- Copper-Catalyzed Ullmann-Type Coupling and Decarboxylation Cascade of Arylhalides with Malonates to Access α-Aryl Esters
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We have developed a high-efficiency and practical Cu-catalyzed cross-coupling to directly construct versatile α-aryl-esters by utilizing readily available aryl bromides (or chlorides) and malonates. These gram-scale approaches occur with turnovers of up to 1560 and are smoothly conducted by the usage of a low catalyst loading, a new available ligand, and a green solvent. A variety of functional groups are tolerated, and the application occurs with α-aryl-esters to access nonsteroidal anti-inflammatory drugs (NSAIDs) on the gram scale.
- Cheng, Fei,Chen, Tao,Huang, Yin-Qiu,Li, Jia-Wei,Zhou, Chen,Xiao, Xiao,Chen, Fen-Er
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supporting information
p. 115 - 120
(2022/01/04)
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- Thermal Stability and Explosive Hazard Assessment of Diazo Compounds and Diazo Transfer Reagents
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Despite their wide use in academia as metal-carbene precursors, diazo compounds are often avoided in industry owing to concerns over their instability, exothermic decomposition, and potential explosive behavior. The stability of sulfonyl azides and other diazo transfer reagents is relatively well understood, but there is little reliable data available for diazo compounds. This work first collates available sensitivity and thermal analysis data for diazo transfer reagents and diazo compounds to act as an accessible reference resource. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and accelerating rate calorimetry (ARC) data for the model donor/acceptor diazo compound ethyl (phenyl)diazoacetate are presented. We also present a rigorous DSC dataset with 43 other diazo compounds, enabling direct comparison to other energetic materials to provide a clear reference work to the academic and industrial chemistry communities. Interestingly, there is a wide range of onset temperatures (Tonset) for this series of compounds, which varied between 75 and 160 °C. The thermal stability variation depends on the electronic effect of substituents and the amount of charge delocalization. A statistical model is demonstrated to predict the thermal stability of differently substituted phenyl diazoacetates. A maximum recommended process temperature (TD24) to avoid decomposition is estimated for selected diazo compounds. The average enthalpy of decomposition (?"HD) for diazo compounds without other energetic functional groups is-102 kJ mol-1. Several diazo transfer reagents are analyzed using the same DSC protocol and found to have higher thermal stability, which is in general agreement with the reported values. For sulfonyl azide reagents, an average ?"HD of-201 kJ mol-1 is observed. High-quality thermal data from ARC experiments shows the initiation of decomposition for ethyl (phenyl)diazoacetate to be 60 °C, compared to that of 100 °C for the common diazo transfer reagent p-acetamidobenzenesulfonyl azide (p-ABSA). The Yoshida correlation is applied to DSC data for each diazo compound to provide an indication of both their impact sensitivity (IS) and explosivity. As a neat substance, none of the diazo compounds tested are predicted to be explosive, but many (particularly donor/acceptor diazo compounds) are predicted to be impact-sensitive. It is therefore recommended that manipulation, agitation, and other processing of neat diazo compounds are conducted with due care to avoid impacts, particularly in large quantities. The full dataset is presented to inform chemists of the nature and magnitude of hazards when using diazo compounds and diazo transfer reagents. Given the demonstrated potential for rapid heat generation and gas evolution, adequate temperature control and cautious addition of reagents that begin a reaction are strongly recommended when conducting reactions with diazo compounds.
- Green, Sebastian P.,Wheelhouse, Katherine M.,Payne, Andrew D.,Hallett, Jason P.,Miller, Philip W.,Bull, James A.
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supporting information
p. 67 - 84
(2020/01/31)
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- Mechanistic studies on gold-catalyzed direct arene c-h bond functionalization by carbene insertion: The coinage-metal effect
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The catalytic functionalization of the Csp2-H bond of benzene by means of the insertion of the CHCO2Et group from ethyl diazoacetate (N2= CHCO2Et) has been studied with the series of coinage-metal complexes IPrMCl (IPr = 1,3-bis- (diisopropylphenyl)imidazol-2-ylidene) and NaBArF 4 (BArF 4 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate). For Cu and Ag, these examples constitute the first use of such metals toward this transformation, which also provides ethyl cyclohepta-2,4,6-trienecarboxylate as a byproduct from the so-called Buchner reaction. In the case of methyl-substituted benzenes, the reaction exclusively proceeds onto the aromatic ring, the Csp3-H bond remaining unreacted. A significant coinage-metal effect has been observed, since the gold catalyst favors the formation of the insertion product into the Csp2-H bond whereas copper and silver preferentially induce the formation of the cycloheptatriene derivative. Experimental studies and theoretical calculations have explained the observed selectivity in terms of the formation of a common Wheland intermediate, resembling an electrophilic aromatic substitution, from which the reaction pathway evolves into two separate routes to each product.
- Fructos, Manuel R.,Besora, Maria,Braga, Ataualpa A. C,Díaz-Requejo, M. Mar,Maseras, Feliu,Perez, Pedro J.
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p. 172 - 179
(2017/04/04)
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- NOVEL TRPV3 MODULATORS
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Disclosed herein are modulators of TRPV3 of formula (II): wherein G1, X1, X2, X3, X4, X5, G2, Ra, Rb, and u are as defined in the specification. Composition
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Paragraph 1810; 1811
(2013/06/04)
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- NOVEL TRPV3 MODULATORS
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Disclosed herein are modulators of TRPV3 of formula (II): wherein G1, X1, X2, X3, X4, X5, G2, Ra, Rb, and u are as defined in the specification. Composition
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Paragraph 335; 336
(2013/05/21)
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- COMPOUNDS FOR THE TREATMENT OF CNS DISORDERS
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The invention relates to novel cycloalkyl- or cycloalkenyl-substituted pyrazolopyrimidinones of formula (I), wherein ā is selected from the group A1 consisting of a C3-C8-cycloalkyl group or a C4-C8-cycloalkenyl group, whereby the members of C3-C8-cycloalkyl group being selected from the group of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl and cyclooctanyl; and the members of the C4-C8-cycloalkenyl group, being selected from cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclopentadienyl, cyclohexadienyl, cycloheptadienyl, cyclooctadienyl, cycloheptatrienyl, cyclooctathenyl, cyclooctatetraenyl. The new compounds shall be used for the manufacture of medicaments, in particular medicaments for improving perception, concentration, learning and/or memory in patients in need thereof. Chemically, the compounds are characterised as pyrazolopyrimidinones with a cycloalkyl-moiety directly bound to the 1 position of the pyrazolopyrimidinone and a second substituent in the 6 position which is bound via an optionally substituted methylene-bridge. Further aspects of the present invention refer to a process for the manufacture of the compounds and their use for producing medicaments.
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Page/Page column 40
(2012/05/20)
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- 1-HETEROCYCLYL-1,5-DIHYDRO-PYRAZOLO[3,4-D] PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS PDE9A MODULATORS
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The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones, Formula (I) with Hc is a mono-, bi- or tricyclic heterocyclyl group, the ring members of which are carbon atoms and at least 1, preferably 1, 2 or 3, heteroatom(s), which are selected from the group of nitrogen, oxygen and sulphur, which is in the form of -S(O)r - with r being 0, 1 or 2, and - said heterocyclyl group is or comprises 1 non-aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member and - said heterocyclyl group is bound to the scaffold by said 1 non- aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member. According to one aspect of the invention the new compounds are for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments for the treatment of Alzheimer's disease.
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Page/Page column 163; 166
(2009/10/30)
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- ALPHA-(TRIFLUOROMETHYL-SUBSTITUTED ARYLOXY, ARYLAMINO, ARYLTHIO OR ARYLMETHYL)-TRIFLUOROMETHYL-SUBSTITUTED PHENYLACETIC ACIDS AND DERIVATIVES AS ANTIDIABETIC AGENTS
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Compounds having a formula (1) or a pharmaceutically acceptable salt or prodrug thereof, are provided, and are useful for the treatment of metabolic disorders.
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Page/Page column 53
(2010/02/13)
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- PROCESS OF PREPARING SUBSTITUTED PYRIMIDINONES
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The present invention relates to a process useful in the preparation of compounds which are useful in treating diseases, such as TNF- alpha , IL-1 beta , IL-6 and/or IL-8 mediated diseases and other maladies. In accordance with the present invention, ther
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Page/Page column 22
(2010/02/03)
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- Electrochemistry of Ethyl α-Bromo-α-fluoro(phenyl)acetate and some Ethyl α-Bromo(trifluoromethylphenyl)acetates and Electrochemical Synthesis of the Corresponding Diastereoisomeric Diethyl Succinates.
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Ethyl α-bromoesters (1)-(5) (ABr) were prepared through NBS bromination of (6)-(10) (AH) respectively.Controlled potential electrolysis of (1)-(5), dissolved in dry dimethylformamide (DMF) containing Et4NClO4 (0.1 M) allows the corresponding succinates (1
- Mattiello, Leonardo,Rampazzo, Liliana,Sotgiu, Giovanni
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p. 2732 - 2754
(2007/10/02)
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- 4-quinolone derivatives having anti-inflammatory, anti-allergic, antitussive, expectorant and antithrombotic activity
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4-Quinolone derivatives of the present invention are useful for their anti-inflammatory, anti-allergenic, antitussive, expectorant and antithrombotic activity. Pharmaceutical compositions containing said compounds and pharmaceutically acceptable salts thereof and methods of treating humans and animals are described herein.
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