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Ammonia is rarely used as the amine component in the Ugi reaction, as it reportedly leads to low yields and extensive by-product formation.
Different alkyl and aryl carboxylic acids were tested under the developed reaction conditions using aniline, the amine component, as a constant (Scheme 1).
SAR studies revealed that the substituents on C6 and C7 positions of quinazoline, the amine component of dithiocarbamate moiety and the linker greatly affected the activity.
The preparation of the amine component was achieved via phthalimide protection strategy which occurred to be more efficient than the traditional nitro group reduction.
Coupling reactions were carried out by mixing the water-dispersible nanoparticles of Boc-protected amino acid and amine component in water using DMTMM and then stirring the mixture under neutral conditions for 12 hours at room temperature (Figure 10).
The results reported in Table 4 also suggested that, when diethyl amine is used as amine component, the reaction is affected by the electronic nature of the substituent on the aromatic ring of the benzoic acid (entry r, entry t Table 4) which probably characterize the reactivity of the reaction intermediates.
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These experimental data were used as a screening tool to enable the selection of the best amine components for designing an optimal blended aqueous amine solution system.
Amine components used may form aggregates as well, which is mediated by hydrophobic effect due to occurrence of long-chain alkyl tails.
Additional experiments, that employed 2-fluoroaniline and 4-methylaniline as amine components, were carried out in order to investigate the electronic effect of the substituent on the aniline nucleophilicity and consequently on the reaction course.
These conditions were successfully applied to a range of Petasis reactions employing either glyoxylic acid or salicylaldehyde as the carbonyl component along with a number of aryl/heteroaryl boronic acids and amine components.
Equilibrium CO2 solubility in each of the blends has been estimated using a software tool developed in Matlab for the prediction of vapour liquid equilibrium using a combination of the known chemical equilibrium reactions and constants for the individual amine components which have been combined into a blend.
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