Preferential Intramolecular Ring Closure of Aminoalcohols with Diethyl Carbonate to Oxazolidinones

Abstract

In connection with our interest in the chemistry of baminoalanines, [1][2][3][4] we have reported the synthetic application of these materials as a synthon for the preparation of a 5-membered oxazolidinone ring system.2) Some of the oxazolidinone derivatives have attracted much attention not only as a synthetic target but also because of the importance of the related compounds in the biological activities. 5,6) This paper deals with the relative rates of ring closure by cyclization with diethyl carbonate (EtO) 2 CO from aminoalcohols as starting material. We report here two typical experimental results for the cyclization that has two possibilities as a function of the ring intramolecular cyclization by (EtO) 2 CO.1 Results and DiscussionsThe objective of this report is to explore the orientation of ring closure of aminoalcohol by (EtO) 2 CO. The compounds (1 7) and 6 8)) are selected as the starting aminoalcohols, which have two hydroxy groups and a basic secondary amine in the molecules, so that the cyclization of these compounds employing (EtO) 2 CO can lead to the corresponding heterocycles (e.g. compounds 2 and 3, respectively, in the case of aminoalcohol 1).Since the experiment using compound 1 under similar reaction conditions reported previously 2) resulted in a quite complex reaction mixture by TLC analysis, it is not used to determine conditions suitable for cyclization of this aminoalcohol (1). Then, we tried the cyclization of (1) under the conditions of this aminoalcohol (1) , 2b). Because a diastereomeric mixture of aminoalcohol (1) (cis : transϭca. 3/1) was used as the starting material (see Experimental), the 5-membered ring products (oxazolidinones) may generate the products 2 as a mixture of four diastereoisomers theoretically.We were able to isolate two cis-isomers (2a, b, a or bstereoisomers, respectively), and our repeated trials for separation of two pure trans-isomers were unsuccessful. However, NMR spectroscopic analysis showed the isolated sample 2c was a mixture of two stereoisomers (see Experimental). In this case, the preferential formation of a 5-membered oxazolidinone ring system apparently indicated that this process (5-Exo-Trig 9) ring closure) is more favorable than that of 6-membered ring derivative 3 by 6-Exo-Trig ring closure. The fact that the 6-membered ring system can be isolated easily in the reaction of a noncompetitive cyclization system, i.e., the formation of compound (5) 10) from the start- Preferential Intramolecular Ring Closure of Aminoalcohols with Diethyl Carbonate to OxazolidinonesFumiko FUJISAKI, Marumi OISHI, and Kunihiro SUMOTO* Science, Fukuoka University; Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Received January 19, 2007; accepted February 22, 2007 The closure by cyclization with diethyl carbonate (EtO) 2 CO from aminoalcohols 1 as starting material can lead to the oxazolidinones 2a, b and 2c, respectively. In the reaction of trans-isomer (6) and (EtO) 2 CO, isolated products were also only 5-membered oxazolidinone derivative (7), containing its deh...

An efficient access to functionally substituted 1,3-oxazolidin-2-ones via cyclization of 1-alkylamino- and 1-arylamino-3-[2-(vinyloxy)ethoxy)]propan-2-ols with dimethyl carbonate

“…2,[25][26][27][28][29] Recently the synthesis of 1,3-oxazolidin-2-one by the reaction of 1,2-amino alcohols with dimethyl carbonate in presence of phosphazene base was reported. 30 Here we report a simple and efficient synthesis of the 3,5-substituted oxazolidin-2-ones containing vinyloxyalkyl moiety 2 from 1-alkylamino-and 1-arylamino-3-[2-(vinyloxy)ethoxy]-2-propanols (1) and dimethyl carbonate (DMC) in the presence of readily available inexpensive bases (sodium methoxide or metallic sodium).…”

Antibacterial Activity of 5-Dialkylaminomethylhydantoins and Related Compounds

“…1,2) Some of the synthesized compounds were evaluated for antibacterial activity with gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) strains, and we found that most of the 4-dialkylaminomethyloxazolidinone-related derivatives (A) 1) showed no significant antibacterial activities against either gram-positive or gram-negative strains. Therefore, we carried out further molecular modification of linezolid to the hydantoin analogue (B).…”

“…Synthesis of 5-Dialkylaminomethyl-3-aryl-hydantoins (3) and Related Compounds In our synthetic studies on b-aminoalanines (1), 9) we have already reported target molecules of 5-dialkylaminomethyl-3-aryl-hydantoins (3) which are easily prepared by cyclization of urea derivatives (2) readily obtained by addition of b-aminoalanines to arylisocyanates (or arylisothiocyanates). 10,11) The hydantoin derivatives (3) described in this paper were prepared in a manner similar to that reported previously.…”