Single crystal growth of lapatinib free base was induced by immersion of a copper wire into a supersaturated methanolic aqueous solution yielding monoclinic anhydrous plates (space group P2 1 /c, Form 1) and needles of a previously unknown channel hydrate (in P4 2 2 1 2). Also, a new method has been developed herein to obtain anhydrous Form 1 via acid−base reaction of lapatinib ditosylate and sodium methoxide, avoiding the usage of an aqueous solution and hydrate formation. Anhydrous Form 2 as well as new solvates were produced via solution mediated transformation experiments, including a dichloromethane solvate with a powder X-ray diffraction pattern similar to that of anhydrous Form 2. Differential scanning calorimetry and solution equilibrium experiments helped to elucidate the interconversion pathways between Form 1, Form 2, and the solvates.

The step‐wise conversion of synthetic porphyrins to derivatives that contain a non‐pyrrolic building block is an appealing method to generate functionalized porphyrinoids. Applied to octaethyloxochlorin oxime, a Beckmann rearrangement is potentially suited to generate a nitrogen‐expanded porphyrinoid. Unexpectedly, this reaction led to a ring‐expansion by an oxygen atom. The mechanism – an abnormal Beckmann reaction, followed by an intramolecular ring‐closing reaction and hydrolysis – was conclusively derived by trapping and structural characterization of the key secochlorin intermediate. The structural and UV/Vis spectral changes observed upon ring‐expansion of the oxochlorin are discussed. Other Beckmann‐rearrangement conditions failed to produce ring‐expanded products altogether. This work demonstrates in many ways how the extraordinary structural stability of the porphyrin macrocycle redirects the reactivity patterns of classic ring‐expansion reactions, which outlines the limits of the “breaking and mending of porphyrins” approach toward pyrrole‐modified porphyrins.

The Schmidt reaction (treatment of a ketone with sodium azide and a mineral acid) is an alternative to the Beckmann rearrangement to expand a cyclic ketone to a lactam. However, when applied toward the conversion of a synthetic porphyrin into a derivative containing a nonpyrrolic building block, this approach failed to generate the expected lactam. Instead, by using sulfuric acid as a catalyst, a novel heptaethyl‐2‐hydroxy‐chlorin‐3‐one was formed, structurally characterized, and its mechanism of formation deduced. The work demonstrates how the extraordinary structural stability of the porphyrin macrocycle redirects the reactivity patterns of classic ring‐expansion reactions. By using hydrochloric acid as a catalyst, a somewhat regioselective chlorination of the meso‐positions of the oxochlorin was observed. The halogenation sites were determined spectroscopically and by X‐ray crystallography of selected derivatives. The regioselectivity of the halogenation was computationally rationalized. This method is superior to alternative halogenation methods for the regioselective generation of 5‐chloro‐, 10‐chloro‐, and 5,10‐dichlorooxochlorins.

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C54H50Cl4N4O8, triclinic, P1̅ (no. 2), a = 11.295(1) Å, b = 11.255(1) Å, c = 11.797(1) Å, α = 108.904(2)°, β = 101.091(2)°, γ = 110.992(2)°, V = 1241.4 Å3, Z = 1, Rgt(F) = 0.056, wRref(F2) = 0.135, T = 100 K.C54H48Cl4CuN4O8, triclinic, P1̅ (no. 2), a = 11.2204(5) Å, b = 11.3499(6) Å, c = 11.7610(6) Å, α = 109.187(1)°, β = 100.830(1)°, γ = 110.681(1)°, V = 1242.7 Å3, Z = 1, Rgt(F) = 0.033, wRref(F2) = 0.092, T = 100 K.C54H48Cl4N4NiO8, triclinic, P1̅ (no. 2), a = 11.196(1) Å, b = 11.329(1) Å, c = 11.785(1) Å, α = 109.486(2)°, β = 101.230(2)°, γ = 110.607(2)°, V = 1233.8 Å3, Z = 1, Rgt(F) = 0.040, wRref(F2) = 0.110, T = 100 K.