Support of this research by the National Science Foundation through grants 1254545 and 1437814 is gratefully acknowledged.

注:t丁基锂溶液（1.7M在戊烷中）和无水叔丁胺购并立即使用，无需纯化。根据我们的经验，该协议效果最好用新鲜购买的试剂。有机锂试剂的标准化可通过滴定可以采用与二溴乙烷28，二苯基乙酸29或N -pivaloylanilines 30中，由于商业有机锂试剂的浓度可以变化，试剂的质量劣化随时间。戊烷使用溶剂纯化系统纯化。溶剂脱气并贮存在活化的分子筛在使用前24小时。 1.胡德空间的研制注:参见图1。 <ol><li>清除所有杂波的发动机罩。 </li><li>填小烧杯中，用甲苯约等于有机锂试剂的体积的体积，以使用（这里，将10毫升的小规模的协议和50毫升的大型协议），并盖有一个大小合适的手表玻璃。 </li><li>制备异丙醇的烧杯用体积所用有机锂试剂的约5倍量（这里，将50ml的小规模和250毫升的大规模）中，用适当尺寸的表玻璃覆盖。 </li><li>制备含有填充到卷线所使用的有机锂试剂的约10倍体积的干冰颗粒的烧杯中（在此，将100ml的小规模和500毫升的大规模）。 </li><li>在进一步讨论之前，检查锂化剂的腐蚀堆积密封/帽。如果密封被破坏，慢慢加入它8-10x其干冰的量在烧杯处置试剂。 </li></ol> 2.程序的小型锂化的胡德注:参见图1。 <ol><li>充电25毫升Schlenk烧瓶用搅拌棒和整齐的牛逼 BuNH 2（1.8毫升，17.1毫摩尔）和用橡胶隔膜适合它。 </li><li>通过打开Schlenk烧瓶活塞，转动舒伦克线真空短暂 （; 吨 BuNH 2是挥发性的，如果真空下保持会蒸发掉约1秒）脱气整齐牛逼 BuNH 2。通过转动的Schlenk旋塞阀惰性气体的惰性气体立即回填。重复两次。关闭烧瓶活栓到烧瓶隔离。 </li><li>三管连接到一个玻璃"T"适配器准备一个惰性气体层。附加一个管到惰性气体源，第二成油鼓泡器，以及第三对鲁尔锁定针适配器。 </li><li>吹扫5分钟用惰性气体毯装置。 </li><li>慢的流速，使得每秒几气泡穿过油起泡。 </li><li>插入惰性气体层针刺入反应烧瓶的隔膜和磁力搅拌器浸入烧瓶在干冰/丙酮浴。轻轻搅拌，直到日Ë瓶冷却。 </li><li>钳的T丁基锂瓶（25毫升，1.7戊烷M）为环立场，并取下外盖。如果存在，删除任何封口膜擦去油脂。 </li><li>选择20ml的玻璃注射器和合适大小的柱塞。柱塞应容易滑动，不应该能够摆动或拨浪鼓。如果一个拇指放置在注射器尖端密封它，柱塞不应该被容易地拔出。 </li><li>适合用长（12英寸）的20个毫升玻璃注射器，柔性注射器针头。永远是一定要选择至少一倍，可以得出试剂的体积量的注射器，并始终确保针牢固地安装在注射器上。 </li><li>卸下针适配器用于从反应烧瓶中的惰性气体层并将其移动到叔丁基锂瓶，刺穿瓶隔膜把试剂瓶在环境惰性气体的压力。 <ol><li>或者，使用隔膜入口转移adapteř从试剂供应商作为惰性气体层。附加隔膜入口传送适配器到试剂瓶和打开侧和顶帽。附加的Schlenk软管到侧臂和用惰性气体吹扫。虽然清洗，更换隔膜顶盖。离开舒伦克线活塞开到隔膜入口传送适配器，以保持它在正压下。 注:商业的厂商建议使用加压惰性气体源，而不是一个毯子。这允许被"推"到注射器而不是通过拉动注射器吸入的试剂。如果背压设定是不正确的，过度加压会导致所述柱塞被压出，露出试剂于空气。此外，背压要求实验者一旦达到所需的体积，使得在注射器中的体积保持恒定，以用拇指柱塞施加相等而相反的压力。这可能会导致试剂喷射当针被从本身被拉ptum。因此，作者喜欢使用的环境压力惰性气体层的。 </li></ol></li><li>使用惰性气体吹扫注射器。打开一个未占用的Schlenk软管到惰性气体，使得存在惰性气体的平缓流出的Schlenk软管。放置注射器的针头松散到软管的端部和绘制柱塞进出多次吹扫惰性气体的注射器的内部。 </li><li>随着注射器活塞完全压下，刺穿隔膜瓶，沉浸针在试剂。 </li><li>轻轻拉回柱塞直到试剂的过量（〜11ml）中已被抽入注射器 （从不反转试剂瓶）。通过弯曲针，使得注射器指向上方，然后压下柱塞，直到没有顶部空间并有10.0在注射器试剂毫升排出从注射器顶部空间气体和过量的试剂。在这一点上，放松注射器针头的屈曲，转动注射器右侧上。 </li><li>随着注射器针头依然在瓶子隔，将惰性气体层针适配器回试剂瓶隔膜和刺穿它。 </li><li>删除使用放开手脚瓶隔的注射器针头（从不注射器将其拉出针，因为针可能会突然关闭）。有些火焰可能在除去从该隔膜的针进行观察。刺穿与长注射器针头反应烧瓶的橡胶隔片和暂停它上面的搅拌吨 BuNH 2。 </li><li>压下活塞慢慢给所有的T丁基锂溶液中滴加加入到搅拌牛逼 BuNH 2。 </li><li>从隔膜中取出长注射器针头，留在反应烧瓶中隔膜的惰性气体层针。 </li><li>从甲苯的烧杯取下手表玻璃和绘制甲苯的体积大致等于T的容积的BuLi使用（〜10毫升）到注射器稀释残渣<html> L T丁基锂。 </li><li>从异丙醇烧杯取下手表玻璃，长针放入异丙醇，并清空注射器中的稀溶液到异丙醇中。 </li><li>数次，用异丙醇冲洗注射器以除去残留的试剂，之后，注射器是干净的。 </li><li>密封的T丁基锂试剂瓶隔一些油脂，以免泄漏在穿刺部位，并放置了一块封口膜在脂隔。更换外盖。 </li><li>从冰浴中取出烧瓶，并在环境惰性气体气氛下搅拌，直到它涉及到室温。 </li><li>取出惰性气体层针。 </li><li>储存在-30℃过夜烧瓶中。在此时间后，固体的[灵吨卜]白色粉末8将被观察到。 </li><li>过滤溶液，在惰性气氛下冲洗用冷戊烷固体，并在真空中干燥。 </li></ol>书名"&gt; 3。程序大型锂化的胡德<ol><li>充有搅拌棒和整齐吨 BuNH 2（9毫升，85.5毫摩尔）的100毫升的Schlenk烧瓶中，并与该保持至少50毫升加料漏斗适合它。夹加料漏斗用一个凯克钳烧瓶中。帽加料漏斗的顶部用橡胶隔膜。关闭加液漏斗的旋塞阀。 </li><li>通过打开Schlenk烧瓶活塞，转动舒伦克线真空短暂 （; 吨 BuNH 2是挥发性的，如果真空下保持会蒸发掉约1秒）脱气整齐牛逼 BuNH 2。通过转动的Schlenk旋塞阀惰性气体的惰性气体立即回填。重复两次。关闭烧瓶活栓到烧瓶中，并在添加漏斗分离。 </li><li>三管连接到一个玻璃"T"适配器准备一个惰性气体层。附加一个管到惰性气体源，第二成油鼓泡器和一个第三到一个路厄锁定针适配器。 </li><li>吹扫5分钟用惰性气体毯装置。 </li><li>慢的流速，使得每秒几气泡穿过油起泡。 </li><li>钳的T丁基锂瓶环立场，并取下外盖。卸下所有封口膜擦去油脂。 </li><li>传送惰性气体层到加料漏斗的隔膜。降低烧瓶成干冰浴冷却。 </li><li>使用另一种惰性气体管线，应用惰性气体的平缓流动，将n丁基锂瓶。 </li><li>插入套管插入的T丁基锂瓶的一端，并暂停它在溶液上方。 </li><li>插入另一端插入加料漏斗使针尖是均压侧臂下面。 </li><li>降低的T丁基锂进入液体上方的套管的端部和通过该惰性气体管线控制加入速度。补加料漏斗向50毫升线。 </li><li>当添加排版勒特，请从锂化试剂溶液套管结束，让它悬浮的T丁基锂试剂以上。 </li><li>除去从加料漏斗套管的另一端。 </li><li>除去在T丁基锂瓶插管的末端。然后，从第t丁基锂瓶惰性气体线。 </li><li>打开加料漏斗的旋塞阀，将n丁基锂逐滴添加到搅拌吨 BuNH 2。 </li><li>密封的T丁基锂试剂瓶隔一些油脂，以免泄漏在穿刺部位，并放置了一块封口膜在脂隔。更换外盖。 </li><li>使用以下步骤移除所述Schlenk烧瓶加料漏斗: <ol><li>通过打开Schlenk烧瓶停止公鸡和舒伦克线塞子放置在惰性气体的正压Schlenk烧瓶。除去凯克钳和从Schlenk烧瓶加料漏斗。 ŧ他烧瓶将由惰性气体的流出烧瓶得到保护，但加料漏斗可吸烟或在暴露于空气火焰短暂。 </li><li>擦去上的Schlenk的内颈部润滑脂使用烧瓶用己烷润湿的纸巾和重复，直到烧瓶内的毛玻璃出现干燥。塞子用橡胶隔膜烧瓶中。 </li><li>放置在惰性气体层针刺入Schlenk烧瓶隔。 </li></ol></li><li>从冰浴中取出烧瓶，并在环境惰性气体气氛下搅拌，直到它涉及到室温。 </li><li>取出惰性气体层针。 </li><li>储存在-30℃过夜烧瓶中。在此时间后，固体的[灵吨卜]白色粉末8将被观察到。 </li><li>过滤溶液，在惰性气氛下冲洗用冷戊烷固体，并在真空中干燥。 </li></ol> 4.在一个手套箱程序锂化<ol><li>将所有试剂，一反应烧瓶中，搅拌棒，一个止动件，和一个脂干燥器（或其它密封的容器被用于废物）成可经由前室的手套箱。 </li><li>收取烧瓶搅拌棒和脱气整齐牛逼 BuNH 2（1.8毫升，17.1毫摩尔）。覆盖用玻璃塞或隔膜，以防止挥发性叔丁基胺的蒸发烧瓶中。 </li><li>钳的T丁基锂瓶（25毫升，1.7戊烷M）为环立场，并取下外盖。可选:删除使用开瓶器隔膜帽，在牢固地夹住瓶子。一旦瓶盖被删除，不删除从手套箱瓶，直到空。如果取出，仔细地在淬火用适当的淬火剂罩其余牛逼丁基锂，如干冰或异丙醇。 </li><li>制备的约10毫升甲苯小瓶加入后洗涤注射器。 </li><li>适合20毫升注射器带针。永远是一定要选择一个与要绘制的试剂中的至少两倍体积的体积注射器，并始终确保针头牢固地附着到注射器。 </li><li>针插入的T丁基锂试剂和轻轻划柱塞背面直到试剂的过量（〜11ml）中已被抽入注射器。然后，倒置注射器，指着针上。 </li><li>持针邻近纸巾轻轻压下柱塞直到试剂的微滴从针的端部出现以除去顶部空间气体。通过将针头插入试剂瓶并按压所述柱塞直到10.0毫升试剂除去从注射器过量的试剂保留在注射器。如果任何试剂溶液泄漏，用纸巾或的Kimwipe擦拭和废物放入废物干燥器。 </li><li>从反应瓶中取出塞或隔膜慢慢的T丁基锂添加到搅拌牛逼 BuNH 2。由于反应没有冷水浴进行，注意避免过快加试剂，作为放热可引起沸腾。塞住反应烧瓶中。 </li><li>借鉴甲苯甲苯小瓶进入注射器稀释残留的试剂，然后将注射器，针头，任何纸巾废为宝的干燥器。密封的干燥器。 </li><li>重新帽和存储的T丁基锂试剂瓶，优选在手套箱冷冻器，以提高寿命。 </li><li>删除包含用于玻璃器皿，用甲苯注射器，并从手套箱任何纸巾的密封干燥器，并立即将其放入一个罩。 </li><li>打开干燥器，并清空含有稀牛逼丁基锂成异丙醇的烧杯中以终止试剂注射器。数次用异丙醇冲洗注射器。 </li><li>储存在-30℃的反应烧瓶过夜，此后白色粉状固体的[灵吨卜] 8被观察ð。 </li><li>过滤溶液，在惰性气氛下冲洗用冷戊烷固体，并在真空中干燥。 </li></ol> 5.如何中止反应或发生火灾时注:参见图1。 <ol><li>如果在任何时候该反应需要被中止，慢慢排空注射器中任何未使用的有机锂试剂入干冰。作为试剂被排空，可能会出现火焰，但干冰应淬火它们。 </li><li>如果在任何时候甲苯或异丙醇失火，只需将手表上的玻璃烧杯中，使火焰将被扼杀了。 </li><li>如果曾经出现的情况，其中一个火不能用这种方法淬火，立即使用灭火器。 </li><li>万一头发或衣物失火，立即使用安全淋浴。 </li></ol>

<ol>
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The authors have nothing to disclose.

对于这种锂化实验， 叔丁基氨基化锂（灵吨卜）经由叔丁基胺（ 叔 BuNH 2），使用叔丁基锂（ 叔丁基锂）的锂化合成的，形成的异丁烷作为副产物。所描述的协议是一个先前报协议31的变形，并进入根据以下反应: ŧBuNH 2 + T丁基锂→T的乌兰布+ 1/8 [灵牛逼卜] 8。 （2） 对于灵吨卜的合成原报告这个协议不同，在于它采用的使用反应性较低的正丁基锂作为有机锂试剂。一般情况下，每个人都应该选择较为活性有机锂试剂只要有可能。然而，FOR该论文的目的，作者选出的以展示更多的活性叔丁基锂溶液的安全使用，让观众可以观察到最具挑战性的试剂的妥善处理。这个协议可以很容易地应用到使用反应性较低的有机锂试剂。 关键步骤 由于有机锂试剂的高度自燃性质，所有的操作都必须在惰性气氛条件下进行，因此需要使用的Schlenk或惰性气体管线，或在惰性气氛手套箱中。而在一个手套箱操作是远更简单的方法，将其与自身的风险有关，从那些在惰性气体管线进行lithiations的不同。因此，这两种方法都需要非常谨慎和遵守协议。这里描述的是用于锂化两个协议:一个在惰性气体（的Schlenk）线，以及一个手套箱内。当执行在惰性气体管线一个锂化，一个FAMIliarity提供免费空气玻璃器皿和协议的运作是无价的。然而，由于不同的实验室可能采用稍微不同的做法，在步一步协议对于每个方法的详尽的描述。化学厂商提供自己的建议玻璃器皿设备和协议正确使用空气敏感的试剂32。该议定书部分概述类似于供应商的一个过程，但已被修饰以对烷基锂协议最大化安全性和缓解，特别。具体过程中的协议部分可用，但在这里，一些重要的点突出，最大限度的安全和成功。 注:在实验室里单独决不工作。 PPE 一个非常重要的考虑因素是采用正确的个人防护装备（PPE），这对于锂化包括适当的拟合实验室外套，护目镜，裤长（最好用不燃米aterial），封闭趾鞋和扎头发（如适用）。虽然最佳实践可以保证出现在大多数情况下没有火灾， 叔丁基锂极其自燃，事故可能发生。当他们这样做，研究人员的安全，如果他们是通过适当的PPE屏蔽更好保护。和T他UCLA校友最显著错误是，她表现没有实验室外套锂化，她穿的衣服制成易燃材料20。 通风 手套箱外Lithiations应该总是在通风橱中进行。如果一个明确的油烟机无法使用，直到无其他易燃化学品清晰，整洁的空间罩固定不执行锂化。窗框应降低尽可能多和尽可能多。加州大学洛杉矶分校校友的另外一个错误是，有在引擎盖（己烷），其中泻并起火等易燃物，点燃了她的衣服20。 惰性气体 锂化需要使用惰性气体。向Schlenk线（惰性气体和真空之间的双歧管切换）是理想的，但具有良好的流动控制的任何惰性气体源会工作。 注射器 玻璃注射器由于其化学惰性和更流畅的运动柱塞，优选塑料注射器。长（1-2英尺）32，柔性针必须始终牢固地连接到输送注射器。另一个加州大学洛杉矶分校校友的错误的是使用一个太短（1.5英寸）20针，其可因此有必要反转试剂瓶来绘制试剂到注射器，从而导致泄漏和火灾。因此，长针应始终使用使瓶子不需要被反转。针头应该使得它不会试剂输送过程中弹出，可以牢固地连接。鲁尔锁式注射器（ 图2）是最好的。如果使用推上＆＃34;滑末端"注射器针系统，确保该针非常好，然后再继续附着的注射器应该总是被选择为至少两次有机锂试剂32的所需量的体积这是由于这样的事实。头部空间始终占据注射器的一些量而绘制的试剂。另一位加州大学洛杉矶分校校友的错误是使用注射器是太小了。当注射器达到容量，它可能会突然打开，溅牛逼丁基锂在她未受保护的臂20 。 猝灭剂 包含小烧杯甲苯（体积约等于有机锂试剂的量交付）应位于内到达罩 - 但不是旁边 - 反应容器。手表玻璃适当大小来弥补这一烧杯在发生火灾时也应放置在烧杯中。此烧杯将用于稀释残渣L试剂污染试剂添加后的注射器（ 图1）。 含有异丙醇的第二烧杯（有机锂试剂的体积约5倍的体积要递送）也应该位于内覆盖罩 - 但不是紧邻 - 反应容器中。适当大小来弥补这一烧杯在发生火灾情况下的第二块手表的玻璃也应放在烧杯上。该容器被用于骤冷残余物留在除了（ 图1）之后的注射器。 第三，（有机锂试剂的大约十倍体积待递送）干冰的烧杯中应设在反应容器的覆盖面。在的注射器针头松动，或别的出错的情况下，本干冰可以用于淬灭在注射器中的剩余的有机锂试剂（ 图1）。 FinallY，灭火器应设在附近的紧急情况下，和安全淋浴的位置，正确的操作应该注意的。 试剂瓶 手套箱外，使用带有隔膜密封瓶盖（ 图3）仅有机锂试剂瓶。购买小瓶自1建议）有机锂试剂随着时间的推移，因此不推荐长期保存，2）隔片可随着时间的推移，露出试剂在空气中，和3）pyrophorics的小体积小于危险大量。将有机试剂瓶应该在板凳上设置和钳位到环站使用前（ 图1）。 反应容器 反应容器应oven-或火焰干燥并在惰性气氛下冷却至室温，以确保没有痕量的水对玻璃的侧面存在。含有试剂的容器，其中该或ganolithium溶液将被加入应搅拌板的上方被夹持并脱气以除去空气。这既可以通过吹扫惰性气体的容器中或通过在Schlenk线执行几个疏散的惰性气体填充周期来完成。可替代地，该烧瓶可以装入试剂和在惰性气氛手套箱中溶剂，并从手套箱取出之前密封。脱气烧瓶应装有隔膜并用惰性气体层保护（见 协议和图1）。如果合成的协议允许，该烧瓶还应当浸入冷水浴如干冰/丙酮以控制添加的有机锂试剂时，这将导致该放热。 在惰性气氛手套箱上锂化笔记 采用无空气的手套箱使得空气敏感试剂变得极其简单的处理，但它与自己的风险。由于有机锂试剂是从空气中日屏蔽Ë手套箱，很容易变得自满，麻痹大意。同时处理的试剂是简单，手套箱内泄漏产生一个难题:溢出的试剂必须擦去用纸巾，但随后的引火试剂和易燃布必须从箱中取出并放回空气，在该点，他们会立即着火。以避免这些危险，试剂和反应烧瓶应始终牢固手套箱内夹紧，打开瓶和瓶不应该被移动或通过手工处理。含有残余试剂的任何材料应该从在密封的干燥器（或类似容器）的手套箱中取出并被打开并暴露于空气中之前移动至罩。 知道紧急设备的位置及操作 知道该实验室的灭火器的位置和操作，使不能用手表玻璃被窒息扑灭火灾的情况下，可以迅速作出反应decisiv伊利。也知道实验室的安全淋浴的位置和操作。在那一件衣服着火万一，立即使用安全淋浴。如果别人的衣服着火，应立即引导他们安全淋浴。如果实验室没有一个既安全淋浴和灭火器， 不要试图一个锂化反应。什么可能是最后的机会，以节省加州大学洛杉矶分校校友的生活时，无论是她还是博士后与她合作使用的安全淋浴或灭火器扑灭火焰被错过了。相反，她的同事博士后试图拍出来的火苗有白大褂，这也起火。最终，她坐在地板上，而她的同事博士后试图浇水的烧杯中，从水槽装满，在火焰上20到扑灭火苗。 有机锂试剂是非常适合的弱酸性氢或去质子作为烷基的来源，并且它们比更标准格氏试剂更积极和反应。这种技术的局限性可以包括动力学迟缓反应，其中，所述协议的情况下，修饰可以有助于化学转变19。此外，organolithiums的高反应性可具有所需化学干扰。例如，负碳离子通常是极好的亲核试剂。试图亲电基片的去质子化（如一个羧酸）是可能导致亲核攻击，而不是脱质子化。因此，选择这个（或任何）之类的试剂时，化学知识和直觉是必需的。锂化反应将继续在合成有机和无机化学中发挥作用，在可预见的未来，因此，使用安全的理解是必不可少的。锂化反应每天都安全地完成，并没有引起担心执行此化学反应。然而，重新代理商应得的尊重和爱护的措施。至关重要的是，所要求的多故障保险遵循以避免伤害的可能性。在这个协议中，一步一步的程序安全的锂化反应论证并发布作为一个开放的访问文章，使世界上任何一个研究人员可以使用它作为培训，免费的。因此，笔者希望这份报告可能使锂化协议访问到多种群体和防止未来的悲剧。

有机锂试剂（的RLi）是利用烃的非极性，强键以生成共轭碱，可以去质子化甚至中等酸度的几乎任何化合物有力基础。它们作为更积极的替代锂酰胺（如 LDA）和格氏试剂。他们令人难以置信的强碱性使得他们在有机和无机合成巨大的效用，其适用性广在最近几个评论1-3被彻底描述。有机锂试剂可以很容易地去质子极弱的酸，例如醇，胺，以及既苄和脂肪烃。该反应通过一个稳定的，强的，烷基CH键的形成驱动。 李+ R - + HX→+的LiX RH（1） 周围的有机锂试剂一般概念进行了审核4-7，但我们在此强调这些试剂的工具来利用不同的PK几个不同的碳氢化合物一个值，以便选择适当的脱质子动力的共轭碱。例如，由于脂族烃的酸度与替代水平的增加（即 1°&gt; 2°&gt; 3°）， 叔丁基锂是最积极的烷基锂试剂，而甲基是最温和减小。苯基比甲基相当温和由于苯环的对离域电荷的去质子化的苯基阴离子的能力。因此，最常用的有机锂试剂，在提高碱度的顺序:PhLi &lt;的MeLi &lt;丁基锂&lt;S -BuLi &lt;T丁基锂。而精确的pK质子化烷烃的值，因为它们缺乏酸度，近似的pK在表中提供一个值是难以量取1 7-10一长与通常通过有机锂试剂在合成化学去质子其他常见的质子试剂。 表1提供了 ，在一目了然，一个可视化工具来预测哪些碱基可用于去质子哪些氨基酸。 超出酸碱化学，烷基锂试剂已在无机和有机金属化学开发，以提供碳基配体11,12，transmetallate试剂在催化13-15，或由光解的M-我键促进的有机金属反应性均裂16的装置， 17。而烷基锂试剂是热力学非常强的碱，它们的反应可以在某些反应迟缓，要求的反应条件18优化。一般地，它们的动力学行为可以通过更换路易斯酸性锂离子用较弱的路易斯酸如氢来改进，如在"施洛瑟碱"的产生由丁基锂和叔丁醇钾看出</EM&gt;丁醇19。 虽然有机锂试剂的合成过程的效用是不可否认的，利用这些试剂需要适当的预防措施。的试剂是自燃，在空气中或水中，并用一个剧烈的放热剧烈反应。它们产生的挥发性有机物频繁点燃，由于分解的高温。因此，可以lithiations过程中发生火灾，特别是当细心的标准作业程序都没有跟上。最臭名昭著的是加利福尼亚州的工作作为研究助理大学洛杉矶分校（UCLA）的新近毕业的本科女毕业生的情况。由于与大多数活性有机锂试剂的锂化反应过程中发生的不幸事件的结果， 叔丁基锂，学生收到致命灼伤，当一个完整的解决方案的注射器来分开，并点燃了她的衣服20。其中所做的错误是使用不适当大小的注射器的第二针，缺乏相应的个人防护装备（PPE），以及未能利用现有的安全淋浴20。常见的碳负离子试剂的敏感性，激发高极性溶剂21更安全的替代品，如共晶混合溶剂22-24的发展，并为格氏试剂，连水25-27。然而，有机锂试剂的多功能性使得在可预见的未来持续效用它们。 这个协议和可视化实验的目的是证明一个深入细致的方法来锂化，任何训练有素化学学生谁拥有需要有机锂试剂进行访问。我们希望，这一开放式访问协议将说明要做什么（什么不该做），以实现成功和安全的锂化，其他的实验室可以使用本出版物作为培训资源，通过这次彻底，视觉demonstrati上，可避免以后发生事故。这里，采用最活性叔丁基锂为锂化一个安全协议中描述，其可适于与任何反应性较低的有机锂试剂的用途。

<table><tbody><tr><td>Schlenk Flask, 25 ml</td><td>Chemglass</td><td>AF-0520-02</td><td>25 ml Flask, Reaction, 14/20 outer joint, 2&amp;nbsp;mm glass stpk, Air-free, Schlenk</td></tr><tr><td>Rubber Septum</td><td>Chemglass</td><td>CG-3024-01</td><td>Septum stopper, suba-seal, For 14/20-14/35 outer joints and 12.5&amp;nbsp;mm ID tubing</td></tr><tr><td>Stir Bar</td><td>Fisher Scientific</td><td>14-512-130</td><td>Various sized stir bars</td></tr><tr><td>&lt;em&gt;tert&lt;/em&gt;-butyllithium</td><td>Sigma-Aldrich</td><td>186198-4X25ML</td><td>1.7 M &lt;em&gt;t&lt;/em&gt;-butyllithium in pentane, 4 x 25&amp;nbsp;ml</td></tr><tr><td>&lt;em&gt;tert&lt;/em&gt;-butylamine</td><td>Sigma-Aldrich</td><td>391433-100ML</td><td>&lt;em&gt;tert&lt;/em&gt;-butylamine, purified by redistillation, &gt;99.5%</td></tr><tr><td>hexanes</td><td>Fisher Scientific</td><td>H292-4</td><td>4 L, certified ACS, hexanes, &gt;98.5%</td></tr><tr><td>isopropanol</td><td>Fisher Scientific</td><td>A416-4</td><td>4 L, 2-propanol, certified ACS plus, &gt;99.5%</td></tr><tr><td>Dry ice</td><td>Airgas</td><td></td><td></td></tr><tr><td>Pure Solv Solvent Purification System</td><td>Inert Technology</td><td>MD-5</td><td>Alumina collumns through which fresh, degassed solvents are passed to remove water.</td></tr><tr><td>Aldrich Sure/Seal septum-inlet transfer adapter</td><td>Sigma-Aldrich</td><td>Z407186</td><td>Adapter for removal of air-sensitive reagents under nitrogen blanket</td></tr><tr><td>Keck Standard Taper Clips</td><td>Chemglass</td><td>CG-145-03</td><td>clamp for securing glassware connections</td></tr><tr><td>Addition Funnel</td><td>Kontes</td><td>K634000-0060</td><td>Funnel for dropwise addition of reagent to flask</td></tr></tbody></table>

a protocol for safe lithiation reactions using organolithium reagents

有机锂试剂是在合成化学家的工具箱中的强大工具。然而，最反应试剂的极端自燃特性值得适当的技术，全面的培训，做好个人防护装备。在使用有机锂试剂，彻底，一步一步协议上的惰性气体管线或内手套箱中描述的安全和有效使用叔丁基锂的研究人员的训练帮助。作为模型反应，通过叔的反应制备锂叔丁基酰胺丁基与叔丁基锂的一当量呈现胺。

该反应的典型产率是〜670毫克（8.5毫摩尔，〜50％）。晶体的额外的作物可以通过浓缩滤液并冷却该溶液而获得。然而，纯度通常是由附加的作物损害。当这个协议是由准备和实践研究人员认真遵守，一般进行无事。在我们的经验，在罕见的情况下，当反应必须被中止或发生火灾，表玻璃盖，干冰和异丙醇骤冷烧杯的可用性，并且操作中的罩定位提供了足够的应变。 通过NMR（ 图4）或产物的确认X射线衍射是必要的，因为使用不纯或水污染试剂经常导致不能得到需要的产物。 1 H NMR谱显示了两个峰，如预期的那样，以1:1的比1:9（代表，分别是单酰胺质子和九叔丁基质子）。从戊烷或己烷中生长的晶体的分度是与产品31的报告晶体结构一致。 NMR（400兆赫，苯-d 6）δ-1.53​​（S，1H，NH），1.37（S，9H，卜t）的 。单元电池:P 2 / N，A = 12.05（2），B = 12.62（2）中，c = 18.24（3）埃，β= 105.52（5）°，V = 2672（14）埃3。 <img alt="图1" src="/files/ftp_upload/54705/54705fig1.jpg" /> 图1:。设备示意图手套箱以外的反应罩内部的外观显示<a href="http://ecsource.jove.com/files/ftp_upload/54705/54705fig1large.jpg" target="_blank">，请点击这里查看该图的放大版本。</a> <img alt="图2"SRC ="/文件/ ftp_upload / 54705 / 54705fig2.jpg"/&gt; 图2:用针注射器 10毫升注射器用鲁尔锁定尖端显示连接针<a href="http://ecsource.jove.com/files/ftp_upload/54705/54705fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图3" src="/files/ftp_upload/54705/54705fig3.jpg" /> 图3:。隔膜密封瓶盖的试剂通过与可能用针刺穿橡胶隔膜密封的金属瓶盖供应商销售的<a href="http://ecsource.jove.com/files/ftp_upload/54705/54705fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图4" src="/files/ftp_upload/54705/54705fig4.jpg" /> 图4:400兆赫灵的1 H NMR光谱。分别为9，:T已卜在C 6 D 6中的产物的NMR谱显示了酰胺和叔丁基的质子预期两个信号，为1的积分比。剩余protiosolvent信号标有*。 <a href="http://ecsource.jove.com/files/ftp_upload/54705/54705fig4large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <table fo:keep-together.within-page="1"><tbody><tr><td> 酸 </td><td> pK a为 </td><td> 基础 </td></tr><tr><td>异丁烷7 </td><td> &gt; 51 </td><td> Ť丁基锂</td></tr><tr><td>正丁烷（O 2碳）7 </td><td> 〜50 </td><td> 小号 -BuLi </td></tr><tr><td>正丁烷（1 O的碳）7 </td><td> 〜50 </td><td>丁基锂</td></tr><tr><td>甲烷7 </td><td> 48 </td><td>将MeLi </td></tR&gt; <tr><td>苯7 </td><td> 43 </td><td> PhLi </td></tr><tr><td>甲苯7 </td><td> 40 </td><td> TolLi </td></tr><tr><td> R 2 NH 8 </td><td> 36 </td><td> RNHLi </td></tr><tr><td> ArNH 2 9 </td><td> 31 </td><td> ArNHLi </td></tr><tr><td> ROH 9 </td><td> 15 </td><td> ROLi </td></tr><tr><td> ArOH 8,9 </td><td> 10 </td><td> ArOLi </td></tr></tbody></table> 表1:碳氢化合物及其相应的锂化的共轭碱的pKa值。

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A Protocol for Safe Lithiation Reactions Using Organolithium Reagents

安全和正确使用有机锂试剂的描述。

使用有机锂试剂的一个协议安全的锂化反应

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents ...

a-protocol-for-safe-lithiation-reactions-using-organolithium-reagents

Research

JoVE Journal

Chemistry

30.9K 次观看.  Temple University. 安全和正确使用有机锂试剂的描述。 

视频: A Protocol for Safe Lithiation Reactions Using Organolithium Reagents

Solid-state Graft Copolymer Electrolytes for Lithium Battery Applications

Battery safety has been a very important research area over the past decade. Commercially available lithium ion batteries employ low flash point (&lt;80 &deg;C), flammable, and volatile organic electrolytes. These organic based electrolyte systems are viable at ambient temperatures, but require a cooling system to ensure that temperatures do not exceed 80 &deg;C. These cooling systems tend to increase battery costs and can malfunction which can lead to battery malfunction and explosions, thus endangering human life. Increases in petroleum prices lead to a huge demand for safe, electric hybrid vehicles that are more economically viable to operate as oil prices continue to rise. Existing organic based electrolytes used in lithium ion batteries are not applicable to high temperature automotive applications. A safer alternative to organic electrolytes is solid polymer electrolytes. This work will highlight the synthesis for a graft copolymer electrolyte (GCE) poly(oxyethylene) methacrylate (POEM) to a block with a lower glass transition temperature (Tg) poly(oxyethylene) acrylate (POEA). The conduction mechanism has been discussed and it has been demonstrated the relationship between polymer segmental motion and ionic conductivity indeed has a Vogel-Tammann-Fulcher (VTF) dependence. Batteries containing commercially available LP30 organic (LiPF6 in ethylene carbonate (EC):dimethyl carbonate (DMC) at a 1:1 ratio) and GCE were cycled at ambient temperature. It was found that at ambient temperature, the batteries containing GCE showed a greater overpotential when compared to LP30 electrolyte. However at temperatures greater than 60 &deg;C, the GCE cell exhibited much lower overpotential due to fast polymer electrolyte conductivity and nearly the full theoretical specific capacity of 170 mAh/g was accessed.

Lithium ion batteries employ flammable and volatile organic electrolytes that are suitable for ambient temperature applications. A safer alternative to organic electrolytes are solid polymer batteries. Solid polymer batteries operate safely at high temperatures (&gt;120 &deg;C), thus making them applicable to high temperature applications such as deep oil drilling and hybrid electric vehicles. This paper will discuss (a) the polymer synthesis, (b) the polymer conduction mechanism, and (c) provide temperature cycling for both solid polymer and organic electrolytes.

接枝共聚物固态电解质的锂离子电池的应用

Battery safety has been a very important research area over the past decade. Commercially available lithium ion batteries employ low flash point (&lt;80 ...

科研

工程学

Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography

The highly diastereoselective preparation of cis-N-Ts-iodoaziridines through reaction of diiodomethyllithium with N-Ts aldimines is described. Diiodomethyllithium is prepared by the deprotonation of diiodomethane with LiHMDS, in a THF/diethyl ether mixture, at -78 &#176;C in the dark. These conditions are essential for the stability of the LiCHI2 reagent generated. The subsequent dropwise addition of N-Ts aldimines to the preformed diiodomethyllithium solution affords an amino-diiodide intermediate, which is not isolated. Rapid warming of the reaction mixture to 0 &#176;C promotes cyclization to afford iodoaziridines with exclusive cis-diastereoselectivity. The addition and cyclization stages of the reaction are mediated in one reaction flask by careful temperature control.
Due to the sensitivity of the iodoaziridines to purification, assessment of suitable methods of purification is required. A protocol to assess the stability of sensitive compounds to stationary phases for column chromatography is described. This method is suitable to apply to new iodoaziridines, or other potentially sensitive novel compounds. Consequently this method may find application in range of synthetic projects. The procedure involves firstly the assessment of the reaction yield, prior to purification, by 1H NMR spectroscopy with comparison to an internal standard. Portions of impure product mixture are then exposed to slurries of various stationary phases appropriate for chromatography, in a solvent system suitable as the eluent in flash chromatography. After stirring for 30 min to mimic chromatography, followed by filtering, the samples are analyzed by 1H NMR spectroscopy. Calculated yields for each stationary phase are then compared to that initially obtained from the crude reaction mixture. The results obtained provide a quantitative assessment of the stability of the compound to the different stationary phases; hence the optimal can be selected. The choice of basic alumina, modified to activity IV, as a suitable stationary phase has allowed isolation of certain iodoaziridines in excellent yield and purity.

A protocol for the diastereoselective one-pot preparation of cis-N-Ts-iodoaziridines is described. The generation of diiodomethyllithium, addition to N-Ts aldimines and cyclization of the amino gem-diiodide intermediate to iodoaziridines is demonstrated. Also included is a protocol to rapidly and quantitatively assess the most appropriate stationary phase for purification by chromatography.

合成和Iodoaziridines纯化涉及定量选择最优固定相的色谱

The highly diastereoselective preparation of cis-N-Ts-iodoaziridines through reaction of diiodomethyllithium with N-Ts aldimines is described. ...

化学

Protocol of Electrochemical Test and Characterization of Aprotic Li-O2 Battery

We demonstrate a method for electrochemical testing of an aprotic Li-O2 battery. An aprotic Li-O2 battery is made of a Li-metal anode, an aprotic electrolyte, and an O2-breathing cathode. The aprotic electrolyte is a solution of lithium salt with aprotic solvent; and porous carbon is commonly used as the cathode substrate. To improve the performance, an electrocatalyst is deposited onto the porous carbon substrate by certain deposition methods, such as atomic layer deposition (ALD) and wet-chemistry reaction. The as-prepared cathode materials are characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray absorption near edge structure (XANES). A Swagelok-type cell, sealed in a glass chamber filled with pure O2, is used for the electrochemical test on a battery test system. The cells are tested under either capacity-controlled mode or voltage controlled mode. The reaction products are investigated by electron microscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, and Raman spectroscopy to study the possible pathway of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). This protocol demonstrates a systematic and efficient arrangement of routine tests of the aprotic Li-O2 battery, including the electrochemical test and characterization of battery materials.

Protocol of Electrochemical Test and Characterization of Aprotic Li-O2 Battery

A protocol for the electrochemical testing of an aprotic Li-O2 battery with the preparation of electrodes and electrolytes and an introduction of the frequently used methods of characterization is presented here.

电化学测试的协议及表征非质子锂的O<sub&gt; 2</sub&gt;电池

We demonstrate a method for electrochemical testing of an aprotic Li-O2 battery. An aprotic Li-O2 battery is made of a Li-metal anode, an aprotic ...

Accessing Valuable Ligand Supports for Transition Metals: A Modified, Intermediate Scale Preparation of 1,2,3,4,5-Pentamethylcyclopentadiene

A reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented, based on modifications of existing protocols that derive from initial 2-bromo-2-butene lithiation followed by acid mediated dienol cyclization. The revised synthesis and purification of the ligand avoids the use of mechanical stirring while still permitting access to significant quantities (39 g) of Cp*H in good yield (58%). The procedure offers other additional benefits, including a more controlled quench of excess lithium during the production of the intermediate heptadienols and a simplified isolation of Cp*H of sufficient purity for metallation with transition metals. The ligand was subsequently used to synthesize [Cp*MCl2]2 complexes of both iridium and ruthenium to demonstrate the utility of the Cp*H prepared and purified by our method. The procedure outlined herein affords substantial quantities of a ubiquitous ancillary ligand support used in organometallic chemistry while minimizing the need for specialized laboratory equipment, thus providing a simpler and more accessible entry point into the chemistry of 1,2,3,4,5-pentamethylcyclopentadiene.

Reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented. The revised protocol for the synthesis and purification of the ligand minimizes the need for specialized laboratory equipment while simplifying reaction workups and product purification. Use of Cp*H in the synthesis of [Cp*MCl2]2 complexes (M = Ru, Ir) is also described.

访问有价值的配体为支持过渡金属:1,2,3,4,5-五甲基环戊二烯的一种改进，中级规模制备

A reliable, intermediate scale preparation of 1,2,3,4,5-pentamethylcyclopentadiene (Cp*H) is presented, based on modifications of existing protocols that ...

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. Recently, we have developed a two-step strategy for ketone enolate umpolung that has enabled the development of methods for chlorination, azidation, and amination using azoles. In addition, we have developed C-C bond&#8211;forming arylation and allylation reactions. At the heart of these methods is the preparation of the intermediate and highly reactive enolonium species prior to addition of a reactive nucleophile. This strategy is thus reminiscent of the preparation and use of metal enolates in classical synthetic chemistry. This strategy allows the use of nucleophiles that would otherwise be incompatible with the strongly oxidizing hypervalent iodine reagents. In this paper we present a detailed protocol for chlorination, azidation, N-heteroarylation, arylation, and allylation. The products include motifs prevalent in medicinally active products. This article will greatly assist others in using these methods.

A two step one-pot protocol for the umpolung of ketone enolates to enolonium species and addition of a nucleophile to the &#945;-position is described. Nucleophiles include chloride, azide, azoles, allyl-silanes, and aromatic compounds.

Enolonium 种极性转换酮功能化的两步协议

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. ...

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the preparation of all-carbon quaternary centers. Though conjugate additions of organometallic reagents are typically performed utilizing highly reactive organolithium or Grignard reagents, organozinc reagents have garnered attention for their enhanced chemoselectivity and mild reactivity. Despite numerous recent advances with more reactive diorganozinc and mixed diorganozinc reagents, the generation of all-carbon quaternary centers via the conjugate addition of functionalized monoorganozinc reagents remains a challenge. This protocol details a convenient and mild &#8220;one-pot&#8221; preparation and copper mediated conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to afford a broad scope of all-carbon quaternary centers in generally excellent yield and diastereoselectivity. Key to the development of this technology is the utilization of DMA as a reaction solvent with TMSCl as a Lewis acid. Notable advantages to this methodology include the operational simplicity of the organozinc reagent preparation afforded by the utilization of DMA as a solvent, as well as an efficient conjugate addition mediated by various Cu(I) and Cu(II) salts. Moreover, an intermediate silyl enol ether can be isolated utilizing a modified workup procedure. The substrate scope is limited to cyclic unsaturated ketones, and the conjugate addition is impeded by stabilized (e.g., allyl, enolate, homoenolate) and sterically encumbered (e.g., neopentyl, o-aryl) monoorganozinc reagents. Conjugate additions to five- and seven-membered rings were effective, albeit in lower yields compared with six-membered ring substrates.

A simple and practical protocol for the efficient conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to furnish all-carbon quaternary centers was developed.

功能化单有机硼化合物共轭法高效合成全碳第四纪中心

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the ...

n-Butyllithium Titration

Source: Vy M. Dong and Diane Le, Department of Chemistry, University of California, Irvine, CA
This experiment will demonstrate a simple technique to titrate and obtain an accurate concentration of the organolithium reagent, n-butyllithium (n-BuLi). Organolithium reagents are extremely air- and moisture-sensitive and proper care must be taken to maintain the quality of the reagent so that it may be used successfully in a reaction. The n-BuLi titration experiments should be performed regularly to obtain accurate concentrations prior to use in a chemical reaction. Subsequently, we will demonstrate the addition of the titrated n-BuLi to benzaldehyde.

Determining n-Butyllithium Concentration by Titration

n-丁基滴定

Source: Vy M. Dong and Diane Le, Department of Chemistry, University of California, Irvine, CA
This experiment will demonstrate a simple technique to ...

教育

JoVE Science Education

有机化学 (2)

Organocatalysis

Source: Vy M. Dong and Faben Cruz, Department of Chemistry, University of California, Irvine, CA
This experiment will demonstrate the concept of organocatalysis by illustrating the proper setup of a reaction that utilizes enamine catalysis. Organocatalysis is a form of catalysis that uses substoichiometric amounts of small organic molecules to accelerate reactions. This type of catalysis is complementary to other forms of catalysis such as transition metal or biocatalysis. Transition metal catalysis involves transition metals as catalysts and biocatalysis uses enzymes as catalysts. Some advantages of organocatalysis include the low toxicity and cost of the organocatalysts in comparison to many metal catalysts. In addition, most organocatalysts are not sensitive to air and moisture, unlike metal catalysts. In contrast to enzymes found in living organisms, the small molecules that act as organocatalysts are typically easy to access. Furthermore, organocatalysis offers complementary and new reactivity not observed with other forms of catalysis.

Organocatalysis: Principles and Applications

催化

Source: Vy M. Dong and Faben Cruz, Department of Chemistry, University of California, Irvine, CA
This experiment will demonstrate the concept of ...

Acid Halides to Alcohols: LiAlH4 Reduction

Acid halides are reduced to alcohols in the presence of a strong reducing agent like lithium aluminum hydride.
The mechanism proceeds in three steps. First, the nucleophilic hydride ion attacks the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs as a leaving group, generating an aldehyde. A second nucleophilic attack by the hydride yields an alkoxide ion, which, upon protonation, gives a primary alcohol as the final product.
<img alt="Organic reaction mechanism diagram, illustrating nucleophilic substitution using AlCl3 catalyst." src="/files/ftp_upload/12364/12364_PT_Figure_1.svg" style="text-align: center; height: 200px;" data-altupdatedat="1747908711000" data-alt="Figure1">
However, it is possible to stop the reaction at the aldehyde by using a milder reducing agent like diisobutylaluminum hydride or lithium tri(t-butoxy)aluminum hydride.

Acid Halides to Alcohols: LiAlH4 Reduction

从酸卤化物到醇类:LiAlH4 还原

Acid halides are reduced to alcohols in the presence of a strong reducing agent like lithium aluminum hydride.
The mechanism proceeds in three steps. ...

JoVE Core

有机化学

Unit 1

Carboxylic Acid Derivatives

关键术语与概念

Acid Halides to Alcohols: Grignard Reaction

Organomagnesium halides, commonly known as Grignard reagents, convert acid halides to tertiary alcohols. The reaction requires two equivalents of the Grignard reagent and proceeds via a ketone intermediate.
Grignard reagents are a source of carbanions and function as nucleophiles. The mechanism begins with the nucleophilic attack by the carbanion at the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs, forming a ketone. The addition of another equivalent of the carbanion generates a tertiary alkoxide ion. Protonation of the alkoxide gives a tertiary alcohol as the final product.
<img alt="Figure1" src="/files/ftp_upload/12827/12827_PT_Figure_1.svg" style="text-align: center; height: 225px;" />

酸卤化物到醇类:格氏反应

Organomagnesium halides, commonly known as Grignard reagents, convert acid halides to tertiary alcohols. The reaction requires two equivalents of the ...