Purinyl N1-Directed Aromatic C–H Oxidation in 6‑Arylpurines and 6‑Arylpurine Nucleosides

Palladium-catalyzed C–H bond activation and oxidation of C6 arylpurines as well as C6 arylpurine nucleosides can be accomplished using Pd­(OAc)₂/PhI­(OAc)₂ in CH₃CN. Despite the presence of four nitrogen atoms in the purine moiety as well as the polyoxygenated saccharide and a labile glycosidic bond in the nucleosides, these reactions can be effectively conducted. Notably, the generally more labile 2′-deoxyribonucleosides also undergo reaction. The reaction conditions can be tuned to yield either monoacetoxylated or diacetoxylated products predominantly. In the course of these investigations, a dimeric Pd^II-containing cyclopalladated C6 naphthylpurine derivative has been obtained and crystallographically characterized. This compound is competent in catalyzing the oxidization with PhI­(OAc)₂, indicating its plausible intermediacy in the chemistry. The X-ray structure of a monoacetoxylated product from this reaction has also been obtained

Purinyl N1-Directed Aromatic C–H Oxidation in 6‑Arylpurines and 6‑Arylpurine Nucleosides

Palladium-catalyzed C–H bond activation and oxidation of C6 arylpurines as well as C6 arylpurine nucleosides can be accomplished using Pd­(OAc)₂/PhI­(OAc)₂ in CH₃CN. Despite the presence of four nitrogen atoms in the purine moiety as well as the polyoxygenated saccharide and a labile glycosidic bond in the nucleosides, these reactions can be effectively conducted. Notably, the generally more labile 2′-deoxyribonucleosides also undergo reaction. The reaction conditions can be tuned to yield either monoacetoxylated or diacetoxylated products predominantly. In the course of these investigations, a dimeric Pd^II-containing cyclopalladated C6 naphthylpurine derivative has been obtained and crystallographically characterized. This compound is competent in catalyzing the oxidization with PhI­(OAc)₂, indicating its plausible intermediacy in the chemistry. The X-ray structure of a monoacetoxylated product from this reaction has also been obtained

Purinyl N1-Directed Aromatic C–H Oxidation in 6‑Arylpurines and 6‑Arylpurine Nucleosides

Palladium-catalyzed C–H bond activation and oxidation of C6 arylpurines as well as C6 arylpurine nucleosides can be accomplished using Pd­(OAc)₂/PhI­(OAc)₂ in CH₃CN. Despite the presence of four nitrogen atoms in the purine moiety as well as the polyoxygenated saccharide and a labile glycosidic bond in the nucleosides, these reactions can be effectively conducted. Notably, the generally more labile 2′-deoxyribonucleosides also undergo reaction. The reaction conditions can be tuned to yield either monoacetoxylated or diacetoxylated products predominantly. In the course of these investigations, a dimeric Pd^II-containing cyclopalladated C6 naphthylpurine derivative has been obtained and crystallographically characterized. This compound is competent in catalyzing the oxidization with PhI­(OAc)₂, indicating its plausible intermediacy in the chemistry. The X-ray structure of a monoacetoxylated product from this reaction has also been obtained

Modular, Metal-Catalyzed Cycloisomerization Approach to Angularly Fused Polycyclic Aromatic Hydrocarbons and Their Oxidized Derivatives

Palladium-catalyzed cross-coupling reactions of 2-bromobenzaldehyde and 6-bromo-2,3-dimethoxybenzaldehyde with 4-methyl-1-naphthaleneboronic acid and acenaphthene-5-boronic acid gave corresponding <i>o</i>-naphthyl benzaldehydes. Corey–Fuchs olefination followed by reaction with <i>n</i>-BuLi led to various 1-(2-ethynylphenyl)­naphthalenes. Cycloisomerization of individual 1-(2-ethynylphenyl)­naphthalenes to various benzo­[<i>c</i>]­phenanthrene (B<i>c</i>Ph) analogues was accomplished smoothly with catalytic PtCl₂ in PhMe. In the case of 4,5-dihydrobenzo­[<i>l</i>]­acephenanthrylene, oxidation with DDQ gave benzo­[<i>l</i>]­acephenanthrylene. The dimethoxy-substituted benzo­[<i>c</i>]­phenanthrenes were demethylated with BBr₃ and oxidized to the <i>o</i>-quinones with PDC. Reduction of these quinones with NaBH₄ in THF/EtOH in an oxygen atmosphere gave the respective dihydrodiols. Exposure of the dihydrodiols to <i>N</i>-bromoacetamide in THF-H₂O led to bromohydrins that were cyclized with Amberlite IRA 400 HO^– to yield the series 1 diol epoxides. Epoxidation of the dihydrodiols with <i>m</i>CPBA gave the isomeric series 2 diol epoxides. All of the hydrocarbons as well as the methoxy-substituted ones were crystallized and analyzed by X-ray crystallography, and these data are compared to other previously studied B<i>c</i>Ph derivatives. The methodology described is highly modular and can be utilized for the synthesis of a wide variety of angularly fused polycyclic aromatic hydrocarbons and their putative metabolites and/or other derivatives

Synthesis, Prediction, and Determination of Crystal Structures of (<i>R</i>/<i>S</i>)- and (<i>S</i>)‑1,6-Dinitro-3,8-dioxa-1,6‑diazaspiro[4.4]nonane-2,7-dione

Spiro-cyclic compounds frequently have screw-type symmetry (<i>C</i>₂) and are therefore optically active even though they do not contain an asymmetric carbon atom. (<i>R</i>/<i>S</i>)-1,6-Dinitro-3,8-dioxa-1,6-diazaspiro­[4.4]­nonane-2,7-dione is such a molecule. A blind crystal structure prediction study of structures containing one molecule in the asymmetric unit and considering all 230 space groups was undertaken using a dispersion-corrected density functional approach, which found a packing that matched the experimental structure of the (<i>R</i>/<i>S</i>) form as the lowest energy packing alternative. The densities of (<i>R</i>/<i>S</i>)<i>-</i> and (<i>S</i>)- or (<i>R</i>)-1,6-dinitro-3,8-dioxa-1,6-diazaspiro­[4.4]­nonane-2,7-dione calculated for the optimized experimental crystal structures confirmed that there is a small difference in the densities of the racemate and the optically active compound, with the optically active material being slightly more dense (1.875 versus 1.842 g/cm³). (<i>R</i>/<i>S</i>)-1,6-Dinitro-3,8-dioxa-1,6-diazaspiro­[4.4]­nonane-2,7-dione was synthesized as previously described. Synthesis of the pure (<i>S</i>)-stereoisomer was accomplished by resolution of the racemic dithiourethane using a previously described method, followed by reaction of the pure enantiomer with acetyl nitrate. The absolute configuration of the <i>l</i>-3,8-dioxa-1,6-diazaspiro­[4.4]­nonane-2,7-dithione was established as (<i>S</i>)- by redetermining the crystal structure at 150 K. The racemate crystallizes in space group <i>P</i>2₁/<i>n</i> with a density of 1.835 g/cm³ (296 K). The (<i>S</i>)-compound crystallizes in space group <i>P</i>2₁2₁2₁ with a density of 1.854 g/cm³ (296 K). This is the first demonstration of a difference in the density between the racemic mixture and the optically pure stereoisomer of an energetic material. It is also an apparent violation of Wallach’s rule, which states that racemic crystals tend to be denser than their optically active counterparts

Synthesis, Prediction, and Determination of Crystal Structures of (<i>R</i>/<i>S</i>)- and (<i>S</i>)‑1,6-Dinitro-3,8-dioxa-1,6‑diazaspiro[4.4]nonane-2,7-dione

Spiro-cyclic compounds frequently have screw-type symmetry (<i>C</i>₂) and are therefore optically active even though they do not contain an asymmetric carbon atom. (<i>R</i>/<i>S</i>)-1,6-Dinitro-3,8-dioxa-1,6-diazaspiro­[4.4]­nonane-2,7-dione is such a molecule. A blind crystal structure prediction study of structures containing one molecule in the asymmetric unit and considering all 230 space groups was undertaken using a dispersion-corrected density functional approach, which found a packing that matched the experimental structure of the (<i>R</i>/<i>S</i>) form as the lowest energy packing alternative. The densities of (<i>R</i>/<i>S</i>)<i>-</i> and (<i>S</i>)- or (<i>R</i>)-1,6-dinitro-3,8-dioxa-1,6-diazaspiro­[4.4]­nonane-2,7-dione calculated for the optimized experimental crystal structures confirmed that there is a small difference in the densities of the racemate and the optically active compound, with the optically active material being slightly more dense (1.875 versus 1.842 g/cm³). (<i>R</i>/<i>S</i>)-1,6-Dinitro-3,8-dioxa-1,6-diazaspiro­[4.4]­nonane-2,7-dione was synthesized as previously described. Synthesis of the pure (<i>S</i>)-stereoisomer was accomplished by resolution of the racemic dithiourethane using a previously described method, followed by reaction of the pure enantiomer with acetyl nitrate. The absolute configuration of the <i>l</i>-3,8-dioxa-1,6-diazaspiro­[4.4]­nonane-2,7-dithione was established as (<i>S</i>)- by redetermining the crystal structure at 150 K. The racemate crystallizes in space group <i>P</i>2₁/<i>n</i> with a density of 1.835 g/cm³ (296 K). The (<i>S</i>)-compound crystallizes in space group <i>P</i>2₁2₁2₁ with a density of 1.854 g/cm³ (296 K). This is the first demonstration of a difference in the density between the racemic mixture and the optically pure stereoisomer of an energetic material. It is also an apparent violation of Wallach’s rule, which states that racemic crystals tend to be denser than their optically active counterparts

Searching for Low-Sensitivity Cast-Melt High-Energy-Density Materials: Synthesis, Characterization, and Decomposition Kinetics of 3,4-Bis(4-nitro-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazole-2-oxide

The most comprehensive approach to analyze and characterize energetic materials is suggested and applied to enable rational, rigorous design of novel materials and targeted improvements of existing materials to achieve desired properties. We report synthesis, characterization of the structure and sensitivity, and modeling of thermal and electronic stability of the energetic, heterocyclic compound, 3,4-bis­(4-nitro-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazole-2-oxide (BNFF). The proposed novel, relatively simple synthesis of BNFF in excellent yields allows for an efficient scale up. Performing careful characterization indicates that these materials offer an unusual combination of properties and exhibit a relatively high energy density, high and controllable stability against decomposition, low melting temperature, and low sensitivity to initiation of detonation. First-principles calculations of activation barriers and reaction rate constants reveal the decomposition scenarios that govern the thermal stability and chemical behavior of BNFF, which appreciably differ from conventional nitro compounds. Details of the electronic structure and calculated electronic properties suggest that BNFF is an excellent candidate energetic material on its own and an attractive ingredient of modern energetic formulations to improve their stability and enable highly controllable chemical decomposition

Regiospecifically Fluorinated Polycyclic Aromatic Hydrocarbons via Julia–Kocienski Olefination and Oxidative Photocyclization. Effect of Fluorine Atom Substitution on Molecular Shape

A modular synthesis of regiospecifically fluorinated polycyclic aromatic hydrocarbons (PAHs) is described. 1,2-Diaryl­fluoroalkenes, synthesized via Julia–Kocienski olefination (70–99% yields), were converted to isomeric 5- and 6-fluorobenzo­[<i>c</i>]­phenanthrene, 5-and 6-fluorochrysene, and 9- and 10-benzo­[<i>g</i>]­chrysene (66–83% yields) by oxidative photocyclization. Photocyclization to 6-fluorochrysene proceeded more slowly than conversion of 1-styrylnaphthalene to chrysene. Higher fluoroalkene dilution led to a more rapid cyclization. Therefore, photocyclizations were performed at higher dilutions. To evaluate the effect of fluorine atom on molecular shapes, X-ray data for 5- and 6-fluorobenzo­[<i>c</i>]­phenanthrene, 6-fluorochrysene, 9- and 10-fluorobenzo­[<i>g</i>]­chrysene, and unfluorinated chrysene as well as benzo­[<i>g</i>]­chrysene were obtained and compared. The fluorine atom caused a small deviation from planarity in the chrysene series and decreased nonplanarity in the benzo­[<i>c</i>]­phenanthrene derivatives, but its influence was most pronounced in the benzo­[<i>g</i>]­chrysene series. A remarkable flattening of the molecule was observed in 9-fluorobenzo­[<i>g</i>]­chrysene, where the short 2.055 Å interatomic distance between bay-region F-9 and H-8, downfield shift of H-8, and a 26.1 Hz coupling between F-9 and C-8 indicate a possible F-9···H-8 hydrogen bond. In addition, in 9-fluorobenzo­[<i>g</i>]­chrysene, the stacking distance is short at 3.365 Å and there is an additional interaction between the C-11–H and C-10a of a nearby molecule that is almost perpendicular