- Reductive lithiation of a trimethyl benzo-1,3-thiazoline: Generation of an α-amino tertiary carbanion and reactions with electrophiles
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Trimethylbenzothiazoline 1 has been reductively lithiated by lithium 4,4'-di-t-butylbiphenylide (LDBB) leading to dianion 3, that has been trapped with electrophiles to give aminodisulfides 4, aminosulfide 8 and aminoalcohols 9.
- Florio,Florio, Saverlo,Capriati,Capriati, Vito,Gallo,Gallo, Antonio,Cohen,Cohen, Theodore
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- Developing potential agents against atherosclerosis: Design, synthesis and pharmacological evaluation of novel dual inhibitors of oxidative stress and Squalene Synthase activity
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For the treatment of multifactorial and complex diseases, it has become increasingly apparent that compounds acting at multiple targets often deliver superior efficacy compared to compounds with high specificity for only a single target. Based on previous studies demonstrating the important antioxidant and anti-hyperlipidemic effect of morpholine and 1,4-benzo(x/thi)azine derivatives (A-E), we hereby present the design, synthesis and pharmacological evaluation of novel dual-acting molecules as a therapeutic approach for atherosclerosis. Analogues 1–10 were rationally designed through structural modifications of their parent compounds (A-E) in order for structure-activity relationship studies to be carried out. Most compounds showed a significant inhibition against Squalene Synthase activity exhibiting at the same time a very potent multimodal antioxidant (against lipid peroxidation and as free-radical scavengers) effect, thus bringing to light the 2-aryl-1,4-benzo(x/thia)zin-2-ol scaffold as an outstanding pharmacophore for the design of potent antioxidants. Finally, the replacement of the octahydro-1,4-benzoxazine moiety of lead compound D with its respective 1,4-benzothiazine (compound 4), although conserved (anti-hypercholesterolemic) or even improved (anti-hyperlipidemic) activity, did not preserve the anti-diabetic effect of D.
- Katselou, Maria G.,Matralis, Alexios N.,Kourounakis, Angeliki P.
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- Iodine-promoted ring-opening methylation of benzothiazoles with dimethyl sulfite
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A halogen-bond promoted ring-opening methylation of benzothiazoles has been developed using dimethyl sulphite as a methylating reagent in the presence of a base. This approach represents a simple and efficient synthesis ofN-methyl-N-(o-methylthio)phenyl amides, and features direct construction of both N-Me and S-Me bonds in a one-pot reaction through the decomposition of easily prepared benzothiazoles.
- Guo, Ying-Qiong,Chen, Fan,Deng, Chen-Liang,Zhang, Xing-Guo
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p. 1923 - 1926
(2021/03/02)
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- Bimetallic Bis-NHC-Ir(III) Complex Bearing 2-Arylbenzo[d]oxazolyl Ligand: Synthesis, Catalysis, and Bimetallic Effects
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Herein, an unprecedented bimetallic bis-NHC Cp*Ir complex 1 bearing 2-arylbenzo[d]oxazolyl and NHC ligands is reported. A significant increase in activity was observed for N-methylation of amines and reduction of aldehydes with MeOH catalyzed by 1 compared to the monometallic analogues (2-11). Under the optimal conditions, it showed to be highly effective in N-methylation of nitroarenes with MeOH as both C1 and H2 source. Substrates, including aromatic amines, ketones, and nitro compounds with various functional groups, can be well-tolerated. Mechanistic studies and DFT calculation highlight the significance of bimetallic centers cooperativity.
- Huang, Shuang,Hong, Xi,Cui, He-Zhen,Zhan, Bing,Li, Zhi-Ming,Hou, Xiu-Feng
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p. 3514 - 3523
(2020/10/09)
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- N -Methylation of ortho -substituted aromatic amines with methanol catalyzed by 2-arylbenzo [d] oxazole NHC-Ir(iii) complexes
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Seven new chelated cyclometalated Ir complexes of ABON,P, ABON,O, and ABON,C(carbene) based on a rigid and tunable 2-arylbenzo[d]oxazole backbone have been prepared for the N-methylation of amines. Among these three coordinated modes, ABON,C(carbene)-chelated iridium-based catalysts exhibited good performance in the monomethylation of aromatic amines with methanol (MeOH) as the green methylation reagent. The steric-modified synthesis of ABON,C(carbene) complexes was described. The most active ABON,C(carbene) complex with marginal steric hindrance as a catalyst was obtained from the benzoxazole ring without a substituent and methyl group of the benzimidazole ring on the N-heterocyclic carbene (NHC) ligand. A variety of amines including para- and meta-substituted aromatic amines, as well as heterocyclic amines, were formulated as suitable substrates. Importantly, this catalyst considerably promoted the yield of the N-methylation of ortho-substituted aromatic amines. Controlled kinetic experiments and deuterium-labeling reactions of these ortho-substituted amines were conducted under optimized conditions. On the basis of the experimental results, a plausible mechanism was proposed.
- Huang, Shuang,Hong, Xi,Cui, He-Zhen,Zhou, Quan,Lin, Yue-Jian,Hou, Xiu-Feng
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p. 5072 - 5082
(2019/04/17)
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- Mono-N-methylation of functionalized anilines with alkyl methyl carbonates over NaY faujasites. 4. Kinetics and selectivity
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(Chemical Equation Presented) In the presence of NaY faujasite as the catalyst, the reaction of bifunctional anilines (1-4: XC6H 4-NH2; X = OH, CO2H, CH2OH, and CONH2) with methyl alkyl carbonates [MeOCO2R′: R′ = Me or MeO(CH2)2O(CH2)2] proceeds with a very high mono-N-methyl selectivity (XC6H 4NHMe up to 99%), and chemoselectivity as well, with other nucleophilic functions (OH, CO2H, CH2OH, CONH2) fully preserved from alkylation and/or transesterification reactions. Aromatic substituents, however, modify the relative reactivity of amines 1-4: good evidence suggests that, not only steric and electronic effects, but, importantly, direct acid-base interactions between substituents and the catalyst are involved. Weakly acidic groups (OH, CH2OH, CONH2, pKa ≥ 10) may help the reaction, while aminobenzoic acids (pK a of 4-5) are the least reactive substrates. The solvent polarity also affects the reaction, which is faster in xylene than in the more polar diglyme. The mono-N-methyl selectivity is explained by the adsorption pattern of reagents within the zeolite pores: a BAl2 displacement of the amine on methyl alkyl carbonate should occur aided by the geometric features of the NaY supercavities. Different factors account for the reaction chemoselectivity. Evidence proves that the polarizability of the two nucleophilic terms (NH 2 and X groups) of anilines is relevant, although adsorption and confinement phenomena of reagents promoted by the zeolite should also be considered.
- Selva, Maurizio,Tundo, Pietro,Foccardi, Tommaso
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p. 2476 - 2485
(2007/10/03)
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- "Novel ortho-mercaptoaniline compounds"
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An ortho-mercaptoaniline derivative having the general formula wherein X is (H,H) or O; n is 1 or 2; and R1is (C1-C6)alkyl or phenyl-(C1-C6)alkylene, optionally substituted at phenyl with a (C1/
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- Reductive Lithiation of Sulfur-containing Heterocycles With Aromatic Radical Anions: Synthetic Applications
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2H-3,4-dihydro-1-benzothiopyran, 1, and 2,3-dihydrobenzothiophene, 8, have been redctively cleaved by lithium 4,4'-di-tert-butylbiphenylide (LDBB) to the anions 2 and 9, respectively.The dianion 2 can be captured with MeOD to give the deuteriated compound 3 and with carbonyl compounds to give the hydroxyalkylbenzenethiols 4a-e, which in turn have been cyclized to the tetrahydrobenzothiepins 5a-e.Similarly, the dianion 9 reacts with MeOD furnishing 10 and with carbonyl compounds yielding the hydroxyalkylbenzenethiols 11.Benzenethiol 11a has beeen cyclized to the thiochromane 12.The reductive lithiation of 2,2,3-trimethylbenzothiazoline, 13, generates the"unstabilized' α-amino tertiary carbanion 14, which has been trapped with a number of electrophiles to give the products 15, 16, 19, 20 and 23-25.
- Florio, Saverio,Capriati, Vito,Gallo, Antonio,Cohen, Theodore,Chen, Fangping,Kulinski, Tomasz
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p. 351 - 358
(2007/10/03)
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- THERMOLYSIS OF QUARTENARY SALTS OF 2-METHYLBENZOTHIAZOLE AND THEIR METHYLENE BASES
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The pathways of the thermal transformations of quartenary salts of 2-methylbenzothiazole and their methylene bases were investigated.The schemes of the thermal fragmentation of these compounds are discussed.The possibility of the formation of methylene bases in the thermolysis of quartenary salts of 2-methylbenzothiazole is demonstrated.
- Al'perovich, M. A.,Khesin, V. G.,Raikhina, R. D.,Medvedeva, T. D.
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p. 1182 - 1187
(2007/10/02)
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- Heterocyclic 8?-Systems, 14. Generation and Reactions of Cyanine Dye Leuko compounds.
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The symmetric cyanine dyes 2a - c, 3a, 4a, and 5a were transformed into the leuko compounds 7 - 10, 12, and 14.Deprotonation of 7 and 8 with lithium diisopropylamide led to the corresponding cyanine dye anions, which yielded derivatives of the leuko compounds (25 - 30 and 34, 35, respectively) with electrophiles.The cyanine dyes 2a, 3a and the leuko compounds 7, 8 delivered with lithium tetracyano-p-quinodimethan anion (LiTCNQ) and tetracyano-p-quinodimethan (TCNQ) simple (36, 37) and complex salts (38, 39), respectively. 39 displayed interesting conductivity.
- Schmidt, Richard R.,Hensen, Hermann
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p. 1723 - 1736
(2007/10/02)
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- INVESTIGATION OF THE PATHWAYS OF THERMAL FRAGMENTATION OF THIACARBOCYANINE DYES
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The pathways of the thermal transformations of thiacarbocyanines with various alkyl groups attached to the ring nitrogen atoms of the heteroresidues, of 3,3'-diethylthiacarbocyanine with various anions, and its anhydro base were investigated.The results of the studies are compared with the results of quantum-chemical calculations of the labilities of the bonds in these compounds by the Pariser-Parr-Pople method.
- Khesin, V. G.,Al'perovich, M. A.,Abramenko, P. I.
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p. 1187 - 1192
(2007/10/02)
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