No abstract

N-Alkylation of 2-azidobenzenesulfonamide with 5-bromopent-1-ene gave an N -pentenyl sulfonamide, which underwent intramolecular aminohydroxylation to give an N -(2-azidoaryl)sulfonyl prolinol, a precursor for the synthesis of a pyrrolobenzothiadiazepine. The attempted N-alkylation of 2-azidobenzamide gave a separable mixture (∼1:1) of a benzotriazinone and a quinazolinone in a 72% combined yield. Other primary alkyl halides (3 examples) gave similar mixtures of benzotriazinones and quinazolinones. Benzylic, allylic, and secondary and tertiary alkyl halides (5 examples) gave only benzotriazinones in moderate yields. The results of mechanistic studies show the likely involvement of nitrene intermediates in the quinazolinone pathway and a second pathway involving a dimethylsulfoxide or dimethylsulfide-mediated conversion of 2-azidobenzamide into benzotriazinones.

Non-ionic surfactants such as polysorbates, known as Tween™ 20 and Tween™ 80, are routinely used within the healthcare and pharmaceutical industry to enhance solubility. This work focuses on analysing the two aforementioned polysorbates, each considered at three purity levels with four model compounds, across the critical micellar concentration (CMC) range for each surfactant. Such data is of interest to investigate the influence of micelle formation upon compound-polysorbate interaction. Two analytical techniques were utilised, namely spectroscopic solubility determination and micellar liquid chromatography (MLC). In all cases it was apparent that the maximum solubility for all four compounds increased substantially at concentrations greater than the CMC and that, in most cases, a different retention profile was observed using MLC once the CMC had been exceeded. This paper is the first to have used such techniques to investigate the behaviour of these polysorbates over a series of concentrations and three levels of polysorbate purity. The findings indicate that the solubilisation potential of polysorbates differs once the CMC has been surpassed and is dependent upon the level of purity selected, i.e. compound-surfactant interactions are partially a consequence of the presence of micelles rather than monomer as well as polysorbate purity.Thus, formulators should include such polysorbates at optimised concentrations and purity if they wish to maximise their solubilisation potential.