Synthesis of Unique Phosphazane Macrocycles via Steric Activation of C-N Bonds.

Herein we describe that oxidation reactions of the dimeric cyclophosphazanes, [{P(µ-NR)}2(µ-NR)]2, R = tBu (1), to produce a series of diagonally dioxidized products P4(µ-N tBu)6E2 [E = O (2), S (3), and Se (4)] and tetraoxidized frameworks. The latter display an unexpected C-N bond activation and cleavage to produce a series of novel phosphazane macrocyclic arrangements containing newly formed N-H bonds. Macromolecules P4(µ-N tBu)4(µ-NH)2O4 (5) and P4(µ-N tBu)3(µ-NH)3E4, E = S (6) and Se (7), dicleaved and tricleaved products, respectively, are rare examples of dimeric macrocycles containing NH bridging groups. Our theoretical and experimental studies illustrate that the extent to which these C-N bonds are cleaved can be controlled by modification of steric parameters in their synthesis, by adjusting either the steric bulk of the substituents in the parent framework or the size of the chalcogen element introduced during the oxidation process. Our findings represent new synthetic pathways for the synthesis of otherwise-elusive macrocycle arrangements within the phosphazane family.

Mechanochemical Synthesis of Phosphazane-Based Frameworks.

Mechanochemistry is emerging as a powerful solvent-free approach to chemical synthesis, having been applied to metal oxides, pharmaceutical materials, organic compounds and to a lesser extent, coordination complex synthesis. Notably, examples of applications of mechanochemical methodologies in the synthesis of main-group compounds are few and far between. Herein, we demonstrate that ball milling enabled the solvent-free synthesis of a range of phosphazane frameworks with a broad substrate scope, yielding seven new acyclic and macrocyclic species. The strength of this methodology is highlighted by a fast, selective and high-conversion product generation from poorly soluble starting materials, thereby demonstrating mechanochemistry as a real alternative to solution-based methods in synthetic main-group chemistry.

The First Synthesis of the Sterically Encumbered Adamantoid Phosphazane P4 (N(t) Bu)6 : Enabled by Mechanochemistry.

All reported attempts to synthesize the tert-butyl-substituted adamantoid phosph(III)azane P4 (N(t) Bu)6 have failed, leading to the classification of this molecule as inaccessible and a literature example of steric control in chemistry of phosphorus-nitrogen compounds. We now demonstrate that this structure is readily accessible by a solvent-free mechanochemical milling approach, highlighting the importance of mechanochemical reaction environments in evaluating chemical reactivity.

Synthesis and Hydrolytic Studies on the Air-Stable [(4-CN-PhO)(E)P(µ-N(t)Bu)]2 (E = O, S, and Se) Cyclodiphosphazanes.

Reaction of 4-CN-PhOH with [ClP(µ-N(t)Bu)]2 (1) (2:1 ratio) in the presence of Et3N produced the functionalized cyclodiphosph(III/III)azane [(4-CN-PhO)P(µ-N(t)Bu)]2 (2). Oxidation of 2 produced cyclodiphosph(V/V)azanes [(4-CN-PhO)(E)P(µ-N(t)Bu)]2 [E = O (3), S (4), and Se (5)]. This is the first example of a series of cyclodiphosph(V/V)azane derivatives obtained from a single cyclophosph(III/III)azane precursor where all the accessible chalcogen oxidized products are air-stable over prolonged periods of time.

Steric C-N bond activation on the dimeric macrocycle [{P(µ-NR)}2(µ-NR)]2.

Dimeric cyclophosphazanes [{P(µ-NR)}2(µ-NR)]2 [R = (t)Bu ( 1) and iPr ( 3)] were oxidized with elemental selenium. During these reactions an unexpected C­N bond cleavage and N­H bond formation occurred. Compound 1 produced P4(µ-N(t)Bu)3(µ-NH)3Se4 ( 2) where three tBu groups were lost in the form of isobutylene. In contrast, during the oxidation of the less sterically hindered 3, the resulting product, P4(µ-N(i)Pr)5(µ-NH)Se4 ( 4), showed only one substituent loss. Theoretical studies confirmed the steric nature of the driving force underlying the different outcomes.

Primary malignant pulmonary tumors in children: a review of the national cancer data base.

BACKGROUND: The purpose is to delineate the clinical and pathological characteristics of rare primary malignant pulmonary tumors in children. METHODS: Utilizing the National Cancer Data Base (NCDB), we analyzed all children (≤ 18 years) with a primary malignant pulmonary tumor from 1998 to 2011 to identify factors associated with better survival. RESULTS: Of 211 children identified, the most common histology was carcinoid tumor (n=133, 63%) followed by mucoepidermoid carcinoma (MEC) (n=37, 18%), squamous cell carcinoma (SCC) (n=19, 9%), adenocarcinoma (n=16, 8%), bronchoalveolar carcinoma (BAC) (n=4, 2%), and small cell carcinoma (SCLC) (n=2, <1%). Factors that significantly affected survival include histology, race, tumor size, lymph node status, and extent of surgery. Patients with MEC and carcinoid tumors had a better overall survival compared to patients with other histologies (p<0.0001). The 5-year overall survival for MEC and carcinoid tumors was 100% and 95% (95% CI 87-98), respectively, versus 50% (95%CI 1-91) for BAC, 28% (95%CI 9-52) for SCC, and 26% (95%CI 5-55) for adenocarcinoma. CONCLUSION: The majority of pediatric patients with a primary malignant pulmonary tumor present with carcinoid tumor or MEC and have an excellent prognosis. Lung cancers which are common in adults, but rare in children, have a worse prognosis.