- Identification of organophosphorus simulants for the development of next-generation detection technologies
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Organophosphorus (OP) chemical warfare agents (CWAs) represent an ongoing threat but the understandable widespread prohibition of their use places limitations on the development of technologies to counter the effects of any OP CWA release. Herein, we describe new, accessible methods for the identification of appropriate molecular simulants to mimic the hydrogen bond accepting capacity of the PO moiety, common to every member of this class of CWAs. Using the predictive methodologies developed herein, we have identified OP CWA hydrogen bond acceptor simulants for soman and sarin. It is hoped that the effective use of these physical property specific simulants will aid future countermeasure developments.
- Ellaby, Rebecca J.,Clark, Ewan R.,Allen, Nyasha,Taylor, Faith R.,Ng, Kendrick K. L.,Dimitrovski, Milan,Chu, Dominique F.,Mulvihill, Daniel P.,Hiscock, Jennifer R.
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p. 2008 - 2014
(2021/03/16)
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- Design, synthesis, and functional assessment of Cmpd-15 derivatives as negative allosteric modulators for the β2-adrenergic receptor
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The β2-adrenergic receptor (β2AR), a G protein-coupled receptor, is an important therapeutic target. We recently described Cmpd-15, the first small molecule negative allosteric modulator (NAM) for the β2AR. Herein we report in details the design, synthesis and structure-activity relationships (SAR) of seven Cmpd-15 derivatives. Furthermore, we provide in a dose-response paradigm, the details of the effects of these derivatives in modulating agonist-induced β2AR activities (G-protein-mediated cAMP production and β-arrestin recruitment to the receptor) as well as the binding affinity of an orthosteric agonist in radio-ligand competition binding assay. Our results show that some modifications, including removal of the formamide group in the para-formamido phenylalanine region and bromine in the meta-bromobenzyl methylbenzamide region caused dramatic reduction in the functional activity of Cmpd-15. These SAR results provide valuable insights into the mechanism of action of the NAM Cmpd-15 as well as the basis for future development of more potent and selective modulators for the β2AR based on the chemical scaffold of Cmpd-15.
- Meng, Kaicheng,Shim, Paul,Wang, Qingtin,Zhao, Shuai,Gu, Ting,Kahsai, Alem W.,Ahn, Seungkirl,Chen, Xin
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p. 2320 - 2330
(2018/03/29)
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- Pyrazole compound and preparation and application methods thereof
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The invention provides a pyrazole compound and preparation and application methods thereof. The pyrazole compound is synthesized by introducing 2-amido-benzoxazole groups into pyrazole. The prepared pyrazole compound is low in toxic and side effects, high in oral bioavailability, significant in inhibition on tumor cells such as human breast cancer cells, human lung cancer cells, human prostatic cancer cells, human gastric cancer cells and human malignant glioma cells and capable of providing new possibilities for developing high-efficiency and low-toxicity anti-tumor drugs. Meanwhile, the pyrazole compound is wide in material sources, simple in synthesizing processes and applicable to industrial production.
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Paragraph 0053; 0055-0060
(2018/10/19)
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- Containing piperazinone quinazoline ketone PARP - 1/2 inhibitor and its preparation method, pharmaceutical composition and use thereof (by machine translation)
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The invention discloses a new class of containing piperazinone quinazoline - 2, 4 (1 H, 3 H) - dione PARP - 1/2 inhibitor, and its preparation and pharmaceutical composition and use. Specifically, the invention relates to the general formula I shown containing of the piperazinone quinazoline - 2, 4 (1 H, 3 H) - dione derivatives and their pharmaceutically acceptable salt, and its preparation method, comprising one or more of the compounds of the composition, and the compounds in the preparation, the prevention and/or treatment with PARP - 1/2 of a disease associated with the use of the medicament. (by machine translation)
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Paragraph 0380; 0381
(2017/09/08)
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- Ionic liquid brush as an efficient and reusable heterogeneous catalytic assembly for the tosylation of phenols and alcohols in neat water
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A very efficient and reusable heterogeneous ionic liquid brush assembly was developed. The catalyst exhibits high catalytic activity for the tosylation of phenols and alcohols in neat water. Moreover, the catalyst shows outstanding stability and reusability, and it can be simply and effectively recovered and reused five times without noticeable loss of catalytic activity.
- Feng, Simin,Li, Jing,Wei, Junfa
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supporting information
p. 4743 - 4746
(2017/07/12)
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- METAL OXIDE CATALYZED RADIOFLUORINATION
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Inter alia, the first titania-catalyzed [18F]-radiofluorination in highly aqueous medium is provided. In embodiments, the method utilizes titanium dioxide, 1 : 1 acetonitrile- thexyl alcohol solvent mixture and tetrabutylammonium bicarbonate as a base. Radiolabeling may be directly performed with aqueous [18F]fluoride without the need for drying/azeotroping step, which reduces radiosynthesis time while keeping high fluoride conversion. The general applicability of the synthetic strategy to the synthesis of the wide range of PET probes from tosylated precursors is demonstrated.
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Paragraph 0109
(2016/02/28)
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- IMIDAZOPYRIDAZINE COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFN ALPHA RESPONSES
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Compounds having the following formula (I), or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.
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Page/Page column 80
(2015/06/25)
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- Titania-catalyzed radiofluorination of tosylated precursors in highly aqueous medium
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Nucleophilic radiofluorination is an efficient synthetic route to many positron-emission tomography (PET) probes, but removal of water to activate the cyclotron-produced [18F]fluoride has to be performed prior to reaction, which significantly increases overall radiolabeling time and causes radioactivity loss. In this report, we demonstrate the possibility of 18F-radiofluorination in highly aqueous medium. The method utilizes titania nanoparticles, 1:1 (v/v) acetonitrile-thexyl alcohol solvent mixture, and tetra-n-butylammonium bicarbonate as a phase-transfer agent. Efficient radiolabeling is directly performed with aqueous [18F]fluoride without the need for a drying/azeotroping step to significantly reduce radiosynthesis time. High radiochemical purity of the target compound is also achieved. The substrate scope of the synthetic strategy is demonstrated with a range of aromatic, aliphatic, and cycloaliphatic tosylated precursors.
- Sergeev, Maxim E.,Morgia, Federica,Lazari, Mark,Wang, Christopher,Van Dam, R. Michael
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supporting information
p. 5686 - 5694
(2015/05/20)
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- A dicationic, podand-like, ionic liquid water system accelerated copper-catalyzed azide-alkyne click reaction
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In this work, an effective, task specific, dicationic, podand-like ionic liquid was synthesized and applied to improve the capability features of click reaction. Moreover, to broaden the scope and decreasing the serious limitations of preparation methods of organic azides, a simple green procedure for the preparation of alkyl azides, the fundamental starting materials in click reactions, from alcohols under solvent-free conditions and microwave irradiation has been reported, for the first time.
- Javaherian, Mohammad,Kazemi, Foad,Ghaemi, Masoumeh
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p. 1643 - 1647
(2015/01/09)
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- One-pot tandem reactions for direct conversion of thiols and disulfides to sulfonic esters, and Paal-Knorr synthesis of pyrrole derivatives catalyzed by TCCA
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A convenient synthesis of sulfonic esters from thiols and disulfides is described. In situ preparation of sulfonyl chlorides from thiols is accomplished by oxidation with trichloroisocyanuric acid (TCCA), tetra-butylammonium chloride (t-Bu4NCl), and water. The sulfonyl chlorides are then further allowed to react with phenol derivatives in the same reaction vessel. Also, a facile synthesis of N-substituted pyrroles by the reaction of hexane-2,5-dione with primary amines has been accomplished using TCCA as a catalyst under mild condition with excellent yields.
- Hemmati, Saba,Mojtahedi, Mohammad Majid,Abaee, Mohammad Saeed,Vafajoo, Zahra,Saremi, Shokufe Ghahri,Noroozi, Mohammad,Sedrpoushan, Alireza,Ataee, Meral
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p. 347 - 357
(2013/09/23)
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- A simple and efficient method for sulfonylation of amines, alcohols and phenols with cupric oxide under mild conditions
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Cupric Oxide efficiently catalyzed the synthesis of sulfonamides and sulfonic esters. This method has been applied to a variety of substrates including nucleophilic and sterically-hindered amines, alcohols and phenols with excellent yields of sulfonamides and sulfonic esters. The remarkable selectivity under mild and neutral conditions of this commercially available inexpensive catalyst is an attractive feature of this method.
- Meshram,Patil, Vishvanath D.
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scheme or table
p. 1117 - 1121
(2009/05/27)
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- Chemoselective and scalable preparation of alkyl tosylates under solvent-free conditions
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The improved method for the efficient tosylation of alcohols has been reported using two procedures (A and B). Procedure A: methanol, ethanol, benzyl alcohols, and valuable ethylene glycols can be converted into their corresponding alkyl tosylates in very fast, simple, and efficient grinding method using potassium carbonate as solid base. Other primary and secondary alcohols need to add potassium hydroxide to reaction mixture (procedure B). High selectivity of tosylation was observed for these two procedures. Scale up ability was found in this method even in 100 mmol of substrate. The present method is the example of solid-state tosylation using tosyl chloride, and is a green chemical process due to solvent-free conditions.
- Kazemi, Foad,Massah, Ahmad R.,Javaherian, Mohammad
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p. 5083 - 5087
(2008/02/01)
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- Mild and efficient indium metal catalyzed synthesis of sulfonamides and sulfonic esters
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A facile and efficient method for synthesizing sulfonamides was developed using a catalytic amount of indium metal. A wide range of sulfonamides were synthesized in excellent yields using the new process. The method showed a generality for substrates including less nucleophilic and sterically hindered anilines, and it is also applicable for preparing sulfonic esters from sulfonyl chlorides and alcohols. Georg Thieme Verlag Stuttgart.
- Kim, Joong-Gon,Doo, Ok Jang
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p. 2501 - 2504
(2008/02/13)
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- Solvent-free and selective tosylation of alcohols and phenols with p-toluenesulfonyl chloride by heteropolyacids as highly efficient catalysts
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Tosylation of some alcohols and phenols has been directly carried out with p-toluenesulfonyl chloride using heterodoxy acids (H3PW 12O40, H3PMo12O40, A 3PW12O40, and AlPMo12O40) as catalysts in the absence of solvent. We found that heteropoly acids AlPW12O40 and AlPMo 12O40 were effective catalysts for the tosylation of alcohols and phenols. In the case of aliphatic alcohols, secondary alcohols undergo tosylation chemoselectively in the presence of primary hydroxyl groups. This new method consistently has the advantage of excellent yields and short reaction time.
- Fazaeli, Razieh,Tangestaninejad, Shahram,Aliyan, Hamid
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p. 812 - 818
(2007/10/03)
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- An efficient one-pot conversion of THP and TMS ethers to sulfonate esters using FeCl3-montmorillonite K-10 clay
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Various tetrahydropyranyl and trimethylsilyl ethers are efficiently transformed into the corresponding sulfonate esters with sulfonyl chlorides in the presence of FeCl3-Montmorillonite K-10 clay.
- Movassagh, Barahman,Shokri, Salman
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p. 763 - 765
(2007/10/03)
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- Cobalt(II) catalyzed tosylation of alcohols with p-toluenesulfonic acid
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Cobalt(II) chloride hexahydrate (CoCl2·6H2O) has been found to catalyze the tosylation of both aliphatic and aromatic alcohols with p-toluenesulfonic acid (p-TsOH) in high yields in 1,2-dichloroethane under reflux (ca. 80°C). In the
- Velusamy, Subbarayan,Kumar, J. S. Kiran,Punniyamurthy
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p. 203 - 205
(2007/10/03)
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- An efficient and selective tosylation of alcohols with p-toluenesulfonic acid
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Silica chloride has been found to be an efficient catalyst for facile tosylation of alcohols directly with p-toluenesulfonic acid in methylene chloride under reflux. The process is associated with selective tosylation of secondary alcohols over primary al
- Das, Biswanath,Reddy, V. Saidi,Reddy, M. Ravinder
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p. 6717 - 6719
(2007/10/03)
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- ZrCl4 as an efficient catalyst for selective tosylation of alcohols with p-toluenesulfonic acid
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Tosylation of alcohols has directly been carried out with p-toluenesulfonic acid in methylene chloride under reflux using ZrCl4 as a catalyst. Primary alcohols were found to be tosylated chemoselectively over secondary alcohols.
- Das, Biswanath,Reddy, Vtukuri Saidi
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p. 1428 - 1429
(2007/10/03)
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- Preparation of optically active β-amino acids from microbial polyester polyhydroxyalkanoates
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An efficient method for the preparation of optically active ethyl β-aminobutyrate from the biopolymer, poly-(R)-(-)-3-hydroxybutyrate (PHB) obtained from bacterial cells has been established using chemical transforamtions: simple recovery of PHB from bacterial cells followed by acidic alcoholysis, tosylation, nucleophilic substitution by azide, and an indium mediated reduction.
- Park, Sang Hyun,Lee, Seung Hwan,Lee, Sang Yup
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p. 498 - 499
(2007/10/03)
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- Synthesis of alkyl sulfonates from sulfonic acids or sodium sulfonates using solid-phase bound reagents
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An efficient and selective method for the synthesis of sulfonic esters from sulfonic acids or sodium sulfonates using polymer-bound primary triazenes based upon the T2* linker has been developed. The purities of the esters obtained are usually greater tha
- Vignola, Nicola,Dahmen, Stefan,Enders, Dieter,Br?se, Stefan
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p. 7833 - 7836
(2007/10/03)
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- Montmorillonite clay catalyzed tosylation of alcohols and selective monotosylation of diols with p-toluenesulfonic acid: An enviro-economic route
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An enviro-economic route for tosylation of alcohols and selective monotosylation of diols in good yield directly using p-toluenesulfonic acid together with metal-exchanged montmorillonite instead of p-toluenesulfonyl chloride or p-toluenesulfonic anhydrid
- Choudary, Boyapati M.,Chowdari, Naidu S.,Kantam, Mannepalli L.
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p. 7291 - 7298
(2007/10/03)
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- Detailed Characterization of p-Toluenesulfonic Acid Monohydrate as a Convenient, Recoverable, Safe, and Selective Catalyst for Alkylation of the Aromatic Nucleus
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Alkylation of the aromatic nucleus, an important reaction in industry and synthetic organic chemistry, has traditionally been carried out by the well-known Friedel-Crafts reaction employing Lewis acid catalysts such as AlCl3 and BF3 or by using highly reactive organometallic reagents. Although protic acids such as anhydrous HF and concentrated H2SO4 have also been used in the alkylation of the aromatic nucleus, the notoriously corrosive, highly toxic, and hazardous nature of these agents has precluded their common use under ordinary laboratory conditions. Various organic sulfonic acids have, on occasion, been used as catalysts in Friedel-Crafts alkylations, but to our knowledge the chemistry and the scope of these reactions for common laboratory use have never been exploited in detail. In the present study we have characterized commercially available p-toluenesulfonic acid monohydrate (TsOH) as an efficient catalyst for the intermolecular coupling of the aromatic nucleus with activated alkyl halides, alkenes, or tosylates under mild conditions in an open atmosphere. In comparison to conventional Friedel-Crafts catalysts such as AlCl3, BF3, HF, and concentrated H2SO4, the extent of the formation of undesired products from side reactions such as transalkylation, polymerization, etc. was minimal with the TsOH-catalyzed reaction. The ability to recover and reuse the catalyst from the reaction mixtures, minimal generation of environmentally unfriendly waste, high specificity of the reaction, and the low cost of the catalyst are important advantages of the TsOH catalyst over the other conventional Friedel-Crafts catalysts.
- Mahindaratne, Mathew P. D.,Wimalasena, Kandatege
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p. 2858 - 2866
(2007/10/03)
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- Process for the production of aniline derivatives
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Industrial process for the efficient production of aniline derivatives which are important intermediates for the manufacture of oxazolidinedione derivatives and tetrahydrophthalimide derivatives which are useful as active ingredients of herbicides. The process starts from 2,4-dihalo-5-aminophenol or bis(2,4-dihalo-5-aminophenyl)carbonate and selectively cycloalkylates or alkynylates the hydroxy group without protecting the amino group, whereby aniline derivatives having the cycloalkyloxy group or alkynyloxy group can be produced in high yield.
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- REACTION OF PHOSPHORUS OXYACID ESTERS WITH p-TOLUENESULFONIC ACID
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The reaction of primary alkyl esters of phosphorus oxyacids with p-toluenesulfonic acid (TsOH) in refluxing solvents gave the corresponding p-toluenesulfonates (TsOR).We found that the secondary alkyl esters reacted with TsOH at lower temperature (r.t.-40 deg C) to afford TsORs in good yields.It is suggested that sulfonic acids may be useful for the selective dealkylation of mixed esters.Keywords-p-toluenesulfonic acid; p-toluenesulfonate; trialkyl phosphate; trialkyl phosphite; dialkyl phenylphosphonate; transesterification; dealkylation; solvolysis.
- Nitta, Yoshihiro,Arakawa, Yasushi,Ueyama, Naoto
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p. 2710 - 2718
(2007/10/02)
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- Solvent Effects on Solvolytic Reactivity. A Diagnostic Test for Neighboring-Group Assistance by ? Conjugation in Solvolysis Reactions
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The solvolysis rates of 13 arenesulfonates have been determined in mixtures of ethanol and water (the E-series solvents) and acetic acid and formic acid (the A-series solvents).The substrates studied include the following: neophyl (1), 2-adamantyl (2), neopentyl (3), and cyclooctyl (4) tosylates; cyclopropylcarbinyl pemsylate (5a) and tosylate (5b); exo-2-norbornyl tosylate (6); cyclobutylcarbinyl (7), cyclobutyl (8), and pinacolyl (9) brosylates; cyclopentyl (10), cyclohexyl (11), and 2-propyl (12) tosylates; and cyclopentylcarbinyl brosylate (13).Correlations of the rate data by eq 1 t(Y) = a + b log kt(neophyl-OTs)> showed that the various substrates responded differently to the examined solvent effects on the solvolytic reactivity.For compounds 2-4, linear correlations were obtained.For compounds 5-9, E-line, A-line dispersions were noted which diverged with increasing ionizing power; for compounds 10-12, parallel E-line, A-line dispersions were obtained; and for compound 13, an E-line, A-line dispersion was observed which converged with increasing ionizing power.Stastistical analyses of the rate data correlations confirmed the significance of the E or A classification of data.The results are interpreted in terms of differences in the involvement of solvent in the transition state for those solvolyses assisted by bridging from those assisted by C-C ? bond hyperconjugation.
- Roberts, Donald D.
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p. 2521 - 2526
(2007/10/02)
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- SOLVOLYSIS OF SECONDARY ALKYL AZOXYTOSYLATES. A NEW REACTION RELATED TO SOLVOLYTIC DEAMINATION AND ARENESULPHONATE SOLVOLYSIS
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The rates of solvolysis of 2-adamantyl azoxytosylate have been measured in hexafluoropropan-2-ol (HFIP), trifluoroethanol (TFE), aqueous hexafluoropropan-2-ol (97HFIP), aqueous trifluoroethanol (97TFE), aqueous ethanol (50E and 80E), and aqueous methanol (80M) at 3-5 temperatures between ca. 23 and 70 deg C, and activation parameters have been determined.The O-2H solvent kinetic isotope effect has been measured for HFIP (kH/kD 1.025 +/- 0.02 at 50.8 deg C) and secondary α-deuterium kinetic isotope effects have been determined in 97HFIP (kH/kD 1.090 +/- 0.005; 40.2 deg C), 50E (1.091 -/+ 0.006; 51.0 deg C), and 80E (1.133 -/+ 0.009; 60.9 deg C).Neither methanesulphonic acid in 80M nor pyridine in TFE gives rise to a significant rate enhancement, and there is hardly any salt effect due to low concentrations of tetrabutylammonium perchlorate in 97TFE. 2-Adamantyl tosylate is formed in parallel with solvolysis product in ethanol and weakly aqueous ethanol, and is the sole organic product from reactions in chloroform and toluene.No relatively long lived intermediate such as 2-adamantyl tosylate is involved in the reaction in 97TFE, 80M, and 90M.The kinetics and product results are satisfactorily accommodated by a mechanism involving initial unimolecular rate-determining synchronous fragmentation of the substrate to give nitrous oxide and an ion-pair.This ion-pair is then either captured by solvent to give solvolysis product or, in the less polar media, undergoes ion-pair combination to yield covalent 2-adamantyl tosyate.Bicyclooctan-2-yl azoxytosylate has also been prepared, and rates and activation parameters have been determined in 97HFIP and 80M.There is no evidence from this limited study of a mechanism different from that of the 2-adamantyl analogue.Rates and activation parameters for the solvolysis of cyclohexyl azoxytosylate have also been determined in an even more limited study using only 97HFIP.Rates are slower than those for the other two compounds, but the mechanism appears to be the same.
- Maskill, H.,Thompson, John T.,Wilson, Alan A.
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p. 1693 - 1704
(2007/10/02)
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- Enamines of 2,2-bis(ethylthio)ethanal: a convenient route to γ-keto crotonate derivatives
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A new α-oxoaldehyde reagent, 2,2-bis(ethylthio)ethanal 1, has been prepared in high yield from ethanedial.Alkylation of the potassium salt of the enamines of 1 with various alkylating agents followed by in situ hydrolysis of the intermediate imine afforded high yields of the alkylation products of 1.This new reagent was used in the synthesis of a chiral potential precursor of the macrocyclic fragment of cytochalasins A,B, and F, as well as in the syntheses of the physiologically active diolides pyrenophorin and norpyrenophorin.
- Bates, Gordon S.,Ramaswamy, S.
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p. 2466 - 2475
(2007/10/02)
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- A SIMPLE METHOD FOR TOSYLATION WITH INVERSION
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In this paper we describe a simple one-step procedure for tosylation with inversion, using zinc tosylate, diethylazodicarboxylate and triphenylphospine.
- Galynker, Igor,Still, W. Clark
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p. 4461 - 4464
(2007/10/02)
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- Photolyse d' arenesulfonates d' alkyle. Influence des bases et mecanisme de la reaction
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Photolysis of alkyl arenesulfonates in various solvents leads to the corresponding alkyl alcohols in good chemical yields.Aromatic hydrocarbons and sulfur dioxide are also characterized in the reaction mixture.In the first step, homolysis of the C-S bond takes place from the sulfonate excited in a singlet state.In basic medium the reaction becomes cleaner and more efficient.Thr quenching of the fluorescence by NaOH, with 3 β-cholestanyl p-toluenesulfonate, seems to be diffusioncontrolled.The role of the base is discussed.
- Pete, Jean-Pierre,Portella, Charles
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p. 275 - 282
(2007/10/02)
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