Synthesis secondary amines via 1,2-addition of organometallic reagents to N-diphenylphosphlnylimines and subsequent alkylation

신현순 Drexel University 2001 해외박사

Part A Stereoselectively protected secondary amines are prepared by reduction of a variety of substituted cyclohexyl N-diphenyphosphinylcyclohexylidineimines with lithium-tri-sec-butylborohydride approach of which is found to occur from the less sterically hindered equatorial face leading to the corresponding axial lithium anions, followed by the treatment with methyl iodide. In the same way, the stereoselectively protected secondary amines are prepared by alkylation of the corresponding axial/equatorial lithiated anions, which are produced from stereoselectively formed axial and equatorial substituted N-diphenylphosphinylcyclohexylamines reduced by L-selectride or t-butylamine-borane complex, respectively under basic conditions such as n-butyl lithium or KHDMS yielded the corresponding lithium anions which were reacted with alkyl halides to afford the corresponding stereoselectively protected N-alkylated secondary amines. Part B Alkylation of N-diphenylphosphinyl imines is a direct and facile route for obtaining the protected secondary N-diphenylphosphinylamines. The addition of organolithium to N-diphenylphosphinylimines formed the anion of N-diphenylphosphinyl amides which can serve as nucleophiles. The subsequent alkylation of the anion of N diphenylphosphinyl amides with alkyl halides provided the corresponding alkylated N diphenylphosphinyl amides. The synthesis of simple protected secondary amines which were produced from N-diphenylphosphinyl aldehyde imines were used as electrophiles to react with orgnometallic reagents such as n-BuLi, PhLi, and CH₃Li to form the anion which was alkylated to the corresponding amides by treatment with alkyl halides.

광학활성 염기를 이용한 Asymmetric deprotonation에 관한 연구

장문희 淑明女子大學校 1994 국내석사

As increasing the demand for development of new drug, synthesis of biologically active compounds play an important role in organic synthetic field. Because of inherent nature of enzyme and receptor in biological system, we should synthesize the biologically active compound in the optically active form. Our project embrace the direct synthesis of chiral ketones and their enolate from racemic or mesomeric ketones with chiral bases to effect enantioselective deprotonation. In future, it is expected that biologically active compounds are synthesized by application of this methodology.

Structural Effect on Electrochemical Performance of 4,4’-Biphenyldicarboxylate Sodium Salts as an Anode for Na-ion Batteries

Aram Choi Graduate School of UNIST 2014 국내석사

The crystal structures and electrochemical performance of 4,4’-biphenyldicarboxylate sodium salts is first introduced as an anode for Na-ion batteries. The structural modification of 4,4’-biphenyldicarboxylate sodium salts showing different degree of deprotonation and the coordination of a water molecule are deliberately accomplished through various precipitation and solvothermal methods, resulting in the formation of three different crystal structures even though they are composed of the same organic (bpdc) and inorganic (Na+) building blocks. The crystal structures are determined by single-crystal X-ray diffraction. The powder X-ray diffraction patterns showed the good agreement with the corresponding simulated patterns, indicating that the phase pure powders have the same crystal structure as the single crystals. The level of deprotonation in 4,4’-biphenyldicarboxylate sodium salts affects not only electrochemical performance but also reaction mechanisms. The fully deprotonated 4,4’-biphenyldicarboxylate disodium salt (Na2bpdc) exhibits promising electrochemical performance including reversible capacity of 220 mA h g-1 at ca. 0.5 V vs. Na/Na+, negligible capacity fading over 150 cycles, and excellent rate performance delivering about 100 mA h g-1 even at a 20C rate, which is better than monosodium 4,4’-biphenyldicarboxylate (NaHbpdc) that is partially deprotonated. This better rate performance of Na2bpdc salts is definitely attributed to the smaller particle size (short diffusion length) of that compared to NaHbpdc. However, even the dehydrated disodium 4,4’-biphenyldicarboxylate monohydrate (h-Na2bpdc) having similar size to NaHbpdc exhibited better rate performance than NaHbpdc. This means that the rate performance is affected by the degree of deprotonation in 4,4’-biphenyldicarboxylate sodium salts. Carboxylic group causes the large amount of electrolyte decomposition to form thick solid electrolyte interphase (SEI) layers, resulting in the increase of polarization due to large charge-transfer resistance. Also, the de/sodiaiton of Na2bpdc salts proceeds in a two-phase reaction, regardless of the degree of deprotonation. And, the amorphization of Na2bpdc salts occurred during cycling, even though the crystal structure is maintained. However, unlike the fully deprotonated showing reversible phase transition during sodiation and desodiation, the partially deprotonated exhibits irreversible phase transition during cyclings. It seems to be occurred the partially phase transition to Na2bpdc which is fully deprotonated due to the ion-exchange between Na+ and H+.

음이온 수용체에서 C-H 수소결합의 역할에 대한 연구

최유선 세종대학교 일반대학원 2015 국내석사

음이온은 생물학적, 의학적 그리고 환경학적 측면에서 매우 중요한 역할을 한다. 그러므로 음이온 수용체에 대한 연구는 다양한 음이온의 검출 및 정량 등을 가능하게 하기 때문에 중요하다. 본 연구에서는 음이온과 수소결합을 통해 결합할 수 있는 수용체를 설계 및 합성 후, titration을 통해 결합상수와 작용기에 따른 결합 경향을 파악하였다. 또한 DFT 계산을 통해 polarization에 따른 결합력 차이도 알아보았다. [part 1]에서는 hydrazone을 binding subuint으로 하는 receptor 1, 2를 합성하였으며, 각각 nitrophenyl기와 phenyl기를 포함하고 있어 nitro group의 유무에 따른 결합력 차이를 확인하였다. 또한 hydrazone의 N-H 수소뿐만 아니라 C-H 수소 역시 결합에 참여한다는 것을 NMR titration을 통해 증명하였다. 그리고 색 변화를 통해 deprotonation 경향을 파악할 수 있었고, 이를 통해 컬러 센서로서의 활용 가능성을 확인할 수 있었다. [part 2]에서는 aromatic ring에 작용기를 달리하여 극성을 다르게 하여 합성한 후, 수용체와 음이온과의 결합력을 비교하였다. 각각 N-methylpyridinium, nitrobenzene, benzene이 포함되어 있는 receptor 3, 4, 5를 합성하여 polarization에 따른 결합력 차이를 확인하였다. 또한 DFT 계산을 통해 이를 증명하였다. 본 연구는 기존에 알려져 있던 N-H 수소에 의한 수소결합뿐만 아니라 C-H 수소에 의한 수소결합을 관찰했다는 것에 의의가 있다. 또한 [part 1]의 경우는 deprotonation현상에 의해 색이 노랑색 - 초록색 - 파랑색 순서로 변화하는 것을 이용하여 육안으로 음이온을 검출하는데 이용할 수 있을 것으로 생각된다. 이러한 연구들을 응용하여 유기용매에서 뿐만 아니라 수용액 상에서 적용할 수 있게끔 개량이 이루어진다면 생물학적, 환경적, 화학적인 음이온 센서로의 응용이 가능해 질 것으로 기대된다.

Quinizarin-based simple and convenient colorimetric sensor for carbon dioxide

성민석 서울대학교 대학원 2017 국내석사

Abstract Quinizarin-based Simple and Convenient Colorimetric Sensor for Carbon Dioxide MinSeok Seong Department of Materials Science and Engineering The Graduate School Seoul National University In search of simple and fast method to estimate the concentration of atmospheric carbon dioxide, the quinizarin and TBD system was discovered and its mechanism was studied and the applications were tried. From UV-VIS spectrum, the reason behind the change in color of the solution was found to be the different electronic forms of quinizarin. In other words, the color of the quinizarin solution was orange yellow when quinizarin was neutral while its color changed to purple once mixed with TBD as a result of deprotonation. Also, the molar ratio of quinizarin to TBD was 1 to 1 because there was no increase in the strength of the absorption band when TBD was excessive whilst there was a decrease when TBD was deficit. Also, the shift of the absorption band was observed as a result of TBD binding with carbon dioxide and giving back protons to quinizarin. From 1H-NMR spectrum, the hydroxyl proton of quinizarin was observed initially but it was soon given to TBD. Also, the fact that TBD bound itself with carbon dioxide was verified by the 13C-NMR spectrum as a new peak was observed at 161 ppm. In assistance with FT-IR spectrums, the proposed mechanism was supported once more. Quinizarin loses a proton to TBD and the protonated TBD loses the proton as it binds with carbon dioxide. As a result, the color of the solution changed from purple to yellow. The intensity of the vibrational modes for the corresponding functional groups changed accordingly; N-H bond decreased and O-H bond increased. For the experimental parts, the saturation volume of carbon dioxide was studied; the total volumetric capacity of the detecting system at different concentrations were measured and it was used to estimate the approximate response time and detectable concentration of carbon dioxide for each concentration of the system. The response time of the system at given concentration of carbon dioxide was figured out in the next step. As predicted, the system with lower concentrations of the chemicals had a shorter response time. However, the systems with the other organic bases such as DBU and piperidine were found to be not fast enough to detect the concentration of carbon dioxide fast compared to the system with TBD at the same concentration. Most importantly, the system could be recycled for at least 3 to 5 times and the performance was maintained relatively well. The system could actually be re-used upto 10 times but it became harder and harder to notice the color change when re-used too many times. Known the properties of the system as sensor, new applications were tried.. For solidification, TBD was physically fixed onto silica and it was successfully done. Nextly, the solid TBD was dipped in the quinizarin solution to become blue. Although the system was seemingly ready, it was not be able to interact with the atmospheric carbon dioxide and did not undergo any color change. Obviously, the solid system failed to interact with carbon dioxide because of too high thermodynamic barrier between solid and gas. The other option was an Agarose gel technique. The quinizarin and TBD solution was made and mixed with hot agarose solution and cooled down. However, the gel had too much viscosity so the response time was significantly increased. Keywords: Carbon dioxide, Chemical dye, Organic base, Protonation, Deprotonation, Adduct, Colorimetric sensor, Student Number: 2015-20829

Benzoylphenylacetate 유도체의 Deprotonation 메카니즘과 제초제로서의 응용 가능성에 관한 연구

김성은 建國大學校 大學院 1996 국내석사

In this study, benzoylphenylacetate derivatives were synthesized as new herbicide candidates. Most of all, We are analyzed the 3D structure of acetyl CoA carbxylase (Accase) inhibitors such as modified aryloxyphenoxypropionate by nsing computer molecular modeling programs. Also, the deprotonation mechanism of carbon acids was studied by analyzing the ESR signals from 77K to 273K matrix.

Synthesis of various expanded porphyrins and studies on their spectroscopic properties

차원영 Graduate School, Yonsei University 2017 국내박사

새로운 확장고리 포르피린 분자체의 합성과 그들의 효과적인 (반)방향성 조절은 많은 유기· 물리 화학자들의 관심사였다. 현재까지는 확장고리 포르리핀 분자체의 내부에 금속 이온의 삽입, 온도 변화, 용매의 변화, 산 첨가에 의한 분자구조와 전자구조 사이의 관계를 밝히는데 방향성이라는 주제가 주로 접목되었다. 최근에는 확장고리 포르피린의 분광학적 물성의 조절이 용이함을 바탕으로, 기초연구의 영역을 넘어 에너지 산업, 전자 산업, 디스플레이 산업, 신소재 산업 등에 새로운 해결책을 제시 할 미래의 핵심과학기술 분야로서 다양한 포르피린 분자체가 주목을 받고 있다. 이에 이 논문에서는 확장고리 포르피린 분자들 ([26]헥사피린, [32]헵타피린, [36]옥타피린, 분자다리 삽입된 [34]옥타피린)의 탈 양성자화 반응, 산화 반응 등을 이용하여 각각의 분자구조 변화와 그에 따른 분광학적 성질변화를 확인하고 이론적으로 증명하여 확장고리 포르피린 계열 분자를 능동적으로 조절하는데 초점을 맞추었다. 헥사피린, 헵타피린, 그리고 옥타피린의 양성자를 제거하였을 때 나타나는 각각의 휴켈 방향성의 증감, 뫼비우스 방향성의 증가, 구조적으로 안정한 휴켈 반방향성 분자체의 실현 등을 고체상태 구조분석, 분광학적 실험, 다양한 양자역학적 계산을 통하여 연구하였다. 흥미롭게도, 양성자가 제거된 헥사피린에서는 이례적으로 상위 들뜬 상태에서 형광을 내는 현상도 연구할 수 있었다. 마지막으로, 하나의 유기 분자체 내에서 두 종류의 독립적인 방향성 고리 전류를 생성시키기 위한 유기분자를 디자인 하였고, 합성에 성공하였으며 양성자 핵자기공명법, 정류상태 흡광법, 그리고 양자역학적 계산 등을 이용하여 그 가능성을 과학적으로 증명하였다. 위의 연구들을 통하여 다양한 분자 시스템들의 분광학적 특성을 이해하고, 분자시스템의 구조, 전자배치에 따른 광 물리적 특성간의 관계를 밝혀내어, 나노 분자 소자 개발을 위한 청사진을 제시할 수 있을 것으로 기대한다. The term aromatic is almost as old as organic chemistry. Efforts to understand the underlying principles of aromaticity and its conceptual converse, antiaromaticity, have led to some of the most notable advances in chemistry, both theoretical and experimental. For instance, in the 1930’s Hückel proposed that planar conjugated systems with [4n+2] π-electrons would display aromatic stabilization, whereas in the 1960’s Breslow coined the term antiaromaticity to highlight the fact that certain non-distorted systems containing [4n] π-electron peripheries would be relatively destabilized. Systems used to test these concepts have included such classics as bridged [10]annulene, cyclobutadiene, kekulene, and the cyclopropenyl cation. The concept of so-called Möbius aromaticity was likewise advanced early on for conjugated systems containing [2n+1] twists within the π-electron circuit, but only demonstrated experimentally for the first time in 2003. In Möbius systems [4n], rather than [4n+2], π-electron conjugation pathways give rise to aromaticity. Baird’s rule also predicts such a reversal for triplet systems, where again [4n], rather than [4n+2], π-electron peripheries should be aromatic. In this regard, I have prepared porphyrinoids ([26]hexaphyrin, [32]heptaphyrin, [36]octaphyrin, bridged [34]octaphyrin) to explain the chemical and physical features of porphyrins and reveal the photophysical properties depending on the number of π-electrons, the molecular structures, π-conjugation and aromaticity. Since the molecular properties of porphyrinoids have been affected by the molecular geometry, symmetry, excited state dynamics under the design condition such as low temperature, (de)protonation and high viscosity to understand the chemical and physical properties of prepared porphyrinoids. First, I have investigated that the hexaphyrin undergoes facile deprotonation reaction upon the treatment with TBAF to generate the monoanion and the dianion, both of which display the sharp absorption spectra, the exceptionally increased fluorescence intensities, and the considerably long-lived singlet and triplet excited states as an indication of the enhanced aromaticity. This work highlights the potential of the deprotonation strategy in tuning the electronic properties of expanded porphyrins. Second, I have investigated that the S2 fluorescence is detected from [26]hexaphyrinin toluene by the steady-state fluorescence spectroscopy. By the broadband fluorescence upconversion spectroscopy, the simultaneous observation of the decay of the S2 fluorescence and the rise of the S1 fluorescence allowed us to reveal the S2 deactivation and S1 population dynamics of deprotonated [26]hexaphyrin. The femtosecond TA spectra revealed the presence of the ultrafast direct decay pathway from the S2 state to the ground state. The observation of S2 fluorescence from highly conjugated molecular systems like hexaphyrins is quite rare and S2 fluorescence beyond 700 nm is also quite rare. Third, I have investigated the effect of organic base (TBAF) to highly distorted nonaromatic [32]heptaphyrin. Upon deprotonation with TBAF, nonaromatic [32]heptaphyrin with a figure-eight conformation and non-aromatic character underwent structural changes to open and twisted Möbius aromatic species and Möbius aromatic heptaphyrin gained stronger aromaticity due to conformational fixation. These changes were accompanied by red-shifted and sharp B-like band, distinct Q-like bands in NIR region, longated S1-state lifetime, and enhanced TPA cross section values. Such changes were not observed for fixed and N-fused [32]heptaphyrin. Through this work, we have demonstrated that deprotonation can be a new effective means to control the conformation of heptaphyrins and hence their aromatic characters dramatically. Fourth, I have investigated that upon deprotonation with TBAF, nonaromatic [36]octaphyrin with a figure-of-eight conformation undergoes conformational changes to twisted Möbius aromatic species and square Hückel antiaromatic species, depending upon the amount of TBAF. Hückel antiaromatic [36]octaphyrin dianion has been revealed to take a square planar shape as a new structural form. Fifth, I have investigated that the bicyclic conjugate compounds allow access to two limiting aromatic states. In their neutral forms, spectroscopic and solid-state structural analyses are consistent with existence of flattened bicyclic species that support two competing aromatic ring currents within the overall non-planar molecular frameworks. On the other hand, two-electron oxidation leads to [4n] π-electron triplet species whose features are consistent with global aromaticity in accord with Baird’s rule. The ability to access two different dual aromatic species using the same synthetic systems leads us to propose that conjugated bicyclic compounds may have a role to play in extending the frontiers of aromaticity beyond the conceptual limits associated with the topographically planar Hückel and Möbius formulations.

Enhanced oxidation of urea by pH swing during chlorination : pH-Dependent reaction mechanism

이지원 서울대학교 대학원 2023 국내석사

Urea reacts with chlorine to form chlorinated urea (chlorourea), and fully chlorinated urea is degraded by hydrolysis. The degradation of urea during chlorination was greatly enhanced by the pH swing, in which urea reacted with chlorine at pH 3 for 30 minutes (first step) and pH was elevated to pH 7 and reacted for 120 minutes (second step). 20% and 16% of urea were degraded at pH 3 and pH 7, respectively, but 92% was degraded by the pH swing method. Moreover, the degradation efficiency of urea by the pH swing increased as the chlorine dose increased. The degradation rate of urea by pH swing increased with increasing pH from 3 to 10, and the speciation changes of the chloroureas were suggested as the reason for this enhancement. The increase in deprotonated monochlorourea (pKa = 9.7±1.1) and dichlorourea (pKa = 5.1±1.4) with increasing pH accelerated the chlorination. The deprotonation of dichlorourea accelerated the degradation rate in the pH 3-7.5 region, and the deprotonation of both monochlorourea and dichlorourea greatly enhanced the degradation rate in the pH 7.5-10 region. Lower concentrations of products were measured in the open system than in the closed system because chloramines are volatile. Moreover, the chloramines were oxidized to form NO3- and gaseous nitrogen compounds were produced as pH increased. 요소는 염소와 반응하여 수소가 염소로 치환된 클로로우레아(chlorourea)를 생성하고, 염소로 모두 치환된 요소는 가수분해에 의해 분해된다. 요소를 산성 조건에서 30분 동안 염소와 반응한 다음 (1단계), pH 7에서 120분 동안 반응하는 (2단계) pH 스윙을 이용한 염소화를 통해 요소의 분해를 크게 향상시켰다. 요소는 pH 3과 pH 7에서 각각 20%와 16%가 분해되었으나, pH 스윙을 이용한 경우에는 92%가 분해되었다. pH 스윙에 의한 요소의 분해 효율은 염소 주입량이 증가함에 따라 증가하였다. 또한, 요소의 분해 속도는 pH 스윙 2단계의 pH가 3에서 10으로 증가함에 따라 증가했으며, 클로로우레아의 종 변화가 분해 속도 향상 원인임을 확인하였다. pH 스윙을 이용한 경우, 2단계의 pH가 증가함에 따라 탈양성자화된(deprotonated) 모노클로로우레아(monochlorourea) 와 디클로로우레아(dichlorouera)가 증가해 염소화 속도를 가속화했다. 디클로로우레아의 탈양성자화는 pH 3-7.5 영역에서 분해 속도를 가속화했고, 모노클로로우레아와 디클로로우레아의 동시 탈양성자화는 pH 7.5-10 영역에서 분해 속도를 크게 향상시켰다. 또한, 다양한 pH 조건에서 폐쇄형과 개방형 시스템일 때 요소의 염소화를 통해 형성된 생성물을 각각 분석하였다. 클로라민(chloramine)이 휘발성이기 때문에 폐쇄형 시스템보다 개방형 시스템에서 더 낮은 농도의 생성물이 측정되었다. 또한, 암모늄(NH4+)과 클로라민은 pH가 증가함에 따라 산화되어 질산염(NO3-)을 형성하였다.

Transformation from Supramolecular 2D Membranes to Vesicles by Spontaneous Deprotonation

Gunhee Seo 고려대학교 KU-KIST융합대학원 2022 국내석사

Cell membranes as a typical example of a supramolecular system perform important functions in living organisms, such as material transport, energy storage, and information transfer. In addition, various proteins or asymmetric lipid bilayers in cell membranes form curvatures, resulting in the structural transformation to vesicles. The fission and fusion process between the vesicles and cell membranes is reversible in living organisms. Although the transformation from a 2D membrane to a 3D vesicle structure is a common natural phenomenon, the lack of a detailed understanding at molecular levels limits the development of synthetic systems for functional materials such as delivery systems, biosensors, catalytic materials. Here, we report a supramolecular membrane system via donor-acceptor interactions using π-deficient [1·2H]2+ (acceptor) and π-rich tetrathiafulvalene (donor) as building blocks. The reduced electrostatic repulsion between ammonium cations and the spontaneously deprotonated neutral amino group induced the anisotropic membrane curvatures, resulting in the membrane fissions to vesicles. Furthermore, the reversible transformation of vesicles to the membranes via a change of pH can provide a novel synthetic system showing the fission and fusion process together with fundamental principles at molecular levels.

Application of Internal Competition Kinetics to Probe the Catalytic Strategies of RNA 2'-O-Transphosphorylation

Kellerman, Daniel Case Western Reserve University ProQuest Dissertat 2016 해외박사(DDOD)

18O kinetic isotope effects for RNA 2’-O-transphosphorylation reactions have been determined, characterizing the bonding in the transition states for RNA cleavage by specific base and by specific acid in solution. These results provide demonstrate a late, product-like transition state for the specific base reaction and provide evidence for equilibrium deprotonation of the 2’O nucleophile. Additionally, they further confirm a step-wise mechanism involving a protonated, phosphorane intermediate for the specific acid catalyzed reaction. Finally, series of structure function studies using internal competition as an analytical tool examine the role of the 2’O nucleophile during the RNA 2’-O-transphosphorylation reaction catalyzed by the HDV ribozyme. These results directly test a hypothetical pairing interaction within the catalytic core of the ribozyme and provided the first atomic level detail on which functional groups contribute to positioning the 2’O nucleophile.