Reductive methylation of primary and secondary amines and amino acids by aqueous formaldehyde and zinc

Silva, Renato A. da; Estevam, Idália Helena Santos; Bieber, Lothar W.

doi:10.1016/j.tetlet.2007.08.092

Cited by 61 publications

(45 citation statements)

References 8 publications

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“…The reversed order gave a poor yield probably due to the steric hindrance of the isopropyl group rendering the necessarily transient ortho iminium cation unreactive to the in situ generated reducing agent (Zn + AcOH, da Silva et al, 2007). This relatively recent approach to the reductive methylation of primary and secondary amines was used since the classical ones gave unsatisfactory results (formaldehyde (aq) and NaBH 4 -the main isolated product were the iminemethyl N-methylenanthranilate and aminal -N-(hydroxymethyl)-derivative, while the direct methylation with MeI gave an irresolvable mixture of the mono-and dialkylated products along with a significant amount of the unreacted methyl anthranilate).…”

Section: Resultsmentioning

confidence: 99%

“…Reductive methylation was accomplished following a literature method (da Silva et al, 2007) employing it for the first time on an ortho substituted aniline. A mixture of 1.51 g of methyl anthranilate (10 mmol), 2.40 g of glacial acetic acid (40 mmol), 0.92 g of 35% aqueous formaldehyde (11 mmol), 1.31 g of zinc dust (20 mmol) and 20 ml of dioxane was stirred and heated at 50-60°C for the duration of 4 h. After completion of the reaction (monitored by TLC) aqueous ammonia was added and the reaction mixture was extracted with chloroform, followed by a usual work-up (drying with MgSO 4 and solvent evaporation) and gave 1.66 g of the crude product (consisting of ca.…”

Section: Reductive Methylation Of Methyl Anthranilatementioning

confidence: 99%

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Identification of a new antinociceptive alkaloid isopropyl N-methylanthranilate from the essential oil of Choisya ternata Kunth

Radulović

Miltojević

McDermott

et al. 2011

Journal of Ethnopharmacology

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Ethnopharmacological relevance: Mexican people employed infusion of leaves of Choisya ternata Kunth for their antispasmodic and "simulative properties". Aim of the study:In the present study the detailed GC and GC-MS analyses of the essential oil of Choisya ternata Kunth (Rutaceae) were performed. The presence of a minor constituent isopropyl N-methylanthranilate (1) was revealed among other identified volatiles. A synthesis of 1 was undertaken in order to corroborate this find and obtain gram quantities that would allow the testing of its biological activity (peripheral and central antinociceptive activity). Material and methods:The oils were investigated by GC and GC-MS. Synthesized compounds were spectrally characterized (UV-Vis, IR, 1D and 2D NMR, MS). The obtained synthetic samples of compounds were assayed for peripheral and central antinociceptive activity in two models (effects on acetic acid induced writhing in mice and the hot plate test for nociception). showed the lowest activity (with the methyl ester at 3 mg/kg still better than acetylsalicylic acid, at 200 mg/kg, in the first, or comparable with morphine, at 5 mg/kg, in the second test). Conclusion:This study once again revealed that detailed investigations of plant species with ethnopharmacologically documented activity may yield new natural compounds -a new alkaloid (ternanthranin), a volatile simple anthranilate that can be considered responsible for the antinociceptive activity of the crude plant extracts.

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Section: Resultsmentioning

confidence: 99%

Section: Reductive Methylation Of Methyl Anthranilatementioning

confidence: 99%

Identification of a new antinociceptive alkaloid isopropyl N-methylanthranilate from the essential oil of Choisya ternata Kunth

Radulović

Miltojević

McDermott

et al. 2011

Journal of Ethnopharmacology

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“…9−11 were synthesized starting from N-methylmemantine (19), which, in turn, was prepared through reductive methylation of the primary amine of 2 with aqueous formaldehyde and zinc dust by means of slight modification of a literature procedure. 24 The synthesis of 9−11 was accomplished by alkylation of 19 to furnish 21−23, and the following activation of the alcohol group was achieved without isolation of the intermediates, which were directly reacted with 20 (Scheme 1). Amides 16−18 were easily prepared by a two-step procedure starting from 2 hydrochloride and the corresponding acylating agents.…”

Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

Combining Galantamine and Memantine in Multitargeted, New Chemical Entities Potentially Useful in Alzheimer’s Disease

et al. 2012

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Herein we report on a novel series of multitargeted compounds obtained by linking together galantamine and memantine. The compounds were designed by taking advantage of the crystal structures of acetylcholinesterase (AChE) in complex with galantamine derivatives. Sixteen novel derivatives were synthesized, using spacers of different lengths and chemical composition. The molecules were then tested as inhibitors of AChE and as binders of the N-methyl-D-aspartate (NMDA) receptor (NMDAR). Some of the new compounds were nanomolar inhibitors of AChE and showed micromolar affinities for NMDAR. All compounds were also tested for selectivity toward NMDAR containing the 2B subunit (NR2B). Some of the new derivatives showed a micromolar affinity for NR2B. Finally, selected compounds were tested using a cellbased assay to measure their neuroprotective activity. Three of them showed a remarkable neuroprotective profile, inhibiting the NMDAinduced neurotoxicity at subnanomolar concentrations (e.g., 5, named memagal, IC 50 = 0.28 nM).

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“…Hua et al demonstrated that ReCl(CO) 5 catalyzes the condensation of aromatic compounds with aqueous formaldehyde to afford diarylmethane derivatives. This dehydrate-type reaction was conducted in solvent-free conditions to give products in good yields.…”

Section: (F) Synthesis Of Diarylmethanesmentioning

confidence: 99%

Aqueous Formaldehyde

Silva¹

2011

Synlett

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This feature focuses on a reagent chosen by a postgraduate, highlighting the uses and preparation of the reagent in current research Aqueous FormaldehydeCompiled by Renato Augusto da Silva Renato Augusto da Silva was born in Recife, Pernambuco, Brazil, in 1980. He graduated in chemistry ( 2005) and received his M.Sc. degree in chemistry ( 2007) from the Universidade Federal de Pernambuco (UFPE). Currently, he is working towards his Ph.D. degree in chemistry under the supervision of Dr. Lothar W. Bieber on the synthesis of N-alkylated amines using new methodologies in aqueous medium.

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Reductive methylation of primary and secondary amines and amino acids by aqueous formaldehyde and zinc

Cited by 61 publications

References 8 publications

Identification of a new antinociceptive alkaloid isopropyl N-methylanthranilate from the essential oil of Choisya ternata Kunth

Identification of a new antinociceptive alkaloid isopropyl N-methylanthranilate from the essential oil of Choisya ternata Kunth

Combining Galantamine and Memantine in Multitargeted, New Chemical Entities Potentially Useful in Alzheimer’s Disease

Aqueous Formaldehyde

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