我们感谢来自纽约州立大学石溪分校大手笔启动资金，支持这项工作。我们也感谢TOSOH F-科技有限公司为我们提供TMSCF 3试剂TOGNI试剂II的合成。

1.前体的制备:4-（N -hydroxyacetamido）苯甲酸（1a）的合成<ol><li> 还原甲基-4-硝基苯甲酸甲酯。 <ol><li>加甲基5.00克4-硝基苯甲酸酯（27.6毫摩尔，1.00当量），5％铑炭（铑/℃，0.300摩尔％的Rh）159毫克，和磁力搅拌棒的烘箱干燥的250个ml的双颈圆底烧瓶中（在150℃下干燥18小时）。 注:试剂可以在环境气氛下进行称重。然而，反应需要在氮气氛下，以进行。 </li><li>烧瓶中的一个颈部连接到氮/真空歧管帽等颈部有隔膜。执行三次真空-再填充循环（即，空气泵出将烧瓶和更换所得真空以氮气），以取代空气中氮气的烧瓶中。 </li><li>添加138毫升无水四氢呋喃（THF，0.200 M），使用气密注射器向反应烧瓶中。酷搅拌反应mixt的茜在0℃下15分钟。 </li><li>添加1.47 ml的一水合肼（1.52克，30.4毫摩尔，1.20当量）滴加到反应混合物在0℃下用气密注射器。监视使用薄层色谱（TLC）的反应。使用己烷:乙酸乙酯（EtOAc）（4:1体积/体积，R F = 0.23）作为洗脱剂来开发薄层。 </li><li>当甲基-4-硝基苯甲酸甲酯被完全消耗，通过硅藻土在60ml的短垫（即，硅藻土，5克）过滤该反应混合物用真空过滤熔块布氏漏斗。洗用EtOAc过滤器（20毫升×3次）。使用旋转蒸发，得到粗的4-（N- -hydroxyamino）苯甲酸甲酯，其直接使用而不需要进一步纯化，真空浓缩滤液。 </li></ol></li><li> 4-（N -hydroxyamino）苯甲酸乙酰保护 <ol><li>添加2.55克碳酸氢钠（ 碳酸氢钠 ，30.4毫摩尔，1.20当量），所有的粗从先前步骤中获得的4-（N- -hydroxyamino）苯甲酸甲酯，和搅拌棒的烘箱干燥的500个毫升双颈圆底烧瓶中。 </li><li>盖上单颈有隔膜且连接另一个脖子氮气/真空歧管。执行三次真空 - 再填充循环更换空气与氮气的烧瓶中。 </li><li>添加138毫升无水二乙醚（Et 2 O等，0.200 M）的使用气密注射器向反应烧瓶中。凉爽和搅拌在0℃下将反应混合物15分钟。 </li><li>在无水Et 2 O等（138毫升，0.220 M）的制备的乙酰氯的溶液（2.17毫升，2.39克，30.4毫摩尔，1.20当量）。添加使用注射泵在0℃的溶液，以将反应混合物在10.0毫升/小时的速度。 </li><li>在添加结束时，通过硅藻土短垫过滤反应混合物（即，硅藻土，5克）在60毫升用真空过滤熔块布氏漏斗。洗用EtOAc过滤器（20毫升×3次）。浓缩使用旋转蒸发滤液在真空中 。 </li><li>纯化粗产物用快速柱色谱法35纯化，用己烷:乙酸乙酯（4:1至1:1（体积/体积））（R F = 0.13，己烷:乙酸乙酯（4:1（体积/体积）），得到5.31克甲基4-（N- -hydroxyacetamido）苯甲酸甲酯，为浅黄色固体（25.4毫摩尔，92％产率）。 </li></ol></li></ol> 2.合成4-（N - （三氟甲氧基）乙酰氨基）苯甲酸甲酯的（2a）的<ol><li>添加2.00的克甲基4-（N- -hydroxyacetamido）苯甲酸甲酯（1a）的 （9.56毫摩尔，1.00当量）的，311毫克的铯2 CO 3（0.956毫摩尔，10.0％摩尔），3.63克TOGNI试剂Ⅱ的（11.5毫摩尔， 1.20当量）和磁搅拌棒的烘箱干燥的250ml园底烧瓶手套箱（氮气氛中）。 注意:此反应也可以使用Schlenk技术手套箱以外进行。 注意:纯TOGNI试剂二是撞击和摩擦敏感，明火S，应避免火花和/或研磨。柔软和抛光工具应该用于操作。此外，该反应混合物应该后面的安全防护罩进行搅拌。36 </li><li>添加95.6 ml的干燥并脱气的氯仿（ 氯仿 ，0.100 M）的反应烧瓶中。 </li><li>帽与隔膜的烧瓶中并搅拌，在23℃ 的 N 2气氛下，将反应混合物的内部或手套箱16小时之外。 </li><li>通过过滤漏斗过滤该反应混合物以除去任何固体残余物​​。集中使用旋转蒸发器将滤液在真空中。 </li><li>二氯甲烷（CH 2 Cl 2中）:用快速柱色谱纯化，用己烷纯化粗产物（7:3至0:1（体积/体积））（R F = 0.44（CH 2 Cl 2中），得到 2.51克的4-（N - （三氟甲氧基）乙酰氨基）苯甲酸甲酯（9.05毫摩尔，95％产率）。 注:TOGNI试剂II准备协议源就文献方法37和在-35℃下储存在手套箱冷冻器以保持其在一段长期的品质。此反应是氧敏感。虽然所有的试剂可以在环境气氛下称出在RT，除去从反应烧瓶所有氧气是至关重要的。干燥并脱气氯仿的制备是通过从CAH 2氮气氛，接着通过进行冷冻-泵-解冻过程的三个周期下蒸馏它。 </li></ol> 经由 OCF 3 -migration（3a）的4-乙酰氨基-3-（三氟甲氧基）苯甲酸甲酯的合成3.甲酯的<ol><li>添加2.51克4-（N - （三氟甲氧基）乙酰氨基）苯甲酸甲酯（9.05毫摩尔，1.0当量），磁搅拌棒，和9.05米诺2（1.00 M）中的溶液到50毫升压力容器中。帽带螺丝帽的容器中。 </li><li>搅拌在120℃的反应混合物中的安全防护罩20小时后。 注意:不纯硝基甲烷是爆炸性的，因此反应混合物应在安全防护罩后面进行搅拌。 </li><li>冷却反应混合物至RT。 </li><li>将反应混合物转移到100ml圆底烧瓶中。 </li><li>集中使用旋转蒸发器在真空下将反应混合物。 </li><li>纯化粗产物用快速柱色谱纯化，用己烷:EtOAc（9:1至7:3（V / V））（R F = 0.51己烷:乙酸乙酯（4:1（体积/体积）），得到 2.13克4-乙酰氨基-3-（三氟甲氧基）苯甲酸甲酯（7.69毫摩尔，85％）。 注意:此反应可以在环境气氛下进行。不需要氮气氛。圆底烧瓶中装有水冷凝器，可作为一种替代的反应装置。 </li></ol>新产品4表征<ol><li>表征的所有新的化合物通过 1 H，13 C NMR光谱和高分辨质谱和使用19 F核磁共振光谱来表征包含氟原子的化合物。34 </li></ol>

<ol>
	<li>Yagupolskii, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sintez+proizvodnykh+feniltriftormetilovogo+efira.">Sintez proizvodnykh feniltriftormetilovogo efira.</a> Dokl. Akad. Nauk SSSR. 105, 100-102 (1955).</li><li>Booth, H. S., Burchfield, P. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluorination+of+halogeno+methyl+ethers.+I.+Fluorination+of+trichlorodimethyl+ether.">Fluorination of halogeno methyl ethers. I. Fluorination of trichlorodimethyl ether.</a> J. Am. Chem. Soc. 57, 2070 (1935).</li><li>McClinton, M. A., McClinton, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trifluoromethylations+and+related+reactions+in+organic-chemistry.">Trifluoromethylations and related reactions in organic-chemistry.</a> Tetrahedron. 48, 6555-6666 (1992).</li><li>Hansch, C., Leo, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Substituent Constants for Correlation Analysis in Chemistry and Biology. , (1979).</li><li>Leroux, F., Jeschke, P., Schlosser, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alpha-fluorinated+ethers,+thioethers,+and+amines:+Anomerically+biased+species.">Alpha-fluorinated ethers, thioethers, and amines: Anomerically biased species.</a> Chem. Rev. 105, 827-856 (2005).</li><li>Jeschke, P., Baston, E., Leroux, F. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alpha-fluorinated+ethers+as+'exotic'+entity+in+medicinal+chemistry.">Alpha-fluorinated ethers as 'exotic' entity in medicinal chemistry.</a> Mini-Rev. Med. Chem. 7, 1027-1034 (2007).</li><li>Leroux, F. R., Manteau, B., Vors, J. P., Pazenok, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trifluoromethyl+ethers+-+synthesis+and+properties+of+an+unusual+substituent.">Trifluoromethyl ethers - synthesis and properties of an unusual substituent.</a> Beilstein J. Org. Chem. 4, (2008).</li><li>Fantasia, S., Welch, J. M., Togni, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reactivity+of+a+hypervalent+iodine+trifluoromethylating+reagent+toward+THF:+ring+opening+and+formation+of+trifluoromethyl+ethers.">Reactivity of a hypervalent iodine trifluoromethylating reagent toward THF: ring opening and formation of trifluoromethyl ethers.</a> J. Org. Chem. 75, 1779-1782 (2010).</li><li>Manteau, B., Pazenok, S., Vors, J. P., Leroux, F. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+trends+in+the+chemistry+of+alpha-fluorinated+ethers,+thioethers,+amines+and+phosphines.">New trends in the chemistry of alpha-fluorinated ethers, thioethers, amines and phosphines.</a> J. Fluorine Chem. 131, 140-158 (2010).</li><li>Landelle, G., Panossian, A., Leroux, F. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trifluoromethyl+ethers+and+-thioethers+as+tools+for+medicinal+chemistry+and+drug+discovery.">Trifluoromethyl ethers and -thioethers as tools for medicinal chemistry and drug discovery.</a> Curr. Top. Med. Chem. 14, 941-951 (2014).</li><li>Liang, T., Neumann, C. N., Ritter, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Introduction+of+fluorine+and+fluorine-containing+functional+groups.">Introduction of fluorine and fluorine-containing functional groups.</a> Angew. Chem. Int. Ed. 52, 8214-8264 (2013).</li><li>Yarovenko, N. N., Vasileva, A. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+method+for+the+introduction+of+trihalomethyl+groups+into+organic+molecules.">A new method for the introduction of trihalomethyl groups into organic molecules.</a> Zh. Obshch. Khim. 28, 2502-2504 (1958).</li><li>Yagupols, L., Troitskaya, V. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+phenyl+trifluoromethyl+ether+derivatives.">Synthesis of phenyl trifluoromethyl ether derivatives.</a> Zh. Obshch. Khim. 31, 915-924 (1961).</li><li>Yagupolskii, L. M., Orda, V. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bis(triftormetoksi+I+triftormetilmerkapto)-proizvodnye+benzola.">Bis(triftormetoksi I triftormetilmerkapto)-proizvodnye benzola.</a> Zh. Obshch. Khim. 34, 1979-1984 (1964).</li><li>Louw, R., Franken, P. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+side-chain+chlorination+of+methoxybenzenes.">Selective side-chain chlorination of methoxybenzenes.</a> Chem Ind-London. , 127-128 (1977).</li><li>Feiring, A. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemistry+in+hydrogen-fluoride.+7.+Novel+synthesis+of+aryl+trifluoromethyl+ethers.">Chemistry in hydrogen-fluoride. 7. Novel synthesis of aryl trifluoromethyl ethers.</a> J. Org. Chem. 44, 2907-2910 (1979).</li><li>Salome, J., Mauger, C., Brunet, S., Schanen, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+conditions+and+activity+of+various+Lewis+acids+for+the+fluorination+of+trichloromethoxy-benzene+by+HF+in+liquid+phase.">Synthesis conditions and activity of various Lewis acids for the fluorination of trichloromethoxy-benzene by HF in liquid phase.</a> J. Fluorine Chem. 125, 1947-1950 (2004).</li><li>Sheppard, W. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alpha-Fluorinated+Ethers.+I.+Aryl+Fluoroalkyl+Ethers.">Alpha-Fluorinated Ethers. I. Aryl Fluoroalkyl Ethers.</a> J. Org. Chem. 29, 1-11 (1964).</li><li>Kuroboshi, M., Suzuki, K., Hiyama, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oxidative+desulfurization-fluorination+of+xanthates+-+a+convenient+synthesis+of+trifluoromethyl+ethers+and+difluoro(methylthio)methyl+ethers.">Oxidative desulfurization-fluorination of xanthates - a convenient synthesis of trifluoromethyl ethers and difluoro(methylthio)methyl ethers.</a> Tetrahedron Lett. 33, 4173-4176 (1992).</li><li>Kanie, K., Tanaka, Y., Suzuki, K., Kuroboshi, M., Hiyama, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+convenient+synthesis+of+trifluoromethyl+ethers+by+oxidative+desulfurization-fluorination+of+dithio+carbonates.">A convenient synthesis of trifluoromethyl ethers by oxidative desulfurization-fluorination of dithio carbonates.</a> Bull. Chem. Soc. Jpn. 73, 471-484 (2000).</li><li>Kuroboshi, M., Kanie, K., Hiyama, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oxidative+desulfurization-fluorination:+A+facile+entry+to+a+wide+variety+of+organofluorine+compounds+leading+to+novel+liquid-crystalline+materials.">Oxidative desulfurization-fluorination: A facile entry to a wide variety of organofluorine compounds leading to novel liquid-crystalline materials.</a> Adv. Synth. Catal. 343, 235-250 (2001).</li><li>Umemoto, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrophilic+perfluoroalkylating+agents.">Electrophilic perfluoroalkylating agents.</a> Chem. Rev. 96, 1757-1777 (1996).</li><li>Umemoto, T., Adachi, K., Ishihara, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CF3+oxonium+salts,+O-(trifluoromethyl)dibenzofuranium+salts:+in+situ+synthesis,+properties,+and+application+as+a+real+CF3++species+reagent.">CF3 oxonium salts, O-(trifluoromethyl)dibenzofuranium salts: in situ synthesis, properties, and application as a real CF3+ species reagent.</a> J. Org. Chem. 72, 6905-6917 (2007).</li><li>Stanek, K., Koller, R., Togni, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reactivity+of+a+10-I-3+hypervalent+iodine+trifluoromethylation+reagent+with+phenols.">Reactivity of a 10-I-3 hypervalent iodine trifluoromethylation reagent with phenols.</a> J. Org. Chem. 73, 7678-7685 (2008).</li><li>Koller, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Zinc-mediated+formation+of+trifluoromethyl+ethers+from+alcohols+and+hypervalent+iodine+trifluoromethylation+reagents.">Zinc-mediated formation of trifluoromethyl ethers from alcohols and hypervalent iodine trifluoromethylation reagents.</a> Angew. Chem. Int. Ed. 48, 4332-4336 (2009).</li><li>Trainor, G. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+preparation+of+O-trifluoromethyl+carbohydrates.">The preparation of O-trifluoromethyl carbohydrates.</a> J. Carbohydr. Chem. 4, 545-563 (1985).</li><li>Nishida, M., Vij, A., Kirchmeier, R. L., Shreeve, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+polyfluoro+aromatic+ethers+-+a+facile+route+using+polyfluoroalkoxides+generated+from+carbonyl+and+trimethysilyl+compounds.">Synthesis of polyfluoro aromatic ethers - a facile route using polyfluoroalkoxides generated from carbonyl and trimethysilyl compounds.</a> Inorg. Chem. 34, 6085-6092 (1995).</li><li>Kolomeitsev, A. A., Vorobyev, M., Gillandt, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Versatile+application+of+trifluoromethyl+triflate.">Versatile application of trifluoromethyl triflate.</a> Tetrahedron Lett. 49, 449-454 (2008).</li><li>Marrec, O., Billard, T., Vors, J. P., Pazenok, S., Langlois, B. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+deeper+insight+into+direct+trifluoromethoxylation+with+trifluoromethyl+triflate.">A deeper insight into direct trifluoromethoxylation with trifluoromethyl triflate.</a> J. Fluorine Chem. 131, 200-207 (2010).</li><li>Marrec, O., Billard, T., Vors, J. P., Pazenok, S., Langlois, B. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+and+direct+trifluoromethoxylation+of+aliphatic+substrates+with+2,4-dinitro(trifluoromethoxy)benzene.">A new and direct trifluoromethoxylation of aliphatic substrates with 2,4-dinitro(trifluoromethoxy)benzene.</a> Adv. Synth. Catal. 352, 2831-2837 (2010).</li><li>Huang, C. H., Liang, T., Harada, S., Lee, E., Ritter, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Silver-mediated+trifluoromethoxylation+of+aryl+stannanes+and+arylboronic+acids.">Silver-mediated trifluoromethoxylation of aryl stannanes and arylboronic acids.</a> J. Am. Chem. Soc. 133, 13308-13310 (2011).</li><li>Rozen, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+fluorinations+by+reagents+containing+the+OF+group.">Selective fluorinations by reagents containing the OF group.</a> Chem. Rev. 96, 1717-1736 (1996).</li><li>Venturini, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+trifluoro-methoxylation+of+aromatics+with+perfluoro-methyl-hypofluorite.">Direct trifluoro-methoxylation of aromatics with perfluoro-methyl-hypofluorite.</a> J. Fluorine Chem. 140, 43-48 (2012).</li><li>Hojczyk, K. N., Feng, P., Zhan, C., Ngai, M. -. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trifluoromethoxylation+of+arenes:+synthesis+of+ortho-trifluoromethoxylated+aniline+derivatives+by+OCF3+migration.">Trifluoromethoxylation of arenes: synthesis of ortho-trifluoromethoxylated aniline derivatives by OCF3 migration.</a> Angew. Chem. Int. Ed. 53, 14559-14563 (2014).</li><li>Still, W. C., Kahn, M., Mitra, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid+chromatographic+technique+for+preparative+separations+with+moderate+Resolution.">Rapid chromatographic technique for preparative separations with moderate Resolution.</a> J. Org. Chem. 43, 2923-2925 (1978).</li><li>Fiederling, N., Haller, J., Schramm, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Notification+about+the+Explosive+Properties+of+Togni's+Reagent+II+and+One+of+Its+Precursors.">Notification about the Explosive Properties of Togni's Reagent II and One of Its Precursors.</a> Org. Process Res. Dev. 17, 318-319 (2013).</li><li>Matousek, V., Pietrasiak, E., Schwenk, R., Togni, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=One-pot+synthesis+of+hypervalent+iodine+reagents+for+electrophilic+trifluoromethylation.">One-pot synthesis of hypervalent iodine reagents for electrophilic trifluoromethylation.</a> J. Org. Chem. 78, 6763-6768 (2013).</li></ol>

The authors declare no competing financial interests.

由于缺乏一个全面和人性化的程序trifluoromethoxylated芳烃的合成，许多OCF 3含芳香族化合物是非常昂贵的。34我们的策略取代了广阔的官能团耐受性，并提供了一个易于访问各种trifluoromethoxylated芳烃。这些化合物可以作为用于新药物，农用化学品，和材料的发现和开发作为有价值积木。 肼用作氢的来源为铑催化的还原硝基芳烃的。其质量是在获得还原产物中高产...

该三氟甲氧基（OCF 3）集团已在1935年2，因为三氟甲基醚的首次合成生命和材料科学的研究产生深远的影响。由于其独特的电负性高的组合（χ= 3.7）3和优良的亲脂性（ΠX = 1.04），4三氟甲氧基发现在医药，农业和材料行业有着广泛的应用。5-10但是，轻便引入OCF 3组分成有机分子，尤其是芳香族化合物，保留在合成化学的一个重大挑战。 在过去的几十年中，努力解决这一挑战导致少数变换为trifluoromethoxylated芳烃的合成的发展5-7,9-11这些包括:（i）氯/氟对三氯化前体交换; 1,12- -17（ⅱ）deoxyfluorination fluoroformates的; 18 </SUP&gt;（ⅲ）氧化fluorodesulfurization; 19-21（ⅳ）醇的亲电三氟甲基化; 22-25（v）的亲核trifluoromethoxylation; 26-30，（ⅵ）过渡金属-介导的芳基硼酸盐和锡烷的trifluoromethoxylation; 31及（vii ）基团trifluoromethoxylation。32,33然而，许多这些方法要么患有差基板范围，或需要使用高毒性和/或热不稳定的试剂。因此，由于缺乏合成OCF 3含化合物的一般的和用户友好的方法，该OCF 3组的潜力还没有得到充分利用在化学。 作为我们在trifluoromethoxylation反应利益的一部分，34我们描述本文的两步协议 （即， 自由基 O2 -trifluoromethylation和热诱导OCF 3 -migration）为甲基-4-乙酰氨基-3-（三氟甲氧基的合成）苯甲酸甲酯（3a）的选自甲基4-（N- -hydroxyacetamido）苯甲酸甲酯（1a）中 。该策略是易于操作，适用于大范围的邻 -trifluoromethoxylated苯胺衍生物的合成。

<table><tbody><tr><td>5% Rhodium on carbon</td><td>Aspira Scientific</td><td>300835</td><td>5% wt% dry loading</td></tr><tr><td>Hydrazine monohydrate</td><td>Sigma-Alderich</td><td>13696HMV</td><td>Reagent grade, 98%</td></tr><tr><td>Acetyl chloride</td><td>Alfa Aesar</td><td>10176887</td><td>98%</td></tr><tr><td>Sodium bicarbonate</td><td>Fisher Scientific</td><td>134826</td><td>Chemical pure</td></tr><tr><td>Cesium carbonate</td><td>Alfa Aesar</td><td>12887</td><td>99.9%, metals basis</td></tr><tr><td>Togni Reagent II</td><td></td><td></td><td>Prepared according to the literature procedure (ref 37). Caution: Pure Togni reagent II is impact and friction sensitive, treat it with great care (see ref. 36).</td></tr><tr><td>Tetrahydrofuran</td><td>BDH</td><td>BDH1149-4LG</td><td>Distilled from deep purple sodium benzophenone ketyl.</td></tr><tr><td>Diethyl Ether</td><td>Fisher Scientific</td><td>148221</td><td>Distilled from deep purple sodium benzophenone ketyl.</td></tr><tr><td>Chloroform</td><td>Fisher Scientific</td><td>141739</td><td>Dried over CaH&lt;sub&gt;2&lt;/sub&gt; and distilled</td></tr><tr><td>Nitromethane</td><td>Alfa Aesar</td><td>J03z053</td><td>Dried over CaSO&lt;sub&gt;4&lt;/sub&gt; and distilled</td></tr><tr><td>Silica gel</td><td>SILICYCLE</td><td>60514</td><td>40-63 &amp;micro;m (230-400 mesh)</td></tr><tr><td>Celite</td><td>EMD</td><td>2012040674</td><td>Not acid washed</td></tr></tbody></table>

protocol for the synthesis of ortho-trifluoromethoxylated aniline derivatives

分子轴承三氟甲氧基（OCF 3）基团常表现所需的药理学和生物学性质。然而，trifluoromethoxylated芳香族化合物的简便合成保持在有机合成中一个巨大的挑战。传统的方法往往来自贫困基底范围受到影响，或要求使用高毒，难以处理，和/或热不稳定的试剂。此，我们报告为甲基-4-乙酰氨基-3-（三氟甲氧基）苯甲酸甲酯的使用合成一个用户友好的协议-1-三氟甲基-1,2-苯碘酰-3-（1H） -酮（TOGNI试剂Ⅱ）。在碳酸铯的催化量存在下处理甲基4-（N- -hydroxyacetamido）苯甲酸甲酯（1a）与 TOGNI试剂II（铯2 CO 3）的氯仿在室温，得到4-（N - （三氟甲氧基）乙酰氨基）苯甲酸甲酯（2a）中 。然后将该中间体转化为最终产物甲基-4-乙酰氨基-3-（trifluoromethoxy）苯甲酸甲酯（3a）的硝基甲烷中，在120℃。此过程是一般性的，可以应用到邻 -trifluoromethoxylated苯胺衍生物的广谱性，这可以作为有用的合成构建模块的新药物，农用化学品和功能材料的发现和开发的合成。

甲基-4-（N- -hydroxyacetamido）苯甲酸甲酯（1a）的合成在92％分离产率，通过一个两步骤的过程（即，减少甲基-4-硝基苯甲酸甲酯用肼用5％的Rh / C作为催化剂，以形成4-（ Ñ-hydroxyamino）苯甲酸甲酯，然后将所得羟胺乙酰保护）1a中与TOGNI试剂II在的碳酸铯的催化量存在的O-三氟甲基化（铯2 CO 3）的氯仿?...

Watch this Scientific Journal Video about Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives at JoVE.com

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

协议的合成<em&gt;邻</em&gt; -trifluoromethoxylated苯胺类化合物

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Aromatic Compounds

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9.9K 次观看.  State University of New York at Stony Brook. An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

视频: Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 &deg;C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. 
The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Herein is described the synthesis, isolation, and reactions of hypervalent iodonium alkynyl triflates (HIATs) with azides to generate cyanocarbenes. The procedures will involve air-sensitive and cryogen techniques, including cold filtration under an inert atmosphere. Handling and safety of the synthesized compounds will also be discussed.

高价碘鎓炔基三氟甲磺酸酯的生成Cyanocarbenes的合成应用

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent ...

科研

化学

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. In this article, an easy method for the modification of the guanidine group in peptidic ligands is provided, with an example of RGD-binding integrin ligands. It was recently demonstrated that the distinct modification of the guanidine group in these ligands allows for the selective modulation of the subtype (e.g., between the subtypes &#945;v and &#945;5). Moreover, a formerly unknown strategy for the functionalization via the guanidine group was demonstrated, and the synthetic approach is reviewed in this document. The modifications described here involve terminally (N&#969;) alkylated and acetylated guanidine groups. For the synthesis, tailor-made precursor molecules are synthesized, which are then subjected to a reaction with an orthogonally deprotected amine to transfer the pre-modified guanidine group. For the synthesis of alkylated guanidines, precursors based on N,N&#8242;-Di-Boc-1H-pyrazole-1-carboxamidine are used to synthesize acylated compounds, the precursor of choice being a correspondingly acylated derivative of N-Boc-S-methylisothiourea, which can be obtained in one- and two-step reactions.

A protocol for the synthesis of alkyl-modified guanidines based on the use of the corresponding precursors is presented.

修改和胍集团的官能通过量身定制的前兆

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. ...

生物化学

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order to streamline synthesis by saving steps, time and material compared to conventional methods that require the introduction and removal of activating or directing groups. Therefore, the functionalization of C-H bonds is also attractive for green chemistry. Under oxidative conditions, two C-H bonds or one C-H and one heteroatom-H bond can be transformed to C-C and C-heteroatom bonds, respectively. Often these oxidative coupling reactions require synthetic oxidants, expensive catalysts or high temperatures. Here, we describe a two-step procedure to functionalize indole derivatives, more specifically tetrahydrocarbazoles, by C-H amination using only elemental oxygen as oxidant. The reaction uses the principle of C-H functionalization via Intermediate PeroxideS (CHIPS). In the first step, a hydroperoxide is generated oxidatively using visible light, a photosensitizer and elemental oxygen. In the second step, the N-nucleophile, an aniline, is introduced by Br&#248;nsted-acid catalyzed activation of the hydroperoxide leaving group. The products of the first and second step often precipitate and can be conveniently filtered off. The synthesis of a biologically active compound is shown.

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

A two-step procedure for the synthesis of pharmaceutically active indole-derivatives by C-H functionalization with anilines is described, using photo- and Br&#248;nsted acid catalysis.

通过中级过氧化物的抗病毒四氢咔唑衍生物的合成光化学和酸催化CH官能（筹）

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order ...

Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are rapidly oxidized, for example by atmospheric oxygen, to indigo type dyes. This reaction enables fast and easy screening in vivo without isolation or purification of enzymes, as well as rapid tests on agar plates or in solution (e.g., blue-white screening, micro-wells) and is used in biochemistry, histochemistry, bacteriology and molecular biology. Unfortunately the synthesis of such substrates proved to be difficult, due to various side reactions and the low reactivity of the indoxyl hydroxyl function. Especially for glucose type structures low yields were observed. Our novel approach employs indoxylic acid ester as key intermediates. Indoxylic acid esters with varied substitution patterns were prepared on scalable pathways. Phase transfer glycosylations with those acceptors and peracetylated glycosyl halides can be performed under common conditions in high yields. Ester cleavage and subsequent mild silver mediated glycosylation yields the peracetylated indoxyl glycosides in high yields. Finally deprotection is performed according to Zempl&#233;n.

Indoxyl glycosides are well-established and widely used tools for enzyme screening and enzyme activity monitoring. Especially for glucose type structures previous syntheses proved to be challenging and low yielding. Our novel approach employs indoxylic acid esters as precious intermediates to yield a considerable number of indoxyl glycosides in good yields.

的吲哚酚苷的检测糖苷酶活动的合成

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are ...

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Representative experimental procedures for the synthesis of N-(2-alkoxyvinyl)sulfonamides and subsequent conversion to phthalan and phenethylamine derivatives are presented in detail.

准备n-(2-alkoxyvinyl) 磺胺从n-tosyl-1,2,3-triazoles 和随后转换为取代 Phthalans 和 Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile ...

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene as representative examples for the practical chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes from the chemoselective iodination of terminal alkynes mediated by hypervalent-iodine reagents. The chemoselectivity was confirmed by using p-tolylethyne as a model substrate to screen a variety of iodine sources and/or the hypervalent-iodine reagents. A combination of tetrabutylammonium iodide (TBAI) and (diacetoxyiodo)benzene (PIDA) selectively generates 1-iodoalkynes, while a combination of KI and PIDA generates 1,2-diiodoalkenes. A one-pot synthesis based on both TBAI-PIDA and KI-PIDA yields the corresponding 1,1,2-triiodoalkenes. These protocols were subsequently applied to the synthesis of synthetically important aromatic and aliphatic 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, which were obtained in good yield with excellent chemoselectivity.

Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

基于末端碘氧化炔烃的 1-Iodoalkynes、12-Diiodoalkenes、11、2 Triiodoalkenes 的 Chemoselective 制备

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and ...

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Maleimide-bearing bifunctional probes have been employed for decades for the site-selective modification of thiols in biomolecules, especially antibodies. Yet maleimide-based conjugates display limited stability in vivo because the succinimidyl thioether linkage can undergo a retro-Michael reaction. This, of course, can lead to the release of the radioactive payload or its exchange with thiol-bearing biomolecules in circulation. Both of these processes can produce elevated activity concentrations in healthy organs as well as decreased activity concentrations in target tissues, resulting in reduced imaging contrast and lower therapeutic ratios. In 2018, we reported the creation of a modular, stable, and easily accessible phenyloxadiazolyl methyl sulfone reagent &#8212; dubbed &#8216;PODS&#8217; &#8212; as a platform for thiol-based bioconjugations. We have clearly demonstrated that PODS-based site-selective bioconjugations reproducibly and robustly create homogenous, well-defined, highly immunoreactive, and highly stable radioimmunoconjugates. Furthermore, preclinical experiments in murine models of colorectal cancer have shown that these site-selectively labeled radioimmunoconjugates exhibit far superior in vivo performance compared to radiolabeled antibodies synthesized via maleimide-based conjugations. In this protocol, we will describe the four-step synthesis of PODS, the creation of a bifunctional PODS-bearing variant of the ubiquitous chelator DOTA (PODS-DOTA), and the conjugation of PODS-DOTA to the HER2-targeting antibody trastuzumab.

In this protocol, we will describe the synthesis of PODS, a phenyoxadiazolyl methyl sulfone-based reagent for the site-selective attachment of cargos to the thiols of biomolecules, particularly antibodies. In addition, we will describe the synthesis and characterization of a PODS-bearing bifunctional chelator and its conjugation to a model antibody.

硫醇反应试剂的合成与生物共轭作用--用于原位选择性修饰免疫共轭的生成

Maleimide-bearing bifunctional probes have been employed for decades for the site-selective modification of thiols in biomolecules, especially antibodies. ...

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyl(tropone)iron

aza-Michael adducts of tricarbonyl(tropone)iron are synthesized by two different methods. Primary aliphatic amines and cyclic secondary amines participate in a direct aza-Michael reaction with tricarbonyl(tropone)iron under solvent-free conditions. Less nucleophilic aniline derivatives and more hindered secondary amines add efficiently to the cationic tropone complex formed by protonation of tricarbonyl(tropone)iron. While the protocol utilizing the cationic complex is less efficient overall for accessing the aza-Michael adducts than the direct, solvent-free addition to the neutral complex, it allows the use of a broader range of amine nucleophiles. Following protection of the amine of the aza-Michael adduct as a tert-butyl carbamate, the diene is decomplexed from the iron tricarbonyl fragment upon treatment with cerium(IV) ammonium nitrate to provide derivatives of 6-aminocyclohepta-2,4-dien-1-one. These products can serve as precursors to diverse compounds containing a seven-membered carbocyclic ring. Because the demetallation requires protection of the amine as a carbamate, the aza-Michael adducts of secondary amines cannot be decomplexed using the protocol described here.

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron

Representative experimental procedures for the addition of amine nucleophiles to tricarbonyl(tropone)iron and subsequent demetallation of the resulting complexes are presented in detail.

通过三碳基(特罗酮)铁制备6-氨基环丙烯-2,4-dien-1-1衍生物

aza-Michael adducts of tricarbonyl(tropone)iron are synthesized by two different methods. Primary aliphatic amines and cyclic secondary amines participate ...

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ketones. The reactions were carried out achieving indoles without any catalyst and with excellent regioselectivity. No traces of 2-aroylindole products were detected. Working with 4-nitronitrosobenzene as starting material, the 3-aroyl-N-hydroxy-5-nitroindole products precipitated from the reaction mixtures and were isolated by filtration without any further purification technique. Differently from the corresponding N-hydroxy-3-aryl indoles that, spontaneously in solution, give dehydrodimerization products, the N-hydroxy-3-aroyl indoles are stable and no dimerization compounds were observed.

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

3-Aroyl-N-hydroxy-5-nitroindoles were synthesized by cycloaddition of 4-nitronitrosobenzene with a conjugated terminal alkynone in a one-step thermal procedure. Preparation of the nitrosoarene and of the alkynones were adequately reported and respectively through oxidation procedures on the corresponding aniline and on the alkynol.

A 直接、再生和原子经济合成3-Aroyl-N-羟基-5-硝基胺基，通过环加4-硝基苯与烷基诺

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ...

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach

Methine-bridged conjugated bicyclic aromatic compounds are common constituents of a range of biologically relevant molecules such as porphyrins, dipyrrinones, and pharmaceuticals. Additionally, restricted rotation of these systems often results in highly to moderately fluorescent systems as observed in 3H,5H-dipyrrolo[1,2-c:2',1'-f]pyrimidin-3-ones, xanthoglows, pyrroloindolizinedione analogs, BODIPY analogs, and the phenolic and imidazolinone ring systems of Green Fluorescent Protein (GFP). This manuscript describes an inexpensive and operationally simple method of performing a Claisen-Schmidt condensation to generate a series of fluorescent pH dependent pyrazole/imidazole/isoindolone dipyrrinone analogs. While the methodology illustrates the synthesis of dipyrrinone analogs, it can be translated to produce a wide range of conjugated bicyclic aromatic compounds. The Claisen-Schmidt condensation reaction utilized in this method is limited in scope to nucleophiles and electrophiles that are enolizable under basic conditions (nucleophile component) and non-enolizable aldehydes (electrophile component). Additionally, both the nucleophilic and electrophilic reactants must contain functional groups that will not inadvertently react with hydroxide. Despite these limitations, this methodology offers access to completely novel systems that can be employed as biological or molecular probes.

The Claisen-Schmidt condensation reaction is an important methodology for the generation of methine-bridged conjugated bicyclic aromatic compounds. Through utilizing a base-mediated variant of the aldol reaction, a range of fluorescent and/or biologically relevant molecules can be accessed through a generally inexpensive and operationally simple synthetic approach.

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