Bis(trichloromethyl)carbonate (BTC, triphosgene) is a versatile compound that enables highly efficient syntheses. In addition, because of its solid state, it is a very convenient compound for small-scale phosgenations. Consequently, this compound is favored as a phosgene substitute in research and development and in small-scale production. Although BTC is highly toxic, safe handling is possible as long as the properties and chemical reactivity of this compound are understood and considered. However, branding as “safe phosgene” or “safer phosgene” is misleading. The solid state of BTC leads to the misconception that there is no significant exposure. However, the vapor pressure is sufficiently high to easily result in toxic concentrations. In addition, proper monitoring is not yet possible. Proper use of BTC could be more complex than the handling of phosgene itself. However, handling of BTC is normally always associated with phosgene and has its own toxicity. Therefore, the use of BTC will become more regulated in the future, which will directly increase responsibility in route selection during process development. A stringent safety concept for phosgenations using BTC is necessary. Because of the interconnection with phosgene, the safety concept for BTC will likely be an extended version of the safety concept for phosgene.

Azelaic acid (AzA), a saturated dicarboxylic acid, is indicated for the treatment of acne vulgaris, rosacea, melasma, and post-inflammatory hyperpigmentation. Its antimicrobial, anti-inflammatory, and antimelanogenic properties support its use; however, its poor aqueous solubility and limited skin permeability constrain its optimal topical delivery. This review summarizes clinical evidence and advances in formulations—including conventional vehicles, polymeric/lipid nanocarriers, and deep eutectic solvent (DES) systems—to promote more effective and well-tolerated use. Across indications, 15–20% azelaic acid (AzA) formulations produced clinically meaningful improvements with mild, transient local irritation. For acne vulgaris, reductions in inflammatory and noninflammatory lesions were comparable to those of topical retinoids/adapalene, and tolerability was superior in some studies. For rosacea, the 15% gel formulation was comparable to metronidazole in reducing papules, pustules, and erythema while maintaining negligible systemic exposure. In melasma and other dyschromias, 20% cream demonstrated efficacy similar to hydroquinone, exhibiting a favorable safety profile. Advanced delivery systems, including liposomes, niosomes/ethosomes, nanostructured lipid carriers, microemulsions, nanosponges, and DES platforms, increased AzA solubilization, cutaneous deposition, and stability. This enabled dose-sparing strategies and improved adherence. Data on AzA cocrystals and ionic salts suggest additional control over release and irritation. AzA remains a versatile and well-tolerated dermatologic agent whose performance is strongly vehicle-dependent. Rational selection and engineering of carriers, particularly DES-integrated polymeric and lipid systems, can mitigate solubility and permeability limitations, enhance skin targeting, and reduce irritation in the treatment of acne and rosacea.

The key intermediate in the synthesis of dorzolamide, (4S,6S)-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol-7,7-dioxide, can be obtained in the diastereoisomerically pure form in two straightforward steps starting from diastereoisomeric mixtures of cis/trans-(6S)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-yl acetate, regardless of their ratio. The reaction of crucial importance in this scheme is a remarkably stereoselective solvolysis of the acetate ester in an acetone/phosphate buffer mixture as the solvent system. Investigation of this so far unrecognized stereoselective reaction reveals that it proceeds via an S_N1-like pathway as indicated by the correlation of the solvolysis rate constants with the Y_OTs values of different solvent mixtures and by trapping of the reaction intermediate with sodium azide. The structure of (4S,6S)-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol-7,7-dioxide was confirmed by single-crystal X-ray analysis.