Preparation of 5-Acyl-2-amino-1,3-selenazoles by the Reaction of Selenazadienes with α-Haloketone

Abstract

Reaction of selenazadienes with a-haloketones gave 5-acyl-2-amino-1,3-selenazoles in high yields.Many syntheses of selenium-containing heterocyclic compounds have been reported because of their interesting reactivities 1 and potential biological interest. 2 For example, 1,3-selenazole derivatives inhibit lipopolysaccharideinduced nitric oxide production in BV-2 cells. From structure-activity relationships, specific substituent groups on the 1,3-seleazole skeleton have been shown to strongly influence the activity. 3 Therefore, the preparation of many kinds of 1,3-selenazoles has been desired for development as potential agents. Heretofore, selenoureas and selenoamides have been used as starting materials for the synthesis of 1,3-selenazoles. 1 Recently, it has been reported that selenazadienes can be employed in the synthesis of 1,3-selenazoles. 4 There have been very few reports of the synthesis of 5-acyl-2-amino-1,3-selenazole, 6 though there are many reports of the syntheses of 2-amino-1,3-selenazole or 5-acyl-1,3-selenazole. 5 We describe here the onepot synthesis of 5-acyl-2-amino-1,3-selenazole derivatives through the reaction of selenazadiene with a-haloketone.Three different selenazadienes (selenocarbamoylamidine) 1 were prepared by a modified route based on reported experimental conditions described for the synthesis of N-thioacylamidine from thiobenzamide. 4 The reaction of N,N-dimethyl-N¢-(dimethylselenocarbamoyl)formamidine (1a; 1 equiv) with chloroacetone (2a; 1 equiv) gave 5-acetyl-2-dimethylamino-1,3-selenazole (3a) in 98% yield under reflux conditions (Scheme 1). Dimethylamine hydro halide was recovered in the reaction mixture. 7 Reactions of three selenazadienes 1 with five a-haloketones 2 also gave the corresponding 5-acyl-2-amino-1,3-selenazole 3 in moderate to high yields. Reaction conditions were optimized taking into account the individual reactivity and solubility of each substrate (Table 1). In the case of the reaction of thioazadiene with 2, base (triethylamine) was required. 8 On the other hand, in the case of selenazadienes 1, the addition of base to the reaction mixture gave unidentifiable mixtures together with 3.The crystal structure of 3e was determined using X-ray diffraction analysis (Figure 1). 9 We next investigated the reactions of 1 (2 equiv) with 1,3-dichloro-2-propanone (2c, Scheme 2). The reactions gave the corresponding bis(2-amino-5-selenazoyl) ketones 4 in high yields. The reaction of 1 with 2c (5 equiv) without base yielded 2-amino-5-chloroacetyl-1,3-selenazoles 3g-i as the major products (Table 1, entries 7-9). The reaction of 1 (2 equiv) with 2c in the presence of triethylamine gave 4a-c as major products together with 3g-i as the minor products (Scheme 2). Without triethylamine, reaction of 1c (2 equiv) with 2c gave the corresponding 4c in only 46% yield as the major product together with 3i as the minor product.The present study provides a one-pot procedure for the synthesis of 5-acyl-2-amino-1,3-selenazoles by the reaction of selenazadienes with a-haloketones in ...

Bis-(2-amino-5-selenazoyl) Ketone as a Superoxide Anion-Scavenger

“…17) A Cypridina luciferin analogue, 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo-[1,2-a]-pyrazin-3-one hydrochloride (MCLA) was obtained from Tokyo Kasei (Tokyo, Japan) for a use as a chemiluminescent probe for superoxide radicals. MCLA was dissolved in doubly distilled water and stored at Ϫ80°C prior to usage.…”

Organoselenium Compounds: Chemistry and Applications in Organic Synthesis

“…Hantzsch condensation can be considered the most employed method for the preparation of 1,3‐selenazoles [238] . A metal‐free decarboxylative cyclization of 2‐chloronitrobenzene, arylacetic acids, and elemental selenium to prepare 2‐phenylbenzoselenazoles of formula 275 has been recently described [239] .…”

“…[229] Hantzsch condensation can be considered the most employed method for the preparation of 1,3-selenazoles. [238] A metal-free decarboxylative cyclization of 2-chloronitrobenzene, arylacetic acids, and elemental selenium to prepare 2-phenylbenzoselenazoles of formula 275 has been recently described. [239] The optimized reaction conditions indicated that this multi-component transformation worked better when Nmethylpiperidine was chosen as the solvent, with the optimal temperature being 130 °C for 24 h. It was observed a negative effect on the reaction yield when this transformation was conducted in the presence of air.…”

Synthesis of selenoureas and heterocycles based thereon

“…Unlike N,N-disubstituted selenoureas 14 carbonyl chlorides 84 which were treated with water, alcohols, or amines [120,121] (Scheme 24). A simple one-pot procedure for the synthesis of 5-acyl-2-amino-1,3-selenazoles 86 in high yield from selenazadienes 22 and α-haloketones was reported [122]. Analogous reaction of 22 with 1,3-dichloropropan-2-one afforded bis(2-amino-1,3-selenazol-5-yl)methanones 87 (Scheme 24).…”