Sulfur-Mediated Decarboxylative Coupling of 2-Nitrobenzyl Alcohols and Arylacetic Acids

Abstract

We report a new method for the synthesis of substituted quinazolines by the condensation of 2-nitrobenzyl alcohols with arylacetic acids. The transformation requires the use of urea as a nitrogen source, elemental sulfur as a promoter, DABCO as a base, and DMSO as a solvent. Functionalities such as chloro, fluoro, trifluoromethyl, thienyl, and indolyl groups were all compatible with the reaction conditions. Because our method uses stable simple substrates to obtain the N,N-heterocycles in the absence of transition metals, it offers a potential pathway for preparing complex structures under mild conditions.

Iron sulfide clusters for annulation of 2-nitrobenzonitriles and benzylamines toward synthesis of 2-aryl-4-quinazolinones

“…Meanwhile, thiourea was inferior to urea, as only 22% yield of 3aa was obtained. The result herein was consistent with that reported with regard to the choice of urea as a NH3 surrogate [13]. Notably, 12% yield of 3aa was obtained if urea was omitted.…”

“…During the investigation, we have noticed that a certain amount of urea was crucial for obtaining the 2-phenyl-4(3H)-quinazolinone 3aa in high yields. Such an effect of urea regarding the transformation of orthosubstituted nitroarenes, presumably as a NH3 surrogate, has been reported [13]. To examine the unique role of urea for this condensation, some ammonium salts as well as an analogous thiourea were attempted.…”

“…In comparison with the previous study [14], the possible mechanism was proposed as that shown in Figure 6. It should be noted that the formation of intermediates such as 4 or 5 could be observed by GC-MS. Urea w a s envisaged to play a pivotal role in the transformation of cyano group to amide group [13]. Meanwhile, DABCO presumably was in charge of the last oxidatio n to afford the desired quinazolinone [15].…”

“…It should be noted that only one example for coupling of 2nitrobenzonitriles and benzyl alcohols to afford quinazolinones in the presence of heterogeneous catalyst Au/TiO2 was known [12]. We hypothesized tha t the use of benzylamines should be appropriate to an Fe/S-promoted six-electron transfer involving nitroarenes [13], thus affording an imine intermediate. Cyclization of the ensuing species with a proximal nitrogen nucleophile (etc.…”

“…Further crystallization with acetone/ethanol mixture would afford 2-phenyl-4(3H)-quinazolinone 3aa as a light yellow solid. The 1 H NMR and 13 C NMR spectra were recorded on a Bruker AV 500 spectrometer using residual solvent peak as a reference.…”