Showing papers on "Diazomethane published in 2016"
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TL;DR: To avoid storage and transportation of the hazardous compound, a representative downstream process in a packed-bed reactor yielding highly functionalized building blocks was developed.
68 citations
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TL;DR: A configurationally simple and robust semibatch apparatus for the in situ on-demand generation of anhydrous solutions of diazomethane (CH2N2) avoiding distillation methods is presented.
Abstract: A configurationally simple and robust semibatch apparatus for the in situ on-demand generation of anhydrous solutions of diazomethane (CH2N2) avoiding distillation methods is presented. Diazomethane is produced by base-mediated decomposition of commercially available Diazald within a semipermeable Teflon AF-2400 tubing and subsequently selectively separated from the tubing into a solvent- and substrate-filled flask (tube-in-flask reactor). Reactions with CH2N2 can therefore be performed directly in the flask without dangerous and labor-intensive purification operations or exposure of the operator to CH2N2. The reactor has been employed for the methylation of carboxylic acids, the synthesis of α-chloro ketones and pyrazoles, and palladium-catalyzed cyclopropanation reactions on laboratory scale. The implementation of in-line FTIR technology allowed monitoring of the CH2N2 generation and its consumption. In addition, larger scales (1.8 g diazomethane per hour) could be obtained via parallelization (numberin...
43 citations
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TL;DR: The efficient synthesis of cyclopropyl boronic esters in library format using a diazomethane flow reactor has been achieved and enables the repeated execution of Pd-catalyzedcyclopropanation reactions without compromising its operation over time.
Abstract: The efficient synthesis of cyclopropyl boronic esters in library format using a diazomethane flow reactor has been achieved. A pivotal component of the system is a fully automated tube-in-tube reactor allowing for safe handling of hazardous diazomethane on repeated small scale and for the generation of larger quantities of product. The setup enables the repeated execution of Pd-catalyzed cyclopropanation reactions without compromising its operation over time.
32 citations
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TL;DR: Reactions of dihetaryl and aryl/hetaryl thioketones with 2-diazopropane, diazoethane, and (trimethylsilyl)diazomethane were studied at variable temperature and the presence of S or Se atoms in the hetaryl rings is of importance for stabilizing diradical intermediates.
Abstract: Reactions of dihetaryl and aryl/hetaryl thioketones with 2-diazopropane, diazoethane, and (trimethylsilyl)diazomethane were studied at variable temperature. The experiments showed that reactions with 2-diazopropane carried out at –75 °C occur mainly via the initially formed, relatively stable 1,3,4-thiadiazolines as products of the [3 + 2]-cycloaddition of the diazo dipole onto the C=S bond. The latter decompose only at higher temperature (ca. −40 °C) to generate thiocarbonyl S-isopropanide. In the absence of the starting thioketone, the corresponding thiiranes and/or ethene derivatives, formed from them via spontaneous desulfurization, are the main products. In contrast, reactions with diazoethane occurred predominantly via initially formed diradicals, which in cascade processes gave sterically crowded 4,4,5,5-tetrahetaryl-1,3-dithiolanes as major products. Finally, the reaction of dihetaryl thioketones with (trimethylsilyl)diazomethane occur smoothly at −75 °C leading to the corresponding 4,4,5,5-tetrahetaryl-1,3-dithiolanes as the exclusive [3 + 2]-cycloadducts formed via a cascade of postulated diradicals. The presence of S or Se atoms in the hetaryl rings is of importance for stabilizing diradical intermediates. Remarkably, in no single case, the ‘head-to-head dimerization’ of aryl/ hetaryl and dihetaryl substituted thiocarbonyl ylides was observed.
30 citations
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TL;DR: The work described herein represents the first report on the use of TMO·BF4 as a viable, stable and safe agent for the methylation of phosphonic acids and their half esters and within the context of an OPCW Proficiency Test sample analysis.
27 citations
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TL;DR: Owing to the sequential generation of several intermediates of multifaceted reactivity, including diazoalkane derivatives and alkylidene carbenes, it is possible to induce novel Grob-type C-C fragmentations, alkyLidene carbene mediated Li-N insertions, and dipolar cycloadditions by controlling the reaction parameters.
Abstract: α,β-Unsaturated ketones generally undergo addition reactions with nucleophiles with a preference for either 1,2- or 1,4-addition, but rarely both. However, the right combination of reagents allows for consecutive 1,4- and 1,2-additions to occur: Cyclic α,β-unsaturated ketones undergo double additions with lithium(trimethylsilyl)diazomethane, effectively generating various molecular frameworks with complexity and diversity. Owing to the sequential generation of several intermediates of multifaceted reactivity, including diazoalkane derivatives and alkylidene carbenes, it is possible to induce novel Grob-type C-C fragmentations, alkylidene carbene mediated Li-N insertions, and dipolar cycloadditions by controlling the reaction parameters.
14 citations
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TL;DR: In this paper, a one-pot synthesis of an α-chloroketone starting from N-Boc-l-phenylalanine in a novel type of "tube-in-flask" semi-batch diazomethane generator was reported.
Abstract: The crucial structural motive in viral protease inhibitors such as atazanavir and darunavir is a chiral aminoalcohol structure. The structure is generally introduced during the synthesis of the protease inhibitor via an α-chloroketone intermediate. The α-chloroketone can be synthesized in a multistep sequence from naturally occurring l-phenylalanine. Herein, we report a onepot synthesis of an α-chloroketone starting from N-Boc-l-phenylalanine in a novel type of “tube-in-flask” semi-batch diazomethane generator. Activation of the amino acid to the mixed anhydride was carried out in the flask, while diazomethane was generated from in situ formed N-nitroso-N-methylurea within a gas-permeable tubing contained inside the flask. The diazomethane diffused through the gas-selective membrane into the flask, and reacted with the anhydride to the diazoketone (Arndt—Eistert reaction). The addition of aqueous hydrogen chloride provided the α-chloroketone and destroyed any excess of diazomethane. The desired product wa...
14 citations
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TL;DR: In this article, the synthesis of conjugates containing a diterpenoid fragment and a pyrazole-ring pharmacophore by 1,3-dipolar cycloaddition of diazomethane to allenoates in the presence of Et3N was demonstrated.
Abstract: Regiospecific synthesis of conjugates containing a diterpenoid fragment and a pyrazole-ring pharmacophore by 1,3-dipolar cycloaddition of diazomethane to allenoates in the presence of Et3N was demonstrated.
12 citations
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TL;DR: The transformation of α-carbonyl diazomethanes to metal-carbene radicals was confirmed to be a two-step process via metal-diazo radicals.
Abstract: Metal-diazo radicals of α-carbonyl diazomethanes are new members of the radical family and are precursors to metal-carbene radicals. Herein, using electron paramagnetic resonance spectroscopy with spin-trapping, we detect diazo radicals of α-carbonyl diazomethanes, induced by [Rh(I)Cl(cod)]2, [Co(II)(por)] and PdCl2, at room temperature. The unique quintet signal of the Rh-diazo radical was observed in measurements of α-carbonyl diazomethane adducts of [Rh(I)Cl(cod)]2 in the presence of 5,5-dimethyl-pyrroline-1-N-oxide (DMPO). DFT calculations indicated that 97.2% of spin density is localized on the diazo moiety. Co- and Pd-diazo radicals are EPR silent but were captured by DMPO to form spin adducts of DMPO-N∙ (triplet-of-sextets signal). The spin-trapping also provides a powerful tool for detection of metal-carbene radicals, as evidenced by the DMPO-trapped carbene radicals (DMPO-C∙, sextet signal) and 2-methyl-2-nitrosopropane-carbene adducts (MNP-C∙, doublet-of-triplets signal). The transformation of α-carbonyl diazomethanes to metal-carbene radicals was confirmed to be a two-step process via metal-diazo radicals.
10 citations
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TL;DR: This sensitive approach for extracting nerve gas markers such as phosphonic acids from urine and other aqueous samples can be flexibly modified to obtain confirmatory information, or address potential problems caused by interferences in some samples.
5 citations
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TL;DR: In this article, aryl/hetaryl thioketones with 2-diazopropane, diazoethane, and (trimethylsilyl)diazomethane were studied at variable temperature.
Abstract: Reactions of dihetaryl and aryl/hetaryl thioketones with 2-diazopropane, diazoethane, and (trimethylsilyl)diazomethane were studied at variable temperature. The experiments showed that reactions with 2-diazopropane carried out at –75 °C occur mainly via the initially formed, relatively stable 1,3,4-thiadiazolines as products of the [3 + 2]-cycloaddition of the diazo dipole onto the C=S bond. The latter decompose only at higher temperature (ca. −40 °C) to generate thiocarbonyl S-isopropanide. In the absence of the starting thioketone, the corresponding thiiranes and/or ethene derivatives, formed from them via spontaneous desulfurization, are the main products. In contrast, reactions with diazoethane occurred predominantly via initially formed diradicals, which in cascade processes gave sterically crowded 4,4,5,5-tetrahetaryl-1,3-dithiolanes as major products. Finally, the reaction of dihetaryl thioketones with (trimethylsilyl)diazomethane occur smoothly at −75 °C leading to the corresponding 4,4,5,5-tetrahetaryl-1,3-dithiolanes as the exclusive [3 + 2]-cycloadducts formed via a cascade of postulated diradicals. The presence of S or Se atoms in the hetaryl rings is of importance for stabilizing diradical intermediates. Remarkably, in no single case, the ‘head-to-head dimerization’ of aryl/ hetaryl and dihetaryl substituted thiocarbonyl ylides was observed.
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01 Dec 2016TL;DR: InChIKey as discussed by the authors is a tool for diazotization of 2,2,2-trifluoroethylamine hydrochloride, which is not commercially available.
Abstract: [371-67-5] C2HF3N2 (MW 110.04)
InChI = InChI=1S/C2HF3N2/c3-2(4,5)1-7-6/h1H
InChIKey = YWUIUNGMQOICND-UHFFFAOYSA-N
(trifluoroethyl carbene source for cyclopropanation; 1,3-dipole reagent for dipolar cycloaddition)
Alternate Names: ethane, 2-diazo-1,1,1-trifluoro-; 1-diazo-2,2,2-trifluoroethane; 2-diazo-1,1,1-trifluoroethane; trifluoromethyl diazomethane; 2,2,2-trifluorodiazoethane
Physical Data: bp 13 °C.
Solubility: sol ether, dichloromethane, toluene.
Form Supplied in: not commercially available.
Preparative Methods: diazotization of 2,2,2-trifluoroethylamine hydrochloride.
Handling, Storage, and Precautions: toxic, explosive, and gaseous at room temperature. Trifluoromethyl diazomethane should be stored in an ethereal solution under anhydrous conditions at low temperature (e.g. −15 °C).
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23 Mar 2016
TL;DR: In this paper, a method and equipment for preparing diazomethane is described, which is used in the field of organic synthesis, with the aim to overcome shortcomings of existing methods.
Abstract: The invention relates to a method and equipment for preparing diazomethane, and belongs to the field of organic synthesis. The method and the equipment have the advantages that the method and the equipment aim to overcome shortcomings of existing methods for preparing diazomethane and are short in process route, low in raw material cost and high in yield, preparation procedures are safe and environmental friendly, and effects of industrial continuous production can be realized; the method for preparing the diazomethane is implemented by the aid of the equipment, the diazomethane can be generated from a N-methyl-N-nitroso material and alkali metal hydroxide by means of completely closed reaction, stable organic solution can be formed by means of timely extraction by the aid of extraction agents, accordingly, the retention time of the diazomethane in water can be shortened, the decomposition rate of the diazomethane which can generate methyl alcohol and nitrogen when in water can be reduced, the diazomethane yield can be increased, and safety risks of operator poisoning and explosion due to leakage of gaseous diazomethane can be prevented.
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TL;DR: In this article, it was shown that the reaction of diazomethane with 5-benzylidene-3-phenylrhodanine (1) in THF at -20° occurs at the exocyclic C=C bond via cyclopropanation to give 3a and methylation to yield 4, respectively.
Abstract: It has been shown previously that the reaction of diazomethane with 5-benzylidene-3-phenylrhodanine (1) in THF at -20° occurs at the exocyclic C=C bond via cyclopropanation to give 3a and methylation to yield 4, respectively, whereas the corresponding reaction with phenyldiazomethane in toluene at 0° leads to the cyclopropane derivative 3b exclusively. Surprisingly, under similar conditions, no reaction was observed between 1 and diphenyldiazomethane, but the 2-diphenylmethylidene derivative 5 was formed in boiling toluene. In the present study, these results have been rationalized by calculations at the DFT B3LYP/6-31G(d) level using PCM solvent model. In the case of diazomethane, the formation of 3a occurs via initial Michael addition, whereas 4 is formed via [3 + 2] cycloaddition followed by N2 elimination and H-migration. The preferred pathway of the reaction of 1 with phenyldiazomethane is a [3 + 2] cycloaddition, subsequent N2 elimination and ring closure of an intermediate zwitterion to give 3b. Finally, the calculations show that the energetically most favorable reaction of 1 with diphenyldiazomethane is the initial formation of diphenylcarbene, which adds to the S-atom to give a thiocarbonyl ylide, followed by 1,3-dipolar electrocyclization and S-elimination.
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01 Jan 2016
TL;DR: In this paper, the reaction of protonated diazomethane with water and hydroxide spontaneously to give methanol and a nitrogen molecule is studied computationally.
Abstract: The reaction of protonated diazomethane with water and hydroxide spontaneously to give methanol and a nitrogen molecule is being studied computationally. Water attacks as the nucleophile following SN2 mechanism and hydroxide attacks as a base as well as a nucleophile. The structures are optimized using software Gaussian 09. The method applied is DFT B3LYP having basis set 6- 311G +(2d,p). The energies are compared relatively. The final product is found to be -34.7kcal/mol stable than the reactant in case of the methane diazonium ion reacting with two water molecules. In case of hydroxide (nucleophile) the final product is found to be-233.2 kcal/mol stable. Reactions of the cation with hydroxide as a base, yields the product diazomethane and water and the energy of the isolated product is-184.3kcal/mol. The driving force of the reaction is removal of nitrogen molecule as a byproduct (triply bonded, very stable).
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22 Jun 2016
TL;DR: In this paper, a method for preparing methylmercaptodiafenthiuron was described, where a methylation reagent with low price was used to reduce the product cost.
Abstract: The invention discloses a method for preparing methylmercaptodiafenthiuron. The method comprises the following reaction formula described in the specification, wherein in the formula, a methylation reagent is selected from methyl chloride, methyl bromide, methyl benzenesulfonate, methyl trifluoromethansulfonate, methyl p-toluenesulfonate, dimethyl carbonate, trimethyl phosphate, dimethyl sulfate, diazomethane, methyl trichloroethanimidate, and formaldehyde+formic acid; an alkali is selected from M2CO3, NCO3, MHCO3, MXR1, N(XR1)2, MH, NH2 or NO; M is selected from Li, Na or K; N is selected from Mg or Ca; X is selected from O or S; R1 is selected from H or C1-C6 alkyl. The compound shown in the reaction formula undergoes a reaction with the methylation reagent and the alkali in a proper solvent to prepare the methylmercaptodiafenthiuron. According to the method, the methylation reagent with low price is used, so the product cost is reduced; and the method is mild in reaction condition, simple, convenient and feasible in post-treatment method, economic and effective, and prone to industrialized production.
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TL;DR: In this paper, a continuous process for the synthesis and inline separation of trifluoromethyl diazomethane in a single continuous flow process is presented, where the diazo building block is generated from the corresponding amine and NaNO2 under acidic, aqueous conditions and subsequently diffuses through a gas-permeable membrane into an organic stream.
Abstract: A continuous process for the synthesis and inline separation of anhydrous trifluoromethyl diazomethane in a single continuous flow process is presented. The diazo building block is generated from the corresponding amine and NaNO2 under acidic, aqueous conditions and subsequently diffuses through a gas-permeable membrane into an organic stream. To avoid storage and transportation of the hazardous compound, a representative downstream process in a packed-bed reactor yielding highly functionalized building blocks was developed.
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TL;DR: In this paper, cycloalkanone oximes were spirofused to 4-oxo-6-methyl-1,2,3,4-tetrahydropyridine fragment through the α-carbon atom and C2, respectively, on heating in polyphosphoric acid.
Abstract: ω-(4-Oxo-1,4-dihydropyridin-2-yl)alkanamides were obtained from cycloalkanone oximes spirofused to 4-oxo-6-methyl-1,2,3,4-tetrahydropyridine fragment through the α-carbon atom and C2, respectively, on heating in polyphosphoric acid. The resulting amides were converted to the corresponding acids and methyl esters. Methylation of 5-(6-methyl-4-oxo-1,4-dihydropyridin-2-yl)pentanamide with diazomethane gave 4-methoxypyridine derivative as the major product and a small amount of N-methyl derivative, 5-(1,6-di-methyl- 4-oxo-1,4-dihydropyridin-2-yl)pentanamide.
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18 May 2016
TL;DR: In this article, a method of acquiring a biomarker compound from bio-degraded crude oil was proposed, which includes the following steps: (S) extracting asphaltene from the bio-degraded crude oil; (S2) oxidizing the asphalte to obtain an oxidized crude product; and (S3) esterifying the oxidised crude product with an esterification reagent to obtain the biomarker compounds.
Abstract: The invention discloses a method of acquiring a biomarker compound from bio-degraded crude oil. The method includes the following steps: (S1) extracting asphaltene from the bio-degraded crude oil; (S2) oxidizing the asphaltene to obtain an oxidized crude product; and (S3) esterifying the oxidized crude product with an esterification reagent to obtain the biomarker compound. The esterification reagent is a boron trifluoride methanol solution, diazomethane or trimethylsilane diazomethane. When the asphaltene is extracted from the bio-degraded crude oil, the asphaltene is oxidized so that the compounds, which are coated by or bonded to the asphaltene, having an aromatic ring structure can be converted into corresponding carboxylic acids to obtain a corresponding oxidized crude product. The oxidized crude product then is esterified to convert the carboxylic acid into esters. The esters can be free from being coated by or bonded to the asphaltene and be dissolved in a chromatographic solvent, thereby providing a basis for oil-source correlation of the biomarker compound and providing a basis for analyzing information of the bio-degraded crude oil.
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01 Jun 2016
TL;DR: The ruthenium carbene catalyst is characterized by being a compound with a structural formula shown in the specification as discussed by the authors, which is a simple and easily obtainable compound, and industrial large-scale production is facilitated.
Abstract: The invention provides a ruthenium carbene catalyst The ruthenium carbene catalyst is characterized by being a compound with a structural formula shown in the specification; the synthetic method of the ruthenium carbene catalyst, namely the compound comprises the following steps: rutheniumchloride hydrate and ligand react to produce a ruthenium complex, the ruthenium complex and a diphenyl diazomethane compound react to produce a ruthenium carbene complex, and then the ruthenium carbene complex and tricyclohexylphosphine react to produce the target ruthenium carbene catalyst The ruthenium carbene catalyst is prepared by selecting rutheniumchloride hydrate, ligand, substituted diphenyl diazomethane and the like as the main materials, therefore the raw materials are simple and easily obtainable, and industrial large-scale production is facilitated
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TL;DR: In this paper, cyclic α,β-unsaturated ketones undergo double additions with lithium(trimethylsilyl)diazomethane, effectively generating various molecular frameworks with complexity and diversity.
Abstract: Cyclic α,β-unsaturated ketones undergo double additions with lithium(trimethylsilyl)diazomethane, effectively generating various molecular frameworks with complexity and diversity.
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TL;DR: In this article, a short review summarizes recent important developments using peroxides as versatile methylating reagents, including direct methylation and sequential methylation together with other functionalization processes.
Abstract: Methylation is an important transformation in organic chemistry. Methods for methylation in industry and academia still frequently employ hazardous and toxic reagents, such as diazomethane, dimethyl carbonate, methyl iodide, and dimethyl sulfate. From the point of view of sustainable and environmentally friendly chemistry, much effort has been devoted to the discovery and development of alternative methylating reagents. A particularly attractive new methyl source that is attracting attention is derived from the cleavage of peroxides. This short review summarizes recent important developments using peroxides as versatile methylating reagents, including direct methylation and sequential methylation together with other functionalization processes. The corresponding reaction mechanisms are also discussed. 1 Introduction 2 Direct Methylation 2.1 Methylation of C–H Bonds 2.2 Methylation of N–H Bonds 2.3 Methylation of O–H Bonds 3 Methylation together with Other Functionalizations 3.1 Oxidation and Methylation 3.2 Decarboxylative Methylation 3.3 Methylation and Cyclization 4 Conclusions and Perspectives
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31 Mar 2016TL;DR: In this article, the diazomethane precursor was synthesized from commercially available 3-(chlorosulfonyl)benzoic acid and was stored at room temperature, but is preferably stored at 0°C.
Abstract: [1018070-32-0] C8H8N2O5S (MW 244.22)
InChI = 1S/C8H8N2O5S/c1-10(9-13)16(14,15)7-4-2-3-6(5-7)8(11)12/h2-5H,1H3,(H,11,12)
InChIKey = QFNPJWWQQCMSQL-UHFFFAOYSA-N
(diazomethane precursor; Diazald® analog)
Alternate Names: 3-(N-methyl-N-nitrososulfamoyl)benzoic acid; 3-[(N-nitrosomethylamino)sulfonyl]benzoic acid.
Solubility: soluble in dichloromethane, dimethyl sulfoxide, methanol.
Form Supplied in: yellow solid.
Preparative Method: synthesized from commercially available 3-(chlorosulfonyl)benzoic acid. The reaction of commercial acid with 5 equiv of methylamine in a mixture of THF/H2O afforded the sulfonamide, which subsequently underwent an N-nitrosation with 10 equiv of sodium nitrite in a mixture of formic acid and dichloromethane at 0 °C.1
Analysis of Reagent Purity: 1H NMR (300 MHz, DMSO) δ 13.69 (s, 1H), 8.41 (s, 1H), 8.33 (d, J = 7.8 Hz, 1H), 8.29–8.23 (m, 1H), 7.85 (t, J = 7.8 Hz, 1H), 3.16 (s, 3H). 13C NMR (100 MHz, DMSO) δ 165.9, 137.3, 136.2, 133.2, 132.2, 131.6, 128.5, 30.2.
Handling, Storage, and Precautions: stable at room temperature, but is preferably stored at 0 °C. The corresponding sodium salt can also be stored as an aqueous solution at 4 °C over a few days (degradation due to slow denitrozation in water). The use of a blast shield during the synthesis is recommended. Classical diazomethane precautions should be taken while generating the diazomethane by decomposition.
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24 Aug 2016
TL;DR: In this paper, a method for the preparation of a benzyl boron ester compound was proposed, where aromatic boric acid Ar-B(OH)2, trimethyl silicon-based diazomethane, pinacol and tetrabutyl ammonium fluoride are subjected to a reaction in an organic solvent.
Abstract: The invention discloses a preparation method of a benzyl boron ester compound. According to the preparation method, aromatic boric acid Ar-B(OH)2, trimethyl silicon-based diazomethane, pinacol and tetrabutyl ammonium fluoride are subjected to a reaction in an organic solvent so as to obtain a benzyl pinacol boron ester compound, wherein Ar represents a non-heterocyclic aromatic group. After the method is adopted, the benzyl boron ester compound is obtained by starting from the aromatic boric acid and converting under a one-pot condition; the method is mild in reaction conditions, the reaction related to the method occurs smoothly in the air without needing strict water-free and oxygen-free conditions, and the method is convenient and simple to operate; the method has better tolerance and universality for functional groups and does not need an expensive metal catalyst and a ligand, thus being lower in reaction cost and being widely used for preparing the benzyl boron ester compound.