One-Pot Preparation of Oxazol-5(4<i>H</i>)-ones from Amino Acids in Aqueous Solvents

Abstract

A method for one-pot synthesis of oxazol-5(4H)-ones has been developed using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which is available for the activation of carboxylic acids in an aqueous solvent. The oxazolones were prepared by the N-acylation of amino acids with carboxylic acids and the subsequent cyclodehydration of the resulting N-acylamino acids by the addition of N,N-diethylaniline. Since both these reactions proceed effectively with the same coupling reagent, DMT-MM, in aqueous solvents, the procedure is simplified and becomes easy to perform. In addition, 5-(triazinyloxy)oxazole derivatives have been synthesized by controlling the basicity of the reaction system. Key words oxazolone; oxazole; dehydrocondensation; cyclodehydration; aqueous solvent Oxazol-5(4H)-ones (henceforth referred to as oxazolones) are useful precursors for the synthesis of substituted heterocyclic compounds, 1) natural products, 2) and chiral amino acids. 3,4)In general, the preparation of oxazolones from amino acids is effected by two-step synthesis: N-acylation of the amino group followed by cyclodehydration involving the activation of the carboxy group. The N-acylation of amino acids can be carried out in an aqueous solvent, typically using Schotten-Baumann conditions, 5) while the cyclodehydration of the resulting N-acylamino acids to form oxazolones is performed under anhydrous conditions with dehydrating reagents, such as carbodiimides and acid anhydrides. Thus, these reactions must be performed in separate vessels. If the latter reaction occurs in an aqueous solvent, both reactions can be conducted in the same vessel using water-soluble amino acids as a starting compound. Therefore, the procedure for preparing oxazolones becomes simplified. In this study, we focused on 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) 6) as a dehydrocondensing reagent because the chemoselective activation of carboxy groups using DMT-MM efficiently proceeds even in an aqueous solvent. 7)We report here a one-pot method for the synthesis of oxazolones from amino acids. In this method, DMT-MM is utilized successfully for both the N-acylation of amino acids with carboxylic acids and the subsequent cyclodehydration of the resulting N-acylamino acids. 8,9) Results and DiscussionTo find the optimum reaction conditions for the one-pot method, we first examined each reaction separately using Lleucine (2a) as a model compound.10,11) After several attempts, we succeeded in finding the optimum reaction conditions for the first reaction. Benzoic acid (1) was treated with DMT-MM in the presence of N-methylmorpholine (NMM) in acetone-H 2 O (3 : 1) at room temperature for 15 min; then an aqueous solution of 2a and NaOH was added (Chart 1). As a result, N-benzoyl-L-leucine (3a) was obtained in a satisfactory yield (91%). The addition of NaOH as a base was found to be essential to complete the coupling reaction.The second reaction needs to follow the final conditions of the former reaction to achie...

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

“…The study was initiated with the preparation of the key intermediate, 5-(triazinyloxy)oxazole 3 , from carboxylic acid 1 and amino acid 2 under conditions improved from [ 23 ] ( Table 1 ). A one-pot sequence involving formation of an activated ester from benzoic acid ( 1a ) with DMT-MM, N -benzoylation of alanine ( 2a ), cyclodehydration, and introduction of the triazinyl group was conducted in 1,4-dioxane/H 2 O to give the desired 5-(triazinyloxy)oxazole 3aa in 78% yield ( Table 1 , entry 1).…”

“…Previously, we reported a one-pot synthesis of oxazolone from carboxylic acids and amino acids using a dehydrative condensing reagent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM [ 19 – 22 ])[ 23 ]. Formation of 5-(triazinyloxy)oxazole is also reported to occur when an excess of DMT-MM was used.…”

NP-hardness of decoding quantum error-correction codes

“…Our result, showing that it is unlikely that a substantially fast algorithm for decoding the most probable quantum error would exist, may become a foundation of a quantum analogue of the classical McEliece cryptosystem. Notice that a proposal of such a quantum McEliece cryptosystem has been proposed recently [12]. This paper is organized as follows.…”