Efficient synthesis of 1,3-benzodioxin-4-one and benzoxazine-2,4-diones

Reactions of stable N -( o -hydroxyarylacyl)benzotriazoles 4a–c / 6a–c with various aldehydes in the presence of base afforded 1,3-benzodioxin-4-ones 1a–d and naphtho-1,3-dioxinones 7a–c . Reaction with isocyanates under similar conditions afforded high yields of benzoxazine-2,4-diones 2a–c and naphthoxazine-1,3-diones 9a–b .

Aliphatic and heteroaryl aldehydes did not give the desired dioxinones under the conditions employed by Mowry 7 (Route i), while the reactions with aromatic aldehydes failed under the base-promoted conditions12 (Route iv) (Scheme 1).One example has however been reported for the synthesis 1,3-benzodioxin-4-ones of aromatic aldehydes in the case of 4-methoxysalicylic acid.Synthesis from 13 o-carboxybenzenediazonium salts (Route ii) has limited synthetic utility since it is accompanied by the formation of phenol, salicylic acid and benzoic acid 8 (Scheme 1).

Results and Discussion
Crystalline N-(o-hydroxyarylacyl)benzotriazoles 4a-c or 6a-c isolated from corresponding salicylic acids, 37 were treated with 4 equivalents of the appropriate aromatic or aliphatic aldehyde in dry THF at room temperature along with 4 equivalents of triethyl amine to give 1a-d and 7a-c respectively in high yields (Scheme 4 and Table 1).Best results were obtained when the base was added to a well stirred mixture of aldehyde and acylbenzotriazoles 4a-c or 6a-c.

Scheme 4
Attempted reaction of N-(o-hydroxybenzoyl)benzotriazole 4a with 4 equivalents of triethylamine and 1.2 equivalents of p-tolyl isocyanate gave a mixture of the desired compound 2a (40%) along with the carbamoyl derivative 8a (40%) (Scheme 4, Table 2).By using 2.2 equivalents of the isocyanate, both benzoxazine-2,4-dione 2a and carbamoylbenzotriazole 8a could be obtained in quantitative yields.The carbamoylbenzotriazoles 8 have been employed in our laboratories in the synthesis of various unsymmetrical ureas. 38We were able to expand the method further to cover various aliphatic and aromatic isocyanates as shown in Table 2.In all cases, the benzoxazines were obtained in high yields.Employing similar reaction conditions as for the synthesis of 2 on N-(o-hydroxyarylacyl)benzotriazoles 6a-b, other benzoxazinones 9a-b were obtained (Scheme 4, Table 2).Sterically demanding isocyanates gave lower yields (Entry 5, Table 2).

Conclusions
A mild and high yielding process for synthesis of 1,3-benzodioxin-4-ones and benzoxazine-2,4diones has been developed using benzotriazole chemistry.The synthesis of both 2-aryl and 2alkyl 1,3-benzodioxin-4-one could be achieved under these conditions.

Experimental Section
General Procedures.Melting points were determined on a hot-stage apparatus and are uncorrected.All NMR spectra were recorded in CDCl 3 (unless specified as DMSO-d 6 ), with TMS as the internal standard for 1 H (300 MHz) or the solvent as the internal standard for 13 C (75 MHz).THF was dried over sodium/benzophenone and used freshly distilled.Column chromatography was conducted on silica gel 200−425 meshes.The compounds 4a-c and 6a-c were synthesized as reported. 37neral procedure for the synthesis of 1,3-benzodioxin-4-ones 1a-d and naphtho-1,3dioxinones 7a-c The appropriate aldehyde (3 eq) was added to N-(o-hydroxyarylacyl) benzotriazoles 4a-c / 6a-c (1mmol) in freshly dried THF (4 mL) under inert atmosphere.The mixture was stirred for 5 min before addition of triethylamine (3 eq).The reaction mixture was stirred at rt for 24 hours before concentrating under vacuum.The residue was refined by flash chromatography on silica gel using 20% ethyl acetate in hexanes to give 1a-d and 7a-c.