A simple and expedient method for the stepwise synthesis of 2-ethoxy-(4H)-3,1-benzoxazine-4-ones (original) (raw)
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A Simple One-Pot Synthesis of Benzoxazine-2,4-diones and Benzothiazine-2,4-diones
HETEROCYCLES, 2003
A simple and efficient procedure has been developed for a one-pot synthesis of substituted benzoxazine-2,4-diones and benzothiazine-2,4-diones directly from salicylic acid (or thiosalicylic acid) and amines. Synthetic chemists are becoming increasingly interested in the synthesis of substituted benzoxazine-2,4diones due to their utility in pharmacology 1-4 and photography. 5 Hence, considerable effort has been devoted to the preparation of benzoxazine-2,4-diones by using a wide variety of synthetic approaches, including palladium-catalyzed cyclocarbonylation of o-iodophenols with heterocumulenes, 6 reaction of phenyl salicylate with isocyanates, 7 cyclization of salicylic acid with isothiocyanate in the presence of silver trifluoroacetate, 8 preparation from salicylamide 9 and other methods. 10 In this paper, we describe a new and efficient process for the synthesis of substituted benzoxazine-2,4-diones in one pot directly from salicylic acid and amines. Initially, compound (4a) was prepared by cyclization of salicylamide with ethyl chloroformate according to the known procedure, 11 which took three steps from commercially available acetylsalicyloyl chloride. Scheme 1 illustrates this synthetic approach. Reaction of acetylsalicyloyl chloride with 3,4-dimethoxyphenethylamine was carried out to give acetylsalicylamide (2a), and then compound (2a) was deacetylated with triethylamine/methanol to afford salicylamide (3a). Compound (3a) was cyclized with ethyl chloroformate to give compound (4a). We realized that the existing methods include multi-step procedures, use of expensive catalyst or conversion of amine to isocyanates for synthesis of benzoxazine-2,4-dione derivatives, which provided us impetus to develop a simple and practical method to synthesize benzoxazine-2,4-dione derivatives. We found that benzoxazine-2,4-dione derivatives could be prepared in a one-pot reaction directly from salicylic acid and amines (Scheme 1). Salicylic acid was treated with ethyl chloroformate and the reaction mixture was evaporated at reduced pressure to remove unreacted ethyl chloroformate. Stirring the resulting residue with amines in the presence of triethylamine afforded the substituted benzoxazine-2,4
Simple and Selective Synthesis of 1,3-Benzoxazine Derivatives
Oriental Journal Of Chemistry, 2012
A simple and selective synthesis of 1,3-benzoxazine-2,4-dione and 4-methylene-1,3benzoxazine-2-one derivatives is reported from the reaction of Schiff bases and triphosgene. The selective synthesis of those 1,3-benzoxazine derivatives were found to be dependent on the type of substituents present on the Schiff base.
Reagent-Controlled Divergent Synthesis of 2-Amino-1,3-Benzoxazines and 2-Amino-1,3-Benzothiazines
The Journal of Organic Chemistry, 2019
A reagent-controlled chemoselective process has been devised for the synthesis of 4H-1,3benzoxazines and related biologically important heterocycles in high yields under mild conditions. These scaffolds could be efficiently constructed using two different chemoselective reactions rely on the choice of reagents and reaction conditions. The treatment of various 2-amino-arylalkyl alcohols with isothiocyanates afforded thiourea intermediates, which were reacted in-situ with molecular iodine in the presence of triethylamine to give the 2-amino-4H-1,3-benzoxazines, whereas the corresponding 2-amino-4H-1,3-benzothiazines were obtained by the reaction of thiourea intermediates in the presence of T3P (a mild cyclodehydrating agent) and triethylamine as base. The described protocol represents as the first example for the synthesis of 4H-1,3-benzoxazines via dehydrosulfurization method using molecular iodine as reagent.
Benzoxazine and their derivatives have been shown to possess a wide spectrum of biological activities. The most notable being antibacterial and antihelmentic properties [1-10]. This observation have led us to synthesize the structurally related compounds. 3&5–disubstituted anthranilic acid by successive reaction with acetic anhydride and benzoyl chloride to form 2-Methyl/Phenyl-6& 8-disubstituted– benzoxazine–4–ones which crytalized and tested for their antimicrobial
Novel 1,4-benzoxazine derivatives were synthesized by an efficient and simple method in high yields. Readily available starting materials, operational simplicity, mild reaction conditions and novelty are the key advantages of this method. The synthetically attractive feature of the procedure is reflected by its applicability to a wide range of isatin and aniline derivatives. Besides their novel structures, these compounds may have important biological activities and industrial applications. Furthermore, we demonstrated that in BaeyereVilliger oxidation reaction, the phenyl group migrate better than amidine groups but not as good as amide group. The migratory ability for these groups in BaeyereVilliger oxidation reaction is ranked amide > phenyl > amidine.
The Journal of Organic Chemistry, 2014
The synthesis of the title compounds was carried out by reacting dicarboxylic acid chlorides with oximes in the presence of excess triethylamine. Disubstituted malonyl chlorides gave 2-alkenyl-4,4-dialkyl-3,5-isoxazolidinediones (8a−f) and 2,2′-ethylidene-bis[4,4-dialkyl-3,5-isoxazolidinedione]s (9a−f). Compounds 9 were formed from 8 and its N-unsubstituted 3,5isoxazolidinedione decomposition product. Phthaloyl chlorides reacted with acetone oxime to yield 3-(1-methylethenyl)-1H-2,3benzoxazine-1,4(3H)-diones (16a−e). Products 16 spontaneously decomposed to give N-unsubstituted 1H-2,3-benzoxazine-1,4(3H)-diones (17a−e) at rates that were dependent on temperature and solvent. Kinetic studies showed that two of the compounds decomposed by zero-order kinetics under neutral conditions. Butanedioyl chloride did not produce a cyclic product.
One-Step Synthesis of Oxazoline and Dihydrooxazine Libraries
Journal of Combinatorial Chemistry, 2007
Oxazolines appear in numerous medicinally active compounds and natural products of biological significance. 1 Additionally, they are valuable as synthetic intermediates or protecting groups 2 in organic synthesis, 3 and commonly appear in ligands for asymmetric synthesis ). 4 The most common mode of oxazoline synthesis involves preparation of a β-hydroxy amide followed by cyclization. Typical cyclization reagents include Burgess reagent, 5 PPh 3 /DIAD, 6 DIC/Cu(OTf) 2 ,7 molybdenum oxide, 8 and DAST/Deoxo-Fluor. 9 The six-membered homologous dihydrooxazines have been prepared by various methods that include [4+2] cycloadditions between N-acyl imines and alkenes, 10 1,4-dipolar cycloaddition reactions between olefins and aminomethyl ions, 11 and from stereochemically defined Nthioacyl-1,3-amino alcohols in the presence of Bu 4 NF and EtI. 12