Synthesis of 1,2-dihydro-1,3,5-triazine derivatives via Cu(ii)-catalyzed C(sp³)–H activation of N,N-dimethylethanolamine with amidines

Abstract

1,2-Dihydro-1,3,5-triazines and symmetrical 1,3,5-triazines were obtained in up to 81% yields from amidines and N,N-dimethylethanolamine catalyzed by CuCl2. The reaction involves three C-N bond formations during the oxidative annulation process...

Construction of a Pyrimidine Framework through [3 + 2 + 1] Annulation of Amidines, Ketones, and N,N-Dimethylaminoethanol as One Carbon Donor

“…Based on both the previous literature reports ,, and our aforesaid experimental results, a possible reaction mechanism is proposed as shown in Scheme . Initially, DMEA coordinates with Cu 2+ and performs Fenton-like reactions to generate a reactive iminium E. Intermediate E couples with substrate 1 to give intermediate F, followed by a removal of the N -methylethanolamine–copper complex to afford iminium B.…”

“…For example, methylene-bridged biindoles and 3-formylindoles were selectively synthesized using DMEA as a carbon synthon catalyzed by Cu(II) and Co(II), respectively. 22 More interestingly, 1,3,5triazine derivatives were obtained from amidines and DMEA catalyzed by Cu(II), 23 which differs from Zhang's report 24 that quinazolines were synthesized from amidines using DMSO as the carbon donor. Intrigued by these findings and to continue our interest in using DMEA as a one carbon synthon, we attempted to employ DMEA as the carbon donor to perform a cyclization of amidines and aromatic/aliphatic ketones for the…”

Co(II)‐Catalyzed Oxidation of N,N‐Dimethylaminoethanol: An Efficient Synthesis of Unsymmetrical (2,4‐) and Symmetrical (2,6‐) Diarylpyridines through Annulation of Aromatic Ketones with a Nitrogen Source

“…Despite these efforts, new synthetic methodologies using different tertiary amines attracted our attention. We have successfully explored N,N ‐dimethylethanolamine (DMEA) as the carbon synthon to perform C‐3 methylenation or formylation of indoles [12a] and annulation of amidines for the synthesis of 1,2‐dihydro‐1,3,5‐triazines [12b] (Scheme 1). Intrigued by these findings, we attempted to use DMEA as one carbon donor to perform an annulation of ketones with ammonium acetate for the synthesis of pyridines.…”

Open-Air Dual-Diamination of Aromatic Aldehydes: Direct Synthesis of Azolo-Fused 1,3,5-Triazines Facilitated by Ammonium Iodide

“…Furthermore, Fan and co-workers found a [5 + 2] annulation of N -aryl amidines with propargylic esters to produce 1,3-benzodiazepines . In addition, the Ma team presented an oxidative annulation of N -arylamidines with N , N -dimethylethanolamine as a C1 synthon to construct a 1,2-dihydro-1,3,5-triazine skeleton . Inspired by the high reactivity exhibited by N -aryl amidines, we hypothesize that simple aldehydes are capable of efficiently accomplishing the first diamination with 3-aminoazoles and a nitrogen source to generate in situ N -azolo amidines and accelerating the implementation of the second diamination.…”

“…10 In addition, the Ma team presented an oxidative annulation of N-arylamidines with N,N-dimethylethanolamine as a C1 synthon to construct a 1,2-dihydro-1,3,5triazine skeleton. 11 Inspired by the high reactivity exhibited by N-aryl amidines, we hypothesize that simple aldehydes are capable of efficiently accomplishing the first diamination with 3-aminoazoles and a nitrogen source to generate in situ Nazolo amidines and accelerating the implementation of the second diamination. It should be noted that this process would require adjusting the reactivity of N-azolo amidines to suppress undesired intramolecular N−N bond coupling.…”