Further Insights into the Chemistry of Acyllithium Compounds R2NC(O)Li:  Characterization of an Amide (R2NLi) Adduct (R2NCHNR2(OLi)) to a Formamide (R2NC(O)H)

J of Physical Organic Chem

2006

Nitric oxide (NO) is known to produce the carcinogenetic nitrosamines but it has also been recently reported, both as a regulator of many important physiological functions and as a possible pharmaceutical delivery system. The present paper describes the NO insertion into N-Li bond of lithium amides, to afford very good to almost quantitative yields of N-nitrosamines. A study of the reaction intermediate suggested a further advantage of this synthetic methodology, widening its scope to its use in tandem reactions. Thus, in situ addition of an organolithium reagent into the N --O bond leads to an almost quantitative conversion into the corresponding hydrazone. This compound could further add a second equivalent of the same (or another) organolithium affording substituted hydrazines. The hydrazines thus prepared have a potential chiral carbon, by running the reaction in the presence of a chiral auxiliary, enantiomeric excess could be obtained. By reducing the compound with Raney Ni, the scope of this methology could be enlarged for the potential preparation of chiral primary amines, project that is currently under progress. RESULTS AND DISCUSSION Reaction of lithium amides with NOThis reaction constitutes a very convenient methodology for the synthesis of alkyl N-nitrosamines, 3, from JOURNAL OF PHYSICAL ORGANIC CHEMISTRY

Section: Preparation Of Lithium Dialkylamidesmentioning

confidence: 99%

Complex intermediates in the NO insertion reactions into lithium amides

Vázquez

J of Physical Organic Chem

2006

“…In all cases, they were distilled from sodium benzophenone ketyl immediately before use. Butyl-and phenyllithium were prepared by a methodology developed in our laboratory [16], and titrated by the double titration method [17].…”

Section: Reagents and Solventsmentioning

confidence: 99%

Solvent and Ligand Effects on the Tandem Addition-Lithiation-Electrophilic Substitution of Phenyllithium on α,β-Unsaturated Carbonyl Compounds

Vázquez

2005

IJMS

Abstract:The reaction of phenyllithium with E-cinnamaldehyde is extremely sensitive to the reaction conditions and surprising changes in the product distribution were observed upon changes in the solvent, concentrations, duration or temperature of the reaction. For these reasons the above mentioned reaction was considered an appropriate model to examine solvent and aggregation effects of PhLi. On the other hand, when two or trhee equiv of phenyllithium are used, instead of one, the reaction transforms into a surprising tandem addition-lithiation-β-alkylation sequence, that can be successfully applied to the synthesis of substituted dihydrochalcones. The observed effects upon changes in the reaction conditions, as well as the effects of additives that modify the PhLi dimer-monomer equilibrium are consistent with a reaction pathway in which dimeric phenyl lithium attacks to the E-cinnamaldehyde without previous deaggregation. Usually, monomers are found to be more reactive than dimers, but, in this reaction the opposite effect is observed, and the tandem reaction spectacularly decreases with the (PhLi) 2 concentration.

“…NMR spectroscopy is a very useful tool for detecting non‐bonding interactions, since it is extremely sensitive to molecular structure, conformational, solvent, and other environmental effects 1. We have recently reported 1 H and 13 C‐NMR studies on matters as diverse as identification of drug photo‐degradation,2–4 detection of intermediates,5–9 and characterization of the natural attenuation of oil spills in Patagonian soils 10, 11. The role of inter‐ and intramolecular hydrogen bonding in determining the arrangement, physical properties, and reactivity of a great diversity of structures is a subject of experimental and theoretical research in chemical12–15 and biological systems 16.…”

Section: Introductionmentioning

confidence: 99%

Inter‐ and intramolecular hydrogen bonds in polyamines: variable‐concentration¹H‐NMR studies

J of Physical Organic Chem

Alvaro

2011

Self Cite

Inter-and intramolecular hydrogen bonding play an important role in determining the arrangement, physical properties, and reactivity of a great diversity of structures in chemical and biological systems. Several aromatic nucleophilic substitutions (ANS) in nonpolar aprotic, (non-HBD), solvents recently studied in our laboratory have demonstrated the importance of self-association of amines by hydrogen-bond interactions. In this paper, we describe 1 H-NMR studies carried out at room temperature on bi-and polyfunctionalized amines, namely: N-(3-amino-1-propyl)morpholine (3-APMo), histamine, 2-guanidinobenzimidazole (2-GB), 1,2-diaminoethane (EDA), 3-dimethylamino-l-propylamine (DMPA), and 1-(2-aminoethyl)piperidine (2-AEPip). By 1 H-NMR measurements of amine solutions at variable concentrations we have shown that 3-APMo, histamine and 2-GB are able to form a six-membered ring by intramolecular hydrogen bonding, while EDA, DMPA, and 2-AEPip form dimers by intermolecular hydrogen bonds. Likewise, variable concentration 1 H-NMR studies allowed estimation of the corresponding equilibrium constants for the dimerization. These results are correlated with experimental kinetic results of ANS, confirming hereto the relevance of the ''dimer mechanism'' in reactions involving these amines.