111359-25-2Relevant academic research and scientific papers
Kinetic mechanism for dimerization of an α-thioamide substituted benzyl carbocation in aqueous solution
Williams, Kathleen B.,Richard, John P.
, p. 701 - 706 (1998)
The products of reaction of the α-(N,N-dimethylthiocarbamoyl)-4-methoxybenzyl carbocation (1+) intermediate of solvolysis of α-(N,N-dimethylthiocarbamoyl)-4-methoxybenzyl benzoate esters (1-O2CAr) show a strong dependence on solvent. The only product from reaction in 1,1,1,3,3,3-hexafluoro-2-propanoI (HFIP) is 2-dimethylamino-6-methoxybenzothiophene (2) from intramolecular cyclization of 1+. The reaction of 1+ in 50:50 (v/v) methanol-water (I = 0.50, NaClO4) gives mainly the adducts to solvent. In 50:50 (v/v) trifluoroethanol-water (I = 0.50, NaClO4), 1+ partitions between reaction with solvent (ks, 27% yield), cyclization to form 2 (kc, 3% yield) and nucleophilic addition of 2 to 1+ (kalk, 70% yield) to form dimeric product 3. The yield of 3 in 50:50 (v/v) trifluoroethanol-water (I = 0.50, NaClO4) is independent of the leaving group at 1-O2CAr and remains constant as the concentration of the substrate is increased fourfold. These data show that the rate-determining step for dimerization of 1-O2CAr is ionization of substrate to form 1+ and that the products of the reaction are determined by the rate constant ratio for partitioning of 1+ between addition of solvent and cyclization. The rate constant ratios determined for the partitioning of 1+ in 50:50 (v/v) trifluoroethanol-water (I = 0.50, NaClO4) were ks/kc = 0.8 M-1 and kalk/ks = 540 000 M-1.
Solvent effects on carbocation - Nucleophile combination reactions: A comparison of π-nucleophilicity in aqueous and organic solvents
Richard, John P.,Szymanski, Paul,Williams, Kathleen B.
, p. 10372 - 10378 (1998)
The following selectivities are reported for partitioning of the α- (N,N-dimethylthiocarbamoyl)-4-methoxybenzyl carbocation 1+ between nucleophilic addition of π-nucleophiles and a solvent of 50:50 (v:v) acetonitrile/water at 25 °C (nucleophile, k(Nu)/k(s)): pyrrole, 23 M-1; 2- methoxythiophene, ?2 M-1. No nucleophile adducts (+, and they provide support for a simple relationship between the Ritchie N+ scale of nucleophilicity in water and the Mayr N scale of nucleophilicity in weakly polar nonnucleophilic solvents. Our data require a large effective molarity for the intramolecular addition of a trisubstituted alkene to an allylic carbocation.
New HIV-1 reverse transcriptase inhibitors based on a tricyclic benzothiophene scaffold: Synthesis, resolution, and inhibitory activity
Krajewski, Krzysztof,Zhang, Yijun,Parrish, Damon,Deschamps, Jeffrey,Roller, Peter P.,Pathak, Vinay K.
, p. 3034 - 3038 (2008/12/21)
We synthesized, separated into enantiomers, and tested for the HIV-1 reverse transcriptase inhibitory activity a group of analogs of dimethyl-1-(1-piperidynyl)cyclobuta[b][1]benzothiophene-2,2a(7bH)-dicarboxylate (NSC-380292). Absolute configurations of the enantiomers were determined based on absolute X-ray structures and analysis of CD spectra. Within pairs of enantiomers the (R,R)-enantiomer was always much more potent HIV-1 reverse transcriptase inhibitor.
Benzothiphene derivatives for treating resistant tumors
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, (2008/06/13)
This invention provides a series of substituted benzo[b]thiophenes useful in reversing multidrug resistance in a resistant neoplasm. The present invention also provides methods for reversing the multidrug resistance in a resistant neoplasm by treating a mammal in need of said treatment with a substituted benzothiophene. This invention also provides methods for treating neoplasms in a mammal which comprises administering to a mammal in need of this treatment a substituted benzothiophene in combination with an oncolytic agent.
How does organic structure determine organic reactivity? Nucleophilic substitution and alkene-forming elimination reactions of α-carbonyl and α-thiocarbonyl substituted benzyl derivatives
Richard, John P.,Lin, Shrong-Shi,Buccigross, Jeanne M.,Amyes, Tina L.
, p. 12603 - 12613 (2007/10/03)
The effect of α-(N,N-dimethylcarbamoyl) and α-(N,N-dimethylthiocarbamoyl) substituents on the rate constants for partitioning of α-substituted 1-(4-methoxyphenyl)ethyl carbocations between nucleophilic addition of 50:50 (v:v) MeOH/H20 (k(s), s-1) and deprotonation by this solvent (k(e), s-1) have been investigated. The data show that these α-amide and α-thioamide substituents result in 80-fold and ≤ 30000-fold decreases, respectively, in k(s) for capture of the 4-methoxybenzyl carbocation by solvent, but that they lead to much smaller changes in k(e), for deprotonation of the corresponding α-substituted 1-(4-methoxyphenyl)ethyl carbocations by solvent. The large effect of the α-thioamide substituent on the partitioning of α-substituted 1-phenylethyl carbocations between formation of the products of solvolysis and elimination is therefore due primarily to the effect of this α-substituent on k(s), for capture of the carbocation by solvent. The results of experimental and computational studies are consistent with the conclusion that the relative magnitude of the rate constants k(s) and k(e) for partitioning of α-substituted 1-phenylethyl carbocations is strongly controlled by the relative thermodynamic stabilities of the neutral products of these reactions.
2-amino-3-aroyl-benzo[β]thiophenes and methods for preparing and using same to produce 6-hydroxy-2-(4-hydroxyphenyl)-3-]benzo[4-(2-aminoethoxy)-benzoyl[β]thiophenes
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, (2008/06/13)
A group of 2-amino-3-aroyl-benzo[β]thiophenes are prepared by preparing an α-hydroxy thioacetamide by silyl mediated condensation of an aldehyde with an anion of dialkylamino thioformamide, cyclizing the α-hydroxy thioamide, and subsequently acylating the benzo[β]thiophene to yield the 2-amino-3-aryl derivative. These compounds may be treated with suitable phenyl Grignard reagents, and after deprotection, yield 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[β]thiophene.
2-amino-3-aroyl-benzo[β]thiophenes and methods for preparing and using same to produce 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-aminoethoxy)-benzoyl]benzo[β]thiophenes
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, (2008/06/13)
A group of 2-amino-3-aroyl-benzo[β]thiophenes are prepared by treating an aldehyde with an anion of dimethylamino thioformamide, cyclizing the α-hydroxy thioamide, and subsequently acylating the benzo[β]thiophene to yield the 2-amino-3-aryl derivative. Th
DESTABILIZED CARBOCATIONS. NUCLEAR MATNETIC RESONANCE DETECTION AND REACTIVITIES OF ARYL α-THIOFORMAMIDYL CATIONS
Ablenas, F. J.,George, B. E.,Maleki, M.,Jain, R.,Hopkinson, A. C.,Lee-Ruff, E.
, p. 1800 - 1803 (2007/10/02)
A series of α-aryl and diarylthioformamidyl cations were observed by low-temperature nuclear magnetic resonance spectroscopy.These ions undergo efficient cyclization and deprotonation to give benzothiophenes.
