这项工作得到了中国国家自然科学基金 (21502023) 的支持。

1. 合成 1-(Iodoethynyl)-4-甲苯 (2, 1-Iodoalkynes)
<ol><li>添加133毫克 (0.36 毫摩尔) 的 TBAI 和3毫升的 CH3CN 到一个反应管, 其中含有磁性搅拌杆, 这是开放的空气。然后, 用微量泵在混合物中加入 38 μ( 0.3 毫摩尔) 的 tolylethyne。</li>
	<li>添加96.6 毫克 (0.3 毫摩尔) 的 PIDA, 以强力搅拌反应混合物10个部分在20分钟的时间内使用刮刀。</li>
	<li>在室温下搅拌反应混合物3小时。</li>
	<li>将产生的混?...

1-Iodoalkynes, 12-diiodoalkenes 和 11, 2-triiodoalkenes 可 chemoselectively 合成使用高价碘试剂作为有效的调解人氧化碘 (s)。这些 chemoselective 碘协议最关键的因素是碘源的性质和负载, 以及溶剂。例如, 1-iodoalkyne 2被获得作为主要产品 (52% 产量), 当 TBAI (2.5 equiv 装载) 被选择作为碘来源与甲醇结合作为溶剂 (2:3:4= 90:5: 5)。在将碘源转化为基时, 没有观察到这种选择?...

Iodoalkynes 和 iodoalkenes 广泛应用于有机合成1、2、3、4、生物活性物质的重要前体和积木, 并在合成材料和复杂分子给出了转换 C I 键5,6,7,8的容易。近年来, 炔烃的氧化碘越来越多地引起了 iodoalkyne 和 iodoalkene 衍生物的合成。迄今为止, 使用金属催化剂的有效方法9、10、11、12、高价-碘催化剂13、14、阳极氧化系统15、离子液体系统16, 基 (或 I2)-氧化剂组合17,18,19,20, 超声波21, 相转移催化剂22, n-iodosuccinimide9,22,23,24,25, N-邓布利多26,27,28,29,30,31, 格利雅试剂32, 和啉催化剂17,33,24,35已开发为碘的炔烃。最近, 我们报告了一个实用的和 chemoselective 的协议, 合成 1-iodoalkynes, 12-diiodoalkenes, 11, 2-triiodoalkenes36。该方法具有绿色实用的特点: (1) 高价碘催化剂作为氧化功能化试剂的毒性较低, 与其他传统的重金属元素氧化剂37、38、 39,40,41,42, 和 (2) TBAI 和/或基被用作碘源。此外, 在温和的条件下, 我们的系统具有良好的选择性。chemoselective 合成 1-iodoalkynes, 12-diiodoalkenes 和 11, 2 triiodoalkenes 需要精确控制各种因素, 包括组成, 氧化剂, 碘源, 和溶剂。其中, 碘源是反应 chemoselectivity 的最重要因素。在对碘源和溶剂的几种类型和荷载进行筛选后, 确定并建立了三种方法。首先, TBAI 作为碘源结合 PIDA (TBAI PIDA) 是选择性的合成 1-iodoalkynes。或者, 用 PIDA 系统有效地获得 12-diiodoalkenes。两种方法均能提供高产、高 chemoselectivity 的相应产品。相应的三 iodinationproducts, i., 11, 2-triiodoalkenes, 得到了良好的产量从一锅合成, 结合了 TBAI-PIDA 和奇 PIDA 系统36。
在这里, 我们将演示如何从 1-iodoalkynes 到 12-diiodoalkenes 和 11, 2-triiodoalkenes 在类似的反应条件下, chemoselectivity 碘的炔烃, 突出精确的控制, 可以通过明智地选择氧化剂, 碘源, 和溶剂施加。针对这种新型合成技术的发展, 对tolylethyne 作了模型基质。虽然以下协议的重点是合成 1-(iodoethynyl)-4-甲苯, (E)-1-(12-diiodovinyl)-4-甲苯和 1-甲基-4-(12, 2-triiodovinyl) 苯, 这些化合物代表 1-iodoalkynes, 12-diiodoalkenes 和 11, 2-triiodoalkenes,即, 协议是广泛的范围内, 同样的技术可以适用于 chemoselective 碘的芳香和脂肪族终端炔烃36。
使用的试剂在 chemoselective 碘的终端炔烃和小偏差的技术所描述的结果, 对目标产品的显著差异。例如, 从 TBAI 到基的碘源的变化和溶剂的变化从 ch3cn 到 ch3cn-H2O 对碘的 chemoselectivity 产生了戏剧性的影响。详细的议定书旨在帮助外地的新从业者与终端炔烃的 chemoselective 碘, 以避免在合成 1-iodoalkynes、12-diiodoalkenes 和11、2-triiodoalkenes 过程中出现许多常见的缺陷。

<table border="0" cellpadding="0" cellspacing="0" width="860">
	<tbody>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">4-ethynyltoluene,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">D080006</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">phenylacetylene,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">W330041</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">1-ethynyl-4-methoxybenzene,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">D080007</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">1-ethynyl-4-fluorobenzene,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">D080005</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:263px;">4-(Trifluoromethyl)phenylacetylene,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">W320273</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:263px;">4-Ethynylbenzoic acid methyl ester,97%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">A020720</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">3-Aminophenylacetylene,97%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">D080001</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">3-Butyn-1-ol,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">A040031</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">Propargylacetate,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">L10031</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">Tetrabutylammonium Iodide,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">E010070</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">Potassium iodide,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">E010364</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">(diacetoxyiodo)benzene,99%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">A020180</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">acetonitrile, HPLC grade</td>
			<td style="width:311px;">fischer</td>
			<td style="width:119px;">A998-4</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">magnetic stirrer</td>
			<td style="width:311px;">IKA</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">rotary evaporator</td>
			<td style="width:311px;">Buchi</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:263px;">Bruker AVANCE III 400 MHz Superconducting Fourier</td>
			<td style="width:311px;">Bruker</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:263px;">High-performance liquid chromatography</td>
			<td style="width:311px;">Shimadzu</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
	</tbody>
</table>

chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes based on the oxidative iodination of terminal alkynes

我们提出了 chemoselective 合成 1-(iodoethynyl)-4-甲苯, 1-(12-diiodovinyl)-4-甲苯, 1-甲基-4-(12, 2-triiodovinyl) 苯作为实际 chemoselective 制备 1-iodoalkynes 的典型例子, 12-diiodoalkenes 和 11, 2-triiodoalkenes 从 chemoselective 碘的终端炔烃介导的高价碘试剂。用p-tolylethyne 作为模型基质筛选各种碘源和/或高价碘试剂, 证实了 chemoselectivity。四丁基碘化 (TBAI) 和 (diacetoxyiodo) 苯 (PIDA) 的组合选择性地产生 1-iodoalkynes, 而基和 PIDA 的组合产生 12-diiodoalkenes。基于 TBAI-PIDA 和 PIDA 的单壶合成, 产生相应的11、2-triiodoalkenes。这些协议随后被应用于合成重要的芳香族和脂质体 1-iodoalkynes, 12-diiodoalkenes 和 11, 2-triiodoalkenes, 得到了良好的产量和优良的 chemoselectivity。

chemoselective 合成 1-iodoalkynes, 12-diiodoalkenes 和 11, 2-triiodoalkenes 的基础上的氧化碘的ptolylethyne 总结在图 1。所有的反应都暴露在空气中。本研究中的所有化合物均采用1H 和13C 核磁共振波谱、质谱和 HPLC 法, 以获得产物的结构和反应的选择性, 并探讨其纯度。所获得的产品稳定后, 在4°c 在一个冰箱四月, i. e., 高效液相色谱和1H ?...

Watch this Scientific Journal Video about Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes at JoVE.com

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

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

本文介绍了用高价碘试剂对炔烃末氧化碘的详细协议, chemoselectively 提供了 1 iodoalkynes、12 diiodoalkenes、11、2 triiodoalkenes。

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

This method can help answer key questions in organic synthesis about chemoselective iodination of terminal alkynes for the synthesis of one-iodoalkynes, one, two-diiodoalkenes, and one, one, two-triiodoalkenes. This technique is green, practical, and affords excellent selectivity under mild conditions. Hypervalent iodine catalysts are much less toxic than heavy-metal-based oxidants, and TBAI and KI are widely available, easy-to-use iodine source.Though this method can provide insight into the chemoselective synthesis of iodoalkyne derivatives, it can also be applied to other reactions, such as material synthesis, intermediates, and biologically active compounds. To begin, place 133 milligrams of tetrabutylammonium iodide in an open reaction tube equipped with a magnetic stir bar. Add three milliliters of HPLC-grade acetonitrile to the tube.Then, draw 38 microliters of p-tolylethyne into a microsyringe, add it to the tube, and start vigorously stirring the mixture at about 1, 000 rpm. Over the course of 20 minutes, add 96.6 milligrams of diacetoxy iodobenzene, or PIDA, in 10 approximately equal portions at two-minute intervals. Continue stirring the reaction mixture at room temperature for three more hours while open to air.Then, place 30 milliliters of deionized water in a separatory funnel, and prepare 0.5 milliliters of 10%by weight aqueous sodium thiosulfate. Pour the reaction mixture into the separatory funnel, and quench it with aqueous sodium thiosulfate. Extract the aqueous layer three times with 10-milliliter portions of ethyl acetate.Then, wash the organic layer with 10 milliliters of saturated brine. Dry the organic layers over about 0.5 grams of anhydrous sodium sulfate, and remove the desiccant by vacuum filtration. Concentrate the filtrate to less than one milliliters under reduced pressure to obtain the crude product.Dissolve the crude product in about 0.5 milliliters of hexane, and purify it on a silica gel column using hexane as the eluent. Identify the product fraction with TLC, and remove the solvent by rotary evaporation to obtain the pure mono-iodinated product as a light yellow liquid. First, add 124.5 milligrams of potassium iodide and one milliliter of HPLC-grade acetonitrile to an open reaction tube equipped with a stir bar.Add 38 microliters of p-tolylethyne with a microsyringe and three milliliters of deionized water with a syringe. While vigorously stirring the reaction mixture at about 1, 000 rpm, add 96.6 milligrams of PIDA in 10 portions over the course of 20 minutes. Continue stirring the reaction mixture at room temperature for 24 hours in ambient air.Then, pour the reaction mixture into a separatory funnel containing 30 milliliters of deionized water, and quench it with one milliliter of 10%aqueous sodium thiosulfate. Extract the aqueous layer three times with 10-milliliter portions of ethyl acetate, wash the organic layer with 10 milliliters of saturated brine, and dry it over 0.5 grams of anhydrous sodium sulfate. Remove the sodium sulfate by vacuum filtration, and concentrate the filtrate under reduced pressure.Purify the crude product by elution from a silica gel column with hexane, and remove the solvent to obtain pure di-iodinated product as a light yellow liquid. First, add 133 milligrams of TBAI and one milliliter of HPLC-grade acetonitrile to a reaction tube equipped with a stir bar and open to air. Add 38 microliters of p-tolylethyne with a microsyringe, and start stirring the mixture vigorously.Add 96.6 milligrams of PIDA to the reaction mixture in 10 portions over the course of 20 minutes. Continue stirring the mixture for three hours at room temperature while open to air. Next, dissolve 124.5 milligrams of potassium iodide in three milliliters of deionized water, and add this solution to the reaction mixture.Then, add 193.2 milligrams of PIDA to the mixture in 10 portions over the course of 20 minutes. Continue stirring the mixture for three more hours in ambient air at room temperature. At that point, dissolve another 124.5 milligrams of potassium iodide in three milliliters of water, and add it to the reaction mixture, along with one milliliter of acetonitrile.Then, stir in another 193.2 milligrams of PIDA in 10 portions over 20 minutes. Continue stirring the mixture for 12 hours at room temperature in ambient air. Then, pour the reaction mixture into a separatory funnel containing 30 milliliters of deionized water, and quench it with two milliliters of 10%aqueous sodium thiosulfate.Extract the product into three 10-milliliter portions of ethyl acetate. Wash the extract with 10 milliliters of saturated brine, and dry it over 0.5 grams of anhydrous sodium sulfate. Filter out the sodium sulfate, concentrate the filtrate, and purify the crude product on a silica gel column with hexane as the eluent.Remove the solvent from the product fraction to obtain the pure tri-iodinated product as a yellow liquid. First, precisely weigh out three compounds in a known molar ratio. Combine the compounds in one milliliter of HPLC-grade acetonitrile.Then, dilute this stock solution 100-fold with more acetonitrile. Load two microliters of the diluted solution onto an HPLC column, and acquire a chromatogram. Calculate the molar attenuation coefficient for each compound for the peak areas and the amounts of each compound injected onto the column.Then, dilute a crude product sample with acetonitrile, and acquire a chromatogram. Calculate the molar ratios between the iodinated compounds to determine the chemoselectivity. Depending on the oxidative iodination reaction conditions, p-tolylethyne could be chemoselectively mono-di-or tri-iodinated.Using one equivalent of PIDA and 1.2 equivalents of TBAI resulted in the chemoselective formation of the mono-iodinated product, as confirmed by HPLC. Proton NMR of the mono-iodinated product showed that the terminal alkyne proton signal at 3.0 ppm had disappeared. The appearance of a carbon NMR signal at 5.1 ppm was consistent with literature reports for the mono-iodination of p-tolylethyne.Using one equivalent of PIDA and 2.5 equivalents of potassium iodide in a one-to-three acetonitrile-water mixture selectively yielded the di-iodinated product. The proton NMR signal at 7.2 ppm indicated the presence of the key proton of the di-iodinated olefin group, and the carbon NMR signals at 96.6 and 80.1 ppm were attributed to the olefin carbons. A three-strep, one-pot method combining the two previous techniques produced the tri-iodinated compound in major yield.The benzene proton showed less splitting in the proton NMR spectrum, and the shifts in the carbon NMR signals were consistent with the tri-iodinated olefin group. While attempting this procedure, remember to keep the reaction mixture stirring vigorously.