Name: synthesis and purification of iodoaziridines involving quantitative selection of the optimal stationary phase for chromatography
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Description: Watch this Scientific Journal Video about Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography at JoVE.com

For financial support we gratefully acknowledge the EPSRC (Career Acceleration Fellowship to J.A.B.; EP/J001538/1), the Ramsay Memorial Trust (Research Fellowship 2009-2011 to J.A.B.), and Imperial College London. Thank you to Prof. Alan Armstrong for generous support and advice.

1. Preparation of Iodoaziridines with Diiodomethyllithium
<ol>
	<li>Flame dry a 100 ml round bottom flask containing a stirrer bar and fitted with a septum, under a stream of argon, then allow to cool to room temperature under an argon atmosphere. NOTE: Glassware dried in an oven overnight (125 &#176;C) and cooled to room temperature in an analogous fashion is also appropriate.</li>
	<li>To the flask, add 5.7 ml anhydrous THF and 2.7 ml anhydrous Et2O via syringe, and freshly distilled hexamethyldis...

<ol>
	<li>Sweeney, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aziridines:+epoxides'+ugly+cousins.">Aziridines: epoxides' ugly cousins.</a> Chem. Soc. Rev. 31 (5), 247-258 (2002).</li><li>Lu, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+developments+in+regioselective+ring+opening+of+aziridines.">Recent developments in regioselective ring opening of aziridines.</a> Tetrahedron. 66 (14), 2549-2560 (2010).</li><li>Wu, B., Parquette, J. R., RajanBabu, T. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regiodivergent+ring+opening+of+chiral+aziridines.">Regiodivergent ring opening of chiral aziridines.</a> Science. 326 (5960), (2009).</li><li>Liew, S. K., He, Z., St Denis, J. D., Yudin, A. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereocontrolled+synthesis+of+1,2-+and+1,3-diamine+building+blocks+from+aziridine+aldehyde+dimers.">Stereocontrolled synthesis of 1,2- and 1,3-diamine building blocks from aziridine aldehyde dimers.</a> J. Org. Chem. , (2013).</li><li>Stankovi&#263;, 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=Regioselectivity+in+the+ring+opening+of+non-activated+aziridines.">Regioselectivity in the ring opening of non-activated aziridines.</a> Chem. Soc. Rev. 41 (2), 643-665 (2012).</li><li>Cardoso, A. L., Pinho e Melo, T. M. V. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aziridines+in+formal+[3+2]+cycloadditions:+synthesis+of+five-membered+heterocycles.">Aziridines in formal [3+2] cycloadditions: synthesis of five-membered heterocycles.</a> Eur. J. Org. Chem. 2012 (33), 6479-6501 (2012).</li><li>Dauban, P., Malik, 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+masked+1,3-dipole+revealed+from+aziridines.">A masked 1,3-dipole revealed from aziridines.</a> Angew. Chem., Int. Ed. 48 (48), 9026-9029 (2009).</li><li>Florio, S., Luisi, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aziridinyl+anions:+generation,+reactivity,+and+use+in+modern+synthetic+chemistry.">Aziridinyl anions: generation, reactivity, and use in modern synthetic chemistry.</a> Chem. Rev. 110 (9), 5128-5157 (2010).</li><li>Vedejs, E., Moss, W. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lithiated+aziridine+reagents.">Lithiated aziridine reagents.</a> J. Am. Chem. Soc. 115 (4), 1607-1608 (1993).</li><li>Satoh, T., Fukuda, Y. <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+synthesis+of+enantiomerically+pure+&#945;-+and+&#946;-amino+acid+derivatives+using+aziridinyl+anions.">A new synthesis of enantiomerically pure &#945;- and &#946;-amino acid derivatives using aziridinyl anions.</a> Tetrahedron. 59 (49), 9803-9810 (2003).</li><li>Satoh, T., Matsue, R., Fujii, T., Morikawa, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cross-coupling+of+nonstabilized+aziridinylmagnesiums+with+alkylhalides+catalyzed+by+Cu(I)+iodide:+a+new+synthesis+of+amines+bearing+a+quaternary+chiral+center+and+an+asymmetric+synthesis+of+both+enantiomers+of+the+amines+from+one+chiral+starting+material.">Cross-coupling of nonstabilized aziridinylmagnesiums with alkylhalides catalyzed by Cu(I) iodide: a new synthesis of amines bearing a quaternary chiral center and an asymmetric synthesis of both enantiomers of the amines from one chiral starting material.</a> Tetrahedron. 57 (18), 3891-3898 (2001).</li><li>Hodgson, D. M., Humphreys, P. G., Hughes, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Widening+the+usefulness+of+epoxides+and+aziridines+in+synthesis.">Widening the usefulness of epoxides and aziridines in synthesis.</a> Pure. Appl. Chem. 79 (2), 269-279 (2007).</li><li>Musio, B., Clarkson, G. J., Shipman, M., Florio, S., Luisi, R. <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+optically+active+arylaziridines+by+regio-+and+stereospecific+lithiation+of+N-Bus-phenylaziridine.">Synthesis of optically active arylaziridines by regio- and stereospecific lithiation of N-Bus-phenylaziridine.</a> Org. Lett. 11 (2), 325-328 (2009).</li><li>Beak, P., Wu, S., Yum, E. K., Jun, Y. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intramolecular+cyclizations+of+-lithioamine+synthetic+equivalents:+convenient+syntheses+of+3-,+5-,+and+6-membered-ring+heterocyclic+nitrogen+compounds+and+elaborations+of+3-membered+ring+systems.">Intramolecular cyclizations of -lithioamine synthetic equivalents: convenient syntheses of 3-, 5-, and 6-membered-ring heterocyclic nitrogen compounds and elaborations of 3-membered ring systems.</a> J. Org. Chem. 59 (2), 276-277 (1994).</li><li>Aggarwal, V. K., Alonso, E., Ferrara, M., Spey, S. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Highly+diastereoselective+aziridination+of+imines+with+trimethylsilyldiazomethane.+Subsequent+silyl+substitution+with+electrophiles,+ring+opening,+and+metalation+of+C-silylaziridines+&#8722;+a+cornucopia+of+highly+selective+transformations.">Highly diastereoselective aziridination of imines with trimethylsilyldiazomethane. Subsequent silyl substitution with electrophiles, ring opening, and metalation of C-silylaziridines &#8722; a cornucopia of highly selective transformations.</a> J. Org. Chem. 67 (7), 2335-2344 (2002).</li><li>Nelson, J. M., Vedejs, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metalated+aziridines+for+cross-coupling+with+aryl+and+alkenyl+halides+via+palladium+catalysis.">Metalated aziridines for cross-coupling with aryl and alkenyl halides via palladium catalysis.</a> Org. Lett. 12 (22), 5085-5087 (2010).</li><li>Theddu, N., Vedejs, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stille+coupling+of+an+aziridinyl+stannatrane.">Stille coupling of an aziridinyl stannatrane.</a> J. Org. Chem. 78 (10), 5061-5066 (2013).</li><li>Hughes, M., Boultwood, T., Zeppetelli, G., Bull, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Palladium-catalyzed+cross-coupling+of+aziridinylmetal+species,+generated+by+sulfinyl&#8722;magnesium+exchange,+with+aryl+bromides:+reaction+optimization,+scope,+and+kinetic+investigations.">Palladium-catalyzed cross-coupling of aziridinylmetal species, generated by sulfinyl&#8722;magnesium exchange, with aryl bromides: reaction optimization, scope, and kinetic investigations.</a> J. Org. Chem. 78 (3), 844-854 (2013).</li><li>Singh, G. S., D'hooghe, M., De Kimpe, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+and+reactivity+of+C-heteroatom-substituted+aziridines.">Synthesis and reactivity of C-heteroatom-substituted aziridines.</a> Chem. Rev. 107 (5), 2080-2135 (2007).</li><li>Bull, J. A., Boultwood, T., Taylor, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Highly+cis-selective+synthesis+of+iodo-aziridines+using+diiodomethyllithium+and+in+situ+generated+N-Boc-imines.">Highly cis-selective synthesis of iodo-aziridines using diiodomethyllithium and in situ generated N-Boc-imines.</a> Chem. Commun. 48 (100), 12246-12248 (2012).</li><li>Boultwood, T., Affron, D. P., Trowbridge, A. D., Bull, J. A. <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+cis-C-iodo-N-tosyl-aziridines+using+diiodomethyllithium:+reaction+optimization,+product+scope+and+stability,+and+a+protocol+for+selection+of+stationary+phase+for+chromatography.">Synthesis of cis-C-iodo-N-tosyl-aziridines using diiodomethyllithium: reaction optimization, product scope and stability, and a protocol for selection of stationary phase for chromatography.</a> J. Org. Chem. 78 (13), 6632-6647 (2013).</li><li>Bull, J. A., Charette, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+procedure+for+the+synthesis+of+gem-diiodoalkanes+by+the+alkylation+of+diiodomethane.+scope+and+limitations.">Improved procedure for the synthesis of gem-diiodoalkanes by the alkylation of diiodomethane. scope and limitations.</a> J. Org. Chem. 73 (20), 8097-8100 (2008).</li><li>Bull, J. A., Charette, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intramolecular+Simmons-Smith+cyclopropanation.+Studies+into+the+reactivity+of+alkyl-substituted+zinc+carbenoids,+effect+of+directing+groups+and+synthesis+of+bicyclo[n.1.0]alkanes.">Intramolecular Simmons-Smith cyclopropanation. Studies into the reactivity of alkyl-substituted zinc carbenoids, effect of directing groups and synthesis of bicyclo[n.1.0]alkanes.</a> J. Am. Chem. Soc. 132 (6), 1895-1902 (2010).</li><li>Lim, D. S. W., Anderson, E. 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-step+preparation+of+functionalized+(E)-vinylsilanes+from+aldehydes.">One-step preparation of functionalized (E)-vinylsilanes from aldehydes.</a> Org. Lett. 13 (18), 4806-4809 (2011).</li><li>Bull, J. A., Mousseau, J. J., Charette, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convenient+one-pot+synthesis+of+(E)-&#946;-aryl+vinyl+halides+from+benzyl+bromides+and+dihalomethanes.">Convenient one-pot synthesis of (E)-&#946;-aryl vinyl halides from benzyl bromides and dihalomethanes.</a> Org. Lett. 10 (23), 5485-5488 (2008).</li><li>Bull, J. A., Mousseau, J. J., Charette, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation+of+(E)-(2-iodovinyl)benzene+from+benzyl+bromide+and+diiodomethane.">Preparation of (E)-(2-iodovinyl)benzene from benzyl bromide and diiodomethane.</a> Org. Synth. 87, 170-177 (2010).</li><li>Boxer, M. B., Yamamoto, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Super+silyl+group+for+a+sequential+diastereoselective+aldol-polyhalomethyllithium+addition+reaction.">Super silyl group for a sequential diastereoselective aldol-polyhalomethyllithium addition reaction.</a> Org. Lett. 10 (3), 453-455 (2008).</li><li>Seyferth, D., Lambert, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Halomethyl-metal+compounds:+LXII.+Preparation+of+diiodomethyl-metal+compounds.">Halomethyl-metal compounds: LXII. Preparation of diiodomethyl-metal compounds.</a> J. Organomet. Chem. 54, 123-130 (1973).</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 (14), 2923-2925 (1978).</li><li>Armarego, W. L. F., Chai, L. L. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Purification of laboratory chemicals. , (2003).</li></ol>

A procedure for the diastereoselective preparation of cis-N-Ts-iodoaziridines is described, along with a stability study protocol to quantitatively indicate the best stationary phase for purification of potentially unstable compounds by flash column chromatography. It is envisaged that access to iodoaziridines through this approach will enable methods to access to a wide range of aziridines to be developed, by derivatization of the intact ring.
An appropriate modification to ...

The aim of this method is to prepare iodoaziridines that offer potential for further functionalization to aziridine derivatives. The method incorporates a protocol for the quantitative selection of the optimal stationary phase for chromatography.
Aziridines, as three-membered rings, posses inherent ring strain that makes them important building blocks in organic chemistry1. They display a vast array of reactivity often involving aziridine ring opening2,3, particularly as intermediates in the synthesis of functionalized amines4,5, or the formation of other nitrogen containing heterocycles6,7. The synthesis of a range of aziridine derivatives by functionalization of a precursor containing an intact aziridine ring has emerged as a viable strategy8. Functional group&#8211;metal exchange, to generate an aziridinyl anion, and reaction with electrophiles has been shown to be effective9,10,11, and recently regio- and stereoselective deprotonation of N-protected aziridines has also been achieved12-15. Very recently, palladium catalyzed cross-coupling methods to form aryl aziridines from functionalized aziridine precursors has been developed by Vedejs16,17, and ourselves18.
The chemistry of heteroatom substituted aziridines opens up fascinating questions of reactivity and stability19. We have been interested in the preparation of iodoaziridines as a novel functional group that offers the potential to provide precursors to a wide range of derivatives with complementary reactivity to existing aziridine functionalization reactions. In 2012 we reported the first preparation of aryl N-Boc-iodoaziridines20, and very recently reported the preparation of aryl and alkyl substituted N-Ts-iodoaziridines21.
The method to access iodoaziridines uses diiodomethyllithium, a reagent which has recently also been employed in the preparation of diiodoalkanes22,23, diiodomethylsilanes22,24, and vinyl iodides25-27. The carbenoid-like nature of this reagent requires preparation and use at low temperatures22,28. The techniques and conditions used for the generation of diiodomethyllithium in the preparation of iodoaziridines are described below.
While silica has emerged as the material of choice for chromatography29, it proved to be unsuitable for the purification of the N-Ts-iodoaziridines. Silica gel is generally the first and only solid phase material employed in flash chromatography in organic chemistry due to the availability and effective separations. However, the acidic nature of silica gel can cause the decomposition of sensitive substrates during purification, preventing isolation of the desired material. While other stationary phases or modified silica gels are available for chromatography30, there was no way to assess compatibility of the target molecule to these different materials. Due to the sensitive nature of the iodoaziridines, we established a protocol to assess the stability of a compound to an array of stationary phases21, which is demonstrated here. This has potential for application in the synthesis of a wide range of compounds with sensitive functional groups. The following protocol provides efficient access to N-Ts iodoaziridines, allowing the diastereoselective synthesis of both alkyl and aromatic cis-iodoaziridines in high yield.

<table border="0" cellpadding="0" cellspacing="0" width="871">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:209px;">Hexamethyldisilazane</td>
			<td style="width:273px;">999-97-3</td>
			<td style="width:197px;">Alfa Aesar</td>
			<td style="width:192px;">Distill from KOH under argon prior to use.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:209px;">n-Butyllithium</td>
			<td style="width:273px;">109-72-8</td>
			<td style="width:197px;">Sigma Aldrich</td>
			<td style="width:192px;">2.5 M in hexanes, titrate prior to use.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:209px;">Diiodomethane</td>
			<td style="width:273px;">75-11-6</td>
			<td style="width:197px;">Alfa Aesar</td>
			<td style="width:192px;">Contains copper as a stabilizer.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">1,3,5-Trimethoxybenzene</td>
			<td style="width:273px;">621-23-8</td>
			<td style="width:197px;">Sigma Aldrich</td>
			<td style="width:192px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">Silica</td>
			<td style="width:273px;">112945-52-5</td>
			<td style="width:197px;">Merck</td>
			<td style="width:192px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">Basic alumina</td>
			<td style="width:273px;">1344-28-1</td>
			<td style="width:197px;">Sigma Aldrich</td>
			<td style="width:192px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">Neutral alumina</td>
			<td style="width:273px;">1344-28-1</td>
			<td style="width:197px;">Merck</td>
			<td style="width:192px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">Florisil</td>
			<td style="width:273px;">1343-88-0</td>
			<td style="width:197px;">Sigma Aldrich</td>
			<td style="width:192px;"></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:23px;width:209px;">THF</td>
			<td colspan="3" rowspan="3" style="width:663px;">All anhydrous solvents were dried through activated alumina purification columns.&#160;</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;width:209px;">Et2O</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;width:209px;">CH2Cl2</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">NMR spectrometer</td>
			<td>Bruker AV 400&#160;</td>
			<td>n/a</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:209px;">NMR processing software</td>
			<td>MestReNova&#160;</td>
			<td>7.0.2-8636</td>
			<td></td>
		</tr>
	</tbody>
</table>

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.

The procedure described affords cis-(&#177;)-2-iodo-3-(4-tolyl)-1-(4-tolylsulfonyl)aziridine as a single diastereoisomer and with excellent purity (Figure 1). Prior to purification, a yield of 59% of the iodoaziridine product was calculated by 1H NMR spectroscopy. However, this iodoaziridine was particularly challenging to purify and underwent significant decomposition on silica. Purification on basic alumina (activity IV) as determined by the stationary phase screen allowed the produ...

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

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.

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

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A Quantitative Glycomics and Proteomics Combined Purification Strategy

There is a growing desire in the biological and clinical sciences to integrate and correlate multiple classes of biomolecules to unravel biology, define ...

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular ...

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have ...