Flash Chromatography1 (FC)[1].
biologicalevaluation：生物学评价
ELECTRONIC SUPPLEMENTARY INFORMATIONFunctionalization of multi-walled carbon nanotubes with coumarin derivatives and their biological evaluationDaniela Iannazzo,a,* Anna Piperno,a Angelo Ferlazzo,a Alessandro Pistone,b,* Candida Milone,b Maurizio Lanza,c Francesco Cimino,d Antonio Speciale,d Domenico Trombetta,dAntonina Saija,d Signorino Galvagno b.∙Materials and techniques page 1 ∙Fourier transform-infrared (FT-IR) spectroscopy page 2 ∙UV/Vis spectroscopy page 3 ∙Preparation of CNT-Link blank sample page 4 ∙Preparation of Coumarin Derivatives page 5 ∙Identification of coumarin isothiocyanate derivatives page 7 ∙Titration Analyses page 9Materials and techniquesSolvents and reagents were used as received from commercial sources. Sonication was carried out in a batch using Bandeling Sonorex Type RK52H equipment. Nuclear magnetic resonance spectra (1H NMR recorded at 300 or 500 MHz, 13C NMR recorded at 75 or 125 MHz) were obtained on Varian Instruments and are referenced in ppm relative to TMS or the solvent signal. Thin-layer chromatographic separations were performed on Merck silica gel 60-F254 precoated aluminum plates. Flash chromatography was accomplished on Merck silica gel (200–400 mesh). Preparative separations were carried out by MPLC Büchi C-601 usingMerck silica gel 0.040–0.063 mm and the eluting solvents were delivered by a pump at the flow-rate of 3.5–7.0 mL min–1.Transmission electron microscopy (TEM), EDX analyses, thermogravimetry (TGA), FTIR analyses and acid-base titration were carried out to characterize pristine and functionalized MWCNTs. The morphology of MWCNTs was analyzed using an HRTEM JEOL JEM 2010 analytical electron microscope (LaB6 electron gun) operating at 200 kV and equipped with a Gatan 794 Multi-Scan CCD camera for digital imaging. HRTEM samples were prepared by placing a drop of the MWCNTs dispersed in isopropanol on holey-carbon coated copper grids. EDX analyses were carried out in a JEOL, JSM 5600 LV, scanning electron microscope using a voltage of 20 kV. Thermogravimetrical studies were performed from 30 to 1000 °C at 10 °C/min under nitrogen on a TA Instruments SDTQ600 (TA instruments). IR spectra were recorded on a Nicolet FT-IR Impact 400D spectromer. UV spectra have been performed by Thermo Nicolet mod, Evolution 500spectrophotometer.Fourier transform-infrared (FT-IR) spectroscopyThe functionalization of various surface-modified MWCNTs was confirmed by FT-IR spectroscopy. FT-IR spectra were recorded on a Nicolet FT-IR Impact 400D spectromer. For pristine CNT, the curve doesn’t show significant absorption peaks whereas for CNT-Ox, carboxylation in nitric acid and sulfuric acid provides a typical absorption peak at 1710 cm-1. For the CNT-Link-Coum-oleic and CNT-Link-Coum the IR spectra show a complex absorbance set around 1600-1730 cm-1indicating the existence of carbonyl groups and the double bounds. The IR spectra of these conjugates also provide the absorbances at 3200-3500cm-1 that can be assigned to the N-H and O-H stretching modes together with the absorbances at around 1050 cm-1 corresponding to the C-O and C-N stretching modes (figure 1).Figure 1. FTIR spectra of the samples: CNT, CNT-Ox, CNT-Link-Coum, CNT-Link-Coum-Oleic.UV/Vis spectroscopyUV spectra have been performed by Thermo Nicolet mod, Evolution 500spectrophotometer. The UV spectra confirm the presence of coumarins covalently bonded to the nanotubes. MWCNTs conjugated with 7-oleate coumarin and 7-hydroxy coumarin show an absorbance at 240-300 nm, while no absorbance was detected for the MWCNTs functionalized with the linker; a different spectrum was registered for isothiocyanatoethoxy-7-oleate coumarin.Figure 2. UV/Vis spectra of the samples: CNT-Link, CNT-Link-Coum, CNT-Link-Coum-Oleic and free Coum-Oleic.Preparation of CNT-L INK BLANK SAMPLE.A mixture of 5-(2-aminoethoxy)-7-hydroxy-2H-chromen-2-one (0.15 mmol, 30 mg) and CNT-Link (100 mg) in absolute ethanol (6 mL) was stirred at room temperature for 12h. The mixture was filtered under vacuum on a 0.1 μm Millipore membrane. The solid residue was washed for three-time with ethanol (3 x 20 mL) and each time sonicated for 10 min and separated from the supernatant by filtration. The solid residue was then dried under vacuum at 50 °C to give sample CNT-Link blank.Figure 3. TGA curve of CNT-Link and CNT-Link (Blank sample)Preparation of Coumarine DerivativesSynthesis of 5-oxyethyl-tert-butyl carbamate-7-hydroxy coumarin 4To a solution of 5,7-dihydroxy-2H-chromen-2-one 1 (601 mg 3.38 mmol) in acetone (30 mL) potassium carbonate (513 mg, 3.72 moles) was added and the solution was refluxed for 1hour, then tert-butyl 2-bromoethylcarbamate 2(832 mg, 3.72 mmol ) was added and the solution was refluxed for 18 h. The reaction was stopped and filtered after cooling to room temperature. The tert-butyl 2-(7-hydroxy-2-oxo-2H-chromen-5-yloxy)ethylcarbamate3 was obtained in 45% yields after MPLC purification using 0.5% methanol:chloroform solvent mixture. 1H NMR (CDCl3, 300 MHz) δ 1.62 (s, 9H), 3.65 (t, 2H, J = 5.5 Hz), 4.22 (t, 2H, J = 5.5 Hz), 5. 20 (bs, 1H), 5.80 (bs, 1H), 6.25 ( d, 1H, J = 8.5 Hz), 6.50 (s, 1H), 6.60 (s, 1H), 8.18 (d, 1H, J = 8.5). 13C NMR (75 MHz, CDCl3, ): 161.1, 160.0, 155.1, 152.49, 125.6, 113.8, 112.1, 101.7, 79.5, 67.7, 39.8, 28.3. HRMS (ES) calcd for C16H19NO6: 321.1212 [M+H]+; Found:321.1208.EA calcd (%) for C16H19NO6: calcd. C 59.81, H 5.96, N 4.36; found C 59.78, H 5.92, N 4.31.To a solution of tert-butyl 2-(7-hydroxy-2-oxo-2H-chromen-5-yloxy)ethylcarbamate 3(400 mg, 1.25 mmol) in dichloromethane (50 mL), 8 ml of trifluoroacetic acid (TFA) was added dropwise and the reaction mixture was stirred at room temperature overnight. After stirring overnight, the solvent was removed and the residue was subjected to flash chromatography using a 9 :1 mixture of CHCl3/MeOH to afford 5-(2-aminoethoxy)-7-hydroxy-2H-chromen-2-one 4 , yellow oil, 80% yield. 1H NMR (CD3OD, 300 MHz) δ 3.75 (t, 2H, J = 5.5 Hz), 4.62 (t, 2H, J = 5.5 Hz), 6.25 ( d, 1H, J = 8.5 Hz), 6.60 (s, 1H), 6.62 (s, 1H), 8.45 (d, 1H, J = 8.5). HRMS (ES) calcd for C11H11NO4: 221.0688 [M+H]+; Found:221.0682.EA calcd (%) for C11H11NO4: calcd. C 59.73, H 5.01, N 6.33; found C 59.70, H 4.98, N 6.30.Synthesis of (9Z)-5-(2-aminoethoxy)-2-oxo-2H-chromen-7-yl octadec-9-enoate 7To a solution of 3 in CH2Cl2 (20 mL) 1.2 eq. of Oleoyl chloride and 1.2 eq. of triethylamine were added and the mixture was then stirred for 12h at r.t. The solvent was, then removed and the residue was subjected to purification by MPLC using a 98/2 mixture of CHCl3/MeOH to obtain (9Z)-5-(2-aminoethoxy)-2-oxo-2H-chromen-7-yl octadec-9-enoate(N-Protected with tert-butyl carbamate), yellow oil, 70% yield. 1H NMR (CDCl3, 300 MHz) δ 0.89 (t, 3H, J = 7.5 Hz), 1.27 (m, 20H), 1.45 (s, 9H), 1.73 (t, 2H, J = 7.2 Hz), 2.01 (m, 4H), 2.18 (t, 2H, J = 7.2 Hz), 3.56 (t, 2H, J = 4.2 Hz), 4.10 (t, 2H, J = 4.2 Hz), 5.01 (bs, 1H), 5.35 (m, 2H), 6.29 (d, 1H, J = 9.5 Hz), 6.48 (s, 1H), 6.69 (s, 1H), 8.04 (d, 1H, J = 9.5 Hz). HRMS (ES) calcd for C34H51NO7: 585.3666 [M+H]+; Found:585.3662.EA calcd (%) for C34H51NO7: calcd. C 69.71, H 8.78, N 2.39; found C 69.68, H 8.80, N 2.35.The obtained compound was deprotected with trifluoroacetic acid to give (9Z)-5-(2-aminoethoxy)-2-oxo-2H-chromen-7-yl octadec-9-enoate.1H NMR (CD3OD, 500 MHz) δ 0.89 (t, 3H, J = 6.9 Hz), 1.27 (m, 20H), 1.75 (qt, 2H, J = 7.2 Hz), 2.05 (m, 4H), 2.60 (t, 2H, J = 7.2 Hz), 3.55 (t, 2H, J = 4.2 Hz), 4.20 (t, 2H, J = 4.2 Hz), 5.35 (m, 2H), 6.34 (d, 1H, J = 10.0 Hz), 6.77 (s, 1H), 6.81 (s, 1H), 8.32 (d, 1H, J = 10.0 Hz). 13C NMR (CD3OD, 125 MHz) δ 36.3, 38.1, 40.7, 63.3, 67.9, 70.5, 71.3, 71.4, 124.1, 124.3, 129.2, 130.1, 130.2, 130.8, 130.9, 133.3, 135.4, 135.5, 146.6, 167.8, 169.7. HRMS (ES) calcd for C29H43NO5: 485.3141 [M+H]+; Found:485.3139.EA calcd (%) for C29H43NO5: calcd. C 71.72, H 8.92, N 2.88;found C 71.69, H 8.90, N 2.85.Identification of coumarin isothiocyanate derivativesTo a solution of 5-(2-aminoethoxy)-7-hydroxy-2H-chromen-2-one (0.15 mmol, 30 mg) in absolute ethanol (5 mL), CS2 (1.5 mmol, 114 mg) and triethylamine (0.15 mmol, 0.02 mL) were added. The reaction mixture was stirred for 30 min at room temperature and then cooled on an ice bath. Di-tert-butyl dicarbonate (Boc2O, 0.15 mmol, 33 mg), dissolved in absolute ethanol, was added followed by the immediate addition of a catalytic amount of dimethylaminopyridine (DMAP, 1-3 mol%) in absolute ethanol (1 mL). The reaction mixture was kept in the ice bath for 5 min and then allowed to reach the room temperature. After that evolution of gas from the reaction mixture had ceased (approximately 15 min), before the CNT-Link and triethylamine addition the reaction mixture was evaporated in vacuo. The the residue was taken up in diethyl ether and triethylammonium hydrochloride was filtered off, and the filtrate was evaporated in vacuo to afford,5-(2-isothiocyanatoethoxy)-7-hydroxy-2H-chromen-2-one, red solid, m.p. 78-80 °C, 95% yield. 1H NMR (CDCl3 , 300 MHz) δ 3.65 (t, 2H, J = 7.5 Hz), 4.66 (t, 2H, J = 7.5 Hz), 6.34 ( d, 1H, J = 9.5 Hz), 6.60 (s, 1H), 6.62 (s, 1H), 8.10 (d, 1H, J = 9.5), 8.15(bs, 1H).13C NMR (75 MHz, CDCl3, ): 160.4, 155.1, 152.5, 149.1, 137.8, 119.4, 114.5, 114.0, 100.6, 99.3, 66.9, 44.5. HRMS (ES) calcd for C12H9NO4S: 263.2692 [M+H]+; Found:263.2690.EA calcd (%) for C12H9NO4S: calcd. C 54.75, H 3.45, N 5.32; found C 54.78, H 3.47, N 5.35.The above reported procedure was applied for detected 5-(2-isothiocyanatoethoxy)-2-oxo-2H-chromen-7-yl oleate, red solid, m.p 68-69 °C, 93% yield. 1H NMR (CDCl3, 500 MHz) δ 0.90 (t, 3H, J = 6.5 Hz), 1.25 (m, 20H), 1.75 (m, 2H), 2.0 (m, 4H), 2.60 (t, 2H, J = 7.2 Hz), 3.95 (t, 2H, J = 4.5 Hz), 4.23 (t, 2H, J = 4.5 Hz), 5.38 (m, 2H), 6.35 (d, 1H, J = 10.0 Hz), 6.55 (s, 1H), 6.78 (s, 1H), 8.10 (d, 1H, J = 10.0 Hz).13C NMR (CDCl3, 125 MHz) δ 14.0, 22.6,27.1, 29.1, 29.3, 29.7, 31.9, 44.5, 45.6, 60.3, 99.8, 101.1, 103.8, 106.6, 114.5, 129.7, 130.0, 137.8, 155.1, 155.4, 155.5, 160.5, 170.2. HRMS (ES) calcd for C30H41NO5S: 527.2705 [M+H]+; Found: 527.2707.EA calcd (%) for C30H41NO5S: calcd. C 68.28, H 7.83, N 2.65; found C 68.31, H 7.85, N 2.69.Titration AnalysesThe NH2 loading of compound 2 was found to be 1.11 mmol g-1 by Kaiser test assay and 1.12 mmol g-1 by potentiometric argentometric titration.The NH2 loading of compound 3 was found to be 1.10 mmol g-1 by Kaiser test assay.Quantitative Kaiser test protocolThree solutions were prepared separately:- (I): 10 g of phenol in 20 mL of absolute ethanol.- (II): 2 mL of potassium cyanide 1 mM (aqueous solution) dissolved in 98 mL of pyridine.- (III): 1 g of ninhydrin in 20 mL of absolute ethanol.A mass of approximately 20 mg of carbon nanotubes was carefully weighted in a haemolysis test tube. Then, 75 μL of solution (I), 100 μL of solution (II), and 75 μL of solution (III) were successively added to the CNTs. The resulting dispersion was sonicated in a water bath for several minutes until disaggregation of the CNTs, heating at 120 °C for 5 min and diluted with 4.75 mL of 60% ethanol. After centrifugation, the supernatant was analyzed by UV-Vis spectroscopy. The absorbance at 570 nm was correlated to the amount of free amine functions on the CNT surface using the equation:Dilution is 5 mL and extinction coefficient is 15000 m-1cm-1.The blank was prepared exactly the same way but without CNTs.The result is expressed as micromole of amino groups per gram of material.The Kaiser test is repeated at least three times for each sample to ensure reproducibility.Potentiometric argentometric titrationThe titration was performed on carefully weighted 20 mg of 2 with an aqueous solution of AgNO30.01M (previously standardized with NaCl 0.02 M standard solution) using as electrode an INGOLD Ag 4805-s7/120 combination silver and conducted on a Mettler Toledo Seven Multi. The titration was carried out in high ionic strength condition by adding 25 mL of 1.0 M KNO3 aqueous solution to the mixture and adjusting the pH to 1 with H2SO4. The NH2 loading was calculated from the equation reported below, where V is the volume of AgNO3 titration solution at the equivalent point, [AgNO3] is the molarity of AgNO3 while “sample weight” is the weight of the sample that is titrated.The loading value is an average of three titrations performed for each batch.。
fc片段分子量
fc片段分子量FC片段分子量（Fragment Constant，简称FC）是描述化合物结构中各个片段的特征的一个参数。
它是通过将化合物分解为一系列片段，并计算每个片段的相对质量来确定的。
FC片段分子量的计算对于化学研究和药物设计具有重要意义，能够帮助科学家们更好地理解和预测分子的性质和活性。
一、什么是FC片段分子量？FC片段分子量是根据分子结构中各个片段的质量计算得出的。
这些片段可以是原子、基团或者它们的组合。
通过计算每个片段的相对质量，并将它们相加，就得到了FC片段分子量。
FC片段分子量可以用来描述化合物的结构特征，如分子大小、极性、芳香性等。
二、FC片段分子量的应用1. 药物设计：FC片段分子量可以帮助药物研究人员评估化合物的药效和药代动力学性质，从而指导药物设计和优化过程。
2. 化学反应：FC片段分子量可以用来预测化学反应的可能性和活性。
不同片段的FC片段分子量可以用来比较反应的亲和力和速率。
3. QSAR分析：FC片段分子量是构建定量构效关系（QSAR）模型的重要参数之一。
它可以用来描述化合物的结构特征，进而预测其生物活性。
三、如何计算FC片段分子量计算FC片段分子量的方法有多种，常见的方法包括原子质量表法、基团质量表法和自定义片段法。
其中，原子质量表法是最常用的方法。
它通过查表得到每个原子的相对质量，并将它们相加得到分子的FC片段分子量。
基团质量表法和自定义片段法则是根据不同基团或片段的质量来计算FC片段分子量。
四、FC片段分子量的意义和局限性1. 意义：FC片段分子量可以提供化合物结构的定量描述，帮助科学家了解分子的特征和性质，从而指导药物设计和化学研究。
2. 局限性：FC片段分子量只是分子结构的一个参数，它不能完全描述分子的性质。
此外，不同的计算方法会得到不同的FC片段分子量，因此在比较和分析时需要注意方法的选择和一致性。
五、FC片段分子量的应用案例1. 药物设计案例：研究人员通过计算药物分子的FC片段分子量，发现某些片段与药物的活性相关性较强。
4类重庆柑橘乙醇提取物类黄酮分析及其体内外抗氧化评价
4类重庆柑橘乙醇提取物类黄酮分析及其体内外抗氧化评价[目的]研究4類重庆柑橘乙醇提取物的类黄酮成分及其体内外抗氧化活性。
[方法]以4种重庆产区柑橘果实（梁平柚、奉节脐橙、万州大红袍红橘和潼南尤力克柠檬）为研究材料，利用Xevo G2-S Qtof高分辨四级杆飞行时间质谱仪中的超高效液相色谱仪（Ultra-performance liquid chromatography with a photodiode array detector，UPLC-PDA）对柑橘果皮和果肉的乙醇提取物中主要的10种类黄酮（橙皮苷、芸香柚皮苷、柚皮苷、地奥司明、橘皮素、川陈皮素、圣草次苷、甜橙黄酮、异橙黄酮和山柰酚）进行了定性和定量分析，并用3种体外抗氧化测定方法（DPPH、ABTS、FRAP）评价柑橘果实乙醇提取物的抗氧化活性。
同时，以酿酒酵母BY4742菌株为试验模型，检测用低、中、高浓度的4类柑橘果实乙醇提取物处理后酵母菌胞内活性氧（Reactive oxygen species，ROS）含量。
[结果]不同柑橘、同种柑橘不同部位的类黄酮种类和含量都存在差异。
总体而言，柑橘果皮类黄酮物质的种类与总含量高于果肉，果皮提取物的内外抗氧化能力高于果肉提取物。
其中，梁平柚果实中含量最高的是柚皮苷，奉节脐橙、万州大红袍红橘和潼南尤力克柠檬果实提取物中含量较高的是橙皮苷。
此外，圣草次苷大量存在于潼南尤力克柠檬果实中，川陈皮素大量存在于万州大红袍红橘中，芸香柚皮苷大量存在于奉节脐橙中，山柰酚主要分布于梁平柚果皮中，地奥司明主要分布于柠檬和柚子的果肉中。
[结论]奉节脐橙具有较好的营养价值。
与其他3种柑橘果肉相比，奉节脐橙果肉含有最高的类黄酮含量、综合抗氧化活性和较高的活性氧清除能力。
我国是柑橘属植物最重要的起源地，拥有丰富的柑橘资源[1-2]。
柑橘作为类黄酮含量丰富的水果之一，具有重要的的营养、保健、医学和经济价值[3-5]。
目前已从柑橘中鉴定出超过60种类黄酮物质，主要是黄烷酮类、黄酮、黄酮醇和花色苷[6]，其具有重要的抗氧化活性[7]。
实验三十四植物叶绿体色素的提取、分离、表征及含量测定
实验三十四植物叶绿体色素的提取、分离、表征及含量测定摘自王尊本主编,综合化学实验(第二版),第226-244页,北京:科学出版社,2007年9月。
实验三十四植物叶绿体色素的提取、分离、表征及含量测定[1-27]一、叶绿体色素的提取(一) 实验目的1)掌握有机溶剂提取叶绿体色素等天然化合物的原理和实验方法。
2)了解皂化-萃取提取胡萝卜素的原理。
3)了解1,4-二氧六环沉淀法提取叶绿素的原理。
(二) 实验原理植物光合作用是自然界最重要的现象,它是人类所利用能量的主要来源。
在把光能转化为化学能的光合作用过程中,叶绿体色素起着重要的作用。
高等植物体内的叶绿体色素有叶绿素和类胡萝卜素两类,主要包括叶绿素a、叶绿素b、胡萝卜素和叶黄素四种。
它们所呈现的颜色和在叶绿体中含量大约比例见表34.1。
表34.1 高等植物体内叶绿体色素的种类、颜色及含量项目叶绿素类胡萝卜素叶绿素a 叶绿素b 胡萝卜素叶黄素颜色蓝绿色黄绿色橙黄色黄色在叶绿体内各色素含量比例 3 1 2 13 1 叶绿素chlorophylls是叶绿酸的酯,它在植物进行光合作用中吸收可见光,并将光能转变为化学能。
叶绿素是植物进行光合作用所必需的催化剂。
在绿色植物中叶绿素主要以叶绿素a(C55H72O5N4Mg)和叶绿素b(C55H70O6N4Mg)两种结构相似的形式存在,其差别仅是叶绿素a中一个甲基被叶绿素b中的甲酰基所取代。
叶绿素的基本结构见图34.1。
在叶绿素分子结构中含有四个吡咯环,它们由四个甲烯基联结成卟啉环,在卟啉环中央有一个镁原子,它以两个共价键和两个配位键与4个吡咯环的氮原子结合成内配盐,形成镁卟啉。
在叶绿素分子中还有两个羧基,其中一个与甲醇酯化成COOCH3,另一个与叶绿醇酯化成COOC20H39长链。
类胡萝卜素carotenoids是一类不饱和的四萜类碳氢化合物(例如胡萝卜素,carotenes,或它们的氧化衍生物(例如叶黄素类,xanthophylls。
奥拉帕尼(Olaparib)合成检索总结报告
奥拉帕尼（Olaparib）合成检索总结报告
一、奥拉帕尼（Olaparib）简介
奥拉帕尼（Olaparib）于2014年12月19日在美国上市。
奥拉帕尼（Olaparib）是聚腺苷酸二磷酸核糖转移酶抑制剂，用于晚期卵巢癌。
奥拉帕尼（Olaparib）不良反应有：恶心、疲乏、呕吐、腹泻、味觉障碍、消化不良等等。
奥拉帕尼（Olaparib）分子结构式如下:
英文名称：Olaparib
中文名称：奥拉帕尼
本文主要对奥拉帕尼（Olaparib）的合成路线、关键中间体的合成方法及实验操作方法进行了文献检索并作出了总结。
二、奥拉帕尼（Olaparib）合成路线一
三、奥拉帕尼（Olaparib）合成路线二
四、奥拉帕尼（Olaparib）合成路线一检索总结报告
(一) 奥拉帕尼（Olaparib）中间体3的合成方法一（路线一）
(二) 奥拉帕尼（Olaparib）中间体3的合成方法二（路线一）
(三) 奥拉帕尼（Olaparib）中间体3的合成方法三（路线一）①奥拉帕尼（Olaparib）中间体8的合成。
快速柱层析技巧
[W W W .R H O D I U M .W S ] [] [C H E M I S T R Y A R C H I V E ]Search 'D R Y F L A S H ' C O L U M N C H R O M A T O G R A P H YHarwood, L. M.; Moody, C. J.; Percy, J. M.Experimental Organic Chemistry, 2nd ed.Blackwell Science: Oxford, 1999.HTML by Rhodium This technique combines the speed and separation of 'flash' chromatography with use of the cheaper TLC grade silica, simple operation and absence of special apparatus requirements. In 'dry flash' column chromatography, the silica column is eluted by suction instead of using top pressure, removing the risk of bursting glassware. Additionally the column is eluted by adding predetermined volumes of solvent and is run dry before addition of the next fraction. These features make the procedure readily adaptable to gradient elution and this is in fact the preferred way of developing such columns. As its name suggests, gradient elution involves developing a column with progressively more polar combinations of eluting solvent. This can confer very real time advantages for the removal of polar compounds from a column in the latter stages of a separation, without losing the separation qualities of a relatively non-polar eluting system at the beginning for the less polar components.Do not forget that this is the only instance when you should allow air to get into a chromatography column during development. In fact the whole procedure appears to fly in the face of all of the principles of classic chromatography. but it can give results at least as good as the standard flash technique at much reduced cost. It is particularly useful for the separation of enormous (in chromatographic terms at least!) quantities of material up to 50g ?although such columns should not be attempted by the inexperienced. This technique has been the subject of a certain degree of quantification by one of the authors (LMH) but has been in fairly general use in various laboratories for a long time.The equipmentThe apparatus needed is simply that for filtration under reduced pressure using a cylindrical porosity 3 sinter funnel attached to a round-bottomed flask by means of a cone and socket adapter with a side arm for attachment to a water aspirator (Fig. 3.74). The amount of sample to be purified determines the size of sinter funnel to use and the volume of fractions to collect. Suggested guidelines are shown in Table 3.14.Choosing the solvent systemThe eluting solvent system used should be that in which the desired component has an R f value of 0.5 by TLC analysis. Although no solvent is particularly disfavoured for this technique, various combinations of hexane, diethyl ether, ethyl acetate and methanol are adequate for the majority of separations. As the system is under reduced pressure, some of the solvent collected will evaporate and may cool the receiving vessel to such an extent that atmospheric moisture condenses on the apparatus. This does not affect the efficiency of the separation but, if the chromatography is prolonged, some water may find its way into the collected fractions. Use of the less volatile heptane instead of light petroleum helps somewhat in this respect.Packing the columnThe silica used for this type of chromatography is TLC grade silica without the gypsum binder. This is cheaper than the silica sold for use in flash chromatography which, in any case, is too free flowing for use in these dry columns. The weight of silica recommended for each size of funnel is sufficient to leaven head space at the top of the funnel for loading solventwhen the column has been packed and compacted under suction. The silica may be weighed out as indicated in the table, but it is easier just to fill the funnel to the brim withlightly packed silica. Application of suction causes the silica to compact, leaving the head space for solvent addition. Duringthis initial compaction there is a tendency, particularly withthe larger sized columns, for the silicate shrink away from the sides of the funnel or to form cracks which may remainunseen in the body of the adsorbant. To ensure good packing, press down firmly on the surface with a glass Table 3.14 Guideline size and volume parameters for 'dry flash' chromatography. Sinter Diameter Weight of Silica Sample Weight Fraction Volume 30 mm 15 g 15-500 mg 10-15 mL 40 mm 30 g 0.5-3 g 15-30 mL 70 mm 100 g 2-15 g 20-50 mLstopper, particularly at the edges, using a grindingmotion. Do not worry about the state of the adsorbantsurface as this can be flattened off easily when finishedby repeated gentle tapping around the sides of the funnel with a spatula. When satisfied that the column has been thoroughly compacted, pre-elute the column with the least polarcomponent of the elution system. If the packing hasbeen carried out properly, the solvent front will be seen descending in a straight, horizontal line. Keep the silica surface covered with solvent during the pre-elution,until solvent passes into the receiving flask, and thenallow the silica to be sucked dry. Remember to check the back as well as the front of the column for anyirregularities. If a regular solvent front is not obtained,simply suck the column dry, recompact it and repeatthe pre-elution procedure. There is no excuse forattempting a separation with an improperly packed column. Note that the surface of the compacted silica isrelatively stable on addition of solvent and does notrequire any protective layer of sand.Loading the sample and eluting the columnDissolve your sample in the minimum possible volumeof pre-elution solvent and apply it evenly to the surface of the silica with the column under suction. Rinse the sample container and add the washings to the column until all of the sample has been transferred. lf the sample does not dissolve easily in the pre-elution solvent, dissolve it in the least polar combination of the elutionsolvents in which it is readily soluble.Commence gradient elution with the same solvent combination as was used to load the sample onto the column, following the guidelines in the table for the size of fraction to use (use the smaller volumes for more difficult separations ).Allow the column to be sucked dry and transfer the first fraction to a test tube or any other convenient receptacle, rinsing both the flask and the stem of the funnel. Whilst the column is being sucked dry, prepare the next fraction. increasing the quantity of the more polar component by about 5%. Repeat the elution procedure. Continue the gradient elution in this manner until eluting with the pure, more polar component alone. and then continue with this as necessary. It is often advantageous to interrupt the gradient elution temporarily when the desired component is eluting from the column and continue with the same solvent mixture for a few fractions.The progress of the separation should be followed by TLC analysis of the fractions. However. as a rough guide, the desired product is usually eluted from the column when the gradient elution reaches that solvent mixture in which the material would have an R f value of 0.5 on TLC. When quantities of material of more than about 100mg are purified. elution of product from the column is often indicated by frothing on the underside of the sinter. If the product is a solid. it may crystallize out in the stem of the funnel or the receiving flask, particularly with separations of larger quantities of material. Be sure to rinse thoroughly both the flask and the funnel stem between fractions, and check that the solid does not obstruct elution from the column.The typically low degree of lateral diffusion of the product bands with this technique usually means that pure compounds elute in relatively few fractions. reducing the number of cross-contaminated fractions. The material recovery from the column should be excellent if the crude sample does not contain polymeric material.Disposal of the silicaAfter the elution is complete, suck the silica dry and then transfer it to the silica residues bin. Generally a sharp tap with the funnel held upside down will cause the whole of the adsorbant to fall out as a single plug of material. As always, care should be taken not to produce large quantities of silica dust in the atmosphere of the laboratory.Fig. 3.74 Apparatus for 'dry flash' column chromatography. F U R T H E R R E A D I N G1.L. M. Harwood, Aldrichimica Acta, Vol. 18, p. 25 (1985)。
reaxys_硼氢化羟基化反应
Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
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O N N B O
N N OH
Rx-ID: 29261853 View in Reaxys 1/3 Yield 100 % Conditions & References 4 :Intermediate 4 : 1 -Benzyl- 1 H-pyrazol-4-ol 1-Benzyl-4-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-1 H-pyrazole (Aldrich, 700 mg, 2.46 mmol) was dissolved in THF (6 ml_) and cooled to 0°C. NaOH 2.5 M (2 ml_, 4.93 mmol) and H202 30percent solution in water (503 μΙ, 4.93 mmol) were added and the reaction mixture was stirred at room temperature for 45 min. Then the pH was adjusted to 2 by the addition of aqueous HCI 2 M and the mixture was extracted with dichloromethane. The organic layer was dried over Na2S04, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel using cyclohexane/EtOAc as eluant. The expected fractions were combined and evaporated under reduced pressure to give the title compound 1 -benzyl- 1 H-pyrazol-4-ol (500 mg, quantitative yield). LCMS: (M+H)+ = 175 ; Rt = 0.61 min. Stage 1: With hydrogen peroxide, sodium hydroxide in tetrahydrofuran, water, Time= 0.75h, T= 0 - 20 °C Stage 2: With hydrochlorid acid in tetrahydrofuran, water, pH= 2 Patent; GLAXOSMITHKLINE LLC; DAUGAN, Alain Claude-Marie; LAMOTTE, Yann; MIRGUET, Olivier; WO2012/119978; (2012); (A1) English View in Reaxys 77 % Compound 244.2. l-Benzyl-lH-pyrazol-4-ol Compound 244.2. l-Benzyl-lH-pyrazol-4-ol. Into a 100-mL three neck round- bottom flask, was placed a solution of l-benzyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)-lH-pyrazole (compound 244.1, 3.47 g, 12.2 mmol) in tetrahydrofuran (35 mL). Sodium hydroxide (980 mg, 24.5 mmol) was added and then the mixture was cooled to 0 °C. Hydrogen peroxide (2.51 mL, 24.4 mmol) was carefully added drop-wise and the resulting mixture was stirred for 2 h at room temperature. The reaction was carefully quenched with aqueous a2S203(sat.) (20 mL). The aqueous phase was extracted with EtOAc (300 mL) and the combined organic layers were washed with brine (2 x 150 mL), dried ( a2S04), filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1/1) as eluent to furnish the title compound as a white solid (1.64 g, 77percent). With hydrogen peroxide, sodium hydroxide in tetrahydrofuran, Time= 2h, T= 0 - 20 °C Patent; 3-V BIOSCIENCES, INC.; HEUER, Timothy Sean; OSLOB, Johan D.; MCDOWELL, Robert S.; JOHNSON, Russell; YANG, Hanbiao; EVANCHIK, Marc; ZAHARIA, Cristiana A.; CAI, Haiying; HU, Lily W.; WO2015/95767; (2015); (A1) English View in Reaxys 77 % With hydrogen peroxide, sodium hydroxide in tetrahydrofuran, water, Time= 0.666667h, T= 0 - 20 °C Westaway, Susan M.; Preston, Alex G. S.; Barker, Michael D.; Brown, Fiona; Brown, Jack A.; Campbell, Matthew; Chung, Chun-Wa; Drewes, Gerard; Eagle, Robert; Garton, Neil; Gordon, Laurie; Haslam, Carl; Hayhow, Thomas G.; Humphreys, Philip G.; Joberty, Gerard; Katso, Roy; Kruidenier, Laurens; Leveridge, Melanie; Pemberton, Michelle; Rioja, Inma; Seal, Gail A.; Shipley, Tracy; Singh, Onkar; Suckling, Colin J.; Taylor, Joanna; Thomas, Pamela; Wilson, David M.; Lee, Kevin; Prinjha, Rab K.; Journal of Medicinal Chemistry; vol. 59; nb. 4; (2016); p. 1370 - 1387 View in Reaxys 23.A :l-Benzyl-4-(4,4,5,5-tetramethyl-[l,3,2]dioxaborolan-2-yl)-lΗ-pyrazole (700 mg,2.46 mmol) was dissolved in THF (6 mL) and cooled to 0 0C. NaOH (2 M in water, 4.93 mmol, 2.5 mL) and H2O2 (30percent in water, 503 μl, 4.93 mmol) were added and the reaction mixture was stirred at RT for 45 min. Then the pH was adjusted to 2 by the addition of aqueous HCl (2 M) and the mixture was extracted with DCM (3x 10 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with hexane/EA) to give the title compound. MS (m/z): 175.0 [M+H+] Stage 1: With water, hydrogen peroxide, sodium hydroxide in tetrahydrofuran, T= 0 - 20 °C Stage 2: With hydrochlorid acid in tetrahydrofuran, water, pH= 2
卤代酮的合成-060123
经典化学合成反应标准操作α-卤代酮的合成目录1．前言 (2)2. 直接卤化 (2)3．经重氮酮制备 (4)4．从weinreb 酰胺制备 (6)5．傅克酰基化合成卤代酮 (7)6 其他合成α-卤代酮的方法 (9)1．前言α-卤代酮的合成广泛应用于现代有机合成中， 多用于溴的烷基化、合成咪唑及噻唑等杂环类化合物，其合成方法常用直接卤化、经重氮酮制备、经Weinreb 酰胺制备、傅克酰基化等方法合成。
2. 直接卤化酮的α-氢易被取代，可以直接合成α-卤代酮。
一般操作是将酮与卤素于醋酸、氯仿、DMF 或水中反应。
除卤素外， 硫酰氯、五卤化磷、过溴化吡啶氢溴酸盐（C5H5NH.Br 3）、三卤化三甲基苄基铵盐等也可以做卤化试剂。
对称酮或只有一个取代方向的酮卤代时，可以良好产率（80~90%）生成α-卤代酮。
不对称酮卤代，往往生成α-及α’-卤代酮的混合物。
由于酮卤代的决定步骤是酮的烯醇化，因此，易形成烯醇的方向优先卤代。
例 2-甲基环己酮与亚硫酰氯作用， 多取代的α-氢优先氯代1。
OCH 3OCH 3Cl 2485%若利用双（二甲基乙酰胺基）三溴化氢做溴化剂，可使不对称酮在少取代一边溴代2。
OOBr[(Me 2NCOCH 3)2H]Br 3384%若将不对称酮首先转变成为一定构型的烯醇盐，继而卤代，是区域定向卤代的新方法3。
OH 3COH 3CCl1. i -Pr 2NLi, THFPhCOOEtO CH 3PhOCH 3Br 1. NaH, DMSO另外，甲基酮可用甲基格式试剂与相应的Weinreb 酰胺来制备， 如下例即是先合成甲基酮，后溴化来合成α-溴代酮的4。
NBocO HONBocO NO NBocODCC, D MAP, N HMeOMe MeMgI , e t h er合成实例一 5OOOOOOBrBr 2, AcOH2B 2AA suspension of ketone 2A (700 mg, 2.17 mmol) in acetic acid (15 ml) was heated to 70℃, followed by addition of bromine (347 mg, 2.17 mmol). After the mixture was stirred at 70℃ for 3h, the solvent was evaporated and the residue was purified by column chromatography to give the compound 2B (591 mg, 68%).合成实例二6OMe MeOO Br OMeMeOOBr232C2DBromine (7.99 g, 50 mmol) in CHCl 3 (20 ml) was added in a dropwise manner to a stirred solution of 2, 5-dimethoxy-4-bromoacetophenone 2C (12.95 g, 40 mmol) in CHCl 3 (100 ml) at 5℃. After the addition was completed, the reaction mixture was allowed to warm to room temperature and stirred for an additional 2 h. The mixture was poured onto crushed ice, the organic portion was separated and washed with water, saturated NaHCO 3 solution, and again with water. The solution was dried MgSO 4, and evaporated to dryness under reduced pressure to give a crude product. The product was recrystallized from MeOH to yield 14.70 g (87%) of the desired bromoacetophenone 2D as a white solid.ON NH 2NON NH 2NBr AcOH, 48% aq. HBr and Br 2To a solution of 1-(2-aminopyrimidin-4yl) ethanone (412 mg, 3 mmol) in glacial acetic acid (1 mL) and 48% aq. HBr (0.3 mL), bromine (0.153 mL) in acetic acid (0.4 mL) was added and the resulting orange solution was stirred at RT for1.5 hours. After diluting with ethyl acetate (15 mL), the precipitate was filtered and washed with ethl acetate thus affording the target compound as a whitish solid (580 mg, 65%).合成实例四8O OSiOOSi Br 2E 2FBenzyltrimethylammonium tribromide (4.17 g, 10.7 mmol) was added to a solution of Compound 2E (4.00 g, 10.7 mmol) in CH 2Cl 2-MeOH (5:2, 25 mL). The mixture was stirred at RT for 3 h. At this time the reaction mixture was concentrated in vacuo and H 2O (15 mL) was added. The mixture was extracted with diethyl ether (3 × 20 mL). The combined organic extracts were washed with brine (15 mL), dried over MgSO 4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (hexanes:EtOAc, 3:1) to afford to afford Compound 2F (3.97 g, 8.8 mmol, 82%) as a thick yellow oil.3．经重氮酮制备不对称酮卤代时，有时无法得到单卤代产物。
氨基的保护
渡岸学术搜索网 繁體中文|加入收藏 首页 | 图文 | 医学 | 药学 | 生物 | 化学 | 理工 | 材料 | 经济 | 国内英语 | 检索 | IT&others |当前位置: 首页 >> 化学 >> 有机&合成 >> 氨基的各种保护氨基的各种保护本文归类于: 氨基 来源：[网络搜索] 发表：2007-06-01 浏览：188188 字号：大 中 小 下载分卷附件前必看===氨基相关链接===● 氨基酸的背诵口诀 [2007/0725]●L-8900 DATA\L8800氨基酸分析仪中文资料\L8800氨基... [2007/0404]●氨基酸分析仪常见问题 [2007/0403]●超临界流体提取氨基酸的一篇外文文献＋SFE －MS 分析... [2007/0105]●洛美沙星注射液与3种氨基糖苷类药物配伍的稳定性 [2006/1226]氨基的各种保护t Bu - (tert -butyl) esterStandard Protection ProcedureTo a solution of the N-protected aminoacid, DMAP (0.5 eq), and tBuOH (1.2 eq) in dry DCM at 0° under an inert atmosphere, is added EDCI (1.1. eq) and stirred for 2 h. The mixture is then stirred at room temperature until complete by TLC (usually 14 h) and concentrated invacuo . The residue is redissolved in ethyl acetate and extracted twice with water, then twice with aqueous saturated sodium bicarbonate.The organic solution is dried (magnesium sulfate) and concentrated in vacuo . The residue is purified by flash chromatography (SiO 2) if necessary.RemovalThe compound is dissolved in formic acid and stirred at room temperature until the reaction is complete by TLC (usually 12 hours). The solution is then concentrated and coconcentrated several times with toluene. The resulting residue can then be purified by flash chromatography (SiO 2) if necessary.ReferencesJ. Chem. Soc., Perkin Trans. 1, 1996, 985-993. JOC, 1982, 47, 1962-1965.[Back to Top ] [Back to Synthetic Procedures]Bn - (benzyl) esterStandard Protection ProcedureThe amino acid is stirred with dry THF and O-benzyl-N,N'-diisopropylisourea (see ref. for synthesis) at room temperature under an inert atmosphere until complete by TLC (usually 2 days). The mixture is cooled to -20 C and filtered. The filtrate is concentrated in vacuo and purified by flash chromatography (SiO2) if necessary.RemovalThe amino acid derivative is dissolved in 1:1 methanol:t-butanol and Pd(OH)2-C is added under a hydrogen atmosphere. The mixture is allowed to stir until complete by TLC (usually >3 h), then filtered and concentrated. The resulting residue can then be purified by flash chromatography (SiO2) if necessary.ReferencesMacromolecules, 1978, 534-539.[Back to Top] [Back to Synthetic Procedures]Allyl - (allyl) esterStandard Protection ProcedureThe compound is dissolved in dry DCM and allyl alcohol (1.1 eq) is added. The solution is stirred under an inert atmosphere at 0° and dicyclohexylcarbodiimide (1 eq) is added followed by 4-N,N-dimethylaminopyridine (0.05 eq). The reaction is allowed to warm to room temperature and is stirred until complete by TLC (usually 1-2 days). Ethyl acetate is added and theresulting precipitate is removed by filtration. The filtrate is concentrated in vacuo and purified by flash chromatography (SiO2) if necessary.RemovalThe amino acid and pyrrolidine (1.2 eq) are dissolved in methylene chloride and cooled to -15°. Triphenylphosphine (0.2 eq) and Tetrakis(triphenylphosphine)palladium (0) (0.05 eq) are added and stirred under an inert atmosphere for approx. 1 h.Water and acetonitrile are added and the resulting mixture is extracted twice with petroleum ether. The acetonitrile layer is evaporated and purified by flash chromatography (SiO2) if necessary.ReferencesTetrahedron, 1996, 52, 12839-12852.[Back to Top] [Back to Synthetic Procedures]PfP - (pentafluorophenyl) esterStandard Protection ProcedureThe acid is dissolved in ethyl acetate and pentafluorophenol (1.2 eq) is added. The solution is cooled to 0° and DCC (1.2 eq) is added. The reaction is allowed to warm to room temperature and stir until complete by TLC (usually overnight, if notcomplete more DCC may be added). The solution is then filtered through celite, rinsed several times with EtOAc, andconcentrated in vacuo. The resulting residue can then be purified by flash chromatography (SiO2) if necessary.ReferencesJ. Chem. Soc., Perkin Trans. 1, 1996, 985-993.[Back to Top] [Back to Synthetic Procedures]Me - (methyl) esterStandard Protection ProcedureThe compound is dissolved in dry MeOH and thionyl chloride (2 eq) is added drop wise at 0° under an inert atmosphere. The result is then refluxed until complete by TLC (usually >4 hours) and concentrated in vacuo. The residue can then be purified by flash chromatography (SiO2) if necessary.RemovalThe ester is dissolved in methanol and 1N NaOH is added (excess). The solution is then heated to reflux and stirred until complete by TLC (usually <1 h). Glacial acetic acid is added until the mixture is neutral and then diluted with chloroform.The organic solution is extracted once with water, once with brine, dried (magnesium sulfate), and concentrated in vacuo.The residue is purified by flash chromatography (SiO2) if necessary.ReferencesEur. J. Org. Chem. 1999, 1127-1135.JOC, 1995, 60, 2318-2319.[Back to Top] [Back to Synthetic Procedures]PMB - (para-methoxybenzyl) esterStandard Protection ProcedureThe acid is dissolved in dry DCM and 4-methoxybenzyl alcohol (1.1 eq) is added. The solution is stirred under an inert atmosphere at 0° and dicyclohexylcarbodiimide (1 eq) is added followed by 4-N,N-dimethylaminopyridine (0.05 eq). The reaction is allowed to warm to room temperature and is stirred until complete by TLC (usually 1-2 days). Ethyl acetate is added and the resulting precipitate is removed by filtration. The filtrate is concentrated in vacuo and purified by flash chromatography (SiO2) if necessary.RemovalThe ester is dissolved in phenol and TFA (1-2 eq) is added under an inert atmosphere at 45°. The reaction is stirred until complete by TLC (usually <2 h) and ethyl acetate/water are added. The aqueous layer is extracted 2 times with EtOAc and the organic layer is back extracted twice with saturated sodium bicarbonate solution. The combined aqueous layers are acidified to a pH of 1 with 10% HCl, then extracted 3 times with EtOAc. The combined organic layers are dried (sodium sulfate) and concentrated in vacuo. The residue is then purified by flash chromatography (SiO2) if necessary.ReferencesTetrahedron, 1996, 52, 12839-12852.Tetrahedron Lett. 1990, 31, 6661-6662.[Back to Top] [Back to Synthetic Procedures]MEM - (methoxyethoxymethyl) esterStandard Protection ProcedureTo compound dissolved in a saturated aqueous sodium bicarbonate solution at room temperature, TBAI (1 eq) andmethoxyethyloxymethyl chloride (1.2 eq) are added. The reaction is stirred until complete by TLC (usually 16 h) anddichloromethane is added. The organic layer is washed with water, dried (sodium sulfate), and concentrated in vacuo. The resulting residue can then be purified by flash chromatography (SiO2) if necessary.RemovalThe ester is dissolved in DCM and magnesium bromide etherate (excess) is added at room temperature under an inertatmosphere. The mixture is stirred for 48 h and water is added. The slurry is stirred vigorously for another 2 h and 1N aqueous hydrochloric acid is added until the pH is 1-2. The mixture is extracted with ethyl acetate three times and the combined organic layers are dried (sodium sulfate), then concentrated in vacuo. The resulting residue can then be purified by flash chromatography (SiO2) if necessary.ReferencesJOC, 1994, 59, 2314-2323.Synthesis, 1979, 957-961.[Back to Top] [Back to Synthetic Procedures]Boc - (t Butyloxy) carbamateStandard Protection ProcedureThe amine is dissolved in water and sodium bicarbonate (2 eq) is added with stirring. The resulting solution is cooled to 5° and BOC anhydride (1.5 eq) is added slowly as a solution in para-dioxane (also cooled). The resulting mixture is stirred at 0° for 1 h and allowed to warm to room temperature overnight. Water is then added and the aqueous layer is extracted 2 times with EtOAc. The organic layer is back extracted twice with saturated sodium bicarbonate solution. The combined aqueous layers are acidified to a pH of 1 with 10% HCl, then extracted 3 times with EtOAc. The combined organic layers are dried (sodium sulfate) and concentrated in vacuo. The resulting residue can then be purified by flash chromatography (SiO2) if necessary.RemovalThe compound is dissolved in 1:1 trifluoroacetic acid:water and stirred at room temperature until complete by TLC (usually <2h). The solution is concentrated in vacuo and purified by flash chromatography (SiO2) if necessary.ReferencesOrganic Synthesis, 1999, 76, 57-76.Novabiochem Catalog, 2002-2003, pg 2.64-2.65.[Back to Top] [Back to Synthetic Procedures]Fmoc - (9-fluorenylmethyl) carbamateStandard Protection ProcedureThe amine is dissolved in water and sodium bicarbonate (2 eq) is added with stirring. The resulting solution is cooled to 5° and Fmoc-OSu or Fmoc-Cl (1.5 eq) is added slowly as a solution in para-dioxane (also cooled). The resulting mixture is stirred at 0° for 1 h and allowed to warm to room temperature overnight. Water is then added and the aqueous layer is extracted 2 times with EtOAc. The organic layer is back extracted twice with saturated sodium bicarbonate solution. The combined aqueous layers are acidified to a pH of 1 with 10% HCl, then extracted 3 times with EtOAc. The combined organic layers are dried (sodium sulfate) and concentrated in vacuo. The resulting residue can then be purified by flash chromatography (SiO2) if necessary.RemovalThe compound is dissolved in a solution of 20% piperidine in DMF. The mixture is stirred for 30 minutes at roomtemperature and concentrated in vacuo. The residue can then be purified by flash chromatography (SiO2) if necessary.ReferencesJ. Am. Chem. Soc., 1997, 4, 656-673.Novabiochem Catalog, 2002-2003, pg 2.64-2.65.[Back to Top] [Back to Synthetic Procedures]Alloc - (allyl) carbamateStandard Protection ProcedureThe amine is dissolved in water and sodium carbonate (2.7 eq) is added with stirring. The resulting solution is cooled to 5° and allyl chloroformate (1.5 eq) is added slowly as a solution in para-dioxane (also cooled). The resulting mixture is stirred at 0° for 1 h and allowed to warm to room temperature overnight. Water is then added and the aqueous layer is extracted 2 times with EtOAc. The organic layer is back extracted twice with saturated sodium bicarbonate solution. The combined aqueous layers are acidified to a pH of 1 with 10% HCl, then extracted 3 times with EtOAc. The combined organic layers are dried (sodium sulfate) and concentrated in vacuo. The resulting residue can then be purified by flash chromatography(SiO2) if necessary.RemovalThe amine is dissolved in dry THF and dimethylmalonate (7 eq) followed by tetrakistriphenylphosphine palladium (0.02 eq) are added at room temperature under an inert atmosphere. The reaction is stirred until complete by TLC (usually 24 h) and filtered. The solution is then concentrated in vacuo and the resulting residue is purified by flash chromatography (SiO2) if necessary.ReferencesTetrahedron, 1996, 39, 12839-12852.Tetrahedron Lett. 1986, 23, 2599-2602.[Back to Top] [Back to Synthetic Procedures]Troc - (trichloroethyl) carbamateStandard Protection ProcedureThe amine is dissolved in water and sodium bicarbonate (2 eq) is added with stirring. The resulting solution is cooled to 5° and Troc-OSu or Troc-Cl (1.5 eq) is added slowly as a solution in para-dioxane (also cooled). The resulting mixture is stirred at 0° for 1 hour and allowed to warm to room temperature overnight. Water is then added and the aqueous layer isextracted 2 times with EtOAc. The organic layer is back extracted twice with saturated sodium bicarbonate solution. The combined aqueous layers are acidified to a pH of 3 with 5% HCl, then extracted 3 times with EtOAc. The combined organic layers are dried (sodium sulfate) and concentrated in vacuo. The resulting residue is purified by flash chromatography(SiO2) if necessary.RemovalThe carbamate is dissolved in glacial acetic acid:THF 1:1 and zinc dust (excess) is added. The resulting suspension is stirredat room temperature until complete by TLC (usually <3 h). The mixture is then filtered, concentrated in vacuo andredissolved in chloroform. The solution is washed once with 5% aqueous sodium bicarbonate, dried (sodium sulfate), and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.ReferencesCan. J. Chem. 1982, 60, 976.Synthesis, 1983, 671.JOC, 1988, 53, 3108.[Back to Top] [Back to Synthetic Procedures]Cbz - (benzylcarboxy) carbamateStandard Protection ProcedureThe amine is dissolved in water and sodium bicarbonate (2 eq) is added with stirring. The resulting solution is cooled to 5° and Cbz-OSu or Cbz-Cl (1.5 eq) is added slowly as a solution in para-dioxane (also cooled). The resulting mixture is stirred at 0° for 1 h and allowed to warm to room temperature overnight. Water is then added and the aqueous layer is extracted 2 times with EtOAc. The organic layer is back extracted twice with saturated sodium bicarbonate solution. The combined aqueous layers are acidified to a pH of 1 with 10% HCl, then extracted 3 times with EtOAc. The combined organic layers are dried (sodium sulfate) and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) ifnecessary.RemovalThe amino acid derivative is dissolved in 1:1 methanol:t-butanol and Pd(OH)2-C is added under a hydrogen atmosphere. The mixture is allowed to stir until complete by TLC (usually >3 h) then filtered and concentrated in vacuo. The resulting residue is purified by flash chromatography (SiO2) if necessary.ReferencesTetrahedron Lett. 1966, 7, 4765-4768.[Back to Top] [Back to Synthetic Procedures]t Bu - (tert-butyl) etherStandard Protection ProcedureSee: JOC,1975, 6, 675-681 for general procedure.RemovalThe ether is dissolved in 1:1 trifluoroacetic acid:water and stirred at room temperature until the reaction is complete byTLC (usually <2 h). The solution is concentrated and purified by flash chromatography (SiO2) if necessary.ReferencesJOC,1975, 6, 675-681Novabiochem Catalog, 2002-2003, pg 2.64-2.65./mcgarveylab/Carbsyn/AminoAcids.html本站一切内容源于互联网搜索,禁止商用！有任何不妥请联系:xu8513879#(将#换成@),我们在24小时内删除相关内容。
芳胺化反应综述
报告人:张 俊 祥
Scheme
NH2
R'
+R +R
Y
Met.Cat., Base Solvent R
N
R'
R1 N
R2
Y
Met.Cat., Base Solvent
R1 N
R2
R
二芳胺化合物
Diarylamines were prepared by the condensation of an aniline with an arenesulfonic acid (8.90 mol) (1.56 mol)
J. Chem. Soc., Perkin Trans. 1, 2000, 2695–2701
三芳胺化合物
Base: KOH
Ullmann condensation of diarylamines with iodobenzenes has been investigated under homogeneous and heterogeneous catalytic conditions with cuprous and curpic salts, as well as powdered copper metal. Copper catalyzed condensation of diarylamines with iodoaromatics is relatively insensitive to substituent (for substituted iodobenzenes p = -0.25; for substituted diphenylamines p = 1.09) but quite sensitive to halogen ( k I / k B , > 200). This hypothesis rationalizes many of the perplexing results which typify the literature associated with copper catalyzed nucleophilic aromatic substitution.
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Under construction Appendix 3
Flash Chromatography1 (FC). Mircea D. GheorghiuColumn chromatography allows multiple components to be separated (therefore it is preparative). Unlike with gravity column chromatography, using air pressure to force the solvent through the column reduces the chromatography time, therefore making the column and running the separation could take less than 10-15 minutes. The absorbent has a much smaller particle size (about the same as that on TLC plate). There are many different of kinds of chromatographic columns. If the column contains a porous plate to support packing, no additional support such as cotton, glasswool and sand is necessary.
Safety Guidelines: 1.Silica gel (SiO2.xH2O) should be weighed and transferred in the hood to avoid inhalation. Silica gel is a fine powder and lung irritant. 2. ----to be added----
Step 1. Finding the solvent system. Find the solvent system that gives an Rf3of approximately 0.35 on a silica gel plate.4 For a general separation it is useful to start with ethyl acetate-petroleum ether (bp 30º C-60º C). For polar compounds use acetone (or methylene chloride) and petroleum ether (bp 30º C-60º C). Dissolve a small amount of the crude material in a minute amount of ether or dichloromethane (1-2% solution, 20-40 mg in 2 mL of the solvent). Make a line at 1 cm from the bottom and another line at 1 cm from the top of 3x7 cm normal-phase silica gel TLC plate. With a micropipet make a spot 1-2 mm in diameter (adding once or twice; overloading causes tailing) on the starting line. Try different solvents until one that results in an Rf of 0.35 is attained. The spot can be easily visualized with a short-wave UV light (254 nm). Carefully circle the spot with a pencil. Calculate the Rf.
Eluotropic series for silica gel (increasing eluting power)______________CyclohexanePetroleum ether
1 Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.
3 Rf stands for ratio to the front.
4 Kodak plastic-backed TLC plate #13181 with fluorescent indicator. CAS number [63231-67-4].
FC-1
WARNING NOTICE: The experiments described in these materials are potentially hazardous and require a high level ofsafety training, special facilities and equipment, and supervision by appropriate individuals. You bear the sole responsibility, liability, and risk for the implementation of such safety procedures and measures. MIT shall have no responsibility, liability, or risk for the content or implementation of any of the material presented. Legal Notices PentaneTrichloromethaneEthyl etherEthyl acetateEthanolWaterAcetoneAcetic acidMethanol______________
Step 2. Selecting the column diameter. There are several set-ups available for FC. The recommended length of a FC column is ca 18 (ca. 46 cm) inches long. However, sample size and the difference in Rf (?Rf) between components to be separated dictates the column diameter you should pick to run the FC. For example if you have a sample of approximately 1 g, and the solvent system separated the two components with ?Rf = 0.2
you should choose a column with a 3 cm diameter, collect fractions of 20 mL size and use ca 400 mL of eluent.
Table 1. Guidelines to choose the diameter of a FC chromatography column.1 Sample loading (g) Column diameter (mm) Fraction size (mL) Eluent volume (mL)?Rf > 0.2 ?Rf ˜ 0.1
0.100 0.040 10 5 100 0.400 0.160 20 10 200 0.900 0.360 30 20 400 1.600 0.600 40 30 600 2.500 1.000 50 50 1000
Step 3. The column preparation. To purify ca 1 g of crude product, choose a 50-cm column with a 20 mm inside diameter. The silica gel height should not exceed 5-6 inches (ca. 12-15 cm). Clamp the column in the upright position. Note: If the column contains a porous plate to support packing omit the cotton and sand support; go to step 3.
1.Using a glass rod, carefully pack a small piece of cotton in the bottom of the column. 2. Add approximately 1/8” of 50-100 mesh sand.5
3.A. Close the stopcock and add solvent until the column is approximately 1/3 full. Add ca. 5-6 inches of 230-400 mesh (23-40 µm) silica gel6 in 100-mL beaker.
5 Coarse Ottawa sand
FC-2