The pretreated membrane with TW 80 or BAK showed significantly less NSB for compounds that had a tendency toward high membrane binding. A modified UF method with pretreatment improved the performance of UF and was able to produce comparable PB results to ED.
We have previously reported 1 an initial investigation of orientation effects in the Pechmann synthesis 2,3 of coumarins which was confined to a study of alkylphenols 1a and 1j (see Table 1) and subsequently extended 6 to meta-methoxyphenol 1d. In the present work an investigation of varying reaction conditions with a series of meta-substituted phenols has been performed.Four reaction procedures were investigated. Method A involved the mixing of the phenol 1 (P), malic acid 9 (M) and sulphuric acid (S) at the outset. In methods B -D, two of the components were mixed initially with the third (S, P and M respectively) added portionwise once the appropriate reaction temperature (85, 115 or 130°C) had been attained. The results are shown in Table 3.The reaction with malic acid 9 is best performed between 80 and 130°C with the reagents mixed at the outset, the stepwise addition of either the phenol or sulphuric acid had only a minimal effect on the isomer ratio. The proportion of 2d (see Table 2) increased with temperature to a maximum of 10%. However, when 9 was added portionwise dealkylation 7,14 occurred leading to the formation of 3e. With meta-chlorophenol 1f, the proportion of 2f decreased with temperature. A 'reversed' steric effect 20 leading to a transient intermediate is proposed to explain this unexpected trend.For the study which involved the influence of the metasubstituent on the reaction, method B was used with 9 whilst the ethylacetoacetate reactions were performed on the steam bath at ca 80°C. The results are shown in Table 4.The proportion of the 5-isomer decreased with the increasing bulk of the alkyl group and was zero for 1c. With electron donating groups (e.g. OMe, OH) about 10% of the 5-isomer was obtained, however, secondary reactions 18,21 at the reactive sites made isomer ratios difficult to establish. The reaction failed with electron withdrawing groups, e.g. 1g. Reactions with ethyl acetoacetate gave the 4,7-isomers only.Products were identified by 1 H and 13 C NMR spectroscopy. Use of the peri-deshielding effect 1 to definitively identify the H-4 signals in the 5-substituted compounds was a valuable assignment aid. Detection of the quaternary carbon resonances in the low abundance 5-isomers was only possible after sample concentration by fractional crystallisation. 114The proportion of 5-/7-substituted coumarins formed in the Pechmann synthesis from meta-substituted phenols and malic acid and ethyl acetoacetate under a variety of reaction conditions, with product analysis by 1 H and 13 C NMR spectroscopy, is reported.
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