Quinazolinone Synthesis through Base-Promoted S_NAr Reaction of ortho-Fluorobenzamides with Amides Followed by Cyclization

Abstract

A transition-metal-free synthesis of quinazolin-4-ones by Cs 2 CO 3 -promoted S N Ar reaction of ortho -fluorobenzamides with amides followed by cyclization in dimethyl sulfoxide has been developed. The present procedure can provide efficient synthetic methods for the formation of both 2-substituted and 2,3-disubstituted quinazolin-4-one rings depending on the use of easily available starting materials and an efficient, one-pot protocol for the synthesis of the marketed drug product of methaqualone.

α-Keto Acids as Triggers and Partners for the Synthesis of Quinazolinones, Quinoxalinones, Benzooxazinones, and Benzothiazoles in Water

“…1,147.2,137.1,134.4,129.8,129.5,127.5,127.5,127.0,126.8,120.1,-one (3ca). 27 Eluent: petroleum ether/ethyl acetate (5:1). White solid (36 mg, 68%); mp 98−101 °C.…”

“…9,161.9,154.2,134.9,129.1,126.4,126.2,124.8,122.8,121.5,114.4,phenyl)benzo[d]thiazole (5ae). 27 Eluent: petroleum ether/ethyl acetate (40:1). White solid (49 mg, 91%); mp 100− 103 °C.…”

Cu(I)/Pd(II)-Catalyzed Intramolecular Hydroamidation and C-H Dehydrogenative Coupling of ortho-Alkynyl-N-arylbenzamides for Access to Isoindolo[2,1-a]Indol-6-Ones

“…In recent years, we have been interested in the applications of ortho -alkynyl aromatic aldehydes/ketones [ 13 ] and functionalized benzamides [ 14 , 15 ] in the synthesis of hetero-/carbo-cyclic compounds. Therefore, in continuation of our interests in development of synthetic methods for the synthesis of nitrogen-heterocyclic compounds via alkyne annulations [ 16 , 17 , 18 ], we herein describe a CuI/Pd(OAc) 2 -catalyzed formation of 11-aryl-6 H -isoindolo-[2,1- a ]-indol-6-ones bearing different functional group(s) from ortho -(1-arylethynyl)- N -arylbenzamides by the stepwise hydroamidation of the alkynyl group [ 19 ], and C-H dehydrogenative coupling reaction [ 20 ] with the use of O 2 as the oxidant ( Scheme 1 , Equation (3)).…”

Base-Promoted Annulation of Amidoximes with Alkynes: Simple Access to 2,4-Disubstituted Imidazoles

“…It is readily apparent to find that, in addition to the requirement of CuCl 2 •2H 2 O and/or ligand (pyridine and 2,2 -bipyridine), in both cases, inorganic bases were used as the additives, indicating that base is the key promoter to realize the formation of imidazoles. Therefore, in continuation of our interest in developing alkyne annulation in the synthesis of nitrogen-heterocyclic compounds [27][28][29][30] and base/DMSO-promoted C-N bond formation [31][32][33][34], we decided to explore the possibility of constructing an imidazole ring with the use of inorganic bases as the promoters, without the use of ligands under transition-metal-free conditions. In this paper, we would like to report a new, simple and efficient procedure to afford a variety of 2,4-disubstituted imidazoles starting with amidoximes and terminal alkynes in the presence of Cs 2 CO 3 in DMSO (Equation (4)) [35].…”