A convenient access to 1-substituted-2-azinyl-1-ethanones via acylation of alkylated azines with N-acylbenzotriazoles

Abstract

Reactions of alkylazines 9a−f (2-methylpyridine, 2-benzylpyridine, 4-benzylpyridine, 2-methylquinoline, 4-methylquinoline or 4-methylpyrimidine) with readily available N-acylbenzotriazoles 8a−j produced 1-substituted-2-azinyl-1-ethanones 10a−p in 50−95% yields.

Transition Metal‐Free Aroylation of Diarylmethanes with N‐Bn‐N‐Boc Arylamides and N‐Acylpyrroles

“…[16] A significant improvement over use of traditional Weinreb amide chemistry would be use of air and moisture stable pronucleophiles that could be readily converted to nucleophiles under experimentally convenient conditions. Less well-known approaches to conversion of amides to ketones, such as Wolfe's use of 2-methyl pyridine based nucleophiles with N,N-dimethyl amides [17] or Katritzky's use of Nacylbenzotriazoles [18] have some advantages, because they use pro-nucleophiles. These approaches, however, are typically performed with the strong base LDA at temperatures that are costly and challenging to access on scale (below -70 o C).…”

(α-Aminoacyl)amino-Substituted Heterocycles and Related Compounds

“…9 (R-Aminoacyl)amino-substituted heterocycles are useful synthetic intermediates (Figure 1) for endomorphin-2 (EM-2) analogues (1), 10 bacterial RND efflux pump inhibitors (EPIs) such as MC-04,124 (2) 11 and MC-02,595 (3), 12 γ-secretase inhibitor LY411575 (4), 13 and inhibitors of tumor necrosis factor-R converting enzyme (TACE) GW 3333 (5). 14 N-Acylbenzotriazoles 15 have been employed for (i) Nacylation 16 in the preparation of primary, secondary, tertiary, 17 and Weinreb amides; 18 (ii) C-acylation for the preparation of β-ketosulfones 19 primary and secondary R-cyanonitriles, 20 R-nitroketones, 21 ketones, 22 and R-ketoazines; 23 and (iii) O-acylation of aldehydes 24 and of steroids 25 to give esters.…”

Alkyl, Unsaturated, (Hetero)aryl, and N-Protected α-Amino Ketones by Acylation of Organometallic Reagents

“…Great advances have been made in the application of N -acylbenzotriazoles in organic synthesis as activated derivatives of carboxylic acids . Efficient N- acylbenzotriazole reagents have been easily prepared from carboxylic acids by (i) thionyl chloride and 1 H -benzotriazole (BtH) or (ii) BtSO 2 Me in the presence of Et 3 N for the N-acylation of amines and amides, , the O-acylation of aldehydes, and the C-acylation of ketones and heteroaromatics, alkylsulfones, alkylcyanides, alkylazines, and α-nitro alkanes . Acylations with stable, crystalline N -acylbenzotriazoles have attracted interest since they offer an effective replacement for the corresponding acid chlorides, which are usually unstable and sometimes difficult to prepare; thus N -acylbenzotriazoles provide a simple and efficient method to prepare peptides …”