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60Co γ-irradiation of both lithium trans-2-butenoate (11) and lithium trans-2-butenoate·formamide (12) affords the same dimer, dilithium trans-5-methyl-2-heptenedioate (13). However, stereochemical analysis of products 22and 24from the analogous trans-2-butenoate-2-dsalts 21and 23established that C–C and C–H bond formation occur stereospecifically by synaddition to the double bond in lithium trans-2-butenoates 11and 21and antiaddition to the double bond in lithium trans-2-butenoate·formamide complexes 12and 23. These reactions, which provide an unprecedented, chemospecific one step synthesis of dicarboxylate 13, add significantly to the synthetic scope of the γ-ray induced reactions of crystalline metal trans-2-butenoates that lead to cyclic and acyclic dimers and acyclic trimers by γ-ray initiated radical chain reactions. The stereochemistry of products 22and 24is that predicted by analysis of crystal packing, consistent with least-motion principles of the topochemical postulate as shown in Fig. 12 and 13. Analysis of the crystal structures, with respect to nearest neighbors, is consistent with the hypothesis that formation of carbon–carbon bonds in propagation step 1 and hydrogen atom transfer in propagation step 2 are topochemical and controlled by the crystal lattice. Analysis of the packing diagrams provides a pathway for chain propagation throughout the crystal that consumes all the molecules in the unit cell. The dimerization of 12is much more rapid and proceeds in much higher yield than that of 11, probably as a result of significantly shorter CC contacts and a more robust pathway for hydrogen transfer. [ABSTRACT FROM AUTHOR]

60Co γ-irradiation of bis(trans-2-butenoato)calcium (4) and triaquabis(trans-2-butenoato)magnesium (11) affords cyclodimerization products cis,trans- and trans,trans-nepetic acids (5and 15), respectively. The products are produced in high yield, based upon conversion, by a γ-ray induced radical chain pathway and provide unprecedented, stereospecific, one-pot syntheses of two of the four possible nepetic acid diastereomers, adding significant generality to the synthetic scope of the γ-ray induced reactions of crystalline metal trans-2-butenoates. Stereochemical analysis of the products from the analogous trans-2-butenoato-3-dcomplexes 19and 27establishes unequivocally that hydrogen atom transfer is also stereospecific and not part of a random process. The stereochemistry of the diastereomers is that predicted by the analysis of crystal packing, consistent with the least-motion principles of the topochemical postulate. Analysis of the crystal structures, with respect to the nearest neighbors, is consistent with the hypothesis that the formation of both carbon–carbon bonds and hydrogen atom transfer are topochemical and controlled by the crystal lattice. Analysis of the packing diagrams provides a pathway for chain propagation throughout the crystal that consumes all the molecules in the unit cell. [ABSTRACT FROM AUTHOR]

Crystalline hydrates and propylene glycol solvates of celecoxib sodium salt (Cel-Na) were prepared and characterized with the aim of improving oral drug absorption by breaking up the H-bonding interactions present in crystals of the poorly soluble marketed form of the drug (Cel-III). The hydrate grows rapidly from aqueous alkaline solution, forming a thick slurry of thin plates. Thicker plates for structure determination were successfully grown by adding up to 1% benzyl alcohol to the solution. The structure of the pentahydrate of the sodium salt is comprised of a bilayer motif where three waters are coordinated to sodium ions in a discrete layer, while the other two waters reside in a one-dimensional channel. At a given temperature, the hydration state changes rapidly and reversibly as a function of relative humidity (RH). The hydrated salt is physically stable in a sealed vial, but reverts rapidly to the crystalline free base if exposed to ambient CO2in air at 40% RH or higher. The propylene glycol (PG) solvate of Cel-Naexists in an anhydrous and trihydrate form. The trihydrated PG solvate of Cel-Nais physically stable above ∼15% RH and does not react measurably with CO2at 66% RH over 4 days, making it the most suitable form for use in solid pharmaceutical formulations. [ABSTRACT FROM AUTHOR]