A Catalytic Deprotection of S,S‐, S,O‐ and O,O‐Acetals Using Bi(NO3)3⋅5 H2O under Air

S,S‐Acetals are smoothly deprotected with air in the presence of a catalytic amount of Bi(NO₃)₃⋅5 H₂O (1–50 mol %) under ambient conditions to regenerate the original carbonyl compounds in good to excellent yield. This mild, simple, and environmentally benign system is successfully applied to the deprotection of S,O‐ and O,O‐acetals and is compatible with various functional groups. From the mechanistic study of the reaction, the catalytic cycle is considered to be composed of the following four steps: (1) the nitrososulfonium ion of the S,S‐acetal is formed by attack of nitrosonium ion (NO ⁺) generated from Bi(NO₃)₃⋅5 H₂O through the equilibrium with NO₂, (2) the nitrososulfonium ion is hydrolyzed to afford the hemithioacetal and thionitrite, (3) the hemithioacetal collapses to the original carbonyl compound and thiol, which is oxidized by NO ⁺ to give disulfide and NO via thionitrite, and (4) the NO captures molecular oxygen from air to regenerate NO₂.     

Synthesis and Characterization of 1,4‐Dimethyl‐5‐Aminotetrazolium 5‐Nitrotetrazolate

1,4‐Dimethyl‐5‐aminotetrazolium 5‐nitrotetrazolate ( 2 ) was synthesized in high yield from 1,4‐dimethyl‐5‐aminotetrazolium iodide ( 1 ) and silver 5‐nitrotetrazolate. Both new compounds ( 1, 2 ) were characterized using vibrational (IR and Raman) and multinuclear NMR spectroscopy (¹H, ¹³C, ¹⁴N, ¹⁵N), elemental analysis and single crystal X‐ray diffraction. 1,4‐Dimethyl‐5‐aminotetrazolium 5‐nitrotetrazolate ( 2 ) represents the first example of an energetic material which contains both a tetrazole based cation and anion. Compound 2 is hydrolytically stable with a high melting point of 190 °C (decomposition). The impact sensitivity of compound 2 is very low (30 J), it is not sensitive towards friction (>360 N). The molecular structure of 1,4‐dimethyl‐5‐aminotetrazolium iodide ( 1 ) in the crystalline state was determined by X‐ray crystallography: orthorhombic, F_ddd, a=1.3718(1) nm, b=1.4486(1) nm, c=1.6281(1) nm, V=3.2354(5) nm³, Z=16, ρ=1.979 g cm⁻¹, R₁=0.0169 (F>4σ(F)), wR₂ (all data)=0.0352.     

Synthesis and Highly Stereoselective Hydrogenation of the Statin Precursor Ethyl (5S)‐5,6‐Isopropylidenedioxy‐3‐oxohexanoate

A search for the large‐scale preparation of (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoates ( 2 ) – a key intermediate in the synthesis of pharmacologially important statins – starting from (S)‐malic acid is described. The synthesis of the required initial compound methyl (3S)‐3,4‐(isopropylidenedioxy)butanoate ( 1 ) by Moriwake’s reduction of dimethyl (S)‐malate ( 3 ) has been improved. Direct 2‐C chain elongation of ester 1 using the lithium enolate of tert‐butyl acetate has been shown to be successful at a 3‐ to 5‐fold excess of the enolate. Unfortunately, the product, tert‐butyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoate ( 2a ) is unstable during distillation. Ethyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐oxohexanoate ( 2b ) was prepared alternatively on a multigram scale from (3S)‐3,4‐(isopropylidenedioxy)butanoic acid ( 7 ) by activation with N,N′‐carbonyldiimidazole and subsequent reaction with Mg(OOCCH₂COOEt)₂. A convenient pathway for the in situ preparation of the latter is also described. Ethyl ester ( 2b ) can be advantageously purified by distillation. The stereochemistry of the catalytic hydrogenation of β‐keto ester ( 2b ) to ethyl (5S)‐5,6‐(isopropylidenedioxy)‐3‐hydrohyhexanoate (syn‐ 6 and anti‐ 6 ) has been studied using a number of homogeneous achiral and chiral Rh(I) and Ru(II) complexes with phosphine ligands. A comparison of Rh(I) and Ru(II) catalysts with (S)‐ and (R)‐BINAP as chiral ligands revealed opposite activity in dependence on the polarity of the solvent. No influence of the chiral backbone of substrate 2b on the enantioselectivity was noted. A ratio of syn‐ 6 /anti‐ 6 =2.3 was observed with an achiral (Ph₃P)₃RuCl₂ catalyst. Ru[(R)‐Tol‐BINAP]Cl₂ neutralized with one equivalent of AcONa afforded the most efficient catalytic system for the production of optically pure syn‐(5S)‐5,6‐isopropylidenedioxy‐3‐hydroxyhexanoate (syn‐ 6 ) at a preparative substrate/catalyst ratio of 1000:1.     

Molecular‐Weight‐Controlled Brittle‐to‐Semiductile‐to‐Ductile Transition in S‐(S/B)‐S Triblock Copolymers

Toughness enhancement of S‐(S/B)‐S triblock copolymers via a molecular‐weight‐controlled pathway is demonstrated. The post‐yield crack toughness behavior of the triblock copolymers uniquely reveal a brittle‐to‐semiductile‐to‐ductile transition with increasing while keeping the basic molecular architecture fixed. TEM and SAXS investigations indicated three distinct morphologies as a function of χ_effN as a consequence of the increase in : (i) a homogeneous structure without phase‐separation, (ii) a weakly segregated structure, and (iii) a lamellar structure. The increase in crack toughness is also reaffirmed from kinetic and strain field analysis studies concerning dynamics of crack growth in block copolymers with high PS content.

     

The High‐Pressure Characterization of Energetic Materials: 1,4‐Dimethyl‐5‐Aminotetrazolium 5‐Nitrotetrazolate

In‐situ high‐pressure room temperature synchrotron X‐ray diffraction and infrared microspectroscopy were used to examine the structural and vibrational properties and the equation of state of 1,4‐dimethyl‐5‐aminotetrazolium 5‐nitrotetrazolate (DMATNT). The X‐ray measurements show a smoothly varying pressure‐volume relationship to 20 GPa. However, the anisotropic ratios of the unit cell parameters reveal a discontinuity near 3.3 GPa, which can be attributed to an irreversible isostructural phase transition. A significant increase in the Infrared spectral intensity near this pressure coupled with Dayvdov splitting of the NO₂ bending and scissoring modes suggest the transition results in a skewing of the NO₂ groups and increasing asymmetry of the hydrogen bonding sublattice.     

Energetic Salts of 5‐(5‐Azido‐1H‐1,2,4‐triazol‐3‐yl)tetrazole

Several metal and nitrogen‐rich salts of the recently presented 5‐(5‐azido‐1H‐1,2,4‐triazol‐3‐yl)tetrazole (AzTT), including silver ( 1 ), copper(I) ( 2 ), potassium ( 3 ), cesium ( 4 ), copper(II) ( 7 ), ammonium ( 8 ), and guanidinium ( 9 ), as well as the respective double‐salts of 3 , 4 , 8 and 9 , were prepared and well characterized by IR and multinuclear (¹H, ¹³C, ¹⁴N) NMR spectroscopy, DSC, mass spectrometry, elemental analysis and one ( 4 ) additionally by single‐crystal X‐ray diffraction. The sensitivities towards impact, friction and electrostatic discharge were determined according to BAM standards, revealing most of the metal salts as highly sensitive and the nitrogen‐rich salts as insensitive. The metal salts were further tested for their ability of being primary explosives.     

Ga2S3‐Sb2S3‐CsI chalcohalide glasses for mid‐infrared applications

In this study, a new chalcohalide glass system, Ga₂S₃‐Sb₂S₃‐CsI, is reported. It has a glass‐forming domain composed of ~0‐35 mol% Ga₂S_3, ~15‐95 mol% Sb₂S₃, and ~0‐55 mol% CsI. The glasses have a wide transparent window of ~0.7‐13.5 μm, high third‐order nonlinear refractive indices of ~1.7‐8.7×10^?14 cm²/W @ 1.55 μm, and relatively short zero group‐velocity‐dispersion wavelengths of 3.8‐5.15 μm. The glasses can dissolve more than 2 mol% active ions (e.g., Dy³⁺), and the doped glasses show intense emissions in the mid‐infrared. These superior properties demonstrate their good potentials for mid‐infrared applications such as thermal imaging, nonlinear photonics and lasers.     

Flexible and flame‐retardant S‐SEB‐S triblock copolymer/PPE nano‐alloy

We observed that modified polyphenylene ether (PPE) was solubilized in thermoplastic styrenic elastomer (TPS) and that a two‐phase lacy structure formed on nanometer scales when the TPS composition was 67 wt % and modified PPE and polystyrene‐block‐poly(styrene‐co‐ethylene‐co‐butylene)‐block‐polystyrene (S‐SEB‐S triblock copolymer) were blended. However, the molecular weight of the outer PS block segments M_outPS and the content of the outer PS block segments ?_outPS were <10,000 g/mol and 20 wt %, respectively. The resulting S‐SEB‐S/modified PPE nano‐alloy exhibited both flexibility and flame retardancy, unlike other materials, where a trade‐off exists between these two properties; that is, the flame retardancy was excellent when the phosphorus additive was present. This combination of properties might be attributed to the two‐phase nanometer‐scale structure consisting of flame‐retardant styrene/PPE domains and a continuous soft, lacy SEB matrix. The results for polystyrene‐block‐poly(ethylene‐co‐butylene)‐block‐polystyrene (S‐EB‐S triblock copolymer)/modified PPE blends were presented for comparison. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40446.     

Zur physikalisch‐chemischen Charakterisierung von 5‐Amino‐1‐aryl‐1H‐tetrazolen: Elektronische Molekülparameter aus der thermischen Isomerisierung zu 5‐Arylamino‐1H‐tetrazolen

The known thermal isomerization of 5‐amino‐1‐aryl‐1H‐tetrazoles ( A ) into corresponding 5‐arylamino‐1H‐tetrazoles ( HB ) was used to derive physicochemical parameters characterizing the electronic substituent effect on isomerism and dissociation equilibria. For a series of 26 tetrazoles A as starting materials the equilibrium constants (pK_i) of isomerization in boiling ethylene glycol at 197 °C and the dissociation constants (pK_a) of the NH‐acidic tetrazoles HB were determined by potentiometric titration of rapidly cooled equilibrium mixtures in water and ethanol/water with KOH at 25 °C. The pK values are closely correlated with Hammett′s electronic substituent constants σ and can be used as electronic molecule parameters in QSAR or QSPR (QSAR = quantitative structure‐activity relationship; QSPR = quantitative structure‐property relationship) studies.     

Synthesis, σ Receptor Affinity,and Pharmacological Evaluation of 5‐Phenylsulfanyl‐ and 5‐Benzyl‐Substituted Tetrahydro‐2‐benzazepines

In accordance with a novel strategy for generating the 2‐benzazepine scaffold by connecting C6–C1 and C3–N building blocks, a set of 5‐phenylsulfanyl‐ and 5‐benzyl‐substituted tetrahydro‐2‐benzazepines was synthesized and pharmacologically evaluated. Key steps of the synthesis were the Heck reaction, the Stetter reaction, a reductive cyclization, and the introduction of diverse N substituents at the end of the synthesis. High σ₁ affinity was achieved for 2‐benzazepines with linear or branched alk(en)yl residues containing at least an n‐butyl substructure. The butyl‐ and 4‐fluorobenzyl‐substituted derivatives, (±)‐5‐benzyl‐2‐butyl‐2,3,4,5‐tetrahydro‐1H‐2‐benzazepine ( 19 b ) and (±)‐5‐benzyl‐2‐(4‐fluorobenzyl)‐2,3,4,5‐tetrahydro‐1H‐2‐benzazepine ( 19 m ), show high selectivity over more than 50 other relevant targets, including the σ₂ subtype and various binding sites of the N‐methyl‐D ‐aspartate (NMDA) receptor. In the Irwin screen, 19 b and 19 m showed clean profiles without inducing considerable side effects. Compounds 19 b and 19 m did not reveal significant analgesic and cognition‐enhancing activity. Compound 19 m did not have any antidepressant‐like effects in mice.     

Optically Active 4‐Substituted (S)‐2‐Phenyl‐2‐oxazolines

(R)‐4‐Hydroxymethyl‐2‐phenyl‐2‐oxazoline (R)‐ 1 ) was prepared from (L)‐serine. The respective tosylate ((S)‐ 2 ) was converted into sulfides (S)‐ 4 and (S)‐ 5 , and sulfone (S)‐ 6 , useful starting materials for the elaboration of additional chiral centers. A previously reported [ α]_D ²⁵ value for (R)‐ 4 is corrected.     

Synthesis and Characterization of the R27S Genetic Variant of Insulin‐like Peptide 5

We report the synthesis and in vitro bioactivity assessment for an insulin‐like peptide 5 (INSL5) analogue that was recently discovered as a genetic mutation in an Amish population. The mutation was associated with improved metabolic status, and receptor‐based antagonism was proposed as a potential mechanism for the altered phenotype. We determined the specific peptide analogue to be fully potent and of maximal efficacy at the human relaxin family peptide receptor 4 (RXFP4), suggesting an alternative basis for the observed effect. In preparation of this synthetically challenging hormone, we have introduced several improvements such as implementation of isoacyl chemistry for high‐efficiency preparation of INSL5 B‐chain and selective intramolecular A6‐11 disulfide formation as a first step in sequential disulfide assembly.     

Copper(I)‐Catalysed Multicomponent Reaction: Straightforward Access to 5‐Hydroxy‐1H‐pyrrol‐2(5H)‐ones

A copper‐catalysed multicomponent coupling reaction between readily available (Z)‐3‐iodoacrylic acids, terminal alkynes, and primary amines was developed to smoothly access a small library of 5‐hydroxy‐1H‐pyrrol‐2(5H)‐ones in good yields. This practical and general process was applied to a short‐steps synthesis of the natural product pulchellalactam.

     

Synthesis and Characterization of 1‐Nitroguanyl‐3‐nitro‐5‐amino‐1,2,4‐triazole

The synthesis of 1‐nitroguanyl‐3‐nitro‐5‐amino‐1,2,4‐triazole (ANTA‐NQ) ( 1 ) with good yield and high purity is described. DSC analysis showed that the material displays good thermal stability. An X‐ray crystallographic analysis confirms the structure of this material, as well as displays intramolecular hydrogen bonding. A gas pycnometry density for this material was measured to be 1.79 g cm⁻³. The heat of formation of this material was also measured. These data, along with the molecular formula were used as inputs to calculate the detonation velocity and detonation pressure using the Cheetah thermochemical code. The sensitivity of this material towards impact, spark and friction was also measured, as well as its vacuum thermal stability. The 3‐azido derivative 2 was also prepared and its properties are described as well. The above data show that (ANTA‐NQ) may be a high performing material with low sensitivity and good thermal stability.     

Vapor‐Phase Transport Crystallization of Micro‐HZSM‐5 Zeolite Coatings

A novel structured catalyst of binderless micro‐HZSM‐5 zeolite coating was prepared on stainless‐steeled tubes (i.d. 2 mm) through wash coating and vapor‐phase transport (VPT) crystallization method. The subsequent crystallization of amorphous SiO₂ binders improved the coatings adhesion tremendously by more than 10 times with the least amount of binders (<20% by weight), attributed to the remarkably enhanced interlock by the formed Mordenite Framework Inverted structure between zeolite particles. Catalytic cracking of supercritical n‐dodecane (500°C, 4 MPa) was used to examine the catalytic performance of the coatings as prepared, indicating that MZC‐V0.2 exhibited a catalytic activity improvement by 8% and a decreased deactivation rate by 48%. The improved catalytic performance may result from its high acid sites amount by incorporating extra‐framework Al into HZSM‐5 framework, and the possible depressing of pore‐mouth deactivation through partial modification of surface acid sites during VPT treatment. This work provides a potential technique to prepare mechanically stable zeolite coatings with high catalytic activity but less binder usage.     

Structure–Activity Relationships of Quinoxaline‐Based 5‐HT3A and 5‐HT3AB Receptor‐Selective Ligands

Until recently, discriminating between homomeric 5‐HT₃A and heteromeric 5‐HT₃AB receptors was only possible with ligands that bind in the receptor pore. This study describes the first series of ligands that can discriminate between these receptor types at the level of the orthosteric binding site. During a recent fragment screen, 2‐chloro‐3‐(4‐methylpiperazin‐1‐yl)quinoxaline (VUF10166) was identified as a ligand that displays an 83‐fold difference in [³H]granisetron binding affinity between 5‐HT₃A and 5‐HT₃AB receptors. Fragment hit exploration, initiated from VUF10166 and 3‐(4‐methylpiperazin‐1‐yl)quinoxalin‐2‐ol, resulted in a series of compounds with higher affinity at either 5‐HT₃A or 5‐HT₃AB receptors. These ligands reveal that a single atom is sufficient to change the selectivity profile of a compound. At the extremes of the new compounds were 2‐amino‐3‐(4‐methylpiperazin‐1‐yl)quinoxaline, which showed 11‐fold selectivity for the 5‐HT₃A receptor, and 2‐(4‐methylpiperazin‐1‐yl)quinoxaline, which showed an 8.3‐fold selectivity for the 5‐HT₃AB receptor. These compounds represent novel molecular tools for studying 5‐HT₃ receptor subtypes and could help elucidate their physiological roles.