Organocatalysis in heterocyclic synthesis: DABCO as a mild and efficient catalytic system for the synthesis of a novel class of quinazoline, thiazolo [3,2-a]quinazoline and thiazolo[2,3-b] quinazoline derivatives

Abstract

BackgroundThere are only limited publications devoted to the synthesis of especially thiazolo[3,2-a]quinazoline which involved reaction of 2-mercaptopropargyl quinazolin-4-one with various aryl iodides catalyzed by Pd-Cu or by condensation of 2-mercapto-4-oxoquinazoline with chloroacetic acid, inspite of this procedure was also reported in the literature to afford the thiazolo [2,3-b] quinazoline. So the multistep synthesis of the thiazolo[3,2-a]- quinazoline suffered from some flaws and in this study we have synthesized a novel class of thiazoloquinazolines by a simple and convenient method involving catalysis by 1,4-diazabicyclo[2.2.2]octane (DABCO).ResultsA new and convenient one-pot synthesis of a novel class of 2-arylidene-2H-thiazolo[3,2-a]quinazoline-1,5-diones 9a-i was established through the reaction between methyl-2-(2-thio-cyanatoacetamido)benzoate (4) and a variety of arylidene malononitriles 8a-i in the presence of DABCO as a mild and efficient catalytic system via a Michael type addition reaction and a mechanism for formation of the products observed is proposed. Moreover 4 was converted to ethyl-2-[(4-oxo-3,4-dihydroquinazolin-2-yl)thio]acetate (10) upon reflux in ethanol containing DABCO as catalyst. The latter was reacted with aromatic aldehydes and dimethylformamide dimethylacetal (DMF-DMA) to afford a mixture of two regioselectively products with identical percentage yield, these two products were identified as thiazolo[3,2-a]quinazoline 9,13 and thiazolo[2,3-b]quinazoline 11,12 derivatives respectively. The structure of the compounds prepared in this study was elucidated by different spectroscopic tools of analyses also the X-ray single crystal technique was employed in this study for structure elucidation, Z/E potential isomerism configuration determination and to determine the regioselectivity of the reactions.ConclusionA simple and efficient one-pot synthesis of a novel class of 2-arylidene-2H-thiazolo[3,2-a]quinazoline-1,5-diones 9a-i was established through DABCO catalyzed Michael type addition reaction. In addition many fused quinazoline and quinazoline derivatives were synthesized which appeared as valuable precursors in synthetic and medicinal chemistry.

Synthesis of A New Class of Pyridazin-3-one and 2-Amino-5-arylazopyridine Derivatives and Their Utility in the Synthesis of Fused Azines

“…In earlier investigations we developed methods for the efficient synthesis of a variety of polyfunctional azoles, azines and their fused derivatives [32,33,34,35,36]. Recent efforts in our laboratories have led to the design of new and general strategies for the preparation of 2-amino-5-arylazo-nicotinates and pyridazinones [37] that involve reactions of 3-oxo-2-arylhydrazonopropanals 1 with active methylene compounds, including ethyl cyanoacetate, and malononitrile, depending on the effect of the substituent present in the arylazo moiety.…”

Synthesis, Antibacterial, and Antioxidant Evaluation of Novel Series of Condensed Thiazoloquinazoline with Pyrido, Pyrano, and Benzol Moieties as Five- and Six-Membered Heterocycle Derivatives

“…Thus, thiazole and quinolone are privileged structures in the designing of a fused thiazoloquinazoline system, which is predictable to biodynamic properties with characteristic features. However, literature revealed a growing demand for the development of new syntheticprocesses includingpotential synthesisofactive substituted thiazole quinazoline systems like thiazolo[3,2-a]quinazoline, thiazolo[2,3-b]quinazoline, thiazolo[4,3-b]quinazoline, thiazolo[5,4-c]quinoline thiazolo[5,4-f]quinazoline, and thiazolo[4,5-h]quinazolin [ 31 ]. Moreover, after the extensive literature survey of the aforesaid, it was observed that there has been an increasing focus in the chemistry ofthiazolo[2,3-b]quinazoline because of the capability to exhibit an enormous variety of biological and pharmacological activities [ 32 , 33 ].…”

Synthesis of new sulfonamide derivatives of thiazolo[3,2-a]quinazolin-5-one

“…Among known catalytic [7][8][9][10] and noncatalytic [11][12][13] synthetic approaches to the targeted heterocyclic system, the most interesting was that based on the condensation of substituted 2-halobenzoyl chlorides with 2-aminothiazole [14] (Scheme 1). This approach implies the use of a substrate containing an activated halogen substituent in the 2-position.…”