N-Formylbenzotriazole: A Stable and Convenient N- and O-Formylating Agent

Katritzky, Alan R.; Chang, Hexi; Yang, Baozhen

doi:10.1055/s-1995-3959

Cited by 93 publications

(55 citation statements)

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“…However, L -tert -leucine (substance 18) is far more suitable for upscaled synthesis due to the ease of its handling and atom economy. (1) by usage of the reported mixed anhydride (64%), or (2) by usage of N -formylbenzotriazole as a formylation reagent (83%) [12,13] . The reason for the decision to introduce the formamide at the end of this route is the ability of formamides to form E/Z isomers, which complicate the spectroscopic analysis [14,15] .…”

Section: Synthesismentioning

confidence: 99%

Improved Synthesis of ADAM10 Inhibitor GI254023X

et al. 2010

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Background: The metalloproteinases ADAM10 and ADAM17 are involved in various diseases: neurodegeneration, cancer and inflammation. Objective: The inhibition of these proteases is a promising target in the treatment of inflammation and cancer. Methods and Results: In this study, we present an improved synthesis of the ADAM10 reference inhibitor GI254023X with a higher overall yield, enhanced detection ability and increased acid stability, providing easier handling. Conclusion: This upscaled synthesis, free of diastereomeric intermediates, ensures single-batch identity, thus warranting its reproducibility in further biological investigations.

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Section: Synthesismentioning

confidence: 99%

Improved Synthesis of ADAM10 Inhibitor GI254023X

et al. 2010

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“…Now we propose the convenient routes to new fivemembered aza-heterocycles derivatives of mono-and diphosphonic acids via addition of tris(trimethylsilyl) phosphite to easily available N-formyl derivatives of fivemembered aza-heterocycles [8] which are obtained by us in situ. It is shown that this reaction proceeds only at the presence of effective catalyst-trimethylsilyl triflate [5,9] -under mild conditions to give phosphonates 1 and diphosphonates 2.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of new functionalized mono‐ and diphosphonic acids with five‐membered aza‐heterocycles moieties

Prishchenko

Alekseyev

Ливанцов

et al. 2016

Heteroatom Chemistry

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The new functionalized hydroxymethylphosphonic and methylenediphosphonic acids are synthesized via unique reaction of tris(trimethylsilyl)phosphite and Nformyl derivatives of five-membered aza-heterocycles at the presence of effective catalyst-trimethylsilyl triflate. Trimethylsilyl esters 1,2 readily react with excess methanol under mild conditions to form water-soluble functionalized mono-or diphosphonic acids, respectively, 3,4 (Scheme 3).The resulting compounds 1-4 can be used for the synthesis of new types of organophosphorus substances, including both heterocyclic fragments and phosphonic groups. These compounds are promising precursors for multitarget drug discovery, perspective plant growth regulators, as well as effective polydentate ligands for various metal complexes with versatile properties.It should be noted that, unlike diethyl acetal formamides, which react readily with esters of phosphorous acid to form N-substituted aminomethylenediphosphonates, [10] reaction of readily available N-diethoxymethyl derivatives of azaheterocycles [11][12][13] with tris(trimethylsilyl) phosphite proceeds via rupture of C-N bonds and leads to diethoxymethylphosphonates 5 in high yields (Scheme 4). | CONCLUSIONSThus, we have proposed the convenient methods of synthesis of new functionalized mono-and diphosphonic acids with five-membered aza-heterocycles moieties via the unique reaction of tris(trimethylsilyl) phosphite with N-formyl azaheterocycles catalyzed by trimethylsilyl triflate. | EXPERIMENTAL | Bis(trimethylsilyl) 1H-imidazol- 1-yl(trimethylsiloxy)methylphosphonate (1a) and tetra(trimethylsilyl) 1H-imidazol-1-ylmethylenediphoshonate (2a)A solution of symm-dicyclohexylcarbodiimide (14.4 g, 0.07 mol) in CH 2 Cl 2 (20 mL) was added under stirring to a solution of 1H-imidazole (3.4 g, 0.05 mol) and formic acid (2.8 g, 0.06 mol) in CH 2 Cl 2 (50 mL). The mixture was stirred for 6 hours and left for 12 hours, then the precipitate is filtered off, the resulting solution was added to a solution of tris(trimethylsilyl) phosphite (44.8 g, 0.15 mol), and a solution of trimethylsilyl triflate (2.9 g, 0.013 mol) in CH 2 Cl 2 (10 mL) was added to this mixture. The mixture was heated in a boiling water bath to complete the stripping of low-boiling compounds and then distilled to give 1.8 g of phosphonate 1a, yield 9%, bp 102°C (1 mm Hg) and diphosphonate (22.0 g) 2a, yield 83%, bp 126°C (1 mm Hg). 4. | 1H-Imidazol-1-yl(hydroxy) methylphosphonic acid (3a)Yield 96%, mp 144-145°C (decomposition ).Phosphonate 5b was obtained similarly.

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“…18 The reported methods for the synthesis of substituted benzoxazine-2,4-diones 2 include i) reaction of phenyl salicylates with isocyanates, 19 ii) silver trifluoroacetate mediated reaction of salicylic acid with isocyanates, 20 iii) palladium catalyzed cyclocarbonylation of o-iodophenols, 21 iv) reaction of salicylamides with ClCO 2 Et 22-23 and v) from 2-(methoxycarbonyloxy)benzoyl chloride [24][25] (Scheme 2). 27 formylation, 28 trifluoroacylation, 29 O-acylation, 30 C-acylation [31][32][33] and the synthesis of polycyclic heteroaromatics. [34][35][36] Recently, we utilized the N-(o-hydroxyarylacyl)benzotriazoles for the syntheses of o-hydroxyaroyl esters / amides (Scheme 3).…”

Section: Introductionmentioning

confidence: 99%