Synthesis of β-lactams and oxazolidines from phenoxyacetic acid and ethanolimines promoted by benzenesulfonyl chloride

Abstract

β−Lactams show diverse and interesting antibiotic activity. The N-(2-hydroxyethyl) β-lactams are very important precursors of N-unsubstituted β-lactams. Literature reports show that their syntheses have been carried out by the annelation of ethanolimines with acetic acids in the presence of phenyl dichlorophosphate 1,2 and Vilsmeier reagents. 3 These β-lactams have also been synthesised using the acid chloride-imine method. 4 Oxazolidines are useful synthetic intermediates. They are usually obtained by the condensation of secondary β-aminoalcohols with either aldehydes or their corresponding acetals. 5 N-Acylated oxazolidines have been synthesised using very drastic conditions. 6-7Here we report the synthesis of some new β-lactams and N-acylated oxazolidines from ethanolimines and phenoxyacetic acid induced by benzenesulfonyl chloride under very mild reaction conditions.Various imines (3a-e) have been synthesised by refluxing substituted primary β-aminoalcohols with aldehydes in methanol for 3-4 h in 93-94% yield. The 1 H NMR data (Table 1) clearly indicated them to exist as Schiff bases, azomethine protons appearing in the range δ 8-8.7 ppm. Further, these imines were protected by trimethylsilyl chloride in the presence of triethylamine by stirring the reactants at room temperature for 1h followed by successive addition of phenoxyacetic acid and benzenesulfonyl chloride at 0°C. The contents were then stirred at room temperature for 19-20 h followed by quenching with water to afford the N-2-hydroxyethyl β-lactams 4a-d in 60-70% yield (Scheme 1). The structures of the β-lactams were assigned on the basis of elemental analysis and spectroscopic (IR, 1 H NMR) data. The protons at C 3 and C 4 of all the βlactams were found to be in cis-orientation as evident from the coupling constants J 3,44 -5 Hz. The IR spectra showed the presence of the β-lactam carbonyl peak in the range of 1740-1755 cm -1 (Table 3) Similar results were obtained when phenoxyacetyl chloride was used instead of mixed anhydride for the β-lactam synthesis.However, the treatment of the unprotected imines with phenoxyacetic acid and benzenesulfonyl chloride in the presence of triethylamine in dichloromethane furnished N-acylated oxazolidines (5a-c) in 65-70% yield (Scheme 2). The IR spectra of these compounds showed amide carbonyl peak in the range of 1660-1670 cm -1 . NH, OH and β−lactam carbonyl stretching bands were found to be absent. 300 MHz 1 H NMR spectra indicated the presence of two singlets at δ 4.5-4.8 corresponding to the methylene protons adjacent to the phenoxy group and another at δ 6.4-6.7 from the C 2 proton of the oxazolidine which is flanked by N, O and aromatic group. In 5c, C 2 -H appeared as a doublet at δ 6.48. (Table 3) This cyclisation reaction under the influence of the acylating species led us to suggest that the reaction proceeds through the intermediacy of iminium ion 6, followed by nucleophilic attack by the hydroxyl group on the incipient carbonium ion to produce the oxazolidines. 8 However, when the hydroxyl group of th...

An approach to determine nickel in aqueous systems through complexation with a Schiff base based on high‐performance liquid chromatography coupled with photodiode array detector

“…Azomethine hydrogen was seen at 3095 cm −1 , and CH 2 and CH 3 were indicated at 3066 and 2964 cm −1 , respectively. ν (C = N) stretching vibration was identified at 1636 cm −1 , while ν (C‐O) and ν (C _ S) were 1430 and 737 cm −1 , respectively [24, 25]. The lack of a strong band from near 1810–1760 cm −1 , which is the characteristic property of the C = O bond, indicates that a condensation reaction took place to result in a new band at 1636 cm −1 due to C = N bond formation (Figure S1).…”

Five-membered oxaza heterocyclic compounds on the basis of epoxides and aziridines

“…Nucleophilic addition of anion 198 to Schiff base 199 was assumed to be the key step in the [3 + 2]-cycloaddition process (Scheme 112). The use of Schiff bases and epoxides separately in syntheses of heterocycles, in particular heterocyclization of 3-hydroxy-substituted and other Schiff bases, is considered below [228][229][230][231][232][233]. Sharma A complementary ambiphilic pairing strategy was applied to study reactions of epoxy compounds having CH 2 OCH 2 Ph, CH 2 OPh, (CH 2 ) 2 CH=CH 2 , and other groups with arene-and alkenesulfonamides 214 [237] under microwave irradiation.…”

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

“…Thiazolines also find use in organic synthesis as building blocks in drug discovery, and as ligands in metal-catalyzed reactions [11][12][13][14][15][16]. Their six-membered homologues (5,6-dihydro-4H-1,3thiazines) are also compounds of broad interest [17], due to their bioactivities [18,19] and as valuable synthetic intermediates [20][21][22].…”