Generation of 6-(Trifluoromethyl)-4,5-dihydro-2(3H)-pyridone and the Application to Synthesis of Some Fused Nitrogen Heterocycles Carrying a Trifluoromethyl Group on the Bridgehead Position via Radical Cyclization of Dihydropyridones

Staudinger/aza-Wittig reaction of 6,6,6-trifluoro-5-oxohexanoyl azide with PPh(3) or PBu(3) was examined. A reactive intermediate acyl imine 1 was trapped by methanol. Without nucleophile, isomerized enamide form 3 was obtained. N-Iodobenzoylation and N-haloalkylation of 3 and following radical cyclization via the 5-exo or 6-exo mode gave benzoindolizidinone, indolizidinone, and quinolizidinone derivatives 10-14, which have a trifluoromethyl group at the bridgehead position adjacent to nitrogen. Although LiAlH(4) reduction of 10 and 11 gave a mixture of saturated benzoindolizidine 15 and amino alcohol 16, reduction with BH(3)/THF selectively gave the desired 15 and indolizidine 17 from 13.     

High throughput continuous titration based on a flow ratiometry controlled with feedback-based variable triangular waves and subsequent fixed triangular waves

We propose a new approach for high-throughput continuous titration based on a flow ratiometry. The method was applied to potentiometric titrations of acids and bases. A base solution, the flow rate F_B of which was varied in response to controller output voltage V_c, was merged with an acid solution under constant total (acid + base) flow rate. Downstream, the pH of the mixed solution was measured with a flow-through glass electrode. Initially, V_c, and thus F_B was increased linearly. At the instant the equivalence point (EP) was sensed, the ramp direction of V_c was reversed from upward to downward. The direction was reversed to upward when EP was sensed again. Such the feedback-based operation gives a triangular waveform of V_c, because there is a delay corresponding mainly to the transit time of merged solutions to reach the sensor. The value of V_c that gives EP composition, V_E, was estimated by averaging the most recent maximum and minimum values of V_c. Next, fixed triangular waves of V_c was used to control F_B. The amplitude and the scan rate of the waves were fixed narrower and faster, respectively, than those in the feedback-based operation in order to improve the throughput rate. The EP can be located as long as the scan range covers V_E. These automated processes limited the titration to just the narrow range around EP, and thus realized extremely high throughput rate of maximally 17.6 titrations per minute (=3.4 s per titration) at R.S.D. = 0.35%.     

Total synthesis and absolute stereochemistry of pentenocin B, a novel interleukin-1 beta converting enzyme inhibitor

Four possible diastereomers of pentenocin B were synthesized in a stereocontrolled manner, and the first total synthesis of a natural enantiomer of (+)-pentenocin B unequivocally established the absolute stereochemistry to be 4S,5R,6R.     

Calculation of vertical ionization potentials of difluoramine by perturbation corrections to koopmans' theorem

The vertical ionization potentials of difluoramine are calculated by perturbation corrections to Koopmans' theorem. The calculation shows that difluoraimine has three overlapping bands between 15 and 16 eV. The calculated results compare well with the experimental values. The photoelectron spectrum of difluoramine is compared with that of OF₂ and CH₂F₂.     

Synthesis of polyamides by the polyaddition of bisimidazoline with dicarboxylic acids

N,N′-Dipropionylethylenediamine was synthesized by the ring-opening addition reaction of 2-ethyl-2-imidazoline with propionic acid at 220°C. By applying this reaction to polymerization, polyamides were synthesized by the ring-opening polyaddition reaction at 220°C. of 1,4-bis(imidazoline-2-yl)butane with adipic acid, succinic acid, sebacic acid, and terephthalic acid. The reaction product of 1,4-bis(imidazoline-2-yl)butane with adipic acid, which was proposed to be nylon 26, was compared with an authentic sample of nylon 26 and shown to possess a very similar infrared spectrum and melting point.     

Short and flexible route to 3,4-diarylpyrrole marine alkaloids: syntheses of permethyl storniamide A, ningalin B, and lamellarin G trimethyl ether

A highly efficient route to 3,4-diarylpyrrole marine alkaloids has been developed using Hinsberg-type pyrrole synthesis and palladium-catalyzed Suzuki cross-coupling of the 3,4-dihydroxypyrrole bis-triflate derivatives as key reactions. Based on this approach, formal syntheses of permethyl storniamide A and ningalin B, and a total synthesis of lamellarin G trimethyl ether have been achieved.     

Observation and analysis of single DNA nano-kinetics by pin-fiber video scope

The nano-kinetic movement of a single DNA molecule was observed and analyzed by a newly developed video-microscope system with an optical fiber, called a pin-fiber video scope. A single lambda-DNA molecule was put in focus using fiber-illumination, and the stretching and shrinking motion was measured. The molecule's kinetics were analyzed by numerical calculations and are discussed. A photocleavage phenomenon of DNA molecules was also visualized by the pin-fiber video scope. The new video-microscope system has the potential to observe and analyze the nano-kinetics of a single molecule.     

Uniaxial alignment of the smallest diamagnetic susceptibility axis using time-dependent magnetic fields

A diamagnetic particle with magnetic susceptibilities chi3 < chi2 = chi1 < 0 was subjected to a rotating magnetic field to obtain an alignment of the chi3 axis (the smallest susceptibility axis) in the direction perpendicular to the plane of the rotating magnetic field. A polymer short fiber, whose fiber axis coincides with the chi3 axis, was suspended in a fluid with the same density, and then a rotating magnetic field generated by a rotation of a pair of permanent magnets was applied. The fiber axis, rotating following the applied field, finally ended up with an alignment perpendicular to the plane of the rotating magnetic field. The experimental data on the time course of the alignment was in good agreement with the numerical calculation based on the equation of rotation.     

Theoretical study of photochemical reactions: Electron assignment and the state correlation diagram

A general way for drawing the state correlation diagram and seeking the reaction path is presented. If a high-symmetry reacting system is given, its least-motion path that maintains the symmetry is primarily examined. For a given state, it is judged whether the least-motion path is symmetry allowed or forbidden. If allowed, it is called the direct process. If forbidden, the symmetry imposed on the system should be relaxed, resulting in the mixing of MO 's. Then, the energy barrier of the avoided crossing for some excited states is removed and the possible reaction path is found. After this procedure, the symmetry-allowed paths may be sought by the geometry optimization with a suitable wave function. By the use of such a procedure, the dissociation of diazomethane and (3H-)diazirine is found to proceed via the C_s and C₂ symmetries.