterized and evaluated in vitro for antimicrobial activity against various infectious pathogens. Compounds 1b and 2c exhibited potent inhibition against clinical Methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentration (MIC) values of 1.56 μg/mL.
- Shang, Jian-Li,Guo, Hui,Li, Zai-Shun,Ren, Biao,Li, Zheng-Ming,Dai, Huan-Qin,Zhang, Li-Xin,Wang, Jian-Guo
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p. 724 - 727
(2013/02/25)
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- [4+2] Cyclohexane ring formation by a tandem of a free radical alkylation of a non-activated δ-carbon atom and intramolecular carbanion cycloalkylation
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A [4+2] cyclohexane ring formation was achieved by the combination of free radical and ionic reaction sequences. Free radical alkylation of the remote non-activated δ-carbon atom involves addition of δ-carbon radicals, generated by 1,5-hydrogen transfer in alkoxyl radical intermediates, to the radicophilic olefins, while the polar sequence involves the enolate anions as intermediates which undergo a cycloalkylation reaction. The cyclohexane rings were constructed using diverse acyclic compounds 15 and 18 as well as cyclic alkyl arenesulfenates (e.g., 5, 24, 27) as the precursors of alkoxyl radicals (four-carbon atom fragment) and methyl vinyl ketone or other activated olefins as two-carbon atom fragments. Annulation of the cyclohexane ring was applied for the synthesis of a variety of cyclic systems including monocyclic (17 and 20), fused-rings (e.g. 23, 26, 29) and spirocyclic systems (7).
- Petrovic, Goran,Cekovic, Zivorad
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p. 1671 - 1679
(2007/10/03)
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- Substituent effect on the competition between hetero-Diels-Alder and cheletropic additions of sulfur dioxide to 1-substituted buta-1,3-dienes
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The reactivity of sulfur dioxide toward variously substituted butadienes was explored in an effort to define the factors affecting the competition between the hetero-Diels-Alder and cheletropic additions. At low temperature (2 in the hetero-Diels-Alder mode in the presence of CF3COOH as promoter. In the case of (E)-1-ethylidene-2-methylidenecyclohexane ((E)-4a), the [4+2] cycloaddition of SO2 is fast at -90° without acid catalyst. (E)-1-(Acyloxy)buta-1,3-dienes (E)-1c, (E)-1y, and (E)-1z with AcO, BzO, and naphthalene-2-(carbonyloxy). substituents, respectively also undergo the hetero-Diels-Alder addition with SO2+CF3COOH at low temperatures, giving a 1:10 mixture of the corresponding cis- and trans-6-(acyloxy)sultines c-2c,y,z and t-2c,y,z, respectively). Above -50°, the sultines undergo complete cycloreversion to the corresponding dienes and SO2, which that add in the cheletropic mode at higher temperature to give the corresponding 2-substituted sulfolenes (=2,5-dihydrothiophene 1,1-dioxides) 3. The hetero-Diels-Alder additions of SO2 follow the Alder endo rule, giving first the 6-substituted cis-sultines that equilibrate then with the more stable trans-isomers. This statement is based on the assumption that the S=O group in the sultine prefers a pseudo-axial rather than a pseudo-equatorial position, as predicted by quantum calculations. The most striking observation is that electron-rich dienes such as 1-cyclopropyl-, 1-phenyl-, 1-(4-methoxyphenyl)-, 1-(trimethylsilyl)-, 1-phenoxy-, 1-(4-chlorophenoxy)-, 1-(4-methoxyphenoxy)-, 1-(4-nitrophenoxy)-, 1-(naphthalen-2-yloxy)-, 1-(methylthio)-, 1-(phenylthio)-, 1-[(4-chlorophenyl)thio]-, 1-[(4-methoxyphenyl)thio]-, 1-[(4-nitrophenyl)thio]-, and 1-(phenylseleno)buta-1,3-diene, as well as 1-(methoxymethylidene)-2-methylidenecyclohexane (4f) do not equilibrate with the corresponding sultines between -100 and -10°, in the presence of a large excess of SO2, with or without acidic promoter. The hetero-Diels-Alder additions of SO2 to 1-substituted (E)-buta-1,3-dienes are highly regioselective, giving exclusively the corresponding 6-substituted sultines. The 1-substituted (Z)-buta-1,3-dienes do not undergo the hetero-Diels-Alder additions with sulfur dioxide.
- Roversi, Elena,Monnat, Frederic,Vogel, Pierre,Schenk, Kurt,Roversi, Pietro
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p. 733 - 760
(2007/10/03)
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- Pyridyl-substituted thioaminyl stable free radicals: Isolation, ESR spectra, and magnetic characterization
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N-[(4-Nitrophenyl)thio]- (1a) and N-[(2,4-dichlorophenyl)thio)]-2,6- diphenyl-4-(3-pyridyl)phenylaminyl (1b), N-[(4-nitrophenyl)thio]- (2a) and N- [(2,4-dichlorophenyl)thio]-4-phenyl-2,6-di(3-pyridyl)-phenylaminyl (2b), and N-[(2,4-dichlorophenyl)thio]-2,6-diphenyl(4-pyridyl)aminyl (3) were generated by PbO2 oxidation of the corresponding precursors. Although 3 was not sufficiently stable to be isolated, both 1 and 2 persisted in solution without decomposition and could be isolated as radical crystals. X-ray crystallographic analysis of 1b revealed that the Ar-N-S-Ar' π-framework is approximately planar and the 2- and 6-phenyl groups are significantly twisted from this plane. The magnetic susceptibility measurements for the isolated radical crystals were carried out using a SQUID magnetometer in the temperature range 1.8-300 K. The susceptibilities of 1a and 2a were explained in terms of a one-dimensional (1D) antiferromagnetic (AFM) regular Heisenberg model with an exchange interaction of 2J/k(B) = -63.4 and -17.8 K, respectively, and that of 1b was interpreted in terms of a 1D AFM alternating Heisenberg model with 2J/k(B) = -12.8 K and α (alternation parameter) = 0.91. On the other hand, that of 2b was explained in terms of a 1D ferromagnetic regular Heisenberg model with 2J/k(B) = 22.4 K.
- Miura, Yozo,Kurokawa, Shinya,Nakatsuji, Masaaki,Ando, Kenjiro,Teki, Yoshio
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p. 8295 - 8303
(2007/10/03)
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- The kinetics and mechanism of the reaction of tricoordinate phosphorus compounds with sulfenate esters
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The kinetics and mechanism of the reaction of tricoordinate phosphorus compounds, ArnP(OCH2CF3)3-n with arylsulfenate esters, ArSOCH2CF3, are reported. Product analysis, kinetic order, activation parameters, Hammett data and solvent effects are the criteria used to elucidate the two step mechanism involving arylthiophosphoranes as intermediates.
- Hall, C. Dennis,Tweedy, Bruce R.,Lowther, Nicholas
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p. 341 - 358
(2007/10/03)
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- Generation, Isolation, ESR and 1H ENDOR Spectra, and Magnetic Characterization of N--2-t-butyl-1-pyrenylaminyl
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The oxidation of N--2-t-butyl-1-aminopyrene yielded a quite persistent and oxygen-insensitive N--2-t-butyl-1-pyrenylaminyl radical (3), which was isolated as reddish-black fine needles.The hyperfine coupling (hfc)
- Miura, Yozo,Oka, Hiroyuki,Yamano, Eiji,Teki, Yoshio,Takui, Takeji,Itoh, Koichi
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p. 1187 - 1192
(2007/10/02)
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- 6-Demethyl-6-halo- and 6-Demethyl-6-thiomitomycins: Synthesis of Novel Mitomycin Derivatives Involving a Tandem Michael Addition/Retro-Mannich Reaction Sequence
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Synthesis of novel 6-demethyl-6-halomitomycins (3, 4, 6, and 7) and 6-demethyl-6-thiomytomycins (5 and 8) is described from key intermediates, namely, 6-demethyl-7,7-(ethylenedioxy)-6,6-dihalo-6,7-dihydromitosanes (18 and 19) and 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-thiomitosane (20), respectively.Compounds 18-20 were prepared through a tandem Michael addition and a retro-Mannich reaction sequence (N-halosucinimide or cationic arylsulfenyl species in the presence of Et2NH) on 10.
- Arai, Hitoshi,Kasai, Masaji
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p. 1087 - 1094
(2007/10/02)
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- Generation, Isolation, and Characterization of N-(Arylthio)-7-tert-butyl- and N-(Arylthio)-2,7-di-tert-butyl-1-pyrenylaminyl Radicals
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N-(Arylthio)-7-tert-butyl-1-pyrenylaminyl (2) and N--2,7-di-tert-butyl-1-pyrenylaminyl radicals (3) are prepared by PbO2 oxidation of N-(arylthio)-7-tert-butyl-1-aminopyrenes and N--2,7-di-tert-butyl-1-aminopyrene, respectively, and studied by ESR and ENDOR spectroscopy.The kinetic ESR study shows that, while aminyls 2 gradually decompose in solution at room temperature, aminyl 3 is quite persistent, even in refluxing benzene, and shows no tendency to dimerize, even at low temperatures.These interesting properties of 3 permit us to isolate 3 as radical crystals in 28-31percent yield.The hyperfine splitting (hfs) constants of 2 and 3, determined by ESR and ENDOR spectroscopic methods, show an extensive delocalization of the unpaired electron onto the pyrene ring.Comparison of the hfs constants of 2 and 3 shows that a more extensive delocalization of the spin into the pyrene ring takes place in 3.This is accounted for in terms of the difference in the conformations of 2 and 3.
- Miura, Yozo,Yamano, Eiji,Tanaka, Akio,Yamauchi, Jun
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p. 3294 - 3300
(2007/10/02)
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- Toxin-targeted design for anticancer therapy. I: Synthesis and biological evaluation of new thioimidate heterobifunctional reagents
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In an effort to obtain a more potent and specific immunotoxin for cancer therapy, we designed a series of heterobifunctional linkers characterized by a thioimidate group linked to a S-acetyl thiol (4, 5) or substituted aryldithio group (6-10). These ligands were synthesized by a Pinner-type process from the corresponding nitrile derivatives obtained by thiol- disulphide exchange reaction, reaction with substituted benzene-sulphenyl chloride, or other known procedures. To check the reagent of choice for immunoconjugate preparation, we studied thioldisulphide exchange kinetics between the intermediate nitrile derivatives and cysteine. Among the tested aryldithio derivatives (6-10), we selected ethyl 3-(4-carboxamido- phenyldithio)propionthioimidate (CDPT, 9) for further studies. By analyzing the rate of incorporation of the linkers 4, 5, and 9 in a model immunoglobulin G protein, we found similar results with CDPT 9 and ethyl S- acetyl 3-mercaptopropionthioimidate ester hydrochloride (AMPT, 5) because both reagents showed a linear correlation between the number of introduced thiol groups and factors such as time and protein and reagent concentrations. Comparison of the two acetylthio-derivative ligands 4 and 5 showed that AMPT 5 was more stable toward deacetylation than ethyl S-acetyl 2- mercaptopropionthioimidate ester hydrochloride (AMAT, 4). By comparing the kinetic and biological parameters of seven new thioimidate linkers, we found that two of these (CDPT and AMPT) could be superior ligands for protein- protein conjugation. They offer advantages over the commercially available compounds, such as minimal perturbation of the protein structure, controlled reactivity, and good stability.
- Delprino,Giacomotti,Dosio,Brusa,Ceruti,Grosa,Cattel
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p. 506 - 512
(2007/10/02)
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- SYNTHESIS OF 3-(ALKYL AND ARYL)THIO-2-ISOCEPHEMS
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Synthesis of 3-S-substituted isocephems has been carried out in a convergent way using readily available intermediates such as 4-mercaptomethylazetidinone 3 and chloropyruvates 4 prepared by the reaction of sulfenyl chlorides with t-butyl diazopyruvate.Du
- Aszodi, Jozsef,Chantot, Jean-Francois,Collard, Jeannine,Teutsch, Georges
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p. 1061 - 1076
(2007/10/02)
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- A MILD AND CONVENIENT PREPARATION OF SULFENYL CHLORIDES FROM THIOLACETATES
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Sulfenyl chlorides are obtained easily and in good yields through the reaction of thiolesters and sulfuryl chloride.
- Thea, Sergio,Cevasco, Giorgio
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p. 2865 - 2866
(2007/10/02)
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- REACTION OF DIARYL DISULFIDES WITH N-CHLOROAMIDES OF CARBOXYLIC ACIDS
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In the reaction of diaryl disulfides with N-chlorocarboxamides arenesulfenyl chlorides and N-acylarenesulfenamides are formed initially.The subsequent reaction path is determined by the reaction of the latter with the N-chlorocarboxamides, and N-acylarenesulfinimidoyl chlorides, N,N'-diacylaryldiazasulfonium chlorides, or N,N'-diacylarenesulfinamidines are formed, depending on the ratio of the reagents and on the reaction conditions.
- Levchenko, E. S.,Dubinina, T. N.,Budnik, L. V.
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p. 1875 - 1880
(2007/10/02)
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- CHEMISTRY OF IMINOSULFINIC ACIDS. REACTION OF N-ACYLIMINOSULFINYL CHLORIDES WITH THIOPHENOLS
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Arene(N-benzoyl)- and arene(N-phenylsulfonyl)iminosulfinyl chlorides on reaction with thiophenols are reduced to N-(benzoyl) or N-(phenylsulfonyl)arenesulfenamides.When N-benzoyliminosulfinyl chlorides are reacted with thiophenols in the presence of triethylamine, a mixture of diaryl sulfides, NN-di(arylthio)benzamide, and N-arylthio-NN'-dibenzoylarenesulfinamidines is obtained.On heating, the latter reversibly dissociate to stable N-arylthio-N-benzoylaminyl radicals.
- Levchenko, E. S.,Pel'kis, N. P.,Kalinin, V. N.,Duzhak, A. A.
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p. 1028 - 1033
(2007/10/02)
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- Pyridine N-Sulphides. Some Simple N-Arylthiopyridinium Salts and a Possible Source of Arylsulphenium Ions
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N,N'-Dipyridinium disulphide dichloride (1) and 1-(4-nitrophenylthio)pyridinium chloride (5) and its 4-NMe2 derivative (2) have been synthesized and their structures established unambiguously; they undergo nucleophilic attack at sulphur rather than in the
- Abramovitch, Rudolph A.,Miller, Adrian L.,Pilski, Jacek
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p. 703 - 704
(2007/10/02)
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- Insecticidal acyl urea derivatives
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This invention is directed to novel urea derivatives of the general formula STR1 wherein A represents one of the groups STR2 X and Y, which may be identical to or different from each other, each represent hydrogen, chlorine or bromine; Z represents hydrog
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- Electrophilic additions to allenes. VI. The role of steric versus electronic effects in the reactions of arenesulphenyl halides with allenes
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The role of steric and electronic effects during the rate and product determining steps for the addition of arenesulphenyl chlorides to 1,3-disubstituted allenes has been briefly examined.Both effects appear to be generally of minimal importance during the rate determinig step.The available rate data indicate the presence of little, if any, build up of positive charge on sulphur.These results are interpreted in terms of an SN2 attack on bivalent sulphur leading to an alkylidenethiiranium ion intermediate.Steric effects are of greater importance in the product determinig step, particularly when the sulphenyl chlorides possess two bulky ortho substituents, as in the case of 2,4,6-triisopropylbenzenesulphenyl chloride.
- Garratt, Dennis G.,Beaulieu, Pierre L.
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p. 2738 - 2744
(2007/10/02)
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