Reactions of alkyl (halomethyl)furancarboxylates with hexamethylenetetramine

Lapina, I. M.; Певзнер, Л. М.; Потехин, А. А.

doi:10.1134/s1070363206080251

Cited by 8 publications

(8 citation statements)

References 6 publications

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“…Alkene, alkyne, pyridyl, methylcyclopentyl, Boc-piperidine, and adamantyl-containing substrates were also well tolerated. Poorer yields were obtained for poorer electrophiles such as unactivated linear alkyl substrate, e.g., compounds 6 , 8 , and 14 with 28%–39% yields, a trend also observed in the literature . Unfortunately, this is an inherent drawback consistent with the reaction itself, and the potential for long reaction times to improve yields, up to multiple weeks, are well documented .…”

Section: Resultssupporting

confidence: 51%

“…The Delépine reaction remains one of the mildest methods of forming a primary amine, avoiding the use of toxic reagents such as hydrazine (often required in the Gabriel reaction, although strong acids and bases have also been reported in the deprotection reaction under prolonged reflux conditions , ) and azides (as per the Curtius, Schmidt, and Staudinger reactions) and avoiding the generation of stoichiometric amounts of triphenylphosphine oxide waste as per the Staudinger reduction. Furthermore, chromatographic purification of products formed by the Delépine reaction are generally not required making this method of amine formation potentially desireable …”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, chromatographic purification of products formed by the Deleṕine reaction are generally not required making this method of amine formation potentially desireable. 9 The current availability of aryl/alkyl chloride, bromide, and iodide building blocks of less than 400 g mol −1 , according to Sigma-Aldrich's online database, showed that there are currently 7496 compounds available compared to 6224 comparable amines. With ∼1200 more halides commercially available, the Deleṕine reaction may provide a rapid and mild route to generate amine building blocks for otherwise unavailable materials.…”

Section: ■ Introductionmentioning

confidence: 99%

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Assessing the Limits of Sustainability for the Delépine Reaction

Jordan

Huang

Sneddon

et al. 2020

ACS Sustainable Chem. Eng.

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Herein, we report our efforts to improve the sustainability of the Delépine reaction for the formation of primary amines from activated alkyl halides. A number of alternative greener, more sustainable solvents to the traditionally employed chloroform were identified, and the use of dimethyl carbonate (DMC) as a solvent was exemplified in the synthesis of a number of pharmaceutically relevant building blocks including the 40 mmol scale synthesis of N-Boc-3-pyrroline. Green chemistry metrics were calculated to identify areas of the Delépine reaction that could potentially be improved upon. Poor atom economy (A.E.) was identified as a key shortcoming of this methodology, although our efforts to improve A.E. and reduce waste were unfortunately unsuccessful. A preliminary thermal safety evaluation was conducted using differential scanning calorimetry due to stability concerns raised over the nature of the products; none of the products were considered to have shock-sensitive or explosive propagating properties. The limits of potential sustainability improvements that could be achieved are critically discussed including the inherent issues with this methodology such as the release of formaldehyde, generation of carcinogenic bis(chloromethyl)ether, and poor atom economy.

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Section: Resultssupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Assessing the Limits of Sustainability for the Delépine Reaction

Jordan

Huang

Sneddon

et al. 2020

ACS Sustainable Chem. Eng.

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“…It has a cage-like structure similar to adamantane. Hexamethylenetetramine has received significant attention as a powerful catalyst for effecting various organic transformations [24][25][26][27] . In our continued interest in the development of highly expedient methods for the synthesis of heterocyclic compounds [28][29][30][31] , we wish to introduce hexamethylenetetramine as a mild and highly efficient catalyst for the preparation of 2-amino-4H-pyrans under room temperature condition (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Hexamethylenetetramine as an Efficient Catalyst for One-Pot, Three Component Synthesis of 2-Amino-4H-Pyran Derivatives

2015

Chem Sci Trans

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“…The bromination of ester III with N-bromosuccinimide in carbon tetrachloride led to the formation of bromomethyl compound IV in 36% yield. The substitution of bromine with amino group was carried out by Delepine reaction which was thoroughly studied for halomethyl derivatives of alkyl furoates [12] (Scheme 2).…”

mentioning

confidence: 99%

Synthesis of alkyl 2-aminomethyl-5-(1,2,3-thiadiazol-4-yl)furan-3-carboxylate and pseudopeptides on its basis

2015

Self Cite

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Cyclization of alkyl 2-methyl-5-acetylfuran-3-carboxylate carbethoxyhydrazone according to Hurd-Mori reaction afforded alkyl 2-methyl-5-(1,2,3-thiadiazol-4-yl)-3-carboxylate. Its bromination with Nbromosuccinimide yielded 2-bromomethyl derivative. The latter was involved in the Delepine reaction to form alkyl 2-aminomethyl-5-(1,2,3-thiadiazol-4-yl)-3-carboxylate. Acylation of the product synthesized with chloroacetyl chloride and subsequent treatment with morpholine or 4-methylpiperidine gave the corresponding pseudopeptides. In the course of these transformations the furylthiadiazole fragment retained its stability.γ-Aminoacetoacetic acid and its derivatives for a long time attract the attention of neurophysiologists as the participants of metabolism of glutamate in brain, and also due to the role played by ketone bodies in the process of epilepsy [1-5]. 2-Aminomethylfuran-3-carboxylic acid is the isostere of Z-enol form of γ-aminoacetoacetic acid. Therefore the search of new pharmaceuticals among the compounds containing this structural fragment seems promising.cule and permits performing a considerably broad range of chemical transformations [8]. Considering the above-mentioned data, in this work the synthesis of the derivatives of 2-aminomethyl-5-(1,2,3-thiadiazol-4-yl)-furan-3-carboxylic acid was carried out. In the first stage it was necessary to establish whether the introduction of an ester group in the position 3 of the furan ring which is not conjugated with the thiadiazole fragment can provide the thermal stability of the system.Easily available ethyl 2-methyl-5-acetylfuran-3-carboxylate I was chosen as the starting substance. It was reacted with carbethoxyhydrazine to give the corresponding hydrazone II. Under the action of thionyl chloride in chloroform the latter underwent cyclization according to Hurd-Mori reaction [9, 10] to form thiadiazolylfuran III in 87% yield. Its structure was established by 1 H and 13 C NMR spectroscopy and mass spectrometry. In the 1 H NMR spectrum of this compound the signal of thiadiazole proton in the position 5 of the thiadiazole ring is observed at 8.58 ppm what coincides with the value of chemical shift of corresponding proton in 4-substituted 1,2,3-thiadiazoles [11]. In the mass spectrum of thiadiazole III an intense peak of molecular ion and the peaks of fragments arising from its decomposition with the elimination of a nitrogen molecule are observed. The isotope composition of such ions corresponds to the calculated one (Scheme 1).

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Reactions of alkyl (halomethyl)furancarboxylates with hexamethylenetetramine

Cited by 8 publications

References 6 publications

Assessing the Limits of Sustainability for the Delépine Reaction

Assessing the Limits of Sustainability for the Delépine Reaction

Hexamethylenetetramine as an Efficient Catalyst for One-Pot, Three Component Synthesis of 2-Amino-4H-Pyran Derivatives

Synthesis of alkyl 2-aminomethyl-5-(1,2,3-thiadiazol-4-yl)furan-3-carboxylate and pseudopeptides on its basis

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