One-pot synthesis of 3-(2-cyanophenyl)quinazolin-4(3H)-one

Abstract

Anthranilonitrile reacting with .[brmic acid at room temperature Jbr three days gave 64% of 3-(2-cvanophenyl)quinazolin-4(3H)-one. Under similar conditions anthranilic acid, 4-nitroaniline, and 2,5-dichloroaniline were Nz/brmylated in good yields.Keywords: anthranilonitrile, 3-(2-cyanophenyl)quinazolin-4(3H)-one, N-lbrmylation.The title quinazolinone was obtained for the first time quite recently [1] by a two-step reaction involving heating of anthranilonitrile (!) with an excess of tbrmic acid in boiling toluene (N-formylation) followed by treatment of the crude product with thionyl chloride and additional amount of 1. The yield of 3-(2-cyanophenyl)quinazolin-4(3H)-one (2) was very low (9%).Recently we have found out that, in contrast to the rather drastic conditions commonly used for N-formylation of anilines [2-4], anthranilic acid, 4-nitroaniline, and 2,5-dichloroaniline react with formic acid at room temperature. The appropriate N-formyl derivatives precipitate from the solutions in good yields as crystalline solids (Scheme 1). This result is rather unexpected, considering the low P/(j values of the anilines. Babayev's conditions is obtained in moderate yield (40%), Moreover, it is contaminated by several impurities. Thus, we assumed that an improvement in N-formylation of 1, using our conditions for formylation of anilines, would lead to a substantial increase in the total yield of 2. Unexpectedly, 1 dissolved in an excess of anhydrous formic acid and, when left for three days at 20-22~ afforded the title quinazolinone 2 in 64% yield (Scheme 2).

Nano-MgO: An Efficient Catalyst for the Synthesis of Formamides from Amines and Formic Acid Under MWI

“…A number of formylating reagents as well as methods are available in the literature [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Acetic formic anhydride is a well known formylating reagent [10], but is sensitive to moisture.…”

“…Acetic formic anhydride is a well known formylating reagent [10], but is sensitive to moisture. Formylation using chloral [11], activated formic acid in the presence of DCC [2], or EDCI [12], activated formic esters [13][14][15], ammonium formate in acetonitrile [16,17], 2,2,2-trifluoroethyl formate [18], formic acid [19], ZnO [20] and polyethylene glycol [21,22] have been used for this purpose. More recently, Akbari et al [23] have reported catalyst-free N-formylation of amines using guanidine derived ionic liquids.…”

Synthesis of 4(3H)quinazolinimines with selective cytotoxic effect on human acute promyelocytic leukemia cells

“…[3][4][5] Among these types of molecules, quinazolinimines have been studied due to their extensive therapeutic potential, for example as selective butyrylcholinesterase inhibitors for Alzheimer's disease and for antiproliferative activities in cancer. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] In general, some reported protocols for synthesizing heterocyclic compounds require long reaction times, 17 high temperature, 19 special setup and workup conditions, 7,8 and subsequently low yields. 7 In this context, our research group has recently reported an accessible way to obtain a set of substituted 2-(phenyl or methyl)-3-aryl-4(3H)-quinazoliniminium chlorides containing diverse substituents around the heterocycle through two alternative pathways.…”

Polycyclic N-Heterocyclic Compounds. Part 60: Reactions of 3-(2-Cyanophenyl)quinazolin-4(3H)-ones with Primary Amines

“…4) We, therefore, wondered if a Dimroth-type rearrangement with primary alkylamines could be applied to substrate 3 to afford 3-alkyl-4-alkyliminoquinazolines. Another possibility was that an addition of the nucleophile, ring opening, and ring closure (ANRORC) reaction could occur to give 3-alkylquinazolin-4(3H)-ones (4).…”

“…mp 192-193°C (lit. 4) 196-197°C General Procedure for the Reaction of 3 with Primary Amines To a solution of 3 (300 mg, 1.21 mmol) was added primary amine (12.1 mmol) and the solution was stirred for the appropriate time. Water (50 ml) was added and extracted with ethyl acetate (50 mlϫ3).…”