Dette arbejde blev støttet af National karakter Science Foundation of China (21502023).

1. Sammenfatning af 1-(Iodoethynyl) -4-Methylbenzene (2, 1-Iodoalkynes)
<ol><li>Tilføje 133 mg (0,36 mmol) af TBAI og 3 mL af CH3CN til en reaktion-rør, der indeholder en magnetisk omrøring bar, som er åbne for luften. Derefter tilsættes 38 μL (0,3 mmol) af p- tolylethyne til blandingen ved hjælp af mikrosprøjte.</li>
	<li>Tilføje 96.6 mg (0,3 mmol) af PIDA til kraftigt omrørt reaktionsmiljøet i 10 portioner over en periode på 20 min. ved hjælp af en spatel.</li>
	<li>Rør reak...

1-Iodoalkynes, 1,2-diiodoalkenes og 1,1,2-triiodoalkenes kan være chemoselectively syntetiseret med hypervalente-jod reagenser som effektiv mæglere for oxidative iodination(s). De mest kritiske faktorer af disse chemoselective iodination protokoller er natur og lastning af jod kilde, som opløsningsmiddel. For eksempel 1-iodoalkyne 2 blev fremstillet som den store produkt (52% udbytte) når TBAI (2,5 equiv lastning) blev valgt som jod kilden i kombination med MeOH som opløsningsmiddel (2:</str...

Iodoalkynes og iodoalkenes er udbredte vigtigt prækursorer og byggesten i organisk syntese1,2,3,4, biologisk aktive stoffer, og nyttige i syntesen af materialer og komplekse molekyler givet lethed af konvertering af C-jeg obligation5,6,7,8. I de seneste år, har den oxidative iodination af terminal Alkyner tiltrak mere opmærksomhed til syntese af iodoalkyne og iodoalkene derivater. Så langt, effektive metoder, der bruger metalkatalysatorer9,10,11,12, hypervalente-iodonium katalysatorer13,14, en anodisk oxidation system 15, ionisk væske systemer16, KI (eller jeg2)-oxidant kombinationer17,18,19,20, ultralyd21, fase-overførsel katalysatorer 22, N- iodosuccinimide9,22,23,24,25, n- BuLi26,27, 28 , 29 , 30 , 31, Grignard reagenser32og morpholin katalysatorer17,33,24,35 er blevet udviklet for iodination af Alkyner. Vi har for nylig rapporteret en praktisk og chemoselective protokol for syntese af 1-iodoalkynes, 1,2-diiodoalkenes og 1,1,2-triiodoalkenes36. Funktionerne i denne metode er grøn og praktiske: (1) toksicitet af hypervalente-jod katalysatorer som oxidative functionalization reagenser er lav i forhold til andre konventionelle heavy-metal-baserede oxidanter37,38, 39,40,41,42, og (2) TBAI og/eller KI anvendes som jod kilder. Hertil kommer, giver vores system fremragende selektivitet milde betingelser. Chemoselective syntese af 1-iodoalkynes, 1,2-diiodoalkenes og 1,1,2-triiodoalkenes kræver præcis kontrol over forskellige faktorer, herunder sammensætningen, oxidant, jod kilde og opløsningsmidlet. Blandt disse er jod kilde den vigtigste faktor for kemoselektivitet reaktion. Efter screening af flere typer og belastninger af jod kilde samt opløsningsmidler, blev tre metoder identificeret og etableret. For det første er TBAI som energikilde jod i kombination med MIKKERS (TBAI-PIDA) selektiv for syntese af 1-iodoalkynes. Alternativt, 1,2-diiodoalkenes fremstilles effektivt ved hjælp af en KI-PIDA system. Begge metoder har råd til de tilsvarende produkter i højt udbytte og høj kemoselektivitet. Tilsvarende tri-iodinationproducts, dvs., 1,1,2-triiodoalkenes, blev fremstillet i gode udbytte fra en-pot syntese, der kombinerer TBAI-PIDA og KI-PIDA systemer36.
Her vil vi vise, hvordan kemoselektivitet for iodination af terminal Alkyner kan styres fra 1-iodoalkynes, at 1,2-diiodoalkenes og 1,1,2-triiodoalkenes under lignende reaktionsbetingelser, fremhæve den præcis kontrol, der kan være udøves af velovervejet vælge oxidant, jod kilde og opløsningsmiddel. For udviklingen af denne nye syntetiske teknik, blev p- tolylethyne brugt som model substrat. Selv om de følgende protokoller fokus på syntesen af 1-(iodoethynyl) -4-methylbenzene, (E) -1-(1,2-diiodovinyl)-4-methylbenzene, og 1-methyl - 4-(1,2,2-triiodovinyl) benzen, disse forbindelser er repræsentant for 1-iodoalkynes, 1,2 - diiodoalkenes, og 1,1,2-triiodoalkenes, henholdsvis, dvs., protokollerne er bredt anvendelsesområde, og de samme teknikker kan anvendes til chemoselective iodination af aromatiske og alifatiske terminal Alkyner36.
Reagenser ansat i chemoselective iodination af terminal Alkyner og små afvigelser fra teknikkerne beskrevet resulterer i dramatiske forskelle med hensyn til target produkter. For eksempel, har ændring af jod kilde fra TBAI KI og ændring af opløsningsmiddel fra CH3CN til en CH3CN-H2O en dramatisk effekt på kemoselektivitet af iodination. Den detaljerede protokollen tager sigte på at hjælpe nye udøvere i feltet med chemoselective iodination af terminal Alkyner at undgå mange fælles faldgruber under syntesen af 1-iodoalkynes, 1,2-diiodoalkenes og 1,1,2-triiodoalkenes.

<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

Vi præsenterer chemoselective syntesen af 1-(iodoethynyl) -4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene og 1-methyl - 4-(1,2,2-triiodovinyl) benzen som repræsentative eksempler for den praktiske chemoselective forberedelse af 1-iodoalkynes , 1,2-diiodoalkenes, og 1,1,2-triiodoalkenes fra chemoselective iodination af terminal Alkyner medieret af hypervalente-jod reagenser. Kemoselektivitet blev bekræftet ved hjælp af p- tolylethyne som model substrat til at screene en bred vifte af jod kilder og/eller hypervalente-jod reagenser. En kombination af tetrabutylammonium Iodid (TBAI) og (diacetoxyiodo) benzen (PIDA) genererer selektivt 1-iodoalkynes, mens en kombination af KI og PIDA genererer 1,2-diiodoalkenes. Et en-pot syntese baseret på både TBAI-PIDA og KI-PIDA udbytter de tilsvarende 1,1,2-triiodoalkenes. Disse protokoller blev efterfølgende anvendt til syntese af syntetisk vigtigt aromatiske og alifatiske 1-iodoalkynes, 1,2-diiodoalkenes og 1,1,2-triiodoalkenes, som blev indhentet i godt udbytte med fremragende kemoselektivitet.

Chemoselective syntese af 1-iodoalkynes, 1,2-diiodoalkenes og 1,1,2-triiodoalkenes baseret på den oxidative iodination af p- tolylethyne er sammenfattet i figur 1. Alle reaktioner blev udsat for luft. Alle forbindelser i denne undersøgelse var karakteriseret ved 1H og 13C NMR spektroskopi og massespektrometri for HPLC adgang til strukturen af produktet og selektivitet af reaktionen, samt at udforske renheden. De fremstillede produkter er s...

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

Chemoselective forberedelse af 1-Iodoalkynes, 1,2-Diiodoalkenes og 1,1,2-Triiodoalkenes baseret på den Oxidative Iodination af Terminal Alkyner

Heri, detaljerede protokoller for den oxidative iodination af terminal Alkyner hypervalente-jod reagenser præsenteres, hvilke chemoselectively råd til 1-iodoalkynes, 1,2-diiodoalkenes og 1,1,2-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.