90408-21-2

Upstream product

• 4238-71-5 1-benzylimidazole 
• 74-88-4 methyl iodide 
• 693-98-1 2-methylimidazole 
• 585-71-7 (1-bromoethyl)benzne 
• 672-65-1 (1-chloroethyl)benzene 

Relevant academic research and scientific papers

Atom Transfer Radical Polymerization-Inspired Room Temperature (sp3)C-N Coupling

A simple nonphotochemical procedure is reported for Cu(I)-catalyzed C-N coupling of aliphatic halides with amines and amides. The process is loosely based on the Goldberg reaction but takes place readily at room temperature. It uses Cu(I)Br, a commonly used and inexpensive atom transfer radical polymerization precatalyst, along with the cheap ligand N,N,N′,N″,N″-pentamethyldiethylenetriamine, to activate the R-X bond of the substrate via inner-sphere electron transfer. The procedure brings about productive C-N bond formation between a range of alkyl halide substrates with heterocyclic aromatic amines and amides. The mechanism of the coupling step, which was elucidated through application of computational methods, proceeds via a unique Cu(I) → Cu(II) → Cu(III) → Cu(I) catalytic cycle, involving (a) inner-sphere electron transfer from Cu(I) to the alkyl halide to generate the alkyl radical; (b) successive coordination of the N-nucleophile and the radical to Cu(II); and finally reductive elimination. In the absence of a nucleophile, debrominative homocoupling of the alkyl halide occurs. Control experiments rule out SN-type mechanisms for C-N bond formation.

N-Substituted acetamidines and 2-methylimidazole derivatives as selective inhibitors of neuronal nitric oxide synthase

A series of N-substituted acetamidines and 2-methylimidazole derivatives structurally related to W1400 were synthesized and evaluated as Nitric Oxide Synthase (NOS) inhibitors. Analogs with sterically hindering isopropyl and phenyl substituents on the benzylic carbon connecting the aromatic core of W1400 to the acetamidine nitrogen, showed good inhibitory potency for nNOS (IC 50= 0.2 and 0.3 μM) and selectivity over eNOS (500 and 1166) and to a lesser extent over iNOS (50 and 100). A molecular modeling study allowed to shed light on the effects of the structural modifications on the selectivity of the designed inhibitors toward the different NOS isoforms.

Lithiation of 1-Benzylimidazole. A Hypothesis on the Regioselectivity of the Electrophilic Attacks on the Lithiated Species

Sequential lithiations of 1-benzylimidazole, 1, and of 1-benzyl-1,2,4-triazole,2, followed by treatment with electrophiles others than alkyl halides result in reactions at C-2.However, benzyl halides and, to a certain extent, iodomethane react at the N-benzyl carbon atom.An explanatory hypothesis based on steric ortho effects is advanced.

2,5-Dilithiation of N-Protected Imidazoles. Syntheses of 2,5-Disubstituted Derivatives of 1-Methoxymethyl-, 1-Triphenylmethyl-, and 1-(N,N-Dimethylsulphonamido)-imidazole

The conditions previously established for the dilithiation of 1-methylimidazole are shown to be applicable to 1-methoxymethyl- and 1-triphenylmethyl-imidazole allowing good-yielding syntheses of 1,2,5-trisubstituted imidazole derivatives.The suitability of the 1-substituted (and of other groups) for the N-protection of imidazoles in dilithiation experiments is discussed and the use of the N,N-dimethylsulphamoyl protecting group is proposed. 1-Sulphamoylimidazole undergoes mono- and 2,5-di-lithiation quantitatively at low temperatures and in short reaction times.The results of work-up of the 2,5-dilithio intermediate with 1 mol equiv. of iodomethane or dimethyl sulphate indicate selectivity in favour of reaction at the 5-position.