16052-42-9Relevant articles and documents
Discovery, characterisation, and utilisation of selenoxide-sulfonic acid salts: A new class of selenoxide-based oxidant and stable selenoxide equivalent
Procter, D. John,Thornton-Pett, Mark,Rayner, Christopher M.
, p. 1841 - 1854 (1996)
The preparation and characterisation of a novel class of salts of selenoxides with sulfonic acids are described. They are readily prepared by simple addition of the sulfonic acid to a solution of selenoxide, and removal of solvent. In most cases they are colourless crystalline solids and are considerably more stable than the parent selenoxides, allowing full characterisation and X-ray crystallographic analysis. They also efficiently oxidise sulfides to sulfoxides, with no overoxidation, and clean regeneration of selenide. Their structure has been confirmed by 1H NMR spectroscopy and X-ray crystallography.
Recyclable Lucas reagent in converting aliphatic alcohols to chlorides
Senaratne, Pushpananda A.,Orihuela, Felix M.,Malcolm, Arcelio J.,Anderson, Keith G.
, p. 185 - 186 (2003)
An industrially viable and environmentally friendly process is developed for the synthesis of menthyl chloride from the corresponding alcohol. Menthyl chloride was made in high yield by the reaction of menthol with the Lucas reagent. This chlorinating reagent was then recycled in the subsequent runs by simply replenishing the HCI, making the process simple and commercially viable. This improved procedure minimized the costly disposal of used Zn salts.
Matteson Reaction under Flow Conditions: Iterative Homologations of Terpenes
Kuhwald, Conrad,Kirschning, Andreas
supporting information, p. 4300 - 4304 (2021/05/26)
The Matteson reaction is ideally suited for flow chemistry since it allows iterative homologation of boronate esters. The present study provides accurate data on reaction times of the individual steps of the Matteson reaction, which occurs in less than 10 s in total. The protocol allows terpenes to be (per-)homologated in a controlled manner to yield homo-, bishomo-, and trishomo-terpenols after oxidative workup. The new terpene alcohols are validated with respect to their olfactoric properties.
Synthesis, characterization and hplc analysis of the (1S,2S,5R)-diastereomer and the enantiomer of the clinical candidate ar-15512
Abás, Sònia,Escolano, Carmen,Galdeano, Carles,Pujol, Eugènia,Rodríguez-Arévalo, Sergio,Vázquez, Santiago
, (2021/06/12)
AR-15512 (formerly known as AVX-012 and WS-12) is a TRPM8 receptor agonist currently in phase 2b clinical trials for the treatment of dry eye. This bioactive compound with menthol-like cooling activity has three stereogenic centers, and its final structure and absolute configuration, (1R,2S,5R), have been previously solved by cryo-electron microscopy. The route of synthesis of AR-15512 has also been reported, revealing that epimerization processes at the C-1 can occur at specific stages of the synthesis. In order to confirm that the desired configuration of AR-15512 does not change throughout the process and to discard the presence of the enantiomer in the final product due to possible contamination of the initial starting material, both the enantiomer of AR-15512 and the diastereomer at the C-1 were synthesized and fully characterized. In addition, the absolute configuration of the (1S,2S,5R)-diastereomer was determined by X-ray crystallographic analysis, and new HPLC methods were designed and developed for the identification of the two stereoisomers and their comparison with the clinical candidate AR-15512.
Method for preparing menthane carboxamide by taking L-menthol as raw material
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Paragraph 0055-0063, (2020/08/18)
The invention relates to a method for preparing menthane carboxamide by taking L-menthol as a raw material. The menthane carboxamide is prepared through the processes of chlorination, a Grignard reaction, acidification, acylating chlorination, amidation, distillation, recrystallization and the like in sequence. The process route is mature, has the advantages of operation management simplicity andsecurity risk reduction, during a chlorination process, lower-layer waste acid water is collected and reduced pressure distillation is carried out; H2O and HCl in the acid water are removed; recoveryof ZnCl2 is realized, reduced pressure distillation completion is realized, and a reagent, namely concentrated HCl, is added into the recovered ZnCl2; a ZnCl2/HCl saturated solution is prepared again,the L-menthol is added for chlorination reaction again, the steps are repeated, the waste acid water in the chlorination reaction can be repeatedly used, the production cost is saved, the wastewatertreatment cost is reduced, and the economic benefit is improved.
Enantiospecific Synthesis of ortho-Substituted 1,1-Diarylalkanes by a 1,2-Metalate Rearrangement/anti-SN2′ Elimination/Rearomatizing Allylic Suzuki–Miyaura Reaction Sequence
Rubial, Belén,Collins, Beatrice S. L.,Bigler, Raphael,Aichhorn, Stefan,Noble, Adam,Aggarwal, Varinder K.
supporting information, p. 1366 - 1370 (2019/01/04)
The one-pot sequential coupling of benzylamines, boronic esters, and aryl iodides has been investigated. In the presence of an N-activator, the boronate complex formed from an ortho-lithiated benzylamine and a boronic ester undergoes stereospecific 1,2-metalate rearrangement/anti-SN2′ elimination to form a dearomatized tertiary boronic ester. Treatment with an aryl iodide under palladium catalysis leads to rearomatizing γ-selective allylic Suzuki–Miyaura cross-coupling to generate 1,1-diarylalkanes. When enantioenriched α-substituted benzylamines are employed, the corresponding 1,1-diarylalkanes are formed with high stereospecificity.
Ti-Catalyzed Radical Alkylation of Secondary and Tertiary Alkyl Chlorides Using Michael Acceptors
Wu, Xiangyu,Hao, Wei,Ye, Ke-Yin,Jiang, Binyang,Pombar, Gisselle,Song, Zhidong,Lin, Song
supporting information, p. 14836 - 14843 (2018/11/10)
Alkyl chlorides are common functional groups in synthetic organic chemistry. However, the engagement of unactivated alkyl chlorides, especially tertiary alkyl chlorides, in transition-metal-catalyzed C-C bond formation remains challenging. Herein, we describe the development of a TiIII-catalyzed radical addition of 2° and 3° alkyl chlorides to electron-deficient alkenes. Mechanistic data are consistent with inner-sphere activation of the C-Cl bond featuring TiIII-mediated Cl atom abstraction. Evidence suggests that the active TiIII catalyst is generated from the TiIV precursor in a Lewis-acid-assisted electron transfer process.
Chiral menthyl phenyl phosphonamide compound and preparation method thereof
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Paragraph 0062; 0067, (2018/07/07)
The invention belongs to the field of organic synthesis, and particularly relates to a chiral menthyl phenylphosphonamide compound and a preparation method thereof. The chiral menthyl phenylphosphonamide compound has the following general formula (referring to the specification), wherein R1 is hydroxyl; R2 is hydroxyl, propyl, butyl, isopropyl, cyclopentyl, 2-chlorobenzyl, 2-methylidenefuran, 1-phenethyl or phenyl. The phosphonamide compound uses a phosphorus atom as a chiral source, has a more obvious chiral induction effect, and is more suitable for use in a chiral catalytic reaction; the phosphonamide compound has potentials of both drug activity and catalytic activity, and has development and application prospects; the phosphonamide compound is simple in synthesis method, easy to obtain and relatively good in application prospect.
Radical Deoxychlorination of Cesium Oxalates for the Synthesis of Alkyl Chlorides
Su, Justin Y.,Grünenfelder, Denise C.,Takeuchi, Kohei,Reisman, Sarah E.
supporting information, p. 4912 - 4916 (2018/08/24)
A radical deoxychlorination of cesium oxalates has been developed for the preparation of hindered secondary and tertiary alkyl chlorides. The reaction tolerates a number of functional groups, including ketones, alcohols, and amides, and provides complementary reactivity to standard deoxychlorination reactions proceeding by heterolytic mechanisms. Preliminary studies demonstrate that the developed conditions can also be applied to deoxybromination and deoxyfluorination reactions.
Rearrangement in Stereoretentive Syntheses of Menthyl Chloride from Menthol: Insight into Competing Reaction Pathways through Component Quantification Analysis
Hintermann, Lukas,Wong, Kit Ming
supporting information, p. 5527 - 5536 (2017/10/06)
The enantiopure reagent menthyl chloride (2) is generally prepared from (–)-(1R)-menthol (1) with Lucas' reagent (ZnCl2 in conc. aqueous HCl) in a stereoretentive reaction that appeared to be free from accompanying rearrangements. The same was assumed for a recent synthesis of 2 through TiCl4-catalyzed extrusion of SO2 from menthyl chlorosulfite (3). The products of both syntheses have now been analyzed by quantitative 1H and 13C NMR methods, and all reaction components have been identified down to the ≤ 0.5 mol-% level. Either reaction is accompanied by cationic rearrangement to the considerable extent of 18–25 mol-%. Besides the expected 2, neomenthylchloride (4) and five rearrangement products have been identified, among them three regioisomeric tertiary chloromenthanes (9, 10, 11), and both a secondary (12) and tertiary chloride (16) derived from ψ-menthane (1-isobutyl-3-methylcyclopentane). A scheme of rearrangement pathways starting from a common menthyl carbenium ion pair is derived. The effect of purification protocols on crude 2 has been studied quantitatively. Either selective solvolysis of tertiary sideproducts (98 mol-% purity) or low-temperature crystallization (≥ 97 mol-% purity) was successful. An improved, scalable synthesis of 2 through the catalytic rearrangement of chlorosulfite 3 is reported.
