- Efficient synthesis of primary amides from carboxylic acids using n,n'-carbonyldiimidazole and ammonium acetate in ionic liquid
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A novel and efficient method for the conversion of carboxylic acids to primary amides using N,N'-carbonyldiimidazole in combination with ammonium acetate/triethyl amine system in [BMIM]BF4 is developed.
- Lee, Kwan Soo,Kim, Kee D.
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- An efficient synthesis of 1,3,7-triazaspiro[4.4]nonane-2,4-dione derivatives and antimicrobial activity thereof
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Efficient methods for the synthesis of 1,3,7-triazaspiro[4.4]nonane-2,4-dione derivatives possessing an unsaturated pyrrolidine cycle have been developed affording intermediates and target compounds in high yields not requiring additional purification. Antimicrobial activity of the synthesized compounds was studied.
- Krolenko, Konstantin Yu.,Silin, Olexiy V.,Vlasov, Sergiy V.,Zhuravel, Irina O.,Kovalenko, Sergiy M.
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- Combined Photoredox and Carbene Catalysis for the Synthesis of γ-Aryloxy Ketones
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N-heterocyclic carbenes (NHCs) have emerged as catalysts for the construction of C?C bonds in the synthesis of substituted ketones under single-electron processes. Despite these recent reports, there still remains a need to increase the utility and practicality of these reactions by exploring new radical coupling partners. Herein, we report the synthesis of γ-aryloxyketones via combined NHC/photoredox catalysis. In this reaction, an α-aryloxymethyl radical is generated via oxidation of an aryloxymethyl potassium trifluoroborate salt, which is then added into styrene derivatives to provide a stabilized benzylic radical. Subsequent radical-radical coupling reaction with an azolium radical affords the γ-aryloxy ketone products. (Figure presented.).
- Wang, Pengzhi,Fitzpatrick, Keegan P.,Scheidt, Karl A.
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supporting information
p. 518 - 524
(2021/12/16)
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- Practical Chemoselective Acylation: Organocatalytic Chemodivergent Esterification and Amidation of Amino Alcohols with N-Carbonylimidazoles
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Chemoselective transformations are a cornerstone of efficient organic synthesis; however, achieving this goal for even simple transformations, such as acylation reactions, is often a challenge. We report that N-carbonylimidazoles enable catalytic chemodivergent aniline or alcohol acylation in the presence of pyridinium ions or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), respectively. Both acylation reactions display high and broad chemoselectivity for the target group. Unprecedented levels of chemoselectivity were observed in the DBU-catalyzed esterification: A single esterification product was obtained from a molecule containing primary aniline, alcohol, phenol, secondary amide, and N?H indole groups. These acylation reactions are highly practical as they involve only readily available, inexpensive, and relatively safe reagents; can be performed on a multigram scale; and can be used on carboxylic acids directly by in situ formation of the acylimidazole electrophile.
- Brown, Hailee,Heller, Stephen T.,Light, Christina,Medlin, Abigail,Nelson, Hope,Richard, William
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supporting information
p. 22818 - 22825
(2021/09/13)
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- Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes
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Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine-or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.
- Bai, Feifei,Fang, Jianguo,Song, Zi-Long,Zhang, Baoxin
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p. 2214 - 2231
(2020/03/06)
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- Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids
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As a key element in the construction of complex organic scaffolds, the formation of C?C bonds remains a challenge in the field of synthetic organic chemistry. Recent advancements in single-electron chemistry have enabled new methods for the formation of various C?C bonds. Disclosed herein is the development of a novel single-electron reduction of acyl azoliums for the formation of ketones from carboxylic acids. Facile construction of the acyl azolium in situ followed by a radical–radical coupling was made possible merging N-heterocyclic carbene (NHC) and photoredox catalysis. The utility of this protocol in synthesis was showcased in the late-stage functionalization of a variety of pharmaceutical compounds. Preliminary investigations using chiral NHCs demonstrate that enantioselectivity can be achieved, showcasing the advantages of this protocol over alternative methodologies.
- Betori, Rick C.,Davies, Anna V.,Fitzpatrick, Keegan P.,Scheidt, Karl A.
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supporting information
p. 9143 - 9148
(2020/03/30)
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- Supported palladium catalyzed aminocarbonylation of aryl iodides employing bench-stable CO and NH3surrogates
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A simple, efficient and phosphine free protocol for carbonylative synthesis of primary aromatic amides under polystyrene supported palladium (Pd?PS) nanoparticle (NP) catalyzed conditions has been demonstrated. Herein, instead of using two toxic and difficult to handle gases simultaneously, we have employed the solid, economical, bench stable oxalic acid as the CO source and ammonium carbamate as the NH3source in a single pot reaction. For the first time, we have applied two non-gaseous surrogates simultaneously under heterogeneous catalyst (Pd?PS) conditions for the synthesis of primary amides using an easy to handle double-vial (DV) system. The developed strategy showed a good functional group tolerance towards a wide range of aryl iodides and afforded primary aromatic amides in good yields. The Pd?PS catalyst was easy to separate and can be recycled up to four consecutive runs with small loss in catalytic activity. We have successfully extended the scope of the methodology to the synthesis of isoindole-1,3-diones from 1,2-dihalobenzene, 2-halobenzoates and 2-halobenzoic acid following double and single carbonylative cyclization approaches.
- Bains, Rohit,Das, Pralay,Kumar, Ajay,Ram, Shankar,Shaifali,Sheetal
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supporting information
p. 7193 - 7200
(2020/10/02)
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- Ketoreductase catalyzed stereoselective bioreduction of α-nitro ketones
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We report here the stereoselective bioreduction of α-nitro ketones catalyzed by ketoreductases (KREDs) with publicly known sequences. YGL039w and RasADH/SyADH were able to reduce 23 class I substrates (1-aryl-2-nitro-1-ethanone (1)) and ten class II substrates (1-aryloxy-3-nitro-2-propanone (4)) to furnish both enantiomers of the corresponding β-nitro alcohols, with good-to-excellent conversions (up to >99%) and enantioselectivities (up to >99% ee) being achieved in most cases. To the best of our knowledge, KRED-mediated reduction of class II α-nitro ketones (1-aryloxy-3-nitro-2-propanone (4)) is unprecedented. Select β-nitro alcohols, including the synthetic intermediates of bioactive molecules (R)-tembamide, (S)-tembamide, (S)-moprolol, (S)-toliprolol and (S)-propanolol, were stereoselectively synthesized in preparative scale with 42% to 90% isolated yields, showcasing the practical potential of our developed system in organic synthesis. Finally, the advantage of using KREDs with known sequence was demonstrated by whole-cell catalysis, in which β-nitro alcohol (R)-2k, the key synthetic intermediate of hypoglycemic natural product (R)-tembamide, was produced in a space-time yield of 178 g L?1 d?1 as well as 95% ee by employing the whole cells of a recombinant E. coli strain coexpressing RasADH and glucose dehydrogenase as the biocatalyst.
- Wang, Zexu,Wu, Xiaofan,Li, Zhining,Huang, Zedu,Chen, Fener
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supporting information
p. 3575 - 3580
(2019/04/14)
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- A convenient synthesis of 2-acyl benzothiazoles/thiazoles from benzothiazole/thiazole and N,N'-carbonyldiimidazole activated carboxylic acids
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A convenient and efficient strategy for the synthesis of 2-acyl benzothiazoles/thiazoles has been developed. The treatment of benzothiazole/thiazole with allylic Grignard reagents readily generates the corresponding 2-Grignard reagents, which is followed by a reaction with N,N'-carbonyldiimidazole activated carboxylic acids to afford various 2-acyl benzothiazoles/thiazoles products. The synthetic method is applicable to a wide array of carboxylic acids and allows easy access to 2-acyl benzothiazoles/thiazoles with considerable yields under mild reaction conditions.
- Huang, Tonghui,Wu, Xin,Yu, Yongbo,An, Lin,Yin, Xiaoxing
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supporting information
p. 1667 - 1670
(2019/06/04)
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- Biology-oriented drug synthesis (BIODS): In vitro β-glucuronidase inhibitory and in silico studies on 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives
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Current study is based on the biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1–26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1'-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS,1H -NMR and13C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50= 1.20 ± 0.01–60.30 ± 1.40 μM as compared to the standard D-saccharic acid 1,4-lactone (IC50= 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9–19, and 21–24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
- Salar, Uzma,Khan, Khalid Mohammed,Taha, Muhammad,Ismail, Nor Hadiani,Ali, Basharat,Qurat-ul-Ain,Perveen, Shahnaz,Ghufran, Mehreen,Wadood, Abdul
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p. 1289 - 1299
(2016/12/06)
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- N-methylimidazole-catalyzed synthesis of carbamates from hydroxamic acids via the lossen rearrangement
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An efficient, one-pot, N-methylimidazole (NMI) accelerated synthesis of aromatic and aliphatic carbamates via the Lossen rearrangement is reported. NMI is a catalyst for the conversion of isocyanate intermediates to the carbamates. Moreover, the utility of arylsulfonyl chloride in combination with NMI minimizes the formation of often-observed hydroxamate-isocyanate dimers during the sequence. Under the present conditions, lowering of temperatures is also possible, enabling a mild protocol.
- Yoganathan, Sabesan,Miller, Scott J.
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supporting information
p. 602 - 605
(2013/04/11)
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- Novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors
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A series of novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors was prepared via treatment of various diaryl amides with tetrachlorosilane/sodium azide. All compounds were tested in cyclooxygenase (COX) assays in vitro to determine COX-1 and COX-2 inhibitory potency and selectivity. Tetrazoles contained a methylsulfonyl or sulfonamide group as COX-2 pharmacophore displayed only low inhibitory potency towards COX-2. Most potent compounds showed IC50 values of 6 and 7 μM for COX-2. All compounds showed IC50 values greater 100 μM for COX-1 inhibition.
- Al-Hourani, Baker Jawabrah,Sharma, Sai Kiran,Suresh, Mavanur,Wuest, Frank
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supporting information; experimental part
p. 2235 - 2238
(2012/04/18)
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- Discovery of Benzamide Analogues as a Novel Class of 5-HT3 Receptor Agonists
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A 5-HT3 receptor agonist based on a benzamide scaffold was identified in a screening of a small commercial compound library, and an elaborate SAR study originating from this hit was performed. The design, synthesis, and functional characterisation of benzamide analogues at the 5-HT3A receptor yielded substantial information concerning the analogues as 5-HT3 receptor agonists. However, the potencies of the derived analogues were not significantly improved over that of the initial hit. The benzamide scaffold constitutes a novel type of 5-HT3 receptor agonist, as it does not possess a positively charged functionality, which is essential for the binding of all orthosteric ligands to the receptor. Preliminary investigations suggest that the compounds may exert their effects on 5-HT3 receptors by binding to an allosteric site in the receptor complex.
- Jorgensen, Charlotte G.,Frolund, Bente,Kehler, Jan,Jensen, Anders A.
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scheme or table
p. 725 - 736
(2012/01/06)
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- Direct regioselective benzoylation of a single C-2 hydroxyl group of β-cyclodextrin and its hydrolysis via benzoyl group migration
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A simple and efficient method for the direct regioselective benzoylation of a single C-2 hydroxyl group of β-cyclodextrin was developed by using a combination of N,N′-carbonyldiimidazole and carbonate buffer in 1,4-dioxane, which does not require highly r
- Wang, Zhi-Zhong,Liu, Meng-Ying,Lu, Run-Hua,Fu, Xue-Yan,Dai, Gui-Dong
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experimental part
p. 1283 - 1287
(2012/06/04)
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- Phthalides by rhodium-catalyzed ketone hydroacylation
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(Chemical Equation Presented) Phthalides are biologically relevant five-membered lactones found in herbs, fruits, and vegetables. Herein we communicate the first atom-economical approach to phthalides by using enantioselective ketone hydroacylation. In the presence of Rh[(Duanphos)]X (X = NO3, OTf, OMs), various 2-ketobenzaldehydes undergo intramolecular hydroacylation to produce phthalide products in good yields and 92-98% ee's. Our study highlights the key role counterions play in controlling both reactivity and enantioselectivity. A concise asymmetric total synthesis of the celery extract (S)-(-)-3-n-butylphthalide is also presented.
- Phan, Diem H. T.,Kim, Byoungmoo,Dong, Vy M.
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supporting information; experimental part
p. 15608 - 15609
(2010/01/30)
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- Indium-mediated one-pot synthesis of benzoxazoles or oxazoles from 2-nitrophenols or 1-aryl-2-nitroethanones
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One-pot reduction-triggered heterocyclizations from 2-nitrophenols to benzoxazoles and from 1-aryl-2-nitroethanones to oxazoles were investigated. In the presence of indium/AcOH in benzene at reflux, 2-nitrophenols and R-C(OMe)3 (R=H, Me, Ph) produced excellent yields of corresponding benzoxazoles within an hour. Similarly, 1-aryl-2-nitroethanones and Ph-C(OMe)3 in the presence of indium/AcOH in acetonitrile transformed into the corresponding oxazoles with good yields.
- Lee, Jung June,Kim, Jihye,Jun, Young Moo,Lee, Byung Min,Kim, Byeong Hyo
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experimental part
p. 8821 - 8831
(2009/12/26)
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- REACTIONS OF SOME 1-(4,5-DIHYDROIMIDAZOL-2-YL)AZOLES WITH AROYL AND ETHOXYCARBONYL ISOTHIOCYANATES
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Three components cyclocondensations of the imidazole derivative (1c) with aroyl isothiocyanates afforded 6,7,8,8a-tetrahydro-3-aroylimidazotriazine-2,4(3H,8H)-dithiones (5a-e) while similar reaction with ethoxycarbonyl isothiocyanate led to the formation of ethyl 5-thioxo-2,3,8,9-tetrahydro-5H-diimidazotriazine-6-carboxylate (10).
- Saczewski, Franciszek
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p. 689 - 692
(2007/10/02)
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- Facile Conversions of Carboxylic Acids into Amides, Esters, and Thioesters Using 1,1'-Oxalyldiimidazole and 1,1'-Oxalyldi(1,2,4-triazole)
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Aliphatic, aromatic, and heteroaromatic carboxylic acids react with 1,1'-oxalyldiimidazole (1) or 1,1'-oxalyldi(1,2,4-triazole) (2) in acetonitrile for 40 min at 40 degC to give the corresponding 1-acylazole intermediates (11), which promptly undergo aminolysis and alcoholysis to form amides (13) including dipeptides (14), esters (16), and thioesters (19).These findings show that both 1 and 2 can be utilized as condensing reagents for the synthesis of carboxylic acid derivatives.Keywords --- 1,1'-oxalyldiimidazole; 1,1'-oxalyldi(1,2,4-triazole); 1,1'-carbonyldiimidazole; 1-acylazole; condensing reagent; amidation; esterification; dipeptide; aminolysis; alcoholysis
- Kitagawa, Tokujiro,Kuroda, Hiroko,Sasaki, Hideaki,Kawasaki, Koichi
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p. 4294 - 4301
(2007/10/02)
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