Regioselectivity of Electrophilic Attack on 4-Methyl-1-Thioxo-1,2,4,5-Tetrahydro[1,2,4]Triazolo[4,3-A]Quinazolin-5-One Part 2: Reactions on Nitrogen Atom

Abstract

Abstract:The regioselectivity on a cyclic thioamide group towards different electrophiles was studied on the model compound 4-methyl-1-thioxo-1,2,4,5-tetrahydro[1,2,4]triazolo [4,3-a]quinazolin-5-one 1. The examined compound 1 reacts with alkyl halides, amines in the presence of formaldehyde, acyl halides and compounds having activated double bonds to afford the N-substituted derivatives 2, 3 and 6. The regioselective reactions on nitrogen atom are due to strong Coulombic attraction. The reaction of 1 with amines in the presence of hydrogen peroxide afforded the aminolysis product 4. Compounds 1-6 were identified by FTIR, 1H NMR, 13C NMR, and mass spectroscopy.

Convenient synthesis of 1-substituted-4-methyl-5-oxo [1,2,4]triazolo[4,3-a]quinazolines

“…14,15 As described in scheme 1, the reaction of triazoloquinazoline 1 with methyl chloroacetate, chloroacetic acid and chloropropanoic acid in the presence of a base afforded the S-alkylation products 2, 5 and 6, respectively. The ester 2 and both acids 5 and 6 are excellent precursors for the simple chemical modification of triazoloquinaoline derivative 1.…”

Synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate

“…20 However a strong query still remains that is the development of simple, mild and efficient methods for preparation of quinazoline derivatives linked to amino acid residues by a spacer and the evaluation of their biological activities. In view of these facts and in continuation of our efforts in studing the chemoselective reactions of heterocyclic amides [21][22][23] and thioamides, 20,[24][25][26][27][28][29][30][31][32][33][34][35][36][37] we found interesting to synthesize a series of quinazoline derivatives linked to amino acids by a spacer. Here in we wish to report a novel synthesis of 3-arylquinazoline-2,4-dione and use this precursor in the synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate.…”

N1‐allyl‐3‐substituted‐6,7‐dimethyl‐1,2‐dihydro‐2‐quinoxalinone as key intermediate for new acyclonucleosides and their regioisomer O‐analogues

“…As part of our continuing interest toward the regioselective reactions of ambident nucleophiles, i.e., thioamides [20][21][22], we have studied the reaction of quinoxalines 1a-c [23][24][25] with electrophiles. Thus, the reaction of the ambident nucleophile 1a-c with allyl bromide in the presence of NaH in N,Ndimethylformamide always afforded a mixture of O-and N-allyl substituted quinoxalines 2a-c and 3a-c, respectively (Scheme 1).…”