Microwave Assisted Synthesis of 2,2′-Arylene-substituted Bis(4H-3,1-Benzoxazin-4-one) Derivatives Using the Complex Cyanuric Chloride/N,N-Dimethylformamide

A new and efficient method has been designed to prepare 2,2′-arylene-substituted bis(4H-3,1-benzoxazin-4-one) derivatives by using the mixture of cyanuric chloride and N,N-dimethylformamide in a microwave-assisted reaction. The method used and presented here has good rate enhancement and excellent yields.

The reported methods for producing 2,2'-arylene-bis(4H-3,1-benzoxazin-4-one) compounds A are based on the preparation of molecules B (Figure 2) as an intermediate from anthranilic acid derivatives and a dichloride of a dicarboxylic acid [1][2][3][4]. Because of the individual structure of molecules B, they can react with organic or inorganic Lewis acids in addition-substitution reactions. The result is the conversion of COOH group to an active ester. In other words, the OH group becomes a better leaving group.
The reaction product of cyanuric chloride (CC) and N,N-dimethylformamide (DMF) acts as an organic Lewis acid in a number of common reactions. For example, it is used for conversion of a wide series of secondary and primary alcohols to the matching alkyl chlorides and iodides [12,13]. Further more, CC/DMF is used for the conversion of β-amino alcohols into the corresponding chlorides [13]. In addition, a variety of ketoximes prepared from the related ketones, undergo the Beckmann rearrangement upon reaction with a mixture of CC/DMF [14].

Results and Discussion
The intermediates B 1-5 can be prepared from anthranilic acid derivatives and dihalides of an aromatic dicarboxylic acid, in refluxing neutral organic solvent in the presence of triethylamine, which produces more than 85% yield (Scheme 2).
In the second step, by using the mixture of cyanuric chloride and N,N-dimethylformamide in a microwave-assisted cyclodehydration reaction, 2,2'-arylene-bis(4H-3,1-benzoxazin-4-one) derivatives A 1-5 were prepared in more than 70% yield (Table 1).  In view of the structural characteristics of intermediates formula B, the iminium cation 1 from CC/DMF can act as a cyclizing agent by conversion of the carboxylic group into an active ester. The proposed mechanism is drawn in Scheme 3. DMF catalyzes the reaction and acts as a solvent too.  In this case the temperature was increased unexpectedly because of the ionic nature of the mixture. In this method, the reaction time is shorter than in previous methods and the reaction is very clean. In addition, the product can be isolated with high purity by a very simple workup.

General
The structures of products A 1-5 and B 1-5 were confirmed by analysis using spectra data (FT-IR, 1 H-NMR, 13 C-NMR, U V and MS). All machines, equipments and instruments were used at analytical laboratories of faculty of science and technology (PPSKTM, FST), University Kebangsaan Malaysia (UKM). The FT-IR spectra were measured on a Perkin Elmer Model GX spectrometer, using KBr pellets. T h e NMR spectra were recorded on a Bruker/AVANCE III 600 MHz spectrometer and chemical shifts are reported relative to TMS. The mass spectra (MS-MS) were recorded using a Dionex/Bruker micro TOF-Q instrument. The elemental analysis (CHN) was recorded by Thermo Finngan instrument. The melting points were measured in open capillary tubes. The UV absorption was measured by a Shimadzu UV-2400PC series instrument. All commercial reagents were used as received without additional purification. The procedures for preparation and purification of reported products are the same.

Conclusions
We have found that a mixture of CC/DMF is an effective reagent in the microwave-assisted synthesis of 2,2'-(arylene)bis(4H-3,1-benzoxazin-4-one) derivatives. Furthermore, in this method, the role of solvent is interesting because the solvent also catalyzed the reaction. The method should be applicable for the synthesis of other 2,2'-arylene-substituted bis(4H-3,1-benzoxazin-4-one) derivatives. The short reaction times, the availability and simplicity of the starting materials, simple workup and the experimental procedure make this new path more efficient than previous methods.