Solvent-free <i>N</i>-Boc deprotection by <i>ex situ</i> generation of hydrogen chloride gas

Verschueren, Rik H.; Gilles, Philippe; Mileghem, Seger Van; Borggraeve, Wim M. De

doi:10.1039/d1ob00728a

Cited by 16 publications

(10 citation statements)

References 39 publications

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“…The initial optimization was performed for the gas‐solid hydrochlorination reaction of model substrate chalcone using HCl gas (Table 1, Figure 2). The reaction conditions for the ex situ generation of HCl gas were already optimized for our previous procedure on the solvent‐free N ‐Boc deprotection [16] . In the optimization of the gas‐solid reaction between HCl and chalcone, two factors revealed to be crucial for quick reaction times and quantitative conversions.…”

Section: Resultsmentioning

confidence: 99%

Solvent‐Free Hydrohalogenation and Deuteriohalogenation by Ex Situ Generation of HX and DX Gas

Verschueren,

Voets,

Saliën

et al. 2023

Eur J Org Chem

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The hydrohalogenation of olefins is one of the most straightforward methods to access alkyl halides. Despite safety hazards, using pure hydrogen halide gas remains the most atom economic way of performing hydrohalogenation reactions. In this work, we describe the solvent‐free hydro‐ and deuteriohalogenation of olefins using down to near‐stoichiometric amounts of hydrogen and deuterium halide gas. Two‐chamber reactors are employed as an enabling platform to access these reactive gases in a laboratory setting. Ex situ generation from inexpensive and readily available precursors provides on‐demand access to these gases (hydrogen chloride, deuterium chloride, hydrogen bromide, deuterium bromide, hydrogen iodide, and deuterium iodide) with precise stoichiometric control. Upon chemo‐ and regioselective conversion of the substrate, the halide products may be isolated without the need for any work‐up or purification steps making it a clean and labor‐, waste‐ and cost‐effective method.

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Section: Resultsmentioning

confidence: 99%

Solvent‐Free Hydrohalogenation and Deuteriohalogenation by Ex Situ Generation of HX and DX Gas

Verschueren,

Voets,

Saliën

et al. 2023

Eur J Org Chem

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“…The developed design of the liners can be used not only to study the temperature profiles of reactions. The tube-in-tube methodology opens a number of new opportunities in practical applications as it is a cost-effective development for H-tube and/or two-chamber reactors [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. The simple design, inexpensive components, and easy-to-handle loading/retrieval of chemicals are valuable advantages in complicated reactions with a shared gaseous atmosphere [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Thermal Mapping of Self-Promoted Calcium Carbide Reactions for Performing Energy-Economic Processes

Rodygin

Лоцман

Erokhin

et al. 2022

IJMS

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The syntheses of various chemical compounds require heating. The intrinsic release of heat in exothermic processes is a valuable heat source that is not effectively used in many reactions. In this work, we assessed the released heat during the hydrolysis of an energy-rich compound, calcium carbide, and explored the possibility of its usage. Temperature profiles of carbide hydrolysis were recorded, and it was found that the heat release depended on the cosolvent and water/solvent ratio. Thus, the release of heat can be controlled and adjusted. To monitor the released heat, a special tube-in-tube reactor was assembled using joining part 3D-printed with nylon. The thermal effect of the reaction was estimated using a thermoimaging IR monitor. It was found that the kinetics of heat release are different when using mixtures of water with different solvents, and the maximum achievable temperature depends on the type of solvent and the amount of water and carbide. The possibility of using the heat released during carbide hydrolysis to initiate a chemical reaction was tested using a hydrothiolation reaction—the nucleophilic addition of thiols to acetylene. In a model experiment, the yield of the desired product with the use of heat from carbide hydrolysis was 89%, compared to 30% in this intrinsic heating, which was neglected.

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“…Indeed, the potential formation of sparks arising from violent shock between the balls and the surface of the reactor both made of stainless steel is not desirable when working with liquid additives having a low flash point such as EtOAc (flash point −4 °C). The pure Boc‐Phe‐Gly‐OMe 1 was then submitted to gaseous hydrochloric acid for removal of the Boc group [11] . This solvent‐free solid‐gas reaction quantitatively yielded the Boc‐deprotected peptide (HCl⋅H‐Phe‐Gly‐OMe 2 ) as a white powder.…”

Section: Methodsmentioning

confidence: 99%

“…The pure Boc-Phe-Gly-OMe 1 was then submitted to gaseous hydrochloric acid for removal of the Boc group. [11] This solvent-free solid-gas reaction quantitatively yielded the Boc-deprotected peptide (HCl•H-Phe-Gly-OMe 2) as a white powder.…”

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confidence: 99%

Gram‐Scale Synthesis of a Hexapeptide by Fragment Coupling in a Ball Mill

et al. 2021

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Synthesis of long peptides is generally considered as being a challenge to peptide chemists, in addition to producing significant amounts of toxic waste, such as DMF. Here we show that using solvent-less methods, such as ball milling, enabled the production of the hexapeptide Boc-(Ala-Phe-Gly)2-OBn at the gram scale with high overall yield (77%, 5 linear steps). This is the longest peptide chain synthesized in a ball mill to date, in which the amino acid sequence is precisely controlled. This study complements the current fundamental knowledge required to synthesize longer and more difficult peptide chains (or small proteins) by using peptide fragment couplings in a ball mill.

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Solvent-free N-Boc deprotection by ex situ generation of hydrogen chloride gas

Abstract: This procedure enables the solvent-free deprotection of the most commonly used amino protecting group (N-Boc) by employing hydrogen chloride gas.

Cited by 16 publications

References 39 publications

Solvent‐Free Hydrohalogenation and Deuteriohalogenation by Ex Situ Generation of HX and DX Gas

Solvent‐Free Hydrohalogenation and Deuteriohalogenation by Ex Situ Generation of HX and DX Gas

Thermal Mapping of Self-Promoted Calcium Carbide Reactions for Performing Energy-Economic Processes

Gram‐Scale Synthesis of a Hexapeptide by Fragment Coupling in a Ball Mill

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