Name: efficient synthesis of polyfunctionalized benzenes in water via persulfate-promoted benzannulation of &#945;,&#946;-unsaturated compounds and alkynes
Uploaded: 2019-12-16T16:00:00
Description: Watch this Scientific Journal Video about Efficient Synthesis of Polyfunctionalized Benzenes in Water via Persulfate-promoted Benzannulation of ÃŽÂ±,ÃŽÂ²-Unsaturated Compounds and Alkynes at JoVE.com

我们感谢圣保罗省（巴西圣保罗，法国人民基金）的财政支持（2017/18400-6年赠款FAPESP）。这项研究部分资金来自巴西高级银行（CAPES）——财务代码001。

注意：在使用本过程中使用化学品之前，请查阅材料安全数据表 （MSDS）。使用适当的个人防护设备 （PPE），包括安全眼镜、实验室涂层和硝化手套，因为几种试剂和溶剂具有毒性、腐蚀性或易燃性。在烟机罩中执行所有反应。该协议中使用的液体是微移液器传输的。
1. 使用烷基和β、β-不饱和化合物的苯化反应
<ol><li>将 2.0 mL 的蒸馏水加入包含搅拌棒的 15 mL 试管（直径 1 ?...

<ol>
	<li>Colacot, T. J. <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 Trends in Cross-Coupling. 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A. L., de Koning, C. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metathesis+in+the+Synthesis+of+Aromatic+Compounds.">Metathesis in the Synthesis of Aromatic Compounds.</a> Chemical Reviews. 109, 3743-3782 (2009).</li><li>Zhou, P., Huang, L. B., Jiang, H. F., Wang, A. Z., Li, X. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Highly+Chemoselective+Palladium-Catalyzed+Cross-Trimerization+between+Alkyne+and+Alkenes+Leading+to+1,3,5-Trienes+or+1,2,4,5-Tetrasubstituted+Benzenes+with+Dioxygen.">Highly Chemoselective Palladium-Catalyzed Cross-Trimerization between Alkyne and Alkenes Leading to 1,3,5-Trienes or 1,2,4,5-Tetrasubstituted Benzenes with Dioxygen.</a> Journal of Organic Chemistry. 75, 8279-8282 (2010).</li><li>Li, S., Wu, X. X., Chen, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Base-promoted+direct+synthesis+of+functionalized+N-arylindoles+via+the+cascade+reactions+of+allenic+ketones+with+indoles.">Base-promoted direct synthesis of functionalized N-arylindoles via the cascade reactions of allenic ketones with indoles.</a> Organic and Biomolecular Chemistry. 17, 789-793 (2019).</li><li>Maezono, S. M. B., Poudel, T. N., Lee, Y. <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+construction+of+sterically+challenging+and+diverse+polyarylphenols+via+transition-metal-free+benzannulation+and+their+potent+in+vitro+antioxidant+activity.">One-pot construction of sterically challenging and diverse polyarylphenols via transition-metal-free benzannulation and their potent in vitro antioxidant activity.</a> Organic and Biomolecular Chemistry. 15, 2052-2062 (2017).</li><li>Shu, W. M., Zheng, K. L., Ma, J. R., Wu, A. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transition-Metal-Free+Multicomponent+Benzannulation+Reactions+for+the+Construction+of+Polysubstituted+Benzene+Derivatives.">Transition-Metal-Free Multicomponent Benzannulation Reactions for the Construction of Polysubstituted Benzene Derivatives.</a> Organic Letters. 17, 5216-5219 (2015).</li><li>Jiang, L., 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=Secondary+amine-catalyzed+[3+benzannulation+to+access+polysubstituted+benzenes+through+iminium+activation.">Secondary amine-catalyzed [3 benzannulation to access polysubstituted benzenes through iminium activation.</a> Synthetic Communications. 48, 336-343 (2018).</li><li>Koening, S. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Scalable Green Chemistry. Case Studies from the Pharmaceutical Industry. , (2013).</li><li>Backvall, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Modern Oxidation Methods. , (2004).</li><li>Narayan, S., 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="On+Water":+Unique+Reactivity+of+Organic+Compounds+in+Aqueous+Suspension.">"On Water": Unique Reactivity of Organic Compounds in Aqueous Suspension.</a> Angewandte Chemie International Edition. 44, 3275-3277 (2005).</li><li>de Souza, G. F. P., Salles, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Persulfate-Mediated+Synthesis+of+Polyfunctionalized+Benzenes+in+Water+via+Benzannulation+of+Alkynes+and+&#945;,&#946;-Unsaturated+Compounds.">Persulfate-Mediated Synthesis of Polyfunctionalized Benzenes in Water via Benzannulation of Alkynes and &#945;,&#946;-Unsaturated Compounds.</a> Green Chemistry. , (2019).</li><li>Prat, D., Wells, A., Hayler, J., Sneddon, H., McElroy, C. R., Abou-Shehada, S., Dunn, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CHEM21+Selection+Guide+of+Classical-+and+Less+Classical-Solvents.">CHEM21 Selection Guide of Classical- and Less Classical-Solvents.</a> Green Chemistry. 18, 288-296 (2015).</li><li>Sheldon, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metrics+of+Green+Chemistry+and+Sustainability:+Past,+Present,+and+Future.">Metrics of Green Chemistry and Sustainability: Past, Present, and Future.</a> ACS Sustainable Chemistry &amp; Engineering. 6, 32-48 (2018).</li></ol>

本文报告的方法设计为一种非常简单和温和的实验设置，用于合成水中的多功能化苯15。在我们的条件下，我们可以通过使用过硫酸铵来观察产品的优异产量。应使用新鲜制备的过硫酸盐水溶液;然而，固体二铵酸铵也可以使用，不损失产量。必须注意反应介质的温度。超过优化温度（85°C）增加10°C对产量有有害影响（表1，条目7）15。反应时间可以...

功能化苯可以说是合成有机化学1，2中最常用的前体。它们是制药、天然产品和功能有机材料的主流。据报道，多代苯衍生物的构造具有强大的方法，其中，芳香核亲基或电亲替代3、交叉耦合反应4和定向金属化5等成熟方法已是普遍方法。然而，这些战略的广泛应用可能会受到基质范围有限、反应过度和重焦选择性问题的影响。
串联循环反应是一种非常有吸引力的替代经典方法快速构建功能化的苯在原子经济时尚6，7，8。在此框架内，苯化反应代表一种合适的方案，可以有效地将不循环构建基块转化为有价值的苯骨架。这种反应是一种通用的方法，具有各种化学原料、机制和实验条件9，10，11。
我们研究的目标是为苯化反应开发一种简单而实用的协议，以产生前所未有的功能化苯环。为此，我们开始探索一种无金属、超硫酸的介导苯，在水中采用廉价的化学原料（β、β-不饱和化合物和烷基奈）。
与文献中报告的方法有若干优点，可以指出。无金属转化具有满足可持续发展要求的所有必要属性。仅举几例，不需要从所需产品中去除昂贵且具有挑战性的金属微量;反应对氧气和水分不太敏感，使其操作更容易，整个过程通常更便宜12。含硫酸盐稳定，易于处理，只产生硫酸盐作为副产品，从而为绿色化学倡议增添动力，尽量减少废物污染13。水被认为是一种适合有机反应的绿色溶剂：它无毒、不易燃、气味低、成本低。即使是水不溶性有机化合物也可以使用"水上"14水悬浮液，这些直接的合成方案多年来越来越受到关注。
我们优化的反应条件和简单的工作/净化程序提供了对多个功能化苯环的访问，为进一步功能化提供了大量机会。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Ammonium persulfate</td>
			<td>Vetec</td>
			<td>276</td>
			<td></td>
		</tr>
		<tr>
			<td>Chloroform-D, (D, 99.8%)</td>
			<td>Sigma Aldrich</td>
			<td>570699-50G</td>
			<td></td>
		</tr>
		<tr>
			<td>2-cyclohexen-1-one &#62;95%</td>
			<td>Sigma Aldrich</td>
			<td>C102814-25ML</td>
			<td></td>
		</tr>
		<tr>
			<td>Ethyl Acetate, 99.9%</td>
			<td>Synth</td>
			<td>01A1010.01.BJ</td>
			<td>ACS</td>
		</tr>
		<tr>
			<td>Hexanes, 98.5%</td>
			<td>Synth</td>
			<td>01H1007.01.BJ</td>
			<td>ACS</td>
		</tr>
		<tr>
			<td>Phenylacetylene 98%</td>
			<td>Sigma Aldrich</td>
			<td>117706-25ML</td>
			<td></td>
		</tr>
		<tr>
			<td>Silica Gel (SiO2)</td>
			<td>Fluka</td>
			<td>60738-5KG</td>
			<td>pore size 60 &#197;, 35-70 &#956;m particle size</td>
		</tr>
		<tr>
			<td>Thin-layer chromatography plates</td>
			<td>Macherey-Nagel</td>
			<td>818333</td>
			<td>0.20 mm silica gel 60 with fluorescent indicator UV254</td>
		</tr>
	</tbody>
</table>

efficient synthesis of polyfunctionalized benzenes in water via persulfate-promoted benzannulation of &#945;,&#946;-unsaturated compounds and alkynes

苯环化反应是一种有效的方案，可将不循环积木转化为结构变化不等的苯骨架。尽管对功能化苯采取了经典和近期的方法，但在水无金属方法中，仍然是一个挑战，并且代表着一个机会，可以进一步扩展用于合成多代苯化合物的工具集。该协议描述了一个操作上简单的实验设置，以探索β、β-不饱和化合物和烷基的苯化，以提供前所未有的高产量功能化苯环。甲硫酸铵是首选试剂，具有稳定性和易操作性等显著优点。此外，使用水作为溶剂和缺乏金属使该方法更具可持续性。避免使用干燥剂的改进处理过程也为协议增加了便利性。产品纯化仅使用一塞二氧化硅进行。基材范围目前仅限于终端烷基和β，β-不饱和脂肪化合物。

使用我们的协议，多替代苯（3b，图1）被分离为无色油（0.2741克，0.920毫摩尔，92%收率）。结构和纯度可以在图2和图3所示的1H和13C NMR光谱中进行评估。中央苯环（±8.37和+7.72ppm）上芳香质子的峰值用作产品形成的诊断信号。
6，8-二苯基-3，4-二氢二苯甲苯-1（2H）-一（3b）。<...

Watch this Scientific Journal Video about Efficient Synthesis of Polyfunctionalized Benzenes in Water via Persulfate-promoted Benzannulation of ÃŽÂ±,ÃŽÂ²-Unsaturated Compounds and Alkynes at JoVE.com

Efficient Synthesis of Polyfunctionalized Benzenes in Water via Persulfate-promoted Benzannulation of ÃƒÅ½Ã‚Â±,ÃƒÅ½Ã‚Â²-Unsaturated Compounds and Alkynes

报道了水中对β、β-不饱和化合物和烷基化合物的超硫酸盐促进的无金属苯化，以合成前所未有的多功能化苯。

通过超硫酸盐促进的β、β-不饱和化合物和烷基奈的苯基的高效合成在水中的多功能苯

Benzannulation reactions represent an effective protocol to transform acyclic building blocks into structurally varied benzene skeletons. Despite ...

这是一个非常简单的实验设置，符合有机化学要求，以获得一系列可行的多功能苯。该技术的主要优点是使用水作为溶剂，使粗混合物易于分离，并有助于有机化学的可持续实践。证明这个程序的将是加布里埃拉·苏扎博士，一个来自我实验室的副研究员。首先，在含有搅拌棒的15毫升试管中加入两毫升蒸馏水。按顺序添加220微升乙二苯酚、96.8微升2环氧1-1、1.5毫升新鲜准备的1.3摩尔铵。使用橡胶隔膜盖住管子，并在管内插入针头，以避免在加热过程中最终积聚压力。将管子放在热板上的铝加热块中，在 1，150 RPM 的剧烈搅拌下，在 85 摄氏度下加热 8 小时。。为了允许反应的进展，采取反应介质的50微升等同，并转移到1.5毫升锥形小瓶。在小瓶中加入50微升乙酸乙酯并摇动。然后用毛细管收集有机顶层，并将其涂在TLC硅涂层玻璃板上。将板浸入92：8乙酸乙基溶液中进行分析。将反应混合物冷却至室温，并在试管中加入一毫升乙酸乙酯。搅拌悬架约一分钟，然后在室温下以 2，336 次 g 离心，进行一分钟。使用巴斯德移液器去除有机顶层，并将其转移到圆形底部烧瓶中。重复添加乙酸乙酯到离心和去除顶层两次。使用旋转蒸发器在减压下将顶层集中，以获得原油。以92：8的比例加入55毫升六烷和乙酸乙酯混合物，放入含有7.5克二氧化硅的烧杯中。搅拌烧瓶以获得均匀的浆料。将泥浆转移到内径为 40 毫米的柱上，以包装柱子。将原油溶解在少量的乙酸乙酯中，然后将溶液转移到柱子上。在试管中收集柱污水。执行 TLC，根据仅显示一种迁移化合物的 TLC 结果获得所需的纯产品。在旋转蒸发器上降低压力下将所需溶液集中，并在高真空下去除最终挥发性液体至少一小时。使用脱化氯仿分析质子和碳-13 NMR纯化产品的样品。在此协议中，多甲苯被分离为无色油。在质子和碳-13 NMR光谱中评估了结构和纯度。8.37 和 7.72 PPM 中央苯环上的芳香质子峰值用作产品形成诊断信号。仔细控制反应介质的温度，确保反应过程中适当搅拌悬浮液非常重要。此过程可用于在水中进行的任何其他转化。保持工作步骤是从反应介质获得粗混合物的一种有效方法。该程序提供了一种简单而有效的方法来研究水作为反应介质，并鼓励设计更可持续的转化。为了操作安全，在用橡胶隔膜盖住管子后，在加热前一定要插入针头。它避免在反应过程中积聚任何压力。

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Unit 1

Efficient Synthesis of Polyfunctionalized Benzenes in Water via Persulfate-promoted Benzannulation of &#945;,&#946;-Unsaturated Compounds and Alkynes

Reactions of Aromatic Compounds

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